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NCBI: db=pubmed; Term=adrenal tumor
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Adrenal Oncocytoma - A Rare Functional Tumor Presenting as Cushing Syndrome.

Sat, 01/13/2018 - 21:28
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Adrenal Oncocytoma - A Rare Functional Tumor Presenting as Cushing Syndrome.

J Assoc Physicians India. 2017 Dec;65(12):100-101

Authors: Runderawala H, Shah S, Manked A

Abstract
Adrenal oncocytoma is very rare pathological variant of adrenal neoplasm. These are usually large and non-functional; however, rarely functional adrenal oncocytomas are also presented as Cushing's syndrome and pheochromocytoma. We report a case of adrenal oncocytoma in 38 year old female presented with symptoms of Cushing Syndrome.

PMID: 29327532 [PubMed - in process]

Single center experience with laparoscopic adrenalectomy on a large clinical series.

Sat, 01/13/2018 - 21:28
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Single center experience with laparoscopic adrenalectomy on a large clinical series.

BMC Surg. 2018 Jan 11;18(1):2

Authors: Conzo G, Gambardella C, Candela G, Sanguinetti A, Polistena A, Clarizia G, Patrone R, Di Capua F, Offi C, Musella M, Iorio S, Bellastella G, Pasquali D, De Bellis A, Sinisi A, Avenia N

Abstract
BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies.
METHODS: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies.
RESULTS: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile.
CONCLUSIONS: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes.

PMID: 29325527 [PubMed - in process]

Laparoscopic Versus Open Adrenalectomy for Localized/Locally Advanced Primary Adrenocortical Carcinoma (ENSAT I-III) in Adults: Is Margin-Free (R0) Resection the Key Surgical Factor that Dictates Outcome?-A Review of the Literature.

Sat, 01/13/2018 - 21:28
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Laparoscopic Versus Open Adrenalectomy for Localized/Locally Advanced Primary Adrenocortical Carcinoma (ENSAT I-III) in Adults: Is Margin-Free (R0) Resection the Key Surgical Factor that Dictates Outcome?-A Review of the Literature.

J Laparoendosc Adv Surg Tech A. 2018 Jan 10;:

Authors: Mpaili E, Moris D, Tsilimigras DI, Oikonomou D, Pawlik TM, Schizas D, Papalampros A, Felekouras E, Dimitroulis D

Abstract
BACKGROUND: The aim of this study was to review the current literature on the role of laparoscopic adrenalectomy (LA) in the treatment of primary adrenocortical carcinoma (ACC; European Network for the Study of Adrenal Tumors [ENSAT] I-III) in adults.
MATERIALS AND METHODS: Nonrandomized controlled trials published between January 1999 and February 2017 were identified by searching the Pubmed, EMBASE, Cochrane Library, and Google Scholar databases. Primary and secondary endpoints included surgical and pathological parameters (patients age, tumor size, ENSAT stage, type of surgical approach, and period of follow-up), surgical outcomes (operative time, estimated blood loss, length of hospital stay, conversion rate to laparotomy, R0 resection, and surgical margin's status), and oncological outcomes (rate of recurrence, disease-free survival [DFS], and overall survival [OS] rates).
RESULTS: A total of 13 studies encompassing data on 1171 patients were included in the review. Compared with open approach, LA demonstrated lower tumor size, shorter operative time, lower intraoperative blood loss, shorter postoperative hospital stay, and equivalent local recurrence rates. No significant differences were observed between groups treated with an open or laparoscopic approach for the following criteria: R0 surgical resection status, tumor overall recurrence, and postoperative DFS and OS rates.
CONCLUSIONS: LA appears to be equivalent to open method for localized/locally advanced primary ACC (ENSAT I-III) in terms of R0 resection rate, overall recurrence, DFS, and OS, therefore suggesting that the extent of surgery with adequate tumor resection is the predominant endpoint, rather than the surgical approach itself. Multicenter randomized controlled trials with long follow-up time periods exploring the long-term oncological outcomes are required to determine the benefits of the laparoscopic over the open approach in adrenocortical carcinoma.

