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Sample records for nephrogenic adenoma arising

  1. Sodium hyaluronate in treatment of diffuse nephrogenic adenoma of the bladder in a child.

    PubMed

    Campobasso, Paolo; Fasoli, Lorella; Dante, Stefania

    2007-04-01

    Nephrogenic adenoma is a rare, benign lesion of the bladder, occurring as an epithelial response to chronic infection or trauma, probably arising from nephrogenic metaplasia. In contrast to nephrogenic adenomas in adults, who present with this tumor in the entire ureteral tract, it has been observed exclusively in the bladder of children thus far. We report and discuss here the case of a 12-year-old boy with diffuse calculus-producing nephrogenic adenoma successfully treated with sodium hyaluronate.

  2. Vesical nephrogenic adenoma: an unusual presentation of a bladder tumour

    PubMed Central

    Martínez-Sanchíz, Carlos; Martínez-Ruiz, Jesús; Anguita-Fernandez, Pedro J.; Giménez-Bachs, José M.; Atiénzar-Tobarra, Manuel; Rodríguez, Julio Antonio Virseda; Salinas-Sánchez, Antonio S.

    2011-01-01

    Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubular structures lined with flattened cuboidal cells without atypia were consistent with the diagnosis of vesical nephrogenic adenoma. PMID:21989174

  3. Successful minimally-invasive management of a case of giant prostatic hypertrophy associated with recurrent nephrogenic adenoma of the prostate

    PubMed Central

    2013-01-01

    Background Benign Prostatic Hypertrophy (BPH) is said to affect at least a third of men over 60. However, the literature contains fewer than 200 reports of prostates over 200g in mass - Giant Prostatic Hypertrophy (GPH). Nephrogenic adenomas are benign lesions of the urinary tract that are believed to represent the local proliferation of shed renal tubular cells implanting at sites of urothelial injury. Case presentation We present the first case in the literature of these two rare pathologies co-existing in the same patient and the successful management and 36-month follow-up of the patient’s symptoms with minimally invasive therapy, including the still-uncommon selective prostatic artery embolisation. We also briefly discuss the role of PAX2 in injured renal tissues and nephrogenic adenomas. Conclusions Symptomatic Giant Prostatic Hypertrophy (GPH) can be successfully managed with a combination of serial TURPs, 5 α-reductase inhibition and selective prostatic artery embolisation (SPAE). PMID:23565707

  4. Nephrogenic Adenoma of the Urinary Bladder: A Review of the Literature

    PubMed Central

    Venyo, Anthony Kodzo-Grey

    2015-01-01

    Background. Nephrogenic adenoma of the urinary bladder (NAUB) is a rare lesion associated with nonspecific symptoms and could inadvertently be misdiagnosed. Aim. To review the literature. Methods. Various internet search engines were used. Results. NAUB is a benign tubular and papillary lesion of the bladder, is more common in men and adults, and has been associated with chronic inflammation/irritation, previous bladder surgery, diverticula, renal transplantation, and intravesical BCG; recurrences and malignant transformations have been reported. Differential diagnoses include clear cell adenocarcinoma, endocervicosis, papillary urothelial carcinoma, prostatic adenocarcinoma of bladder, and nested variant of urothelial carcinoma; most NAUBs have both surface papillary and submucosal tubular components; both the papillae and tubules tend to be lined by a single layer of mitotically inactive bland cells which have pale to clear cytoplasm. Diagnosis may be established by using immunohistochemistry (positive staining with racemase; PAX2; keratins stain positive with fibromyxoid variant), electron microscopy, DNA analysis, and cytological studies. Treatment. Endoscopic resection is the treatment but recurrences including sporadic malignant transformation have been reported. Conclusions. There is no consensus on best treatment. A multicentre study is required to identify the treatment that would reduce the recurrence rate, taking into consideration that intravesical BCG is associated with NAUB. PMID:27347540

  5. Recurrence of childhood nephrogenic adenoma in urinary bladder developed four years after previous surgery despite intravesical sodium hyaluronate therapy

    PubMed Central

    Özçift, Burak; Kaçar, Ayper; Tiryaki, Hüseyin Tuğrul

    2016-01-01

    Nephrogenic adenoma (NA) is a rarely seen benign metaplastic lesion of the urinary tract. Its etiology is uncertain, but induced by chronic inflammation, irritation, and trauma. NA is located in the urinary tract, most commonly in the bladder. NA usually presents with hematuria and lower urinary tract symptoms. In the literature it is mostly seen in adults but about 30 cases of NA’s have been reported in children. Treatment of intravesical lesions consists of transurethral resection (TUR) and fulguration and rarely partial or total cystectomy may be required in ineffective TUR. Recurrence rate is high during long-term follow-up. The intravesical application of sodium hyaluronate produces a protective effect on the glycosaminoglycan layer and delays or prevents its recurrence. We report a case of recurrent NA of the bladder in a pediatric male patient who was presented four years after previous surgery despite intravesical sodium hyaluronate therapy. PMID:27909627

  6. [Nephrogenic metaplasia. A particular clinical and anatomopathologic entity].

    PubMed

    Messinetti, S; Iavarone, C; Von Heland, M; Minocchi, L; Porcelli, C; Nicolucci, D; Stio, F; Di Silverio, E

    1997-03-01

    Two cases of nephrogenic adenoma are presented. The authors consider nephrogenic metaplasia as a reaction to inflammatory agents and point out the importance of differential diagnosis with nephrogenic adenocarcinoma, in which a different surgical procedure is requested.

  7. Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus.

    PubMed

    El-Kares, Reyhan; Hueber, Pierre-Alain; Blumenkrantz, Miriam; Iglesias, Diana; Ma, Kim; Jabado, Nada; Bichet, Daniel G; Goodyer, Paul

    2009-07-01

    We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.

  8. Retroauricular Pleomorphic Adenoma Arising from Heterotopic Salivary Gland Tissue

    PubMed Central

    Bacaj, Patrick; Borah, Gregory

    2016-01-01

    Summary: A 38-year-old woman is described who presented with a slowly growing mass on the posterior aspect of the left ear. Excision and histopathologic evaluation revealed a pleomorphic adenoma (PA) originating from heterotopic salivary gland tissue. Many authors have presented cases of PAs originating from ceruminous glands in the external auditory canal or of so-called chondroid syringoma originating from apocrine and eccrine sweat glands. This is the only case in the recent literature of a PA originating from a heterotopic rest of salivary gland tissue in the retroauricular region. The 3 main sources of PAs, their embryologic derivation, and treatment are described. PMID:27757344

  9. Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN-4 cocktail (p63, AMACR, and CK903) and GATA-3.

    PubMed

    McDaniel, Andrew S; Chinnaiyan, Arul M; Siddiqui, Javed; McKenney, Jesse K; Mehra, Rohit

    2014-12-01

    Nephrogenic adenoma (NA) is a benign lesion of the urinary tract associated with injury to the urothelium. The varied morphologic patterns of NA make it a potential diagnostic pitfall, because it can mimic closely prostatic adenocarcinoma and urothelial carcinoma. In current practice, an antibody cocktail comprising p63, CK903, and AMACR (PIN-4 cocktail) is frequently utilized to evaluate foci suspicious for prostatic adenocarcinoma. Although the staining characteristics of the individual components of the PIN-4 cocktail have been reported for NA, no study has described the expression patterns for NA when the stains are applied as a cocktail. GATA-3 is an emerging marker of urothelial carcinoma; however, the GATA-3 staining characteristics of NA have yet to be described. Sixty-three NA specimens (M:F=36:27, average age=51.4 y) from various locations in the urinary tract including urinary bladder (n=40), ureter (n=3), and urethra (n=20) were collected from the archives of 2 institutions. Immunohistochemical analysis with the PIN-4 cocktail and GATA-3 antibodies was performed, and the distribution and intensity of staining was recorded for each antibody in each case. PIN-4 cocktail staining revealed AMACR expression in 56% of cases, CK903 expression in 97%, and rare p63 positivity (in only 2 cases). Only 2 NA cases displayed an overall PIN-4 staining pattern compatible with prostate cancer. GATA-3 expression was noted in 40% of NAs. No correlation between AMACR, CK903, or GATA-3 positivity and histologic pattern or anatomic location was identified. Although heterogenous staining patterns were seen within individual cases, use of the PIN-4 cocktail effectively discriminates NA from prostate cancer because of the high frequency of coexpression of AMACR and CK903 within NA. In addition, GATA-3 is not a useful marker in differentiating between NA and urothelial carcinoma.

  10. Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation.

    PubMed

    Touska, Philip; Srikanthan, Ahgi; Amarasinghe, Kavita; Jawad, Susan

    2016-07-20

    A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article.

  11. Diabetes insipidus - nephrogenic

    MedlinePlus

    Nephrogenic diabetes insipidus; Acquired nephrogenic diabetes insipidus; Congenital diabetes insipidus; NDI ... of very dilute urine. NDI is rare. Congenital diabetes insipidus is present at birth. It is a ...

  12. Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa.

    PubMed

    Maskens, A P; Dujardin-Loits, R M

    1981-01-01

    Detailed histologic analyses were performed on tumors of the large intestine obtained in 152 dimethylhydrazine (DMH)-treated rats. Of a total 539 glandular neoplasms, 45 were benign; 494 (92%) were locally invasive; of which 222 (41%) were invading the muscularis propria. One-hundred-forty-one tumors were smaller than or equal to 3mm in diameter. Among those, 127 (90%) were invasive. In addition to macroscopic nodules, several appeared after longer latency periods than did serial sections of flat mucosa. The benign polyps usually appeared after longer latency periods than did carcinomas. A review of the literature indicates that in the majority of rat experiments most or all DMH-induced tumors were frequently reported. All these data constitute strong evidence that most experimental adenocarcinomas do arise de novo in flat mucosa, i.e., without a prior adenoma stage. However, most DMH-induced tumors in mice were reported to be adenomas, either alone or coexisting with carcinomas. It is suggested that "de novo arising carcinomas" and adenomatous polyps, which are both inducible by the same carcinogens, and which can coexist in some experimental systems, nonetheless constitute independent and distinct pathologic entities; they can be separated by genetic susceptibility.

  13. Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in the bladder: a case report and review of the literature

    PubMed Central

    2013-01-01

    Background Villous adenoma arising in the urinary tract is rare tumor. Most cases have been identified as benign neoplasm in the colon. Villous adenoma of the gastrointestinal tract is thought arise from premalignant polyps. Here, we report a case of concurrence of villous adenoma and non-muscle invasive bladder cancer. Case presentation An 85-year-old woman presented at our office because of gross hematuria. Cystoscopic examination detected two papillary tumors in the bladder. Each tumor was resected and diagnosed, respectively. Histopathology confirmed that the resected one tumor was a villous adenoma, and the other was urothelial carcinoma (T1, high grade). Immunostaining for cytokeratin (CK) 7, CK20 and Ki-67 confirmed that CK7: (−), CK20: (+) and Ki-67: (<=30%) in villous adenoma while CK7: (+), CK20: (+), and Ki-67: (70%) in urothelial carcinoma. Three months later from TUR, urothelial carcinoma recurred in the trigone. She received adjuvant intravesical immunotherapy with BCG post TUR for the recurrence site. Conclusion There were no specific findings on ultrasonography, CT, MRI or cystoscopic examination morphologically. Therefore, pre-pathological villous adenoma of the bladder is extremely difficult to diagnose. There are some case reports of solitary villous adenoma in the bladder or with coexisting adeno carcinoma. However, to the best of our knowledge, this is only the second report of villous adenoma in the bladder of coexisting urothelial carcinoma that has been published in the literature. Premalignant villous adenoma of the bladder is extremely rare and difficult to diagnose without histologic examination. Any suspicious lesion of the bladder should be biopsied and/or resected to confirm histology. PMID:23870731

  14. Primary vaginal adenocarcinoma of intestinal type arising from an adenoma: case report and review of the literature.

    PubMed

    Mudhar, H S; Smith, J H; Tidy, J

    2001-04-01

    A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year-old woman with no history of diethylstilbestrol exposure that on microscopic examination was a moderately differentiated adenocarcinoma of intestinal type. The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated sialomucin, a specific marker of large intestinal differentiation. The initial interpretation favored a metastasis from a colonic adenocarcinoma, but clinical investigations showed no evidence of a primary gastrointestinal lesion. The morphology, histochemical, and differential cytokeratin profile led to the lesion being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina arising from a tubular adenoma. Although a very rare tumor, awareness of this lesion is important as it must be distinguished from metastatic adenocarcinomas from other sites.

  15. A Rare Case of Mucoepidermoid Carcinoma ex Pleomorphic Adenoma arising in Minor Salivary Gland: Histopathological and Immunohistochemical Analysis.

    PubMed

    Daltoe, Felipe Perozzo; Grando, Liliane Janete; Meurer, Maria Inês; Rivero, Elena Riet Correa; Modolo, Filipe

    2015-07-01

    Mucoepidermoid carcinoma ex pleomorphic adenoma (MCxPA) is a rare salivary gland tumor predominantly found in major salivary glands. A case of MCxPA involving the soft tissue and bone of the retromolar region of a 26-year-old man is presented. The histopathological features revealed a neoplasm with predominance of pleomorphic adenoma (PA) elements, and presence of mucoepidermoid carcinoma malignant epithelial cells in several areas. Histochemical and immunohistochemical studies were positive for periodic acid Schiff, alcian blue, cytokeratins 7, 13, 14, and 19, Bcl-2, c-erbB-2, FGF-2 and maspin in the malignant areas. The patient underwent a partial resection of the left side of the mandible with neck dissection and MCxPA diagnosis was confirmed.

  16. [Nephrogenic diabetes insipidus].

    PubMed

    Bichet, Daniel Georges

    2006-11-01

    Nephrogenic diabetes insipidus which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine-vasopressine (AVP). Polyuria, with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. Hypercalcemia, hypokaliemia, lithium administration and chronic renal failure are the principal causes of acquired nephrogenic diabetes insipidus. About 90 percent of patients with congenital nephrogenic diabetes insipidus are males with X-linked recessive nephrogenic diabetes insipidus who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. The gene is located in chromosome region Xq28. In about 10 percent of the families studied, congenital nephrogenic diabetes insipidus has an autosomal recessive or autosomal dominant mode of inheritance. In these cases, mutations have been identified in the aquaporin-2 gene (AQP2), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter's syndrome and Cystinosis. Identification of the molecular defect underlying congenital nephrogenic diabetes insipidus is of immediate clinical significance because early diagnosis and treatment of affected infants can avert the physical and mental retardation associated with episodes of dehydration.

  17. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus

    PubMed Central

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness. PMID:26504422

  18. Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus.

    PubMed

    Aksakal, Nihat; Erçetin, Candaş; Özçınar, Beyza; Aral, Ferihan; Erbil, Yeşim

    2015-01-01

    Lithium-associated hyperparathyroidism is the leading cause of hypercalcemia in lithium-treated patients. Lithium may lead to exacerbation of pre-existing primary hyperparathyroidism or cause an increased set-point of calcium for parathyroid hormone suppression, leading to parathyroid hyperplasia. Lithium may cause renal tubular concentration defects directly by the development of nephrogenic diabetes insipidus or indirectly by the effects of hypercalcemia. In this study, we present a female patient on long-term lithium treatment who was evaluated for hypercalcemia. Preoperative imaging studies indicated parathyroid adenoma and multinodular goiter. Parathyroidectomy and thyroidectomy were planned. During the postoperative course, prolonged intubation was necessary because of agitation and delirium. During this period, polyuria, severe dehydration, and hypernatremia developed, which responded to controlled hypotonic fluid infusions and was unresponsive to parenteral desmopressin. A diagnosis of nephrogenic diabetes insipidus was apparent. A parathyroid adenoma and multifocal papillary thyroid cancer were detected on histopathological examination. It was thought that nephrogenic diabetes insipidus was masked by hypercalcemia preoperatively. A patient on lithium treatment should be carefully followed up during or after surgery to prevent life-threatening complications of previously unrecognized nephrogenic diabetes insipidus, and the possibility of renal concentrating defects on long-term lithium use should be sought, particularly in patients with impaired consciousness.

  19. A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus.

    PubMed

    Kim, Kitae; Lee, Jae Hyoung; Kim, Sun Chul; Cha, Dae Ryong; Kang, Young Sun

    2014-12-01

    Aldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37-year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient's urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain.

  20. Parathyroid adenoma

    MedlinePlus

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... Parathyroid adenomas are the most common cause of hyperparathyroidism (overactive parathyroid glands), which leads to an increased ...

  1. [Nephrogenic systemic fibrosis].

    PubMed

    Cavallini, L; Abaterusso, C; Bedogna, V; Pertica, N; Loschiavo, C; Lupo, A

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a new, rare, and severe disease occurring in patients with renal failure who have been exposed to gadolinium. The pathogenesis of NSF is not completely known. In fact, the first warning about a significant relationship between NSF and gadolinium (a contrast medium used in magnetic resonance imaging) was only issued in 2006. No cases of NSF have been reported in Italy to date. A nationwide investigation should therefore be carried out to assess the real prevalence of NSF within the Italian uremic population. Furthermore, we need guidelines to reduce the risk of NSF in renal patients undergoing MRI with contrast medium.

  2. Nephrogenic diabetes insipidus.

    PubMed

    Bichet, Daniel G

    2006-04-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800) who have mutations in the arginine-vasopressin receptor 2 (AVPR2) gene that codes for the vasopressin V2 receptor. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800). In these families, mutations have been identified in the aquaporin-2 gene (AQP2) (OMIM 107777), which codes for the vasopressin-sensitive water channel. Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. Similarly, most AQP2 mutant proteins are also misrouted. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value because early diagnosis and treatment can avert the physical and mental retardation associated with repeated episodes of dehydration.

  3. [Nephrogenic systemic fibrosis].

    PubMed

    Artunc, F; Schanz, S; Metze, D; Heyne, N

    2008-01-01

    Nephrogenic systemic fibrosis (NSF) is a novel disease entity, increasingly diagnosed over the last years in patients with renal functional impairment and chronic kidney disease. Recently, gadolinium-containing MR contrast agents have been causally associated with the development NSF. Herein, we present the case of a dialysis-dependent young patient with systemic lupus erythematodes, who developed disabling cutaneous sclerosis of extremities, abdomen and mammae. Clinical and laboratory investigations revealed no signs of activity of the underlying disease. Histopathological examination of a skin biopsy was consistent with NSF showing profound thickening of tissue septae with mucine deposition and slight fibroblast proliferation without inflammatory reaction. Analysis of the patient's medical history revealed that she had undergone repeated contrast enhanced MR scans, including MR angiographies with high doses of gadopentetate. UV phototherapy was little effective, and not until kidney transplantation two years later with good allograft function, improvement of clinical symptoms was observed. Discussion of this case summarizes the current knowledge of clinical features and pathogeneses of NSF, including the role of gadolinium-containing contrast agents. Evolving clinical implications are summarized in the current Tübingen University Hospital guideline for the use of contrast-enhanced MR scans in patients with impaired renal function.

  4. [Congenital nephrogenic diabetes insipidus].

    PubMed

    Morin, D; Delenne, A L; Kervran, A

    2005-01-01

    Nephrogenic diabetes insipidus is a rare hereditary disease, characterized by a resistance of the renal collecting duct to the action of the antidiuretic hormone, arginine vasopressin, responsible for the inability of the kidney to concentrate urine. More than 90% of the patients are males and have the X-linked recessive form of the disease usually presenting with polyuria and polydipsia in infancy. This mode of inheritance is related to mutations in the V(2) receptor gene, located in the Xq28 chromosomal region. Less than 10% of the patients have an autosomal-recessive or an autosomal-dominant mode of inheritance with clinical manifestations occurring in males and females, related to mutations in the aquaporin-2 gene, located in chromosome region 12q13. The aim of the treatment is to avoid chronic and acute dehydration episodes. It remains symptomatic, mainly based on an hypoosmotic diet and the use of hydrochlorothiazide and indomethacin. Recent findings showed that pharmacological chaperones, such as V(2) nonpeptide antagonists, are able to rescue some of the V(2) receptor mutants and could be useful tools for treatment in the future.

  5. Papillary tubular adenoma with marked tubular vacuolization.

    PubMed

    Hattori, N; Imakado, S; Kikuchi, K; Murakami, T; Furue, M

    1997-12-01

    We report a case of papillary tubular adenoma, arising on the knee joint. The overall histologic structure of the tumor is consistent with that of papillary tubular adenoma with slight interluminal papillary changes, but most of the tumor cells present vacuolization outlined by carcinoembryonic antigen staining, suggesting that this adenoma may have resulted from microlumen formation. This is, to our knowledge, the first reported case of a papillary tubular adenoma with marked tubular vacuolization.

  6. Clear cell myoepithelial carcinoma ex pleomorphic adenoma.

    PubMed

    Rabade, Nikhil R; Goel, Naina A

    2014-01-01

    Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma.

  7. Gadolinium deposition in nephrogenic fibrosing dermopathy.

    PubMed

    Boyd, Alan S; Zic, John A; Abraham, Jerrold L

    2007-01-01

    There is growing recognition of the association between the use of gadolinium-containing radiocontrast agents for magnetic resonance imaging and the serious dermal and systemic disease nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF). The pathogenesis of this entity remains unclear; however, our recent observations suggest a likely mechanism for the initial dermal manifestations of this gadolinium toxicity.

  8. Nephrogenic Syndrome of Inappropriate Antidiuresis

    PubMed Central

    Feldman, Brian J.; Rosenthal, Stephen M.; Vargas, Gabriel A.; Fenwick, Raymond G.; Huang, Eric A.; Matsuda-Abedini, Mina; Lustig, Robert H.; Mathias, Robert S.; Portale, Anthony A.; Miller, Walter L.; Gitelman, Stephen E.

    2017-01-01

    SUMMARY The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient’s V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients’ SIADH-like clinical picture, which we have termed “nephrogenic syndrome of inappropriate antidiuresis.” PMID:15872203

  9. NEPHROGENIC SYSTEMIC FIBROSIS: CURRENT CONCEPTS

    PubMed Central

    Basak, Prasanta; Jesmajian, Stephen

    2011-01-01

    Nephrogenic systemic fibrosis (NSF) was first described in 2000 as a scleromyxedema-like illness in patients on chronic hemodialysis. The relationship between NSF and gadolinium contrast during magnetic resonance imaging was postulated in 2006, and subsequently, virtually all published cases of NSF have had documented prior exposure to gadolinium-containing contrast agents. NSF has been reported in patients from a variety of ethnic backgrounds from America, Europe, Asia and Australia. Skin lesions may evolve into poorly demarcated thickened plaques that range from erythematous to hyperpigmented. With time, the skin becomes markedly indurated and tethered to the underlying fascia. Extracutaneous manifestations also occur. The diagnosis of NSF is based on the presence of characteristic clinical features in the setting of chronic kidney disease, and substantiated by skin histology. Differential diagnosis is with scleroderma, scleredema, scleromyxedema, graft-versus-host disease, etc. NSF has a relentlessly progressive course. While there is no consistently successful treatment for NSF, improving renal function seems to slow or arrest the progression of this condition. Because essentially all cases of NSF have developed following exposure to a gadolinium-containing contrast agent, prevention of this devastating condition involves the careful avoidance of administering these agents to individuals at risk. PMID:21572795

  10. Pemetrexed-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    Fung, Enrica; Anand, Shuchi; Bhalla, Vivek

    2016-10-01

    Pemetrexed is an approved antimetabolite agent, now widely used for treating locally advanced or metastatic nonsquamous non-small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed.

  11. Genetics Home Reference: nephrogenic diabetes insipidus

    MedlinePlus

    ... Review. Citation on PubMed Fujiwara TM, Bichet DG. Molecular biology of hereditary diabetes insipidus. J Am Soc Nephrol. 2005 Oct;16(10):2836-46. Epub 2005 Aug 10. Review. Citation on ... NV, Deen PM. Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr ...

  12. Spontaneous rupture of the kidney in the patients with synchronous renal hemangioma and nephrogenic hypertension

    PubMed Central

    Memmedoğlu, Akif; Musayev, Jamal

    2015-01-01

    Most renal neoplasms in adults are epithelial in origin and mesenchymal tumors are rarely encountered. Vascular tumors and tumor-like lesions account for a very small subset. Hemangioma of the kidney is a rarely seen benign vascular neoplasm that probably arises from angioblastic cells. Its general sign is macroscopic hematuria with or without pain. Preoperative diagnosis is difficult or impossible. Previously, spontaneous rupture of the kidney caused by renal hemangioma was not reported in the English literature. In this study, two cases with a history of nephrogenic hypertension who presented with spontaneous renal rupture are presented. There wasn’t any trauma history in the background of our patients. A long-standing nephrogenic hypertension was present in both patients. Patients underwent radical nephrectomy due to rupture of the renal tumor. In histopathological examination, capillary hemangioma was detected in the renal medulla in both cases. Patients didn’t need antihypertensive therapy during the postoperative period. PMID:26623154

  13. Bendamustine-induced nephrogenic diabetes insipidus
.

    PubMed

    Derman, Benjamin A; Jain, Milli; McAninch, Elizabeth A; Gashti, Casey

    2017-01-01

    A 59-year-old man presented with polyuria and polydipsia immediately following his sixth cycle of rituximab and bendamustine for chronic lymphocytic leukemia. He initially compensated by increasing his oral fluid intake at home, but later developed septic shock and was admitted with orders to be kept nil per os (NPO). This prompted an episode of acute hypernatremia during which he exhibited continued polyuria with inappropriately dilute urine. Desmopressin challenge yielded no response in the urine osmolality, indicating a nephrogenic source of his diabetes insipidus (DI). He had no known exposure to other causative agents and had demonstrated a robust response to chemotherapy. The patient became eunatremic once oral intake was resumed and his infection was treated. Two months after presentation, he remained symptomatic. A trial with hydrochlorothiazide resulted in a significant increase in urine osmolality and subsequent decrease in urine output. To our knowledge, this is the first case of nephrogenic diabetes insipidus after rituximab and bendamustine exposure. We propose that bendamustine, similar to the alkylating agent ifosfamide, is toxic to the glomerulus and proximal tubule cells and is the most likely cause of the patient's nephrogenic DI.
.

  14. Imatinib in the treatment of nephrogenic systemic fibrosis.

    PubMed

    Chandran, Sindhu; Petersen, Jeffrey; Jacobs, Charlotte; Fiorentino, David; Doeden, Katherine; Lafayette, Richard A

    2009-01-01

    Nephrogenic systemic fibrosis is a disabling progressive condition that is being reported with increased frequency in patients with kidney disease. Treatment is extremely limited and largely supportive. We report a case of severe nephrogenic systemic fibrosis in a dialysis patient exposed to multiple doses of gadolinium who improved clinically and histologically with treatment with imatinib.

  15. ARISE antenna

    NASA Astrophysics Data System (ADS)

    Chmielewski, Arthur B.; Noca, Muriel; Ulvestad, James

    2000-03-01

    Supermassive black holes are among the most spectacular objects in the Universe, and are laboratories for physics in extreme conditions. Understanding the physics of massive black holes and related phenomena is a primary goal of the ARISE mission. The scientific goals of the mission are described in detail on the ARISE web site http://arise.ipl.nasa.gov and in the ARISE Science Goals document. The following paper, as the title suggests, is not intended to be a comprehensive description of ARISE, but deals only with one aspect of the ARISE mission-the inflatable antenna which is the key element of the ARISE spacecraft. This spacecraft,due to the extensive reliance on inflatables, may be considered as the first generation Gossamer spacecraft

  16. [Broncho-pulmonary adenomas].

    PubMed

    Sousa, Vítor; Pinto, Eugénia; Franca, Teresa; Carvalho, Lina

    2004-01-01

    Adenomas of solitary gland type together with papillomas are the true benign tumours in or around the bronchial tree. Alveolar adenoma and papillary adenoma are more frequently observed in peripheral parenchime although this group of tumours is very rare and often incidentally diagnosed. Presenting usually as solitary nodules in adults after 45 years, are easily recognized because of distinct morphology but alveolar adenomas may be difficult to evaluate in frozen sections. Two cases of pleomorphic adenoma and alveolar adenoma are presented and a review of literature is made.

  17. Novel Genetic Causes of Pituitary Adenomas.

    PubMed

    Caimari, Francisca; Korbonits, Márta

    2016-10-15

    Recently, a number of novel genetic alterations have been identified that predispose individuals to pituitary adenomas. Clinically relevant pituitary adenomas are relatively common, present in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior lobe of the pituitary gland, and cause disease due to hormonal alterations and local space-occupying effects. The pathomechanism of pituitary adenomas includes alterations in cell-cycle regulation and growth factor signaling, which are mostly due to epigenetic changes; somatic and especially germline mutations occur more rarely. A significant proportion of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and McCune-Albright syndrome. Pituitary tumors have also been described in association with neurofibromatosis type 1, DICER1 syndrome, and SDHx mutations. Pituitary adenomas with no other associated tumors have been described as familial isolated pituitary adenomas. Patients with AIP or GPR101 mutations often present with pituitary gigantism either in a familial or simplex setting. GNAS and GPR101 mutations that arise in early embryonic age can lead to somatic mosaicism involving the pituitary gland and resulting in growth hormone excess. Senescence has been suggested as the key mechanism protecting pituitary adenomas turning malignant in the overwhelming majority of cases. Here we briefly summarize the genetic background of pituitary adenomas, with an emphasis on the recent developments in this field. Clin Cancer Res; 22(20); 5030-42. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS

  18. Oncocytic changes in pleomorphic adenoma: Report of a rare case

    PubMed Central

    Kaur, Milanjeet; Bhogal, Jasmine

    2015-01-01

    Pleomorphic adenoma is the most common benign salivary gland tumor, accounting for almost three-fourths of all such tumors. Cells with oncocytic change are a common finding in salivary glands and in salivary gland tumors. When found within pleomorphic adenomas, cells with oncocytic changes may be perceived as evidence of malignancy, and lead to a misdiagnosis of carcinoma ex-pleomorphic adenoma. A case of pleomorphic adenoma arising de novo in the minor salivary glands with oncocytic changes is discussed here. PMID:26392734

  19. TSH secreting pituitary adenoma.

    PubMed

    Jha, S; Kumar, S

    2009-07-01

    Thyrotropin (TSH) secreting pituitary adenomas are a very rare cause of hyperthyroidism. They typically present with signs and symptoms of hyperthyroidism and rarely can be asymptomatic. TSH secreting tumors account for 1 percent of all pituitary adenoma. They are a rare cause of thyrotoxicosis in which adenomas completely or partially lose feedback regulation of thyroid hormones and lead to sustained stimulation of thyroid gland. The most definitive treatment of thyrotropin (TSH)-secreting pituitary adenomas is transsphenoidal removal of tumor after restoring euthyroidism. We report a case of pituitary adenoma associated with elevated serum free thyroid hormones and non-suppressed TSH levels.

  20. Nephrogenic diabetes insipidus in a dog with intestinal leiomyosarcoma.

    PubMed

    Cohen, M; Post, G S

    1999-12-15

    Nephrogenic diabetes insipidus was diagnosed in a dog with an intestinal leiomyosarcoma. The diagnosis of nephrogenic diabetes insipidus was made on the basis of results of serum biochemical tests, urinalyses, and a water-deprivation test, along with a lack of response to exogenous administration of vasopressin following the water-deprivation test. The temporal association between resection of the intestinal mass and resolution of clinical signs of diabetes insipidus (i.e., polyuria and polydipsia) and between recurrence of clinical signs and detection of metastatic disease suggests that there may have been a causal relationship, and nephrogenic diabetes insipidus may have developed as a paraneoplastic syndrome in this dog.

  1. Carcinoma ex pleomorphic adenoma of parotid gland with hepatic metastasis: clinic-radiological case report.

    PubMed

    Dhillon, Manu; Tomar, Divya; Sharma, Manu; Goel, Samta; Srivastava, Siddharth

    2014-04-01

    Pleomorphic adenoma originally called the mixed tumour is a neoplasm commonly involving major salivary glands. The spectrum of malignancy in pleomorphic adenoma comprises three distinct entities - Carcinoma ex pleomorphic adenoma, carcinosarcoma and benign metastasising pleomorphic adenoma. Carcinoma ex pleomorphic adenoma consists of pleomorphic adenoma with a malignant epithelial component. Occasionally, carcinomas ex pleomorphic adenoma develops metastasis. Here we are reporting here a case of benign pleomorphic adenoma arising in parotid gland which turned into malignancy after four years. The patient developed facial nerve paralysis suggesting malignant transformation. Along the course of the disease, the patient developed regional metastasis to lymph nodes and neck and distant metastasis to liver. This case report emphasises the role of advanced imaging modalities in the early diagnosis of the condition and evaluation of metastasis. The patients with this condition should be treated early for favorable outcome and investigated for distant metastasis.

  2. Physiopathology and diagnosis of nephrogenic diabetes insipidus.

    PubMed

    Devuyst, Olivier

    2012-04-01

    Nephrogenic diabetes insipidus (NDI) is caused by an improper response of the kidney to the antidiuretic hormone arginine vasopressin (AVP), leading to a decreased ability to concentrate urine which results in polyuria and polydipsia. The clinical diagnosis of NDI relies on demonstration of subnormal ability to concentrate urine despite the presence of AVP. NDI is most commonly acquired, secondary to kidney disorders, electrolyte imbalance and various drugs. Congenital forms of NDI are rare, and most commonly inherited in a X-linked manner with mutations of the AVP receptor type 2 (AVPR2). Mutations of the water channel aquaporin-2 (AQP2) can be detected in autosomal recessive or dominant forms of NDI. Management of NDI should focus on free access to drinking water and reduction of polyuria.

  3. Nephrogenic Systemic Fibrosis in Denmark– A Nationwide Investigation

    PubMed Central

    Elmholdt, Tina R.; Olesen, Anne B. B.; Jørgensen, Bettina; Kvist, Stinne; Skov, Lone; Thomsen, Henrik S.; Marckmann, Peter; Pedersen, Michael

    2013-01-01

    Background Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal impairment. Methods The prevalence of nephrogenic systemic fibrosis has so far never been determined at a national level. In 2009, Denmark was the first country to design a guideline for the tracing of nephrogenic systemic fibrosis patients. The aim of this paper is to communicate the main findings of this quest. Results The outcome of the nationwide investigation revealed that Denmark had 65 patients with nephrogenic systemic fibrosis and thereby the highest prevalence of nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or 12 per million. Conclusions The nationwide investigation in Denmark revealed the highest prevalence of NSF worldwide. This may be rooted in a high level of awareness of NSF both among doctors, politicians and, not least, the media, combined with the fact that a nationwide NSF investigation was initiated. PMID:24349178

  4. Pleomorphic Adenoma of Minor Salivary Gland in a 14 year Old Child.

    PubMed

    Pramod Krishna, B

    2013-06-01

    Salivary gland tumours are rare in childhood, and almost all of them occur in parotid gland. Minor salivary gland tumours are even rarer, pleomorphic adenoma being the most frequently found tumour. Only seventeen cases of pleomorphic adenoma arising in the minor salivary gland tumour have been reported in children and adolescents. Pleomorphic adenoma of minor salivary gland represents about 45% of all the tumours of the minor salivary glands. Pleomorphic adenoma is slowly enlarging tumour indistinguishable from adenoid cystic carcinoma clinically, except for pain and ulceration, which is more common in the latter. Carcinoma arising from pleomorphic adenoma has been reported in 3% cases amongst the minor salivary gland tumours. This report presents a case of pleomorphic adenoma of minor salivary gland in a 14 year old female patient with a brief review of literature.

  5. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    PubMed

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

  6. Parotid tail pleomorphic adenoma extending to the parapharyngeal space.

    PubMed

    Polat, Kerem; Doğan, Mansur; Yüce, Salim; Uysal, Ismail Önder; Müderris, Suphi

    2013-03-01

    Parapharyngeal space tumors are rare, accounting for 0.5% of head and neck neoplasms. Most of them are benign and originate in the salivary glands, especially the pleomorphic adenoma. We presented a 47-year-old man with parotid tail pleomorphic adenoma extending to the parapharyngeal space. The patient applied to our clinic with the complaints of a painless mass on his neck and in his mouth for 3 months. After fine needle aspiration biopsy, the mass was diagnosed as pleomorphic adenoma. The patient was hospitalized and operated in our clinic. As we see in literature review, parapharyngeal space tumors are rare, and most of them are pleomorphic adenomas arising from the deep lobe of the parotid gland and extend into the PPS.

  7. Endobronchial pleomorphic adenoma

    PubMed Central

    Ali, Syed Rizwan; Arrossi, Andrea Valeria; Mehta, Atul C.; Frye, Laura; Mazzone, Peter; Almeida, Francisco

    2016-01-01

    Pleomorphic adenomas are the most common tumors of the salivary glands. Rarely, they occur as benign lesions in the lungs in both the central airways and the lung parenchyma. Herein, we present a case of a 60-year-old smoker who was incidentally found to have an endobronchial mass while undergoing evaluation for a lung nodule. During bronchoscopy, a smooth globular nodule was identified at the main carina and removed using electrocautery snare. Histopathology examination revealed this to be a pleomorphic adenoma. PMID:28031854

  8. Lithium-induced nephrogenic diabetes insipidus after coronary artery bypass.

    PubMed

    Leeman, Matthew F; Vuylsteke, Alain; Ritchie, Andrew J

    2007-08-01

    We present a case of nephrogenic diabetes insipidus that occurred after on-pump coronary artery bypass grafting in a patient taking long-term lithium carbonate. Lithium toxicity (2.79 mmol/L) was identified on postoperative day 9. Serum sodium peaked at 175 mmol/L on postoperative day 21. Serum osmolality peaked at 384 mOsm/kg H2O, with a urinary osmolality of 403 mOsm/kg H2O. The patient was ultimately managed with hemofiltration and high-dose 1-desamino-8-D-arginine-vasopressin. Recommendations are made based on our experience of this case. In patients on long-term lithium therapy, the potentially life-threatening complication of lithium-induced nephrogenic diabetes insipidus should be specifically anticipated and managed.

  9. Carcinoma ex pleomorphic adenoma: Diagnostic dilemma and treatment protocol.

    PubMed

    Keerthi, R; Raut, Rohan P; Vaibhav, N; Ghosh, Abhishek

    2014-07-01

    Carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. The entity is difficult to diagnose preoperatively. Pathological assessment is the gold standard for making the diagnosis. Treatment for CXPA often involves an ablative surgical procedure, which may be followed by radiotherapy. We report a case of a 65-year-old lady with a history of recurrent swelling in the left preauricular region and a history of surgery 10 years back, in the same region. Preoperatively, a diagnosis of pleomorphic adenoma of the parotid gland metastasizing to the cervical lymph node was made, but postoperatively it was reported as CXPA adenoma of the parotid gland. A radical parotidectomy involving en bloc resection of the facial nerve along with deep and superficial lobes of the parotid was performed followed by radiotherapy. The fact that pleomorphic adenomas are classified as benign tumors should not overshadow the wide range of biological behaviors associated with these tumors. On account of the potential for malignant transformation, surgical treatment must be properly performed. Surgery followed by radiotherapy should be considered as the standard care for a patient with carcinoma ex pleomorphic adenoma.

  10. Treatment Options for Villous Adenoma of the Ampulla of Vater

    PubMed Central

    Cugat, E.; Veloso, E.; Marco, C.

    2000-01-01

    Introduction: Duodenal villous adenoma arising from the ampulla of Vater has a high risk of malignant development. Excluding associated malignant disease prior to resection of an adenoma of the ampulla is not always possible. Therefore, the surgical procedure of choice to treat this rare tumour is still controversial. Objective: To evaluate retrospectively results of treatment of villous adenoma arising from ampulla of Vater with dysplasia or associated carcinoma limited to the ampulla. Patients and Methods: From 1985 to 1996, eight patients have been diagnosed with ampullary villous adenoma suitable for resection. We have reviewed treatment, morbidity, mortality, follow-up and final outcome. Results: Pancreatoduodenectomy (PD) was performed in 4 patients. Transduodenal ampullectomy and endoscopic resection was performed in 2 patients each. There was no perioperative mortality. None of the patients had biliary, pancreatic or intestinal leakage but two patients who underwent PD had minor postoperative complications. The mean follow-up was 44 (range: 6–132) months. Villous adenoma was associated with adenocarcinoma in 50% of the cases (4/8 patients). During the followup both patients who underwent transduodenal ampullectomy developed recurrent disease. All patients initially treated by PD are alive without evidence of recurrent disease. Conclusions: Treatment of villous adenoma of the ampulla must be individualized within certain limits. In our series, PD achieve good results and it appears to be the procedure of choice in order to treat villous adenomas with proved presence of carcinoma, carcinoma in situ or severe dysplasia. Endoscopic or local resection may be appropriate for small benign tumours in high risk patients. PMID:10674748

  11. [Vasopressin V2 receptor-related pathologies: congenital nephrogenic diabetes insipidus and nephrogenic syndrome of inappropiate antidiuresis].

    PubMed

    Morin, Denis

    2014-12-01

    Congenital nephrogenic diabetes insipidus is a rare hereditary disease with mainly an X-linked inheritance (90% of the cases) but there are also autosomal recessive and dominant forms. Congenital nephrogenic diabetes insipidus is characterized by a resistance of the renal collecting duct to the action of the arginine vasopressin hormone responsible for the inability of the kidney to concentrate urine. The X-linked form is due to inactivating mutations of the vasopressin 2 receptor gene leading to a loss of function of the mutated receptors. Affected males are often symptomatic in the neonatal period with a lack of weight gain, dehydration and hypernatremia but mild phenotypes may also occur. Females carrying the mutation may be asymptomatic but, sometimes, severe polyuria is found due to the random X chromosome inactivation. The autosomal recessive and dominant forms, occurring in both genders, are linked to mutations in the aquaporin-2 gene. The treatment remains difficult, especially in infants, and is based on a low osmotic diet with increased water intake and the use of thiazides and indomethacin. The main goal is to avoid hypernatremic episodes and maintain a good hydration state. Potentially, specific treatment, in some cases of X-linked congenital nephrogenic diabetes insipidus, with pharmacological chaperones such as non-peptide vasopressin-2 receptor antagonists will be available in the future. Conversely, the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is linked to a constitutive activation of the V(2)-receptor due to activating mutations with clinical and biological features of inappropriate antidiuresis but with low or undetectable plasma arginine vasopressin hormone levels.

  12. Undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a young soldier.

    PubMed

    Kim, Hyung Jin; Shin, Y S; Choi, H; Kim, M K; Jeong, Y B; Park, J K

    2016-10-01

    We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a 21-year-old male soldier. Soldiers live in close quarters, and have a regimented lifestyle that may not allow for frequent voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in acute urinary retention.

  13. Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

    PubMed

    Uwumugambi, Nsabimana A; Sanchorawala, Vaishali; Shelton, Anthony C; Stern, Lauren; Gordon, Craig E

    2017-02-01

    Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy.

  14. Molecular screening of pituitary adenomas for gene mutations and rearrangements

    SciTech Connect

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. )

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  15. Undescended parathyroid adenoma

    PubMed Central

    Maawy, Ali A; Oh, Deborah K; Bouvet, Michael

    2015-01-01

    Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels. PMID:25737222

  16. Spontaneous pituitary adenoma occurring after resection of a Rathke's cleft cyst.

    PubMed

    Chaudhry, Nauman S; Raber, Michael R; Cote, David J; Laws, Edward R

    2016-11-01

    Rathke's cleft cysts (RCC) are benign cystic lesions that originate from remnants of the epithelial lining of Rathke's pouch. RCC are known rarely to occur together with a concomitant pituitary adenoma. Here, we report a patient with a pituitary adenoma arising in the same location as a previously-resected RCC, 3 years post-operatively, and review the literature of "collision" sellar lesions. Consecutive transsphenoidal operations from a single-center between 2008 and 2016 were reviewed to identify patients with pituitary adenoma arising after surgical resection of RCC, and a systematic search of the literature was also performed to identify such patient reports, as well as reports of concomitant pituitary adenoma and RCC. Of 837 transsphenoidal operations from our own experience, one patient with pituitary adenoma occurring after RCC resection was identified and is reported here. A systematic review of the literature resulted in identification of 34 patients with concomitant RCC and pituitary adenoma and no incidents of pituitary adenoma occurring after resection of RCC. Concomitant occurrence of RCC and pituitary adenoma was more commonly diagnosed in women (61%), at a median age of diagnosis of 44 years. The RCC histological analysis in these patients consistently described ciliated columnar or cuboidal epithelium. Although rare, the presence of a new, pathologically-distinct lesions in the sella after prior surgical treatment, is possible. During post-operative monitoring, physicians should consider that what appears as a "recurrent" lesion may actually be growth of a new and entirely different lesion.

  17. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment.

    PubMed

    Moeller, Hanne B; Rittig, Søren; Fenton, Robert A

    2013-04-01

    The water channel aquaporin-2 (AQP2), expressed in the kidney collecting ducts, plays a pivotal role in maintaining body water balance. The channel is regulated by the peptide hormone arginine vasopressin (AVP), which exerts its effects through the type 2 vasopressin receptor (AVPR2). Disrupted function or regulation of AQP2 or the AVPR2 results in nephrogenic diabetes insipidus (NDI), a common clinical condition of renal origin characterized by polydipsia and polyuria. Over several years, major research efforts have advanced our understanding of NDI at the genetic, cellular, molecular, and biological levels. NDI is commonly characterized as hereditary (congenital) NDI, arising from genetic mutations in the AVPR2 or AQP2; or acquired NDI, due to for exmple medical treatment or electrolyte disturbances. In this article, we provide a comprehensive overview of the genetic, cell biological, and pathophysiological causes of NDI, with emphasis on the congenital forms and the acquired forms arising from lithium and other drug therapies, acute and chronic renal failure, and disturbed levels of calcium and potassium. Additionally, we provide an overview of the exciting new treatment strategies that have been recently proposed for alleviating the symptoms of some forms of the disease and for bypassing G protein-coupled receptor signaling.

  18. Pleomorphic adenoma of the trachea.

    PubMed

    Sim, Da Woon; Oh, In Jae; Kim, Kyu Sik; Choi, Yoo Duk; Kwon, Yong Soo

    2014-07-01

    Endobronchial pleomorphic adenoma is an extremely rare condition. A 32-year-old woman with exertional dyspnea and cough presented with a carinal mass on chest CT scan. The tumor was successfully removed by rigid bronchoscopy using argon plasma coagulation. Biopsy confirmed the diagnosis of pleomorphic adenoma.

  19. [Treatment of pituitary adenomas].

    PubMed

    Mezosi, Emese; Nemes, Orsolya

    2009-09-27

    According to epidemiological studies, the prevalence of pituitary adenomas is 16.5% and the majority of them are "incidentalomas". The symptoms of pituitary disorders are often non-specific; disturbances of pituitary function, compression symptoms, hypophysis apoplexy or accidental findings may help the diagnosis. The hormonal evaluation of pituitary adenomas is different from the algorithm used in the disorders of peripheral endocrine organs. The first-line therapy of prolactinomas are the dopamine agonists, and the aims of the treatment are to normalize the prolactin level, restore fertility in child-bearing age, decrease tumor mass, save or improve the residual pituitary function and inhibit the relapse of the disease. The available dopamine agonists in Hungary are bromocriptine and quinagolide. In case of tumors with good therapeutic response, medical therapy can be withdrawn after 3-5 years; hyperprolactinemia will not recur in 2/3 of these patients. Neurosurgery is the primary therapy of GH-, ACTH-, TSH-producing and inactive adenomas. In the last decades, significant improvement has been reached in surgical procedures, resulting in low mortality rates. Acromegalic patients with unresectable tumors have a great benefit from somatostatin analog treatment. The growth hormone receptor antagonist pegvisomant is the newest modality for the treatment of acromegaly. The medical therapy of Cushing's disease is still based on the inhibition of steroid production. A new, promising somatostatin analog, pasireotide is evaluated in clinical trials. The rare TSH-producing tumor can respond to both dopamine agonist and somatostatin analog therapy. The application of conventional radiotherapy has decreased; radiotherapy is mainly used in the treatment of invasive, incurable or malignant tumors. Further studies are needed to elucidate the exact role of radiosurgery and fractionated stereotaxic irradiation in the treatment of pituitary tumors.

  20. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-08

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions.

  1. Mechanisms of prolonged lithium therapy-induced nephrogenic diabetes insipidus.

    PubMed

    Behl, Tapan; Kotwani, Anita; Kaur, Ishneet; Goel, Heena

    2015-05-15

    Nephrogenic diabetes insipidus is a clinical sub-type of a diversely expounded disorder, named diabetes insipidus. It is characterized by inability of the renal cells to sense and respond to the stimulus of vasopressin. Amongst its various etiologies, one of the most inevitable causes includes lithium-induced instigation. Numerous studies reported marked histological damage to the kidneys upon long-term treatment with lithium. The recent researches have hypothesized many lithium-mediated mechanisms to explain the damage and dysfunction caused in the kidneys following lithium exposure. These mechanisms, widely, intend to justify the lithium-induced electrolyte imbalance, its interference with some vital proteins and a specific steroidal hormone, obstruction caused to a certain imperative transducer pathway and the renal tubular acidification defect produced on its prolonged therapy. Thorough study of such mechanisms aids in better understanding of the role of lithium in the pathophysiology of this disorder. Hence, the ameliorated knowledge regarding disease-pathology might prove beneficial in developing therapies that aim on disrupting the various lithium-mediated pathways. Hence, this may effectively lead to the demonstration of a novel treatment for nephrogenic diabetes insipidus, which is, at present, limited to the use of diuretics which block lithium reuptake into the body.

  2. Heterogeneous AVPR2 gene mutations in congenital nephrogenic diabetes insipidus.

    PubMed Central

    Wildin, R. S.; Antush, M. J.; Bennett, R. L.; Schoof, J. M.; Scott, C. R.

    1994-01-01

    Mutations in the AVPR2 gene encoding the receptor for arginine vasopressin in the kidney (V2 ADHR) have been reported in patients with congenital nephrogenic diabetes insipidus, a predominantly X-linked disorder of water homeostasis. We have used restriction-enzyme analysis and direct DNA sequencing of genomic PCR product to evaluate the AVPR2 gene in 11 unrelated affected males. Each patient has a different DNA sequence variation, and only one matches a previously reported mutation. Cosegregation of the variations with nephrogenic diabetes insipidus was demonstrated for two families, and a de novo mutation was documented in two additional cases. Carrier detection was accomplished in one family. All the variations predict frameshifts, truncations, or nonconservative amino acid substitutions in evolutionarily conserved positions in the V2 ADHR and related receptors. Of interest, a 28-bp deletion is found in one patient, while another, unrelated patient has a tandem duplication of the same 28-bp segment, suggesting that both resulted from the same unusual unequal crossing-over mechanism facilitated by 9-mer direct sequence repeats. Since the V2 ADHR is a member of the seven-transmembrane-domain, G-protein-coupled receptor superfamily, the loss-of-function mutations from this study and others provide important clues to the structure-function relationship of this and related receptors. Images Figure 1 Figure 2 Figure 3 PMID:7913579

  3. Nephrogenic fibrosing dermopathy: a comprehensive review for the dermatologist.

    PubMed

    Scheinfeld, Noah

    2006-01-01

    Nephrogenic fibrosing dermopathy (NFD) is an acquired, idiopathic, chronic, progressive eruption of the skin sometimes accompanied by systemic fibrosis that occurs in the context of renal failure. The age of patients with NFD ranges from 8 to 87 years at the time of onset, with a mean age of 46.4 years. Most cases have been reported in the US and Europe, but recently cases have also been reported in India. About 175 cases have been noted in a registry established for NFD patients. Even in the setting of renal disease, NFD still occurs rarely and its cause is unknown. Patients present with hard, indurated, sometimes peau d'orange plaques. They often show a distinctive physical appearance, with elbows and knees angled inward, and most patients complain of a loss of range of motion. Histology demonstrates thickened collagen bundles with surrounding clefts, mucin, and a proliferation of fibroblasts and elastic fibers, sometimes with reticular, dermal, large epithelioid or stellate spindle cells. Fibrosis of NFD can affect the internal organs and thus the term nephrogenic systemic fibrosis has been used by some analysts to describe this fibrosing process. The fibrosis of NFD appears to be due to the effects of a cell referred to as the circulating fibrocyte. Rare cases of partial-to-complete spontaneous resolution have been reported in the absence of specific therapy. Treatments yield inconsistent results and include restoration of renal function, extracorporeal photopheresis, photodynamic therapy, high-dose intravenous immunoglobulin, and other immunosuppressive therapies.

