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Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

Sun, 03/04/2018 - 13:34
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Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

Surg Endosc. 2018 Feb 27;:

Authors: Donatini G, Kraimps JL, Caillard C, Mirallie E, Pierre F, De Calan L, Antoine H, Larin O, Tovkay O, Cherenko S

Abstract
BACKGROUND: Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery.
METHODS: A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up.
RESULTS: PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/β blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications.
CONCLUSIONS: PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

PMID: 29488089 [PubMed - as supplied by publisher]

Benign diaphragmatic neurilemmoma mimicking a left adrenal cyst.

Sun, 03/04/2018 - 13:34
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Benign diaphragmatic neurilemmoma mimicking a left adrenal cyst.

Turk J Urol. 2018 Jan;44(1):87-90

Authors: Bhattar R, Tomar V, Dhakad DS, Agarwal N

Abstract
Neurilemmomas are benign, slow growing, encapsulated nerve sheath tumor. These tumors arise from the schwann cells of neural crest. Neurilemmomas can manifest in various form according to site, extent and severity of involvement of organ. Diaphragmatic neurilemmomas are very unusual and even difficult to diagnose on preoperative imaging. We will report a case of 39 year old male, who presented with complaints of occasional left flank pain for one year and subsequently investigated, which showed left adrenal cyst with haemorrhagic fluid content. On the contrary, when surgical exploration of the lesion was done, it showed a cyst within the diaphragm, completely separated from left kidney and left adrenal with haemorrhagic content in situ. Histopathological examination of the lesion showed it to be a benign neurilemmoma with cystic degeneration. Post opearatively patient did well. We believe that this is the first case report, which is addressing such kind of initial manifestation of diaphragmatic neurilemmomas.

PMID: 29484235 [PubMed]

Adrenal mass of unusual etiology: Ewing sarcoma in a young man.

Sun, 03/04/2018 - 13:34
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Adrenal mass of unusual etiology: Ewing sarcoma in a young man.

Radiol Case Rep. 2017 Dec;12(4):838-844

Authors: Soydan L, Demir AA, Sayman E, Onomay Celik B, Oven Ustaalioglu BB

Abstract
Ewing sarcoma and peripheral primitive neuroectodermal tumor belong to the Ewing sarcoma (ES) family of tumors originating from a primitive neural tube. We report a 31-year-old man who was admitted to the urology clinic with complaints of fever, nausea, and dysuria. A right-sided adrenal mass was detected during ultrasonography. The lesion was then evaluated with magnetic resonance imaging, which showed areas of necrosis amid heterogeneous solid areas. Whole body scan with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography and bone scan studies showed pulmonary and osseous metastatic foci. The mass and right kidney were removed by an open approach. An immunohistochemical and molecular workup enabled the diagnosis of ES. The patient also underwent radiotherapy and chemotherapy. The patient remained in fairly good health during the 18-month follow-up period, but showed progression of all metastatic foci and died 26 months after treatment. In conclusion, adrenal ES should be included in the differential diagnosis of nonfunctional adrenal lesions despite its rare occurrence.

PMID: 29484083 [PubMed]

Primary carcinosarcoma of the liver: imaging features and clinical findings in six cases and a review of the literature.

Sun, 03/04/2018 - 13:34
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Primary carcinosarcoma of the liver: imaging features and clinical findings in six cases and a review of the literature.