PMID: 29319399 [PubMed - as supplied by publisher]

Adrenal Oncocytic Neoplasm with Paradoxical Loss of Important Mitochondrial Steroidogenic Protein: The 18 kDA Translocator Protein.

Sat, 01/13/2018 - 21:28
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Adrenal Oncocytic Neoplasm with Paradoxical Loss of Important Mitochondrial Steroidogenic Protein: The 18 kDA Translocator Protein.

Case Rep Endocrinol. 2017;2017:6734695

Authors: Ruiz-Cordero R, Gupta A, Jayakumar AR, Ciancio G, Nielsen GP, Jorda M

Abstract
The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body's physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm.

PMID: 29318061 [PubMed]

Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management.

Sat, 01/13/2018 - 21:28
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Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management.

Cancer. 2018 Jan 03;:

Authors: Barroso-Sousa R, Ott PA, Hodi FS, Kaiser UB, Tolaney SM, Min L

Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, because ICIs block coinhibitory molecules on T cells and other immune cells, unleashing them to mediate tumor cell killing, they also can disrupt the maintenance of immunological tolerance to self-antigens. Compared with chemotherapy, ICIs have a different toxicity profile, especially the occurrence of autoimmune-like manifestations against multiple organ systems, including endocrine glands, commonly referred to as immune-related adverse events. The aim of this review was to provide practical recommendations regarding the proper assessment and clinical management related to the new onset of endocrinopathies after the use of ICIs in patients with cancer. Cancer 2018. © 2018 American Cancer Society.

PMID: 29313945 [PubMed - as supplied by publisher]

[Surgical strategies for non-metastatic adrenocortical carcinoma].

Sat, 01/13/2018 - 21:28
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[Surgical strategies for non-metastatic adrenocortical carcinoma].

Chirurg. 2018 Jan 08;:

Authors: Rayes N, Quinkler M, Denecke T

Abstract
Adrenocortical carcinomas (ACC) are rare but highly aggressive tumors. It is very difficult to differentiate small locally limited ACCs from benign adenomas. A spontaneous density >10 Hounsfield units in non-enhanced CT scan and a slow washout after contrast injection are suspicious of malignancy but with a low specificity. Preoperatively, a hormonal work-up is mandatory for all adrenal tumors. Each patient should be discussed in an interdisciplinary board. For non-metastatic ACCs (ENSAT stages I-III) radical resection is the treatment of choice. R0-resection and avoiding violation of the tumor capsule are the most important prognostic factors for long-term survival. Although discrepant reports regarding the benefits of lymphadenectomy have been published, lymph node dissection at least in the periadrenal area and in the renal hilum (optional extension to paraaortal and paracaval nodes) should be performed in the case of lymph node involvement. The role of prophylactic lymphadenectomy needs to be analyzed in further studies. The gold standard remains the open approach but minimally invasive procedures are also an option, especially in stage I-II tumors, if the principles of oncological surgery are respected. In this case, long-term survival rates are comparable. As local recurrence rates are lower and time to local recurrence is longer in patients who are operated on at a dedicated center (>10 adrenalectomies/year), adrenalectomy for ACC should be performed by an experienced surgeon.

PMID: 29313128 [PubMed - as supplied by publisher]

Adrenocortical oncocytoma: 11 Case reports and review of the literature.

Sat, 01/13/2018 - 21:28
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Adrenocortical oncocytoma: 11 Case reports and review of the literature.