  4. [Perioperative management of a child with congenital nephrogenic diabetes insipidus].

    PubMed

    Mizushima, T; Kitamura, S; Kinouchi, K; Taniguchi, A; Fukumitsu, K

    2001-03-01

    The key point in perioperative management of a patient with congenital nephrogenic diabetes insipidus is fluid and electrolytes management. Since the urine of these patients consists mainly of solute free water, replacement fluids should be fluids which provide free water. A 2-year-old girl with congenital nephrogenic diabetes insipidus was scheduled for dental extraction. Her daily fluid intake was 10 liter. She had a history of recurrent fever, polyuria and polydipsia since 2 months of age. Her previous perioperative course for gastric volvulus at another hospital was complicated with postoperative hyponatremia and convulsion. A venous line was secured the day before surgery and 5% dextrose in water was infused at a rate of 12 ml.kg-1.hr-1. Intraoperative infusion was mainly with 5% dextrose in water combined with maintenance fluid. Five hours after surgery oral intake was started. Her intraoperative electrolytes levels were low (Na 133 mEq.l-1, K 2.8 mEq.l-1), but otherwise her perioperative course was uneventful.

  5. [Congenital nephrogenic diabetes insipidus: about a case report].

    PubMed

    Esselmani, Hicham; Yassine, Asmaa; Bouabdellah, Mounya; Benchekroun, Laila; Handor, Najat; Elalami, Sanae; Chabraoui, Layachi

    2013-01-01

    Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

  6. Adenomatous Metaplasia Arising in a Horse-Shoe Kidney - A Rare Entity.

    PubMed

    Kaur, Sukhpreet; Hasan, Shariq Ul

    2015-09-01

    Urinary adenomatous metaplasia (nephrogenic adenomas) is uncommon, benign, apparently metaplastic response of the urothelium to chronic inflammation, trauma, surgery, urolithiasis, long-term indwelling urethral catheterization, and immunosuppressive therapy instillation. Gross or microscopic hematuria and some irritable urinary tract symptoms are often observed. A diagnosis is primarily based on the histopathological examination. We are reporting this case because adenomatous metaplasia is very rarely reported in the kidney especially in a horse shoe kidney with a large renal stone and these lesions could be mistakenly diagnosed as malignancy. In our knowledge this is the very first case of its kind. An awareness of this entity is critical to prevent over-diagnosis of cancer and to avoid unnecessary treatment.

  7. [Hepatocellular nodular hyperplasias, adenomas and carcinomas].

    PubMed

    Altmann, H W

    1995-01-01

    Nodular hyperplasias ("hyperplasiomas") are new formations whose development as a required and regulated response can be traced either to compensatory reactions to the loss of cells (regeneration in a narrow sense) and to decreased cellular performance, or to primary growth impulses. Included in this group are: the "macroregenerative nodules" after extensive cell losses; solitary nodules of uncertain etiology; and the minute foci of "micronodular transformation" whose origin can be traced to a particular disturbance of the hepatic blood supply. The so-called "adenomatous hyperplasias" of the cirrhotic liver that have a tendency towards carcinomatous change are not included in this group and are perhaps better considered as "hyperplasiogenic adenomas". The so-called "focal nodular hyperplasia" too, it must be stressed, should be separated from the simple hyperplasias, for it is more closely related to the adenomas, but represents a new formation of limited growth potential. Morphologically it is conspicuously subdivided by multiple connective tissue bands and scars, but it is above all characterized by metaplastically derived neoductuli, and hence it is appropriately designated as a "combined nodule". Among the true uninodular adenomas there are several variants differing in their morphology,--the so-called "atypical" or "intermediate" forms, that can give rise to carcinomas. The hepatocellular carcinoma, that may arise in a variety of ways, presents multiple cytological and histological variants, but only the so-called "fibrolamellar carcinoma" presents also a clinical peculiarity. "Hepatoblastomas" differ from the common hepatocellular carcinomas by their origin in early childhood from immature early precursor cells and, in the later phases of life, from redifferentiated cells that can even give rise to mesenchymal elements. There is no evidence of the existence of particular pluripotential stem cells.

  8. Gadolinium contrast agent-induced CD163+ ferroportin+ osteogenic cells in nephrogenic systemic fibrosis.

    PubMed

    Swaminathan, Sundararaman; Bose, Chhanda; Shah, Sudhir V; Hall, Kimberly A; Hiatt, Kim M

    2013-09-01

    Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis is characterized by abnormal tissue repair: fibrosis and ectopic ossification. The mechanisms by which gadolinium could induce fibrosis and ossification are not known. We examined in vitro the effect of a gadolinium-based contrast agent on human peripheral blood mononuclear cells for phenotype and function relevant to the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow cytometry, real-time PCR, and osteogenic assays. We also examined tissues from patients with nephrogenic systemic fibrosis, using IHC to identify the presence of cells with phenotype induced by gadolinium. Gadolinium contrast induced differentiation of human peripheral blood mononuclear cells into a unique cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast transcription factors Runt-related transcription factor 2, and osterix, and show an osteogenic phenotype in in vitro assays. We show in vivo the presence of CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.

  9. Inherited secondary nephrogenic diabetes insipidus: concentrating on humans.

    PubMed

    Bockenhauer, D; Bichet, D G

    2013-04-15

    The study of human physiology is paramount to understanding disease and developing rational and targeted treatments. Conversely, the study of human disease can teach us a lot about physiology. Investigations into primary inherited nephrogenic diabetes insipidus (NDI) have contributed enormously to our understanding of the mechanisms of urinary concentration and identified the vasopressin receptor AVPR2, as well as the water channel aquaporin-2 (AQP2), as key players in water reabsorption in the collecting duct. Yet, there are also secondary forms of NDI, for instance as a complication of lithium treatment. The focus of this review is secondary NDI associated with inherited human diseases, such as Bartter syndrome or apparent mineralocorticoid excess. Currently, the underlying pathophysiology of this inherited secondary NDI is unclear, but there appears to be true AQP2 deficiency. To better understand the underlying mechanism(s), collaboration between clinical and experimental physiologists is essential to further investigate these observations in appropriate experimental models.

  10. A novel therapeutic effect of statins on nephrogenic diabetes insipidus.

    PubMed

    Bonfrate, Leonilde; Procino, Giuseppe; Wang, David Q-H; Svelto, Maria; Portincasa, Piero

    2015-02-01

    Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional 'pleiotropic' effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed.

  11. Pleomorphic adenoma of an accessory submandibular salivary gland: a rare entity.

    PubMed

    Desai, Rajiv S; Meshram, Deepashree; Jangam, Sagar S; Singh, Jatinder S

    2015-10-01

    An accessory submandibular salivary gland is a rare anatomical variant, and a tumour within one is even rarer. We describe a 54-year-old man who presented with a slowly-enlarging mass in the right submandibular region which on magnetic resonance imaging (MRI) seemed to be close to, but not arising from, the right submandibular salivary gland. This was found to be a benign pleomorphic adenoma arising from an accessory submandibular salivary gland. To our knowledge it is only the second report of a pleomorphic adenoma that developed within an accessory submandibular salivary gland.

  12. Giant pleomorphic adenoma of the parotid gland: an unusual case presentation and literature review.

    PubMed

    Tarsitano, A; Pizzigallo, A; Giorgini, F; Marchetti, C

    2015-10-01

    Pleomorphic adenoma is the most common type of all salivary gland tumours. Although uncommon, cases of giant pleomorphic adenomas have been described in the medical literature, the majority involving the parotid gland. This paper describes an unusual case of a giant adenoma arising in the parotid gland. The patient underwent surgical resection of the giant tumour, which was one of the largest pleomorphic adenoma reported in recent literature. This case has prompted us to evaluate the behaviour of those benign tumours, which suggested that aesthetic and social morbidity is sufficient to justify, when possible, early tumour excision, despite the relatively low risk of malignant transformation. Management of this unusual tumour is discussed, and the literature on giant parotid tumours is reviewed.

  13. Basal cell adenoma of nasal septum: report of a case and review of literature.

    PubMed

    Wang, Qinying; Chen, Haihong; Wang, Shenqing

    2015-01-01

    Basal cell adenoma is an uncommon benign salivary gland neoplasm, presenting isomorphic basaloid cells with a prominent basal cell layer. Basal cell adenoma arising from the nasal septum is exceptionally rare. Reports on positron emission tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose (18FDG-PET) imaging for basal cell adenoma are limited. Here, we present the case of a 49-year-old man who had the symptoms of intermittent repeated bleeding from the left nose for half a year. 18FDG-PET scanning showed increased accumulation of 18FDG with its characteristic benign pathology has a potential to malignancy. After removal of the mass, the patient became symptom free. Pathology showed basal cell adenoma. The evidence of active and growing cells was present in the specimen.

  14. Villous adenoma of the distal appendix.

    PubMed

    Taylor, J V; Thomas, M G; Kelly, S; Sutton, R

    1997-04-01

    Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

  15. [Thyrotropin-secreting pituitary adenomas].

    PubMed

    Caron, Philippe

    2009-01-01

    TSH-secreting pituitary adenomas represent 0.5 to 1% of all pituitary adenomas. They are recognized with increasing frequency due to the measurement of TSH level in patients with hyperthyroidism, the ultra sensitive TSH assays and the improvement in pituitary imaging. Patients present mild or moderate signs of hyperthyroidism. Hormonal evaluation shows increased free thyroid hormone concentration with detectable, normal or increased serum TSH level, raising the differential diagnosis with pituitary resistance to thyroid hormone syndrome. Magnetic resonance imaging reveals pituitary adenomas in most patients. Transphenoidal surgery remains the treatment of choice in patients with TSH-secreting pituitary microadenomas, while long-acting somatostatin analogs seem to be an alternative medical treatment to surgery in patients with macroadenomas or invasive pituitary tumors.

  16. Expression of p21 is dependent on or independent of p53 in carcinoma ex pleomorphic adenoma (undifferentiated and adenocarcinoma types).

    PubMed

    Tarakji, Bassel; Baroudi, Kusai; Hanouneh, Salah; Nassani, Mohammad Z; Alotaibi, Abdullah M; Kharma, M Yaser; Azzeghaiby, Saleh N

    2012-12-01

    Our study is aimed to characterize alteration in the immunohistochemical expression of p21 and p53 in normal tissue of the salivary gland surrounding carcinoma arising in pleomorphic adenoma, and the tumor cells of carcinoma arising in pleomorphic adenoma as well as to identify whether the induction of expression p21 is dependent on or independent of p53 in carcinoma arising in pleomorphic adenoma. A selected series of 27 cases of carcinoma ex pleomorphic adenoma (undifferentiated and adenocarcinoma types) was examined. The results showed that p21 and p53 expression was negative in the most components of normal tissue of the salivary gland surrounding carcinoma arising in pleomorphic adenoma. p21 was strongly expressed in carcinoma cells in 9 (33.3%) cases out of 27. p53 was strongly expressed in carcinoma cells in 10 (37%) cases out of 27. Also a co-expression of p21 and p53 showed negative nuclear staining in 9 cases, while 8 cases expressed positive staining. p21 expressed negative nuclear staining in 4 cases but p53 expressed positive staining in the same cases. p21 expressed positive nuclear staining in 6 cases but p53 expressed negative nuclear staining in the same cases. Our data suggest that inactivation of p53 and p21 may play an important role in the evolution of carcinoma ex pleomorphic adenoma. Also p21 behaves as dependent on or independent of p53 in carcinoma arising in pleomorphic adenoma.

  17. V2R mutations and nephrogenic diabetes insipidus.

    PubMed

    Bichet, Daniel G

    2009-01-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. Thus, the broadest definition of the term NDI embraces any antidiuretic hormone-resistant urinary-concentrating defect, including medullary disease with low interstitial osmolality, renal failure, and osmotic diuresis. About 90% of patients with congenital NDI are males with X-linked recessive NDI (OMIM 304800)(1) and have mutations in the AVP receptor 2 (AVPR2) gene that codes for the vasopressin V(2) receptor; the gene is located in chromosome region Xq28. In about 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance (OMIM 222000 and 125800)(1). Mutations have been identified in the aquaporin-2 gene (AQP2, OMIM 107777)(1), which is located in chromosome region 12q13 and codes for the vasopressin-sensitive water channel. NDI is clinically distinguishable from neurohypophyseal diabetes insipidus (OMIM 125700(1); also referred to as central or neurogenic diabetes insipidus) by a lack of response to exogenous AVP and by plasma levels of AVP that rise normally with increase in plasma osmolality. Hereditary neurohypophyseal diabetes insipidus is secondary to mutations in the gene encoding AVP (OMIM 192340)(1). Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM

  18. Pedunculated carcinoma ex pleomorphic adenoma of the nasal cavity

    PubMed Central

    Liao, Po-Wu; Chen, Yen-Lin; Chen, Jeng-Wen

    2016-01-01

    Abstract Background: A carcinoma ex pleomorphic adenoma (CXPA) is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma. The parotid gland is the most common location of CXPAs. Minor salivary gland CXPAs of the nasal cavity are exceedingly rare, with only 6 documented in the literature. Methods and Result: We present a 7th case: an unusual pedunculated intranasal CXPA, which had a favorable outcome after a wide endoscopic excision and the longest follow-up period reported to date. The clinical features, immunohistochemical characteristics, treatment choices, and disease outcomes of the intranasal CXPAs reported in previous studies are also reviewed. Conclusion: This case demonstrates the importance of considering the possibility of CXPA in the differential diagnosis of minor salivary gland malignancies in the nasal cavity. PMID:27684860

  19. Tubulovillous Adenoma in the Bladder in a Dual Pancreas-Kidney Transplant Patient

    PubMed Central

    Remondini, Taylor; Van Zyl, Stephan; Bismar, Tarek A.; Yilmaz, Serdar

    2017-01-01

    Abstract Background: A rare report of a tubulovillous adenoma arising in the setting of a dual pancreas-kidney transplant patient. Case Presentation: This adenoma was discovered in a 60-year-old male with a dual pancreas-kidney transplant that presented with urinary retention and gross hematuria. Management of this patient required both transurethral resection of the tumor as well as a laparotomy after recurrence. Follow-up with cystoscopy has shown no further recurrence of the tumor. Conclusion: This case adds to the few cases documented of adenomas arising in bladders augmented with gastrointestinal tract tissue. The tumor may reflect growth from donor duodenal graft tissue, however, the metaplasia of urothelial tissue cannot be fully ruled out. Based on this case, our understanding of these rare tumors and their clinical course is deepened. PMID:28265591

  20. An intracapsular carcinoma ex pleomorphic adenoma with lung metastases composed exclusively of benign elements: histological evidence of a continuum between metastasizing pleomorphic adenoma and carcinoma ex pleomorphic adenoma.

    PubMed

    Weissferdt, Annikka; Langman, Gerald

    2010-07-15

    Malignant mixed tumors of the salivary glands, encompassing carcinoma ex pleomorphic adenoma (ca ex PA), carcinosarcoma and metastasizing pleomorphic adenoma (mPA), are rare neoplasms. Ca ex PA arises in a pre-existing pleomorphic adenoma (PA). When the malignant component does not breach the capsule of the parent PA, the lesion is termed intracapsular ca ex PA, a neoplasm which is thought to have no metastatic potential. Metastatic deposits of ca ex PA are composed exclusively of malignant elements or mixed benign and malignant components. We describe the case of a 62-year-old female with an intracapsular ca ex PA of the buccal mucosa with subsequent metastases to the lung. The metastatic deposits resembled benign PA with no histological evidence of malignancy. This pattern of spread is described with mPA, an entity that caused controversy in the past regarding its exact classification as a benign or malignant tumor. The possibility that ca ex PA originates from a mPA, with intracapsular ca ex PA representing an intermediate lesion in a histological continuum, is discussed.

  1. Clinical characteristics of eight patients with congenital nephrogenic diabetes insipidus.

    PubMed

    Mizuno, Haruo; Sugiyama, Yukari; Ohro, Yoichiro; Imamine, Hiroki; Kobayashi, Masanori; Sasaki, Sei; Uchida, Sinichi; Togari, Hajime

    2004-06-01

    Congenital nephrogenic diabetes insipidus (NDI) is characterized by the insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge of this disease is based largely on case reports. For this study, we investigated the clinical findings of eight patients in terms of age at onset, age at diagnosis, main complaint, results of physical examination, the diagnosis, the effect of treatment, kidney function, and presence or absence of gene defects. The main complaints of all eight cases at initial examination were unknown fever, failure to thrive, and short stature. Polyuria and polydipsia are not always the chief complaints with congenital NDI. In one case, diabetes insipidus could be diagnosed based only on the results of a 5% hypertonic saline test. In six cases, we found abnormalities in the V2 receptor gene. Initially, trichlormethiazide therapy was shown to have a significant effect on polyuria; however, this effect decreased over time. In one patient with partial NDI, the addition of trichlormethiazide twice a day to 1-desamino-8-D-arginine vasopressin increased urine osmolality in the morning and caused nocturia to disappear. Results of 99mTc-diethylenetriamine pentaacetic acid kidney scintigraphy revealed a slight decrease in glomerular filtration rate in three patients. No patient experienced serious renal dysfunction.

  2. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus.

    PubMed

    Bockenhauer, Detlef; Bichet, Daniel G

    2015-10-01

    Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.

  3. Transcranial surgery for pituitary adenomas.

    PubMed

    Youssef, A Samy; Agazzi, Siviero; van Loveren, Harry R

    2005-07-01

    Although the transsphenoidal approach is the preferred approach to the vast majority of pituitary tumors with or without suprasellar extension, the transcranial approach remains a vital part of the neurosurgical armamentarium for 1 to 4% of these tumors. The transcranial approach is effective when resection becomes necessary for a portion of a pituitary macroadenoma that is judged to be inaccessible from the transsphenoidal route because of isolation by a narrow waist at the diaphragma sellae, containment within the cavernous sinus lateral to the carotid artery, projection anteriorly onto the planum sphenoidale, or projection laterally into the middle fossa. The application of a transcranial approach in these circumstances may still be mitigated by response to prolactin inhibition of prolactinomas, the frequent lack of necessity to remove asymptomatic nonsecretory adenomas from the cavernous sinus, and the lack of evidence that sustained chemical cures can be reliably achieved by removal of secretory adenomas (adrenocorticotropic hormone, growth hormone) from the cavernous sinus. Cranial base surgical techniques have refined the surgical approach to pituitary adenomas but have had less effect on actual surgical indications than anticipated. Because application of the transcranial approach to pituitary adenomas is and should be rare in clinical practice, it is useful to standardize the technique to a default mode with which the surgical team is most experienced and, therefore, most comfortable. Our default mode for transcranial pituitary surgery is the frontotemporal-orbitozygomatic approach.

  4. Middle ear adenoma is an amphicrine tumor: why call it adenoma?

    PubMed

    Ketabchi, S; Massi, D; Franchi, A; Vannucchi, P; Santucci, M

    2001-01-01

    Middle ear adenoma (MEA) is a rare tumor postulated to take origin from the lining epithelium of the middle ear cavity. The authors report on a case of MEA arising in a 53-year old woman suffering from a sensation of fullness in her left ear, otalgia, and light left-sided hearing loss. Histopathologically, the lesion was composed of cuboidal and polygonal cells displaying a trabecular, tubulo-glandular, and solid pattern of growth. Immunohistochemically, neoplastic cells diffusely stained with anti-vimentin antibodies and were focally positive for chromogranin A, neuron-specific enolase, lysozyme, and cytokeratins AE1/AE3. The majority of tumor cells showed weak and diffuse staining with both anti-PP and anti-ACTH antibodies and intense positivity with anti-glucagon and anti Leu-7 antibodies. Ultrastructural investigation revealed both mucinous-glandular and neuroendocrine differentiation. The authors suggest that the appropriate terminology would be adeno-carcinoid or amphicrine tumor of the middle ear rather than "adenoma," a term that does not reflect its dual nature.

  5. An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland.

    PubMed

    Rossi, Luigi; Giordani, Erika; Fontana, Antonella; Di Cristofano, Claudio; Cavallaro, Giuseppe; Bagni, Oreste; Filippi, Luca; Bianchi, Loredana; Rinaldi, Giulia; Congedi, Francesca Perrone; Papa, Anselmo; Caruso, Davide; Verrico, Monica; Silecchia, Gianfranco; Tomao, Silverio

    2014-01-23

    Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

  6. Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer

    PubMed Central

    Calderwood, Audrey H; Lasser, Karen E; Roy, Hemant K

    2016-01-01

    AIM To review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODS We performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTS Our search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSION Data on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification. PMID:28035253

  7. Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.

    PubMed

    Kissiedu, Juliana O; Prayson, Richard A

    2016-02-01

    We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.

  8. Metformin improves urine concentration in rodents with nephrogenic diabetes insipidus

    PubMed Central

    Efe, Orhan; Klein, Janet D.; LaRocque, Lauren M.; Ren, Huiwen; Sands, Jeff M.

    2016-01-01

    Urine concentration is regulated by vasopressin. Congenital nephrogenic diabetes insipidus (NDI) is caused by vasopressin type 2 receptor (V2R) mutations. We studied whether metformin could improve urine concentration in rodent models of congenital NDI by stimulating AMPK. To block the V2R in rats, tolvaptan (10 mg/kg/d) was given by oral gavage with or without metformin (800 mg/kg/d). Control rats received vehicle with or without metformin. Tamoxifen-induced V2R KO mice were given metformin (600 mg/kg) or vehicle twice daily. Urine osmolality in tolvaptan-treated rats (1,303 ± 126 mOsM) was restored to control levels by metformin (2,335 ± 273 mOsM) within 3 days and was sustained for up to 10 days. Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation. Outer medullary Na+-K+-2Cl– cotransporter 2 (NKCC2) abundance increased (117%) with AMPK stimulation in control rats but not in V2R-blocked rats. Metformin increased V2R KO mouse urine osmolality within 3 hours, and the increase persisted for up to 12 hours. Metformin increased AQP2 in the V2R KO mice similar to the tolvaptan-treated rats. These results indicate that AMPK activators, such as metformin, might provide a promising treatment for congenital NDI. PMID:27478876

  9. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    de Groot, Theun; Sinke, Anne P; Kortenoeven, Marleen L A; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F; Deen, Peter M T

    2016-07-01

    To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.

  10. Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology.

    PubMed

    Singh, Kanika; Agarwal, Charu; Pujani, Mukta; Verma, Pragya; Chauhan, Varsha

    2017-03-06

    Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 βE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017. © 2017 Wiley Periodicals, Inc.

  11. Octreotide Uptake in Parathyroid Adenoma

    PubMed Central

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  12. Tuberous sclerosis and parathyroid adenoma.

    PubMed Central

    Mortensen, L S; Rungby, J

    1991-01-01

    Very little is known about the pathogenesis of tuberous sclerosis. Over the past 10 years, however, increasing numbers of reports on adenomatous diseases in association with tuberous sclerosis have been published. A case of hypercalcaemia and parathyroid adenoma in association with tuberous sclerosis is presented, of which there has been one such report published previously. This association might be another manifestation of this complex disease: it is therefore recommended that plasma calcium concentrations should be measured in such patients. PMID:1752991

  13. Fibrosarcoma complicating irradiated pituitary adenoma

    SciTech Connect

    Shi, T.; Farrell, M.A.; Kaufmann, J.C.

    1984-09-01

    Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

  14. Pleomorphic adenoma of the upper lip.

    PubMed

    Küçük, Ulkü; Tan, Serdar

    2011-01-01

    Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotis followed by the submandibular glands. Its localization in the minor salivary glands is mostly reported in the palate. Few publications report pleomorphic adenoma cases located in the lip. We present a 35-year-old male patient with a pleomorphic adenoma located in the upper lip.

  15. Giant Pleomorphic Adenoma of the Parotid Gland.

    PubMed

    Sajid, Muhammad; Rehman, Sajid; Misbah, Junaid

    2015-10-01

    Salivary gland tumours are a relatively rare entity. Pleomorphic adenoma is the most common amongst these, comprising 60 - 70% of all parotid tumours. Pleomorphic adenomas are benign and tend to increase in size slowly. Here we are presenting a case of giant pleomorphic adenoma of the parotid, being the largest in size to be excised in Pakistan in recorded literature measuring 24 x 22 x 12 cm and weighing 1.8 kgs. Superficial parotidectomy was done with an excellent cosmetic outcome.

  16. Pleomorphic adenoma of the soft palate: major tumor in a minor gland.

    PubMed

    Hmidi, Mounir; Aatifi, Hicham; Boukhari, Ali; Zalagh, Mohammed; Messary, Abdelhamid

    2015-01-01

    Salivary gland tumors are a relatively rare and morphologically diverse group of lesions. Pleomorphic adenoma is a benign tumor of the salivary gland that consists of a combination of epithelial and mesenchymal elements. The tumor most commonly arises from the parotid (60-70%) or submandibular glands. It develops less frequently in a minor salivary gland, presenting as an intraoral mass depend on the soft palate. We describe a case of benign pleomorphic adenoma of soft palate in a 45 year old female with computed tomography and histopathological findings. This patient presented in ENT department with history of gradually increasing mass lesion in the palatal region over a period of few months.

  17. Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

    ClinicalTrials.gov

    2017-02-17

    Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia

  18. Epithelioid schwannoma of the facial nerve masquerading as pleomorphic adenoma: a case report.

    PubMed

    Ciau, Nancy; Eisele, David W; van Zante, Annemieke

    2014-01-01

    Schwannomas arising in the parotid gland or peri-parotid region is frequently misdiagnosed as pleomorphic adenoma on cytologic preparations. The epithelioid variant of schwannoma is particularly susceptible to misdiagnosis because this neoplasm typically has epithelioid and spindled cells, which are associated with fibrillar stroma and mimic the epithelial, myoepithelial, and stromal components of a pleomorphic adenoma. Preoperative diagnosis of schwannoma is critical in order to plan appropriate management and to avoid inadvertent injury to the associated nerve during surgical resection. Thus, awareness of the distinct clinical, radiological, and cytomorphological features of schwannoma is important in order to guide clinical management. If the cytomorphological features are equivocal, immunohistochemical staining may provide a valuable alternative for distinguishing between pleomorphic adenoma and schwannoma.

  19. Arise the systems physician.

    PubMed

    Scott, I; Phelps, G; Dalton, S

    2014-12-01

    Healthcare in Australia faces significant challenges. Variations in care, suboptimal safety and reliability, fragmentation of care and unsustainable cost increases are compounded by substantial overuse and underuse of clinical interventions. These problems arise not from intentional actions of individual clinicians, but from deficiencies in the design, operations and governance of systems of care. Physicians play an important role in optimising systems of care and, in doing so, must rely on enhanced skills in a range of domains. These include: how to evaluate and improve quality and safety of clinical processes; analyse and interpret clinical and administrative data in ways that can be used to enhance care delivery; build and lead cohesive multidisciplinary teams capable of solving operational defects and inefficient workarounds; and implement new and effective innovations in clinical service delivery. While clinical skills are essential in individual patient care, skills that improve systems of care targeting whole patient populations will become increasingly desirable and recognised as core skills.

  20. Liver cell adenoma and liver cell adenomatosis

    PubMed Central

    Barthelmes, Ludger

    2005-01-01

    During the last three decades liver cell adenoma and liver cell adenomatosis have emerged as new clinical entities in hepato-logical practice due to the widespread use of oral contraceptives and increased imaging of the liver. On review of published series there is evidence that 10% of liver cell adenomas progress to hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision biopsy, and the preferred treatment modality is resection of the liver cell adenoma to prevent bleeding and malignant transformation. In liver cell adenomatosis, the association with oral contraceptive use is not as high as in solitary liver cell adenomas. The risk of malignant transformation is not increased compared with solitary liver cell adenomas. Treatment consists of close monitoring and imaging, resection of superficially located, large (>4 cm) or growing liver cell adenomas. Liver transplantation is the last resort in case of substantive concern about malignant transformation or for large, painful adenomas in liver cell adenomatosis after treatment attempts by liver resection. PMID:18333188

  1. Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary.

    PubMed

    Occhi, G; Albiger, N; Berlucchi, S; Gardiman, M; Scanarini, M; Scienza, R; Fassina, A; Mantero, F; Scaroni, C

    2007-07-01

    Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.

  2. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013 ... AB, Korbonits M. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic ...

  3. Unusual Presentation of Lacrimal Gland Pleomorphic Adenoma.

    PubMed

    Pokhrel, S M; Badu, B P; Lavaju, P; Shrestha, B G; Pant, A R; Agarwal, M

    2014-01-01

    The pleomorphic adenoma of lacrimal gland presents as a painless, progressive, slowly growing supero-temporal swelling with variable proptosis. This tumor is usually found in adults and extremely rare in teenage. We report a case of a 15-year-old boy with pleomorphic adenoma of lacrimal gland which mimicked pseudotumor of orbit due to its presentation as an orbital inflammatory disease and the age distribution. Neuroimaging also suggested pseudotumor and oral steroid was started. But, there was no improvement on steroids and ultrasound guided Fine Needle Aspiration Cytology (FNAC) was performed which suggested Pleomorphic adenoma of the lacrimal gland. En-bloc excision of the mass through antero-lateral orbitotomy was done with satisfactory final outcome The histopathological evaluation was consistent with pleomorphic adenoma of the lacrimal gland.

  4. Cushing's disease due to a giant pituitary adenoma in early infancy: CT and MRI features.

    PubMed

    Maeder, P; Gudinchet, F; Rillet, B; Theintz, G; Meuli, R

    1996-01-01

    We report the case of a 12-month-old girl presenting with diabetes insipidus and Cushing s disease. Brain magnetic resonance imaging (MRI) demonstrated a large tumour arising from the sella turcica, extending up to the foramen of Monro and invading the cavernous sinuses. Surgery was performed to remove the suprasellar part of the tumour, and histology revealed an adrenocorticotrophin (ACTH) secreting pituitary adenoma. This entity is very rare in this age group and the MRI features have not previously been described.

  5. [Pleomorphic adenoma with bilateral pulmonary metastasis].

    PubMed

    De Kerangal, X; Poirrier, P; Soulard, R; Dot, J M; Ségneuric, J B; L'Her, P; Jancovici, R; Saint-Blancart, P

    2001-11-01

    We report a new case of pleomorphous adenoma of the submaxillary glands with multiple lung metastases. Histological proof was obtained on the thoracoscopic surgical specimen. Clinically, this benign tumor presents as a malignant tumor. Diagnosis has been a subject of debate; surgical resection is indicated. Diagnosis is achieved by elimination in a patient with one or several nodules occurring in a context of recurrent pleomorphous adenoma.

  6. Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

    PubMed

    de Brito, Beatriz Samara; Giovanelli, Natália; Egal, Erika Said; Sánchez-Romero, Celeste; Nascimento, Juliana de Souza do; Martins, Antonio Santos; Tincani, Álfio José; Del Negro, André; Gondak, Rogério de Oliveira; Almeida, Oslei Paes de; Kowalski, Luiz Paulo; Altemani, Albina; Mariano, Fernanda Viviane

    2016-11-01

    PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.

  7. Pituitary lymphoma developing within pituitary adenoma.

    PubMed

    Morita, Ken; Nakamura, Fumihiko; Kamikubo, Yasuhiko; Mizuno, Naoaki; Miyauchi, Masashi; Yamamoto, Go; Nannya, Yasuhito; Ichikawa, Motoshi; Kurokawa, Mineo

    2012-06-01

    Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.

  8. Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening side effect of chronic lithium therapy.

    PubMed

    Sze, L; Ulrich, B; Brändle, M

    2006-11-01

    Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic diabetes insipidus is the most frequently encountered complication, but often remains unrecognised because of the rather benign symptoms. We present a patient with long-term lithium therapy who developed life-threatening hypernatraemia due to insufficient oral fluid intake after elective spinal surgery. Careful daily substitution of up to 25 l of hypotonic fluids led to full recovery within 9 days. Nephrogenic diabetes insipidus should always be considered in lithium-treated patients undergoing elective surgery in order to avoid severe hypernatraemia.

  9. ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation

    PubMed Central

    El-Zammar, Diala; Akagami, Ryojo

    2011-01-01

    Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870

  10. Carcinoma ex pleomorphic adenoma in the oral cavity: a huge oral cavity mass with neck metastasis.

    PubMed

    Hong, Hyun Jun; Byeon, Hyung Kwon; Bae, Seong Hoon; Park, Ah Young; Choi, Eun Chang; Choi, Hong-Shik

    2013-11-01

    Carcinoma ex pleomorphic adenoma (CEPA) is a rare, aggressive, poorly understood malignancy. In CEPA, an epithelial malignancy develops in association with a primary or recurrent benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma is very difficult to identify before surgery because the clinical presentation of many cases is similar to that of pleomorphic adenomas. The risk for malignancy increases with the duration of a mixed tumor. Treatment of CEPA must be individualized on the basis of the tumor location, involvement of adjacent structures, histologic subtype, and grade. The authors recently experienced a case of CEPA arising in the oral cavity with neck metastasis. The patient was a 70-year-old man presenting a huge mass that was present for 20 years and that slowly grew on the left side of the neck. We treated it with a total excision with wide margins and neck dissection. There was no recurrence during the follow-up period of 5 years up until now. We present a case of an unusually huge CEPA in the oral cavity.

  11. DNA–Methylome Analysis of Mouse Intestinal Adenoma Identifies a Tumour-Specific Signature That Is Partly Conserved in Human Colon Cancer

    PubMed Central

    Grimm, Christina; Chavez, Lukas; Vilardell, Mireia; Farrall, Alexandra L.; Tierling, Sascha; Böhm, Julia W.; Grote, Phillip; Lienhard, Matthias; Dietrich, Jörn; Timmermann, Bernd; Walter, Jörn; Schweiger, Michal R.; Lehrach, Hans; Herwig, Ralf; Herrmann, Bernhard G.; Morkel, Markus

    2013-01-01

    Aberrant CpG methylation is a universal epigenetic trait of cancer cell genomes. However, human cancer samples or cell lines preclude the investigation of epigenetic changes occurring early during tumour development. Here, we have used MeDIP-seq to analyse the DNA methylome of APCMin adenoma as a model for intestinal cancer initiation, and we present a list of more than 13,000 recurring differentially methylated regions (DMRs) characterizing intestinal adenoma of the mouse. We show that Polycomb Repressive Complex (PRC) targets are strongly enriched among hypermethylated DMRs, and several PRC2 components and DNA methyltransferases were up-regulated in adenoma. We further demonstrate by bisulfite pyrosequencing of purified cell populations that the DMR signature arises de novo in adenoma cells rather than by expansion of a pre-existing pattern in intestinal stem cells or undifferentiated crypt cells. We found that epigenetic silencing of tumour suppressors, which occurs frequently in colon cancer, was rare in adenoma. Quite strikingly, we identified a core set of DMRs, which is conserved between mouse adenoma and human colon cancer, thus possibly revealing a global panel of epigenetically modified genes for intestinal tumours. Our data allow a distinction between early conserved epigenetic alterations occurring in intestinal adenoma and late stochastic events promoting colon cancer progression, and may facilitate the selection of more specific clinical epigenetic biomarkers. PMID:23408899

  12. Giant serous microcystic pancreas adenoma.

    PubMed

    Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa

    2012-10-10

    Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.

  13. Nephrogenic systemic fibrosis in a patient with renal failure demonstrating a "reverse superscan" on bone scintigraphy.

    PubMed

    Khor, Lih Kin; Tan, Kong Bing; Loi, Hoi Yin; Lu, Suat-Jin

    2013-03-01

    Nephrogenic systemic fibrosis (NSF) has been linked to utilization of gadolinium-based contrast agents in patients with renal impairment. We present a 19-year-old female patient with end-stage renal failure presenting with joint pains and subcutaneous nodules. She had a prior gadolinium-enhanced magnetic resonance angiography when she was 14 years old. Clinical findings revealed firm subcutaneous nodules in both thighs. Whole-body bone scan demonstrates tracer uptake predominantly in the soft tissues and muscles of the extremities with minimal bony uptake. Incisional biopsy of the left thigh nodule revealed features of NSF with a total pathological score of 4, highly consistent with NSF.

  14. Response to low dose indomethacin in two children with nephrogenic diabetes insipidus.

    PubMed

    Dayal, Devi; Verma Attri, Savita; Kumar Bhalla, Anil; Kumar, Rakesh

    2015-01-01

    Two children with nephrogenic diabetes insipidus (NDI) were treated with oral indomethacin (0.75-1.2 mg/kg/day) three times a day for a mean duration of 3 yrs. Remission occurred in both patients in terms of achieving a normal fluid balance and body growth and the drug was withdrawn in one patient after 2 yrs. The treatment was well tolerated and no side effects were noted. The mean duration of follow-up was 6.5 yrs. These long-term observations of a favourable response to low dose indomethacin in 2 children with NDI need to be tested on larger number of patients.

  15. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  16. Association of craniopharyngioma and pituitary adenoma.

    PubMed

    Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia

    2013-08-01

    Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

  17. Advanced endoscopic imaging to improve adenoma detection

    PubMed Central

    Neumann, Helmut; Nägel, Andreas; Buda, Andrea

    2015-01-01

    Advanced endoscopic imaging is revolutionizing our way on how to diagnose and treat colorectal lesions. Within recent years a variety of modern endoscopic imaging techniques was introduced to improve adenoma detection rates. Those include high-definition imaging, dye-less chromoendoscopy techniques and novel, highly flexible endoscopes, some of them equipped with balloons or multiple lenses in order to improve adenoma detection rates. In this review we will focus on the newest developments in the field of colonoscopic imaging to improve adenoma detection rates. Described techniques include high-definition imaging, optical chromoendoscopy techniques, virtual chromoendoscopy techniques, the Third Eye Retroscope and other retroviewing devices, the G-EYE endoscope and the Full Spectrum Endoscopy-system. PMID:25789092

  18. Choroid plexus acinar adenoma: a case report.

    PubMed

    Rembao-Bojórquez, Daniel; Vega, Rosalba; Bermúdez-Maldonado, Luis; Gutiérrez, Ramón; Salinas, Citlaltepetl; Tena-Suck, Martha

    2007-06-01

    Mucus-secreting adenomas or acinar adenoma of the choroid plexus are very rare. We report the case of a 79-year-old male with a 3-year history of occipital headaches with vomiting, ataxia and cerebellar signs. He was first seen due to difficulty while walking. He was admitted to the hospital with significant tumor expansion and clinical deterioration. CT and MRI revealed obstructive hydrocephalus secondary to a large fourth ventricular cyst mass, which enhanced markedly on contrast administration. Pathological findings were consistent with an acinar choroid plexus adenoma. The tumor was attached to the ependymal lining and was strongly adhered to the walls and floor of the IV ventricle. Post-operative bleeding complicated partial removal of this tumor. The patient died 6 h after surgery.

  19. TSH-secreting adenoma improved with cabergoline.

    PubMed

    Mouton, F; Faivre-Defrance, F; Cortet-Rudelli, C; Assaker, R; Soto-Ares, G; Defoort-Dhellemmes, S; Blond, S; Wemeau, J-L; Vantyghem, M-C

    2008-06-01

    TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.

  20. Preoperative volume determination for pituitary adenoma

    NASA Astrophysics Data System (ADS)

    Zukic, Dženan; Egger, Jan; Bauer, Miriam H. A.; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher

    2011-03-01

    The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92%+/-7.24%. A manual segmentation took about four minutes and our algorithm required about one second.

  1. [Pleomorphic adenoma causing a peritonsillar abscess].

    PubMed

    Glazer, Daniel Victor; Rømeling, Frans

    2014-12-22

    Pleomorphic adenoma located in the soft palate is extremely rare. We report a 42-year-old woman, who presented to the ear nose & throat department with a mucosal swelling of the right soft palate mimicking a peritonsillar abscess. Drainage was attempted several times without significant results. Emergency tonsillectomy was carried out, which showed a tumour intraorally beside the right tonsil. The tumour and the tonsil were radically excised. Histological analysis of the tumour revealed a pleomorphic adenoma. At three-month follow-up the patient was doing well and MRI scan revealed a residual tumour of 6 mm.

  2. The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas.

    PubMed

    Heliövaara, Elina; Raitila, Anniina; Launonen, Virpi; Paetau, Anders; Arola, Johanna; Lehtonen, Heli; Sane, Timo; Weil, Robert J; Vierimaa, Outi; Salmela, Pasi; Tuppurainen, Karoliina; Mäkinen, Markus; Aaltonen, Lauri A; Karhu, Auli

    2009-12-01

    Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AIPmut-) pituitary adenomas by immunohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor 1-alpha were examined in 14 AIPmut+ and 53 AIPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed in AIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, HEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor 1-alpha, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling.

  3. Value of Renal Biopsy in Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.

    PubMed

    Joyce, Emily; Ho, Jacqueline; El-Gharbawy, Areeg; Salgado, Cláudia M; Ranganathan, Sarangarajan; Reyes-Múgica, Miguel

    2017-01-01

    Cystinosis is the most common cause of inherited renal Fanconi syndrome in young children, and typically presents with laboratory findings of a proximal tubulopathy and corneal crystals by one year of age. We describe here renal biopsy findings in a 20-month-old patient with an atypical presentation of distal renal tubular acidosis, diabetes insipidus, and the absence of corneal crystals. Although renal biopsy is usually not necessary to establish the diagnosis of cystinosis, when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. A 20-month-old boy presented with failure to thrive, polyuria, polydipsia, and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency, and nephrogenic diabetes insipidus. His initial ophthalmologic examination did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance, and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.

  4. Evolutionary Influenced Interaction Pattern as Indicator for the Investigation of Natural Variants Causing Nephrogenic Diabetes Insipidus.

    PubMed

    Grunert, Steffen; Labudde, Dirk

    2015-01-01

    The importance of short membrane sequence motifs has been shown in many works and emphasizes the related sequence motif analysis. Together with specific transmembrane helix-helix interactions, the analysis of interacting sequence parts is helpful for understanding the process during membrane protein folding and in retaining the three-dimensional fold. Here we present a simple high-throughput analysis method for deriving mutational information of interacting sequence parts. Applied on aquaporin water channel proteins, our approach supports the analysis of mutational variants within different interacting subsequences and finally the investigation of natural variants which cause diseases like, for example, nephrogenic diabetes insipidus. In this work we demonstrate a simple method for massive membrane protein data analysis. As shown, the presented in silico analyses provide information about interacting sequence parts which are constrained by protein evolution. We present a simple graphical visualization medium for the representation of evolutionary influenced interaction pattern pairs (EIPPs) adapted to mutagen investigations of aquaporin-2, a protein whose mutants are involved in the rare endocrine disorder known as nephrogenic diabetes insipidus, and membrane proteins in general. Furthermore, we present a new method to derive new evolutionary variations within EIPPs which can be used for further mutagen laboratory investigations.

  5. The Value Of Renal Biopsy In Diagnosing Infantile Nephropathic Cystinosis Associated With Secondary Nephrogenic Diabetes Insipidus.

    PubMed

    Joyce, Emily; Ho, Jacqueline; El-Gharbawy, Areeg; Salgado, Cláudia M; Ranganathan, Sarangarajan; Reyes-Múgica, Miguel

    2015-11-18

    Cystinosis is a rare autosomal recessive disorder and the most common cause of inherited renal Fanconi syndrome in young children. Renal biopsy is usually not necessary to establish the diagnosis, but when the patient presents with atypical signs and symptoms, a renal biopsy may be extremely valuable. We describe here renal biopsy findings in a patient with cystinosis. A 20-month-old male presented with failure to thrive, polyuria, polydipsia and rickets. He initially showed evidence of a renal tubular acidosis, mild renal insufficiency and nephrogenic diabetes insipidus. His initial ophthalmologic exam did not demonstrate corneal crystals. His subsequent workup revealed phosphaturia, suggesting a partial proximal tubulopathy. Concomitantly, a renal biopsy revealed prominent podocytes with an immature glomerular appearance and electron microscopy analysis showed numerous intracellular crystals within tubular epithelial cells. Subsequent laboratory and genetic testing confirmed a diagnosis of infantile nephropathic cystinosis. This case highlights the variability in the clinical presentation of cystinosis, resulting in an uncommon clinical picture of a rare disease. Given that treatment is available to prolong renal function and minimize the extra-renal manifestations of this disorder, early diagnosis is essential. It is important to raise the index of suspicion of cystinosis by recognizing its subtle morphological changes in young patients, and that nephrogenic diabetes insipidus can be secondary to this disorder.

  6. Germline Variants and Advanced Colorectal Adenomas: Adenoma Prevention with Celecoxib Trial Genomewide Association Study

    PubMed Central

    Wang, Jiping; Carvajal-Carmona, Luis G.; Chu, Jen-Hwa; Zauber, Ann G.; Kubo, Michikai; Matsuda, Koichi; Dunlop, Malcolm; Houlston, Richard S.; Sieber, Oliver; Lipton, Lara; Gibbs, Peter; Martin, Nicholas G.; Montgomery, Grant W.; Young, Joanne; Baird, Paul N.; Ratain, Mark J.; Nakamura, Yusuke; Weiss, Scott T.; Tomlinson, Ian; Bertagnolli, Monica M.

    2014-01-01

    Purpose Identification of single nucleotide polymorphisms (SNPs) associated with development of advanced colorectal adenomas. Experimental Design Discovery Phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with post-polypectomy disease recurrence. Genome-wide significance was defined as false discovery rate < 0.05, unadjusted p=7.4×10−7. Validation Phase: Results were further evaluated using 4,175 familial colorectal adenoma or CRC cases and 5,036 controls from patients of European ancestry (COloRectal Gene Identification consortium, Scotland, Australia and VQ58). Results Our study identified eight SNPs associated with advanced adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at p<10–7 level with odds ratio – OR>2). Five variants in strong pairwise linkage disequilbrium (rs7278863, rs2837237, rs741864, rs741864 and rs2837241, r2=0.8–1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 (minor allele frequency 0.11; OR 2.09; 95% confidence interval 1.50–2.91), also predicted CRC development in a validation analysis (p=0.019) using a series of adenoma cases or CRC (CORGI study) and 3 sets of CRC cases and controls (Scotland, VQ58 and Australia, N=9,211). Conclusions Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing CRC. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance. PMID:24084763

  7. Etiology and management of recurrent parotid pleomorphic adenoma.

    PubMed

    Witt, Robert L; Eisele, David W; Morton, Randall P; Nicolai, Piero; Poorten, Vincent Vander; Zbären, Peter

    2015-04-01

    The objective of this review study was to encompass the relevant literature and current best practice options for this challenging, sometimes incurable problem. The source of the data was Ovid MEDLINE from 1946 to 2014. Review methods consisted of articles with clinical correlates. The most important cause of recurrence is enucleation with rupture and incomplete tumor excision at operation. Incomplete pseudocapsule, extracapsular extension, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule are also likely linked to recurrent pleomorphic adenoma. Most recurrent pleomorphic adenoma are multinodular. Magnetic resonance imaging is the imaging study of choice for recurrent pleomorphic adenoma. Nerve integrity monitoring may reduce morbidity for recurrent pleomorphic adenoma. Treatment of recurrent pleomorphic adenoma must be individualized. Total parotidectomy, given the multicentricity of recurrent pleomorphic adenoma, is appropriate in many patients, but may be inadequate to control recurrent pleomorphic. There is accumulating evidence from retrospective series that postoperative radiation therapy results in significantly better local control.

  8. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2.

    PubMed

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R; Fagerberg, Christina; Dieperink, Hans; Rittig, Søren; Jensen, Boye L

    2016-04-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls.

  9. Clinical analysis of infarction in pituitary adenoma

    PubMed Central

    Xiao, Deyong; Wang, Shousen; Huang, Yinxing; Zhao, Lin; Wei, Liangfeng; Ding, Chenyu

    2015-01-01

    Objectives: This study is to summarize the clinical manifestations, imaging findings, treatment and prognosis of pituitary apoplexy caused by ischemic infarction. Methods: From January 2010 to March 2014, 412 patients with pituitary adenoma were admitted in the Department of Neurosurgery at Fuzhou General Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging examinations were performed, including computed tomography and magnetic resonance imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar, parasellar, anterior and posterior classification. Hematoxylin and eosin staining and immunohistochemical staining were used for identifying pituitary adenoma. Results: Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients had typical clinical stroke symptoms. Preoperatively, high blood growth hormone concentration was presented in 6 cases, full hypopituitarism in 2 cases, dysfunction of corticosteroids and gonads in 4 cases, and single gonadal dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed computed tomography or magnetic resonance images, and sellar settlement in 7 cases. Eight patients were conducted with transsphenoidal resection, and secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5 cases, and few dark blood clots in 2 cases. Conclusions: Pituitary ischemic infarction stroke is clinically rare, but can be correctly diagnosed before surgery by imaging examinations. The pathological characteristics of the tumor are necrosis and fibrosis, which are easy for resection. Therefore, pituitary adenoma usually has good prognosis. PMID:26221291

  10. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  11. URINARY MUTAGENICITY AND COLORECTAL ADENOMA RISK

    EPA Science Inventory

    Abstract

    We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...

  12. Fractionated proton beam irradiation of pituitary adenomas

    SciTech Connect

    Ronson, Brian B.; Schulte, Reinhard W.; Han, Khanh P.; Loredo, Lilia N.; Slater, James M.; Slater, Jerry D. . E-mail: jdslater@dominion.llumc.edu

    2006-02-01

    Purpose: Various radiation techniques and modalities have been used to treat pituitary adenomas. This report details our experience with proton treatment of these tumors. Methods and Materials: Forty-seven patients with pituitary adenomas treated with protons, who had at least 6 months of follow-up, were included in this analysis. Forty-two patients underwent a prior surgical resection; 5 were treated with primary radiation. Approximately half the tumors were functional. The median dose was 54 cobalt-gray equivalent. Results: Tumor stabilization occurred in all 41 patients available for follow-up imaging; 10 patients had no residual tumor, and 3 had greater than 50% reduction in tumor size. Seventeen patients with functional adenomas had normalized or decreased hormone levels; progression occurred in 3 patients. Six patients have died; 2 deaths were attributed to functional progression. Complications included temporal lobe necrosis in 1 patient, new significant visual deficits in 3 patients, and incident hypopituitarism in 11 patients. Conclusion: Fractionated conformal proton-beam irradiation achieved effective radiologic, endocrinological, and symptomatic control of pituitary adenomas. Significant morbidity was uncommon, with the exception of postradiation hypopituitarism, which we attribute in part to concomitant risk factors for hypopituitarism present in our patient population.