Cancer Imaging. 2018 Feb 27;18(1):7

Authors: Li J, Liang P, Zhang D, Liu J, Zhang H, Qu J, Gao J

Abstract
BACKGROUND: Carcinosarcoma of the liver is a very rare tumor composed of a mixture of carcinomatous and sarcomatous elements. Less than 25 adequately documented cases have been reported, with inadequate description of imaging features. In order to improve the awareness of this rare tumor, this study aimed to analyze the clinicopathologic and imaging features of six cases of hepatic carcinosarcoma (HCS) confirmed by surgical pathologic evaluation.
METHODS: We retrospectively studied the clinicopathologic and imaging features of six cases of HCS (matching the World Health Organization definition) and discussed the differential diagnosis on the basis of imaging findings. The patients, including five men and one woman, were 38 to 69 years of age. Five patients underwent CT scans, one underwent MRI scans.
RESULTS: While 3 patients were positive for hepatitis-B surface antigen, 2 had cirrhosis. The largest tumor diameter ranged from 5.0 to 21.0 cm. Satellite nodules, venous thrombi, and organ invasion (gastric wall, gallbladder, and right adrenal gland) were identified. Pathologically, the carcinomatous components corresponded to hepatocellular carcinoma in three cases, cholangiocellular carcinoma in one case, and adenocarcinoma in two cases. The sarcomatous components exhibited complex features, with undifferentiated spindle cells in five cases and a leiomyosarcoma in one. All tumors showed heterogeneous density/intensity with extensive cystic change and necrosis; spot calcification was observed in one case. Capsule was not identified. While four tumors showed heterogeneous hypervascular enhancement, two showed hypovascular enhancement. All patients underwent surgical resection. The follow-up period ranged from 2 to 18 months. Four patients died from recurrence and metastasis.
CONCLUSIONS: The clinical and imaging features of HCS are heterogeneous. Due to the heterogenous nature and very low morbidity of HCS, combination of careful analysis of imaging findings and clinical features might be useful for a more accurate diagnosis of HCS.

PMID: 29482629 [PubMed - in process]

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

Sun, 03/04/2018 - 13:34
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Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

Am J Med Sci. 2018 Feb;355(2):191-194

Authors: Chaaya G, Morales J, Castiglioni A, Subhani N, Asmar A

Abstract
Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations.

PMID: 29406048 [PubMed - indexed for MEDLINE]

New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma.

Sun, 03/04/2018 - 13:34
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New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma.

Trends Endocrinol Metab. 2017 Nov;28(11):807-817

Authors: Taïeb D, Pacak K

Abstract
Pheochromocytomas and paragangliomas (PPGLs) belong to the family of neural crest cell-derived neoplasms. In up to 70% of cases they are associated with germline and somatic mutations in 15 well-characterized PPGL driver or fusion genes. PPGLs can be grouped into three main clusters, where cluster 1 includes PPGLs characterized by a pseudohypoxic signature. Although cluster 1 tumors share several common features, they exhibit unique behaviors. We present here unique insights into the imaging phenotypes of cluster 1 PPGLs based on glucose uptake, catecholamine metabolism, and somatostatin receptor expression. Recent data suggest that succinate is a major player in the imaging phenotype of succinate dehydrogenase-deficient PPGLs. This review emphasizes the emerging stromal cell-succinate interaction and highlights new perspectives in PPGL theranostics.

PMID: 28867159 [PubMed - indexed for MEDLINE]

Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.

Sun, 03/04/2018 - 13:34
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Solitary Adrenal Metastases from Breast Invasive Ductal Carcinoma.

Chirurgia (Bucur). 2017 Jul-Aug;112(4):473-476

Authors: Stroescu C, Gilca I, Chirita D, Poenaru R, Puşcaşu A, Pescaru D, Birceanu A, Niţipir C, Copcă N

Abstract
The usual neoplastic dissease involving suprarenal glands are adrenal metastaes. The majority of suprarenal metastatic disease arise from lung cancer, followed by the stomach and colon cancer, oesophagus, the liver/bile ducts cancer and renal cell carcinoma. Invasive mammary carcinoma usually spreads to the bones, lungs, lymph nodes, liver and the brain. Adrenal gland metastases from invasive no special type carcinoma represents an extremly low rate number of cases. We discuss about a 66 year old patient who presented with a solitary adrenal metastases from triple negative breast invasive carcinoma. The patient underwent total left adrenalectomy in June 2016. No further adjuvants therapies were performed. At the time of writing the patient is in good condition, without any evidence of recurrence. The role of surgical and adjuvant therapy in treating adrenal metastases after breast cancer in survival rate will be determined in future studies.