Medicine (Baltimore). 2017 Dec;96(48):e8750

Authors: Hong Y, Hao Y, Hu J, Xu B, Shan H, Wang X

Abstract
RATIONALE: Adrenocortical oncocytoma is an extremely rare tumor of the adrenal gland. Its diagnostic criteria and biological behavior has not yet reached a consensus. The purpose of this study is to investigate the clinical characteristics of adrenocortical oncocytoma.
PATIENT CONCERNS: The clinical data from 11 cases of adrenocortical oncocytoma were retrospectively analyzed. Five patients found the tumor incidentally during the healthy examination, and 3 cases found the tumor during the diagnostic work-up for the evaluation of flank pain or hypertension. A female patient manifested virilization, and Cushing's syndrome showed in two patients. The tumor diameter was ranging from 2.0-13.0 cm.
DIAGNOSES: The serum cortisol, plasma aldosterone and catecholamine metabolites were used to evaluate the function of the tumors, and enhanced CT scan was used to confirm the tumor boundary, enhancement, and lymph nodes condition.
INTERVENTIONS: Seven cases underwent laparoscopic adrenal tumor resection, 4 patients underwent open surgery. Pathological report indicated adrenocortical oncocytoma in all cases, three of which were potentially malignant.
OUTCOMES: The patients were followed up for 19-72 months, no local recurrence and distant metastases were detected in 3 cases of malignant potential cases.
LESSONS: The majority of adrenocortical oncocytoma with or without function are benign, and close follow-up observation is essential.

PMID: 29310349 [PubMed - in process]

ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas.

Sat, 01/13/2018 - 21:28
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ERCC1 as predictive biomarker to platinum-based chemotherapy in adrenocortical carcinomas.

Eur J Endocrinol. 2018 Feb;178(2):183-190

Authors: Laufs V, Altieri B, Sbiera S, Kircher S, Steinhauer S, Beuschlein F, Quinkler M, Willenberg HS, Rosenwald A, Fassnacht M, Ronchi CL

Abstract
OBJECTIVE: Platinum-based chemotherapy (PBC) is the most effective cytotoxic treatment for advanced adrenocortical carcinoma (ACC). Excision repair cross complementing group 1 (ERCC1) plays a critical role in the repair of platinum-induced DNA damage. Two studies investigating the role of ERCC1 immunostaining as a predictive marker for the response to PBC in ACC had reported conflicting results. Both studies used the ERCC1-antibody clone 8F1 that later turned out to be not specific. The aim of this study was to evaluate the predictive role of ERCC1 with a new specific antibody in a larger series of ACC.
DESIGN AND METHODS: 146 ACC patients with available FFPE slides were investigated. All patients underwent PBC (median cycles = 6), including cisplatin (n = 131) or carboplatin (n = 15), in most cases combined with etoposide (n = 144), doxorubicin (n = 131) and mitotane (n = 131). Immunostaining was performed with the novel ERCC1-antibody clone 4F9. The relationship between ERCC1 expression and clinicopathological parameters, as well as best objective response to therapy and progression-free survival (PFS) during PBC was evaluated.
RESULTS: High ERCC1 expression was observed in 66% of ACC samples. During PBC, 43 patients experienced objective response (29.5%), 49 stable disease (33.6%), 8 mixed response (5.5%) and 46 progressive disease (31.5%) without any relationship with the ERCC1 immunostaining. No significant correlation was also found between ERCC1 expression and progression-free survival (median 6.5 vs 6 months, P  =  0.33, HR = 1.23, 95% CI = 0.82-2.0).
CONCLUSION: ERCC1 expression is not directly associated with sensitivity to PBC in ACC. Thus, other predictive biomarkers are required to support treatment decisions in patients with ACC.

PMID: 29187510 [PubMed - indexed for MEDLINE]

Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1.

Sat, 01/13/2018 - 21:28
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Next-generation panel sequencing identifies NF1 germline mutations in three patients with pheochromocytoma but no clinical diagnosis of neurofibromatosis type 1.

Eur J Endocrinol. 2018 Feb;178(2):K1-K9

Authors: Gieldon L, Masjkur JR, Richter S, Därr R, Lahera M, Aust D, Zeugner S, Rump A, Hackmann K, Tzschach A, Januszewicz A, Prejbisz A, Eisenhofer G, Schrock E, Robledo M, Klink B