  13. Black adrenal adenoma causing preclinical Cushing's syndrome.

    PubMed

    Inomoto, Chie; Sato, Haruhiro; Kanai, Genta; Hirukawa, Takashi; Shoji, Sunao; Terachi, Toshiro; Kajiwara, Hiroshi; Osamura, Robert Yoshiyuki

    2010-07-20

    Functioning black adrenal adenoma (BAA) rarely causes preclinical Cushing's syndrome (CS). In the present case, a 46-year-old Japanese Peruvian woman presented with left flank pain and hypertension. Abdominal computed tomography showed that she had a 15-mm in diameter, round, left adrenal adenoma. She had no physical features of CS, such as moon face, buffalo hump, truncal obesity, or purple striae. Endocrinological examination showed that the plasma adrenocorticotropic hormone (ACTH) level was below the detectable level, despite a serum cortisol level within the normal range. A normal cortisol circadian rhythm was not present. Dexamethasone (1 mg and 8 mg) suppression testing did not decrease serum cortisol levels to the reference levels. These findings were compatible with preclinical CS. The left adrenal adenoma was laparoscopically removed. Examination of the surgical specimen revealed unilateral double adrenal adenomas of the left adrenal gland, one of which was a BAA. The BAA measured 20 × 11 × 10 mm. Microscopically, the BAA showed proliferation of compact cells containing numerous brown-pigmented granules. There were also foci of myelolipomatous degenerative changes in the tumor. The compact cell zones remained in the adrenal cortex adjacent to the BAA showed atrophic change. These findings indicated that BAA appeared to have caused preclinical CS in this patient.

  14. Suprasellar salivary gland-like pleomorphic adenoma.

    PubMed

    Yao, Kun; Duan, Zejun; Bian, Yu; Wang, Mengyang; Qi, Xueling

    2014-01-01

    Suprasellar salivary gland-Like pleomorphic adenoma is not a common disease and seldom reported so far. We are reporting a case of a 23-year-old man with recurrent suprasellar salivary gland-like pleomorphic adenoma, who underwent an operation of subtotal, subfrontal resection under the wrong pathology diagnosis of benign teratoma in another hospital 4-year-ago. Four years later, he was admitted to our hospital for additional visual loss of the right eye (left, 1.0; right, 0.4) resulting from tumor regrowth. Magnetic resonance imaging revealed that suprasellar extension and compressed optic chiasm resulted in visual disturbance of the patient. The tumor was totally excised and histological examination evidenced the pathological features of intrasellar salivary gland-like pleomorphic adenoma. The patient did not receive any further treatment and he is free from tumor recurrence for 30 months after the operation. From this point of view, clinical prognosis of intrasellar salivary gland-like pleomorphic adenoma was good after total surgical resection.

  15. Thyroid Adenomas After Solid Cancer in Childhood

    SciTech Connect

    Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, Andre; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de

    2012-10-01

    Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

  16. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update.

    PubMed

    Idée, Jean-Marc; Fretellier, Nathalie; Robic, Caroline; Corot, Claire

    2014-11-01

    Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.

  17. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

    PubMed Central

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H.; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-01-01

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2. PMID:28233855

  18. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  19. Congenital Nephrogenic Diabetes Insipidus Presented With Bilateral Hydronephrosis and Urinary Infection: A Case Report.

    PubMed

    Zheng, Kewen; Xie, Yi; Li, Hanzhong

    2016-05-01

    Nephrogenic diabetes insipidus (NDI) is a condition resulting from the kidney's impaired response to circulating antidiuretic hormone (ADH), leading to polydipsia and polyuria. Urinary tract dilatation caused by NDI is a rare situation. Here, we report a case of congenital NDI presented with bilateral hydronephrosis.A 15-year-old boy complaining a history of intermittent fever was admitted to Peking Union Medical College Hospital. He voided 10 to 15 L of urine daily. Radiographic examination revealed severe dilatation of bilateral renal pelvis, ureter, and bladder. Urinalysis shows hyposthenuria.He was diagnosed NDI since born. Transient insertion of a urethral catheter helped to relieve fever. Medical therapy of hydrochlorothiazide and amiloride was prescribed and effective.Dilatation of urinary tract caused by diabetes insipidus is rare, but may be present in severe condition. Therefore, it is crucial for clinicians to perform early treatment to avoid impairment of renal function.

  20. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus.

    PubMed

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-02-24

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2.

  1. Dysregulation of renal aquaporins and epithelial sodium channel in lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Nielsen, Jakob; Kwon, Tae-Hwan; Christensen, Birgitte Mønster; Frøkiaer, Jørgen; Nielsen, Søren

    2008-05-01

    Lithium is used commonly to treat bipolar mood disorders. In addition to its primary therapeutic effects in the central nervous system lithium has a number of side effects in the kidney. The side effects include nephrogenic diabetes insipidus with polyuria, mild sodium wasting, and changes in acid/base balance. These functional changes are associated with marked structural changes in collecting duct cell composition and morphology, likely contributing to the functional changes. Over the past few years, investigations of lithium-induced renal changes have provided novel insight into the molecular mechanisms that are responsible for the disturbances in water, sodium, and acid/base metabolism. This includes dysregulation of renal aquaporins, epithelial sodium channel, and acid/base transporters. This review focuses on these issues with the aim to present this in context with clinically relevant features.

  2. Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

    PubMed Central

    Seo, Ji Yeon; Choi, Seung Ho; Chun, Jaeyoung; Choi, Ji Min; Jin, Eun Hyo; Hwang, Sung Wook; Im, Jong Pil; Kim, Sang Gyun; Kim, Joo Sung

    2016-01-01

    Background/Aims The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. Methods Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. Results Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. Conclusions Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy. PMID:27433150

  3. Pleomorphic adenoma (formerly chondroid syringoma) of the eyelid margin with a pseudocystic appearance.

    PubMed

    Palioura, Sotiria; Jakobiec, Frederick A; Zakka, Fouad R; Iwamoto, Mami

    2013-01-01

    Among the adenomas and adenocarcinomas spawned by the adnexal glands of the eyelids, pleomorphic adenoma (also referred to as benign mixed tumor or chondroid syringoma in dermatopathology) is among the rarest. Pleomorphic adenomas (PAs) can arise from sweat glands in the dermis of the eyelid skin and must be distinguished from those of the accessory lacrimal glands of Krause and Wolfring. We describe an eyelid margin skin PA that appeared clinically to be a cyst and was not associated with an accessory lacrimal gland. Histopathologically, the lesion was circumscribed but nonencapsulated and composed of branching ductular structures with a double layer of epithelial cells set in a myxoid and sclerotic stroma that did not contain cartilage. The outer ductular (myoepithelial) cells delaminated to populate the stroma. Histochemistry disclosed abundant extracellular mucopolysaccharides that conferred the "cystic" character clinically. The inner ductular cells were uniformly positive for cytokeratin 7 and focally for gross cystic fluid disease protein-15, an apocrine marker. The inner and outer ductular cells were negative for alpha-smooth muscle actin. These pathologic findings support an apocrine (gland of Moll) origin for this tumor, which is consistent with the fact that there are no eccrine glands at the eyelid margin.

  4. Sessile serrated adenoma/polyps: Where are we at in 2016?

    PubMed Central

    Singh, Rajvinder; Zorrón Cheng Tao Pu, Leonardo; Koay, Doreen; Burt, Alastair

    2016-01-01

    It is currently known that colorectal cancers (CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway (50%-70%); the mutator “Lynch syndrome” route (3%-5%); and the serrated pathway (30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA), the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders, submucosal injection of a dye solution (for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions. PMID:27678358

  5. Pleomorphic adenoma of submandibular gland: A case report with review of literature

    PubMed Central

    Patil, Preeti; Burde, Krishna; Naikmasur, Venkatesh G.; Thorawat, Amit

    2014-01-01

    Neoplasms that arise in the salivary glands are relatively rare, yet they represent a wide variety of both benign and malignant histologic subtypes. Approximately 70% of the salivary gland tumors affect parotid gland with the submandibular gland being affected in 5-10% of the cases, sublingual gland in 1% and minor glands in 5-15% of the cases. Submandibular gland tumors are relatively rare and very few studies have been reported in the literature that is exclusively conducted on tumors affecting submandibular gland. In this paper, we describe a case of pleomorphic adenoma affecting submandibular gland with brief review of current literature on submandibular gland tumors. PMID:25097655

  6. Pituitary tumours: TSH-secreting adenomas.

    PubMed

    Beck-Peccoz, Paolo; Persani, Luca; Mannavola, Deborah; Campi, Irene

    2009-10-01

    Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.

  7. Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

    PubMed

    Doster, A R; Armstrong, D L; Bargar, T W

    1989-05-01

    A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.

  8. Pituitary Adenoma Volumetry with 3D Slicer

    PubMed Central

    Nimsky, Christopher; Kikinis, Ron

    2012-01-01

    In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%. PMID:23240062

  9. Are metaplasias in colorectal adenomas truly metaplasias?

    PubMed Central

    Bansal, M.; Fenoglio, C. M.; Robboy, S. J.; King, D. W.

    1984-01-01

    Five thousand seven hundred seventy-eight adenomas or adenomas containing carcinoma from 3215 patients were examined by routine histologic methods for the presence of epithelial metaplasias. Three forms of epithelial metaplasia were encountered: squamous cell metaplasia (0.44%), Paneth cell metaplasia (0.20%), and melanocytic metaplasia (0.017%). In several instances multiple forms of metaplasia were encountered in the same polyp. In those cases in which the paraffin blocks were available, a Grimelius stain was performed. Grimelius-positive cells were present in 63% of the adenomas containing a metaplastic cell type. All cases with Paneth cell differentiation were immunoreactive for lysozyme; all lesions containing areas of squamous differentiation were immunoreactive for keratin except 2. The histopathologic features of these cases are discussed, and it is concluded that rather than representing a true metaplastic process, Paneth cell, squamous cell, and melanocyte differentiation represent the full range of cellular differentiation that endodermally derived tissues can exhibit, particularly when they undergo neoplastic alterations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:6202148

  10. Phenotypic variation in colorectal adenoma/cancer expression in two families. Hereditary flat adenoma syndrome.

    PubMed

    Lynch, H T; Smyrk, T C; Lanspa, S J; Lynch, P M; Watson, P; Strayhorn, P C; Bronson, E K; Lynch, J F; Priluck, I A; Appelman, H D

    1990-09-01

    Clinical, pathologic, and genetic studies on two colorectal cancer-prone families have disclosed right-sided colonic flat adenomas and colorectal cancer. Adenomatous polyp counts exceeded those found in hereditary nonpolyposis colorectal cancer (HNPCC) but were fewer than in familial adenomatous polyposis (FAP). Colon cancer occurred at a later age than in HNPCC or FAP and showed right-sided predominance. The older age of patients with colonic cancer, the right-sided predominance of colon cancer, and the paucity of rectal adenomas make FAP unlikely. Vertical transmission of polyps and colon cancer fit the pattern of autosomal dominant inheritance. A characteristic feature of this phenotype is the predominance of flat adenomas. Molecular genetic studies, with careful description of phenotype, should help clarify classification.

  11. Ectopic Pituitary Adenomas Presenting as Sphenoid or Clival Lesions: Case Series and Management Recommendations.

    PubMed

    Tajudeen, Bobby A; Kuan, Edward C; Adappa, Nithin D; Han, Joseph K; Chandra, Rakesh K; Palmer, James N; Kennedy, David W; Wang, Marilene B; Suh, Jeffrey D

    2017-04-01

    Background An ectopic pituitary adenoma presenting as a clival or sphenoid mass is a rare clinical occurrence that may mislead the clinician and result in unnecessary interventions or potential medicolegal consequences. Here, we present one of the largest multi-institutional case series and review the literature with an emphasis on radiological findings and critical preoperative workup. Methods Retrospective chart review. Results Nine patients were identified with ectopic pituitary adenomas of the sphenoid or clivus. There were four females and five males. Median age was 60 years old (range, 36-73 years). The most common presenting symptom was headache (56%). Five (56%) patients presented with a mass arising from the clivus while four (44%) presented with a mass in the sphenoid. Six (67%) patients demonstrated biochemical evidence of hypersecretion on full endocrinology panel. All masses showed evidence of enhancement with gadolinium with a propensity for adjacent bone involvement. Lesions also had a predilection for growth toward the cavernous sinus, carotid artery, or sellar floor. Surgical intervention was performed in eight patients (89%). In eight patients (89%), tumors demonstrated immunoreactivity to prolactin. Conclusions Pituitary adenomas can rarely present as an isolated sphenoid or clival mass. Lesions displayed similar magnetic resonance imaging findings with an erosive growth pattern toward the sellar floor, cavernous sinus, or adjacent carotid artery. Patients with clival or parasellar lesions with comparable features should have a preoperative workup which includes prolactin level and alert the physician to consider an ectopic pituitary adenoma in the differential to prevent unnecessary surgery and potential complications.

  12. Isolated double pituitary adenomas: A silent corticotroph adenoma and a microprolactinoma.

    PubMed

    Eytan, Shira; Kim, Ki-Yoon; Bleich, David; Raghuwanshi, Maya; Eloy, Jean Anderson; Liu, James K

    2015-10-01

    We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37-2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team.

  13. Small cell carcinoma of the colon arising in a carcinoid tumor.

    PubMed

    Saif, M Wasif

    2013-04-01

    Small cell carcinomas of the gastrointestinal tract are rare and clinically aggressive tumors. A case is presented of a 70 year-old woman who presented with small bowel obstruction and was found to have a cecal mass. She underwent right hemicolectomy, and histopathology showed a small cell carcinoma arising in the background of a carcinoid tumor. Although small cell carcinomas of the colon have frequently been found in association with colonic adenomas, this appears to be the first report of a low-grade carcinoid tumor in combination with a small cell carcinoma.

  14. Contemporary issues in the evaluation and management of pituitary adenomas.

    PubMed

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current

  15. Prolactin-secreting pituitary adenomas: CT appearance in diffuse invasion

    SciTech Connect

    Virapongse, C.; Bhimani, S.; Sarwar, M.; Greenberg, A.; Jung, K.

    1984-08-01

    The authors describe 2 diffusely invasive prolactin-secreting pituitary adenomas which produced marked destruction of the base of the skull thought to be diagnostic of chordoma on computed tomography (CT). Failure to recognize this pattern led to biopsy, which was diagnostic. The authors emphasize the need to recognize this rare growth pattern of diffusely invasive pituitary adenoma on CT.

  16. [A case of gigantic pleomorphic adenoma of the parotid gland].

    PubMed

    Namysłowski, G; Misiołek, M; Kubik, P; Misiołek, H; Morawski, K

    1996-01-01

    The case of big size pleomorphic adenoma of the partoid gland was presented. Attention was paid on the necessity of the surgical treatment of pleomorphic adenomas by superficial or total parotidectomies. Possibility of the post operative complications avoidance, even in such big cases was emphasized.

  17. Protean Presentations of Parathyroid Adenoma in Childhood

    PubMed Central

    Dey, Subrata; Beawarwala, Aziz; Gupta, Saikat

    2017-01-01

    Parathyroid adenoma is a rare disease which is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. It is known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. We encountered two such cases who presented to us with varied presentation, in which nuclear scintigraphy along with intraoperative parathyroid hormone assay played a major role in diagnosis and management. PMID:28082776

  18. Molecular Heterogeneity in Aldosterone-Producing Adenomas

    PubMed Central

    Nanba, Kazutaka; Chen, Andrew X.; Omata, Kei; Vinco, Michelle; Giordano, Thomas J.; Else, Tobias; Hammer, Gary D.

    2016-01-01

    Context: The use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status. Objective: The objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity. Methods: Fifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections. Results: Of 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424_V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal. Conclusions: Adrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone

  19. Massive transcranial parotid pleomorphic adenoma: recurrence after 30 years.

    PubMed

    Strub, Graham M; Georgolios, Alexandros; Graham, Robert S; Powers, Celeste N; Coelho, Daniel H

    2012-10-01

    Pleomorphic adenoma, also known as benign mixed tumor, is the most common tumor affecting the parotid gland and can reach massive size; however, intracranial invasion is rare. Recurrence of pleomorphic adenoma after excision is a well-known phenomenon and can present decades after resection of the primary tumor. Here we present the case of a 53-year-old man who presented to our clinic with ear fullness, otalgia, and hearing loss 30 years after undergoing total parotidectomy and external beam radiotherapy for pleomorphic adenoma. Magnetic resonance imaging revealed a massive transcranial tumor invading the mastoid cavity, the dura of the posterior fossa, the fallopian and semicircular canals, the jugular foramen, the lateral infratemporal fossa skull base, the sigmoid and transverse sinuses, and the superior parapharyngeal region. Gross examination and histopathological studies confirmed that the mass was a recurrent pleomorphic adenoma. Here we discuss the features of recurrent pleomorphic adenoma and review the current literature.

  20. Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges in management during infancy.

    PubMed

    Rugpolmuang, Rottanat; Deeb, Asma; Hassan, Yousef; Deekajorndech, Tawatchai; Shotelersuk, Vorasuk; Sahakitrungruang, Taninee

    2014-01-01

    Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.

  1. Application of extracellular gadolinium-based MRI contrast agents and the risk of nephrogenic systemic fibrosis.

    PubMed

    Heverhagen, J T; Krombach, G A; Gizewski, E

    2014-07-01

    Nephrogenic systemic fibrosis (NSF) is a serious, sometimes fatal disease. Findings in recent years have shown that a causal association between gadolinium containing contrast media and NSF is most likely. Therefore, the regulatory authorities have issued guidelines on the use of gadolinium-containing contrast media which have reduced the number of new cases of NSF to almost zero. However, it is for precisely this reason that the greatest care must still be taken to ensure that these guidelines are complied with. The most important factors are renal function, the quantity of gadolinium administered and coexisting diseases such as inflammation. All of these factors crucially influence the quantity of gadolinium released from the chelat in the body. This free gadolinium is thought to be the trigger for NSF. Other important factors are the stability of the gadolinium complex and furthermore the route of its elimination from the body. Partial elimination via the liver might be an additional protective mechanism. In conclusion, despite the NSF risk, contrast-enhanced MRI is a safe diagnostic procedure which can be used reliably and safely even in patients with severe renal failure, and does not necessarily have to be replaced by other methods.

  2. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus.

    PubMed

    Kortenoeven, Marleen L A; Li, Yuedan; Shaw, Stephen; Gaeggeler, Hans-Peter; Rossier, Bernard C; Wetzels, Jack F M; Deen, Peter M T

    2009-07-01

    Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the beneficial effect of amiloride may be through inhibiting lithium entry. Using a mouse collecting duct cell line, we found that vasopressin caused an increase in Aquaporin 2 (AQP2) expression which was reduced by clinically relevant lithium concentrations similar to what is seen with in vivo models of this disease. Further amiloride or benzamil administration prevented this lithium-induced downregulation of AQP2. Amiloride reduced transcellular lithium transport, intracellular lithium concentration, and lithium-induced inactivation of glycogen synthase kinase 3beta. Treatment of rats with lithium downregulated AQP2 expression, reduced the principal-to-intercalated cell ratio, and caused polyuria, while simultaneous administration of amiloride attenuated all these changes. These results show that ENaC is the major entry site for lithium in principal cells both in vitro and in vivo. Blocking lithium entry with amiloride attenuates lithium-induced diabetes insipidus, thus providing a rationale for its use in treating this disorder.

  3. Congenital nephrogenic diabetes insipidus with a novel mutation in the aquaporin 2 gene.

    PubMed

    Park, Youn Jong; Baik, Haing Woon; Cheong, Hae Il; Kang, Ju Hyung

    2014-07-01

    Congenital nephrogenic diabetes insipidus (CNDI) is a rare disorder caused by mutations of the arginine vasopressin (AVP) V2 receptor or aquaporin 2 (AQP2) genes. The current study presented the case of CNDI in a 1-month-old male with a novel mutation in the AQP2 gene. The patient was referred due to the occurrence of hypernatremia and mild-intermittent fever since birth. An AVP stimulation test was compatible with CNDI as there was no significant response to desmopressin. Molecular genetic analysis demonstrated two mutations in exon 1 of the AQP2 gene: C to T transition, which resulted in a missense mutation of (108)Thr (ACG) to Met (ATG); and a 127, 128 delCA, which resulted in a deletion mutation of glutamine in position 43 at codon CAG as the first affected amino acid, with the new reading frame endign in a termination codon at position 62. The molecular genetic analysis of the parents showed that the missense mutation was inherited maternally and the deletion mutation was inherited paternally. The parents showed no signs or symptoms of CNDI, indicating autosomal recessive inheritance. The (108)Thr (ACG) to Met (ATG) mutation was confirmed as a novel mutation. Therefore, the molecular identification of the AQP2 gene has clinical significance, as early recognition of CNDI in infants that show only non-specific symptoms, can be facilitated. Thus, repeated episodes of dehydration, which may cause physical and mental retardation can be avoided.

  4. Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion.

    PubMed

    Yang, Baoxue; Zhao, Dan; Qian, Liman; Verkman, A S

    2006-08-01

    Transgenic mouse models of defective urinary concentrating ability produced by deletion of various membrane transport or receptor proteins, including aquaporin-2 (AQP2), are associated with neonatal mortality from polyuria. Here, we report an inducible mouse model of AQP2 gene deletion with severe polyuria in adult mice. LoxP sequences were inserted into introns 1 and 2 in the mouse AQP2 gene by homologous recombination in embryonic stem cells. Mating of germ-line AQP2-loxP mice with tamoxifen-inducible Cre-expressing mice produced offspring with inducible homozygous Cre-AQP2-loxP, which had a normal phenotype. Tamoxifen injections over 10 days resulted in AQP2 gene excision, with undetectable full-length AQP2 transcript in kidney and a >95% reduction in immunoreactive AQP2 protein. Urine osmolality decreased from approximately 2,000 to <500 mosmol/kgH(2)O after 4-5 days, with urine output increasing from 2 to 25 ml/day. Urine osmolality did not increase after water deprivation. Interestingly, AQP3 protein expression in the collecting duct was increased by about fivefold after AQP2 gene excision. Mild renal damage was seen after 6 wk of polyuria, with collecting duct dilatation, yet normal creatinine clearance and serum chemistries. These results establish the first adult model of nephrogenic diabetes insipidus (NDI) caused by AQP2 deficiency, with daily urine output comparable to body weight, although remarkable preservation of renal function compared with non-inducible NDI models.

  5. An unusual case of hereditary nephrogenic diabetes insipidus (HNDI) affecting mother and daughter.

    PubMed

    Giri, Dinesh; Hart, Rachel; Jones, Caroline; Ellis, Ian; Ramakrishnan, Renuka

    2016-01-01

    Hereditary nephrogenic diabetes iInsipidus (HNDI) is an uncommon disorder due to a resistance to anti-diuretic hormone leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes. We report a mother and daughter in the same family with HNDI due to a heterozygous deletion in exon 1 of the AVPR2 gene, not previously described in the literature. A 5-year-old girl was referred for investigation of polyuria and polydipsia. The patient had a water deprivation test elsewhere at the age of 3 that was inconclusive. A degree of water restriction was imposed leading to headaches. The thyroid, cortisol, renal, and calcium profiles were normal. Her mother showed similar symptoms that had not been previously investigated. AQP2 (Aquaporin) and initial AVPR2 gene sequencing had not identified a mutation, but subsequent quantitative polymerase chain reaction analysis revealed a heterozygous large exon 1 deletion of the AVPR2 gene. The same deletion was also found in the child's mother. The patient's symptoms have significantly improved on appropriate treatment. Further analysis revealed skewed X inactivation in mother and daughter.

  6. X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

    PubMed

    Hong, Che Ry; Kang, Hee Gyung; Choi, Hyun Jin; Cho, Min Hyun; Lee, Jung Won; Kang, Ju Hyung; Park, Hye Won; Koo, Ja Wook; Ha, Tae-Sun; Kim, Su-Yung; Il Cheong, Hae

    2014-01-01

    A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

  7. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  8. Membrane Protein Stability Analyses by Means of Protein Energy Profiles in Case of Nephrogenic Diabetes Insipidus

    PubMed Central

    Heinke, Florian; Labudde, Dirk

    2012-01-01

    Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems. PMID:22474537

  9. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus

    PubMed Central

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D.; Saeed, Fahad; Michael Payne, D.; Chen, Shu-Hui; Fenton, Robert A.; Pisitkun, Trairak

    2015-01-01

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID:26674602

  10. Managing prolactin-secreting adenomas during pregnancy

    PubMed Central

    Imran, Syed Ali; Ur, Ehud; Clarke, David B.

    2007-01-01

    OBJECTIVE To determine an appropriate approach to managing prolactin-secreting adenomas of varying severity in pregnant women. SOURCES OF INFORMATION MEDLINE was searched using the key words “hyperprolactinemia,” “prolactinoma,” “pregnancy,” and “management.” Experience from a multidisciplinary tertiary care centre was also reviewed. Recommendations are based on mostly levels II and III evidence. MAIN MESSAGE With appropriate management, most women with hyperprolactinemia can achieve pregnancy. Although most women with prolactin-secreting adenomas during pregnancy need only careful observation, others might require medical treatment or even surgical evacuation. Ideally, such patients should be managed by multidisciplinary teams. In the absence of such teams, most pregnant women with small tumours can be managed safely by their primary physicians. Those with large tumours should be referred to specialists. CONCLUSION Family physicians play an important role in managing women with prolactinomas during pregnancy. Knowledge of current approaches to management is crucial in determining when and how to refer these patients. PMID:17872715

  11. Radiation therapy in the management of pituitary adenomas.

    PubMed

    Pashtan, Itai; Oh, Kevin S; Loeffler, Jay S

    2014-01-01

    Radiation therapy in the form of fractionated treatment or radiosurgery has an important role in the management of pituitary adenomas. Radiation is a reliable way of gaining local control for radiographically progressing pituitary adenomas. For functioning adenomas that are biochemically recurrent or persistent, radiation therapy is less consistent in offering biochemical normalization and often requires a latency period of years or decades. The decision of when to use radiation therapy is a delicate balance between its benefits and late sequelae, especially in the context of benign disease. Recent technological advances in radiation oncology hold the potential to minimize dose to uninvolved normal tissue and therefore reduce the risk of toxicity.

  12. Laparoscopic partial adrenalectomy for bilateral cortisol-secreting adenomas.

    PubMed

    Domino, Jeffrey P; Chionh, Siok Bee; Lomanto, Davide; Katara, Avinash N; Rauff, Abu; Cheah, Wei-Keat

    2007-04-01

    Bilateral cortisol-secreting adenomas are a rare cause of Cushing's syndrome. We report a case of a 35-year-old woman who presented with ACTH-independent Cushing's syndrome and bilateral adrenal adenomas. Adrenal venous sampling confirmed both adenomas to be hyper-secreting cortisol. She underwent bilateral laparoscopic adrenalectomy; total right and partial left adrenalectomies. At 2-year follow-up, she is maintained on low-dose fludrocortisone and hydrocortisone, and without recurrence of hypercorticolism. Laparoscopic partial adrenalectomy is a feasible option for this rare condition; however, long-term follow-up is needed to determine her total independence from steroid usage.

  13. Adenomas of the common bile duct in familial adenomatous polyposis.

    PubMed

    Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong

    2015-03-14

    Familial adenomatous polyposis (FAP) or Gardner's syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner's syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option.

  14. Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

    PubMed

    Seltzer, Justin; Lucas, Joshua; Commins, Deborah; Lerner, Olga; Lerner, Alexander; Carmichael, John D; Zada, Gabriel

    2015-02-01

    Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged

  15. Radiolabelled spiroperidol: Possible pituitary adenoma imaging agent

    SciTech Connect

    Otto, C.A.; Marshall, J.C.; Lloyd, R.V.; Sherman, P.S.; Wieland, D.M.

    1984-01-01

    Prolactin-secreting pituitary adenomas are the most common type of pituitary tumors. Detection currently depends on physical symptoms, elevated serum prolactin levels and CT scans. An imaging agent which specifically localized in prolactinomas based on some functional characteristic of the tumor would be of considerable clinical value not only for early detection but also for monitoring of therapy. Tritiated spiroperidol (/sup 3/H-Sp) was selected for evaluation based on 1) the presence of D-2 receptors in normal anterior pituitary and adenoma tissue and 2) the high affinity of spiroperidol for D-2 receptors. Recent data have established that implantation of diethylstilbestrol (DES) in Fischer F344 rats induced prolactin-secreting tumors in the pituitary. /sup 3/HSp was evaluated in pituitary tissue of both control and DES-treated rats. /sup 3/HSp concentration in normal female anterior pituitary tissue was found to be about 0.27% kg dose/g from 5 min to 4hrs. This value was about 10 times levels in cortex, cerebellum and striatum. In DES-treated rats the % kg dose/g values remained approximately the same. A 5-fold increase in serum prolactin was associated with a 6-fold increase in both pituitary weight and % dose/organ. The data suggests that although total pituitary weight has increased due to tumor growth (reflected in increased values for % dose/organ), the relative number of receptors per g of tissue has remained constant. This result is in agreement with observations of others on D-2 receptor concentration in prolactinomas.

  16. Middle ear adenomas stain for two cell populations and lack myoepithelial cell differentiation.

    PubMed

    Lott Limbach, Abberly A; Hoschar, Aaron P; Thompson, Lester D R; Stelow, Edward B; Chute, Deborah J

    2012-09-01

    Middle ear adenomas (MEAs) are benign neoplasms along a spectrum with neuroendocrine neoplasms (carcinoid tumors). Immunohistochemical (IHC) staining for myoepithelial markers has not been reported in these tumors. The archives of the Cleveland Clinic, University of Virginia and Armed Forces Institute of Pathology were retrospectively searched for tumors arising within the middle ear with material available for IHC staining. Twelve cases of MEAs, four cases of jugulotympanic paragangliomas (JPGs), 10 cases of ceruminous adenomas (CAs) and four cases of ceruminous adenocarcinomas (CACs) were obtained. IHC staining was performed for smooth muscle actin (SMA), p63, S-100 protein, cytokeratin 5/6 (CK5/6), and cytokeratin 7 (CK7). The MEAs were positive for: CK7 (92 %, luminal), CK5/6 (92 %, abluminal), p63 (83 %, abluminal), and negative for SMA and S-100 protein. The JPGs were negative for CK7, CK5/6, p63 and SMA; S-100 protein highlighted sustentacular cells. The CAs were positive for: CK7 (100 %, luminal), CK5/6 (100 %, abluminal), S-100 protein (80 %, abluminal), p63 (100 %, abluminal), and SMA (90 %, abluminal). CACs demonstrated two patterns, (1) adenoid cystic carcinoma-type: positive for CK7 (100 %, luminal), CK5/6, S-100 protein, p63, and SMA (all 100 %, abluminal); and (2) conventional-type: CK7 (50 % luminal), and no CK5/6, SMA, S-100 protein, or p63 expression. The IHC profile of MEAs suggests that these tumors harbor at least two cell populations, including luminal and basal cells. However, unlike ceruminous adenomas, MEAs lack true myoepithelial differentiation given the absence of S-100 protein and SMA staining in all cases.

  17. Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo.

    PubMed

    Budhathoki, Sanjeev; Iwasaki, Motoki; Yamaji, Taiki; Sasazuki, Shizuka; Tsugane, Shoichiro

    2015-07-15

    Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48-0.93; ptrend  = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44-0.95; ptrend  = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39-0.99; ptrend  = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49-0.96; ptrend  = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44-0.95; ptrend  = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer.

  18. X-linked nephrogenic diabetes insipidus: From the ship Hopewell to RFLP studies

    SciTech Connect

    Bichet, D.G.; Lonergan, M.; Arthus, M.F.; Ligier, S.; Kluge, R. ); Hendy, G.N.; Pausova, Z.; Zingg, H.; Morgan, K.; Saenger, P. )

    1992-11-01

    Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V[sub 2] vasopression receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and DNI has been reported. In 1969, Bode and Crawford proposed, under the term, the Hopewell hypothesis' that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell earlier settlers, either by haplotype or by genealogical analysis. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration. 39 refs., 7 figs., 3 tabs.

  19. Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus—update and epidemiology

    PubMed Central

    El Tarazi, Abdulah; Matar, Jessica; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Bockenhauer, Detlef; Bissonnette, Pierre

    2012-01-01

    It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a ‘pure’ type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt-losing tubulopathies have a complex phenotype with loss of water and ions. They have polyhydramnios, hypercalciuria and hypo- or isosthenuria and were found to bear KCNJ1 (ROMK) and SLC12A1 (NKCC2) mutations. Patients with polyhydramnios, profound polyuria, hyponatremia, hypochloremia, metabolic alkalosis and sensorineural deafness were found to bear BSND mutations. These clinical phenotypes demonstrate the critical importance of the proteins ROMK, NKCC2 and Barttin to transfer NaCl in the medullary interstitium and thereby to generate, together with urea, a hypertonic milieu. This editorial describes two new developments: (i) the genomic information provided by the sequencing of the AQP2 gene is key to the routine care of these patients, and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families and (ii) the expression of AQP2 mutants in Xenopus oocytes and in polarized renal tubular cells recapitulates the clinical phenotypes and reveals a continuum from severe loss of function with urinary osmolalities <150 mOsm/kg H2O to milder defects with urine osmolalities >200 mOsm/kg H2O. PMID:26069764

  20. Substitution of gadolinium ethylenediaminetetraacetate with phosphites: towards gadolinium deposit in nephrogenic systemic fibrosis.

    PubMed

    Gao, Song; Chen, Mao-Long; Zhou, Zhao-Hui

    2014-01-14

    In neutral media, reactions of gadolinium ethylenediaminetetraacetates with phosphorous acid result in the formation of the mixed-ligand polymeric complex K3n[Gd(EDTA)(HPO3)]n·7nH2O () and dimeric complex Na6[Gd2(EDTA)2(HPO3)2]·2.5NaCl·21H2O () (H4EDTA = ethylenediaminetetraacetic acid) in warm solution. Further substitution with citric acid gives the monomeric gadolinium citrate with EDTA (NH4)2Na[Gd(EDTA)(H2cit)]·4H2O (). The compounds were characterized by elemental analysis, single crystal X-ray diffraction, FT-IR, ESI-MS and thermogravimetric analysis. Structural analysis indicates that three coordinated water molecules in the gadolinium ethylenediaminetetraacetate trihydrates are replaced by phosphite ions (HPO3(2-)) in the compounds and . Gadolinium atoms are octa-coordinated by EDTA and the phosphite ion, the latter links adjacent Gd-EDTA units to generate an infinite one-dimensional chain in compound and a dimeric octatomic ring in . In complex , coordinated water molecules were substituted by the α-hydroxy, α-carboxy and β-carboxy groups of citrate. Citrate is favourable for inhibiting the formation of Gd-EDTA phosphite. All the complexes are very easily soluble in water. The solution behavior of the isostructural lanthanum complexes was probed with (13)C and (31)P NMR spectra in D2O for comparison. ESI-MS analysis and recrystallization proved that complexes and dissociate to the monomeric unit of Gd-EDTA and free HPO3(2-) in aqueous solution. Substitutions of gadolinium ethylenediaminetetraacetates to and are attributed to be the cause of nephrogenic systemic fibrosis in some way.

  1. Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Poulsen, Søren Brandt; Kristensen, Tina Bøgelund; Brooks, Heddwen L; Kohan, Donald E; Rieg, Timo; Fenton, Robert A

    2017-04-06

    Psychiatric patients treated with lithium (Li(+)) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li(+)-induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li(+) inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6(-/-)) mice and potentially novel connecting tubule/principal cell-specific AC6 knockout (AC6(loxloxCre)) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls. Dietary Li(+) administration increased water intake and reduced urine osmolality in control, AC6(-/-), and AC6(loxloxCre) mice. Consistent with AC6(-/-) mice, medullary AQP2 and pS256-AQP2 abundances were lower in AC6(loxloxCre) mice compared with controls under standard conditions, and levels were further reduced after Li(+) administration. AC6(loxloxCre) and control mice had a similar increase in the numbers of proliferating cell nuclear antigen-positive cells in response to Li(+). However, AC6(loxloxCre) mice had a higher number of H(+)-ATPase B1 subunit-positive cells under standard conditions and after Li(+) administration. Collectively, AC6 has a minor role in Li-NDI development but may be important for determining the intercalated cell-to-principal cell ratio.

  2. Synchrotron X-ray Analyses Demonstrate Phosphate-Bound Gadolinium in Skin in Nephrogenic Systemic Fibrosis

    PubMed Central

    George, Simon J.; Webb, Samuel M.; Abraham, Jerrold L.; Cramer, Stephen P.

    2010-01-01

    Background Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to Gadolinium based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many NSF patients contain micron-sized insoluble Gd-containing deposits. However, the precise composition and chemical nature of these particles is unclear. Objectives To clarify the precise chemical structure of the Gd-containing deposits in NSF tissues. Methods Autopsy skin tissues from a NSF patient are examined in situ using synchrotron x-ray fluorescence (SXRF) microscopy and extended absorption fine structure (EXAFS) spectroscopy and in correlation with light microscopy and the results of SEM/EDS analyses. Results The insoluble Gd deposits are shown to contain Gd no longer coordinated by GBCA chelator molecules but rather in a sodium calcium phosphate material. SXRF microscopy shows a clear correlation between Gd, Ca and P. EXAFS spectroscopy shows a very different spectrum from the GBCAs, with Gd-P distances at 3.11 Å and 3.72 Å as well as Gd-Gd distances at an average of 4.05 Å, consistent with a GdPO4 structure. Conclusions This is the first direct evidence for the chemical release of Gd from GBCA in human tissue. This supports the physical-chemical, clinical, and epidemiological data indicating a link between stability and dose of GBCA to the development of NSF. PMID:20560953

  3. Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus-update and epidemiology.

    PubMed

    Bichet, Daniel G; El Tarazi, Abdulah; Matar, Jessica; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Bockenhauer, Detlef; Bissonnette, Pierre

    2012-06-01

    It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a 'pure' type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt-losing tubulopathies have a complex phenotype with loss of water and ions. They have polyhydramnios, hypercalciuria and hypo- or isosthenuria and were found to bear KCNJ1 (ROMK) and SLC12A1 (NKCC2) mutations. Patients with polyhydramnios, profound polyuria, hyponatremia, hypochloremia, metabolic alkalosis and sensorineural deafness were found to bear BSND mutations. These clinical phenotypes demonstrate the critical importance of the proteins ROMK, NKCC2 and Barttin to transfer NaCl in the medullary interstitium and thereby to generate, together with urea, a hypertonic milieu. This editorial describes two new developments: (i) the genomic information provided by the sequencing of the AQP2 gene is key to the routine care of these patients, and, as in other genetic diseases, reduces health costs and provides psychological benefits to patients and families and (ii) the expression of AQP2 mutants in Xenopus oocytes and in polarized renal tubular cells recapitulates the clinical phenotypes and reveals a continuum from severe loss of function with urinary osmolalities <150 mOsm/kg H2O to milder defects with urine osmolalities >200 mOsm/kg H2O.

  4. 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress.

    PubMed

    Zheng, Peili; Lin, Yu; Wang, Feifei; Luo, Renfei; Zhang, Tiezheng; Hu, Shan; Feng, Pinning; Liang, Xinling; Li, Chunling; Wang, Weidong

    2016-10-01

    Endoplasmic reticulum (ER) stress has been implicated in some types of glomerular and tubular disorders. The objectives of this study were to elucidate the role of ER stress in lithium-induced nephrogenic diabetes insipidus (NDI) and to investigate whether attenuation of ER stress by 4-phenylbutyric acid (4-PBA) improves urinary concentrating defect in lithium-treated rats. Wistar rats received lithium (40 mmol/kg food), 4-PBA (320 mg/kg body wt by gavage every day), or no treatment (control) for 2 wk, and they were dehydrated for 24 h before euthanasia. Lithium treatment resulted in increased urine output and decreased urinary osmolality, which was significantly improved by 4-PBA. 4-PBA also prevented reduced protein expression of aquaporin-2 (AQP2), pS256-AQP2, and pS261-AQP2 in the inner medulla of kidneys from lithium-treated rats after 24-h dehydration. Lithium treatment resulted in increased expression of ER stress markers in the inner medulla, which was associated with dilated cisternae and expansion of ER in the inner medullary collecting duct (IMCD) principal cells. Confocal immunofluorescence studies showed colocalization of a molecular chaperone, binding IgG protein (BiP), with AQP2 in principal cells. Immunohistochemistry demonstrated increased intracellular expression of BiP and decreased AQP2 expression in IMCD principal cells of kidneys from lithium-treated rats. 4-PBA attenuated expression of ER stress markers and recovered ER morphology. In IMCD suspensions isolated from lithium-treated rats, 4-PBA incubation was also associated with increased AQP2 expression and ameliorated ER stress. In conclusion, in experimental lithium-induced NDI, 4-PBA improved the urinary concentrating defect and increased AQP2 expression, likely via attenuating ER stress in IMCD principal cells.

  5. Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus

    PubMed Central

    Poulsen, Søren Brandt; Kristensen, Tina Bøgelund; Brooks, Heddwen L.; Kohan, Donald E.; Rieg, Timo

    2017-01-01

    Psychiatric patients treated with lithium (Li+) may develop nephrogenic diabetes insipidus (NDI). Although the etiology of Li+-induced NDI (Li-NDI) is poorly understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in the kidney collecting ducts. A mechanism postulated for this is that Li+ inhibits adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2 abundance, and less membrane targeting. We hypothesized that Li-NDI would not develop in mice lacking AC6. Whole-body AC6 knockout (AC6–/–) mice and potentially novel connecting tubule/principal cell–specific AC6 knockout (AC6loxloxCre) mice had approximately 50% lower urine osmolality and doubled water intake under baseline conditions compared with controls. Dietary Li+ administration increased water intake and reduced urine osmolality in control, AC6–/–, and AC6loxloxCre mice. Consistent with AC6–/– mice, medullary AQP2 and pS256-AQP2 abundances were lower in AC6loxloxCre mice compared with controls under standard conditions, and levels were further reduced after Li+ administration. AC6loxloxCre and control mice had a similar increase in the numbers of proliferating cell nuclear antigen–positive cells in response to Li+. However, AC6loxloxCre mice had a higher number of H+-ATPase B1 subunit–positive cells under standard conditions and after Li+ administration. Collectively, AC6 has a minor role in Li-NDI development but may be important for determining the intercalated cell–to–principal cell ratio.

  6. Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

    2017-01-27

    Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

  7. Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes Insipidus.

    PubMed

    Mamenko, Mykola; Dhande, Isha; Tomilin, Viktor; Zaika, Oleg; Boukelmoune, Nabila; Zhu, Yaming; Gonzalez-Garay, Manuel L; Pochynyuk, Oleh; Doris, Peter A

    2016-07-01

    Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.

  8. Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2.

    PubMed

    Shi, Peijun P; Cao, Xiao R; Qu, Jing; Volk, Ken A; Kirby, Patricia; Williamson, Roger A; Stokes, John B; Yang, Baoli

    2007-05-01

    In mammals, the hormonal regulation of water homeostasis is mediated by the aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD principal cells, accompanied by increased water permeability. Mutations of AQP2 gene in humans cause both recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. In this study, we generated a line of mice with the distal COOH-terminal tail of the Aqp2 deleted (Aqp2(Delta230)), including the protein kinase A phosphorylation site (S256), but still retaining the putative apical localization signal (221-229) at the COOH-terminal. Mice heterozygous for the truncation appear normal. Homozygotes are viable to adulthood, with reduced urine concentrating capacity, increased urine output, decreased urine osmolality, and increased daily water consumption. Desmopressin increased urine osmolality in wild-type mice but had no effect on Aqp2(Delta230/Delta230) mice. Kidneys from affected mice showed CD and pelvis dilatation and papillary atrophy. By immunohistochemical and immunoblot analyses using antibody against the NH(2)-terminal region of the protein Aqp2(Delta230/Delta230) mice had a markedly reduced protein abundance. Expression of the truncated protein in MDCK cells was consistent with a small amount of functional expression but no stimulation. Thus we have generated a mouse model of NDI that may be useful in studying the physiology and potential therapy of this disease.

  9. Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Sim, Jae H; Himmel, Nathaniel J; Redd, Sara K; Pulous, Fadi E; Rogers, Richard T; Black, Lauren N; Hong, Seongun M; von Bergen, Tobias N; Blount, Mitsi A

    2014-01-01

    Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in ∼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy.

  10. Targeting renal purinergic signalling for the treatment of lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Kishore, B K; Carlson, N G; Ecelbarger, C M; Kohan, D E; Müller, C E; Nelson, R D; Peti-Peterdi, J; Zhang, Y

    2015-06-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development of nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulphate (Plavix(®)) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unravelled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action.

  11. Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

    PubMed

    Ingemi, Amanda I; Bota, Vasile M; Peguero, Anyeri; Charpentier, Margaret

    2012-01-01

    Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option.

  12. Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter.

    PubMed

    Sinke, Anne P; Kortenoeven, Marleen L A; de Groot, Theun; Baumgarten, Ruben; Devuyst, Olivier; Wetzels, Jack F M; Loffing, Johannes; Deen, Peter M T

    2014-03-01

    Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI). Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in Li-NDI. The paradoxical antidiuretic action of HCTZ in Li-NDI is generally attributed to increased sodium and water uptake in proximal tubules as a compensation for increased volume loss due to HCTZ inhibition of the Na-Cl cotransporter (NCC), but alternative actions for HCTZ have been suggested. Here, we investigated whether HCTZ exerted an NCC-independent effect in Li-NDI. In polarized mouse cortical collecting duct (mpkCCD) cells, HCTZ treatment attenuated the Li-induced downregulation of aquaporin-2 (AQP2) water channel abundance. In these cells, amiloride reduces cellular Li influx through the epithelial sodium channel (ENaC). HCTZ also reduced Li influx, but to a lower extent. HCTZ increased AQP2 abundance on top of that of amiloride and did not affect the ENaC-mediated transcellular voltage. MpkCCD cells did not express NCC mRNA or protein. These data indicated that in mpkCCD cells, HCTZ attenuated lithium-induced downregulation of AQP2 independently of NCC and ENaC. Treatment of Li-NDI NCC knockout mice with HCTZ revealed a significantly reduced urine volume, unchanged urine osmolality, and increased cortical AQP2 abundance compared with Li-treated NCC knockout mice. HCTZ treatment further resulted in reduced blood Li levels, creatinine clearance, and alkalinized urinary pH. Our in vitro and in vivo data indicate that part of the antidiuretic effect of HCTZ in Li-NDI is NCC independent and may involve a tubuloglomerular feedback response-mediated reduction in glomerular filtration rate due to proximal tubular carbonic anhydrase inhibition.

  13. Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

    PubMed

    Zhang, Yue; Peti-Peterdi, János; Brandes, Anna U; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

    2017-02-23

    Previously, we localized ADP-activated P2Y12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N = 5/group) were fed either regular rodent chow (CNT), or with added LiCl (40 mmol/kg chow) or PRSG in drinking water (10 mg/kg bw/day) or a combination of LiCl and PRSG for 14 days and then euthanized. Water intake and urine output were determined and blood and kidney tissues were collected and analyzed. PRSG administration completely suppressed Li-induced polydipsia and polyuria and significantly prevented Li-induced decreases in AQP2 protein abundance in renal cortex and medulla. However, PRSG either alone or in combination with Li did not have a significant effect on the protein abundances of NKCC2 or NCC in the cortex and/or medulla. Immunofluorescence microscopy revealed that PRSG administration prevented Li-induced alterations in cellular disposition of AQP2 protein in medullary collecting ducts. Serum Li, Na, and osmolality were not affected by the administration of PRSG. Similar to CLPD, PRSG administration had no effect on Li-induced increase in urinary Na excretion. However, unlike CLPD, PRSG did not augment Li-induced increase in urinary arginine vasopressin (AVP) excretion. Taken together, these data suggest that the pharmacological inhibition of P2Y12-R by the thienopyridine group of drugs may potentially offer therapeutic benefits in Li-induced NDI.

  14. Targeting Renal Purinergic Signalling for the Treatment of Lithium-induced Nephrogenic Diabetes Insipidus

    PubMed Central

    Kishore, B. K.; Carlson, N. G.; Ecelbarger, C. M.; Kohan, D. E.; Müller, C. E.; Nelson, R. D.; Peti-Peterdi, J.; Zhang, Y.

    2015-01-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats, and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulfate (Plavix®) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unraveled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. PMID:25877068

  15. Aliskiren Increases Aquaporin-2 Expression and Attenuates Lithium-induced Nephrogenic Diabetes Insipidus.

    PubMed

    Lin, Yu; Zhang, Tiezheng; Feng, Pinning; Qiu, Miaojuan; Liu, Qiaojuan; Li, Suchun; Zheng, Peili; Kong, Yonglun; Levi, Moshe; Li, Chunling; Wang, Weidong

    2017-02-22

    The direct renin inhibitor aliskiren has been shown to retain and persist in medullary collecting ducts even after treatment was discontinued, suggesting a new mechanism of action for this drug. The purpose of the present study was to investigate whether aliskiren regulates renal aquaporin expression in the collecting ducts and improves urinary concentrating defect induced by lithium in mice. The mice were either fed with normal chow or LiCl diet (40mM/kg dry food/day for 4 days and 20mM/kg dry food/day for last 3 days) for seven days. Some mice were intraperitoneally injected with aliskiren (50mg/kg BW/day in saline). Aliskiren significantly increased protein abundance of AQP2 in the kidney inner medulla in mice. In inner medulla collecting duct cell suspension, aliskiren markedly increased AQP2 and pS256-AQP2 protein abundance which was significantly inhibited either by adenylyl cyclase inhibitor MDL-12330A or by PKA inhibitor H89, indicating an involvement of the cAMP-PKA signaling pathway in aliskiren-induced increased AQP2 expression. Aliskiren treatment improved urinary concentrating defect in lithium-treated mice, and partially prevented the decrease of AQP2 and pS256-AQP2 protein abundance in inner medulla of the kidney. In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus (NDI) likely via cAMP-PKA pathways.

  16. [Efficacy of prostatic adenoma treatment with alfusozine depending on sexuality].

    PubMed

    Kogan, M I; Kireev, A Iu

    2011-01-01

    Blood levels of total PSA and testosterone, size of the prostatic gland, Qmax were measured in 40 patients with prostatic adenoma symptoms treated with alfusozine in a dose 10 mg/day before the treatment, on the treatment week 4, 12 and 24. At the same time the examinees were questioned using IPSS, MSHQ, IIEF questionnaires. The sexuality phenotype was estimated according to the Rostov Questionnaire of Integral Male Sexuality. It was found that sexuality phenotypes (hypo-, normo- and hypersexuality) occur with the same frequency in males with prostatic adenoma symptoms. Hypersexual men with prostatic adenoma have more definite lower urinary tract symptoms, worse erection and ejaculation, more frequent signs of hypogonadism. The highest alfusozine efficacy was observed in normo- and hyposexual men with prostatic adenoma who achieved better results in improvement of Qmax, symptoms of the lower urinary tract, erectile and ejaculation function. The treatment efficacy in the hypersexual men is low.

  17. Gut microbiome development along the colorectal adenoma-carcinoma sequence.

    PubMed

    Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

    2015-03-11

    Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

  18. [Aspects of the operative treatment of prostatic adenoma].

    PubMed

    Gogichaev, Z Kh; zolotarev, I I

    1977-02-01

    The authors have gained minimum blood losses when suturing with provisional catgut ligature through the urinary bladder bottom between interureteral fold and internal urethral orifice yet before dessection of adenoma surgical capsule and tumor enucleation. Depending on the functional state of the upper urinary tract, the bladder tonus and adenoma size, the method of postoperative drainage of the urinary bladder is selected: cystostomy, microirrigation, active suction, etc.

  19. Pleomorphic adenoma of the frontal sinus masquerading as a mucocele.

    PubMed

    Chew, Yok Kuan; Brito-Mutunayagam, Sushil; Chong, Aun Wee; Prepageran, Narayanan; Chandran, Patricia Ann; Khairuzzana, Baharudin; Lingham, Omkara Rubini

    2015-12-01

    Pleomorphic adenoma is the most common type of benign salivary gland tumor. It can also be found in the larynx, ear, neck, and nasal septum. It is rarely found in the maxillary sinus, and it has never been reported in the frontal sinus. We report a case of pleomorphic adenoma of the frontal sinus that masqueraded as a mucocele. We discuss the clinical presentation, diagnosis, and treatment of this patient, and we review the literature.