PMID: 28862125 [PubMed - indexed for MEDLINE]

Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer.

Sun, 03/04/2018 - 13:34
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Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer.

Intern Med. 2017;56(15):1987-1992

Authors: Nishioka M, Kamei S, Kinoshita T, Sanada J, Fushimi Y, Irie S, Hirata Y, Tanabe A, Hirukawa H, Kimura T, Obata A, Tatsumi F, Kohara K, Shimoda M, Nakanishi S, Mune T, Kaku K, Kaneto H

Abstract
Werner syndrome is a rare genetic disease characterized by progeria, diabetes mellitus, cataracts and various types of malignancy. However, there are few reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein report an extremely rare case of Werner syndrome accompanied by adrenal cortex cancer. Based on the data obtained from blood samples, computed tomography, magnetic resonance imaging and 131I adosterol scintigraphy, we diagnosed this subject with adrenal cortex cancer and Cushing's syndrome. Since the prognosis of adrenal cancer is very poor, we should be aware of the possibility of adrenal cancer occurring in subjects with Werner syndrome.

PMID: 28768969 [PubMed - indexed for MEDLINE]

Inadvertent Arterial Injection of 123I-MIBG Does Not Necessarily Cause Any Symptoms.

Sun, 03/04/2018 - 13:34
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Inadvertent Arterial Injection of 123I-MIBG Does Not Necessarily Cause Any Symptoms.

Clin Nucl Med. 2017 Sep;42(9):723-724

Authors: Zhang W, Zhuang H

Abstract
An 123I-MIBG scan was obtained to evaluate a right adrenal mass in a 10-year-old boy, which showed no elevated activity in the lesion. However, diffuse increased activity was noted in the right forearm with typical manifestation of an "arterial injection." Different from a prior case report, no symptoms or signs related to arterial injection were observed in our patient.

PMID: 28632699 [PubMed - indexed for MEDLINE]

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies.

Sun, 03/04/2018 - 13:34
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Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies.

Endocr Relat Cancer. 2017 Jun;24(6):R239-R259

Authors: Angelousi A, Dimitriadis GK, Zografos G, Nölting S, Kaltsas G, Grossman A

Abstract
Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours, which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and in gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary, and parathyroid glands. Due to the rarity of these tumours and the lack of prospective studies, current guidelines are mostly based on retrospective data derived from surgical, locoregional and ablative therapies, and studies with systemic chemotherapy. In addition, in many of these malignancies the prognosis remains poor with individual patients responding differently to currently available treatments, necessitating the development of new personalised therapeutic strategies. Recently, major advances in the molecular understanding of endocrine tumours based on genomic, epigenomic, and transcriptome analysis have emerged, resulting in new insights into their pathogenesis and molecular pathology. This in turn has led to the use of novel MTTs in increasing numbers of patients. In this review, we aim to present currently existing and evolving data using MTT in the treatment of adrenal, pituitary and malignant parathyroid tumours, and explore the current utility and effectiveness of such therapies and their future evolution.

PMID: 28400402 [PubMed - indexed for MEDLINE]

Resection of Pheochromocytoma Improves Diabetes Mellitus in the Majority of Patients.

Sun, 03/04/2018 - 13:34
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Resection of Pheochromocytoma Improves Diabetes Mellitus in the Majority of Patients.