Abstract
OBJECTIVE: Our objective was to improve molecular diagnostics in patients with hereditary pheochromocytoma and paraganglioma (PPGL) by using next-generation sequencing (NGS) multi-gene panel analysis. Derived from this study, we here present three cases that were diagnosed with NF1 germline mutations but did not have a prior clinical diagnosis of neurofibromatosis type 1 (NF1).
DESIGN: We performed genetic analysis of known tumor predisposition genes, including NF1, using a multi-gene NGS enrichment-based panel applied to a total of 1029 PPGL patients. We did not exclude genes known to cause clinically defined syndromes such as NF1 based on missing phenotypic expression as is commonly practiced.
METHODS: Genetic analysis was performed using NGS (TruSight Cancer Panel/customized panel by Illumina) for analyzing patients' blood and tumor samples. Validation was carried out by Sanger sequencing.
RESULTS: Within our cohort, three patients, who were identified to carry pathogenic NF1 germline mutations, attracted attention, since none of the patients had a clinical suspicion of NF1 and one of them was initially suspected to have MEN2A syndrome due to co-occurrence of a medullary thyroid carcinoma. In these cases, one splice site, one stop and one frameshift mutation in NF1 were identified.
CONCLUSIONS: Since phenotypical presentation of NF1 is highly variable, we suggest analysis of the NF1 gene also in PPGL patients who do not meet diagnostic NF1 criteria. Co-occurrence of medullary thyroid carcinoma and PPGL was found to be a clinical decoy in NF1 diagnostics. These observations underline the value of multi-gene panel NGS for PPGL patients.

PMID: 29158289 [PubMed - indexed for MEDLINE]

Glucose metabolism disorders in patients with non-functioning adrenal adenomas - single-centre experience.

Sat, 01/13/2018 - 21:28
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Glucose metabolism disorders in patients with non-functioning adrenal adenomas - single-centre experience.

Endokrynol Pol. 2017;68(4):416-421

Authors: Krzyżewska K, Niemczuk E, Myśliwiec BJ, Junik R

Abstract
INTRODUCTION: The presence of glucose metabolism disorders and their possible correlation with degree of cortisol secretion were evaluated in patients with non-functioning adrenal incidentalomas (NFAIs).
MATERIAL AND METHODS: The study group consisted of 131 patients with hormonally inactive adrenal incidentalomas. In each patient, besides hormonal and radiological evaluation, was assessed for fasting glucose and insulin concentrations, and the oral glucose tolerance test (OGTT) was performed in all participants without previous history of glucose disturbances. The HOMA-IR, QUICKI, and TyG indices were calculated.
RESULTS: Diabetes was diagnosed in 30.5% of the studied group. Among glucose tolerance abnormalities, impaired fasting glucose (IFG) was found in 23.7%, impaired glucose tolerance (IGT) in 4.6%, and combined IFG and IGT in 11.5%. Normoglycaemia was recognised in 29.8% of NFAIs patients. The occurrence rate of glucose aberrations increased with age. There was a significant difference in all insulin resistance indices shown between normoglycaemic patients and those with impairments in glucose tolerance. There was no significant correlation between fasting glucose, insulin resistance indices, and adrenal tumour size or degree of cortisol secretion.
CONCLUSIONS: The prevalence of diabetes and impaired fasting glucose among NFAIs patients is much higher than in the general population. Therefore, patients with incidentally discovered adrenal tumours should be tested for glucose tolerance.

PMID: 28585681 [PubMed - indexed for MEDLINE]

Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication.

Sat, 01/13/2018 - 21:28
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Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication.

Transplant Proc. 2017 Jun;49(5):1160-1164

Authors: Ohira M, Nishida S, Tryphonopoulos P, Ruiz P, Ohdan H, Tzakis AG

Abstract
BACKGROUND: Natural killer (NK) cells play important roles in killing tumor and virus-infected cells. Immunosuppression used after organ transplantation is thought to increase the risk of tumor recurrence and viral infections. However, the effect of immunosuppressive drugs on NK cells has not yet been clearly established. Therefore, we examined the effect of immunosuppression on NK cells.
METHODS: NK cells were cultured for 7 days in the presence of interleukin-2 (100 U/mL) with or without the following immunosuppressive drugs: tacrolimus, cyclosporine A, corticosteroid (methylprednisolone [MP]), mycophenolate mofetil, and rapamycin. The effect of the drugs on NK cell activation was tested on the basis of the following: NK cell phenotype, NK cell proliferation, cytotoxicity against K562 cells, cytokine production by NK cells, and anti-hepatitis C virus (HCV) activity with HCV genomic replicon cells.
RESULTS: NK cells showed relatively robust functions in the presence of tacrolimus and cyclosporine A. Mycophenolate mofetil and rapamycin significantly prevented only NK cell proliferation (P < .05). In contrast, MP significantly inhibited the proliferation, cytotoxicity, and anti-HCV effect (10.9%, 18.5%, and 1.9%, respectively) of NK cells. Furthermore, MP specifically inhibited the expression of NK cell activation markers and the production of interferon-γ (P < .05).
CONCLUSIONS: Corticosteroids have distinct effects on NK cells, which may have important implications for NK cell function in cytotoxicity and HCV effect after transplantation.