  20. Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus.

    PubMed

    Olesen, Emma T B; Rützler, Michael R; Moeller, Hanne B; Praetorius, Helle A; Fenton, Robert A

    2011-08-02

    In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause X-linked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus.

  1. Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.

    PubMed

    Goji, K; Kuwahara, M; Gu, Y; Matsuo, M; Marumo, F; Sasaki, S

    1998-09-01

    Novel mutations of the aquaporin-2 (AQP2) gene have been detected in Japanese female siblings with autosomal-recessive nephrogenic diabetes insipidus. The patients were compound heterozygote for point mutations at nucleotide position 374 (C374T) and at position 523 (G523A) in exon 2 of the AQP2 gene, resulting in substitution of methionine for threonine at codon 125 (T125M) and arginine for glycine at codon 175 (G175R). The water permeability (Pf) of oocytes injected with wild-type complementary RNA increased 9.0-fold compared with the Pf of water-injected oocytes, whereas the increases in the Pf of oocytes injected with T125M and G175R complementary RNA were only 1.7-fold and 1.5-fold, respectively. Immunoblot and immunocytochemistry indicated that the plasma membrane expressions of T125M and G175R AQP2 proteins were comparable to that of the wild-type, suggesting that although neither the T125M nor G175R mutation had a significant effect on plasma membrane expression, they both distorted the structure and function of the aqueous pore of AQP2. These results provide evidence that the nephrogenic diabetes insipidus in patients with T125M and G175R mutations is attributable not to the misrouting of AQP2, but to the disrupted water channel function.

  2. Intermittent facial spasms as the presenting sign of a recurrent pleomorphic adenoma

    PubMed Central

    Machado, Rosalie A; Moubayed, Sami P; Khorsandi, Azita; Hernandez-Prera, Juan C; Urken, Mark L

    2017-01-01

    The intimate anatomical relationship of the facial nerve to the parotid parenchyma has a significant influence on the presenting signs and symptoms, diagnosis and treatment of parotid neoplasms. However, to our knowledge, hyperactivity of this nerve, presenting as facial spasm, has never been described as the presenting sign or symptom of a parotid malignancy. We report a case of carcinoma arising in a recurrent pleomorphic adenoma of the left parotid gland (i.e., carcinoma ex pleomorphic adenoma) that presented with hemifacial spasms. We outline the differential diagnosis of hemifacial spasm as well as a proposed pathophysiology. Facial paralysis, lymph node enlargement, skin involvement, and pain have all been associated with parotid malignancies. To date the development of facial spasm has not been reported with parotid malignancies. The most common etiologies for hemifacial spasm are vascular compression of the ipsilateral facial nerve at the cerebellopontine angle (termed primary or idiopathic) (62%), hereditary (2%), secondary to Bell’s palsy or facial nerve injury (17%), and hemifacial spasm mimickers (psychogenic, tics, dystonia, myoclonus, myokymia, myorthythmia, and hemimasticatory spasm) (17%). Hemifacial spasm has not been reported in association with a malignant parotid tumor but must be considered in the differential diagnosis of this presenting symptom. PMID:28246588

  3. Many Private Mutations Originate From The First Few Divisions Of A Human Colorectal Adenoma

    PubMed Central

    Kang, Haeyoun; Salomon, Matthew P.; Sottoriva, Andrea; Zhao, Junsong; Toy, Morgan; Press, Michael F.; Curtis, Christina; Marjoram, Paul; Siegmund, Kimberly; Shibata, Darryl

    2015-01-01

    Intratumoral mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumor is commonly observed in human tumors. The mechanisms generating such ITH are uncertain. Here we find ITH can be remarkably well-structured by measuring point mutations, chromosome copy numbers and DNA passenger methylation from opposite sides and individual glands of a 6 cm human colorectal adenoma. ITH was present between tumor sides and individual glands, but the private mutations were side specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumor originates from the first few divisions. Much of the early history of a tumor, especially the first few divisions, may be embedded within the detectable ITH of tumor genomes. PMID:26119426

  4. ACTH adenomas transforming their clinical expression: report of 5 cases.

    PubMed

    Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio

    2015-02-01

    OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous

  5. Giant serous microcystic adenoma of the pancreas safely resected after preoperative arterial embolization

    PubMed Central

    TAJIMA, HIDEHIRO; OHTA, TETSUO; KITAGAWA, HIROHISA; SHINBASHI, HIROYUKI; HIROSE, ATSUSHI; SAKAI, SEISHO; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAGAWARA, HISATOSHI; ONISHI, ICHIRO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; FUSHIDA, SACHIO; TANI, TAKASHI; FUJIMURA, TAKASHI; KAYAHARA, MASATO; KODA, WATARU; MATSUI, OSAMU

    2010-01-01

    Serous microcystic adenomas are rare and account for 1–2% of all exocrine pancreatic tumors and 25% of all pancreatic cystic neoplasms. Recently, with advances in imaging techniques, these adenomas have been identified at an increasing frequency. A 63-year-old woman visited her doctor in 1999 due to a gastric deformity detected by upper gastrointestinal endoscopy. An abdominal computed tomography scan revealed a cystic lesion measuring 6.0 cm in diameter, resulting in a diagnosis of serous microcystic adenoma of the pancreatic head. During follow-up, the tumor increased steadily in size, measuring 6.0 cm in diameter in 1999 and 13.0 cm in 2008, while remaining asymptomatic throughout this period of time. The risk of malignant transformation appears to be low even over the long-term. However, some cases of malignant transformation to serous cystadenocarcinoma have recently been reported. In this case, assessment of the relationship between the tumor and adjacent vascular structures, such as massive drainage vein development on the surface or tumor flow into the portal and superior mesenteric veins and the celiac and superior mesenteric arteries, was critical for determining tumor resectability. The risk of massive intra-operative hemorrhage was felt to be considerable, given the extent of the veins on the surface of the tumor, as well as the size and location of the primary pancreatic mass. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed. Tumor resection with pancreaticoduodenectomy was performed without a blood transfusion, with an estimated blood loss of 570 ml. The final pathology confirmed the diagnosis of serous microcystic adenoma. The patient is currently alive and disease-free. Preoperative partial embolization of the tumor feeding arteries and intra-operative resection of the right gastric and inferior pancreatoduodenal arteries, allowed

  6. Somatotroph Pituitary Adenoma with Acromegaly and Autosomal Dominant Polycystic Kidney Disease – SSTR5 polymorphism and PKD1 mutation

    PubMed Central

    Syro, Luis V.; Sundsbak, Jamie L.; Scheithauer, Bernd W.; Toledo, Rodrigo A.; Camargo, Mauricio; Heyer, Christina M.; Sekiya, Tomoko; Uribe, Humberto; Escobar, Jorge I.; Vasquez, Martin; Rotondo, Fabio; Toledo, Sergio P. A.; Kovacs, Kalman; Horvath, Eva; Babovic-Vuksanovic, Dusica; Harris, Peter C.

    2014-01-01

    A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0–5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48–255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.143C>A (p.L48M, rs4988483) change in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subject to extensive morphological, ultrastructural, cytogenetic and molecular studies. The question arises whether the physical proximity of the PKD1 and SSTR5 genes on chromosome 16 indicates a causal relationship between ADPKD and the somatotroph adenoma. PMID:21744088

  7. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature

    PubMed Central

    Yadav, Achla Bharti; Narwal, Anjali; Devi, Anju; Kumar, Sanjay; Yadav, Sumit Kumar

    2015-01-01

    Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature. PMID:26535412

  8. Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypical adenomas.

    PubMed

    Zaidi, Hasan A; Cote, David J; Dunn, Ian F; Laws, Edward R

    2016-12-01

    Despite formal pathological criteria, not all atypical pituitary adenomas display clinically aggressive behavior. We set out to determine which factors predict a clinically aggressive phenotype among a cohort of atypical pituitary adenomas. Medical records were retrospectively reviewed from April 2008 to July 2015. Of 569 pituitary adenomas, 47 (8.3%) patients were surgically treated for atypical adenomas as defined by the WHO criteria. Clinically aggressive adenomas were defined as occurring in those patients who necessitated additional therapeutic intervention after the index (first) surgery, including additional surgery, medical therapy, or radiosurgery. Forty-seven patients with histopathological and immunohistochemical confirmation of atypical adenomas were identified and of these, 23 were noted to have a clinically aggressive course. Among the remaining 24 patients, the disease remained quiescent after the index surgery. On univariate analysis, clinically aggressive lesions were more likely to have a larger axial diameter on MRI (2.9±1.9cm vs. 1.9±0.7cm, p=0.02), greater incidence of cavernous sinus invasion (65.2% vs. 20.8%, p<0.01), and greater incidence of clival extension (60.9% vs. 0, p<0.01) on preoperative imaging. The two groups were equivalent with regard to immunohistochemical staining for ACTH, HGH, LH, FSH, PRL, and TSH. Clinically aggressive lesions, however, trended towards a greater average MIB-1 proliferative index (7.5%±4.9 vs. 6.0%±3.6, p=0.03). On multivariate analysis, the MIB-1 proliferative index trended towards statistical significance (p=0.06) as an independent predictor of clinical aggressiveness. Atypical pituitary adenomas are defined by a rigid set of immunohistochemical markers, but not all necessarily demonstrate an aggressive clinical phenotype.

  9. Autofluorescence ratio imaging of human colonic adenomas

    NASA Astrophysics Data System (ADS)

    Imaizumi, Katsuichi; Harada, Yoshinori; Wakabayashi, Naoki; Yamaoka, Yoshihisa; Dai, Ping; Tanaka, Hideo; Takamatsu, Tetsuro

    2011-02-01

    Recently autofluorescence imaging (AFI) endoscopy, visualizing tissue fluorescence in combination with reflected light, has been adopted as a technique for detecting neoplasms in the colon and other organs. However, autofluorescence colonoscopy is not infallible, and improvement of the detection method can be expected to enhance the performance. Colonic mucosa contains metabolism-related fluorophores, such as reduced nicotinamide adenine dinucleotide, which may be useful for visualizing neoplasia in autofluorescence endoscopy. We examined sliced cross-sections of endoscopically resected tubular adenomas under a microscope. Fluorescence images acquired at 365-nm excitation (F365ex) and 405-nm excitation (F405ex), and reflectance images acquired at 550 nm (R550) were obtained. Fluorescence ratio (F365ex/F405ex) images and reflectance/fluorescence ratio (R550/F405ex) images were calculated from the acquired images. The fluorescence ratio images could distinguish adenomatous mucosa from normal mucosa more clearly than the reflectance/fluorescence ratio images. The results showed that the autofluorescence ratio imaging is a potential technique for increasing the diagnostic power of autofluorescence endoscopy.

  10. Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas

    PubMed Central

    Lu, Yingying; Chen, Jing; Zheng, Junyuan; Hu, Guoyong; Wang, Jingjing; Huang, Chunlan; Lou, Lihong; Wang, Xingpeng; Zeng, Yue

    2016-01-01

    Recent reports have suggested that the gut microbiota is involved in the progression of colorectal cancer (CRC). The composition of gut microbiota in CRC precursors has not been adequately described. To characterize the structure of adherent microbiota in this disease, we conducted pyrosequencing-based analysis of 16S rRNA genes to determine the bacterial profile of normal colons (healthy controls) and colorectal adenomas (CRC precursors). Adenoma mucosal biopsy samples and adjacent normal colonic mucosa from 31 patients with adenomas and 20 healthy volunteers were profiled using the Illumina MiSeq platform. Principal coordinate analysis (PCoA) showed structural segregation between colorectal adenomatous tissue and control tissue. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with adenomas. Taxonomic analysis illustrated that abundance of eight phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Cyanobacteria, Candidate-division TM7, and Tenericutes) was significantly different. In addition, Lactococcus and Pseudomonas were enriched in preneoplastic tissue, whereas Enterococcus, Bacillus, and Solibacillus were reduced. However, both PCoA and cluster tree analyses showed similar microbiota structure between adenomatous and adjacent non-adenoma tissues. These present findings provide preliminary experimental evidence supporting that colorectal preneoplastic lesion may be the most important factor leading to alterations in bacterial community composition. PMID:27194068

  11. Familial pituitary adenomas - who should be tested for AIP mutations?

    PubMed

    Korbonits, Márta; Storr, Helen; Kumar, Ajith V

    2012-09-01

    Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with low penetrance is being increasingly recognized. FIPA families can be divided into two distinct groups based on genetic and phenotypic features. Patients with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are characterized by young-onset somatotroph or lactotroph macroadenomas, while in the other, larger group of FIPA patients with typically adult-onset disease and more varied adenoma types, no causative gene(s) has been identified. Young-onset macroadenoma patients can also be identified with germline AIP mutation without an apparent family history. Further data and longer follow-up are necessary to establish formal guidelines, but the current data suggest genetic screening of the AIP gene in patients with a pituitary adenoma and no other associated features who have (i) a family history of pituitary adenoma, (ii) childhood-onset pituitary adenoma or (iii) a pituitary somatotroph or lactotroph macroadenoma diagnosed before the age of 30 years.

  12. Altered tissue metabolites correlate with microbial dysbiosis in colorectal adenomas.

    PubMed

    Nugent, Julia L; McCoy, Amber N; Addamo, Cassandra J; Jia, Wei; Sandler, Robert S; Keku, Temitope O

    2014-04-04

    Several studies have linked bacterial dysbiosis with elevated risk of colorectal adenomas and cancer. However, the functional implications of gut dysbiosis remain unclear. Gut bacteria contribute to nutrient metabolism and produce small molecules termed the "metabolome", which may contribute to the development of neoplasia in the large bowel. We assessed the metabolome in normal rectal mucosal biopsies of 15 subjects with colorectal adenomas and 15 nonadenoma controls by liquid chromatography and gas chromatography time-of-flight mass spectrometry. Quantitative real-time PCR was used to measure abundances of specific bacterial taxa. We identified a total of 274 metabolites. Discriminant analysis suggested a separation of metabolomic profiles between adenoma cases and nonadenoma controls. Twenty-three metabolites contributed to the separation, notably an increase in adenoma cases of the inflammatory metabolite prostaglandin E2 and a decrease in antioxidant-related metabolites 5-oxoproline and diketogulonic acid. Pathway analysis suggested that differential metabolites were significantly related to cancer, inflammatory response, carbohydrate metabolism, and GI disease pathways. Abundances of six bacterial taxa assayed were increased in cases. The 23 differential metabolites demonstrated correlations with bacteria that were different between cases and controls. These findings suggest that metabolic products of bacteria may be responsible for the development of colorectal adenomas and CRC.

  13. Colorectal villous adenoma: transrectal US in screening for invasive malignancy.

    PubMed

    Hulsmans, F H; Tio, T L; Mathus-Vliegen, E M; Bosma, A; Tytgat, G N

    1992-10-01

    Exclusion of focal infiltrating malignancy in colorectal villous adenoma is a prerequisite when nonsurgical treatment is considered. In a study of 81 patients with endoscopically identified colorectal villous adenoma screened for malignancy with transrectal ultrasonography (US), 15 patients were excluded because of incomplete follow-up. Twelve carcinomas were present, confirmed with either histopathologic examination after surgical resection (n = 9) or biopsies during laser treatment (n = 3). Nine of them were detected with transrectal US on the basis of disruption of the anatomic wall layers (sensitivity, 75%). In 46 of the 54 adenomas transrectal US helped confirm the benign nature of the lesion (specificity, 85%). Seven of the eight false-positive cases happened to be previously treated with surgery or coagulation. Treatment-associated inflammatory changes in the wall layers seemed responsible for this misinterpretation. Because of the high predictive value for a negative result (benign adenoma, 94%), transrectal US is recommended for the evaluation of villous adenomas to detect malignancy, especially when nonsurgical treatment is considered. Transrectal US should be performed before diagnostic polypectomy.

  14. Pleomorphic adenoma of the tongue base: case report and review.

    PubMed

    Nascimento, Luiz Augusto; Vilela, Thais Gonçalves Pinheiro

    2014-07-01

    Introduction Pleomorphic adenoma, also known as mixed tumor, is the most common benign tumor of the major and minor salivary glands. The occurrence of pleomorphic adenoma of the tongue base is very rare, and very few cases have been reported in the literature. Objective The authors present a rare case of pleomorphic adenoma of the tongue base and a review of the literature. Case Report A 55-year-old woman had an extensive cervical mass, with little pain, from the submental level to the level below the hyoid bone. Fiberoptic endoscopic examination showed an extensive mass at the base of the tongue with considerable reduction in the airway. Magnetic resonance image scan revealed a contrast-enhancing mass of heterogeneous density over the base of the tongue of 8 × 8 × 7 cm and a reduction of the hypopharyngeal airway. Biopsy of the lesion was performed along with a tracheostomy due to the bulging tongue base and acute respiratory failure. Histologic examination with an immunohistochemistry study revealed a diagnosis of pleomorphic adenoma. The excision of the tumor was performed by a lateral pharyngotomy approach and the total mass was excised. Conclusion The authors consider the rarity of this case and show that this is the 11th and the largest pleomorphic adenoma reported in the English-language medical literature.

  15. [Pleomorphic adenoma of the parotid gland, rules for resection].

    PubMed

    de Ridder, Mischa; Smeele, Ludi E; Balm, Alfons J M

    2012-01-01

    The importance of complete excision of a benign pleomorphic adenoma is illustrated by two patients' histories. A 28-year-old man underwent a local excision of a nodule under the left ear without histological confirmation. Ten years later he returned to our institute with a large multilocular process and subcutaneous nodules. Cytology showed pleomorphic adenoma. Patient was treated with total facial nerve preserving parotidectomy and radiotherapy. An 81-year-old male underwent a surgical removal of a swelling under his left ear eight years before admission for a large diffusely infiltrating tumor in the neck. Repeated cytology showed carcinoma ex pleomorphic adenoma. This tumor was inoperable and he was treated by palliative irradiation. In case of incomplete resection, pleomorphic adenoma cells are spilled with an increasing chance of local recurrence. Also degeneration into carcinoma ex pleomorphic adenoma is possible after incomplete resection, with impact on survival. These risks of residual disease determine the need of centralization of diagnosis and treatment of this benign parotid tumor.

  16. [A case of parotid pleomorphic adenoma metastasis to multiple organs].

    PubMed

    Kessoku, Hisashi; Yoshimura, Tsuyoshi; Iino, Takashi; Tanaka, Yasuhiro

    2014-01-01

    In January 2011, a 64-year-old woman who had undergone tumor resection for pleomorphic adenoma of the left parotid gland four times since her first operation in 1996 visited an orthopedist in our hospital complaining of pain in her right lower limb. Computed tomography (CT) of the whole body showed multiple tumors on the left parotid gland, right kidney, the sacrum, and both lungs. Biopsy of the sacral region and right nephrectomy were performed based on a clinical diagnosis of sacral and pulmonary metastases from renal cell carcinoma, and palliative radiation therapy was immediately begun on the sacral region. Given the definitive pathological diagnosis of metastasis of pleomorphic adenoma of the parotid gland, the recurrent tumor of the left parotid gland and the surrounding lymph nodes were first removed. Postoperative findings demonstrated that the pleomorphic adenoma had metastasized to the lymph nodes. The lung tumors were resected subsequently, and postoperative findings led to the diagnosis of pleomorphic adenoma. Metastasis of pleomorphic adenoma is known to be extremely rare, and to our knowledge this case of metastasis to a kidney is the first reported in Japan.

  17. Synchronous melanomas arising within nevus spilus*

    PubMed Central

    de Brito, Maria Helena Toda Sanches; Dionísio, Cecília Silva Nunes de Moura; Fernandes, Cândida Margarida Branco Martins; Ferreira, Joana Cintia Monteiro; Rosa, Maria Joaninha Madalena de Palma Mendonça da Costa; Garcia, Maria Manuela Antunes Pecegueiro da Silva

    2017-01-01

    Nevus spilus is a melanocytic cutaneous lesion consisting of a light brown background macule with numerous superimposed darker maculopapular speckles. Melanoma arising from a nevus spilus is rare, with less than 40 cases reported to date. The absolute risk for malignant transformation is not well defined, lacking a standardized management approach. We report a new case of melanoma arising from nevus spilus, with the additional peculiarity of multifocality. We offer our recommendations for the management of the condition. PMID:28225967

  18. Synchronous melanomas arising within nevus spilus.

    PubMed

    Brito, Maria Helena Toda Sanches de; Dionísio, Cecília Silva Nunes de Moura; Fernandes, Cândida Margarida Branco Martins; Ferreira, Joana Cintia Monteiro; Rosa, Maria Joaninha Madalena de Palma Mendonça da Costa; Garcia, Maria Manuela Antunes Pecegueiro da Silva

    2017-01-01

    Nevus spilus is a melanocytic cutaneous lesion consisting of a light brown background macule with numerous superimposed darker maculopapular speckles. Melanoma arising from a nevus spilus is rare, with less than 40 cases reported to date. The absolute risk for malignant transformation is not well defined, lacking a standardized management approach. We report a new case of melanoma arising from nevus spilus, with the additional peculiarity of multifocality. We offer our recommendations for the management of the condition.

  19. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.

    PubMed

    Robben, Joris H; Knoers, Nine V A M; Deen, Peter M T

    2006-08-01

    In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. The disorder nephrogenic diabetes insipidus (NDI) is characterized by the kidney's inability to concentrate pro-urine in response to AVP, which is mostly acquired due to electrolyte disturbances or lithium therapy. Alternatively, NDI is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.

  20. Nephrogenic diabetes insipidus partially responsive to oral desmopressin in a subject with lithium-induced multiple endocrinopathy.

    PubMed

    Kamath, C; Govindan, J; Premawardhana, A D; Wood, S J; Adlan, M A; Premawardhana, L D

    2013-08-01

    Lithium (Li) may cause multiple endocrinopathies, including hypercalcaemia, thyroid dysfunction and nephrogenic diabetes insipidus (NDI), but rarely in the same patient. The management of NDI remains a challenge. We report on a patient on long-term Li who had simultaneous NDI (paired serum and urine samples had abnormal osmolalities, typical of NDI, and treatment with parenteral desmopressin failed to affect urinary volume and serum osmolality), 'destructive' thyroiditis (hyperthyroidism, absent radioiodine uptake and absent thyrotrophin receptor antibodies) and primary hyperparathyroidism (compatible biochemistry, urine calcium excluding 'set point' anomalies and hypocalciuric hypercalcaemia, and normal parathyroid imaging). The thyroiditis resolved spontaneously and hypercalcaemia responded to reduction of Li dose. The NDI was unresponsive to amiloride, thiazides and ibuprofen in combination. However, urine output was reduced by 50% when a high dose of oral desmopressin was given. We conclude that Li-induced multiple endocrinopathy remains rare and, although NDI is difficult to manage, high dose oral desmopressin should be tried when other medications fail.

  1. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    PubMed

    Beckers, Albert; Aaltonen, Lauri A; Daly, Adrian F; Karhu, Auli

    2013-04-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  2. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

    PubMed Central

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  3. Nonfunctioning giant pituitary adenomas: Invasiveness and recurrence

    PubMed Central

    Landeiro, José Alberto; Fonseca, Elissa Oliveira; Monnerat, Andrea Lima Cruz; Taboada, Giselle Fernandes; Cabral, Gustavo Augusto Porto Sereno; Antunes, Felippe

    2015-01-01

    Background: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. Methods: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. Results: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. Conclusion: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence. PMID:26674325

  4. MRI of mediastinal parathyroid cystic adenoma causing hyperparathyroidism

    SciTech Connect

    Soler, R.; Bargiela, A.; Cordido, F.; Aguilera, C.; Argueeso, R.; Cao, I.

    1996-01-01

    Primary hyperparathyroidism is a common disorder that results from an increased secretion of parathyroid hormone, most often due to a solitary and solid parathyroid adenoma usually found in the inferior group of parathyroid glands. Parathyroid gland is ectopic in approximately 10 to 20% of the cases, and the retrosternal and prevascular mediastinum is the most common location. Most mediastinal parathyroid adenomas are solid and <3 cm, but mediastinal parathyroid cysts are very uncommon and rarely cause hyperparathyroidism. We know of 18 cases of mediastinal parathyroid cysts that have been previously reported and only four of them presented with hyperparathyroidism. We report an unusual case of hyperparathyroidism due to a large cystic parathyroid adenoma located in the anterior mediastinum diagnosed by MRI. 2 refs., 1 fig.

  5. [Giant parathyroid adenoma causing early recurrence of renal stones].

    PubMed

    Traxer, Olivier; Mouton, Albert; Abbecassis, Rémy; Tassard, Marc; Vigneau, Cécile; Gattegno, Bernard; Thibault, Philippe

    2004-06-01

    Primary hyperparathyroidism (PHPT) is not a rare disease. Renal stones are the most frequent complication of PHPT The authors report the case of a patient with giant parathyroid adenoma responsible for early recurrence of renal stones. Ultrasound examination of the neck, parathyroid MRI and Technetium99m-Sestamibi scintigraphy confirmed the parathyroid adenoma. Surgical exploration allowed resection of a giant adenoma (6.5 x 2.5 x 1.5 cm weighing 17 g). In the light of this case, the authors describe the characteristics of HPT define the place of preoperative imaging and emphasize the need for systematic aetiological work-up looking for HPT in all patients with a first episode of renal stones.

  6. PLAG1 expression is maintained in recurrent pleomorphic adenoma.

    PubMed

    de Brito, Beatriz Samara; Gaspar, Natália Giovanelli; Egal, Erika Said Abu; Sanchez-Romero, Celeste; Martins, Antonio Santos; Tincani, Álfio José; de Oliveira Gondak, Rogério; de Almeida, Oslei Paes; Kowalski, Luiz Paulo; Altemani, Albina; Mariano, Fernanda Viviane

    2016-10-01

    The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA.

  7. [Intrasellar small TSH secreting pituitary adenomas, 2 case reports].

    PubMed

    Ogawa, Yoshikazu; Tominaga, Teiji; Ikeda, Hidetoshi

    2007-07-01

    Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma accounts for 1% of pituitary adenoma and often manifests as invasive macroadenoma. If the TSH value is not high enough to cause clinical symptoms presenting as inappropriate secretion of TSH, the tumor may be missed or misdiagnosed as Graves disease. Some of these patients receive inadequate treatment with the antithyroid agent, radioiodine treatment, and thyroidectomy. This tumor is also known as a tough and firm tumor because of the significant interstitial fibrosis. We report two cases of TSH-secreting pituitary adenomas which were comparatively small. Although a tough and difficult operation was expected, actual tumor dissection was easy and gross total removal was achieved within less than 3 hours. We discuss the relationship between the intraoperative findings and histopathology, as well as the ultrastructure and endocrinology.

  8. Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

    PubMed

    Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

    2011-01-01

    Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

  9. Carcinoma ex-pleomorphic adenoma -- a giant tumor.

    PubMed

    Lung, T; Juncar, M

    2013-01-01

    Pleomorphic adenoma is one of the most frequent tumors that involve the parotid gland. The tumor constantly increases in dimension if not cured in due time and may become malignant. A case of a patient suffering from a carcinoma ex-pleomorphic adenoma that had a 20-year-evolution and reached impressive dimensions is presented. The tumor holds the second place worldwide among the largest carcinoma ex-pleomorphic adenoma in terms of size and the ninth place worldwide among the most voluminous parotid tumors ever surgically excised, as far as we know. Nevertheless, the regional invading character of the tumor in this particular case has been limited, without generating local lymph node invasion or metastases.

  10. Remarkable Triple Pleomorphic Adenoma Affecting both Parotid and Submandibular Glands

    PubMed Central

    Pingarrón-Martín, Lorena; Arias-Gallo, L. J.; Demaría-Martínez, G.; Chamorro Pons, M.

    2014-01-01

    The objective of this article is to present the first case reported in the literature of metachronous pleomorphic adenoma of bilateral parotid glands and submaxillary gland. The authors report the case of a 27-year-old female with metachronous mixed tumors in her right parotid and submandibular glands. The patient has no history of previous radiotherapy. All three lesions were diagnosed by fine-needle aspiration. The histopathologic evaluation of all three major salivary gland masses demonstrated pleomorphic adenomas, with no occult malignancy observed on serial sections. The presentation of pleomorphic adenomas in the parotids and submandibular glands probably represents three unrelated primary sites of tumor, yet the possibility of metastasis from one gland to the other cannot be excluded. PMID:26000084

  11. Gadolinium Deposition in Nephrogenic Systemic Fibrosis: An Examination of Tissue using Synchrotron X-ray Fluorescence Spectroscopy

    SciTech Connect

    High, W.; Ranville, J; Brown, M; Punshon, T; Lanzirotti, A; Jackson, B

    2010-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder associated with gadolinium (Gd)-based contrast agents dosed during renal insufficiency. In two patients, Gd deposition in tissue affected by nephrogenic systemic fibrosis was quantified using inductively coupled plasma mass spectrometry. The presence of Gd was confirmed and mapped using synchrotron x-ray fluorescence spectroscopy. Affected skin and soft tissue from the lower extremity demonstrated 89 and 209 ppm ({micro}g/g, dry weight, formalin fixed) in cases 1 and 2, respectively. In case 2, the same skin and soft tissue was retested after paraffin embedding, with the fat content removed by xylene washes, and this resulted in a measured value of 189 ppm ({micro}g/g, dry weight, paraffin embedded). Synchrotron x-ray fluorescence spectroscopy confirmed Gd in the affected tissue of both cases, and provided high-sensitivity and high-resolution spatial mapping of Gd deposition. A gradient of Gd deposition in tissue correlated with fibrosis and cellularity. Gd deposited in periadnexal locations within the skin, including hair and eccrine ducts, where it colocalized to areas of high calcium and zinc content. Because of the difficulty in obtaining synchrotron x-ray fluorescence spectroscopy scans, tissue from only two patients were mapped. A single control with kidney disease and gadolinium-based contrast agent exposure did not contain Gd. Gd content on a gravimetric basis was impacted by processing that removed fat and altered the dry weight of the specimens. Gradients of Gd deposition in tissue corresponded to fibrosis and cellularity. Adnexal deposition of Gd correlated with areas of high calcium and zinc content.

  12. A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

    PubMed

    Saglar, Emel; Deniz, Ferhat; Erdem, Beril; Karaduman, Tugce; Yönem, Arif; Cagiltay, Eylem; Mergen, Hatice

    2014-05-01

    X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

  13. Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas

    PubMed Central

    Newey, Paul J.; Nesbit, M. Andrew; Rimmer, Andrew J.; Attar, Moustafa; Head, Rosie T.; Christie, Paul T.; Gorvin, Caroline M.; Stechman, Michael; Gregory, Lorna; Mihai, Radu; Sadler, Greg; McVean, Gil; Buck, David

    2012-01-01

    Context: Genetic abnormalities, such as those of multiple endocrine neoplasia type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary (sporadic) parathyroid adenomas. Objective: To identify genetic abnormalities in nonhereditary parathyroid adenomas by whole-exome sequence analysis. Design: Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte DNA samples from 16 postmenopausal women without a family history of parathyroid tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland disease was cured by surgery. Somatic variants confirmed in this discovery set were assessed in 24 other parathyroid adenomas. Results: Over 90% of targeted exons were captured and represented by more than 10 base reads. Analysis identified 212 somatic variants (median eight per tumor; range, 2–110), with the majority being heterozygous nonsynonymous single-nucleotide variants that predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in six of 16 (∼35%) parathyroid adenomas, in association with loss of heterozygosity on chromosome 11. However, no other gene was mutated in more than one tumor. Mutations in several genes that may represent low-frequency driver mutations were identified, including a protection of telomeres 1 (POT1) mutation that resulted in exon skipping and disruption to the single-stranded DNA-binding domain, which may contribute to increased genomic instability and the observed high mutation rate in one tumor. Conclusions: Parathyroid adenomas typically harbor few somatic variants, consistent with their low proliferation rates. MEN1 mutation represents the major driver in sporadic parathyroid tumorigenesis although multiple low-frequency driver mutations likely account for tumors not harboring somatic MEN1 mutations. PMID:22855342

  14. Non-functioning pituitary adenoma: immunohistochemical analysis of 85 cases.

    PubMed

    Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad

    2007-01-01

    Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

  15. Long QT Syndrome and Duodenal Ampullary Adenoma: A New Association

    PubMed Central

    Hughes, Laura; Talha Khan, Muhammad; Khalid Hasan, Muhammad; Inayat, Irteza

    2016-01-01

    KCNQ1 gene mutation has a well-known association with long QT syndrome (LQTS). However, recent studies suggest that it may be implicated in intestinal neoplasia. We present a 27-year-old Hispanic man with a known history of LQTS secondary to KCNQ1 mutation, who presented with painless jaundice. Endoscopic retrograde pancreatic cholangiography revealed a prominent ampulla, with histology consistent with ampullary adenoma with high-grade dysplasia. Further endoscopic studies did not suggest familial adenomatous polyposis. To date, this is the index case of duodenal ampullary adenoma in the setting of KCNQ1 mutation. PMID:27921062

  16. Neuroendocrine Adenoma of the Middle Ear: A Rare Histopathological Diagnosis

    PubMed Central

    McGinness, Sam; Coleman, Hedley; Varikatt, Winny; da Cruz, Melville

    2016-01-01

    Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours. PMID:27429819

  17. Multiple, zonal and multi-zone adenoma detection rates according to quality of cleansing during colonoscopy

    PubMed Central

    Hassan, Cesare; Maselli, Roberta; Pontone, Paolo; Angelini, Rita; Brighi, Manuela; Patrizi, Gregorio; Pironi, Daniele; Magliocca, Fabio Massimo; Filippini, Angelo

    2016-01-01

    Background The safety and diagnostic accuracy of colonoscopy depend on the quality of colon cleansing. The adenoma detection rate is usually used as a quality measurement score. Objective We aimed to introduce and evaluate three new parameters to determine polyps and adenomas segmental localization and their distribution in association with different bowel preparation levels during colonoscopy. We introduce the multiple adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy), the zonal adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas (rectum, sigmoid, descending, transverse, ascending and cecum colon)), and multi-zone adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas with at least a segment between them with or without lesions (i.e. rectum and descending colon with or without lesions in the sigmoid)). Methods We prospectively enrolled outpatients who underwent colonoscopy from January 2013 to October 2014. The bowel preparation quality, according to the Aronchick modified scale, number and location of lesions, Paris classification and histology, were recorded. The multiple adenoma/polyp detection rate, zonal adenoma/polyp detection rate, and multi-zone adenoma/polyp detection rate were determined. Results In total, 519 consecutive patients (266/253 M/F; mean age 55.3 ± 12.8 years) were enrolled. The adenoma and polyp detection rates were 21% and 35%, respectively. Multiple adenomas were detected in 28 patients. Adenoma and polyp detection rate and new parameters were statistically significantly higher in the optimal as compared with the adequate bowel preparation. Conclusions An optimal level of bowel preparation was strongly associated not only with a higher adenoma detection rate, but also with a higher chance of detecting multiple clinically relevant lesions in adjacent or

  18. Accumulation of I-123 IMP in hepatic cell adenoma

    SciTech Connect

    Suto, Yuji; Kodama, Fumiko; Kato, Takashi

    1995-07-01

    I-123 IMP is now widely used as a radioactive material for cerebral blood flow scintigraphy. It is also known that this substance will accumulate in certain types of tumors. The authors present a case of a 47-year-old woman who showed accumulation of I-123 IMP in hepatic cell adenoma. 6 refs., 3 figs.

  19. Canalicular adenoma: a case report of an unusual parotid lesion

    PubMed Central

    Butler, Colin; Kulendra, Kevin N; Menon, Gopind; D’Souza, Alwyn R

    2009-01-01

    The present report describes a case of an 85-year-old woman who underwent an excisional biopsy of a preauricular lesion centred over the zygoma and subsequently developed an immediate iatrogenic facial palsy. Histopathological diagnosis revealed a canalicular adenoma of the parotid gland. PMID:21686469

  20. Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma

    PubMed Central

    Lee, Min Ho; Lee, Ju Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Jong Hyun; Kong, Doo-Sik

    2016-01-01

    Background Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. Methods We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. Results Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. Conclusion With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID:27195254

  1. Diagnosis and management of acromegaly: giant invasive adenoma.

    PubMed

    Cahyanur, Rahmat; Setyawan, Wawan; Sudrajat, Dedy G; Setyowati, Susie; Purnamasari, Dyah; Soewondo, Pradana

    2011-04-01

    Acromegaly is a rare disorder caused by excessive growth hormone. Majority of acromegaly are due to pituitary adenoma. It is estimated that 5% of pituitary adenoma become invasive and may grow to gigantic sizes (>4 cm in diameter). We would like to describe a man with giant invasive adenoma. We describe the case of 52-year-old man with acromegaly. The patient was presented to medical care because of hemichorea. He also had visual field defect, uncontrolled diabetes, and dyslipidemia. Hormonal profile showed increment of GH 2-hour after a standard 75-g oral glucose load and of high IGF-1 level with low level of FSH and LH. The next was performed by pituitary imaging. Magnetic resonance imaging showed a macroadenoma with diameter 2.3x3.5x6.6 cm3 that fills the sella tursica, and enlarges into suprasella, genu of corpus collosum, and invades third ventricle. This report describes a rare case of acromegalic patient with giant invasive adenoma. This could be a demonstrative case and lesson for diagnosis and manage acromegalic patient.

  2. Intrathyroidal parathyroid adenoma: preoperative identification and localization by parathyroid imaging

    SciTech Connect

    Al-Suhaili, A.R.; Lynn, J.; Lavender, J.P.

    1988-07-01

    The authors report, probably for the first time, a successful pre-operative localization of 7 mm intrathyroidal parathyroid adenoma which was successfully removed by using parathyroid imaging using a dual tracer (T1-201 and Tc-99m) and subtraction technique.

  3. CT of adenomas of the middle ear and mastoid cavity

    SciTech Connect

    Van Thong Ho; Rao, V.J.; Mikaelian, D.O.

    1996-03-01

    A case of mixed type adenoma of the middle ear and mastoid is presented in which CT showed complete opacification of the middle ear and mastoid air cells with bulging of the tympanic membrane but without ossicular or bony destruction. 7 refs., 1 figs.

  4. Concurrent somatotroph and plurihormonal pituitary adenomas in a cat.

    PubMed

    Sharman, Mellora; FitzGerald, Louise; Kiupel, Matti

    2013-10-01

    An 8-year-old, male neutered, domestic longhair cat was referred for investigation of insulin-resistant diabetes mellitus. Routine haematology, serum biochemistry, urinalysis (including culture), total T4 and urine creatinine:cortisol ratio were unremarkable, but markedly increased insulin-like growth factor-1 concentration was identified and a pituitary mass was subsequently documented. The cat was treated conservatively with the dopamine agonist L-deprenyl and was re-presented 16 months later for worsening polyuria, polydipsia, polyphagia, marked lumbar muscle atrophy, development of a pendulous abdomen and marked thinning of the abdominal skin. Hyperadrenocorticism was diagnosed based on abdominal ultrasonography, dexamethasone suppression testing and endogenous adrenocorticotropic hormone (ACTH). The cat was treated with trilostane (30 mg q24h PO) and showed some clinical improvement, but developed an opportunistic fungal infection and skin fragility syndrome 4.5 months after commencing treatment, and was euthanased. A double-pituitary adenoma comprising a discrete somatotroph adenoma and a separate plurihormonal adenoma (positive immunoreactivity for ACTH, melanocyte-stimulating hormone and follicle-stimulating hormone) was identified on post-mortem examination. These two pituitary adenomas were suspected to have arisen as independent neoplastic entities with the plurihormonal tumour either being clinically silent at the initial presentation or having developed over the subsequent 16 months.

  5. Whole-exome sequencing identifies variants in invasive pituitary adenomas

    PubMed Central

    Lan, Xiaolei; Gao, Hua; Wang, Fei; Feng, Jie; Bai, Jiwei; Zhao, Peng; Cao, Lei; Gui, Songbai; Gong, Lei; Zhang, Yazhuo

    2016-01-01

    Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of

  6. Assessment of Mitotic Activity in Pituitary Adenomas and Carcinomas.

    PubMed

    Thapar, Kamal; Yamada, Yukio; Scheithauer, Bernd; Kovacs, Kalman; Yamada, Shozo; Stefaneanu, Lucia

    1996-01-01

    Assessment of mitotic activity represents one of the oldest and most routinely used histopathologic methods of evaluating the biological aggressiveness of human tumors. In the case of pituitary tumors, however, the relevance of this approach as a means of gauging tumor behavior remains ill-defined. In this article, the relationship between the mitotic index and biological aggressiveness of pituitary tumors was evaluated in a series of 54 pituitary adenomas and 6 primary pituitary carcinomas. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross, operatively, or radiologically apparent infiltration of dura or bone. Mitotic figures were present in 11 tumors, 10 being either invasive adenomas or pituitary carcinomas. A significant association between the presence of mitotic figures and tumor behavior was noted, as evidenced by progressive increments in the proportion of cases expressing mitotic figures in the categories of noninvasive adenoma, invasive adenoma, and pituitary carcinoma (3.9, 21.4, and 66.7%, respectively; Fisher's exact test, two-tailed, p < 0.001). The mitotic index, however, appeared to be a less informative parameter, being extremely low in all cases (mean = 0.016% +/- 0.005 [+/- SEMI). Although the mean mitotic index in pituitary carcinomas (0.09% +/- 0.035) was significantly higher than the mean mitotic index of either noninvasive adenomas (0.002% +/- 0.002) or invasive adenomas (0.013% +/- 0.005), no practical threshold value capable of distinguishing these three groups was evident. Comparison of the mitotic index with Ki-67 derived growth fractions in these tumors revealed a significant but weak linear correlation (r = 0.41, p < 0.01). These data suggest that when, mitotic figures are present, they do provide some indication of the behavior and invasive potential of pituitary tumors. For routine diagnostic

  7. Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression.

    PubMed

    Jin, L; Chandler, W F; Smart, J B; England, B G; Lloyd, R V

    1993-03-01

    The distribution of chromogranin/secretogranin (Cg/Sg) mRNAs, determined by Northern and in situ hybridization, was analyzed in 14 cultured pituitary adenomas characterized by immunohistochemistry and hormone secretion in a defined medium in vitro. There were 5 functional GH adenomas, 1 silent GH adenoma, 7 null cell adenomas, and 1 oncocytoma. The null cell adenomas, oncocytoma, and silent GH adenomas were also analyzed by electron microscopy. Most null cell adenomas and the oncocytoma secreted FSH and LH into the culture medium. GH adenomas, which are examples of well differentiated tumors based on morphological examination, expressed significantly more SgIII mRNA compared to the null cell adenomas and oncocytoma (70 +/- 6% vs. 22 +/- 5%; P < 0.001). GH adenomas also expressed significantly less CgA mRNA compared to the less well differentiated null cell adenomas and oncocytoma (27 +/- 6% vs. 67 +/- 4%; P < 0.001), which could be considered less well differentiated based on ultrastructural morphological features. After treatment with phorbol 12-myristate 13-acetate (10(-7) M) for 7 days, there was an increase in the mRNA for CgB and SgII mRNAs in GH and null cell tumors, while dexamethasone treatment for 7 days increased CgA mRNA in GH and null cell adenomas. GnRH treatment for 7 days increased CgB mRNA in null cell adenomas. Phorbol 12-myristate 13-acetate also decreased the percentage of immunoreactive GH cells and GHm RNA, determined by in situ and Northern hybridization analyses. These results indicate that pituitary adenomas have a distinct pattern of Cg/Sg mRNA expression, which appears to be related to the degree of morphological differentiation of these neoplasms, and suggest that the effects of secretagogues on various Cg/Sg mRNA levels may be related to the stimulation of hormone secretion.

  8. Squamous cell carcinoma arising in a meningomyelocele.

    PubMed Central

    Saksun, J. M.; Fisher, B. K.

    1978-01-01

    Squamous cell carcinoma developed in the meningomyelocele of a 25-year-old man. This is the third such case reported. The possibility of malignant disease arising in this congenital defect must be taken into account when treatment is being considered. Images FIG. 1 FIG. 2 FIG. 3 PMID:709475

  9. ARISE: American renaissance in science education

    SciTech Connect

    1998-09-14

    The national standards and state derivatives must be reinforced by models of curricular reform. In this paper, ARISE presents one model based on a set of principles--coherence, integration of the sciences, movement from concrete ideas to abstract ones, inquiry, connection and application, sequencing that is responsive to how people learn.

  10. Food intake and colorectal adenomas: a case-control study in Malaysia.

    PubMed

    Ramadas, Amutha; Kandiah, Mirnalini

    2009-01-01

    It is well established that almost all colorectal cancers arise from benign, neoplastic adenomatous polyps. In previous studies, intake of fruits, vegetables and legumes were found to decrease the risk for colorectal adenomas (CRA) and colorectal cancer. This case-control study aimed to evaluate the roles of a variety of foods in contributing to the risk of CRA in Malaysian subjects. One hundred and eighteen subjects were recruited into case (n=59) and control (n=59) groups at Hospital Kuala Lumpur (HKL). A pre-tested quantitative food frequency questionnaire (FFQ) was used to record the types of food items and frequency consumed. Logistic regression was used to determine the crude and adjusted odds ratios of the independent variables. Soy bean and soy products were associated with a reduced risk for CRA (OR = 0.38, 95% CI = 0.15-0.98), while tubers were associated with increase in risk four-fold (OR = 4.14, 95% CI = 1.60-10.70) and red meat intake was found to increase the risk two and a half-fold (OR = 2.51, 95% CI = 1.02-6.28). Higher servings of fruits and vegetables were found to significantly decrease the risk (OR fruits = 0.47, 95% CI = 0.30-0.74; OR vegetables = 0.49, 95% = 0.29-0.80). In conclusion, our data support protective roles for soy, fruits and vegetables in the aetiology of colorectal adenomas and increase in risk in those with high intakes of red meat and tubers. Food intake of an individual may have an influence on one's risk for developing CRA. This finding warrants further investigation before the protective effect of these food items is to be accepted. New studies should explore the possibility of these associations among individuals in the general population especially with regard to different ethnic or other groups in Malaysia with low fruit and vegetable consumption.

  11. RT-01FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR PITUITARY ADENOMA WITH NOVALIS

    PubMed Central

    Arakawa, Yoshiki; Mizowaki, Takashi; Ogura, Kengo; Sakanaka, Katsuyuki; Hojo, Masato; Hiraoka, Masahiro; Miyamoto, Susumu; Murata, Daiki

    2014-01-01

    BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.

  12. Circulating levels of inflammatory cytokines and risk of colorectal adenomas

    PubMed Central

    Kim, Sangmi; Keku, Temitope O.; Martin, Christopher; Galanko, Joseph; Woosley, John T.; Schroeder, Jane C.; Satia, Jessie A.; Halabi, Susan; Sandler, Robert S.

    2009-01-01

    The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-α in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-α were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between levels of inflammatory cytokines, colorectal adenomas, and known risk factors. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines such as older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-α, and to a lesser degree, with CRP. For IL-6, adjusted odds ratios for colorectal adenomas were 1.78 (95% confidence interval [CI]: 1.18–2.68) for the second highest plasma level, and 1.84 (95% CI: 1.24– 2.74) for the highest level compared with the reference level. A similar association was found with TNF-α, with adjusted odds ratios of 1.54 (95% CI: 1.02–2.33) and 1.65 (95% CI: 1.09–2.50), respectively. Our findings indicate that inflammation might be involved in the early development of colorectal neoplasia, and suggest that systemic inflammatory cytokines might be an indicator of obesity and other risk factors for colorectal neoplasia. PMID:18172326

  13. Two Phenotypes of Traditional Serrated Adenomas Nationwide Survey in Iceland.

    PubMed

    Rubio, Carlos A; Jónasson, Jón G

    2015-09-01

    Iceland has a total population of 300,000 inhabitants. All patients consulting for symptoms of the lower digestive tract during a four-year period (2003-2006) were subjected to a colonoscopic examination; all polyps were endoscopically removed. Out of the total 3,037 colorectal adenomas (CRAs), 308 (10.2%) were traditional serrated adenomas (TSAs). TSAs were divided according the predominant histological phenotype (>50%) into those with ectopic crypt formations (ECF), and those with unlocked serrations (US). ECF-TSA accounted for 5.9% (178/3037) and US-TSA for 4.3% (130/3037). The majority of patients with ECF-TSA and US-TSA were ≥ 60 years of age (74.1% and 76.2%, respectively). Notwithstanding, when patients having advanced adenomas (with high-grade dysplasia, with or without intramucosal carcinoma) were listed by age, those with ECF-TSA were significantly younger than those with US-TSA (p<0.05). ECF-TSA were more frequently left-sided (71.8%), whereas US-TSA were more frequently right-sided (60.0%). Invasive carcinoma evolved more frequently in ECF-TSA (7.8%) and in US-TSA (7.7%) than in tubular adenomas and in villous/tubulovillous adenomas (0.1% and 4.4%, respectively). Comparative studies indicated that the incidence rates/year of ECF-TSA and US-TSA were significantly higher in Iceland than in Sweden or in Italy (p<0.05). Genetic and putative epigenetic (environmental) factor(s) might account for the high incidence rate/year of ECF-TSA and US-TSA in this country.

  14. Transanal endoscopic microsurgery for rectal adenomas: single center experience

    PubMed Central

    Samalavicius, Narimantas Evaldas; Mikelis, Kipras; Samalavicius, Robertas

    2015-01-01

    Introduction Transanal endoscopic microsurgery (TEM) is a method of choice for the local treatment of rectal adenomas. Though generally considered as a safe method, some authors have expressed skepticism about the anorectal function following TEM. Aim To review our experience in using TEM for removal of rectal adenomas. We focused on morbidity, local recurrence rates, and anorectal function following the operation. Material and methods The study included 72 patients who underwent TEM for rectal adenomas from December 2009 to November 2014 at the Department of Surgical Oncology, National Cancer Institute. Of the 72 patients, 31 (43.1%) were lost in the follow-up. We recorded the demographics, operative details, final pathology, post-operative length of stay, post-operative complications, recurrences and functional outcome for each of the 41 (56.9%) remaining participants. Results Of the 41 eligible patients, 19 (46.3%) were male and 22 (53.7%) were female. The mean age of our patients was 66.8 years. There were no intraoperative complications. In 4 (9.8%) cases, postoperative complications were observed – urinary retention (2 cases, 4.9%) and postoperative hemorrhage (2 cases, 4.9%). All complications were treated conservatively. There was a single case (2.4%) of adenoma recurrence during the follow-up period. The mean score of the FISI questionnaire was 7.6 ±9.2 (ranging from 0 to 36), and the mean Wexner score was 2.3 ±3.4 (ranging from 0 to 17). Conclusions Transanal endoscopic microsurgery in our experience demonstrated low complication and recurrence rates, and good functional results. We conclude that TEM is an effective and safe method for the treatment of rectal adenomas. PMID:28133497

  15. Meat intake and the recurrence of colorectal adenomas.

    PubMed

    Mathew, A; Sinha, R; Burt, R; Caan, B; Paskett, E; Iber, F; Kikendall, W; Lance, P; Shike, M; Weissfeld, J; Schatzkin, A; Lanza, E

    2004-06-01

    A large multicenter randomized controlled trial was re-assessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (T0) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at T0, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from T0 to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence.