Ann Surg Oncol. 2017 May;24(5):1208-1213

Authors: Beninato T, Kluijfhout WP, Drake FT, Lim J, Kwon JS, Xiong M, Shen WT, Gosnell JE, Liu C, Suh I, Duh QY

Abstract
BACKGROUND: Catecholamine excess in patients with pheochromocytoma often results in impaired glucose tolerance, leading to diabetes mellitus. Little data are available on the long-term effect of surgery on diabetes.
OBJECTIVE: The primary aim of this study was to determine the likelihood of diabetes cure after surgery, while secondary objectives were to determine risk factors for development of diabetes preoperatively and persistence of diabetes postoperatively.
METHODS: All patients undergoing surgery for pheochromocytoma from 1996 to 2015 were retrospectively reviewed to identify those with a preoperative diagnosis of diabetes. Demographic and diabetes-specific data were collected. Median follow-up was 52.1 months.
RESULTS: Overall, 153 patients underwent surgery. Diabetes was seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were removed from the final analysis, while 22 (78.6%) patients had complete resolution of diabetes. Four patients remained on medication with improved control. Overall, 93.0% of patients had improvement of their diabetes; two patients did not improve. Patients with large, symptomatic tumors were more likely to develop preoperative diabetes, and diabetes was more likely to persist in patients who had an elevated body mass index (BMI).
CONCLUSIONS: Diabetes was found concurrently with pheochromocytoma in 23% of patients, more often in those with large, symptomatic tumors. The majority of patients had long-term resolution of diabetes after successful resection; however, some patients may continue to require treatment of diabetes after operation, especially those with a higher BMI.

PMID: 27896511 [PubMed - indexed for MEDLINE]

Cardiac Metastases from A Lung Tumor.

Sun, 03/04/2018 - 13:34
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Cardiac Metastases from A Lung Tumor.

Arch Bronconeumol. 2017 Feb;53(2):80-81

Authors: Cabrera César E, Fernández Aguirre MC, Hidalgo Sanjuan MV

PMID: 27381972 [PubMed - indexed for MEDLINE]

Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

Sun, 03/04/2018 - 13:34
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Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies.

Clin Nutr. 2017 Apr;36(2):497-505

Authors: Alhagamhmad MH, Lemberg DA, Day AS, Tan LZ, Ooi CY, Krishnan U, Gupta N, Munday JS, Leach ST

Abstract
BACKGROUND & AIMS: Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti-inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF.
METHODS: Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF.
RESULTS: DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-α, IL-6 and IL-8 levels from cultured biopsies.
CONCLUSIONS: Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients.

PMID: 26833290 [PubMed - indexed for MEDLINE]

adrenal tumor; +27 new citations

Sun, 02/25/2018 - 10:45

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Anterior Approach to En Bloc Resection in Left-Sided Retroperitoneal Sarcoma with Adjacent Organ Involvement: A Study of 25 Patients in a Single Center.

Sun, 02/18/2018 - 08:55
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Anterior Approach to En Bloc Resection in Left-Sided Retroperitoneal Sarcoma with Adjacent Organ Involvement: A Study of 25 Patients in a Single Center.

Med Sci Monit. 2018 Feb 16;24:961-969

Authors: Wang Z, Wu JH, Lv A, Li CP, Tian XY, Hao CY

Abstract
BACKGROUND There is no standard surgical approach for the management of retroperitoneal sarcoma. The aim of this clinical study was to describe the experience of an anterior approach to en bloc resection in left-sided retroperitoneal sarcoma with adjacent organ involvement. MATERIAL AND METHODS This retrospective clinical study included 25 patients who were diagnosed with left-sided retroperitoneal sarcoma and underwent tumor resection at a single center between May 2012 and July 2017. All patients had tumors that were adjacent to the left colon, pancreas, left kidney, left adrenal gland, and psoas major; some of the tumors were adjacent to the diaphragm, stomach, and small intestine. An anterior approach was used to remove the left-sided retroperitoneal tumor with the adhesive organs en bloc, an approach that is described in detail. The value of this surgical approach was evaluated based on the histopathological findings, postoperative complications, and patient follow-up. RESULTS The median number of resected organs, in addition to the retroperitoneal tumor, was 8 (range, 6-10). Complete macroscopic tumor resection was achieved in 23 cases (92%). Twenty-four patients (96%) had tumor infiltration of at least one organ or the surrounding fat. Three patients (12%) experienced Grade III and IV postoperative morbidities. The one-year disease-free survival rate was 91.3% among patients with macroscopically complete resections. The one-year overall survival rate was 83.2%. CONCLUSIONS In selected patients, left-sided retroperitoneal sarcoma associated with local organ involvement can be surgically managed using an anterior approach with en bloc resection of adjacent organs.