PMID: 28583548 [PubMed - indexed for MEDLINE]

Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans.

Sat, 01/13/2018 - 21:28
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Pyrexia's effect on the CBG-cortisol thermocouple, rather than CBG cleavage, elevates the acute free cortisol response to TNF-α in humans.

Stress. 2017 Mar;20(2):183-188

Authors: Nenke MA, Nielsen ST, Lehrskov LL, Lewis JG, Rankin W, Møller K, Torpy DJ

Abstract
Corticosteroid-binding globulin (CBG) cleavage promotes local cortisol delivery in inflammation. Enzymatic cleavage of high-affinity CBG to low-affinity CBG (haCBG to laCBG) occurs at inflammatory sites and is now measurable in vivo; however, the time kinetics of haCBG depletion following an inflammatory stimulus is unknown. Hence our aim was to determine the immediate effect of the key pro-inflammatory cytokine TNF-α on CBG levels and cleavage. We performed a crossover study of 12 healthy males receiving a TNF-α versus saline infusion, measuring total CBG, haCBG, laCBG and free and total cortisol hourly for 6 h. There was no change in total CBG or haCBG levels in the first 6 h of inflammation between the groups, suggesting that CBG cleavage is not activated nor is hepatic CBG production affected by TNF-α in this time frame. There was an early increase in the ratio of free:total cortisol, in association with pyrexia. This accords with data indicating that CBG acts a thermocouple in vivo, increasing free cortisol levels independent of elastase-driven cleavage.

PMID: 28166688 [PubMed - indexed for MEDLINE]

Assessing the Risk for Diabetes in Patients With Unexpectedly Identified Tumors in the Adrenal Glands.

Sat, 01/13/2018 - 21:28
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Assessing the Risk for Diabetes in Patients With Unexpectedly Identified Tumors in the Adrenal Glands.

Ann Intern Med. 2016 Oct 18;165(8):

Authors:

PMID: 27479093 [PubMed - indexed for MEDLINE]

A case of added value of 123I-mIBG SPECT/CT imaging in the diagnosis of a pheochromocytoma extending into the left adrenal vein.

Sat, 01/13/2018 - 21:28
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A case of added value of 123I-mIBG SPECT/CT imaging in the diagnosis of a pheochromocytoma extending into the left adrenal vein.

Acta Chir Belg. 2017 Jun;117(3):192-195

Authors: Paques F, Hamoir E, Lovinfosse P, Hustinx R, Withofs N

Abstract
We present the case of a 48-year-old patient with a left adrenal incidentaloma found on computed tomography (CT) for which the diagnosis of pheochromocytoma was confirmed by a 24-hour urinary dosage of norepinephrine. The 123I-mIBG scintigraphy showed a high uptake of 123I-mIBG in the left adrenal gland and, additionally, the single photon emission computed tomography combined with a low-dose CT (SPECT/CT) suggested the extension into the adrenal vein. The diagnostic CT and magnetic resonance images agreed with these findings and the subsequent surgery confirmed the vascular invasion.

PMID: 27735216 [PubMed - indexed for MEDLINE]

Evaluation of a large adrenal carcinoma with 3D reconstruction of computed tomography images: A case report and literature review.

Sat, 01/13/2018 - 21:28
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Evaluation of a large adrenal carcinoma with 3D reconstruction of computed tomography images: A case report and literature review.