  16. Thymosin ß4 expression in colorectal polyps and adenomas

    PubMed Central

    Nemolato, Sonia; Cabras, Tiziana; Restivo, Angelo; Zorcolo, Luigi; Di Felice, Eliana; Fanni, Daniela; Gerosa, Clara; Messana, Irene; Castagnola, Massimo; Faa, Gavino; Casula, Giuseppe

    2013-01-01

    OBJECTIVE: Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis. METHODS: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry. RESULTS: Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells. CONCLUSIONS: Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown. PMID:24141838

  17. Long-Term Outcomes of Radiotherapy for Pituitary Adenomas

    SciTech Connect

    Snead, Felicia E. Amdur, Robert J. M.D.; Morris, Christopher G. M.S.; Mendenhall, William M.

    2008-07-15

    Purpose: To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). Methods and Materials: The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6-20.2 years) for all patients and 6.2 years (range, 2-20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43-50.4 Gy). Results: The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively (p 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS (p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS (p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. Conclusions: This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.

  18. Gigantism caused by growth hormone secreting pituitary adenoma.

    PubMed

    Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

    2014-06-01

    Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

  19. New challenges of the ARISE project

    NASA Astrophysics Data System (ADS)

    Blanc, Elisabeth

    2015-04-01

    It has been robustly demonstrated that variations in the circulation of the middle atmosphere influence weather and climate throughout the troposphere all the way to the Earth's surface. A key part of the coupling between the troposphere and stratosphere occurs through the propagation and breaking of planetary-scale Rossby waves and gravity waves. Limited observation of the middle atmosphere and these waves in particular limits the ability to faithfully reproduce the dynamics of the middle atmosphere in numerical weather prediction and climate models. The ARISE project combines for the first time international networks with complementary technologies such as infrasound, lidar and airglow. This joint network provided advanced data products that started to be used as benchmarks for weather forecast models. The ARISE network also allows enhanced and detailed monitoring of other extreme events in the Earth system such as erupting volcanoes, magnetic storms, tornadoes and tropical thunderstorms. In order to improve the ability of the network to monitor atmospheric dynamics, ARISE proposes to extend i) the existing network coverage in Africa and the high latitudes, ii) the altitude range in the stratosphere and mesosphere, iii) the observation duration using routine observation modes, and to use complementary existing infrastructures and innovative instrumentations. Data will be collected over the long term to improve weather forecasting to monthly or seasonal timescales, to monitor atmospheric extreme events and climate change. ARISE focuses on the link between models and observations for future assimilation of data by operational weather forecasting models. Among the applications, ARISE2 proposes infrasound remote volcano monitoring to provide notifications to civil aviation.

  20. Gene expression profiling analysis of MENX-associated rat pituitary adenomas contributes to understand molecular mechanisms of human pituitary adenomas

    PubMed Central

    ZHANG, HONGZHI; XU, CHUAN; SUN, NINGYANG; ZHOU, YINTING; YU, XIAOFEI; YAN, XUE; ZHANG, QIUJUAN

    2016-01-01

    The present study aimed to screen potential genes associated with pituitary adenomas to obtain further understanding with regard to the pathogenesis of pituitary adenomas. The microarray GSE23207 dataset, containing 16 pituitary adenoma samples from multiple endocrine neoplasia syndrome-associated rats and 5 normal pituitary tissue samples, was downloaded from Gene Expression Omnibus. The Linear Models for Microarray Data package was used to identify the differentially-expressed genes (DEGs) with the cut-off criteria of a |log2fold change (FC)|>1 and adjusted P-values of <0.05. The potential functions of the DEGs were predicted by functional and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery. Furthermore, the interaction associations of the up- and downregulated DEGs obtained from the Search Tool for the Retrieval of Interacting Genes database were respectively revealed by the protein-protein interaction networks visualized with Cytoscape. A total of 391 upregulated and 238 downregulated DEGs in were screened in the pituitary adenoma samples. The upregulated DEGs with a higher degree in the protein-protein interaction network (e.g., CCNA2, CCNB1 and CDC20) were significantly involved in cell cycle and cell division. Notably, PTTG1 was enriched in every functional term. These DEGs interacted with each other. The downregulated DEGs (e.g., GABRA1, GABRA4 and GABRB1) also interacted with each other, and were relevant to neuroactive ligand-receptor interaction; the DEG POU1F1, interacting with POMC, was correlated with the development of the pituitary gland, adenohypophysis and endocrine system. Certain DEGs, including CCNB1, CCNA2, CDC20, GABRA1, GABRA4, GABRB1, POU1F1 and POMC, and particularly PTTG1, were shown to be closely involved in the pathogenesis of pituitary adenomas. PMID:26870179

  1. Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

    PubMed Central

    Lim, Chul-Hyun; Cho, Young-Seok

    2016-01-01

    Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

  2. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas

    PubMed Central

    Jogunoori, Wilma; Menon, Vipin; Majumdar, Avijit; Chen, Jiun-Sheng; Gi, Young Jin; Jeong, Yun Seong; Phan, Liem; Belkin, Mitchell; Gu, Shoujun; Kundra, Suchin; Mistry, Nipun A.; Zhang, Jianping; Su, Xiaoping; Li, Shulin; Lin, Sue-Hwa; Javle, Milind; McMurray, John S.; Rahlfs, Thomas F.; Mishra, Bibhuti; White, Jon; Rashid, Asif; Beauchemin, Nicole; Weston, Brian R.; Shafi, Mehnaz A.; Stroehlein, John R.; Davila, Marta; Akbani, Rehan; Weinstein, John N.; Wu, Xifeng; Mishra, Lopa

    2016-01-01

    Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression. PMID:27100181

  3. Gallium-67 uptake by a benign adrenocortical adenoma

    SciTech Connect

    Jackson, J.A.; Naul, L.G.; Montgomery, J.L.; Carpentier, W.R.; Roberts, J.W.

    1988-08-01

    A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by /sup 67/Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because /sup 67/Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormal /sup 67/Ga uptake and atypical MR findings.

  4. Urolithiasis and primary parathyroid adenoma: report of one case.

    PubMed

    Lee, Jing-Sheng; Lau, Beng-Huat; Yeh, Ming-Lun; Lee, Chin-Cheng

    2003-01-01

    A 12-year-old girl was admitted to ward because of persistent left flank pain, vomiting, and hematuria. A stone was located at the ureteropelvic junction of the left kidney, as determined by means of abdominal sonography. Metabolic investigation for a renal stone revealed that she had hypercalcemia, hypophosphatemia, and hypercalciuria. Hyperparathyroidism was diagnosed based on the hypercalcemia and inappropriately elevated serum parathyroid hormone level. A parathyroid adenoma was successfully diagnosed by using thallium/technetium subtraction parathyroid scanning. Extracorporeal shock wave lithotripsy was performed to treat the renal stone, and the parathyroid adenoma was successfully removed. The patient's postoperative course was uneventful. This case is presented because urolithiasis and hyperparathyroidism are rare in children. Metabolic evaluation is mandatory in children with a renal stone. Further investigation for the hyperparathyroidism should be performed if hypercalcemia associated with hypercalciuria is documented.

  5. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

    PubMed

    Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

    2008-07-28

    Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

  6. Pituitary adenomas: historical perspective, surgical management and future directions

    PubMed Central

    Theodros, Debebe; Patel, Mira; Ruzevick, Jacob; Lim, Michael; Bettegowda, Chetan

    2016-01-01

    Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity. PMID:26497533

  7. Pure Androgen-Secreting Adrenal Adenoma Associated with Resistant Hypertension

    PubMed Central

    Rodríguez-Gutiérrez, René; Bautista-Medina, Mario Arturo; Teniente-Sanchez, Ana Eugenia; Zapata-Rivera, Maria Azucena; Montes-Villarreal, Juan

    2013-01-01

    Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed. PMID:23819074

  8. Pure androgen-secreting adrenal adenoma associated with resistant hypertension.

    PubMed

    Rodríguez-Gutiérrez, René; Bautista-Medina, Mario Arturo; Teniente-Sanchez, Ana Eugenia; Zapata-Rivera, Maria Azucena; Montes-Villarreal, Juan

    2013-01-01

    Pure androgen-secreting adrenal adenoma is very rare, and its diagnosis remains a clinical challenge. Its association with resistant hypertension is uncommon and not well understood. We present an 18-year-old female with a 10-year history of hirsutism that was accidentally diagnosed with an adrenal mass during the evaluation of a hypertensive crisis. She had a long-standing history of hirsutism, clitorimegaly, deepening of the voice, and primary amenorrhea. She was phenotypically and socially a male. FSH, LH, prolactin, estradiol, 17-hydroxyprogesterone, and progesterone were normal. Total testosterone and DHEA-S were elevated. Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonclassic congenital adrenal hyperplasia were ruled out. She underwent adrenalectomy and pathology reported an adenoma. At 2-month followup, hirsutism and virilizing symptoms clearly improved and blood pressure normalized without antihypertensive medications, current literature of this unusual illness and it association with hypertension is presented and discussed.

  9. X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking

    PubMed Central

    Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Öberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J.; Deen, Peter M. T.; Törnroth-Horsefield, Susanna

    2014-01-01

    Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein–protein interactions involved in cellular sorting of AQP2. Two Cd2+-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking. PMID:24733887

  10. Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus

    SciTech Connect

    Yuasa, Hiromitsu; Ito, Masafumi; Oiso, Yutaka; Kurokawa, Masaei; Saito, Hidehiko; Watanabe, Tohru; Oda, Yoshihiko; Ishizuka, Toshie; Tani, Nagayuki; Ito, Seiki; Shibata, Akira

    1994-08-01

    Novel mutations in the V2 vasopressin receptor gene were identified in two Japanese pedigrees with X-linked congenital nephrogenic diabetes insipidus. The V2 receptor belongs to the family of G-protein-coupled receptors that contain seven distinct transmembrane domains, and the V2 receptor gene is encoded by three exons. The coding regions amplified by polymerase chain reaction were directly sequenced. In a pedigree, one of four consecutive guanine sequences (nucleotides 528-531) in the second exon was deleted (528delG). This deletion mutation results in a frame shift beginning at codon 154 in the second intracellular domain and a premature termination at codon 161. In another pedigree, a missense mutation (A{yields}G) was identified at nucleotide position 310 in the second exon. This point mutation, H80R, changes a histidine at codon 80 in the second transmembrane domain to an arginine that is more positively charged than histidine under the neutral environment. Each mutation cosegregated with the phenotype of diabetes insipidus and supposed to be a cause for resistance to arginine vasopressin. 35 refs., 4 figs., 2 tabs.

  11. A novel SLC12A1 gene mutation associated with hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus, and nephrocalcinosis in four patients.

    PubMed

    Wongsaengsak, Sariya; Vidmar, Alaina P; Addala, Ananta; Kamil, Elaine S; Sequeira, Paola; Fass, Benjamin; Pitukcheewanont, Pisit

    2017-04-01

    Solute Carrier Family 12 member 1 (SLC12A1) gene encodes the sodium-potassium-chloride co-transporter (NKCC2) at the apical membrane of the thick ascending loop of Henle (TAL). Bartter's syndrome (BS) type I is a rare, autosomal recessive, renal tubular disorder associated with mutation of the SLC12A1 gene. Presenting features include: hypokalemic metabolic alkalosis, hypercalciuria and nephrocalcinosis. The many allelic variants reported present with a spectrum of phenotypes, biochemical abnormalities and clinical severities. However, to date, only two reports have described hyperparathyroidism and hypercalcemia in patients with SLC12A1 gene mutations. We describe 4 patients with 4 novel mutation variants in the SLC12A1 gene (c.735C>G, c.1137del, c.2498-2499del, and c.1833delT) presenting with variable degrees of hyperparathyroidism, hypercalcemia, hypokalemic metabolic alkalosis, nephrocalcinosis, and nephrogenic diabetes insipidus. The link between calcium and parathyroid hormone abnormalities in patients with SLC12A1 mutations is unclear; the cases described suggest an association between primary hyperparathyroidism and loss of function mutation of SLC12A1, which may result in an aberrant threshold of the calcium sensing receptor at the level of the kidney.

  12. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

    PubMed

    Bichet, Daniel G; Bockenhauer, Detlef

    2016-03-01

    Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration.

  13. A novel AVPR2 gene mutation of X-linked congenital nephrogenic diabetes insipidus in an Asian pedigree.

    PubMed

    Guo, Wei-Hong; Li, Qiang; Wei, Hong-Yan; Lu, Hong-Yan; Qu, Hui-Qi; Zhu, Mei

    2016-08-25

    Polyuria and polydipsia are the characteristics of congenital nephrogenic diabetes insipidus (CNDI). Approximately 90% of all patients with CNDI have X-linked hereditary disease, which is due to a mutation of the arginine vasopressin receptor 2 (AVPR2) gene. This case report describes a 54-year-old male with polyuria and polydipsia and several male members of his pedigree who had the same symptoms. The proband was diagnosed with diabetes insipidus using a water-deprivation and arginine vasopressin stimulation test. Genomic DNA from the patient and his family members was extracted and the AVPR2 gene was sequenced. A novel missense mutation of a cytosine to guanine transition at position 972 (c.972C > G) was found, which resulted in the substitution of isoleucine for methionine at amino acid position 324 (p.I324M) in the seventh transmembrane domain of the protein. The proband's mother and daughter were heterozygous for this mutation. The novel mutation of the AVPR2 gene further broadens the phenotypic spectrum of the AVPR2 gene.

  14. X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking.

    PubMed

    Frick, Anna; Eriksson, Urszula Kosinska; de Mattia, Fabrizio; Oberg, Fredrik; Hedfalk, Kristina; Neutze, Richard; de Grip, Willem J; Deen, Peter M T; Törnroth-Horsefield, Susanna

    2014-04-29

    Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary hormone arginine vasopressin and defective trafficking results in nephrogenic diabetes insipidus (NDI). Here we present the X-ray structure of human AQP2 at 2.75 Å resolution. The C terminus of AQP2 displays multiple conformations with the C-terminal α-helix of one protomer interacting with the cytoplasmic surface of a symmetry-related AQP2 molecule, suggesting potential protein-protein interactions involved in cellular sorting of AQP2. Two Cd(2+)-ion binding sites are observed within the AQP2 tetramer, inducing a rearrangement of loop D, which facilitates this interaction. The locations of several NDI-causing mutations can be observed in the AQP2 structure, primarily situated within transmembrane domains and the majority of which cause misfolding and ER retention. These observations provide a framework for understanding why mutations in AQP2 cause NDI as well as structural insights into AQP2 interactions that may govern its trafficking.

  15. Combination of secretin and fluvastatin ameliorates the polyuria associated with X-linked nephrogenic diabetes insipidus in mice.

    PubMed

    Procino, Giuseppe; Milano, Serena; Carmosino, Monica; Barbieri, Claudia; Nicoletti, Maria C; Li, Jian H; Wess, Jürgen; Svelto, Maria

    2014-07-01

    X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

  16. Cooperative mechanisms involved in chronic antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Moosavi, S M S; Karimi, Z

    2014-03-01

    Previous studies of central diabetes insipidus suggested that thiazides acutely exerted a paradoxical antidiuresis by either indirectly activating volume-homeostatic reflexes to decrease distal fluid-delivery, or directly stimulating distal water-reabsorption. This study investigated whether the direct and indirect actions of bendroflumethiazide (BFTZ) simultaneously cooperated and also whether the renal nerves were involved in inducing long-term antidiuresis in nephrogenic diabetes insipidus (NDI). BFTZ or vehicle was gavaged into bilateral renal denervated and innervated rats with lithium-induced NDI for 10 days, constituting four groups. At one day before (D0) and one, five and ten days after starting administration of BFTZ or vehicle, rats were placed in metabolic cages to collect urine for 6 hours. BFTZ-treatment in both renal innervated and denervated rats caused equivalent reductions in urine-flow, creatinine clearance, lithium clearance and free-water clearance, but rises in urine-osmolality, fractional proximal reabsorption and fractional distal reabsorption at all days compared to D0, as well as to those of their relevant vehicle-received group. Therefore, the chronic antidiuretic response to BFTZ in conscious NDI rats was exerted through a concomitant cooperation of its direct distal effect of stimulating water-reabsorption and its indirect effect of reducing distal fluid-delivery by activating volume-homeostatic mechanisms, which appeared independent of the renal nerves.

  17. Huge Parathyroid Adenoma with Dysphagia Presentation; A Case Report from Southern Iran

    PubMed Central

    Ziaeean, Bizhan; Sohrabi-Nazari, Sahar

    2016-01-01

    Parathyroid adenoma is a benign tumor of the parathyroid glands. The cause of most parathyroid adenomas is unknown. Parathyroid adenoma increases the secretion of parathyroid hormone and results in primary hyperparathyroidism. High amounts of parathyroid hormone in the blood cause the imbalance of calcium, which leads to various complications such as kidney stones, depression, lethargy, nausea, vomiting, abdominal pain, myalgia, bone and joint pain, hoarseness, etc. Oropharyngeal dysphagia is defined as having problem in swallowing due to abnormalities in the structure and function of oropharynx and other related organs. The exact prevalence of dysphagia caused by parathyroid adenoma is unknown, but since this complication can lead to increased mortality and morbidity, its diagnosis is important. It is difficult to distinguish parathyroid malignancies from parathyroid adenoma even after surgery. Therefore, the final diagnosis is possible through surgery and histopathological evaluation. Here, a case of parathyroid adenoma with first presentation of generalized weakness and dysphagia has been reported. PMID:27582595

  18. Endoscopic innovations to increase the adenoma detection rate during colonoscopy

    PubMed Central

    Dik, Vincent K; Moons, Leon MG; Siersema, Peter D

    2014-01-01

    Up to a quarter of polyps and adenomas are missed during colonoscopy due to poor visualization behind folds and the inner curves of flexures, and the presence of flat lesions that are difficult to detect. These numbers may however be conservative because they mainly come from back-to-back studies performed with standard colonoscopes, which are unable to visualize the entire mucosal surface. In the past several years, new endoscopic techniques have been introduced to improve the detection of polyps and adenomas. The introduction of high definition colonoscopes and visual image enhancement technologies have been suggested to lead to better recognition of flat and small lesions, but the absolute increase in diagnostic yield seems limited. Cap assisted colonoscopy and water-exchange colonoscopy are methods to facilitate cecal intubation and increase patients comfort, but show only a marginal or no benefit on polyp and adenoma detection. Retroflexion is routinely used in the rectum for the inspection of the dentate line, but withdrawal in retroflexion in the colon is in general not recommended due to the risk of perforation. In contrast, colonoscopy with the Third-Eye Retroscope® may result in considerable lower miss rates compared to standard colonoscopy, but this technique is not practical in case of polypectomy and is more time consuming. The recently introduced Full Spectrum Endoscopy™ colonoscopes maintains the technical capabilities of standard colonoscopes and provides a much wider view of 330 degrees compared to the 170 degrees with standard colonoscopes. Remarkable lower adenoma miss rates with this new technique were recently demonstrated in the first randomized study. Nonetheless, more studies are required to determine the exact additional diagnostic yield in clinical practice. Optimizing the efficacy of colorectal cancer screening and surveillance requires high definition colonoscopes with improved virtual chromoendoscopy technology that visualize the

  19. Pleomorphic adenoma of the lacrimal gland. Case report.

    PubMed

    Ostrosky, Alejandro; Klurfan, Federico Juan; Gonzalez, Maximiliano Jorge; Camaly, Diego; Villa, Diego

    2005-01-01

    Lacrimal gland tumors are rare. We present a case of a 69 year old male patient with a one year history of an orbital tumor (Pleomorphic Adenoma). The tumor was surgically enucleated and patient recovery was very satisfactory, with no signs of recurrence after one year of follow-up. A review of the clinical symptoms, radiologic features, treatment and histopathology of this kind of tumors is also made.

  20. Kapteyn series arising in radiation problems

    NASA Astrophysics Data System (ADS)

    Lerche, I.; Tautz, R. C.

    2008-01-01

    In discussing radiation from multiple point charges or magnetic dipoles, moving in circles or ellipses, a variety of Kapteyn series of the second kind arises. Some of the series have been known in closed form for a hundred years or more, others appear not to be available to analytic persuasion. This paper shows how 12 such generic series can be developed to produce either closed analytic expressions or integrals that are not analytically tractable. In addition, the method presented here may be of benefit when one has other Kapteyn series of the second kind to consider, thereby providing an additional reason to consider such series anew.

  1. Eccrine Poroma Arising within Nevus Sebaceous

    PubMed Central

    Girdwichai, Natnicha; Chanprapaph, Kumutnart; Vachiramon, Vasanop

    2016-01-01

    Nevus sebaceous is a congenital, benign hamartomatous lesion, characterized by a yellowish to skin-colored, hairless, verrucous plaque on the head and neck region. In later life, a secondary tumor, either benign or malignant, can develop within nevus sebaceous. Eccrine poroma developing on nevus sebaceous is extremely rare. There are few case reports of eccrine poroma developing within nevus sebaceous. We report a case of a 30-year-old female who presented with a congenital, hairless, verrucous, yellowish lesion on the scalp and an erythematous nodule arising within the yellowish lesion for 8 months. Her clinical presentation and histopathological findings were compatible with nevus sebaceous and eccrine poroma. PMID:27194975

  2. Glomangiosarcoma Arising from a Prior Biopsy Site

    PubMed Central

    Maselli, Amy M.; Jambhekar, Amani V.

    2017-01-01

    Summary: Glomangiosarcoma represents a rare malignant variant of the benign glomus tumor that typically presents as a tender, slowly growing nodule with a predilection for the lower extremities. Unlike their benign counterparts, glomangiosarcomas may display aggressive characteristics such as large size, local invasion, and a tendency to recur after excision. Although wide local excision remains the treatment of choice, rare cases of systemic metastasis have been previously reported. We present a case of glomangiosarcoma arising at a prior biopsy site after excision of an unknown soft tissue lesion. PMID:28203514

  3. MRI appearances of an ectopic pituitary adenoma: case report and review of the literature.

    PubMed

    Slonim, S M; Haykal, H A; Cushing, G W; Freidberg, S R; Lee, A K

    1993-01-01

    MR images of an ectopic pituitary adenoma have been published in only a single case, a suprasellar mass. We present a patient with Cushing's disease in whom MRI revealed a pituitary adenoma within the sphenoid sinus. Radiologic characteristics of ectopic pituitary adenomas are reviewed, with emphasis on MRI, which demonstrates a soft tissue mass, isointense with gray matter on T1-weighted images, which enhances in a heterogeneous manner.

  4. Pleomorphic adenoma of the nasal septum: a case report

    PubMed Central

    Gana, Polycarp; Masterson, Liam

    2008-01-01

    Introduction Pleomorphic adenomas are the most common benign tumour of the major salivary glands. In addition, they may also occur in the minor salivary glands of the hard and soft palate. Intranasal pleomorphic adenomas are unusual and may be misdiagnosed because they have greater myoepithelial cellularity and fewer myxoid stromata compared to those elsewhere. Case presentation We present the case of a 61-year-old man who presented with a 2-year history of left nasal obstruction, occasional epistaxis and facial pain. Radiological examination demonstrated well pneumatised paranasal sinuses and a soft tissue mass in the anterior aspect of the left nasal cavity. In this patient, an intranasal approach was used to achieve a wide local resection. Conclusion Pleomorphic adenomas are rare tumours of the nasal cavity and have been shown to be misdiagnosed in over half of cases leading to more aggressive treatment than is necessary. If unilateral nasal obstruction is the main presenting complaint, we suggest consideration of this diagnosis. In view of the potential for tumour recurrence, long-term follow-up and careful examination of the nose with an endoscope are necessary. PMID:19014678

  5. Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas

    SciTech Connect

    Russo, D.; Arturi, F.; Filetti, S.

    1996-04-01

    Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors. 28 refs., 2 tabs.

  6. Multifocal canalicular adenoma of the minor labial salivary glands

    PubMed Central

    Samar, María Elena; Avila, Rodolfo Esteban; Fonseca, Ismael Bernardo; Anderson, William; Fonseca, Gabriel M; Cantín, Mario

    2014-01-01

    Canalicular adenoma (CA) is an uncommon benign neoplasia of salivary glands which is clinically difficult to recognise. Despite having an excellent prognosis, the histological diagnosis and clinical management of this entity can be troublesome. While the main differential diagnosis to consider is basal cell adenoma (BCA), similar histological patterns and multifocality have been observed in adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA), both locally-aggressive malignancies which require radically different treatment to CA. An emphasis has been placed on the value of immunohistochemistry in avoiding diagnostic and surgical errors. CA is positive for AE1/AE3, CD117 and S-100 protein, and negative for p63, α-SMA, Ki 67 and vimentin. Here we discuss the case of a 61-year-old female with CA in her right upper lip, showing multifocal growth histologically. The differential diagnosis with other adenomas is discussed in addition to the role of immunohistochemical studies that can confirm the clinical and surgical findings. PMID:25550873

  7. Clinicopathologic analysis of pituitary adenoma: a single institute experience.

    PubMed

    Cho, Hwa Jin; Kim, Hanna; Kwak, Yoon Jin; Seo, Jeong Wook; Paek, Sun Ha; Sohn, Chul-Ho; Yun, Jung Min; Kim, Da Seu Ran; Kang, Peter; Park, Peom; Park, Sung-Hye

    2014-03-01

    Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

  8. Adenoma of the ampulla of Vater: a case report

    PubMed Central

    2014-01-01

    Introduction Lesions of the ampulla of Vater are rare histological entities with an incidence of between 0.1 and 0.2% of gastrointestinal tumors. Until recently the main response to this kind of lesion was duodenopancreatectomy, regardless of the cellular atypia and local edema. In this study, we propose the application of transduodenal local excision of the ampulla of Vater especially in recognized cases of nonmalignant adenomas. Case presentation In this case report we analyze the case of a 78-year-old Greek man who revealed symptoms such as icterus, abdominal pain without constipation and bloody stools. A physical examination showed painless swelling of the gallbladder (Courvoisier sign). No previous abdominal operations or hernias were identified. Blood tests, computed tomography scan analysis, gastroscopy and endoscopic retrograde cholangiopancreatography along with biopsies and cytological tests diagnosed nonmalignant adenoma of the ampulla of Vater with high-grade dysplasia. The treatment we followed was transduodenal local excision of his ampulla of Vater. Conclusions Transduodenal local excision of the ampulla of Vater has limited side effects and postoperative complications, suggesting this particular technique to be the proper treatment for nonmalignant cases of adenomas. PMID:24965285

  9. Intraosseous pleomorphic adenoma: case report and review of the literature.

    PubMed

    Aver-De-Araujo, L M; Chaves-Tarquinio, S B; Neuzling-Gomes, A P; Etges, A

    2002-01-01

    Pleomorphic adenoma is the most common neoplasm of the salivary glands, affecting mainly the parotid gland. The preferential intraoral site of this tumor is the palate. A case of a 31-year-old woman with an intraosseous pleomorphic adenoma located in the maxilla (left paramedian region), showing an approximate evolution of one year is reported. The present intraosseous case represents a rare location, with the tumor probably originating from glandular epithelial remnants captured during embryogenesis. In a review of the literature of 142 cases of intragnathic localization (24% in the maxilla) are identified. A slight predominance of women was observed (56%), with 55% of the patients being affected during the 5th to 7th decade of life. The tumors were malignant in 94% of the cases, with special predominance of mucoepidermoid carcinoma (65%). Intraosseous pleomorphic adenomas are rare, with the present patient being the 6th case reported in the literature and the second found in the maxilla. Mean age of the 5 previously reported cases was 58.8 years.

  10. Traditional serrated adenomas of the upper digestive tract

    PubMed Central

    Rubio, CA

    2016-01-01

    For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma–carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract. PMID:26468393

  11. Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    PubMed

    Daly, Adrian F; Beckers, Albert

    2015-03-01

    The most frequent conditions that are associated with inherited/familial pituitary adenomas are familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 1 (MEN1), which together account for up to 5% of pituitary adenomas. One important genetic cause of FIPA are inactivating mutations or deletions in the aryl hydrocarbon receptor interacting protein (AIP) gene. FIPA is the most frequent clinical presentation of AIP mutations. This article traces the current state of knowledge regarding the clinical features of FIPA and the particular genetic, pathologic, and clinical characteristics of pituitary adenomas due to AIP mutations.

  12. Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas.

    PubMed

    Jia, Ruichao; Li, Mu; Chang, Binge; Chen, Laichao; Ma, Jingjian

    2015-12-01

    The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

  13. [Pleomorphic adenoma of salivary glands: diagnostic pitfalls and mimickers of malignancy].

    PubMed

    Skálová, A; Andrle, P; Hostička, L; Michal, M

    2012-10-01

    Pleomorphic adenoma is the most common salivary gland tumor, characterized by a complex biphasic proliferation of epithelial and myoepithelial cells intermingled with a mezenchymal component with frequent metaplastic changes and protean histomorphology of the cells. This review describes several unusual histological findings in pleomorphic adenoma that may mimic malignancy, and therefore they represent a diagnostic pitfall. Intravascular invasion of tumor cells is generally suspicious of malignancy; however, intravascular tumor deposits may be rarely found within the capsule of clinically benign salivary pleomorphic adenomas. It is important not to render a malignant diagnosis in such neoplasms, in the absence of other evidence of malignancy. Pleomorphic adenomas, particularly of minor glands of palate, may contain large areas of squamous and mucinous metaplasia suspicious of mucoepidermoid carcinoma (MEC). In contrast to MEC, metaplastic pleomorphic adenomas do not harbour the distinctive translocations t(11;19) and t(11;15), they are not invasive, in contrast they reveal at least focally myxochondroid stroma. Cribriform structures in pleomorphic adenoma may mimic adenoid cystic carcinoma. Oncocytic metaplasia in cellular rich pleomorphic adenoma/myoepithelioma may be associated with significant nuclear polymorphism and hyperchromasia suspicious of malignancy. The most common pitfall in diagnosis of pleomorphic adenoma is so called "atypical PA" that must be distinguished from early malignant transformation to in situ-carcinoma ex pleomorphic adenoma.

  14. Small "flat adenoma" of the large bowel with special reference to its clinicopathologic features.

    PubMed

    Muto, T; Kamiya, J; Sawada, T; Konishi, F; Sugihara, K; Kubota, Y; Adachi, M; Agawa, S; Saito, Y; Morioka, Y

    1985-11-01

    Thirty-three small "flat adenomas," not more than 1 cm in diameter, were collected from surgically and colonoscopically removed specimens, and their colonoscopic and histologic characteristics were described. There were 14 adenomas with mild atypia, five with moderate atypia, 14 with severe atypia (or focal carcinoma limited to the mucosa). The grade of atypia seems to increase with the size of lesions, and these lesions were assumed to play an important role in the adenoma-carcinoma sequence. The importance of recognizing the presence of these small "flat adenomas" in everyday practice is stressed.

  15. Expression of Cold-Inducible RNA-Binding Protein (CIRP) in Pituitary Adenoma and its Relationships with Tumor Recurrence

    PubMed Central

    Wang, Mingguang; Zhang, Huan; Heng, Xueyuan; Pang, Qi; Sun, Aigang

    2015-01-01

    Background The aim of this study was to detect the expression of cold-inducible RNA-binding protein in pituitary adenoma and to determine its effects on tumor recurrence. Material/Methods We collected a total of 60 post-op samples collected from pituitary adenoma patients (including 20 cases of invasive pituitary adenoma, 20 cases of non-invasive adenoma, and 20 cases of non-invasive recurrent adenoma) admitted in our hospital. Both protein and mRNA levels of CIRP in 3 types of pituitary adenoma samples were quantified by Western blotting and real-time PCR, respectively. Results Western blotting revealed significantly elevated CIRP expression levels in invasive pituitary adenoma compared to non-invasive tumors, with statistical significance (p<0.05). Recurrent pituitary adenoma expressed significantly higher CIRP levels compared to non-recurrent tumors (p<0.05). Real-time PCR for CIRP mRNA obtained consistent results: transcript levels were significantly higher in invasive pituitary adenoma compared to non-invasive adenoma (p<0.05); recurrent adenoma also had significantly higher CIRP mRNA levels compared to non-recurrent tumors (p<0.05). Among all 3 types of pituitary adenoma, recurrent tumors had the highest levels of CIRP mRNA and protein. Conclusions The expression of CIRP in pituitary adenoma is closely related with tumor proliferation and invasion, and its significantly elevated expression level indicates post-op recurrence. PMID:25934796

  16. The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does not impair the function of a bacterial homolog.

    PubMed

    Klein, Noreen; Kümmerer, Nadine; Hobernik, Dominika; Schneider, Dirk

    2015-01-01

    Several point mutations have been identified in human aquaporins, but their effects on the function of the respective aquaporins are mostly enigmatic. We analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic diabetes insipidus in humans, on aquaporin structure and activity, using the bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and structure around the V71M mutation is highly conserved between aquaporin 2 and GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely active, but cellular trafficking is probably impaired.

  17. Leiomyosarcoma arising from the inferior mesenteric vein

    PubMed Central

    Clemente, Gennaro; Sarno, Gerardo; Barbaro, Brunella; Nuzzo, Gennaro

    2009-01-01

    Leyomiosarcomas arising from the portal/mesenteric venous system are very rare tumours, and only a few cases have been reported in the global literature. As the other leyomiosarcomas of vascular origin, they are associated with a poor prognosis. The present report describes the case of a 66-year-old woman with a leyomiosarcoma of the inferior mesenteric vein, unexpectedly found during a CT scan performed for another indication. A brief review of the literature is also given. The patient underwent radical surgical excision and enjoys a good health, without radiological signs of recurrence, 24 months after surgery. In this case, an early incidental diagnosis determined an early treatment and, probably, a favourable prognosis. This is the second case of leyomiosarcoma of the inferior mesenteric vein reported in the literature. PMID:21686492

  18. Microbial diversity arising from thermodynamic constraints

    PubMed Central

    Großkopf, Tobias; Soyer, Orkun S

    2016-01-01

    The microbial world displays an immense taxonomic diversity. This diversity is manifested also in a multitude of metabolic pathways that can utilise different substrates and produce different products. Here, we propose that these observations directly link to thermodynamic constraints that inherently arise from the metabolic basis of microbial growth. We show that thermodynamic constraints can enable coexistence of microbes that utilise the same substrate but produce different end products. We find that this thermodynamics-driven emergence of diversity is most relevant for metabolic conversions with low free energy as seen for example under anaerobic conditions, where population dynamics is governed by thermodynamic effects rather than kinetic factors such as substrate uptake rates. These findings provide a general understanding of the microbial diversity based on the first principles of thermodynamics. As such they provide a thermodynamics-based framework for explaining the observed microbial diversity in different natural and synthetic environments. PMID:27035705

  19. [Nursing care of a patient with bipolar disorder and lithium-induced nephrogenic diabetes insipidus].

    PubMed

    García de la Orden, Lucía; García Carretero, Rafael

    2015-01-01

    Bipolar disorder is one of the most common, severe and persistent mental disorders. The evaluation of all data and variables related to bipolar disorder is a difficult task, because there is no clear agreement on what should be included in this category. One of the traditional treatments for this disease is the lithium metal that is administered in the form of lithium salt. Lithium has a narrow therapeutic window and there is a significant risk of complications arising from its use, mainly neurological and renal. In the case presented, the preparation of a care plan is described for a patient diagnosed with bipolar disorder who suffered a complication with lithium treatment. To do this, it was decided to use a standardized care plan and later completed it with diagnostic, objectives and interventions to the specific needs of the patient, aimed at achieving optimal levels of independence.

  20. Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas.

    PubMed

    Weigand, Isabel; Ronchi, Cristina L; Rizk-Rabin, Marthe; Dalmazi, Guido Di; Wild, Vanessa; Bathon, Kerstin; Rubin, Beatrice; Calebiro, Davide; Beuschlein, Felix; Bertherat, Jérôme; Fassnacht, Martin; Sbiera, Silviu

    2017-12-01

    Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.

  1. Extramammary Paget’s Disease of Anal Canal Associated With Rectal Adenoma Without Invasive Carcinoma

    PubMed Central

    Chumbalkar, Vaibhav; Jennings, Timothy A.; Ainechi, Sanaz; Lee, Edward C.; Lee, Hwajeong

    2016-01-01

    Extramammary Paget’s disease (EMPD) is a rare disease which is found in apocrine-rich locations such as anogenital region, axilla and rarely in other sites. Perianal EMPD is often reported as the involvement of perianal skin, but involvement of anal mucosa is very rare. Based on pathogenesis and association with either synchronous or metachronous malignancy, EMPD can be divided into primary and secondary types. Treatment approach for these two types of Paget’s disease and their prognosis is different, thus it is important to make the distinction. Secondary type of Paget’s disease is almost always described in association with invasive malignancy. While secondary Paget’s disease arising in association with ductal carcinoma in situ of the breast is common, secondary EMPD associated with precursor lesion of the rectum without invasion is exceedingly rare. We report a very rare case of secondary Paget’s disease of the anal canal in association with rectal tubular adenoma (precursor lesion) without malignancy. PMID:28058078

  2. Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.

    PubMed

    Lang, Dianna; Mead, Jennifer S; Sykes, David B

    2015-05-01

    In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.

  3. 32 CFR 536.112 - Settlement authority for claims arising under international agreements (for those claims arising...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Settlement authority for claims arising under international agreements (for those claims arising in the United States). 536.112 Section 536.112 National... arising under international agreements (for those claims arising in the United States)....

  4. Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation.

    PubMed

    Yang, Baoxue; Zhao, Dan; Verkman, A S

    2009-02-01

    Mutations in aquaporin-2 (AQP2) that interfere with its cellular processing can produce autosomal recessive nephrogenic diabetes insipidus (NDI). Prior gene knock-in of the human NDI-causing AQP2 mutation T126M produced mutant mice that died by age 7 days. Here, we used a novel "conditional gene knock-in" strategy to generate adult, AQP2-T126M mutant mice. Mice separately heterozygous for floxed wild-type AQP2 and AQP2-T126M were bred to produce hemizygous mice, which following excision of the wild-type AQP2 gene by tamoxifen-induced Cre-recombinase gave AQP2(T126M/-) mice. AQP2(T126M/-) mice were polyuric (9-14 ml urine/day) compared to AQP2(+/+) mice (1.6 ml/day) and had reduced urine osmolality (400 vs. 1800 mosmol). Kidneys of AQP2(T126M/-) mice expressed core-glycosylated AQP2-T126M protein in an endoplasmic reticulum pattern. Screening of candidate protein folding "correctors" in AQP2-T126M-transfected kidney cells showed increased AQP2-T126M plasma membrane expression with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). 17-AAG increased urine osmolality in AQP2(T126M/-) mice by >300 mosmol but had no effect in AQP2(-/-) mice. Kidneys of 17-AAG-treated AQP2(T126M/-) mice showed partial rescue of defective AQP2-T126M cellular processing. Our results establish an adult mouse model of NDI and demonstrate partial restoration of urinary concentration function by a compound currently in clinical trials for other indications.

  5. New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes.

    PubMed

    Leduc-Nadeau, Alexandre; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Martinez-Aguayo, Alejandro; Riveira-Munoz, Eva; Devuyst, Olivier; Bissonnette, Pierre; Bichet, Daniel G

    2010-06-15

    Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (approximately 20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems.

  6. Cooperative mechanisms of acute antidiuretic response to bendroflumethiazide in rats with lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Moosavi, S Mostafa Shid; Haghani, Masoud

    2010-12-01

    The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis-diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis-diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.

  7. Differential expression in normal-adenoma-carcinoma sequence suggests complex molecular carcinogenesis in colon.

    PubMed

    Lee, Seungkoo; Bang, Seunghyun; Song, Kyuyoung; Lee, Inchul

    2006-10-01

    The majority of colon cancers develop from pre-existing adenomas. We analyzed the expression profiles in the sequence of normal colon crypts, adenomas and early-stage carcinomas using microdissected cells from tubular adenomas with foci of malignant transformation. Differentially expressed genes were detected between normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns of expression changes in the sequence. Down-regulated genes in the sequence included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1, galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in mice, but the pathobiological role in humans has been controversial. Our data showed continuous down-regulation of PLA2G2A in the sequence supporting an implication in human colon cancer. Tumor suppressor and/ or proapoptotic activities have also been reported in other genes. Up-regulated genes included ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were up-regulated in carcinoma but not in adenoma, supporting the pathobiological roles in malignant transformation. Differentially expressed genes partly coincided with those in the adenoma-carcinoma sequence of the stomach, which was published previously, suggesting a partial overlap between the adenoma-carcinoma sequences of the colon and stomach.

  8. Pathological study of thyrotropin-secreting pituitary adenoma: plurihormonality and medical treatment.

    PubMed

    Teramoto, Akira; Sanno, Naoko; Tahara, Shigeyuki; Osamura, Yoshiyuki R

    2004-08-01

    Thyrotropin (TSH)-secreting adenomas are rare and, as most adenomas are large, invasive and difficult to cure by surgery only, many require additional medical treatment. Many TSH-secreting adenomas cosecrete growth hormone (GH) and/or prolactin (PRL). We evaluated the relationship between pathology and the effect of dopamine agonist bromocriptine and somatostatin analogue octreotide in 20 operated patients with TSH-secreting adenomas. The four men and 16 women ranged in age from 23 to 62 years; three had clinically overt acromegaly; two manifested galactorrhea-amenorrhea. Endocrinologically, elevated serum GH, and/or IGF-1 were observed in six patients and elevated serum PRL was observed in eight. Immunohistochemically, 16 of the 20 adenomas were positive for GH and/or PRL (GH-positive, n=13; PRL-positive, n=9). Pituitary-specific transcription factor Pit-1 was demonstrated in the nuclei of all adenoma cells. Octreotide tests showed suppression of serum TSH (<50%) in ten of 14 patients. Preoperative octreotide treatment effectively reduced serum TSH and tumor size in two patients. Electron micrographs of octreotide-treated TSH-secreting adenomas showed shrinkage of the cytoplasm and diffuse distribution of secretory granules. Our study suggests that cosecretion of GH and/or PRL from TSH-secreting adenoma has no correlation with response of tumor cells to medical treatment.

  9. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

    PubMed Central

    PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

    2016-01-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

  10. Association between dietary fat intake and colorectal adenoma in korean adults

    PubMed Central

    Kim, Jeehyun; Oh, Seung-Won; Kim, Young-Sun; Kwon, Hyuktae; Joh, Hee-Kyung; Lee, Ji-Eun; Park, Danbee; Park, Jae-Hong; Ko, Ah-Ryoung; Kim, Ye-Ji

    2017-01-01

    Abstract The incidence of colorectal cancer is rapidly increasing in South Korea. It is important to clarify the association between colorectal cancer and diet, being one of the main modifiable risk factors, as such studies in the Korean population are lacking. A cross-sectional study was performed using data from participants who had undergone a screening colonoscopy and a nutritional assessment during a routine health check-up from January 2008 to December 2011. Dietary intake data were derived from 1-day food records; colorectal adenoma was histopathologically confirmed by biopsy during colonoscopy. Eventually, 2604 participants were included in the analysis. The risk of colorectal adenoma by quintile of dietary fat intake was analyzed using logistic regression. Subgroup analyses by degree of risk and by location of colorectal adenoma were additionally performed. In men, total fat intake was not associated with risk of colorectal adenoma. However, risk of colorectal adenoma increased with higher saturated fatty acid (SFA) intake. The adjusted odds ratio in the highest quintile was 1.71 (95% confidence interval, 1.01–2.91) compared with that in the lowest quintile. There was no significant association between fat intake and risk of colorectal adenoma characterized by subsite. In female participants, total fat and specific fatty acid intake were not associated with risk of colorectal adenoma. These data support that high SFA intake is associated with risk of colorectal adenoma in Korean men. PMID:28072719

  11. Coexisiting adenoma and granuloma involving the right inferior parathyroid gland with adjacent ectopic thymic tissue

    PubMed Central

    Gupta, Mayank; Kandasamy, Subramaniam

    2014-01-01

    Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. PMID:24957592

  12. Hyperplasia-adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation.

    PubMed

    Villa, Chiara; Lagonigro, Maria Stefania; Magri, Flavia; Koziak, Maria; Jaffrain-Rea, Marie-Lise; Brauner, Raja; Bouligand, Jerome; Junier, Marie Pierre; Di Rocco, Federico; Sainte-Rose, Christian; Beckers, Albert; Roux, François Xavier; Daly, Adrian F; Chiovato, Luca

    2011-06-01

    Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.

  13. A large neglected pleomorphic adenoma of the lung: Report of a rare case.

    PubMed

    Gakidis, Ioannis; Mihos, Petros T; Chatziantoniou, Christos; Stamatelopoulos, Athanasios; Eftychiadis, Christos; Mantas, Constantinos

    2014-06-01

    Primary pleomorphic adenomas of the lung are very rare tumors that have peculiar clinical and oncologic features. We report here on the diagnostic and therapeutic approach for a patient with a large neglected pulmonary pleomorphic adenoma that presented initially as pneumonia.

  14. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature.

    PubMed

    Pu, Jiujun; Wang, Zhiming; Zhou, Hui; Zhong, Ailing; Jin, Kai; Ruan, Lunliang; Yang, Gang

    2016-07-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.

  15. Fibrous dysplasia arising from the calcaneus.

    PubMed

    Isefuku, S; Hatori, M; Ehara, S; Hosaka, M; Ito, K; Kokubun, S

    1999-11-01

    A case of an 18-year-old woman with fibrous dysplasia arising in the calcaneus, which is extremely rare, is reported, with the emphasis placed on differential diagnosis from low-grade central osteosarcoma. She had a severe pain in her left ankle after sprain. Plain radiographs showed a radiolucent lesion measuring 6.3 x 2.5 cm with a sclerotic margin in the left calcaneus. CT scans showed a well-defined lytic lesion with disruption of the lateral cortex and an ossification or calcification in its center. On MR imaging, the lesion had isointensities and high intensities on T1 and T2 weighted images, respectively, but its central portions showed lower intensities both on T1 and T2 weighted images. The lesion was enhanced with gadolinium except for the central portions. The specimen obtained by open biopsy consisted of fibrous tissue and foci of irregular woven bone. None of the nuclear atypia, mitoses, longitudinal stream of bone or invasive nature of growth was detected. The diagnosis of fibrous dysplasia was histologically made. The lesion was curetted and packed with autogenous bone chips. No evidence of recurrence was noted postoperatively.

  16. Chemodectomas arising in temporal bone structures

    SciTech Connect

    Dickens, W.J.; Million, R.R.; Cassisi, N.J.; Singleton, G.T.

    1982-02-01

    Eighteen patients with chemodectomas arising in temporal bone structures were evaluated and treated at the University of Florida. Seventeen patients have each been followed a minimum of 3 years. Patients were retrospectively staged as having ''local'' or ''advanced'' disease, depending on the presence or absence of bone destruction and/or cranial nerve involvement. Fourteen of the patients received radiation therapy as all or part of their therapy; 6 patients were treated with radiation therapy alone, 3 patients were irradiated immediately postoperatively for residual disease, and 5 patients had radiation therapy for recurrence after operation. They were treated with cobalt-60 radiation with doses ranging from 3760 to 5640 rad. All irradiated patients demonstrated evidence of tumor regression, and none have had tumor recurrence with followup of 3-12 years. Of the 8 patients with cranial nerve paralysis prior to therapy, 5 had return of function of 1 or more cranial nerves. One of 6 patients treated initially with radiation therapy had a complication, while 6 of 8 patients irradiated postoperatively had complications. None of the complications were fatal. Three patients treated by operation for early disease limited to the hypotympanum had the disease controlled for 11-12 years. Guidelines for the selection of initial therapy are discussed.

  17. [Chemical hazards arising from shale gas extraction].

    PubMed

    Pakulska, Daria

    2015-01-01

    The development of the shale industry is gaining momentum and hence the analysis of chemical hazards to the environment and health of the local population is extreiely timely and important. Chemical hazards are created during the exploitation of all minerals, but in the case of shale gas production, there is much more uncertainty as regards to the effects of new technologies application. American experience suggests the increasing risk of environmental contamination, mainly groundwater. The greatest, concern is the incomplete knowledge of the composition of fluids used for fracturing shale rock and unpredictability of long-term effects of hydraulic fracturing for the environment and health of residents. High population density in the old continent causes the problem of chemical hazards which is much larger than in the USA. Despite the growing public discontent data on this subject are limited. First of all, there is no epidemiological studies to assess the relationship between risk factors, such as air and water pollution, and health effects in populations living in close proximity to gas wells. The aim of this article is to identify and discuss existing concepts on the sources of environmental contamination, an indication of the environment elements under pressure and potential health risks arising from shale gas extraction.

  18. Occult invasive pituitary adenoma predisposing to fatal bacterial meningitis.

    PubMed

    Laszewski, M J; Moore, S A

    1990-01-01

    Pituitary adenomata are benign neoplasms which usually grow slowly and present with manifestations relating to an associated endocrinopathy or visual disturbance. Rarely these neoplasms will demonstrate a more aggressive behavior with extracranial extension and symptoms of upper airway obstruction or anosmia. Several reported cases suggest that although these neoplasms behave aggressively the overall survival and prognosis for these patients remains good. We present the clinical and postmortem findings of an occult invasive pituitary adenoma leading to the development of bacterial meningitis, coma and death. This communication stresses the necessity for the early diagnosis and treatment of the invasive adenomata to prevent the development of potentially fatal infectious sequelae.

  19. Non-functioning adrenal adenomas discovered incidentally on computed tomography

    SciTech Connect

    Mitnick, J.S.; Bosniak, M.A.; Megibow, A.J.; Naidich, D.P.

    1983-08-01

    Eighteen patients with unilateral non-metastatic non-functioning adrenal masses were studied with computed tomography (CT). Pathological examination in cases revealed benign adrenal adenomas. The others were followed up with serial CT scans and found to show no change in tumor size over a period of six months to three years. On the basis of these findings, the authors suggest certain criteria of a benign adrenal mass, including (a) diameter less than 5 cm, (b) smooth contour, (c) well-defined margin, and (d) no change in size on follow-up. Serial CT scanning can be used as an alternative to surgery in the management of many of these patients.

  20. Improved Techniques for Endoscopic Mucosal Resection (EMR) in Colorectal Adenoma

    PubMed Central

    Sold, Moritz; Kähler, Georg

    2014-01-01

    Summary Background Endoscopic therapy of colorectal adenomas and early cancers is a standard method. Besides oncological criteria, the method is limited by polyp location, size, and texture. Method Based on the current literature, technical modifications and developments in endoscopic mucosal resection are described. Results Numerous approaches exist to improve the conditions of resection, including optimisation of mucosal elevation and modification of techniques, tools, and devices. Conclusion Endoscopic therapy of sessile and flat colorectal polyps remains a challenge. Some of the presented modifications can help to address this challenge. PMID:26286120

  1. Secondary abscess formation in pituitary adenoma after tooth extraction. Case report.

    PubMed

    Kroppenstedt, S N; Liebig, T; Mueller, W; Gräf, K J; Lanksch, W R; Unterberg, A W

    2001-02-01

    The presence of an abscess in a pituitary tumor is a very rare finding. The authors report the case of a 69-year-old man with a pituitary adenoma confirmed by neuroimaging results, in whom a high fever, meningismus, and left-sided ophthalmoplegia developed 4 days after tooth extraction. The results of serial cranial magnetic resonance imaging were highly indicative of an abscess formation within the pituitary adenoma. During surgery the tumor was approached transsphenoidally and removed. Histological examination confirmed the presence of an abscess formation within the pituitary adenoma. It is most likely that the tooth extraction caused a bacteremia, which led to an inflammation with abscess formation within the pituitary adenoma. The authors conclude that invasive dental procedures should be avoided before planned resection of a pituitary adenoma.