PMID: 29449525 [PubMed - in process]

Retroperitoneal laparoscopic adrenalectomy with transient renal artery occlusion for large adrenal tumors (≥8 cm).

Sun, 02/18/2018 - 08:55
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Retroperitoneal laparoscopic adrenalectomy with transient renal artery occlusion for large adrenal tumors (≥8 cm).

J Surg Oncol. 2018 Feb 15;:

Authors: Gong B, Ma M, Xie W, Yang X, Sun T

Abstract
OBJECTIVES: To analyze our experience in retroperitoneal laparoscopic adrenalectomy (RLA) with transient renal artery occlusion for large adrenal tumors (≥8 cm) and to explore the safety and feasibility of this surgical procedure.
METHODS: A retrospective cohort study was conducted with a surgical data review of 18 patients with large adrenal tumors who underwent RLA with transient renal artery occlusion in our hospital.
RESULTS: Eighteen patients were treated by RLA with transient occlusion of the renal artery, and none were converted to open adrenalectomy. The renal artery occlusion time, operative time, estimated blood loss, perirenal drainage time, postoperative hospital stay, and postoperative drainage were 7.6 ± 1.0 min, 176.3 ± 49.7 min, 247.2 ± 274.1 mL, 4.1 ± 1.02 days, 6.3 ± 1.4 days, and 73.6 ± 47.9 mL, respectively. No severe complications occurred, with the exception of hemodynamic instability in one patient with a pheochromocytoma and one transfusion during the operation. Only one case of adrenal crisis occurred postoperatively. Pathological examination revealed 9 cases of pheochromocytoma, 6 cases of adrenal myelolipoma, 1 case of adrenal ganglioneuroma, 1 case of hygromata, and 1 case of adrenal teratoma. No recurrence or evidence of metastasis was observed during the 7-to-30-month follow-up period.
CONCLUSION: RLA with transient renal artery occlusion is a feasible, effective, and safe treatment for large adrenal tumors (≥8 cm).

PMID: 29448302 [PubMed - as supplied by publisher]

Adrenal myelolipoma with hyperandrogenemia and schizophrenia.

Sun, 02/18/2018 - 08:55
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Adrenal myelolipoma with hyperandrogenemia and schizophrenia.

Cancer Manag Res. 2018;10:177-180

Authors: Liu N, Zhang W, Tan J, Zhou J, Yu X, Ren N, Fang Z, Jiao W, Fan Y, Liu C

Abstract
Adrenal myelolipoma with hyperandrogenemia is extremely rare. We report a case of a 26-year-old Chinese female with schizophrenia, who presented with a hormonally active tumor causing hyperandrogenemia. The mass was found by computerized tomography when she had her gynecologic examination for secondary amenorrhea, and it was confirmed to be an adrenal myelolipoma after a histopathological study. She was referred for a left adrenal laparoscopic excision, and the size of adrenal myelolipoma was found to be more than 10 cm. We report this case because large adrenal myelolipomas with hyperandrogenemia and schizophrenia are rare, and adrenal myelolipoma associated with hyperandrogenemia might be determined by the enzymes involved in the production of hormones.

PMID: 29440927 [PubMed]

Intratumoral Delivery of Interferon γ-secreting MSCs Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo.

Sun, 02/18/2018 - 08:55
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Intratumoral Delivery of Interferon γ-secreting MSCs Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo.