J Xray Sci Technol. 2016 Oct 06;24(5):665-671

Authors: Chen L, Zeng X, Li S, Gong C, Peng E, Wu B, Zhang W, Zhang Y

Abstract
Adrenocortical carcinoma (ACC) is an extremely rare disease caused by a cancerous growth in the adrenal cortex. Although most of adrenal tumors are benign, the functional ACC is malignant resulting in endocrine dysfunction and necessitates surgical removal. Retroperitoneal laparoscope adrenalectomy is often used to perform adrenal gland surgery. Here, we reported a case of huge ACC with the size of 6.8 cm × 5.2 cm. To achieve better surgical outcome, we integrated 3D reconstructed CT images into a dynamic video for preoperative planning and intraoperative guiding to resect the diseased adrenal gland completely without neighbor organ's injury and surgery complications. Moreover, we reviewed associated applications using 3D reconstructed CT imaging in surgery field. Finally, the evaluation and effect of such technology were discussed to reveal that the 3D dynamic video can help surgeon to make better preoperative assessment so as to give patients better therapy.

PMID: 27567750 [PubMed - indexed for MEDLINE]

Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas.

Sat, 01/13/2018 - 21:28
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Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas.

Endocr Relat Cancer. 2016 Sep;23(9):727-37

Authors: Creemers SG, van Koetsveld PM, van Kemenade FJ, Papathomas TG, Franssen GJ, Dogan F, Eekhoff EM, van der Valk P, de Herder WW, Janssen JA, Feelders RA, Hofland LJ

Abstract
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Discrimination of ACCs from adrenocortical adenomas (ACAs) is challenging on both imaging and histopathological grounds. High IGF2 expression is associated with malignancy, but shows large variability. In this study, we investigate whether specific methylation patterns of IGF2 regulatory regions could serve as a valuable biomarker in distinguishing ACCs from ACAs. Pyrosequencing was used to analyse methylation percentages in DMR0, DMR2, imprinting control region (ICR) (consisting of CTCF3 and CTCF6) and the H19 promoter. Expression of IGF2 and H19 mRNA was assessed by real-time quantitative PCR. Analyses were performed in 24 ACCs, 14 ACAs and 11 normal adrenals. Using receiver operating characteristic (ROC) analysis, we evaluated which regions showed the best predictive value for diagnosis of ACC and determined the diagnostic accuracy of these regions. In ACCs, the DMR0, CTCF3, CTCF6 and the H19 promoter were positively correlated with IGF2 mRNA expression (P<0.05). Methylation in the most discriminating regions distinguished ACCs from ACAs with a sensitivity of 96%, specificity of 100% and an area under the curve (AUC) of 0.997±0.005. Our findings were validated in an independent cohort of 9 ACCs and 13 ACAs, resulting in a sensitivity of 89% and a specificity of 92%. Thus, methylation patterns of IGF2 regulatory regions can discriminate ACCs from ACAs with high diagnostic accuracy. This proposed test may become the first objective diagnostic tool to assess malignancy in adrenal tumours and facilitate the choice of therapeutic strategies in this group of patients.

PMID: 27535174 [PubMed - indexed for MEDLINE]

Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.

Sat, 01/13/2018 - 21:28
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Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.

Clin Cancer Res. 2016 Dec 15;22(24):6247-6255

Authors: Pinto EM, Rodriguez-Galindo C, Choi JK, Pounds S, Liu Z, Neale G, Finkelstein D, Hicks JM, Pappo AS, Figueiredo BC, Ribeiro RC, Zambetti GP

Abstract
PURPOSE: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly treated children with adrenocortical carcinomas.
EXPERIMENTAL DESIGN: We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric adrenocortical tumors by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays.
RESULTS: MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 ×10-6) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%).
CONCLUSIONS: MHC class II expression, which is produced by tumor-infiltrating immune cells, is an indicator of disease aggressiveness in pediatric adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247-55. ©2016 AACR.

PMID: 27307598 [PubMed - indexed for MEDLINE]

Purkinje cell protein 4 expression is associated with DNA methylation status in aldosterone-producing adenoma.

Sat, 01/06/2018 - 19:14
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Purkinje cell protein 4 expression is associated with DNA methylation status in aldosterone-producing adenoma.