  2. Pleomorphic adenoma in the nasal cavity: a clinicopathological study of ten cases in Finland.

    PubMed

    Vento, S I; Numminen, J; Kinnunen, I; Rautiainen, M; Tarkkanen, J; Hagström, J; Mäkitie, A A

    2016-11-01

    The objective of the study was to investigate the nationwide occurrence of sinonasal pleomorphic adenoma in Finland. A retrospective study was conducted at The Departments of Otorhinolaryngology-Head and Neck Surgery, and Pathology at the five university hospitals in Finland. Data were obtained by searching for sinonasal pleomorphic adenoma cases in the clinical and histopathological registries at these institutions for the past two to four decades. All patients who had had a histologically proven pleomorphic adenoma in the sinonasal area were included as participants. Ten cases with pleomorphic adenoma of the nasal cavity were found. The majority of these tumours originated in the septum, and there were no malignant transformations. Pleomorphic adenomas of the nasal cavity were found to be extremely rare in this nationwide investigation.

  3. [Expression of CD10 in tumor-associated fibroblast of cancerized or recurrent colorectal adenomas].

    PubMed

    Zheng, Jiangjiang; Zhu, Yin; Li, Changshui; Li, Yinya; Nie, Qianqian; Zhu, Ziling; Deng, Hong

    2016-05-25

    Objective: To investigate the expression of CD10 in tumor-associated fibroblasts (TAF) in colorectal adenomas and its relation to cancerization and recurrence of adenoma. Methods: Tissue samples of low-grade adenoma (n=50), high-grade adenoma (n=50) and colorectal adenocarcinoma (n=50) were collected, and tissue samples at the distal margin of corresponding colorectal lesions were taken as controls. The expression of CD10 in the stromal TAFs, and the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry (Envision). The correlation of CD10 expression in stromal TAFs with the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed by Spearmen. One hundred samples of low-grade colorectal adenoma were collected, including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF CD10 were determined and compared among groups. Results: There was no TAF in normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma, high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%, respectively (all P<0.05). The expression of Ki-67 and β-catenin in low-grade adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all P<0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in colorectal adenocarcinoma and low-grade adenoma (all P>0.05). The expression of p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in low grade adenoma (all P<0.01). The expression of TAF CD10 was correlated with the expression of p53, Ki-67 and β-catenin-nucleus(r=0.264、0.307、0.320, all P<0.01),but not correlated with CyclinD1 and β-catenin-membrane (r=0.012、-0.073, all P>0.05). The TAF CD10 level was significantly higher in low-grade adenoma with recurrence than that in those without recurrence (P<0.05).The expression of CD10 in

  4. Endoscopic discrimination of sessile serrated adenomas from other serrated lesions

    PubMed Central

    Hasegawa, Shin; Mitsuyama, Keiichi; Kawano, Hiroshi; Arita, Keiko; Maeyama, Yasuhiko; Akagi, Yoshito; Watanabe, Yasutomo; Okabe, Yoshinobu; Tsuruta, Osamu; Sata, Michio

    2011-01-01

    Sessile serrated adenoma (SSA) is a proposed precursor of colorectal carcinogenesis. This study aimed to analyze the potential of endoscopy to discriminate SSA from other serrated lesions, specifically traditional serrated adenoma (TSA) and hyperplastic polyp (HP). Of 145 serrated lesions, 111 sessile serrated lesions including 32 TSAs, 25 SSAs and 54 HPs were analyzed for size, color, location and morphologic features using conventional endoscopy and magnifying chromoendoscopy. SSA was preferentially located in the right colon, whereas TSA and HP were located in the left colon. The sizes of SSA and TSA were larger than those of HP. The lesion color was indistinguishable among TSA, SSA and HP. Macroscopically, a pinecone-like or two-tier raised appearance were found more frequently in TSA than in SAA and HP. Under magnified chromoendoscopic observation, the stellar IIIL pit pattern and fern-like appearance were observed more frequently in TSA than in SAA and HP. In conclusion, endoscopic discrimination between SSA and other sessile serrated lesions based on morphological features was difficult. However, size and location of the lesions facilitated diagnosis. PMID:22866127

  5. Hyponatremia and pituitary adenoma: think twice about the etiopathogenesis.

    PubMed

    Zogheri, A; Di Mambro, A; Mannelli, M; Serio, M; Forti, G; Peri, A

    2006-09-01

    Pituitary adenomas may be the cause of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), although few cases have so far been reported. We described a case of hypotonic hyponatremia in a 76-yr-old man with a pituitary macroadenoma. He had a recent history of two syncopal attacks which had occurred in the last two months. Baseline assessment demonstrated a sodium serum level of 114 mEq/l. Clinically, the patient appeared euvolemic. Thyroid and adrenal function testing did not show any abnormality. Plasma and urinary osmolality (238 and 186 mOsm/kg, respectively) were in agreement with the diagnosis of SIADH. Accordingly, 3% hypertonic saline solution was started, followed by water intake restriction when natremia reached 126 mEq/l. A computed tomography (CT) scan of the chest revealed the presence of a 2-cm lesion in the azygos-esophageal recess. Because the nature of the lesion appeared uncertain, antibiotic therapy was initiated. After one month, a new CT scan did not show any evidence of the mediastinic mass. Sodium serum level was within the normal range (141 mEq/l) and remained stable thereafter, without fluid restriction. This case very well demonstrates that, in the presence of hyponatremia due to SIADH, more frequently associated co-morbidities (ie mediastinic diseases) have to be searched, even in the presence of a possible, yet rare, cause of this syndrome (ie pituitary adenoma).

  6. Pleomorphic adenoma of a deep orbital ectopic lacrimal gland.

    PubMed

    Misra, Somen; Bhandari, Akshay; Misra, Neeta; Gogri, Pratik; Mahajan, Shruti

    2016-10-01

    Ectopic lacrimal gland, being one of the choristomas, is comprised of lacrimal gland tissue outside the lacrimal gland fossa in the fronto-lateral part of the orbital roof. Ectopic lacrimal gland is a rare condition where the gland may be found in the orbit, eyelids, ocular adnexa or within the globe. Neoplastic transformation of such tissue may occur. A sixty-two-year old male patient presented with right eye proptosis and slight nasal displacement of the globe. Computerized tomography scan revealed a well-defined hypodense lesion of size 19 x 18 x 20 mm supero-lateral to lateral rectus muscle, with mild proptosis and thinning of the right lateral orbital wall. Excisional biopsy was performed through a lateral orbitotomy approach. A well circumscribed globular mass was removed from the right orbit, well behind the fossa for the lacrimal gland in the retrobulbar space. Histopathology was suggestive of pleomorphic adenoma of lacrimal gland. Pleomorphic adenoma is an epithelial tumor of the lacrimal gland which is extremely rare from an ectopic lacrimal gland and only few cases have been reported in literature till date.

  7. Testosterone-secreting adrenal adenoma in a peripubertal girl

    SciTech Connect

    Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

    1987-11-13

    A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

  8. Discrimination of prolactinoma from hyperprolactinemic non-functioning adenoma.

    PubMed

    Hong, Jae Won; Lee, Mi Kyung; Kim, Sun Ho; Lee, Eun Jig

    2010-02-01

    The objective of this study was to evaluate characteristics that discriminate prolactinoma from non-functioning pituitary macroadenoma with hyperprolactinemia. We included 117 patients with hyperprolactinemic pituitary macroadenomas. Patients were divided into three groups according to treatment outcomes and pathologic results: (A) prolactinoma that responded to dopamine agonist (DA) treatment (PRDA); (B) prolactinoma requiring surgical treatment (PRS); and (C) non-functioning pituitary adenoma with hyperprolactinemia (NFPAH). Old age, low serum prolactin levels, and extrasellar extension were associated with NFPAH. Most patients with NFPAH had serum prolactin levels less than 100 ng/ml. Visual defects and GH deficiency were more common in patients with NFPAH compared with patients with PRS and PRDA, without difference of tumor size. Galactorrhea and amenorrhea were less frequent in patients with NFPAH than in patients with PRS and PRDA. Post-operative remission of hyperprolactinemia was achieved in 100% of patients with NFPAH and in 72.5% of patients with PRS. DA administration was required in 25.5% of patients with PRS; however, no patients with NFPAH required DA administration. In conclusion, old age, extrasellar tumor extension with relatively low prolactin levels, visual defect, and GH deficiency were considered suggestive of non-functioning pituitary adenoma rather than prolactinoma in hyperprolactinemic pituitary macroadenoma.

  9. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management.

    PubMed

    Amlashi, Fatemeh G; Tritos, Nicholas A

    2016-06-01

    Inappropriate secretion of TSH was first described in 1960 in a patient with evidence of hyperthyroidism and expanded sella on imaging. It was later found that a type of pituitary adenoma that secretes TSH (thyrotropinoma) was the underlying cause. The objective of the present review article is to summarize data on the epidemiology, pathogenesis, diagnosis, and management of thyrotropinomas. The prevalence of thyrotropinomas is lower than that of other pituitary adenomas. Early diagnosis is now possible thanks to the availability of magnetic resonance imaging and sensitive laboratory assays. As a corollary, many patients now present earlier in the course of their disease and have smaller tumors at the time of diagnosis. Treatment also has evolved over time. Transsphenoidal surgery is still considered definitive therapy. Meanwhile, radiation therapy, including radiosurgery, is effective in achieving tumor control in the majority of patients. In the past, radiation therapy was used as second line treatment in patients with residual or recurrent tumor after surgery. However, the availability of somatostatin analogs, which can lead to normalization of thyroid function as well as shrink these tumors, has led to an increase in the role of medical therapy in patients who are not in remission after pituitary surgery. In addition, dopamine agonists have shown some efficacy in the management of these tumors. Better understanding of the molecular pathogenesis of thyrotropinomas may lead to rationally designed therapies for patients with thyrotropinomas.

  10. Human Pituitary Adenoma Proteomics: New Progresses and Perspectives

    PubMed Central

    Zhan, Xianquan; Wang, Xiaowei; Cheng, Tingting

    2016-01-01

    Pituitary adenoma (PA) is a common intracranial neoplasm that impacts on human health through interfering hypothalamus–pituitary–target organ axis systems. The development of proteomics gives great promises in the clarification of molecular mechanisms of a PA and discovery of effective biomarkers for prediction, prevention, early-stage diagnosis, and treatment for a PA. A great progress in the field of PA proteomics has been made in the past 10 years, including (i) the use of laser-capture microdissection, (ii) proteomics analyses of functional PAs (such as prolactinoma), invasive and non-invasive non-functional pituitary adenomas (NFPAs), protein post-translational modifications such as phosphorylation and tyrosine nitration, NFPA heterogeneity, and hormone isoforms, (iii) the use of protein antibody array, (iv) serum proteomics and peptidomics, (v) the integration of proteomics and other omics data, and (vi) the proposal of multi-parameter systematic strategy for a PA. This review will summarize these progresses of proteomics in PAs, point out the existing drawbacks, propose the future research directions, and address the clinical relevance of PA proteomics data, in order to achieve our long-term goal that is use of proteomics to clarify molecular mechanisms, construct molecular networks, and discover effective biomarkers. PMID:27303365

  11. Acute appendicitis following endoscopic mucosal resection of cecal adenoma.

    PubMed

    Nemoto, Yukako; Tokuhisa, Junya; Shimada, Nagasato; Gomi, Tatsuya; Maetani, Iruru

    2015-07-21

    Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions, laterally spreading tumors, and carcinoma of the colon or the rectum limited to the mucosa or the superficial submucosa. Acute appendicitis is the most common abdominal emergency requiring emergency surgery, and it is also a rare complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR. In the case presented here, a 53-year-old female underwent colonoscopy due to a positive fecal occult blood test and was diagnosed with cecal adenoma. She was referred to our hospital and admitted for treatment. The patient had no other symptoms. EMR was performed, and 7 h after the surgery, the patient experienced right -lower abdominal pain. Laboratory tests performed the following day revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C-reactive protein level of 2.20 mg/dL, indicating an inflammatory response. Computed tomography also revealed appendiceal wall thickening and swelling, so acute appendicitis following EMR was diagnosed. Antibiotics were initiated leading to total resolution of the symptoms, and the patient was discharged on the sixth post-operative day. Pathological analysis revealed a high-grade cecal tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR of the cecum may be a rare cause of acute appendicitis.

  12. Immunohistochemical phenotype and molecular pathological characteristics of metanephric adenoma

    PubMed Central

    Sun, Zhulei; Kan, Shihai; Zhang, Leilei; Zhang, Yan; Jing, Hong; Huang, Gui; Yu, Qichun; Wu, Jiang

    2015-01-01

    To assess the clinicopathological, immunohistochemical and molecular features of metanephric adenoma (MA). Clinicopathologic data were obtained for 5 cases of MA with follow-up information. Specimens from these patients were stained by HE and immunohistochemistry for the detection of WT1, vimentin, S-100 protein, CK7, P504s, CD10 and renal cell carcinoma marker (RCC). Fluorescence in situ hybridization (FISH) was performed on 4 tumors. The patients included 1 male and 4 females, aged from 30 to 49 (mean=39) years. Tumor diameters ranged from 3 to 5.5 cm. Histologically, the tumors had tubular, papillary, or glomeruloid architectures, and were composed of cells with uniform and round nuclei, inconspicuous nucleoli, and high ratio of nucleus to cytoplasm. Nuclear polymorphism and mitotic figures were not observed. Immunohistochemically, they expressed WT1 (5/5), vimentin (5/5), S-100 (4/5), CK7 (2/5), P504s (2/5), and CD10 (1/5) and not RCC. FISH study was carried out on 4 metanephric adenoma cases, and no abnormalities were observed in chromosomes 3, 7, 17, and P16 gene of chromosomes 9. MA is an uncommon renal tumor. Its diagnosis depends on morphological, immunohistochemical and molecular features. PMID:26261480

  13. Pituitary null cell adenoma in a domestic llama (Lama glama).

    PubMed

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  14. Immunohistochemical detection of glycoprotein hormone alpha subunit in somatoprolactinic and pure somatotroph adenomas.

    PubMed

    Vantyghem, M C; Cortet, C; Bauters, C; Gevaert, M H; Dewailly, D; Lefebvre, J; Mazzucca, M

    1998-01-01

    Glycoprotein hormone alpha subunit (alpha SU) is expressed in nearly all thyreotroph adenomas and most gonadotrophinomas, but is less well documented in plurisecreting adenomas. We therefore examined the immunohistochemical (IHC) expression of alpha SU in a generally accepted model of plurisecreting adenomas (somatoprolactinic type) by comparison to a series of pure monosecreting somatotroph tumors. Fifty patients (32 females, 18 males) aged 15 to 68 years with clinical and/or biological acromegaly requiring adenomectomy were studied. Forty-five had clinical acromegaly and 5 had isolated amenorrhea and/or galactorrhea syndromes. Forty-eight of the 49 patients who had baseline assessments of plasma GH had a mean concentration of 5 ng/ml or more (normal value < 5). Fifteen of the 46 patients who had baseline measurements of plasma PRL had a prolactinemia value greater than 20 ng/ml (normal value < 20) but below 100 ng/ml, except for one patient. All the adenomas studied were positive by GH immunohistochemistry; 21 were immunostained by an antiPRL antibody and formed the "somatoprolactinic" (GH-PRL) group. Five of these 21 patients were male. The 12 female patients younger than 50 years had amenorrhea or galactorrhea, and one male patient complained of impotence. Eleven patients (9 females, 2 males) in this GH-PRL group had hyperprolactinemia. Sixteen of these GH-PRL adenomas were immunolabeled by alpha SU antiserum. The remaining 29 adenomas, which were immunonegative with the PRL antibody and formed the "somatotroph adenoma" (GH) group, were more frequent in male patients (13/29; 45%) compared to GH-PRL group. Eight amenorrhea or galactorrhea syndromes occurred among the 14 women younger than 50 years, 3 of whom had hyperprolactinemia. Thirteen of these 29 adenomas (45%) were immunopositive with alpha SU antibody. Compared to the GH group, the GH-PRL group had a significant higher frequency of amenorrhea and/or galactorrhea syndromes among women under 50 years (100

  15. Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma

    PubMed Central

    Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. PMID:26336987

  16. Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

    PubMed

    Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

    2006-02-01

    The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

  17. [AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature].

    PubMed

    Fajardo-Montañana, Carmen; Daly, Adrian F; Riesgo-Suárez, Pedro; Gómez-Vela, José; Tichomirowa, María A; Camara-Gómez, Rosa; Beckers, Albert

    2009-01-01

    Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age.

  18. Localization of carboxyl ester lipase in human pituitary gland and pituitary adenomas.

    PubMed

    La Rosa, Stefano; Vigetti, Davide; Placidi, Claudia; Finzi, Giovanna; Uccella, Silvia; Clerici, Moira; Bartolini, Barbara; Carnevali, Ileana; Losa, Marco; Capella, Carlo

    2010-10-01

    Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.

  19. Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease.

    PubMed

    Mehta, Gautam U; Montgomery, Blake K; Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K; Patronas, Nicholas; Oldfield, Edward H; Chittiboina, Prashant

    2015-05-01

    We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration.

  20. Etiology, prognosis, and management of secondary pituitary abscesses forming in underlying pituitary adenomas.

    PubMed

    Awad, Ahmed J; Rowland, Nathan Christopher; Mian, Matthew; Hiniker, Annie; Tate, Matthew; Aghi, Manish Kumar

    2014-05-01

    Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment.

  1. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas

    PubMed Central

    2011-01-01

    Background The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas. Methods Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel. Results Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa. Conclusions The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection. PMID:21777459

  2. Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing’s disease

    PubMed Central

    Mehta, Gautam U.; Montgomery, Blake K.; Raghavan, Pooja; Sharma, Susmeeta; Nieman, Lynnette K.; Patronas, Nicholas; Oldfield, Edward H.; Chittiboina, Prashant

    2015-01-01

    We report a patient with Cushing’s disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5 mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a nonfunctional adenoma. At early repeat surgical exploration a 10 mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration. PMID:25827866

  3. Increased Pulse Wave Velocity Reflecting Arterial Stiffness in Patients with Colorectal Adenomas

    PubMed Central

    Lim, Yun Jeong; Kwack, Won Gun; Lee, Youg-Sup; Hahm, Ki Baik; Kim, Young-Kwon

    2010-01-01

    The obese patients with diabetes or cardiovascular risk factors are associated with increased risk of colorectal cancer as well as adenomas under the shared pathogenesis related to atherosclerosis. Here we determined the association between increased arterial stiffness and colorectal adenomas incorporating parameters including age, gender, waist circumference, body mass index, lipid profiles, fasting glucose, and blood pressure. Subjects who simultaneously underwent colonoscopies and pulse wave velocity (PWV) determinations between July 2005 and September 2006 were analyzed, based on which the subjects were classified into two groups as patients group with colorectal adenomas (n = 49) and control group (n = 200) with normal, non-polypoid benign lesions or hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV were significantly associated with adenomas (p<0.05) and multiple logistic regression analysis showed that the heart-femoral PWV, waist circumference, and the levels of LDL-C were significant risk factor for colorectal adenoma. However, arterial stiffness did not affect the progression of colon adenoma. The finding that hfPWV, reflecting aortic stiffness, was increased in patients with colorectal adenomas lead to conclusion that patients who have prominently increased arterial stiffness can be recommended to undergo colonoscopic examinations and at the same time we also recommend counseling about the risk for atherosclerosis in those who have colorectal adenomas. PMID:21103036

  4. Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk.

    PubMed

    Wong, Hui-Lee; Peters, Ulrike; Hayes, Richard B; Huang, Wen-Yi; Schatzkin, Arthur; Bresalier, Robert S; Velie, Ellen M; Brody, Lawrence C

    2010-09-01

    While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear. We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy. We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global gene-based)=0.92). Frequencies of identified common haplotypes did not differ between cases and controls (P(global haplotype test)=0.97). However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR)=3.27; 95% confidence interval (CI)=1.08-9.88). The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet (P(interaction)=0.03). Similar interactions were not observed with HRT use. In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma. Fat intake modified the APC D1822V-adenoma association, but further studies are warranted.

  5. Advanced Colorectal Adenomas in Patients Under 45 Years of Age Are Mostly Sporadic

    PubMed Central

    Nalbantoglu, ILKe; Watson, Rao; Goodwin, Jonathan; Safar, Elyas; Chokshi, Reena V.; Azar, Riad R.; Davidson, Nicholas O.

    2014-01-01

    Background The presence of advanced adenomas in younger individuals is a criterion for Lynch syndrome (LS). However, the utility of screening advanced adenomas for loss of mismatch repair (MMR) protein expression to identify suspected LS remains unclear. Aims Determine the prevalence of MMR defects to understand whether these patients harbor a defined genetic risk for CRC. Methods The study cohort included adult patients ≤45 years of age with advanced adenomas (villous histology, ≥1 cm in diameter, ≥3 polyps of any size) endoscopically removed between 2001 and 2011. Clinical records were reviewed along with detailed pathological review and immunohistochemical MMR analysis. Results A total of 76 (40.1 % male, age 40.6 ± 5.4 years) patients met inclusion and exclusion criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39 (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20 (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1–4), mean diameter of 12.9 ±7.1 mm, 40 (52.6 %) with villous histology. The mean follow-up duration was 3.3 ± 2 years. Recurrent adenomas developed in 24 (31.6 %), of which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC. One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing revealed loss of MLH1 and PMS2. Conclusions IHC screening of advanced adenomas from patients younger than 45 years of age identified potential LS in one of 64 patients. The low yield of IHC screening in this population suggests that universal IHC screening of advanced adenomas from patients younger than 45 years of age for MMR defects is not an efficient strategy for identifying LS subjects. PMID:24925148

  6. Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

    PubMed Central

    Cooper, Odelia; Ben-Shlomo, Anat; Bonert, Vivien; Bannykh, Serguei; Mirocha, James

    2010-01-01

    Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994–2008 with follow-up time ranging from 1–15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissue-specific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p<0.0001). Fifty-four percent of patients with SCAs had new onset postoperative hypopituitarism vs. 17% of nonfunctioning adenomas (p<0.025). SCAs (n=18) were immunopositive for ACTH, cytoplasmic and nuclear SF-1, NeuroD1, DAX-1, and alpha-gonadotropin subunit, but Tpit negative, and co-expression of tumor ACTH with either SF-1 or LH was detected. In contrast, functional corticotroph adenomas (n=11) were immunopositive for ACTH, nuclear SF-1, NeuroD1, and Tpit, but negative for DAX-1, a gonadotroph cell transcription factor. Gonadotroph adenomas (n=23) were immunonegative for ACTH and Tpit but positive for nuclear SF-1, NeuroD1, and DAX-1. SCA electron microscopy demonstrated ultrastructural features consistent with corticotroph and gonadotroph cells. As SCAs exhibit features consistent with both corticotroph and gonadotroph cytologic origin, we propose a pathologic and clinically distinct classification of SCAs as silent corticogonadotroph adenomas. PMID:20717480

  7. Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.

    PubMed

    Katabi, Nora; Ghossein, Ronald; Ho, Alan; Dogan, Snjezana; Zhang, Lei; Sung, Yun-Shao; Antonescu, Cristina R

    2015-01-01

    Carcinoma ex-pleomorphic adenoma (CA ex-PA) is a malignant salivary gland tumor that arises in association with pleomorphic adenoma (PA). Both PA and CA ex-PA have a broad spectrum of histology, and distinction from their histologic mimics may be difficult based on morphology alone. PLAG1 and HMGA2 abnormalities are the most common genetic events in both PA and CA ex-PA; however, the use of PLAG1 and HMGA2 as adjunct molecular tests has not been well established. Fluorescence in situ hybridization for PLAG1 and HMGA2 was performed on 22 CA ex-PA (10 myoepithelial carcinomas [MECAs], 10 salivary duct carcinomas [SDCs], 1 carcinoma with squamoglandular features, and 1 mixed MECA-adenocarcinoma not otherwise specified), 20 de novo carcinomas (11 MECAs and 9 SDCs), 16 PAs, and 11 PA-histologic mimics. All except 3 CAs ex-PA (86%) were positive for PLAG1 or HMGA2 rearrangements/amplifications. In contrast, 18 (90%) of 20 de novo carcinomas lacked abnormalities in PLAG1 or HMGA2 (P < .01). PLAG1 or HMGA2 rearrangements were identified in 6 (67%) of 9 hypocellular myxoid PAs and in 2 (29%) of 7 cellular PAs. Furthermore, all morphologic mimics of PA were negative for PLAG1 or HMGA2. PLAG1 and HMGA2 rearrangements are the most common genetic events in CA ex-PA regardless of the histologic subtype. Unlike CA ex-PA, de novo carcinomas were negative for PLAG1 and HMGA2. Interestingly, rearrangements of PLAG1/HMGA2 were identified in most hypocellular PAs but only in a small subset of cellular PAs. Fluorescence in situ hybridization for PLAG1 or HMGA2 can be used to distinguish between PA and CA ex-PA and their morphologic mimics.

  8. 32 CFR 536.110 - Notification of incidents arising under international agreements (for claims arising in the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Notification of incidents arising under international agreements (for claims arising in the United States). 536.110 Section 536.110 National Defense... Claims Cognizable Under International Agreements § 536.110 Notification of incidents arising...

  9. Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas. A necropsy study in New Zealand.

    PubMed Central

    Jass, J R; Young, P J; Robinson, E M

    1992-01-01

    Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not

  10. Vulvar lactating adenoma associated to a fibroadenoma: common neoplasms in an uncommon site.

    PubMed

    Dhaoui, Amen; Nfoussi, Haifa; Kchir, Nidhameddine; Haouet, Slim

    2012-01-01

    Ectopic breast tissue is defined as glands located outside of the breast. Ectopic breast tissue should be excised because it may develop benign (fibroadenoma) or malignant pathologic processes. Less than forty cases of fibroadenomas have been reported in the literature. Although lactation changes can occur, lactating adenoma in the vulva are extremely rare. Only four cases have been reported. We report a case of a young woman who presented with vulvar mass during her lactation. The mass was excised, and histology confirmed vulvar lactating adenoma associated with fibroadenoma. This is the first case of vulvar heterotopic breast lesion associating lactating adenoma and fibroadenoma.

  11. Metastasizing "benign" pleomorphic salivary adenoma: a dramatic case-report and literature review.

    PubMed

    Tarsitano, Achille; Foschini, Maria Pia; Farneti, Paolo; Pasquini, Ernesto; Marchetti, Claudio

    2014-12-01

    Pleomorphic salivary adenomas are the most common benign neoplasms affecting the salivary glands. Very occasionally however, metastatic lesions are identified in patients with a history of PSA, which, on detailed pathological evaluation, are found to exhibit all the histological hallmarks of the preceding benign lesions. Diagnosis of benign metastasizing pleomorphic adenoma of the salivary gland is extremely rare and still under debate. We present the first case-report in literature of multiple metachronous nasal cavity, scalp and encephalic metastases of a pleomorphic adenoma of the parotid gland in a young girl.

  12. [Somatotropic pituitary adenoma with lesions of the oculomotor nerve in a cat].

    PubMed

    Allgoewer, I; Grevel, V; Philipp, K; Schmidt, P; Brunnberg, L

    1998-07-01

    A case of a 6.5-year-old castrated male European Shorthair Cat with an unilateral lesion of the oculomotor nerve is described. Nuclear magnetic resonance imaging revealed a mass in the area of the pituitary gland which could be identified as a somatotrope adenoma by immunochemistry. Unlike the feline somatotrope adenoma cases described in the literature this cat showed clinically no acromegalic features or hyperglycemia. An oculomotor nerve lesion in conjunction with a feline somatotropic pituitary adenoma has also not been described before.

  13. Mathematical problems arising in interfacial electrohydrodynamics

    NASA Astrophysics Data System (ADS)

    Tseluiko, Dmitri

    In this work we consider the nonlinear stability of thin films in the presence of electric fields. We study a perfectly conducting thin film flow down an inclined plane in the presence of an electric field which is uniform in its undisturbed state, and normal to the plate at infinity. In addition, the effect of normal electric fields on films lying above, or hanging from, horizontal substrates is considered. Systematic asymptotic expansions are used to derive fully nonlinear long wave model equations for the scaled interface motion and corresponding flow fields. For the case of an inclined plane, higher order terms are need to be retained to regularize the problem in the sense that the long wave approximation remains valid for long times. For the case of a horizontal plane the fully nonlinear evolution equation which is derived at the leading order, is asymptotically correct and no regularization procedure is required. In both physical situations, the effect of the electric field is to introduce a non-local term which arises from the potential region above the liquid film, and enters through the electric Maxwell stresses at the interface. This term is always linearly destabilizing and produces growth rates proportional to the cubic power of the wavenumber - surface tension is included and provides a short wavelength cut-off, that is, all sufficiently short waves are linearly stable. For the case of film flow down an inclined plane, the fully nonlinear equation can produce singular solutions (for certain parameter values) after a finite time, even in the absence of an electric field. This difficulty is avoided at smaller amplitudes where the weakly nonlinear evolution is governed by an extension of the Kuramoto-Sivashinsky (KS) equation. Global existence and uniqueness results are proved, and refined estimates of the radius of the absorbing ball in L2 are obtained in terms of the parameters of the equations for a generalized class of modified KS equations. The

  14. Progress in the Diagnosis and Classification of Pituitary Adenomas

    PubMed Central

    Syro, Luis V.; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M.; Serna, Carlos A.; Kovacs, Kalman

    2015-01-01

    Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype. PMID:26124750

  15. Progress in the Diagnosis and Classification of Pituitary Adenomas.

    PubMed

    Syro, Luis V; Rotondo, Fabio; Ramirez, Alex; Di Ieva, Antonio; Sav, Murat Aydin; Restrepo, Lina M; Serna, Carlos A; Kovacs, Kalman

    2015-01-01

    Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are difficult to treat due to their tendency to recur despite standardized treatment. Functional tumors present other challenges for normalizing their biochemical activity. Novel approaches for early diagnosis, as well as different perspectives on classification, may help to identify subgroups of patients with similar characteristics, creating opportunities to match each patient with the best personalized treatment option. In this paper, we present the progress in the diagnosis and classification of different subgroups of patients with pituitary tumors that may be managed with specific considerations according to their tumor subtype.

  16. New technologies and techniques to improve adenoma detection in colonoscopy

    PubMed Central

    Bond, Ashley; Sarkar, Sanchoy

    2015-01-01

    Adenoma detection rate (ADR) is a key component of colonoscopy quality assessment, with a direct link between itself and future mortality from colorectal cancer. There are a number of potential factors, both modifiable and non-modifiable that can impact upon ADR. As methods, understanding and technologies advance, so should our ability to improve ADRs, and thus, reduce colorectal cancer mortality. This article will review new technologies and techniques that improve ADR, both in terms of the endoscopes themselves and adjuncts to current systems. In particular it focuses on effective techniques and behaviours, developments in image enhancement, advancement in endoscope design and developments in accessories that may improve ADR. It also highlights the key role that continued medical education plays in improving the quality of colonoscopy and thus ADR. The review aims to present a balanced summary of the evidence currently available and does not propose to serve as a guideline. PMID:26265990

  17. Pathologic Fractures: A Neglected Clinical Feature of Parathyroid Adenoma

    PubMed Central

    Abshirini, Hassan; Rashidi, Iran; Saki, Nader

    2010-01-01

    The pattern of clinical presentation of primary hyperparathyroidism (pHPT) has changed dramatically from a severe disease to an asymptomatic condition in Western countries. The story is completely different in Eastern countries. Bone and joint related sign and symptoms like bone pain and multiple fractures are common in these patients. Imaging and nuclear medicine studies will be helpful specially in patient who candidate for surgical removal of the abnormal parathyroid gland. Here, we present a 48-year-old man with multiple typical fractures in long bones and a single adenoma in his right inferior parathyroid gland. pHPT is a severe, symptomatic disease with serious complications and high morbidity in Iran. Advanced skeletal disease is the most common pattern of presentation. PMID:21209742

  18. Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist

    SciTech Connect

    Charbonnel, B.; Chatal, J.F.; Ozanne, P.

    1981-12-01

    An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland.

  19. Metachronous bilateral pleomorphic adenoma of the parotid gland.

    PubMed

    Silva, Sindeval José da; Costa Junior, Gabriel Tadeu; Brant Filho, Adalberto Caldeira; Faria, Paulo Rogério; Loyola, Adriano Mota

    2006-03-01

    Bilateral salivary gland tumors are very rare, accounting for 3% of all parotid gland tumors. Although the most common tumor with bilateral development is the Warthin tumor, pleomorphic adenomas (PA) have been diagnosed simultaneously as well, but in a smaller incidence. Because of this, the prevalence, etiology, pathogenesis, and behavior of the PA in this context are poorly understood. We present a case of bilateral metachronous PA affecting the parotid gland in a 63-year-old woman. Clinically, the lesions presented with similar aspects as seen in cases of solitary PA with slow-growing asymptomatic nodule. Both lesions were diagnosed by fine-needle aspiration biopsy at an interval of 2 years between them. A total and superficial parotidectomy for left and right tumors, respectively, was performed. Only on the left side some facial nerve branches were removed that induced partial paralysis in the patient. A review of the pertinent literature is included.

  20. Laparoscope resection of ectopic corticosteroid-secreting adrenal adenoma.

    PubMed

    Wang, Xian-Ling; Dou, Jing-Tao; Gao, Jiang-Ping; Zhong, Wen-Wen; Jin, Du; Hui, Lüzhao; Lu, Ju-Ming; Mu, Yi-Ming

    2012-01-01

    Tumors originating from ectopic adrenal tissue are relatively rare. In this article, we describe a case with Cushing's syndrome caused by an ectopic adrenal adenoma. A 38 year-old male patient presenting with cushingoid appearance for 2 years was diagnosed to have ACTH-independent Cushing's syndrome based on endocrinological evaluation. Mutiple radiological examinations detected bilateral adrenal atrophy. When the images were investigated in a more expanded scope, a 3.0×3.5×5.3 cm mass was detected in the anterior of left renal hilum and left renal vein. The mass was successfully resected with intraoperative endoscopy and pathological evaluation revealed an ectopic adrenal tumor. It is suggested that when the endocrinlogically confirmed adrenal neoplasm could not be well and definitely localized, the possibility of ectopic adrenal should be presumed and further radiography examinations should extend to the field where ectopic adrenal usually presents.

  1. Crystalline structures in human pancreatic beta cell adenoma.

    PubMed

    Mori, H; Kawai, T; Tanaka, T; Fujii, M; Takahashi, M; Miyashita, T

    1978-05-01

    An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.

  2. The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma.

    PubMed

    Gao, Mingtong; An, Yanyan; Huang, Zhihong; Niu, Jianyi; Yuan, Xunhui; Bai, Yun'an; Guo, Liemei

    2016-03-01

    Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated.

  3. [Radiation therapy for pleomorphic adenoma of the parotid].

    PubMed

    Jardel, P; Fakhry, N; Makeieff, M; Ferrie, J-C; Milin, S; Righini, C; Lacout, A; Costes, V; Malard, O; Marcy, P-Y; Guevara, N; Odin, G; Bensadoun, R-J; Thariat, J

    2014-01-01

    Parotid pleomorphic adenoma is the most frequent tumor of salivary glands. The prognosis depends on the recurrences because they could lead to iatrogenic events (facial paralysis). Moreover the risk of malignant transformation increases with the number of local relapses. This article aims at reviewing histological and radiological criteria and the surgical techniques. To improve local control, adjuvant irradiation (in first intention or after recurrence) may be useful but is still controversial for benign tumors in young patients with a risk of radio-induced cancer. We listed studies in which adjuvant radiotherapy was used so as to define its place in the treatment strategy. Prognostic factors were found by some authors. Other studies have to be done before strong evidence-based recommendations are issued.

  4. ESR1 and its antagonist fulvestrant in pituitary adenomas.

    PubMed

    Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo

    2017-03-05

    Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X(2) = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs.

  5. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

    PubMed

    Losa, Marco; Bogazzi, Fausto; Cannavo, Salvo; Ceccato, Filippo; Curtò, Lorenzo; De Marinis, Laura; Iacovazzo, Donato; Lombardi, Giuseppe; Mantovani, Giovanna; Mazza, Elena; Minniti, Giuseppe; Nizzoli, Maurizio; Reni, Michele; Scaroni, Carla

    2016-02-01

    Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

  6. Frequency of coexistent carcinoma in sessile serrated adenoma/polyps and traditional serrated adenomas removed by endoscopic resection

    PubMed Central

    Saiki, Hirotsugu; Nishida, Tsutomu; Yamamoto, Masashi; Hayashi, Shiro; Shimakoshi, Hiromi; Shimoda, Akiyoshi; Amano, Takahiro; Sakamoto, Aisa; Otake, Yuriko; Sugimoto, Aya; Takahashi, Kei; Mukai, Kaori; Matsubara, Tokuhiro; Nakajima, Sachiko; Fukui, Koji; Inada, Masami; Yamamoto, Katsumi; Tokuda, Ryozo; Adachi, Shiro

    2016-01-01

    Background and study aims: Sessile serrated adenoma/polyps (SSA/Ps) have a different potential than traditional adenomatous polyps for developing into malignant colorectal cancer. However, little is known about the coexistent cancer rate. Here, we evaluate the frequency of carcinoma in serrated polyps removed by endoscopic resection (ER). Patients and methods: This was a retrospective single-center cohort study of consecutive patients with colorectal polyps who underwent ER from March 2003 to October 2014. We determined the frequency of serrated polyps among all resected colorectal polyps and analyzed the clinicopathological findings as well as the frequency and characteristics of coexistent carcinoma in the serrated polyps resected by ER based on pathology reports. Results: A total of 21,048 polyps from 15,326 patients were identified, including 15,984 traditional adenomatous polyps (75.9 %), 621 SSA/Ps (3.0 %), 136 traditional serrated adenomas (TSAs) (0.6 %), 1,121 hyperplastic polyps (5.3 %), and 3,186 polyps of other types (15.1 %). The clinical and endoscopic findings of SSA/Ps revealed a male predominance (68.6 %), with 61.7 % of the polyps located in the proximal colon. Males accounted for 77.2 % of all patients with TSAs, and 77.2 % of these polyps were located in the distal colon. The mean sizes of the SSA/Ps and TSAs were 8.8 and 10.7 mm, respectively. Among the SSA/Ps, 8 (1.3 %) cases had coexistent carcinoma, and 1 (0.7 %) patient with TSA showed coexistent carcinoma. In the patients with SSA/Ps, female sex and a tumor size ≥ 10 mm were predictive factors for coexistent carcinoma. Conclusions: The frequency of SSA/Ps with carcinoma was lower than that for traditional adenoma. Female sex and tumor size ≥ 10 mm were significant predictive factors for coexistent carcinoma. PMID:27092327

  7. Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair.

    PubMed

    Dnyanmote, Ankur V; Sawant, Sharmilee P; Lock, Edward A; Latendresse, John R; Warbritton, Alan A; Mehendale, Harihara M

    2006-03-01

    Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate beta-lyase, the enzyme that bio-activates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephro-protection. These findings suggest that pre-placement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure.

  8. Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair

    SciTech Connect

    Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-03-01

    Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-L-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate {beta}-lyase, the enzyme that bioactivates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephroprotection. These findings suggest that preplacement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure.

  9. Identification of a subtype-specific ENC1 gene related to invasiveness in human pituitary null cell adenoma and oncocytomas.

    PubMed

    Feng, Jie; Hong, Lichuan; Wu, Yonggang; Li, Chuzhong; Wan, Hong; Li, Guilin; Sun, Yilin; Yu, Shenyuan; Chittiboina, Prashant; Montgomery, Blake; Zhuang, Zhengping; Zhang, Yazhuo

    2014-09-01

    Non-functioning pituitary adenomas (NFPAs) may be locally invasive. Surgery is a treatment option, but unlike the case for functional pituitary adenomas, there are almost no drug treatments available for NFPAs. Markers of invasiveness are needed to guide therapeutic decision-making and identify potential adjuvant drugs. Owing to the highly heterogeneous nature of NFPAs, little is known regarding the subtype-specific gene expression profiles associated with invasiveness. To identify important biomarkers of invasiveness, we selected 23 null cell adenomas and 20 oncocytomas. These tumors were classified as invasive or non-invasive adenomas based on magnetic resonance imaging, pathology slides and surgical findings. Firstly, we observed that there were significant differences in expression between invasive (n = 3) and non-invasive (n = 4) adenomas by gene expression microarray. A total of 1,188 genes were differentially expressed in the invasive and non-invasive adenomas. Among these 1,188 genes, 578 were upregulated and 610 were downregulated in invasive adenomas. Secondly, the expression of ENC1, which displayed the significant alterations, was further confirmed by qRT-PCR and Western blot analysis in all 43 tumor samples and three normal pituitary glands. Low levels of ENC1 were found in tumor samples, while high levels were detected in normal pituitary glands. Interestingly, the ENC1 expression level was low in invasive null cell adenomas compared with non-invasive adenomas, but this relationship was not observed in invasive oncocytomas. Immunohistochemistry also demonstrated that the staining of ENC1 was different between invasive and non-invasive null cell adenomas. In addition, bioinformatics studies, including gene ontology and protein interaction analyses, were also performed to better understand the critical role of ENC1 in the development and progression of null cell adenomas and oncocytomas. Consequently, ENC1 may be an important biomarker for null cell

  10. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    PubMed

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.

  11. Strangulated adenoma of the liver: a unique cause of acute abdomen.

    PubMed

    Portinari, Mattia; Liboni, Alberto; Feo, Carlo V

    2014-03-20

    Hepatic adenomas are uncommon benign tumours of the liver which may eventually present with acute onset following rupture of the lesion and haemorrhage. We present here a unique case of strangulated adenoma of the liver presenting as acute abdomen. A 27-year-old woman taking oral contraceptives, presented to the emergency department with abdominal pain, palpable abdominal mass, fever, and neutrophilia. An abdominal ultrasound showed a 3-cm hepatic nodule and an 11-cm mesogastric mass. Computed tomography of the abdomen revealed a 2.3-cm liver adenoma and a 13-cm pedunculated mass of the liver showing no contrast enhancement suggestive of pedicle torsion with ischemia of the mass. The patient underwent an emergent open resection of the strangulated liver mass, she recovered without complications, and was discharged home after three days. Final pathology confirmed an hepatocellular adenoma with areas of necrosis and hemorrhage. The clinical significance of the disease is discussed.

  12. Carcinoma ex pleomorphic adenoma originating from ectopic salivary gland in the neck region: case report.

    PubMed

    Ismı, Onur; Vayısoğlu, Yusuf; Arpaci, Rabia Bozdogan; Eti, Can; Pütürgeli, Tuğçe; Gorur, Kemal; Ozcan, Cengiz

    2015-12-01

    Carcinoma ex pleomorphic adenoma (CEPA) is the malignant salivary gland tumor originating from primary (de novo) or recurrent pleomorphic adenoma. Although parotid gland is the most common site, it can also be seen in submandibular gland or minor salivary glands. It can be seen rarely in head and neck region, such as oral cavity, trachea, nasal cavity and lacrimal gland. Although pleomorphic adenoma cases originating from ectopic salivary gland tissue in the neck region are present in the English literature, there is no published pleomorphic adenoma ex carcinoma case. In this case report we presented a CEPA as a 7.5 cm long neck mass in a 72-year-old woman originating from the submandibular region apart from submandibular gland. Difficulties in diagnosis and way to appropriate treatment are discussed with current literature.

  13. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  14. [Ceruminous gland adenoma of the external auditory canal: a case report].

    PubMed

    Namysłowski, Grzegorz; Scierski, Wojciech; Misiołek, Maciej; Czecior, Eugeniusz; Lange, Dariusz

    2003-01-01

    Ceruminous adenoma (ceruminoma) of the external auditory meatus is a rare neoplasm with benign clinical behavior. This tumor is mainly composed of the ceruminous gland cells (modified apocrine sweat glands). These glands are localized deep in the skin mostly in the cartilaginous part of the external auditory meatus. The most often symptom of the ceruminous adenoma of external auditory meatus is the unilateral conductive hearing loss. Occasionally symptoms of this tumor (pain, otorrhoea) can result from an otitis externa secondary to meatus obstruction. Ceruminous adenoma should be radical excised with adequate margins of the normal tissues. The prognosis of these tumors is good. The difficulties of nomenclature, histological structure of the auditory external meatus ceruminoma, as well as symptomatology, treatment and clinical behavior are discussed on the basis of the literature. A case of histologically confirmed ceruminoma (ceruminous adenoma) of the external auditory meatus in a surgically treated 53 years old men is presented.

  15. Immunohistochemical profile of canalicular adenoma of the upper lip: a case report.

    PubMed

    Pereira, Michele Conceição; Pereira, Alessandro Antônio Costa; Hanemann, João Adolfo Costa

    2007-01-01

    Canalicular adenoma is an uncommon benign salivary gland neoplasm that has a marked predilection for occurrence in the upper lip. It is composed of columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. This tumor has an excellent prognosis after conservative surgical treatment in all locations. In the present report we describe, using immunohistochemistry, the expression of cytokeratins (CK), S-100 protein and EMA in a canalicular adenoma that arose in the upper lip of a 55-year-old female. Cells of the canalicular adenoma showed an immunohistochemical profile that indicates an excretory duct origin: most of these cells positively expressed AE1/AE3 cytokeratins and S100 protein. A comparison of the immunohistochemical features of canalicular adenoma with other salivary gland neoplasms that share similar histological features is discussed.

  16. Transsphenoidal approach for pituitary adenomas in patients with McCune-Albright syndrome.

    PubMed

    Dou, Wanchen; Di, Xiao; Wang, Renzhi; Zhu, Huijuan; Yao, Yong; Deng, Kan; Feng, Ming; Li, Guilin; Wei, Junji

    2013-06-01

    The feasibility of transsphenoidal approach under a guidance of neuronavigation was explored to remove pituitary adenomas for patients with McCune-Albright syndrome (MAS). From August, 2008 to July, 2010, there were 5 patients diagnosed with MAS associated with a pituitary adenoma in our department of Peking Union Medical College Hospital. All the patients underwent transsphenoidal surgery for the removal of pituitary adenomas with the assistant of neuronavigation and all the procedures went uneventfully. Four of the five patients have got cured radiologically by imaging and 3 of them have got cured based on endocrinological criteria. Transsphenoidal approach under the neuronavigational guidance is a safe and effective management for the MAS patients with pituitary adenomas.

  17. Geometric survey on magnetic resonance imaging of growth hormone producing pituitary adenoma.

    PubMed

    Bakhtiar, Yuriz; Hanaya, Ryosuke; Tokimura, Hiroshi; Hirano, Hirofumi; Oyoshi, Tatsuki; Fujio, Shingo; Bohara, Manoj; Arita, Kazunori

    2014-04-01

    Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

  18. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

  19. Duodeno-gastric reflux and gastric adenomas: a scintigraphic study in patients with familial adenomatous polyposis.

    PubMed Central

    Spigelman, A D; Granowska, M; Phillips, R K

    1991-01-01

    To test whether the presence of gastric adenomas (dysplasia) was associated with gastric reflux of duodenal contents, six patients with familial adenomatous polyposis (FAP) who had gastric adenomas and nine matched FAP patients without gastric adenomas underwent scintigraphic duodeno-gastric reflux scanning. Reflux was graded 0-6, where 0 = no reflux, 1 = intermittent reflux into antrum only, 2 = prolonged reflux into antrum only, 3 = intermittent reflux into body, 4 = prolonged reflux into body, 5 = intermittent reflux into body and fundus, and 6 = prolonged reflux into body and fundus. FAP patients with gastric adenomas had more severe reflux (median 6, range 4-6) than did controls (median 3, range 0-6; P = 0.009, Mann-Whitney U test). These results are consistent with a role for bile in the development of gastric adenomatous polyps and suggest that bile is involved in the dysplasia-carcinoma sequence. PMID:1653358

  20. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  1. Does physical activity modify the association between body mass index and colorectal adenomas?

    PubMed

    Guilera, Magda; Connelly-Frost, Alexandra; Keku, Temitope O; Martin, Christopher F; Galanko, Joseph; Sandler, Robert S

    2005-01-01

    Although both physical inactivity and obesity have been associated with an increased risk of colorectal adenomas, it is unclear whether physical activity modifies the relationship between obesity and colorectal adenomas or through what mechanism this might occur. The aim of this study is to evaluate whether physical activity modifies the relationship between body mass index (BMI) and colorectal adenomas and whether apoptosis is a plausible mechanism responsible for this effect modification. Study subjects were part of a large, cross-sectional study, the Diet and Health Study III. Consecutive patients underwent colonoscopy between August 1998 and March 2000. Apoptosis was measured by morphological evaluation of hematoxylin and eosin-stained sections obtained from rectal pinch biopsy samples. There were 226 patients with adenomas and 494 adenoma-free controls. When comparing overweight subjects with the referent group (high physical activity/normal BMI), the relative odds of having an adenoma decreased as physical activity increased: low (odds ratio, OR=1.6; 95% confidence interval, CI=0.7-3.4); moderate (OR=1.1; 95% CI=0.6-2.0); and high (OR=0.8; 95% CI=0.4-1.6). When comparing obese subjects with the referent group, relative odds of having an adenoma were increased regardless of physical activity level. Apoptosis was not associated with obesity or physical activity. Our results suggest that physical activity may modify the association between obesity and colorectal adenoma until a high level of obesity is achieved. Apoptosis does not appear to be associated with obesity or physical activity.

  2. Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

    PubMed

    Skorić, T; Korsić, M; Zarković, K; Plavsić, V; Besenski, N; Breskovac, L; Giljević, Z; Paladino, J

    1999-06-01

    A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

  3. Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk: the self defense forces study.

    PubMed

    Yoshimitsu, Shinichiro; Morita, Makiko; Hamachi, Tadamichi; Tabata, Shinji; Abe, Hiroshi; Tajima, Osamu; Uezono, Kousaku; Ohnaka, Keizo; Kono, Suminori

    2012-10-01

    Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3' untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30 mL/d), but not in those with low alcohol consumption (interaction P = 0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.

  4. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  5. Effects of cabergoline in a pituitary adenoma secreting follicle-stimulating hormone.

    PubMed Central

    Leese, G.; Jeffreys, R.; Vora, J.

    1997-01-01

    A patient with a pituitary adenoma secreting follicle-stimulating hormone with co-existent primary hyperaldosteronism is described. After his second transsphenoidal surgery, the patient developed a Staphylococcus aureus pituitary abscess. Symptoms improved after abscess drainage. Subsequent cabergoline therapy arrested the deterioration of symptoms. and decreased serum follicle-stimulating hormone concentrations. Cabergoline may be a useful treatment for aggressively growing non-prolactin-secreting pituitary adenomas. PMID:9307745

  6. Postirradiation sarcomatous transformation of a pituitary adenoma: a combined pituitary tumor. Case report

    SciTech Connect

    Pieterse, S.; Dinning, T.A.; Blumbergs, P.C.

    1982-02-01

    A case is reported in which a fibrosarcoma developed 20 years after irradiation of a pituitary chromophobe adenoma. This rare lesion, like most of the other documented postirradiation pituitary sarcomas, was a combination of fibrosarcoma and pituitary adenoma. These lesions tend to behave in a characteristic fashion, with onset after a long latent interval following irradiation, growth to a large size, and failure to metastasize.

  7. Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas.

    PubMed

    Wang, Junwen; Voellger, Benjamin; Benzel, Julia; Schlomann, Uwe; Nimsky, Christopher; Bartsch, Jörg W; Carl, Barbara

    2016-09-15

    Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy.