Stem Cells. 2018 Feb 12;:

Authors: Relation T, Yi T, Guess AJ, La Perle K, Otsuru S, Hasgur S, Dominici M, Breuer C, Horwitz EM

Abstract
Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely utilized to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFNγ) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME). Despite this, clinical trials of systemic IFNγ therapy have failed due to the high blood concentration required and associated systemic toxicities. Here, we developed an intra-adrenal model of neuroblastoma, characterized by liver and lung metastases. We then engineered MSCs to deliver IFNγ directly to the TME. In vitro, these MSCs polarized murine macrophages to the M1 phenotype. In vivo, we attained a therapeutically active TME concentration of IFNγ without increased systemic concentration or toxicity. The TME-specific IFNγ reduced tumor growth rate and increased survival in two models of T cell deficient athymic nude mice. Absence of this benefit in NSG immunodeficient mouse model indicates a mechanism dependent on the innate immune system. IL-17 and IL-23p19, both uniquely M1 polarization markers, transiently increased in the tumor interstitial fluid. Finally, the MSC vehicle did not promote tumor growth. These findings reveal that MSCs can deliver effective cytokine therapy directly to the tumor while avoiding systemic toxicity. This method transiently induces inflammatory M1 macrophage polarization, which reduces tumor burden in our novel neuroblastoma murine model. This article is protected by copyright. All rights reserved.

PMID: 29430789 [PubMed - as supplied by publisher]

Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

Sun, 02/18/2018 - 08:55
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Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

Indian J Nucl Med. 2018 Jan-Mar;33(1):55-56

Authors: Kashyap R

Abstract
Testicular adrenal rest tumors (TARTs) are secondary to hypertrophy of adrenal rest cells in the rete testis in settings of hypersecretion of androgens. We present a case of congenital adrenal hyperplasia with TART with clues to the diagnosis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). To the best of our knowledge, this is the first reported case on the role of 18F-FDG PET/CT in TART.

PMID: 29430117 [PubMed]

BCL9 Upregulation in Adrenocortical Carcinoma: A Novel Wnt/β-Catenin Activating Event Driving Adrenocortical Malignancy.

Sun, 02/18/2018 - 08:55
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BCL9 Upregulation in Adrenocortical Carcinoma: A Novel Wnt/β-Catenin Activating Event Driving Adrenocortical Malignancy.

J Am Coll Surg. 2018 Feb 08;:

Authors: Brown TC, Nicolson NG, Korah R, Carling T

Abstract
BACKGROUND: B-Cell CLL/Lymphoma 9 (BCL9) is a recently described oncogene that promotes tumorigenesis via activation of the Wnt/β-Catenin signaling cascade. Though constitutively active Wnt/β-Catenin signaling is a molecular hallmark of adrenocortical carcinoma (ACC), a potential role for BCL9 to promote Wnt/β-Catenin pathway dysregulation in adrenocortical tumorigenesis remains to be elucidated.
STUDY DESIGN: This study involved a retrospective analysis at a tertiary academic referral center of 27 patients with adrenocortical tumors, including in vitro investigation of BCL9. Wnt signaling pathway PCR array analysis queried comparative mRNA expression profiles of canonical Wnt pathway components including BCL9. Real-time quantitative PCR determined BCL9 mRNA expression levels in tumor samples. BCL9 mRNA expression levels were evaluated for correlation with tumor characteristics. RNA interference (RNAi) gene silencing was performed in ACC cell lines SW-13 and NCI-H295R to test the role of BCL9 on clonal cell growth.
RESULTS: BCL9 gene expression levels were found to be significantly elevated in ACC compared to normal adrenal tissue (p<0.05). Furthermore, a significant correlation was observed between BCL9 mRNA levels and the malignant status of adrenocortical tumors (p<0.05). RNAi gene silencing of BCL9 inhibited clonal cell growth of SW-13 cells (p<0.05), but not NCI-H295R cells, which carry a constitutively active β-Catenin mutation.
CONCLUSIONS: BCL9 is overexpressed in malignant adrenocortical tumors and promotes clonal ACC cell growth. These findings suggest that BCL9 overexpression may serve as an alternative driver of constitutive Wnt/β-Catenin activation in ACC and could represent a potential molecular and diagnostic marker of tumor malignancy.

PMID: 29428231 [PubMed - as supplied by publisher]

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