J Clin Endocrinol Metab. 2017 Dec 26;:

Authors: Kobuke K, Oki K, Gomez-Sanchez CE, Ohno H, Itcho K, Yoshii Y, Yoneda M, Hattori N

Abstract
CONTEXT: Aldosterone production is stimulated by activation of calcium signaling in aldosterone-producing adenoma (APA), and epigenetic factors such as DNA methylation may be associated with the expression of genes involved in aldosterone regulation.
OBJECTIVE: Our aim was to investigate the DNA methylation of genes related to calcium signaling cascades in APA, and the association of mutations in genes linked to APA with DNA methylation levels.
METHODS: Non-functioning adrenocortical adenoma (NF, n=12) and APA (n=35) samples were analyzed. The KCNJ5 T158A mutation was introduced into human adrenocortical cell lines (HAC15 cells) using lentiviral delivery. DNA methylation array analysis was conducted using adrenal tumor samples and HAC15 cells.
RESULTS: The Purkinje cell protein 4 (PCP4) gene was one of the most hypo-methylated in APA. DNA methylation levels in two sites of PCP4 showed a significant inverse correlation with the mRNA expression in adrenal tumors. Bioinformatics and multiple regression analysis revealed that CEBPA (CCAAT/enhancer binding protein alpha) may bind to the methylation site of PCP4 promoter. CEBPA bound to PCP4 hypo-methylated region by Chromatin immunoprecipitation assay. There was no significant difference of PCP4 methylation levels among APA genotypes. Moreover, KCNJ5 T158A did not influence PCP4 methylation levels in HAC15 cells.
CONCLUSIONS: We showed that the PCP4 promoter was one of the most hypo-methylated in APA, and PCP4 transcription may be associated with demethylation as well as CEBPA in APA. KCNJ5 mutations known to result in aldosterone overproduction were not related with PCP4 methylation in either clinical or in vitro studies.

PMID: 29294065 [PubMed - as supplied by publisher]

Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation.

Sat, 01/06/2018 - 19:14
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Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation.

J Neurogastroenterol Motil. 2018 Jan 30;24(1):138-146

Authors: Ait-Belgnaoui A, Payard I, Rolland C, Harkat C, Braniste V, Théodorou V, Tompkins TA

Abstract
Background/Aims: Visceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis.
Methods: After a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured.
Results: A pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic.
Conclusion: The combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.

PMID: 29291614 [PubMed]

Robotic-assisted laparoscopic surgery for pediatric tumors: a bicenter experience.

Sat, 01/06/2018 - 19:14
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Robotic-assisted laparoscopic surgery for pediatric tumors: a bicenter experience.

J Robot Surg. 2017 Dec 29;:

Authors: Meignan P, Ballouhey Q, Lejeune J, Braik K, Longis B, Cook AR, Lardy H, Fourcade L, Binet A

Abstract
Mini-invasive surgery is more and more integrated in pediatric surgery. The robotic-assisted surgery brought new advantages from which the patient and the surgeon could benefit compared to laparoscopy. Its use in oncological surgery is still controversial. 12 robotic-assisted tumor resections with the da Vinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA) were attempted in 11 children (mean age 7.65 years; age range 0.75-16.75 years; mean weight 30.3 kg; weight range 8.6-62 kg) in two centers. Mean total operative time was 145 min (range 72-263 min). 1 procedure (8.3%) was converted. The pathology included renal tumors (n = 2; one nephroblastoma, one metanephric adenoma), adrenal tumors (n = 9; three neuroblastomas, two pheochromocytomas, two adrenocortical adenomas, one cystic lymphangioma, one paraganglioma) and a pancreatic tumor (n = 1; one pancreatic cyst). 4 tumors (33.3%) were malignant. Every patient underwent a R0 resection. 1 child (8.3%) developed a post operative complication. Mean length of hospitalization was 3.0 days (range 2-5 days). Followup averaged 3.3 years with no recurrence. All children are alive. Robot-assisted MIS seems to be safe and feasible in pediatric tumors. The oncological surgical principles were respected in our series with low morbi/mortality and good long-term results. Robotic surgery and its technical advantages bring potential benefits for children with cancer. It has a role to play in pediatric oncological surgery but its place and indications still need to be better defined.

PMID: 29288372 [PubMed - as supplied by publisher]

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