  8. Expression and Clinical Significance of miR-26a and Pleomorphic Adenoma Gene 1 (PLAG1) in Invasive Pituitary Adenoma

    PubMed Central

    Yu, ChuanTing; Li, JiXia; Sun, FengNan; Cui, JinPeng; Fang, HuaLi; Sui, GuoLang

    2016-01-01

    Background Although pituitary adenoma is a malignant tumor, it can present as invasive growth in some cases. MicroRNA (miR)-26a has been found to be abnormally highly expressed in pituitary adenoma, indicating possible involvement in pathogenesis. As a known target gene of miR-26a, PLAG1 has abnormally low expression in pituitary adenoma. The correlation between miR-26a or PLAG1 expressional abnormality and occurrence of pituitary adenoma is still unknown, as is its association with invasiveness of pituitary adenoma. Material/Methods Pituitary adenoma tissues, including both invasive and non-invasive subtypes, were collected from our Neurosurgery Department, in parallel with normal pituitary tissues from postmortem autopsy. qRT-PCR was used to detect mRNA expression of miR-26a and PLAG1, while Western blotting was used to test PLAG1 protein expression. The correlation between miR-26a and PLAG1, and with pathological features, were analyzed. ROC analysis revealed the utility of miR-26a and PLAG1 in differential diagnosis of invasive/non-invasive pituitary tumors and in analyzing their effects on patient prognosis. Results MiR-26a was remarkably upregulated in pituitary tumors, while PLAG1 was downregulated, especially in invasive pituitary tumors. miR-26a and PLAG1 had higher diagnostic values for differentiating between invasive and non-invasive pituitary tumors (AUC=0.889 and 0.818, respectively). Those patients with miR-26 overexpression and PLAG1 downregulation had unfavorable prognosis. miR-26 and PLAG1 are independent factors affecting patient diagnosis. Conclusions MiR-26a can facilitate occurrence of pituitary tumor and invasiveness, probably via inhibiting PLAG1 expression. PMID:28012286

  9. Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas

    PubMed Central

    Kim, Won; Clelland, Claire; Yang, Isaac; Pouratian, Nader

    2012-01-01

    Despite advances in surgical techniques and medical therapies, a significant proportion of pituitary adenomas remain endocrinologically active, demonstrate persistent radiographic disease, or recur when followed for long periods of time. While surgical intervention remains the first-line therapy, stereotactic radiosurgery is increasingly recognized as a viable treatment option for these often challenging tumors. In this review, we comprehensively review the literature to evaluate both endocrinologic and radiographic outcomes of radiosurgical management of pituitary adenomas. The literature clearly supports the use of radiosurgery, with endocrinologic remission rates and time to remission varying by tumor type [prolactinoma: 20–30%, growth hormone secreting adenomas: ~50%, adrenocorticotrophic hormone (ACTH)-secreting adenomas: 40–65%] and radiographic control rates almost universally greater than 90% with long-term follow-up. We stratify the outcomes by tumor type, review the importance of prognostic factors (particularly, pre-treatment endocrinologic function and tumor size), and discuss the complications of treatment (with special attention to endocrinopathy and visual complications). We conclude that the literature supports the use of radiosurgery for treatment-refractory pituitary adenomas, providing the patient with a minimally invasive, safe, and effective treatment option for an otherwise resistant tumor. As such, we provide literature-based treatment considerations, including radiosurgical dose, endocrinologic, radiographic, and medical considerations for each adenoma type. PMID:22826820

  10. Congenital Pleomorphic Adenoma in a SubmandibularGland of a Newborn- A Case Report

    PubMed Central

    Azma, Roxana; Fallahi, Minoo; Khoddami, Maliheh; Shamsian, Bibi Shahin; Alavi, Samin

    2016-01-01

    Introduction: Pleomorphic adenoma is a rare benign salivary gland neoplasm in children, which can be treated by simple excision. This tumor is rarely included in the differential diagnosis of solid submandibular masses in children. In the neonates, congenital pleomorphic adenoma usually presents in the nasopharynx. Surgical excision is the treatment of choice and recurrence is not expected. We report what appears to be the first case of congenital pleomorphic adenoma in the submandibular region in a one-day-old newborn. Case Report: The case of a one-day-old term baby is presented with a 5x2 cm left submandibualr mass with extension to the oral cavity. The mass was hard and non-mobile. During Ultrasonography and Contrast-enhanced Computed Tomography (CT) scan, the mass was solid with a heterogeneous internal structure. The tumor was completely excised and proved to be a pleomorphic adenoma during histopathological examination. Conclusion: Congenital pleomorphic adenoma rarely occurs in the nasopharynx and is treated by surgical excision. Our case is unique because the congenital pleomorphic adenoma is located in the submandibular gland of a newborn. PMID:27280103

  11. Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin-secreting pituitary adenoma.

    PubMed

    Pappa, Theodora; Papanastasiou, Labrini; Markou, Athina; Androulakis, Ioannis; Kontogeorgos, George; Seretis, Andreas; Piaditis, George

    2010-01-01

    Thyrotoxic Periodic Paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. Thyroid-Stimulating Hormone (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism. Even more rare is the occurrence of TPP as the first manifestation of a TSH-secreting pituitary adenoma. We report a 31-year-old Asian male patient suffering from TPP caused by a TSH-secreting adenoma, who was evaluated for persistent episodes of muscle paralysis. Laboratory investigation revealed hypokalemia as well as elevated levels of both thyroid hormones and TSH. The Magnetic Resonance Imaging (MRI) of the pituitary gland revealed a microadenoma, thus suggesting the presence of a TSH-secreting adenoma. The patient underwent transphenoidal resection and the pathological investigation confirmed the diagnosis of TSH-secreting pituitary adenoma. After the adenomectomy and the restoration of euthyroidism, the patient did not experience any episode of hypokalemic paralysis or weakness. Despite its rarity, TSH-secreting pituitary adenoma should be included in the differential diagnosis of TPP.

  12. Helicobacter pylori infection with intestinal metaplasia: An independent risk factor for colorectal adenomas

    PubMed Central

    Yan, Ye; Chen, Yi-Na; Zhao, Qian; Chen, Chao; Lin, Chun-Jing; Jin, Yin; Pan, Shuang; Wu, Jian-Sheng

    2017-01-01

    AIM To explore the association between Helicobacter pylori (H. pylori) infection status, intestinal metaplasia (IM), and colorectal adenomas. METHODS We retrospectively reviewed 1641 individuals aged ≥ 40 years who underwent physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy, and an interview to ascertain baseline characteristics and general state of health. Histopathological results were obtained by gastric and colorectal biopsies. RESULTS The prevalence of H. pylori infection and adenomas was 51.5% (845/1641) and 18.1% (297/1641), respectively. H. pylori infection was significantly correlated with an increased risk of colorectal adenomas (crude OR = 1.535, 95%CI: 1.044-1.753, P = 0.022; adjusted OR = 1.359, 95%CI: 1.035-1.785, P = 0.028). Individuals with IM had an elevated risk of colorectal adenomas (crude OR = 1.664, 95%CI: 1.216-2.277, P = 0.001; adjusted OR = 1.381, 95%CI: 0.998-1.929, P = 0.059). Stratification based on H. pylori infection stage and IM revealed that IM accompanied by H. pylori infection was significantly associated with an increased risk of adenomas (crude OR = 2.109, 95%CI: 1.383-3.216, P = 0.001; adjusted OR = 1.765, 95%CI: 1.130-2.757, P = 0.012). CONCLUSION H. pylori-related IM is associated with a high risk of colorectal adenomas in Chinese individuals. PMID:28293091

  13. Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma.

    PubMed

    Sekine, Shigeki; Yamashita, Satoshi; Tanabe, Taro; Hashimoto, Taiki; Yoshida, Hiroshi; Taniguchi, Hirokazu; Kojima, Motohiro; Shinmura, Kazuya; Saito, Yutaka; Hiraoka, Nobuyoshi; Ushijima, Toshikazu; Ochiai, Atsushi

    2016-06-01

    The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.

    PubMed

    Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi; Ren, Song-Guang; Wawrowsky, Kolja; Melmed, Shlomo

    2015-04-01

    Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.

  15. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    PubMed

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-02-06

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

  16. Spitz nevus arising upon a congenital glomuvenous malformation.

    PubMed

    Arica, Deniz A; Arica, Ibrahim E; Yayli, Savas; Cobanoglu, Umit; Akay, Bengu N; Anadolu, Rana; Bahadir, Sevgi

    2013-01-01

    There are several reports of the collision of vascular and pigmentary anomalies (e.g., phakomatosis pigmentovascularis) and the association between congenital melanocytic nevi and infantile hemangiomas. We report a case of Spitz nevus arising in skin overlying a congenital plaque-like glomuvenous malformation (GVM). This is the first report of a Spitz nevus arising in direct contiguity to a GVM.

  17. 32 CFR 537.19 - Demands arising from maritime claims.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Demands arising from maritime claims. 537.19 Section 537.19 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY CLAIMS AND ACCOUNTS CLAIMS ON BEHALF OF THE UNITED STATES § 537.19 Demands arising from maritime claims. (a) It...

  18. 12 CFR 221.110 - Questions arising under this part.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Questions arising under this part. 221.110 Section 221.110 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL... CARRYING MARGIN STOCK (REGULATION U) Interpretations § 221.110 Questions arising under this part. (a)...

  19. [Pilot results of prostatic adenoma treatment with diode laser Medilas D UroBeam in the Ukraine].

    PubMed

    Kogut, V V; Dzhuran, B V

    2012-01-01

    Pilot results of prostatic adenoma treatment with diode laser (940 nm) in 94 patients showed high efficacy of laser vaporization of the prostate. The effect was achieved in all the patients in minimal number of complications and in satisfactory tolerance of the surgery. Laser vaporization has some advantages over standard treatment (TUR) and is a method of choice in small and middle-size adenomas. In large adenoma good results were obtained in combination of laser vaporization with bipolar TUR.

  20. [Endoscopic pleomorphic adenoma of nasal septum resection assisted by low-temperature plasm radiofrequency: a case report].

    PubMed

    Zhang, Dagong; Xiao, Liu; Tian, Huan

    2014-11-01

    We present an extremely rare case of pleomorphic adenoma of the nasal septum in a 24-year old woman who went to consultation because of right nasal neoplasm. The radiologic discoveries by computerized tomography showed a tumor in the right nasal septum. Incisional biopsy was done, with a histopathological report of pleomorphic adenoma. Later, nasal endoscopy was used to remove the neoplasm and histology revealed pleomorphic adenoma of the nasal septum.

  1. Flat adenoma and flat mucosal carcinoma (IIb type)--a new precursor of colorectal carcinoma? Report of two cases.

    PubMed

    Adachi, M; Muto, T; Morioka, Y; Ikenaga, T; Hara, M

    1988-03-01

    Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."

  2. Investigation into the controversial association of Streptococcus gallolyticus with colorectal cancer and adenoma

    PubMed Central

    2009-01-01

    Background The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-κB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis. Methods ELISA was used to measure IgG antibodies of S. gallolyticus and B. fragilis in sera of 50 colorectal cancer, 14 colorectal adenoma patients, 30 age- and sex- matched apparently healthy volunteers (HV) and 30 age- and sex- matched colonoscopically-proven tumor-free control subjects. NF-κB and IL-8 mRNA expression was evaluated in tumorous and non-tumorous tissue sections of carcinoma and adenoma patients in comparison with that of control subjects by using in situ hybridization assay. Results Colorectal cancer and adenoma patients were associated with higher levels of serum S. gallolyticus IgG antibodies in comparison with HV and control subjects (P < 0.05) while no similar association was found with serum IgG antibodies of B. fragilis (P > 0.05). ELISA cutoff value for the seropositivity of S. gallolyticus IgG was calculated from tumor-free control group. The expression of NF-κB mRNA was higher in tumorous than non-tumorous tissue sections of adenoma and carcinoma, higher in carcinoma/adenoma sections than in control subjects, higher in tumorous sections of carcinoma than in adenoma patients, and higher in S. gallolyticus IgG seropositive than in seronegative groups in both tumorous and non-tumorous sections (P < 0.05). IL-8 mRNA expression in tumorous sections of adenoma and carcinoma was higher than in non-tumorous sections, higher in carcinoma/adenoma than in control subjects, and higher in S. gallolyticus IgG seropositive than in seronegative groups in tumorous

  3. Immunohistochemical detection of human natural killer cell like immunoreactivity in human pituitary adenomas, using monoclonal antibody NK-1.

    PubMed

    Sanno, N; Itoh, J; Teramoto, A; Itoh, Y; Hori, S; Osamura, R Y

    1997-10-01

    Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was

  4. 32 CFR 536.111 - Investigation of claims arising under international agreements (for those claims arising in the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Investigation of claims arising under international agreements (for those claims arising in the United States). 536.111 Section 536.111 National... UNITED STATES Claims Cognizable Under International Agreements § 536.111 Investigation of claims...

  5. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations

    PubMed Central

    Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; Tuppurainen, Karoliina; Mäkinen, Markus J.; Vierimaa, Outi; Paschke, Ralf; Saeger, Wolfgang; van der Luijt, Rob B.; Sane, Timo; Robledo, Mercedes; De Menis, Ernesto; Weil, Robert J.; Wasik, Anna; Zielinski, Grzegorz; Lucewicz, Olga; Lubinski, Jan; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.

    2007-01-01

    Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP. PMID:17360484

  6. LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population.

    PubMed

    Xiao, Lan; Tu, Chaofeng; Chen, Shuai; Yu, Zhibin; Lei, Qianqian; Wang, Zeyou; Xu, Gang; Wu, Minghua; Li, Guiyuan

    2014-04-01

    Pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations such as GNAS, MEN1, CNC, and FIPA. LRRC4 is relatively tissue-specific expressed gene in the normal brain and downregulated expression in glioma (87.5%), meningioma (80.9%), and pituitary adenoma (85.5%). It has been suggested that the aberrant expression of LRRC4 contributes to tumorigenesis in glioma. However, little is known yet about association between LRRC4 and risk of pituitary adenoma. In this study, we genotyped three LRRC4 haplotype-tagging SNPs (htSNP) by direct sequencing in case-control studies, which included 183 Han Chinese patients diagnosed with pituitary adenoma and 183 age-, gender-matched, and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNP. We observed statistically significant differences regarding the genotype TT + CT of rs6944446 in the NCA. Haplotype AC of rs3823994-rs6944446 is suggested to have a protective effect in the development of pituitary adenoma (OR 0.339; 95% CI 0.123-0.934). However, haplotype GT of rs3808058-rs6944446 (OR 1.575; 95% CI 1.048-2.368) and AGT of rs3823994-rs6944446-rs3808058 (OR 1.673; 95% CI 1.056-2.651) might be a risk factor for pituitary adenoma development. In a brief, the results support the hypothesis that polymorphisms or haplotypes in the LRRC4 may have important research significance and could be used to predict the risk of pituitary adenoma.

  7. Assessing Individual Risk for High-Risk Colorectal Adenoma at First-Time Screening Colonoscopy

    PubMed Central

    Cao, Yin; Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.

    2015-01-01

    Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective U.S. studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs 1.8% for men in the bottom decile (Odds Ratio[OR]=9.41), and 6.6% vs 2.1% for women (OR=3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the U.S. population that may provide guidance for first-time colorectal cancer screening. PMID:25820865

  8. Assessing individual risk for high-risk colorectal adenoma at first-time screening colonoscopy.

    PubMed

    Cao, Yin; Rosner, Bernard A; Ma, Jing; Tamimi, Rulla M; Chan, Andrew T; Fuchs, Charles S; Wu, Kana; Giovannucci, Edward L

    2015-10-01

    Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening.

  9. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    PubMed Central

    Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé

    2010-01-01

    Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020

  10. Diagnostic challenges of composite colorectal tumors of adenoma-mantle cell lymphoma type.

    PubMed

    Handra-Luca, Adriana

    2013-12-01

    Composite intestinal tumors of adenoma-lymphoma type are rare. To our knowledge 1 tumor showing this association has been previously reported, the histologic diagnosis being made retrospectively. We report the case of an 80-year old male patient complaining for epigastric pain, rectorrhagia, diarrhea, and weight loss. At endoscopy, a rectal lesion (3 cm) of villous low-grade dysplasia adenoma type was detected. Due to persistence of symptoms, new gastro- and coloscopies were performed, the biopsies showing low-grade dysplasia adenomas (right colon, and rectum) and an abundant lymphoid infiltrate (gastroduodenal anastomosis, small intestine, sigmoid, right and left colon, transverse colon, and rectum) of mantle cell lymphoma type, the rectal polyp being composed of both tumor types. The muscularis mucosa was focally infiltrated by the lymphoma, the bulk of the lymphoma being submucosal. After the treatment of 8 mini-cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone cures, lymphoma persisted. On endoscopic ultrasound examination, after the 6 cures of bendamustine following the cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone treatment, the signal of the rectal villous lesion disappeared in the peripheral layers, including of the muscular layer, suggestive of an invasive lesion or persistence of lymphoma. Biopsies confirmed the persistence of the rectal adenoma with low and high-grade adenoma, without lymphoma. In conclusion, the biopsic diagnosis of composite intestinal tumors of adenoma-mantle cell lymphoma type may be challenging, the bulk of the lymphoma being submucosal as in the present case. Although the malignant tumor treatment is the priority in such cases, the effects of chemotherapy on the evolution of benign tumors such as adenomas should be carefully assessed.

  11. Stereotactic Irradiation of GH-Secreting Pituitary Adenomas

    PubMed Central

    Minniti, G.; Scaringi, C.; Amelio, D.; Maurizi Enrici, R.

    2012-01-01

    Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques. PMID:22518123

  12. PPAR-γ receptor ligands: novel therapy for pituitary adenomas

    PubMed Central

    Heaney, Anthony P.; Fernando, Manory; Melmed, Shlomo

    2003-01-01

    Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug therapies are available, and surgical excision is currently the only effective treatment. We show here abundant expression of nuclear hormone receptor PPAR-γ in all of 39 human pituitary tumors. PPAR-γ activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion. In vivo development and growth of murine somatolactotroph and gonadotroph tumors, generated by subcutaneous injection of prolactin-secreting (PRL-secreting) and growth hormone–secreting (GH-secreting) GH3 cells, luteinizing hormone–secreting (LH-secreting) LβT2 cells, and α-T3 cells, was markedly suppressed in rosiglitazone-treated mice, and serum GH, PRL, and LH levels were attenuated in all treated animals (P < 0.009). These results demonstrate that PPAR-γ is an important molecular target in pituitary adenoma cells and PPAR-γ ligands inhibit tumor cell growth and GH, PRL, and LH secretion in vitro and in vivo. TZDs are proposed as novel oral medications for managing pituitary tumors. PMID:12727930

  13. Somatostatin and dopamine receptor regulation of pituitary somatotroph adenomas.

    PubMed

    Ben-Shlomo, Anat; Liu, Ning-Ai; Melmed, Shlomo

    2017-02-01

    Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations. Although their main action on somatotroph cells is acute inhibition of GH secretion, they also may inhibit GH production and possibly somatotroph proliferation. These receptors have been reported to create complexes that exhibit functions distinct from that of receptor monomers. Somatostatin suppression of GH is mediated mainly by somatostatin receptor subtype 2 and to a lesser extent by SST5. Human somatostatin receptor subtype 5 has also been shown to harbor mutations associated with GH levels, somatotroph tumor behavior, and somatostatin receptor ligand (SRL) responsiveness. Reviewing current knowledge of somatostatin and dopamine receptor expression and signaling in normal and tumoral somatotroph cells offers insights into mechanisms underlying SRL and dopamine agonist effectiveness in patients with acromegaly.

  14. Activating mutations in CTNNB1 in aldosterone producing adenomas

    PubMed Central

    Åkerström, Tobias; Maharjan, Rajani; Sven Willenberg, Holger; Cupisti, Kenko; Ip, Julian; Moser, Ana; Stålberg, Peter; Robinson, Bruce; Alexander Iwen, K.; Dralle, Henning; Walz, Martin K.; Lehnert, Hendrik; Sidhu, Stan; Gomez-Sanchez, Celso; Hellman, Per; Björklund, Peyman

    2016-01-01

    Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5–10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for β-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3β binding domain in exon 3. The mutations were associated with stabilized β-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation. PMID:26815163

  15. Incidence of cerebral infarction after radiotherapy for pituitary adenoma

    SciTech Connect

    Flickinger, J.C.; Nelson, P.B.; Taylor, F.H.; Robinson, A.

    1989-06-15

    The incidence of cerebral infarction was studied in 156 patients irradiated for treatment of pituitary adenomas. Seven patients experienced strokes at intervals of 3.2 to 14.6 years after irradiation. The observed incidence was not significantly greater than the expected value of 3.5 strokes (P = 0.078). Six strokes occurred in patients receiving equivalent doses (ED) of 1070 ret or more (observed to expected ratio 3.87, significantly elevated; P less than 0.001). Univariate log-rank analysis showed that the risk of stroke was significantly higher (P = 0.010) in patients receiving an ED of 1070 ret or more (4180 cGy/22 fractions) than those receiving lower doses. Multivariate analysis, however, demonstrated that the increased risk of stroke was associated only with increasing age (P less than 0.0001), not ED (P = 0.148). Due to these inconsistent statistical results, no definitive conclusions could be reached about the relationship between radiation dose to the pituitary and subsequent cerebral infarction.

  16. Imaging of Resected Nonfunctioning Pituitary Adenomas: The Cost of Surveillance

    PubMed Central

    Kistka, Heather M.; Kasl, Rebecca A.; Nayeri, Arash; Utz, Andrea L.; Weaver, Kyle D.; Chambless, Lola B.

    2015-01-01

    Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003–2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26–76), and the median interval between scans was 357 days (IQR: 225–434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline. PMID:26401475

  17. Middle ear adenoma. A tumor displaying mucinous and neuroendocrine differentiation.

    PubMed

    Wassef, M; Kanavaros, P; Polivka, M; Nemeth, J; Monteil, J P; Frachet, B; Tran Ba Huy, P

    1989-10-01

    Middle ear adenoma (MEA) is a distinctive, rare entity that appears to be derived from the lining epithelium of the middle ear mucosa. We report four cases of MEA displaying the typical histologic growth pattern. Two distinct tumor cell immunophenotypes were identified in all cases; the first type exhibited positivity with anti-epithelial membrane antigen and anti-keratin antibodies, and the second type showed immunoreactivity with anti-keratin, anti-vimentin, and anti-neuron-specific enolase antibodies. Ultrastructural studies revealed bidirectional mucinous and neuroendocrine differentiation, demonstrated by the presence of two distinct cell types containing apically located mucous granules and basally concentrated neuroendocrine granules, respectively. The presence of neuroendocrine differentiation was supported by the immunohistochemical detection of vasoactive intestinal polypeptide in the tumor cells in one case and neuron-specific enolase in three cases. These findings suggest that the potential for mixed mucinous/neuroendocrine differentiation described in other endodermally derived tumors also exists in middle ear mucosa. We also believe that the rare lesions diagnosed as primary carcinoid tumors of the middle ear might in fact be MEA with predominant or only neuroendocrine differentiation. The clinical course of our four cases and our review of the pertinent literature confirm the benign nature of MEA and indicate that these tumors should be treated by complete local excision without additional therapy.

  18. Confocal laser endomicroscopy features of sessile serrated adenomas/polyps

    PubMed Central

    Parikh, Neil D; Gibson, Joanna; Nagar, Anil; Ahmed, Ali A

    2015-01-01

    Background and aims Sessile serrated adenomas/polyps (SSA/Ps) are difficult to differentiate from non-neoplastic tissue on white-light endoscopy. Confocal laser endomicroscopy (CLE) provides subcellular imaging and real-time “optical biopsy”. The aim of this study was to prospectively describe CLE features of SSA/Ps. Patients and methods Consecutive patients with SSA/Ps were prospectively evaluated with probe-based CLE imaging. CLE images and polyp histology were independently reviewed by three endoscopists and an expert gastrointestinal (GI) pathologist. Distinguishing CLE features of SSA/Ps were identified in conjunction with pathologic correlation. Results In total, 260 CLE images were generated from nine SSA/Ps evaluated in seven patients. Four consensus CLE features of SSA/P were identified: (1) a mucus cap with a bright, cloud-like appearance; (2) thin, branching crypts; (3) increased number of goblet cells and microvesicular mucin-containing cells; and (4) architectural disarray, with dystrophic goblet cells and lack of regular circular crypts Conclusion This is a novel description of characteristic CLE features of SSA/Ps. The four features we identified are easy to detect and may allow for CLE to serve as a diagnostic modality. PMID:27536371

  19. Tenosynovial Giant Cell Tumor Arising on the Scapular Region

    PubMed Central

    Fukuda, Asako; Ueno, Takashi; Takayama, Ryoko; Ansai, Shin-ichi; Futagami, Ayako; Kawana, Seiji

    2013-01-01

    Tenosynovial giant cell tumor (TSGCT) is a benign soft tissue tumor arising from the synovial membrane that composes the lining of joints, tendons and bursae. TSGCT is a common tumor occurring in the hands and fingers, and also consecutively in the knees, ankles, feet and hips. It is rarely found in the scapular region. To the best of our knowledge, only 2 cases arising on the upper back have been reported. This report presents the case of a 44-year-old Japanese female with a TSGCT arising on her right scapular region. PMID:24403889

  20. Hepatocellular Adenomas and Carcinoma in Asymptomatic, Non-Cirrhotic Type III Glycogen Storage Disease.

    PubMed

    Oterdoom, Leendert H; Verweij, K Evelyne; Biermann, Katharina; Langeveld, Mirjam; van Buuren, Henk R

    2015-12-01

    Glycogen storage diseases (GSDs) are a group of inherited metabolic disorders characterized by accumulation of abnormal glycogen in muscle or liver or both. Specific hepatic complications include liver adenomas and hepatocellular carcinoma (HCC). Hepatocellular carcinomas described in GSD type I are often due to the degeneration of liver adenomas. Hepatocellular carcinoma in GSD type III, however, is rare and is thought to be associated with underlying cirrhosis.We present the case of a 63-year old male who was admitted for assessment of suitability for liver transplantation because of development of recurrent HCC in the presence of multiple liver adenomas. A diagnosis of GSD type III was made in this patient without underlying cirrhosis or metabolic disturbances resembling GSD. This case report is the first documentation of HCC development in an asymptomatic, non-cirrhotic patient with GSD type III. This raises the possibility that in GSD type III, the adenoma - carcinoma sequence can occur as it is also seen in GSD type I. Physicians taking care of GSD patients should be aware of this and some form of surveillance for cirrhosis and HCC should be considered. Also male patients with adenomas should have a thorough workup to reveal any underlying disease such as GSD.

  1. An Interesting Case of Life-Threatening Hypercalcemia Secondary to Atypical Parathyroid Adenoma versus Parathyroid Carcinoma

    PubMed Central

    Mishra, Ankur; Newman, David

    2014-01-01

    Context. Severe hypercalcemia is a life-threatening condition. Atypical parathyroid adenoma and parathyroid carcinomas are uncommon causes which can be difficult to differentiate. Objective. We report a case of a 36-year-old male with very high serum calcium due to a possible atypical parathyroid adenoma versus parathyroid carcinoma. Case Illustration. A serum calcium level of 23.2 mg/dl was noted on admission. He was initially treated with IV hydration, pamidronate, and salmon calcitonin to lower his calcium levels. He also underwent a surgical en bloc resection of parathyroid mass. Pathology showed a mixed picture consistent with possible atypical adenoma versus parathyroid carcinoma. However, due to the possible involvement of the recurrent laryngeal nerve, parathyroid carcinoma was more likely. Also after operation the patient developed hungry bones syndrome and his calcium was replaced vigorously. He continues to be on calcium, vitamin D, and calcitriol supplementation. Results. A review of the literature was conducted to identify previous studies pertaining to parathyroid adenomas and parathyroid cancer. Conclusion. We thereby conclude that hypercalcemia requires very careful monitoring especially after operation. Also it can be very difficult to distinguish between atypical parathyroid adenomas and parathyroid carcinomas as in our case and no clear cut guidelines yet exist to differentiate the two based on histology. PMID:24959180

  2. Segmentation of pituitary adenoma: a graph-based method vs. a balloon inflation method.

    PubMed

    Egger, Jan; Zukić, Dženan; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher

    2013-06-01

    Among all abnormal growths inside the skull, the percentage of tumors in sellar region is approximately 10-15%, and the pituitary adenoma is the most common sellar lesion. A time-consuming process that can be shortened by using adequate algorithms is the manual segmentation of pituitary adenomas. In this contribution, two methods for pituitary adenoma segmentation in the human brain are presented and compared using magnetic resonance imaging (MRI) patient data from the clinical routine: Method A is a graph-based method that sets up a directed and weighted graph and performs a min-cut for optimal segmentation results: Method B is a balloon inflation method that uses balloon inflation forces to detect the pituitary adenoma boundaries. The ground truth of the pituitary adenoma boundaries - for the evaluation of the methods - are manually extracted by neurosurgeons. Comparison is done using the Dice Similarity Coefficient (DSC), a measure for spatial overlap of different segmentation results. The average DSC for all data sets is 77.5±4.5% for the graph-based method and 75.9±7.2% for the balloon inflation method showing no significant difference. The overall segmentation time of the implemented approaches was less than 4s - compared with a manual segmentation that took, on the average, 3.9±0.5min.

  3. Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

    PubMed

    Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

    2008-12-01

    Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

  4. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus

    SciTech Connect

    Zhu, J.; Leon, S.P.; Beggs, A.H.; Busque, L.; Gilliland, D.G.; Black, P.M.

    1994-04-01

    The retinoblastoma tumor suppressor gene (RB1) is inactivated in hereditary and sporadic forms of retinoblastoma as well as in a number of other sporadic tumors. The majority of human pituitary tumors have been shown to be monoclonal neoplasms, suggesting that 1 or more somatic mutations are involved in the clonal expansion of a single progenitor cell. Recently, a high percentage of transgenic mice containing a disrupted RB1 allele have been shown to develop pituitary tumors. To investigate whether RB1 inactivation contributes to the development of human pituitary adenomas, the authors searched for loss of heterozygosity (LOH) within the RB1 gene locus in a variety of human pituitary adenomas. They screened 34 adenomas for LOH using a polymerase chain reaction (PCR)-based microsatellite polymorphic marker at the RB1 gene locus. In addition, a variable number of tandem repeat markers from within the RB1 gene was also used to search for LOH in 14 tumors. They found no LOH or microsatellite instability at the RB1 locus in any of the informative cases (30 of 34). Additionally, they showed that 4 representative adenomas from female patients are monoclonal in origin using a PCR-based clonality analysis assay. They conclude that the RB1 gene shows no LOH in a variety of human pituitary adenomas and that PCR-based microsatellite markers can serve as a useful tool for LOH analysis in human pituitary tumors. 42 refs., 3 figs., 1 tab.

  5. Polymorphisms in WNT6 and WNT10A and Colorectal Adenoma Risk

    PubMed Central

    Galbraith, Rachel L.; Poole, Elizabeth M.; Duggan, David; Muehling, Jill; Hsu, Li; Makar, Karen; Xiao, Liren; Potter, John D.; Ulrich, Cornelia M.

    2015-01-01

    The WNT/β-catenin signaling pathway upregulates transcription of genes involved in cell proliferation and cancer progression; it has been implicated in colorectal adenoma formation. To date, no studies have examined polymorphisms in WNT genes or WNT gene–environment interactions in relation to adenoma risk. Within a colonoscopy-based case-control study of 628 adenoma cases and 516 polyp-free controls, we analyzed two tagSNPs in WNT6 (rs6747776 G > C, rs6754599 G > C) and WNT10A (rs7349332 G > A, rs10177996 A > G). The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma (OR = 2.75, 95% CI: 1.03–7.31). We observed a statistically significant interaction between WNT6 rs6747776 and the proportion of calories from total fat (P-int = 0.02), where the highest risk was observed among those with minor alleles and lowest fat intake. We also detected a marginally significant (0.05 < P ≤ 0.10) interaction with fish intake (P-int = 0.09). Additionally, a marginally significant interaction was observed between proportion of calories from saturated fat and the WNT10A rs7349332 polymorphism. Our results suggest that genetic variability in the WNT pathway may play a role in colorectal adenoma formation or may partly mediate the increased risk of colorectal cancer associated with fat intake. PMID:21547848

  6. Polymorphisms in WNT6 and WNT10A and colorectal adenoma risk.

    PubMed

    Galbraith, Rachel L; Poole, Elizabeth M; Duggan, David; Muehling, Jill; Hsu, Li; Makar, Karen; Xiao, Liren; Potter, John D; Ulrich, Cornelia M

    2011-01-01

    The WNT/β-catenin signaling pathway upregulates transcription of genes involved in cell proliferation and cancer progression; it has been implicated in colorectal adenoma formation. To date, no studies have examined polymorphisms in WNT genes or WNT gene-environment interactions in relation to adenoma risk. Within a colonoscopy-based case-control study of 628 adenoma cases and 516 polyp-free controls, we analyzed two tagSNPs in WNT6 (rs6747776 G > C, rs6754599 G > C) and WNT10A (rs7349332 G > A, rs10177996 A > G). The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma (OR = 2.75, 95% CI: 1.03-7.31). We observed a statistically significant interaction between WNT6 rs6747776 and the proportion of calories from total fat (P-int = 0.02), where the highest risk was observed among those with minor alleles and lowest fat intake. We also detected a marginally significant (0.05 < P ≤ 0.10) interaction with fish intake (P-int = 0.09). Additionally, a marginally significant interaction was observed between proportion of calories from saturated fat and the WNT10A rs7349332 polymorphism. Our results suggest that genetic variability in the WNT pathway may play a role in colorectal adenoma formation or may partly mediate the increased risk of colorectal cancer associated with fat intake.

  7. Ectopic pituitary adenoma of the clivus presenting with apoplexy: case report and review of the literature.

    PubMed

    Mudd, Pamela A; Hohensee, Samantha; Lillehei, Kevin O; Kingdom, Todd T; Kleinschmidt-Demasters, Bette K

    2012-01-01

    Ectopic pituitary adenomas usually occur within sphenoid sinus or nasopharynx, and seldom within the clivus. There is only a single reported example of ectopic adenoma with clinical apoplexy, albeit not from clivus. We report a 78-year-old male with known prostate carcinoma admitted with acute onset of blurred vision, suggestive of apoplexy. Work-up revealed unilateral cranial nerve VI palsy and neuroimaging showed a mass confined to the clivus; sellar region was normal. Preoperative considerations included chordoma, chondrosarcoma, or metastatic prostate carcinoma to bone. Resection was via endoscopic transsphenoidal approach to the clivus. An ectopic null cell pituitary adenoma with bland infarction was identified as the cause of the patient's clinical apoplexy. No antecedent precipitating factors for apoplexy were present; specifically the patient had not received leuprolide preoperatively, a known precipitant of pituitary apoplexy in prostate cancer patients who receive drug. We review the literature on ectopic clival pituitary adenomas, apoplexy in ectopic adenomas, and the link between apoplexy and leuprolide usage.

  8. Relationship between RSUME and HIF-1α/VEGF-A with invasion of pituitary adenoma.

    PubMed

    He, Wei; Huang, Ling; Shen, Xiaoli; Yang, Yanlin; Wang, Dapeng; Yang, Yue; Zhu, Xingen

    2017-03-01

    The RWD-containing sumoylation enhancer (RSUME) can stabilize hypoxia-inducible factor-1α (HIF-1α) which promotes vascular endothelial growth factor-A (VEGF-A) expression. RSUME plays an important role in promoting the invasion of pituitary adenoma. In this study, we compared the mRNA and protein levels of RSUME, HIF-1α, and VEGF-A in pituitary adenoma tissue and analyzed the correlation. We found that the expression levels of RSUME, HIF-1α, and VEGF-A in invasive pituitary adenoma were significantly higher than in noninvasive pituitary adenoma. Moreover, a positive correlation was found between RSUME and HIF-1α/VEGF pathways. RSUME and HIF-1α were treated with hypoxia-mimicking CoCl2 and transfected into AtT-20 and GT1.1 cell lines to determine the relationship between them. It was found that RSUME effects post-transcriptional expression of HIF-1α regulated VEGF-A secretion. Reducing RSUME expression using siRNA transfection resulted in a decrease of the invasion inhibition rate of AtT-20 cells, as determined using Transwell and MTT assays. Together, we found that RSUME silencing can inhibit the invasion of pituitary adenoma cells.

  9. In vivo measurement of dopamine receptors in pituitary adenomas using positron emission tomography.

    PubMed

    Muhr, C; Bergström, M; Lundberg, P O; Bergström, K; Långström, B

    1986-01-01

    Patients with pituitary adenomas were examined with positron emission tomography (PET) with the administration of the 11C-labelled dopamine-D2 antagonists N-methylspiperone and raclopride. The studies were repeated after protection of the D2-receptors with Haloperidol to enable a separation of specific and unspecific receptor binding. The receptor binding was evaluated by visual inspection and with the application of a kinetic model. The results showed marked specific dopamine-D2 receptor binding in the prolactinomas and minimal or no such binding in the hormonally inactive adenomas. The two tracers 11C-raclopride and 11C-N-methylspiperone showed qualitatively the same result although raclopride resulted in a higher tumor to normal brain ratio. In conclusion, PET is a valuable complement to other radiologic techniques like computed tomography and magnetic resonance imaging in the evaluation of pituitary adenomas. An assessment of the dopamine-D2 receptors in the adenomas has a direct influence on the choice of treatment because adenomas with high amounts of receptors are in most cases effectively treated with dopamine agonists like bromocriptine.

  10. ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    EPA Science Inventory

    ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    Humans are exposed to a variety of mutagens from diet, smoking, or occupation. To explore if exposure to mutagens was related to the risk of colorectal adenomas i...

  11. Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

    PubMed

    Stojadinovic, Alexander; Brennan, Murray F; Hoos, Axel; Omeroglu, Atilla; Leung, Denis H Y; Dudas, Maria E; Nissan, Aviram; Cordon-Cardo, Carlos; Ghossein, Ronald A

    2003-08-01

    We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

  12. MMP-14 and TGFβ-1 methylation in pituitary adenomas

    PubMed Central

    Ruskyte, Kornelija; Liutkevicienė, Rasa; Vilkeviciute, Alvita; Vaitkiene, Paulina; Valiulytė, Indre; Glebauskiene, Brigita; Kriauciuniene, Loresa; Zaliuniene, Dalia

    2016-01-01

    Pituitary adenoma (PA) is one of the most common abnormalities in the sellar region. Despite the fact that PA is a benign monoclonal neoplasm, it can cause serious complications, including ophthalmological, neurological and endocrinological abnormalities. Currently, the causes that increase the progression of tumors are unknown. Epigenetic silencing of the matrix metalloproteinase-14 (MMP-14) and transforming growth factor beta-1 (TGFβ-1) genes may be associated with the development of PA, since these genes are important in the processes of tumor metastasis and angiogenesis. The purpose of the present study was to determine if the methylation status of the MMP-14 and TGFβ-1 promoters is associated with PA development. In the present study, 120 tissue samples of PA were used. The methylation status of the MMP-14 and TGFβ-1 promoters was investigated by methylation specific-polymerase chain reaction. Statistical analysis was conducted to investigate the associations between the methylation status, age and gender of PA patients, PA tumoral activity, recurrence and invasiveness. The MMP-14 gene was methylated in 30.00% (17/56 functioning and 19/64 non-functioning) of patients with PA, while the TGFβ-1 gene was methylated in 13.33% (9/56 functioning and 7/64 non-functioning) of patients with PA. It was also observed that promoter methylation of MMP-14 correlated with the male gender (58.8 vs. 35.7%, P=0.022), while unmethylated (non-silenced) MMP-14 correlated with the female gender (64.3 vs. 41.7%, P=0.027). Associations between the promoter methylation status of the MMP-14 and TGFβ-1 genes and PA functioning or recurrence were not identified. The present study reveals that silencing of the MMP-14 gene correlates with patients' gender. However, MMP-14 and TGFβ-1 promoter methylation cannot be considered as a prognostic marker in PAs. PMID:27698891

  13. Sphenoid sinus ectopic pituitary adenomas: CT and MRI findings

    PubMed Central

    Yang, B T; Chong, V F H; Wang, Z C; Xian, J F; Chen, Q H

    2010-01-01

    Ectopic pituitary adenomas (EPAs) are rare lesions. The purpose of this study was to describe the CT and MRI features of sphenoid sinus EPAs. Eight patients with histology-proven EPAs in the sphenoid sinus, all of whom underwent CT and MRI, were reviewed retrospectively. The following imaging features were analysed: (i) size, (ii) margin, (iii) CT attenuation characteristics and (iv) MRI signal intensity. In addition, the involvement of adjacent structures and the time–intensity curve (TIC) of dynamic contrast-enhanced (DCE) MRI were analysed. All EPAs had well-defined margins and showed no relationship to the intrasellar pituitary gland. The mean size was 28 mm (range, 20–46 mm). On non-enhanced CT, the lesions appeared isodense to grey matter in 7 (88%) patients and hypodense in 1 (12%) patient. Only two patients underwent post-contrast CT, and they showed moderate enhancement. On T1 weighted images, EPAs appeared isointense in 6 (75%) patients and hypointense in 2 (25%). On T2 weighted images, the lesions appeared hyperintense in 2 (25%) patients and isointense in 6 (75%). EPAs showed mild to moderate heterogeneous contrast enhancement and exhibited a cribriform-like appearance. Two patients underwent DCE MRI; the TIC showed a rapidly enhancing and slow washout pattern. The following features were also seen: an empty sella, bone changes and involvement of the cavernous sinus (5 patients; 62.5%). In conclusion, a high index of suspicion for EPA and a familiarity with the imaging findings may help to diagnose this rare entity accurately. PMID:19651706

  14. Cell-surface markers for colon adenoma and adenocarcinoma.

    PubMed

    Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L

    2016-04-05

    Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

  15. Middle ear adenoma with neuroendocrine differentiation: relate of two cases and literature review

    PubMed Central

    Bittencourt, Aline Gomes; Tsuji, Robinson Koji; Cabral, Francisco; Pereira, Larissa Vilela; Fonseca, Anna Carolina de Oliveira; Alves, Venâncio; Bento, Ricardo Ferreira

    2013-01-01

    Summary Introduction: Adenomas with neuroendocrine differentiation are defined as neuroendocrine neoplasms, and they are rarely found in the head and neck. Objective: To describe two cases of a middle ear adenoma with neuroendocrine differentiation, with a literature review. Case Report: Patient 1 was a 41-year-old woman who presented with a 3-year history of left aural fullness associated with ipsilateral “hammer beating” tinnitus. Patient 2 was a 41-year-old male who presented with unilateral conductive hearing loss. Conclusion: Adenoma with neuroendocrine differentiation of the middle ear is a rare entity, but it should be considered in patients with tinnitus, aural fullness, and a retrotympanic mass and remembered as a diferential diagnosis of tympanic paraganglioma. PMID:25992031

  16. hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

    PubMed

    Sáez, C; Japón, M A; Ramos-Morales, F; Romero, F; Segura, D I; Tortolero, M; Pintor-Toro, J A

    1999-09-23

    The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

  17. Endophytic malignant transformation within flat adenoma of the colon: a potential diagnostic pitfall.

    PubMed

    Bégin, L R; Gordon, P H; Alpert, L C

    1993-01-01

    A 74-year-old man was found to have a 1 cm, slightly elevated and flat, red mucosal lesion of the descending colon. An endoscopic biopsy showed a structure characteristic of a tubular adenoma. The surgical specimen revealed an inverted, transmural, solid and cystic lesion. The superficial (intra-mucosal) component of the neoplasm was histologically characteristic of a flat adenoma, showing epithelial dysplasia. However, the contiguous deep component was a well-differentiated adenocarcinoma extending to the serosa and demonstrating the unusual features of a circumscribed lobulated topography and the absence of an inflammatory/desmoplastic stromal reaction. Endophytic malignant transformation within a flat adenoma should be distinguished from conditions of misplaced glandular epithelium such as localized colitis cystica profunda. Complete and full mucosal thickness endoscopic snare removal is indicated in order to assess the degree of epithelial dysplasia and detect endophytic malignant transformation.

  18. Small intestinal tubular adenoma in a pediatric patient with Turner syndrome.

    PubMed

    Tang, Wen-Juan; Huang, Ying; Chen, Lian; Zheng, Shan; Dong, Kui-Ran

    2013-04-07

    Turner syndrome (TS) is a female chromosomal disorder caused by the lack of an X chromosome. The loss of this chromosome may result in the deficiency of tumor-suppressive or DNA repair genes, leading to tumorigenesis. Recombinant human growth hormone (GH) has been popularly used for treatment in TS patients for growth promotion. Although treatment with GH has been correlated with precancerous and cancerous lesions in TS children, its associations with gastric or colonic tumors, especially ileal tubular adenomas, have not been reported frequently. We here report a case of a 16-year-old patient with TS and tubular adenoma of the small intestine. Whether the ileal adenoma was caused by TS itself or GH therapy was discussed.

  19. Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery

    PubMed Central

    Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

    2016-01-01

    Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients’ ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. PMID:27106613

  20. Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

    PubMed

    Castinetti, Frederic; Brue, Thierry

    2010-08-01

    Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

  1. Laparoscopic bilateral partial adrenalectomy for adrenocortical adenomas causing Cushing's syndrome: report of a case.

    PubMed

    Inoue, Tomoko; Ishiguro, Kiyosuke; Suda, Takako; Ito, Norimasa; Suzuki, Yoshimasa; Taniguchi, Yuji; Ohgi, Shigetsugu

    2006-01-01

    Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushing's syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushing's syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.

  2. Successful Management of a Giant Pituitary Lactosomatotroph Adenoma Only with Cabergoline

    PubMed Central

    Bozkirli, Emre; Bakiner, Okan; Ersozlu Bozkirli, Emine Duygu; Ertorer, Eda; Bascil Tutuncu, Neslihan; Guvener Demirag, Nilgun

    2013-01-01

    Although advances in endocrinologic and neuroradiologic research allow easier recognition of pituitary adenomas, giant pituitary tumours are relatively rare. In the literature, the term “giant” is generally used when a pituitary tumour becomes larger than 4 cm in diameter. Cabergoline is a potent and long-acting inhibitor of prolactin secretion, which exhibits high specificity and affinity for dopamine D2 receptor. Herein, we report a 46-year-old woman with a giant lactosomatotroph pituitary adenoma, sized 6 × 5 × 5.5 cm, who is treated successfully only with cabergoline. The patient showed dramatic response to cabergoline treatment by means of clinical, biochemical and radiological imaging findings. Cabergoline seems to be safe and effective in the treatment of prolactin and growth hormone cosecreting pituitary adenomas as well as prolactinomas. However, surgical or more aggressive approach must be considered where indicated. PMID:23762662

  3. [The importance for improving the cure rate of lacrimal gland benign pleomorphic adenoma].

    PubMed

    Xiao, L H

    2016-04-11

    The pleomorphic adenoma was the most common epithelial tumor of the lacrimal gland. The 2 major factors determining the prognosis of pleophormic adenoma of lacrimal gland were likelihood of recurrence and evidence of malignant transformation. Management of the recurrent pleomorphic adenoma was difficult. Moreover, the malignant transformation was danger for life. The reason for orbital recurrent involved many factors, but the main reasons may be related to correct preoperative judgment of the nature of the tumor, taking the appropriate surgical approach and operative techniques. Long-term follow-up was available for the patient. It could help doctors detect recurrence of tumor earlier and treat it timely. (Chin J Ophthalmol, 2016, 52: 241-243).

  4. Cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a New Zealand white rabbit (Oryctolagus cuniculus).

    PubMed

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-06-01

    Pituitary adenoma in a rabbitA 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit.

  5. Cushing's disease due to mixed pituitary adenoma-gangliocytoma of the posterior pituitary gland presenting with Aspergillus sp. sinus infection.

    PubMed

    Bridenstine, Mark; Kerr, Janice M; Lillehei, Kevin O; Kleinschmidt-DeMasters, Bette K

    2013-01-01

    Gangliocytic lesions of the pituitary gland producing Cushing's disease are extremely rare entities that may exist with or without a pituitary adenoma. The latter have been designated mixed pituitary adenoma-gangliocytomas, the majority of which produce growth hormone, not adrenocorticotropin (ACTH), and are localized to the anterior gland. We now report an immunocompetent woman with hypercortisolism who presented with an intranasal aspergilloma eroding the bony sellar floor. The fungal ball was contiguous with, and extended into, a large neurohypophyseal-centered mass. Transsphenoidal resection revealed a gangliocytic lesion of the posterior gland with small clusters of intimately admixed ACTH-immunoreactive adenoma cells as the cause of her Cushing's disease. Rare transitional sizes and shapes of cells coupled with immunohistochemical findings supported interpretation as advanced neuronal metaplasia within an ACTH adenoma. This mixed ACTH adenoma-gangliocytoma is the first example to present clinically with an opportunistic infection.

  6. Gene-specific DNA methylation of DNMT3B and MTHFR and colorectal adenoma risk.

    PubMed

    Ho, Vikki; Ashbury, Janet E; Taylor, Sherryl; Vanner, Stephen; King, Will D

    2015-12-01

    DNA methyltransferase 3B (DNMT3B) and methylenetetrahydrofolate reductase (MTHFR) are genes which encode enzymes critical to one-carbon metabolism. Polymorphisms in these genes have been implicated in colorectal cancer etiology; however, epigenetic modifications such as gene-specific DNA methylation also affect gene expression. DNA methylation of DNMT3B and MTHFR was quantified in blood leukocytes using Sequenom EpiTYPER® among 272 participants undergoing a screening colonoscopy. DNA methylation was quantified in 66 and 28CpG sites of DNMT3B and MTHFR respectively, and conceptualized using two approaches. First, measures representing average methylation across all CpG sites were created. Second, unsupervised principal component (PC) analysis was used to identify summary variables representing methylation around the transcription start site and in the gene-coding area for both DNMT3B and MTHFR. Logistic regression was used to compare methylation levels between participants diagnosed with colorectal adenoma(s) versus those with a normal colonoscopy via the estimation of odds ratios (ORs) and 95% confidence intervals (95% CIs) for the risk of colorectal adenomas. No association was observed between average DNA methylation of either DNMT3B or MTHFR and colorectal adenoma risk. For DNMT3B, increasing DNA methylation of CpG sites in the gene-coding area was associated with a higher risk of colorectal adenomas (OR=1.34; 95% CI: 1.01-1.79 per SD). This research provides preliminary evidence that methylation of DNMT3B may have functional significance with respect to colorectal adenomas, precursors to the vast majority of colorectal cancers.

  7. Somatomammotrophic cells in GH-secreting and PRL-secreting human pituitary adenomas.

    PubMed

    Bassetti, M; Brina, M; Spada, A; Giannattasio, G

    1989-11-01

    A morphological study has been carried out on 20 GH-secreting adenomas removed from acromegalic normoprolactinemic patients, on 29 PRL-secreting adenomas removed from hyperprolactinemic patients without signs of acromegaly and on one normal human anterior pituitary gland collected at autopsy. The protein A-gold immunoelectron microscopic technique has been utilized in order to verify the presence of mixed cells producing both GH and PRL (somatomammotrophs) in these pituitary tissues. In the normal pituitary a considerable number of somatomammotrophs (15-20%) was found, thus supporting the idea that these cells are normal components of the human anterior pituitary gland. In 10 GH-secreting adenomas and in 10 PRL-secreting adenomas somatomammotrophs were present in a variable number (from 4 to 20% of the whole cell population in GH adenomas and from 1 to 47% in PRL tumors). It can be concluded therefore that these cells, largely present in all GH/PRL-secreting adenomas, can also be found in GH-secreting and PRL-secreting tumors without clinical evidence of a mixed secretion. Adenomatous somatomammotrophs displayed ultrastructural features of adenomatous somatotrophs and mammotrophs (prominent Golgi complexes, abundant rough endoplasmic reticulum, irregular nuclei). The size and the number of granules were variable. In some cells GH and PRL were stored in distinct secretory granules, in others in mixed granules or both in mixed and distinct granules, thus suggesting that in adenomatous somatomammotrophs the efficiency of the mechanisms of sorting of the two hormones varies from one cell to another.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis.

    PubMed

    Calderaro, Julien; Nault, Jean C; Balabaud, Charles; Couchy, Gabrielle; Saint-Paul, Marie-Christine; Azoulay, Daniel; Mehdaoui, Dalila; Luciani, Alain; Zafrani, Elie S; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica

    2016-01-01

    Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

  9. Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β

    PubMed Central

    Wiener, Zoltán; Band, Arja M.; Kallio, Pauliina; Högström, Jenny; Hyvönen, Ville; Kaijalainen, Seppo; Ritvos, Olli; Haglund, Caj; Kruuna, Olli; Robine, Sylvie; Louvard, Daniel; Ben-Neriah, Yinon; Alitalo, Kari

    2014-01-01

    In the majority of microsatellite-stable colorectal cancers (CRCs), an initiating mutation occurs in the adenomatous polyposis coli (APC) or β-catenin gene, activating the β-catenin/TCF pathway. The progression of resulting adenomas is associated with oncogenic activation of KRas and inactivation of the p53 and TGF-β/Smad functions. Most established CRC cell lines contain mutations in the TGF-β/Smad pathway, but little is known about the function of TGF-β in the early phases of intestinal tumorigenesis. We used mouse and human ex vivo 3D intestinal organoid cultures and in vivo mouse models to study the effect of TGF-β on the Lgr5+ intestinal stem cells and their progeny in intestinal adenomas. We found that the TGF-β–induced apoptosis in Apc-mutant organoids, including the Lgr5+ stem cells, was mediated by up-regulation of the BH3-only proapoptotic protein Bcl-2–like protein 11 (Bim). BH3-mimetic compounds recapitulated the effect of Bim not only in the adenomas but also in human CRC organoids that had lost responsiveness to TGF-β–induced apoptosis. However, wild-type intestinal crypts were markedly less sensitive to TGF-β than Apc-mutant adenomas, whereas the KRas oncogene increased resistance to TGF-β via the activation of the Erk1/2 kinase pathway, leading to Bim down-regulation. Our studies identify Bim as a critical mediator of TGF-β–induced apoptosis in intestinal adenomas and show that the common progression mutations modify Bim levels and sensitivity to TGF-β during intestinal adenoma development. PMID:24825889

  10. [Prognostic implications of folliculo-stellate cells in pituitary adenomas: relationship with tumoral behavior].

    PubMed

    Tortosa, F; Pires, M; Ortiz, S

    2016-10-01

    Introduccion. A pesar del progreso en la comprension de su patogenia, no se ha encontrado ningun marcador predictivo independiente del comportamiento agresivo de los adenomas hipofisarios que facilite el tratamiento y seguimiento de pacientes afectados. Objetivo. Analizar la expresion de celulas foliculo-estrelladas, mediante inmunomarcacion con proteina S-100, en una serie de pacientes con adenomas hipofisarios seguidos durante al menos siete años. Pacientes y metodos. Estudio retrospectivo de 51 pacientes diagnosticados de adenoma hipofisario entre 2006 y 2008, segun los criterios vigentes de la Organizacion Mundial de la Salud. Se evaluo inmunohistoquimicamente la expresion de S-100 en celulas foliculo-estrelladas, y se correlaciono con parametros clinicorradiologicos e histopatologicos del tumor y la progresion/recurrencia postoperatoria. Resultados. De 51 tumores, 40 se clasificaron como adenomas hipofisarios tipicos y 11 como atipicos. La mayoria de los tipicos mostro celulas foliculo-estrelladas positivas para S-100 (media: 3,93%); los atipicos tenian pocas o ninguna celula S-100 positivas (media: 0,83%). No hubo diferencias significativas en la expresion de S-100 con respecto a la edad o sexo del paciente, tamaño, invasividad o recidiva tumoral posquirurgica. Conclusiones. En el grupo de estudio, a excepcion de los adenomas no funcionantes inmunopositivos para prolactina, con la media mas baja y mas alta de todos los subtipos en ambos grupos (tipicos, 0,25%, frente a atipicos, 9,24%; p = 0,0028), el factor predictivo de agresividad tumoral para los adenomas hipofisarios no esta representado por un bajo valor de S-100 en las celulas foliculo-estrelladas, lo que no permite seleccionar a pacientes para un tratamiento postoperatorio intensivo.

  11. Whole-exome sequencing identified mutational profiles of high-grade colon adenomas

    PubMed Central

    Kim, Tae-Min; Rhee, Je-Keun; Park, Hyeon-Chun; Sung, Min Kim; Kim, Sung Soo; Hyeok, Chang An; Lee Hyung, Sug; Chung, Yeun-Jun

    2017-01-01

    Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them. Mutational profiling of high-grade colon adenoma (HGCA) that just precedes colon carcinoma might identify not only novel adenoma-specific genes but also critical genes for its progression to carcinoma. For this, we performed whole-exome sequencing (WES) of 12 HGCAs and identified 11 non-hypermutated and one hypermutated (POLE-mutated) cases. We identified 22 genes including APC, KRAS, TP53, GNAS, NRAS, SMAD4, ARID2, and PIK3CA with non-silent mutations in the cancer Census Genes. Bi-allelic and mono-allelic APC alterations were found in nine and one HGCAs, respectively, while the other two harbored wild-type APC. Five HGCAs harbored either mono-allelic (four HGCAs) or bi-allelic (one HGCA) SMAD4 mutation or 18q loss that had been known as early carcinoma-specific changes. We identified MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations for the first time in colon adenomas. Our WES data is largely matched with the earlier ‘adenoma-carcinoma model’ (APC, KRAS, NRAS and GNAS mutations), but there are newly identified SMAD4, MTOR, ACVR1B, GNAQ, ATM, CNOT1, EP300, ARID2, RET and MAP2K4 mutations in this study. Our findings provide resource for understanding colon premalignant lesions and for identifying genomic clues for differential diagnosis and therapy options for colon adenomas and carcinomas. PMID:28179590

  12. Rapid Reticulin Fiber Staining Method is Helpful for the Diagnosis of Pituitary Adenoma in Frozen Section.

    PubMed

    Noh, Songmi; Kim, Sun Ho; Cho, Nam Hoon; Kim, Se Hoon

    2015-05-01

    Approximately 90% of neoplasms found in the sellar region are adenoma of the pituitary gland. The use of frozen sections for the diagnosis of pituitary adenomas has an accuracy of 90% and is useful in evaluating complete tumor removal. However, it is sometimes difficult to diagnose pituitary adenomas using frozen sections because of the small sample size and marked artifact, and the contiguity of the pituitary adenoma with normal pituitary gland tissue. In this study, we evaluated the use of our modified reticulin stain to make correct decision in frozen section with reduced stain time and investigated the objective diagnostic criteria of pituitary adenoma with reticulin stain. We used Gomori's silver impregnation methods to stain reticulin fibers in frozen pituitary gland sections of 36 samples from 24 patients. We modified the conventional staining method by reducing the overall staining time. We diagnosed pituitary lesion according to our interpretation criteria and compared the results to those of the conventional method and findings of hematoxylin and eosin-stained slides. Reticulin fiber staining of normal adenohypophysis outlines the supporting stroma around the blood vessels and shows regular of the gland meshwork interconnecting the capillaries. In contrast, reticulin fiber staining of the adenomatous tissue shows loss of meshwork or frequent fragmentation. Our modified reticulin stain is more rapid than the established method and shows similar levels of accuracy. Independent evaluation by two pathologists showed discrepancies in diagnosis in four out of 36 cases with modified reticulin stain. Our rapid modified reticulin staining method for frozen sections may be useful as a diagnostic tool for pituitary adenomas and can complement routine hematoxylin and eosin staining.

  13. Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas

    PubMed Central

    Sbiera, Silviu; Tryfonidou, Marianna A.; Weigand, Isabel; Grinwis, Guy C. M.; Broeckx, Bart; Herterich, Sabine; Allolio, Bruno; Deutschbein, Timo

    2016-01-01

    Purpose Cushing’s disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher. This makes the dog an obvious model for studying the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite certain similarities identified at the molecular level, the question still remains whether the two species have a shared oncogenetic background. Recently, hotspot recurrent mutations in the gene encoding for ubiquitin specific protease 8 (USP8) have been identified as the main driver behind the formation of ACTH-secreting pituitary adenomas in humans. In this study, we aimed to verify whether USP8 mutations also play a role in the development of such tumours in dogs. Methods Presence of USP8 mutations was analysed by Sanger and PCR-cloning sequencing in 38 canine ACTH-secreting adenomas. Furthermore, the role of USP8 and EGFR protein expression was assessed by immunohistochemistry in a subset of 25 adenomas. Results None of the analysed canine ACTH-secreting adenomas presented mutations in the USP8 gene. In a subset of these adenomas, however, we observed an increased nuclear expression of USP8, a phenotype characteristic for the USP8 mutated human tumours, that correlated with smaller tumour size but elevated ACTH production in those tumours. Conclusions Canine ACTH-secreting pituitary adenomas lack mutations in the USP8 gene suggesting a different genetic background of pituitary tumourigenesis in dogs. However, elevated nuclear USP8 protein expression in a subset of tumours was associated with a similar phenotype as in their human counterparts, indicating a possible end-point convergence of the different genetic backgrounds in the two species. In order to establish the dog as a useful animal model for the study of CD, further comprehensive studies are

  14. WT1 expression in salivary gland pleomorphic adenomas: a reliable marker of the neoplastic myoepithelium.

    PubMed

    Langman, Gerald; Andrews, Claire L; Weissferdt, Annikka

    2011-02-01

    Pleomorphic adenoma is a benign salivary gland neoplasm with a diverse morphology. This is considered to be a function of the neoplastic myoepithelium, which shows histological and immunophenotypical variability. Wilms' tumor 1 gene (WT1) protein, involved in bidirectional mesenchymal-epithelial transition, has been detected by reverse transcription PCR in salivary gland tumors showing myoepithelial-epithelial differentiation. The aim of this study was to investigate the immunoreactivity of WT1 in pleomorphic adenomas and to compare the pattern of staining with p63 and calponin, two reliable markers of myoepithelial cells. A total of 31 cases of pleomorphic adenoma were selected. The myoepithelium was classified as myoepithelial-like (juxtatubular and spindled), modified myoepithelium (myxoid, chondroid and plasmacytoid) and transformed myoepithelium (solid epithelioid, squamous and basaloid cribriform). Immunohistochemistry for WT1, p63 and calponin was assessed in each myoepithelial component, as well as in nonneoplastic myoepithelial cells and inner tubular epithelial cells. There was no immunostaining of tubular epithelial cells by any of the markers. In contrast to p63 and calponin, WT1 did not react with normal myoepithelial cells. Cytoplasmic WT1 staining was present in all pleomorphic adenomas, and in 29 cases (94%), >50% of neoplastic myoepithelial cells were highlighted. p63 and calponin stained the myoepithelium in 30 tumors. In comparison, 50% of cells were positive in 21 (68%) and 9 (29%) cases of p63 and calponin, respectively. Staining with WT1 showed less variability across the spectrum of myoepithelial differentiation with the difference most marked in the transformed myoepithelium. WT1 is a sensitive marker of the neoplastic myoepithelial cell in pleomorphic adenomas. The role of this protein in influencing the mesenchymal-epithelial state of cells suggests that WT1 and the myoepithelial cell have an important role in the histogenesis of

  15. Dietary protein and fat intake in relation to risk of colorectal adenoma in Korean.

    PubMed

    Yang, Sun Young; Kim, Young Sun; Lee, Jung Eun; Seol, Jueun; Song, Ji Hyun; Chung, Goh Eun; Yim, Jeong Yoon; Lim, Sun Hee; Kim, Joo Sung

    2016-12-01

    Consumption of red meat and alcohol are known risk factors for colorectal cancer, but associations for dietary fat remain unclear. We investigated the associations of dietary fat, protein, and energy intake with prevalence of colorectal adenoma.We performed a prospective cross-sectional study on asymptomatic persons who underwent a screening colonoscopy at a single center during a routine health check-up from May to December 2011. Dietary data were obtained via a validated Food Frequency Questionnaire (FFQ), assisted by a registered dietician. We also obtained information on alcohol consumption and smoking status, and measured metabolic syndrome markers including abdominal circumference, blood pressure, fasting glucose, serum triglyceride and high-density lipoprotein cholesterol. We calculated odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations using the polytomous logistic regression models. As a secondary analysis, we also conducted a matched analysis, matched by age and sex (557 cases and 557 non-cases).The study sample included 557 cases (406 males and 151 females) with histopathologically confirmed colorectal adenoma, and 1157 controls (650 males and 507 females). The proportion of advanced adenoma was 28.1% of men and 18.5% of female, respectively. Although vegetable protein intake was inversely associated with the prevalence of colorectal adenoma, further adjustment for potential confounding factors attenuated the association, resulting in no significant associations. There were no significant associations between dietary fat intake and colorectal adenoma in energy-adjusted models. For vegetable protein in women, the OR for the comparison of those in the highest tertile with those in the lowest tertile was 0.47 (95% CI 0.25-0.91, P for trend = 0.07) after adjustment for total energy intake. However, after controlling for metabolic syndrome markers, body mass index, smoking status, alcohol consumption, and family history of

  16. [Multiple large hepatocellular adenomas in a patient with glycogen storage disease type Ia].

    PubMed

    Uemura, Shuichiro; Ariizumi, Shun-Ichi; Takahashi, Yutaka; Omori, Akiko; Kotera, Yoshihito; Katagiri, Satoshi; Hashimoto, Etsuko; Nakano, Masayuki; Yamamoto, Masakazu

    2014-04-01

    A man diagnosed at birth with glycogen storage disease type Ia was found to have multiple hepatocellular adenomas at 15 years of age. At 18 years of age, he underwent transarterial tumor embolization in segments 4 and 5. At 27 years of age, the tumor in segment 4 had increased in size on follow-up computed tomography, and he was referred to our hospital. Because the tumor was large, increasing in size, and we could not exclude malignancy, we performed resection of segments 4 and 8 of the liver and partial resection of segment 5 for excisional biopsy. The pathological diagnosis was multiple inflammatory hepatocellular adenomas.

  17. MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

    PubMed Central

    Wan, Heng; Chihiro, Ohye; Yuan, Shubin

    2009-01-01

    Background Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas. Methods Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated. Results MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level. Conclusion MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study

  18. Primary hyperparathyroidism due to an intrathyroidal parathyroid adenoma associated with chronic lymphocytic thyroiditis.

    PubMed

    Cating-Cabral, Monica Therese; Cabungcal, Arsenio Claro; Villafuerte, Cesar Vincent; Añel-Quimpo, Joselynna

    2012-06-08

    This is a case of a 44-year-old woman with an anterior neck mass and hypothyroidism who presented with an incidental finding of an elevated serum calcium level and was found to have primary hyperparathyroidism and osteoporosis. During surgical exploration no parathyroid adenoma was found, although a nodule was palpated within the right thyroid lobe. Examination of the excised right thyroid lobe revealed an intrathyroidal parathyroid adenoma and chronic lymphocytic thyroiditis. After surgery, she did not develop severe hypocalcaemia and this was attributed to preoperative treatment with pamidronate. In the months following surgery, parathyroid hormone remained undetectable.

  19. Optochiasmatic syndrome from adhesive arachnoiditis with coexisting hypophyseal adenoma: case report.

    PubMed

    Iraci, G; Carteri, A; Marin, G

    1977-03-01

    Adhesive arachnoiditis is an occasional finding during neurosurgical operations for pituitary adenoma, previously treated by radiation therapy. A case where an arachnoidal process was found in combination with an eosinophilic pituitary adenoma, which had never been treated by irradiation, is reported. A 44-year-old woman at the time of surgery with scarce endocrinologic symptoms had suffered visual loss from 2 episodes, 18 years apart. Analysis of her symptoms, neuro-ophthalmologic findings and neurodadiologic features suggest that her visual damage was due to an optochiasmatic arachnoiditis, rather than to the tumor itself.

  20. Dietary protein and fat intake in relation to risk of colorectal adenoma in Korean

    PubMed Central

    Yang, Sun Young; Kim, Young Sun; Lee, Jung Eun; Seol, Jueun; Song, Ji Hyun; Chung, Goh Eun; Yim, Jeong Yoon; Lim, Sun Hee; Kim, Joo Sung

    2016-01-01

    Abstract Consumption of red meat and alcohol are known risk factors for colorectal cancer, but associations for dietary fat remain unclear. We investigated the associations of dietary fat, protein, and energy intake with prevalence of colorectal adenoma. We performed a prospective cross-sectional study on asymptomatic persons who underwent a screening colonoscopy at a single center during a routine health check-up from May to December 2011. Dietary data were obtained via a validated Food Frequency Questionnaire (FFQ), assisted by a registered dietician. We also obtained information on alcohol consumption and smoking status, and measured metabolic syndrome markers including abdominal circumference, blood pressure, fasting glucose, serum triglyceride and high-density lipoprotein cholesterol. We calculated odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations using the polytomous logistic regression models. As a secondary analysis, we also conducted a matched analysis, matched by age and sex (557 cases and 557 non-cases). The study sample included 557 cases (406 males and 151 females) with histopathologically confirmed colorectal adenoma, and 1157 controls (650 males and 507 females). The proportion of advanced adenoma was 28.1% of men and 18.5% of female, respectively. Although vegetable protein intake was inversely associated with the prevalence of colorectal adenoma, further adjustment for potential confounding factors attenuated the association, resulting in no significant associations. There were no significant associations between dietary fat intake and colorectal adenoma in energy-adjusted models. For vegetable protein in women, the OR for the comparison of those in the highest tertile with those in the lowest tertile was 0.47 (95% CI 0.25–0.91, P for trend = 0.07) after adjustment for total energy intake. However, after controlling for metabolic syndrome markers, body mass index, smoking status, alcohol consumption, and family history

  1. [Prostagut forte treatment of patients with prostatic adenoma with comorbid chronic prostatitis].

    PubMed

    Avdoshin, V P; Pul'bere, S A

    2012-01-01

    The study consisting of four visits included 69 patients with prostatic adenoma and concomitant chronic prostatitis. The patients received either monotherapy with an alpha adrenoblocker or combined treatment including phytodrug prostagut forte. The results of the study showed that the above combined treatment produces more pronounced and persistent improvement of urodynamic indices, leads to reduction of leukocyte count in the urine and prostatic secretion, upgrades quality of life. The absence of side effects allows recommendation of prostagut forte for treatment of presenile and senile patients with prostatic adenoma and associated pathology.

  2. Colonic and duodenal flat adenomas in children with classical familial adenomatous polyposis.

    PubMed

    Cohen, Marta; Thomson, Mike; Taylor, Chris; Donatone, Jorge; Quijano, Graciela; Drut, Ricardo

    2006-04-01

    Flat adenomas of the colon and duodenum have been described as associating with familial adenomatous polyposis (FAP), its attenuated variant, and the so-called hereditary nonpolyposis colorectal cancer. There seem to be no report on the occurrence of flat adenomas in pediatric patients with family history of FAP. We are reporting 4 children from 2 cancer-prone families in whom colonic and duodenal moderately dysplastic flat adenomas were found. Gastrointestinal endoscopy and biopsies were performed in 3 female siblings (7, 9, and 11 years old) and 1 male (9 years old) when referred for screening owing to familial history of bowel cancer (family 1) or evidence of bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE), which is known to be associated with FAP (family 2). Endoscopic visualization of the mucosa was improved by use of 0.2% indigo carmine solution spray. Biopsies were routinely processed for H&E and immunohistochemistry staining. Present patients were asymptomatic, with the exception of 2 weeks rectal bleeding in 1 of them. The colonic videoendoscopy showed in 2/3 siblings hundreds of flat or slightly raised plaques less than 1 cm in diameter as well as some classic polyps throughout the colon. The other sibling showed 40 flat-topped lesions with minimal elevation and central umbilication in the cecum. Upper endoscopy demonstrated a few flat lesions in the nonperiampullary area of the duodenum in 2/4 patients. The colonic videoendoscopy performed on the 9-year-old boy revealed multiple small sessile polyps. Microscopic study demonstrated tubular adenomas with a few neoplastic crypts, slight disarray of the overall architecture, and moderate (low-grade) dysplasia of the epithelium. These features were more obvious at the center and superficial areas of the adenomas. The 4 children had multiple flat adenomas of the colon and duodenum (2/4) matching with those described in adult patients. Flat adenomas in the context of FAP probably

  3. Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies

    PubMed Central

    Kim, Nam Hee; Suh, Jung Yul; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Choi, Kyuyong

    2017-01-01

    Purpose Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy. Materials and Methods This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling. Results The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26–1.77; ptrend<0.001], 1.22 (95% CI, 1.04–1.43; ptrend=0.024), 1.22 (95% CI, 1.02–1.46; ptrend=0.046), 1.36 (95% CI, 1.14–1.63; ptrend=0.004), and 1.19 (95% CI, 0.99–1.42; ptrend=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas. Conclusion The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas. PMID:28120565

  4. A Rare Case of a Benign Primary Pleomorphic Adenoma of the Lung

    PubMed Central

    Saladi, Swetha; Patolia, Setu; Mahmoud Assaf, Sara; Stoeckel, David

    2017-01-01

    Salivary gland tumors (SGT) constitute a small proportion of primary respiratory system neoplasms. Benign SGT comprises pleomorphic adenoma and is exceedingly rare in the lungs. We hereby present a rare case of a benign primary pleomorphic adenoma of the lung. The histological pattern of the tumor was indistinguishable from the head and neck SGT counterparts and showed biphasic morphology. Malignant features were not observed and a metastatic SGT was ruled out. Although little is known about the clinical progression of these rare tumors, surgical resection and interval surveillance remains the treatment of choice.

  5. Expression of RUNX3 and β-catenin in the carcinogenesis of sporadic colorectal tubular adenoma.

    PubMed

    Wang, Linna; Li, Dan; Liu, Yang; Wang, Yuan; Cui, Jinfeng; Cui, Airong; Wu, Wenxin

    2014-06-01

    The aim of this study is to investigate the possible roles of runt-related transcription factor 3 (RUNX3) and β-catenin in the carcinogenesis of sporadic colorectal tubular adenomas. The expression of the RUNX3 and β-catenin proteins was evaluated by immunohistochemistry in 23 normal colorectal mucosa (NCM), 81 sporadic colorectal tubular adenomas with different dysplasias (SCTA-D) (mild n=33, moderate n=23, and severe n=25 dysplasia), and 48 sporadic colorectal tubular adenomas with cancerous changes (SCTA-Ca). RUNX3 methylation was assessed by methylation-specific polymerase chain reaction (MSP), combined with laser capture microdissection (LCM), in 17 NCM, 41 SCTA-D (mild n=15, moderate n=12, and severe n=14 dysplasia), and 17 SCTA-Ca tissues. Compared to NCM (82.6 %), RUNX3 in SCTA-D (54.3 %) and SCTA-Ca (27.1 %) was significantly downregulated (P<0.05). In NCM, SCTA-D, and SCTA-Ca, the incidence of positive expression for β-catenin was 13.0, 60.5, and 79.2 %, respectively. A statistically significant difference was observed (P<0.05). RUNX3 levels were markedly higher in adenoma with mild dysplasia (75.8 %) and moderate dysplasia (60.9 %) than in adenoma with severe dysplasia (20.0 %) (both with P<0.05). Likewise, the expression of β-catenin in severe dysplasia adenoma was 84.0 %, which was significantly higher than that in mild dysplasia adenoma (39.4 %). An inverse correlation was found between the protein expression of RUNX3 and β-catenin in SCTA-D and SCTA-Ca (P<0.05). MSP results showed that RUNX3 methylation in NCM, SCTA-D, and SCTA-Ca was 5.9, 17.1, and 41.2 %, respectively, with a statistically significant difference between NCM and SCTA-Ca (P<0.05). However, no significant difference of RUNX3 methylation was observed among different dysplasia groups. RUNX3 and β-catenin play important roles in the carcinogenesis of sporadic colorectal tubular adenomas. In addition, hypermethylation of RUNX3 can downregulate its expression.

  6. Pleomorphic adenoma--unusual presentation of a salivary gland tumor in the neck of a child.

    PubMed

    Arunkumar, K V; Kumar, Sanjeev; Bansal, Vishal; Saxena, Susmita; Elhence, Poonam

    2011-01-01

    Ectopic salivary gland tumors are rare in children. When salivary gland tumors do develop, they preferentially affect major salivary glands and then minor salivary glands. Pleomorphic adenoma, also referred to as a benign mixed tumor, is the most common tumor of the salivary glands. Approximately 90% of these tumors occur in the parotid gland, while the remaining 10% affect the minor salivary glands. However, it is uncommon to find them elsewhere in the head and neck region. We report a rare case of pleomorphic adenoma in the upper neck, an unusual site in an 8-year-old boy.

  7. Pleomorphic Adenoma With Prominent Clear Cell Myoepithelioma Component of the Lacrimal Gland.

    PubMed

    Adekunle, Adewumi N; Mendoza, Pia R; Wojno, Ted H; Grossniklaus, Hans E

    2016-01-01

    A case of a pleomorphic adenoma of the lacrimal gland with a prominent clear cell myoepitheliomatous component was reported. An 81-year-old Caucasian woman experienced a 2-month history of right supraorbital swelling and proptosis. Excisional biopsy revealed a multicomponent lesion including a stromal component featuring glandular structures made of small epithelioid and spindle cells and a trabecular component with small islands of vacuolated cells, displaced nuclei, and clear cytoplasm. Immunohistochemical analysis revealed strong cytokeratin AE1/3 reactivity and focal smooth muscle actin positivity. The pathologic findings including immunohistochemistry results were consistent with a pleomorphic adenoma with prominent clear cell myoepithelioma component.

  8. [Efficacy and safety of use of likoprofit in patients with chronic prostatitis and prostatic adenoma].

    PubMed

    Spivak, L G

    2013-01-01

    The article summarizes the results of the clinical trials on application of likoprofit in patients with a chronic prostatitis and prostate adenoma, which were conducted by the Russian urologists for the last 8 years. Application of likoprofit in patients after TURP contributes to significantly earlier and effective restoration of microcirculation, which decreases the risk of development of postoperative complications and accelerates rehabilitation of patients. Studies in which likoprofit was applied in patients with a chronic prostatitis and prostate adenoma, proved that likoprofit also has antiedematous effect, improves the urination act, improves ejaculate parameters, positively impacts on sexual function, and has a high safety profile.

  9. Villous Adenoma in Renal Pelvis With Manifestation of Percutaneous Fistula and Mucus Secretion.

    PubMed

    Liu, Danqi; Tan, Jing; Huang, Kai; Jiang, Zhiqiang; He, Leye; Yin, Guangming

    2017-01-06

    A 70-year-old man, complaining of percutaneous fistula with jelly-like yellow mucus in the right kidney for a month, was admitted to our department. From computed tomography, stones and severe hydronephrosis but no suspicious mass was found in right kidney. Nephrectomy of right kidney was performed and pathological examination revealed a villous adenoma in the renal pelvis with moderate to severe atypical hyperplasia of glandular epithelium. Primary villous adenoma in renal pelvis is rare and believed to be related to chronic irritation of stone and inflammation. Mostly nephrectomy was performed before diagnosis was made.

  10. Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus.

    PubMed

    Los, E L; Deen, P M T; Robben, J H

    2010-05-01

    According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.

  11. Novel treatment for lithium-induced nephrogenic diabetes insipidus rat model using the Sendai-virus vector carrying aquaporin 2 gene.

    PubMed

    Suga, Hidetaka; Nagasaki, Hiroshi; Kondo, Taka-Aki; Okajima, Yoshiki; Suzuki, Chizuko; Ozaki, Nobuaki; Arima, Hiroshi; Yamamoto, Tokunori; Ozaki, Noriyuki; Akai, Masaro; Sato, Aiko; Uozumi, Nobuyuki; Inoue, Makoto; Hasegawa, Mamoru; Oiso, Yutaka

    2008-11-01

    Congenital nephrogenic diabetes insipidus (NDI) is a chronic disorder involving polyuria and polydipsia that results from unresponsiveness of the renal collecting ducts to the antidiuretic hormone vasopressin. Either of the genetic defects in vasopressin V2 receptor or the water channel aquaporin 2 (AQP2) cause the disease, which interfere the water reabsorption at the epithelium of the collecting duct. An unconscious state including a perioperative situation can be life threatening because of the difficulty to regulate their water balance. The Sendai virus (SeV) vector system deleting fusion protein (F) gene (SeV/DeltaF) is considered most suitable because of the short replication cycle and nontransmissible character. An animal model for NDI with reduced AQP2 by lithium chloride was used to develop the therapy. When the SeV/DeltaF vector carrying a human AQP2 gene (AQP2-SeV/DeltaF) was administered retrogradely via ureter to renal pelvis, AQP2 was expressed in the renal collecting duct to reduce urine output and water intake by up to 40%. In combination with the retorograde administration to pelvis, this system could be the cornerstone for the applicable therapies on not only NDI patients but also other diseases associate with the medullary collecting duct.

  12. SIMS imaging of gadolinium isotopes in tissue from Nephrogenic Systemic Fibrosis patients: Release of free Gd from magnetic resonance imaging (MRI) contrast agents

    NASA Astrophysics Data System (ADS)

    Abraham, Jerrold L.; Chandra, Subhash; Thakral, Charu; Abraham, Joshua M.

    2008-12-01

    Recently, Gd-based magnetic resonance imaging (MRI) contrast agents (GBMCA) have been linked to a new disease, Nephrogenic Systemic Fibrosis (NSF), with skin and systemic toxicity and death in certain patients with renal failure. Due to widespread use of GBMCA in diagnostic MRI, it is essential to study their excretion, metabolism, and target sites in cells and tissues. A CAMECA IMS-3f SIMS ion microscope and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) were used for imaging Gd isotopes in relation to calcium distributions in histologic sections of human tissues. SIMS imaging revealed two types of Gd localization in skin biopsies of patients who received GBMCA. The Gd was present in micrometer size deposits in association with calcium, and in detectable amounts in a more diffuse cellular distribution. Only the Gd-containing deposits associated with Ca and P were detectable using SEM/EDS. As only insoluble deposits remain in the biopsy tissues after aqueous and organic solvent processing of the tissue, our observations support release of free Gd from the GBMCA and selective localization of insoluble Gd in the target tissue from patients with NSF. This study opens new novel applications of SIMS for characterization of the safety of GBMCA.

  13. V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists.

    PubMed

    Takahashi, Kazuhiro; Makita, Noriko; Manaka, Katsunori; Hisano, Masataka; Akioka, Yuko; Miura, Kenichiro; Takubo, Noriyuki; Iida, Atsuko; Ueda, Norishi; Hashimoto, Makiko; Fujita, Toshiro; Igarashi, Takashi; Sekine, Takashi; Iiri, Taroh

    2012-01-13

    Inactivating mutations of the V2 vasopressin receptor (V2R) cause cross-linked congenital nephrogenic diabetes insipidus (NDI), resulting in renal resistance to the antidiuretic hormone AVP. In two families showing partial NDI, characterized by an apparently normal response to diagnostic tests and an increase in the basal ADH levels suggesting AVP resistance, we have identified two V2R mutations, Ser-333del and Y128S. Both mutant V2Rs, when expressed in COS-7 cells, show partial defects in vasopressin-stimulated cAMP accumulation and intracellular localization. The inhibition of internalization does not rescue their localization. In contrast, the non-peptide V2R antagonists OPC41061 and OPC31260 partially rescue the membrane localization and basal function of these V2R mutants, whereas they inhibit the basal activity of the wild-type V2R. These results indicate that a partial loss of function of Ser-333del and Y128S mutant V2Rs results from defective membrane trafficking. These findings further indicate that V2R antagonists can act as protean agonists, serving as pharmacological chaperones for inactivating V2R mutants and also as inverse agonists of wild-type receptors. We speculate that this protean agonism could underlie the possible dual beneficial effects of the V2R antagonist: improvement of hyponatremia with heart failure or polycystic kidney disease and potential rescue of NDI.

  14. A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus.

    PubMed

    Li, Jian Hua; Chou, Chung-Lin; Li, Bo; Gavrilova, Oksana; Eisner, Christoph; Schnermann, Jürgen; Anderson, Stasia A; Deng, Chu-Xia; Knepper, Mark A; Wess, Jürgen

    2009-10-01

    X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present,no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. To develop what we believe to be the first viable animal model of XNDI, we generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen.Radioligand-binding studies confirmed the lack of V2R-binding sites in kidneys following 4-OH-tamoxifen treatment, and further analysis indicated that upon V2R deletion, adult mice displayed all characteristic symptoms of XNDI, including polyuria, polydipsia, and resistance to the antidiuretic actions of vasopressin. Gene expression analysis suggested that activation of renal EP4 PGE2 receptors might compensate for the lack of renal V2R activity in XNDI mice. Strikingly, both acute and chronic treatment of the mutant mice with a selective EP4 receptor agonist greatly reduced all major manifestations of XNDI, including changes in renal morphology.These physiological improvements were most likely due to a direct action on EP4 receptors expressed on collecting duct cells. These findings illustrate the usefulness of the newly generated V2R mutant mice for elucidating and testing new strategies for the potential treatment of humans with XNDI.

  15. Iodomethylnorcholesterol uptake in an aldosteronoma shown by dexamethasone-suppression scintigraphy: Relationship to adenoma size and functional activity

    SciTech Connect

    Nomura, K.; Kusakabe, K.; Maki, M.; Ito, Y.; Aiba, M.; Demura, H. )

    1990-10-01

    Dexamethasone-suppression (DS) adrenal scintigraphy localizes an aldosteronoma, but with false-negative results, i.e. 2 of 19 cases in our study. Our aim was to clarify the clinical meaningfulness of this test. Adrenal iodomethyl-norcholesterol (NP-59) uptake on the adenoma side correlated with the estimated adenoma volume (n = 15, r = 0.843, P less than 0.001). Accordingly, the uptake ratio on the adenoma side to that on the opposite side depended on the adenoma volume (r = 0.683, P less than 0.01). This explains the false-negative results (uptake ratio less than 2) in two cases with small adenomas. The NP-59 uptake correlated weakly with the plasma aldosterone level (r = 0.516, P less than 0.05). This result indicates the low correlation between NP-59 uptake and the ability to secrete aldosterone. NP-59 accumulation in the surgically removed gland was analyzed by autoradiography in six cases where DS scintigraphy was done just before surgery. The density was higher in the adenoma cells than in the adjacent cortical cells in five cases, but the difference was rather small, i.e., within a 2-fold difference in four cases. In one case, almost the same density was observed in both types of cells. Thus, the laterality of NP-59 uptake primarily depends on the adenoma volume although NP-59 uptake somewhat reflects the adenoma's ability to secrete aldosterone or the adenoma cell's activity in accumulating NP-59. Care must be taken in interpreting the findings from DS scintigraphy where the adenoma is small or adrenal uptake is low.

  16. Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

    PubMed Central

    Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

    2015-01-01

    Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

  17. Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa

    PubMed Central

    Nogueira, Renan Brito; Pires, Andréa Rodrigues Cordovil; Soares, Thélia Maria Santos; Rodrigues, Simone Rabello de Souza; Campos, Mariane Antonieta Menino; Toloi, Giovanna Canato; Waisberg, Jaques

    2013-01-01

    ABSTRACT Objective: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. Methods: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. Results: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. Conclusion: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa. PMID:24488384

  18. Somatostatin receptor subtypes mRNA in TSH-secreting pituitary adenomas: a case showing a dramatic reduction in tumor size during short octreotide treatment.

    PubMed

    Horiguchi, Kazuhiko; Yamada, Masanobu; Umezawa, Ryohei; Satoh, Teturo; Hashimoto, Koshi; Tosaka, Masahiko; Yamada, Shozo; Mori, Masatomo

    2007-06-01

    TSH-secreting adenoma is a rare pituitary adenoma, and the expression levels of the specific subtypes of somatostatin receptors (sstr) mRNAs have remained obscure. To determine the quantitative expression of the sstr1-5 mRNAs in TSH-secreting adenomas that may be related to the efficacy of treatment with a somatostatin analogue, expression of the sstr1-5 mRNAs was examined and compared in TSH-secreting adenomas and other pituitary adenomas. The pituitary adenomas were obtained at transsphenoidal surgery from 4 cases of TSH-secreting adenoma, including 1 patient showing a significant shrinkage of the tumor size after only 10 days of octreotide treatment, 2 patients without tumor size reduction and 1 patient without treatment, and 5 GH-secreting adenomas, 6 prolactinomas, 5 nonfunctioning adenomas, 4 ACTH-secreting adenomas and normal pituitaries at autopsy from 4 normal subjects. In comparison to the normal pituitary, sstr2A>sstr1>sstr5>sstr3 mRNAs were expressed in the TSH-secreting adenomas examined. No expression of sstr2B or sstr4 mRNA was observed. The expression level of sstr2 mRNA was significantly higher than those in normal pituitary, prolactinomas, ACTH-secreting and nonfunctioning pituitary adenomas. The patient with marked shrinkage of the tumor showed the highest expression of both sstr2 and sstr5 mRNAs among all the cases of pituitary adenoma. A TSH-secreting tumor without shrinkage showed a similar expression level of sstr2 mRNA. These findings demonstrated that TSH-secreting adenomas express sstr1, 2A, 3 and 5 mRNAs, predominantly sstr2A, and in addition to the expression of sstr2 mRNA, the expression level of sstr5 mRNA may be a factor affecting the tumor shrinkage by somatostatin analogues against TSH-secreting adenomas.

  19. Gastrointestinal Stromal Tumor Arising From a Gastric Duplication Cyst

    PubMed Central

    Machicado, Jorge; Davogustto, Giovanni

    2016-01-01

    Gastric duplication cysts (GDC) are rarely diagnosed in adults, but previous cases have been associated with malignancy. We present a case of gastrointestinal stromal tumor (GIST) arising from a GDC in a 71-year-old woman who presented with 3 years of early satiety, anorexia, abdominal distention, and weight loss. Abdominal CT showed a 9.3 x 5.2 x 9.5-cm well-circumscribed cystic mass arising 3 cm above the gastroduodenal junction. The cyst was resected, and histopathology was consistent with GDC. Future studies are needed to clarify the malignant potential of GDC and the molecular pathways for its development. PMID:27144196

  20. Papillary serous carcinoma arising from adenomyosis presenting as intramural leiomyoma.

    PubMed

    Izadi-Mood, Narges; Samadi, Nasrin; Sarmadi, Soheila; Eftekhar, Zahra

    2007-04-01

    Adenocarcinoma arising from adenomyosis uteri is rare. Herein, we reported a patient with papillary serous carcinoma arising from adenomyosis. The patient was a 61-year-old woman who received tamoxifen for treatment of her breast cancer over the past five years. In hysterectomy specimen taken for investigating her uncontrolled bleeding with suspicion of uterine myoma, multiple adenomyotic foci were found in the uterine wall. In one of these foci, papillary serous carcinoma was found. No evidence of tumor was seen in endometrial surface, peritoneum, and both adnexa.

  1. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

    PubMed

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

    2017-02-09

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca(2+) signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca(2+) concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca(2+) concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca(2+) signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

  2. BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

    PubMed Central

    Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

    2017-01-01

    Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

  3. A case of metastasizing pleomorphic adenoma in the maxillary bone appearing twenty years after initial resection of pleomorphic adenoma of the hard palate.

    PubMed

    Akiba, Jun; Harada, Hiroshi; Kawahara, Akihiko; Todoroki, Keita; Nagata, Shuji; Yano, Hirohisa

    2013-09-01

    Metastasizing pleomorphic adenoma (MPA) is the inexplicable metastasis of a histologically benign pleomorphic adenoma (PA). Approximately 50 cases have been reported. A 62-year-old woman noticed pain in the upper molar area. Her medical history included an operation for PA in the hard palate that was performed 20 years previously. On imaging, four relatively well-defined lesions were demonstrated in the maxillary bone. She underwent an operation for these lesions. Each lesion revealed the same histological features. Morphological findings displayed typical features of PA. Immunohistochemical staining showed that tumor cells of both primary and metastasizing lesions were positive for pleomorphic adenoma gene (PLAG) 1, which is a sensitive marker for PA. Gene fusions involving PLAG1 were examined by reverse transcription-polymerase chain reaction. However, no gene rearrangements of PLAG1 were found. We report here on a case of MPA in the maxillary bone, which appeared 20 years after resection of the primary tumor and review the relevant literature.

  4. Outcomes of Proton Therapy for Patients With Functional Pituitary Adenomas

    SciTech Connect

    Wattson, Daniel A.; Tanguturi, Shyam K.; Spiegel, Daphna Y.; Niemierko, Andrzej; Biller, Beverly M.K.; Nachtigall, Lisa B.; Bussière, Marc R.; Swearingen, Brooke; Chapman, Paul H.; Loeffler, Jay S.; Shih, Helen A.

    2014-11-01

    Purpose/Objective(s): This study evaluated the efficacy and toxicity of proton therapy for functional pituitary adenomas (FPAs). Methods and Materials: We analyzed 165 patients with FPAs who were treated at a single institution with proton therapy between 1992 and 2012 and had at least 6 months of follow-up. All but 3 patients underwent prior resection, and 14 received prior photon irradiation. Proton stereotactic radiosurgery was used for 92% of patients, with a median dose of 20 Gy(RBE). The remainder received fractionated stereotactic proton therapy. Time to biochemical complete response (CR, defined as ≥3 months of normal laboratory values with no medical treatment), local control, and adverse effects are reported. Results: With a median follow-up time of 4.3 years (range, 0.5-20.6 years) for 144 evaluable patients, the actuarial 3-year CR rate and the median time to CR were 54% and 32 months among 74 patients with Cushing disease (CD), 63% and 27 months among 8 patients with Nelson syndrome (NS), 26% and 62 months among 50 patients with acromegaly, and 22% and 60 months among 9 patients with prolactinomas, respectively. One of 3 patients with thyroid stimulating hormone—secreting tumors achieved CR. Actuarial time to CR was significantly shorter for corticotroph FPAs (CD/NS) compared with other subtypes (P=.001). At a median imaging follow-up time of 43 months, tumor control was 98% among 140 patients. The actuarial 3-year and 5-year rates of development of new hypopituitarism were 45% and 62%, and the median time to deficiency was 40 months. Larger radiosurgery target volume as a continuous variable was a significant predictor of hypopituitarism (adjusted hazard ratio 1.3, P=.004). Four patients had new-onset postradiosurgery seizures suspected to be related to generously defined target volumes. There were no radiation-induced tumors. Conclusions: Proton irradiation is an effective treatment for FPAs, and hypopituitarism remains the primary

  5. Transcultural Knowledge and Skills Transfer: Issues Arising from Evaluation Processes

    ERIC Educational Resources Information Center

    Green, Anita J.; Holloway, David G.

    2007-01-01

    The transfer of knowledge, policy and practice between nations increasingly involves knowledge of the theory and practice of evaluation. This article examines issues arising from the transcultural evaluation of a drug and alcohol misuse knowledge and skills transfer programme for nurses, nurse teachers and medical staff in the narcology service in…

  6. 5 CFR 359.404 - Removal: Conditions arising before appointment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of Career Appointees During Probation § 359.404 Removal: Conditions arising before appointment. (a) Coverage. (1) This section covers the removal of a career appointee from the SES during the probationary...) This section does not apply, however, when the career appointee was covered under 5 U.S.C....

  7. 5 CFR 359.404 - Removal: Conditions arising before appointment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... of Career Appointees During Probation § 359.404 Removal: Conditions arising before appointment. (a) Coverage. (1) This section covers the removal of a career appointee from the SES during the probationary...) This section does not apply, however, when the career appointee was covered under 5 U.S.C....

  8. 5 CFR 359.404 - Removal: Conditions arising before appointment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... of Career Appointees During Probation § 359.404 Removal: Conditions arising before appointment. (a) Coverage. (1) This section covers the removal of a career appointee from the SES during the probationary...) This section does not apply, however, when the career appointee was covered under 5 U.S.C....

  9. 5 CFR 359.404 - Removal: Conditions arising before appointment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... of Career Appointees During Probation § 359.404 Removal: Conditions arising before appointment. (a) Coverage. (1) This section covers the removal of a career appointee from the SES during the probationary...) This section does not apply, however, when the career appointee was covered under 5 U.S.C....

  10. 5 CFR 359.404 - Removal: Conditions arising before appointment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... of Career Appointees During Probation § 359.404 Removal: Conditions arising before appointment. (a) Coverage. (1) This section covers the removal of a career appointee from the SES during the probationary...) This section does not apply, however, when the career appointee was covered under 5 U.S.C....

  11. Associations of Calcium and Milk Product Intakes with Incident, Sporadic Colorectal Adenomas.

    PubMed

    Um, Caroline Y; Fedirko, Veronika; Flanders, W Dana; Judd, Suzanne E; Bostick, Roberd M

    2017-04-01

    Calcium intake has been consistently, modestly inversely associated with colorectal neoplasms, and supplemental calcium reduced adenoma recurrence in clinical trials. Milk products are the major source of dietary calcium in the United States, but their associations with colorectal neoplasms are unclear. Data pooled from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n = 807 cases, 2,185 controls) were analyzed using multivariable unconditional logistic regression. Residuals from linear regression models of milk with dietary calcium were estimated as the noncalcium, insulin-like growth factor 1-containing component of milk. For total, dietary, and supplemental calcium intakes, the adjusted odds ratios (ORs) comparing the highest to the lowest intake quintiles were 0.94 (95% confidence interval [CI] 0.69-1.30), 0.86 (CI 0.62-1.20), and 0.99 (CI 0.77-1.27), respectively. The corresponding ORs for consumption of total milk products, total milk, nonfat milk, total milk product residuals, and nonfat milk residuals were, respectively, 0.99, 0.90, 0.92, 0.94, and 0.95; all CIs included 1.0. For those who consumed any whole milk relative to those who consumed none, the OR was 1.15 (CI 0.89-1.49). These results are consistent with previous findings of modest inverse associations of calcium intakes with colorectal adenoma, but suggest that milk products may not be associated with adenoma.

  12. [Trabecular hyalinizing adenoma of the thyroid (HAT): A report of two cases].

    PubMed

    Román-González, Alejandro; Simón-Duque, Carlos; Camilo-Pérez, Juan; Vélez-Hoyo, Alejandro

    2016-01-01

    The hyalinizing trabecular adenoma is a rare lesion of the thyroid. There is controversy in the literature about the correct name for this disease. Dr. Carney defended the benign nature of this condition and therefore continues calling it adenoma, the World Health Organization calls for the potential of tumor malignancy, and others qualify it as a variant of papillary carcinoma based on the presence of rearranged in transformation/papillary thyroid carcinoma (RET/PTC) rearrangements. In Latin America there are few reported cases. Two cases of hyalinizing trabecular adenoma are reported. The first is a 40-year-old woman with a thyroid nodule of 3x3 cm. The immunohistochemistry was positive for thyroglobulin and calcitonin and negative for cytokeratin 19 and chromogranin. The second case is a 36-year-old patient with a thyroid nodule of 4x4 cm with an immunohistochemical pattern identical to the first case. Trabecular hyalinizing adenoma is a benign disease, easily confused with papillary or medullary thyroid carcinoma. Awareness of this entity will allow a better classification and management of thyroid conditions.

  13. Lectin histochemistry as a predictor of dysplasia grade in colorectal adenomas.

    PubMed

    Lazaris, A C; Chatzigianni, E B; Paraskevakou, H; Tseleni-Balafouta, S; Davaris, P S

    2000-01-01

    Lectins are sugar-binding proteins that bind to specific cellular carbohydrates, commonly affecting cellular physiology. Phaseolus vulgaris leucoagglutinin (PHA), ulex europaeus isoagglutinin-I (UEA-I), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) are among the most well studied lectins in various tissues. The purpose of this study was to detect the above lectins binding sites and so examine alterations in glycoconjugate expression in neoplastic cells of 52 colorectal adenomas with various clinicopathologic characteristics and proliferation rates. Lectin histochemistry was performed in paraffin sections with and without neuraminidase treatment. Proliferative fraction was determined by immunolabelling for Proliferating Cell Nuclear Antigen. PHA was the more frequently positive lectin in the examined specimens; however, it was simultaneously detected in normal colonic mucosa and so was WGA. The frequency of high grade dysplasia was significantly greater in older patients and in samples with UEA-I positivity without neuraminidase pretreatment. UEA-I-reactive adenomas were generally characterized by high cell proliferation rates. A statistical model based on patients age and UEA-I binding without neuraminidase treatment can generally predict grade of dysplasia in 83% of adenomas and particularly high grade dysplasia in up to 93% of adenomas; so, such a model may be potentially useful for the early detection of neoplasia, for instance in exfoliative cells from the large intestine.

  14. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation

    PubMed Central

    Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N.; Machaidze, Revaz; Vestal, Matthew L.; Laws, Edward R.; Dunn, Ian F.; Santagata, Sandro; Agar, Nathalie Y. R.

    2015-01-01

    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  15. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.

    PubMed

    Ibáñez-Costa, Alejandro; Gahete, Manuel D; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D; Dieguez, Carlos; Castaño, Justo P; Luque, Raúl M

    2015-03-04

    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.

  16. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features

    PubMed Central

    Ibáñez-Costa, Alejandro; Gahete, Manuel D.; Rivero-Cortés, Esther; Rincón-Fernández, David; Nelson, Richard; Beltrán, Manuel; de la Riva, Andrés; Japón, Miguel A.; Venegas-Moreno, Eva; Gálvez, Ma Ángeles; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Morgan, Jennifer; Tsomaia, Natia; Culler, Michael D.; Dieguez, Carlos; Castaño, Justo P.; Luque, Raúl M.

    2015-01-01

    Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increased GH and ACTH secretion, Ca2+ and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors. PMID:25737012

  17. Adrenal Cortical Adenoma: The Fourth Component Of Carney Triad and an Association With Subclinical Cushing Syndrome

    PubMed Central

    Carney, J. Aidan; Stratakis, Constantine A.; Young, William F.

    2013-01-01

    Carney triad is the combination of gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma. Herein, we describe the clinical, imaging, pathologic, and follow-up findings from 14 patients for a fourth component of the syndrome, adrenal adenoma, and clinical and imaging findings consistent with the tumor from 14 others. The adrenal neoplasm was asymptomatic and usually a late finding. Results of adrenocortical function tests were normal. Computed tomography revealed low-density adrenal masses that were consistent with adenomas. Bilateral lesions were present in 4 patients. In 13 of the 14 patients who underwent surgery, resected adrenal glands and biopsy specimens featured 1 or more circumscribed, yellow tumors, up to 3.5 cm in diameter, composed of well-differentiated polygonal cells with clear vacuolated cytoplasm and a smaller component of eosinophilic cells. The extratumoral cortex had combinations normal histologic features, discrete clear cell micronodules, zonal clear cell hypertrophy, or marked atrophy. The lesion in the 14th patient was different, grossly and microscopically resembling the usual sporadic cortisol-secreting adenoma. After the tumor was excised, the patient required glucocorticoid support. None of the tumors recurred or metastasized. Fourteen additional patients had unilateral or bilateral adrenal tumors consistent with adenomas detected by imaging studies. PMID:23681078

  18. Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas.

    PubMed

    Chauvet, N; Romanò, N; Meunier, A-C; Galibert, E; Fontanaud, P; Mathieu, M-N; Osterstock, G; Osterstock, P; Baccino, E; Rigau, V; Loiseau, H; Bouillot-Eimer, S; Barlier, A; Mollard, P; Coutry, N

    2016-02-01

    Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, β-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.

  19. Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

  20. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    SciTech Connect

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-07-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor.