Adrenocortical Carcinoma

In the paper

“Immunohistochenistry was informative in most cases; however, all tested ACCs were microsatellite stable at the usual microsatellite markers.”

What the sources say

• Not checked yetcites [62] Raymond, 2013, Adrenocortical carcinoma is a Lynch syndrome-associated cancer, J Clin Oncol source

In the paper

“In the Michigan Endocrine Oncology Repository, roughly 5% of all patients diagnosed with ACC will have a disease course of >10 years (T.E., unpublished results).”

In the paper

“Furthermore, there were more R1 or R2 resections or notation of intraoperative tumor spill (50% vs 18%).”

What the sources say

• Not checked yetcites [262] Miller, 2010, Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma, World J Surg source

In the paper

“and 37% of all patients had no data regarding margin status.”

What the sources say

• Not checked yetcites [261] Brix, 2010, Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients, Eur Urol source

In the paper

“Patients with tumor bed recurrence who have undergone LA are much more likely to have disease too small to be detected by imaging elsewhere in the peritoneal cavity compared with those having undergone OA based on our experience.”

In the paper

“time to visible tumor bed recurrence or peritoneal recurrence in stage 2 patients was shorter in LA patients.”

In the paper

“Overall survival for patients with stage 2 ACC was longer in those undergoing OA”

In the paper

“Although overall recurrence rates were similar”

What the sources say

• Not checked yetcites [262] Miller, 2010, Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma, World J Surg source

In the paper

“These results were confirmed in an extended follow-up study of 110 patients undergoing OA and 46 undergoing LA.”

In the paper

“Overall, 30% of patients show stable disease or partial remission after treatment with mitotane (Table 7).”

In the paper

“Although there are relapses in patients after more than 5 years, this is rare and, in our experience, occurs in <3% of patients that were treated with an initial curative approach.”

In the paper

“This is mainly attributed to the high prevalence of the p.R337H low-penetrance allele of TP53 (6–8).”

What the sources say

• Not checked yetcites [6] Figueiredo, 2006, Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation, J Med Genet source
• Not checked yetcites [7] Garritano, 2010, Detailed haplotype analysis at the TP53 locus in p.R337H mutation carriers in the population of Southern Brazil: evidence for a founder effect, Hum Mutat source
• Not checked yetcites [8] Pinto, 2004, Founder effect for the highly prevalent R337H mutation of tumor suppressor p53 in Brazilian patients with adrenocortical tumors, Arq Bras Endocrinol Metabol source

In the paper

“A hallmark is alterations of DNA methylation of the 11p15 locus, which harbors the coding regions for IGF2, the cell cycle regulator CDKN1C, and the nontranslated RNA, H19 (41).”

What the sources say

• Not checked yetcites [41] Weksberg, 2005, Beckwith-Wiedemann syndrome, Am J Med Genet C Semin Med Genet source

In the paper

“A small fraction of patients with MEN1 will develop ACC (46–51).”

What the sources say

• Not checked yetcites [46] Skogseid, 1995, Adrenal lesion in multiple endocrine neoplasia type 1, Surgery source
• Not checked yetcites [47] Waldmann, 2007, Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening, Langenbecks Arch Surg source
• Not checked yetcites [48] Gatta-Cherifi, 2012, Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database, Eur J Endocrinol source
• Not checked yetcites [49] Griniatsos, 2011, Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene, World J Surg Oncol source
• Not checked yetcites [50] Langer, 2002, Adrenal involvement in multiple endocrine neoplasia type 1, World J Surg source
• Not checked yetcites [51] Skogseid, 1992, Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1, J Clin Endocrinol Metab

In the paper

“A bimodal distribution was definitely observed in a concise review of case series reported and in the SEER data (13, 14).”

What the sources say

• Not checked yetcites [13] Wooten, 1993, Adrenal cortical carcinoma. Epidemiology and treatment with mitotane and a review of the literature, Cancer source
• Not checked yetcites [14] Wasserman, 2012, Towards an understanding of the role of p53 in adrenocortical carcinogenesis, Mol Cell Endocrinol source

In the paper

“Beckwith-Wiedemann syndrome (BWS) spectrum disorders, such as classical BWS and idiopathic isolated hemihypertrophy, also increase the risk for ACC (Table 1).”

What the sources say

• Not checked yetcites Table 1

In the paper

“The high frequency of germline mutations in the Southern Brazilian population has also recently been confirmed in a population-based screening study (40).”

What the sources say

• Not checked yetcites [40] Custódio, 2013, Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors, J Clin Oncol source

In the paper

“Due to the low overall incidence (<1% of children with BWS will develop an ACC), no specific screening recommendations for ACC exist.”

What the sources say

• Not checked yetcites [43] Lapunzina, 2005, Risk of tumorigenesis in overgrowth syndromes: a comprehensive review, Am J Med Genet C Semin Med Genet source
• Not checked yetcites [44] Wiedemann, 1983, Tumours and hemihypertrophy associated with Wiedemann-Beckwith syndrome, Eur J Pediatr source

In the paper

“One particular hot spot mutation has been described to date, which is the low-penetrance tetramerization domain p.R337H mutation in Southern Brazil (14, 37–39).”

What the sources say

• Not checked yetcites [14] Wasserman, 2012, Towards an understanding of the role of p53 in adrenocortical carcinogenesis, Mol Cell Endocrinol source
• Not checked yetcites [37] Custódio, 2012, Molecular epidemiology of adrenocortical tumors in southern Brazil, Mol Cell Endocrinol source
• Not checked yetcites [38] Latronico, 2001, An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors, J Clin Endocrinol Metab source
• Not checked yetcites [39] Ribeiro, 2001, An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma, Proc Natl Acad Sci U S A source

In the paper

“Associated adrenal lesions, mainly ACAs and uni- or bilateral hyperplasia, occur in 20% to 55% of MEN1 cases (45–48).”

What the sources say

• Not checked yetcites [45] Gibril, 2004, Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature, Medicine (Baltimore) source
• Not checked yetcites [46] Skogseid, 1995, Adrenal lesion in multiple endocrine neoplasia type 1, Surgery source
• Not checked yetcites [47] Waldmann, 2007, Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening, Langenbecks Arch Surg source
• Not checked yetcites [48] Gatta-Cherifi, 2012, Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database, Eur J Endocrinol source

In the paper

“Aside from genetic predisposition (see below), no risk factors have been firmly established.”

In the paper

“As observed with other embyronal tumors that exhibit a developmental window of presentation, the cancer risk of children with BWS decreases through adolescence and then remains at the level of the general population.”

In the paper

“However, the contribution of germline TP53 mutations to ACC development in adults had been not well researched until 2 recent studies determined the prevalence of TP53 mutations between 3% and 7% in the adult population (35, 36).”

What the sources say

• Not checked yetcites [35] Herrmann, 2012, TP53 germline mutations in adult patients with adrenocortical carcinoma, J Clin Endocrinol Metab source
• Not checked yetcites [36] Raymond, 2013, Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“Furthermore, there is currently no support for this association from large CAH registries.”

In the paper

“Patients with ACC only rarely present with classical tumor symptoms, such as cachexia or night sweats (3, 10).”

What the sources say

• Not checked yetcites [3] Allolio, 2006, Clinical review: Adrenocortical carcinoma: clinical update, J Clin Endocrinol Metab source
• Not checked yetcites [10] Luton, 1990, Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy, N Engl J Med source

In the paper

“Biochemically or clinically apparent adrenocortical hormone production is evident in up to 45% to 70% (9, 10, 85).”

What the sources say

• Not checked yetcites [9] Fassnacht, 2009, Clinical management of adrenocortical carcinoma, Best Pract Res Clin Endocrinol Metab source
• Not checked yetcites [10] Luton, 1990, Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy, N Engl J Med source
• Not checked yetcites [85] Abiven, 2006, Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients, J Clin Endocrinol Metab source

In the paper

“There are 3 main clinical scenarios in which ACC patients present.”

In the paper

“Another third present with nonspecific symptoms due to local tumor growth, such as abdominal or flank pain, abdominal fullness, or early satiety (9, 10).”

What the sources say

• Not checked yetcites [9] Fassnacht, 2009, Clinical management of adrenocortical carcinoma, Best Pract Res Clin Endocrinol Metab source
• Not checked yetcites [10] Luton, 1990, Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy, N Engl J Med source

In the paper

“This hypothesis has now been tested in several phase 1 to phase 3 clinical trials (78).”

What the sources say

• Not checked yetcites [78] NIH

In the paper

“ACC has also been reported in patients with Lynch syndrome (53–56).”

What the sources say

• Not checked yetcites [53] Karamurzin, 2012, Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature, Hum Pathol source
• Not checked yetcites [54] Medina-Arana, 2011, Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome, Fam Cancer source
• Not checked yetcites [55] Berends, 2000, Adrenocortical adenocarcinoma in an MSH2 carrier: coincidence or causal relation?, Hum Pathol source
• Not checked yetcites [56] Broaddus, 2004, Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome, Mod Pathol source

In the paper

“Hypercortisolism is the most common presentation of patients presenting with hormone excess (50%–80% of hormone-secreting ACCs), causing classic symptoms including plethora, diabetes mellitus, muscle weakness/atrophy, and osteoporosis.”

What the sources say

• Not checked yetcites [9] Fassnacht, 2009, Clinical management of adrenocortical carcinoma, Best Pract Res Clin Endocrinol Metab source
• Not checked yetcites [10] Luton, 1990, Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy, N Engl J Med source
• Not checked yetcites [85] Abiven, 2006, Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients, J Clin Endocrinol Metab source

In the paper

“There are several reports of ACCs in patients with familial adenomatous polyposis (FAP), neurofibromatosis type 1, and Werner syndrome (63–72).”

What the sources say

• Not checked yetcites [63] Takazawa, 2004, Unusual double primary neoplasia: adrenocortical and ureteral carcinomas in werner syndrome, Urol Int source
• Not checked yetcites [64] Seki, 1992, Loss of normal allele of the APC gene in an adrenocortical carcinoma from a patient with familial adenomatous polyposis, Hum Genet source
• Not checked yetcites [65] Wakatsuki, 1998, Adrenocortical tumor in a patient with familial adenomatous polyposis: a case associated with a complete inactivating mutation of the APC gene and unusual histological features, Hum Pathol source
• Not checked yetcites [66] Painter, 1985, Adrenal adenomas and adrenal carcinomas in association with hereditary adenomatosis of the colon and rectum, Cancer source
• Not checked yetcites [67] Fienman, 1970, Neurofibromatosis in childhood, J Pediatr source
• Not checked yetcites [68] Sørensen, 1986, Long-term follow-up of von Recklinghausen neurofibromatosis. Survival and malignant neoplasms, N Engl J Med source
• Not checked yetcites [69] Else, 2010, Overview of genetic syndromes associated with adrenocortical cancer
• Not checked yetcites [70] Marshall, 1967, Gardner's syndrome with adrenal carcinoma, Australas Ann Med source
• Not checked yetcites [71] Traill, 1995, Adrenal carcinoma in a patient with Gardner's syndrome: imaging findings, AJR Am J Roentgenol source
• Not checked yetcites [72] Wagner, 2005, Pediatric adrenal cortical carcinoma: brain metastases and relationship to NF-1, case reports and review of the literature, J Neurooncol source

In the paper

“However, the co-occurrence of a rare tumor and a fairly common genetic syndrome make this association unconvincing at this point (76).”

What the sources say

• Not checked yetcites [76] Barzon, 2007, The role of 21-hydroxylase in the pathogenesis of adrenal masses: review of the literature and focus on our own experience, J Endocrinol Invest source

In the paper

“For 40% to 60% of patients, the major presenting complaints are symptoms and signs of hormone excess (3, 9, 10).”

What the sources say

• Not checked yetcites [3] Allolio, 2006, Clinical review: Adrenocortical carcinoma: clinical update, J Clin Endocrinol Metab source
• Not checked yetcites [9] Fassnacht, 2009, Clinical management of adrenocortical carcinoma, Best Pract Res Clin Endocrinol Metab source
• Not checked yetcites [10] Luton, 1990, Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy, N Engl J Med source

In the paper

“It cannot, however, distinguish benign from malignant adrenocortical lesions.”

What the sources say

• Not checked yetcites [113] Khan, 2003, 11C-Metomidate PET imaging of adrenocortical cancer, Eur J Nucl Med Mol Imaging source

In the paper

“ACCs are typically large tumors upon clinical presentation, often measuring more than 6 cm in diameter (Figure 3 and Table 4) (97).”

What the sources say

• Not checked yetcites [97] Johnson, 2009, Adrenal mass imaging with multidetector CT: pathologic conditions, pearls, and pitfalls, Radiographics source

In the paper

“ACCs can be distinguished from lipid-rich ACAs, which tend to be small, homogeneous masses that measure ≤10 HU on unenhanced CT or demonstrate loss of signal on chemical-shift MRI (102).”

What the sources say

• Not checked yetcites [102] Haider, 2004, Chemical shift MR imaging of hyperattenuating (>10 HU) adrenal masses: does it still have a role?, Radiology source

In the paper

“The latter will also give an estimate of the extent of hypercortisolism (93).”

What the sources say

• Not checked yetcites [93] Nieman, 2008, The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab source

In the paper

“Autonomous aldosterone secretion (which classically leads to hypertension and hypokalemia) is rare in ACC (85, 86).”

What the sources say

• Not checked yetcites [85] Abiven, 2006, Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients, J Clin Endocrinol Metab source
• Not checked yetcites [86] Seccia, 2005, Aldosterone-producing adrenocortical carcinoma: an unusual cause of Conn's syndrome with an ominous clinical course, Endocr Relat Cancer source

In the paper

“In a meta-analysis of published data to determine the diagnostic utility of [18F]FDG PET/CT for distinguishing benign from malignant adrenal tumors, [18F]FDG PET/CT had sensitivity of 97% and specificity of 91% (109).”

What the sources say

• Not checked yetcites [109] Sundin, 2012, Imaging of adrenal masses with emphasis on adrenocortical tumors, Theranostics source

In the paper

“Therefore, hypokalemia and hypertension are commonly observed in ACC patients with hypercortisolism.”

In the paper

“Most ACCs are diagnosed at an advanced stage, although this might be predicted to change in the near future due to the persistently increasing use of abdominal imaging procedures.”

In the paper

“At the time of presentation, ACCs are generally large tumors, measuring on average 10 to 13 cm (9, 85, 89).”

What the sources say

• Not checked yetcites [9] Fassnacht, 2009, Clinical management of adrenocortical carcinoma, Best Pract Res Clin Endocrinol Metab source
• Not checked yetcites [85] Abiven, 2006, Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients, J Clin Endocrinol Metab source
• Not checked yetcites [89] Sturgeon, 2006, Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy?, J Am Coll Surg source

In the paper

“More commonly, mineralocorticoid effects are mediated by high cortisol levels or possibly steroid precursors with mineralocorticoid activity, such as 11-deoxycorticosterone (87, 88).”

What the sources say

• Not checked yetcites [87] Egoshi, 1998, 11-Deoxycorticosterone-producing adrenocortical carcinoma, Urol Int source
• Not checked yetcites [88] Müssig, 2005, Adrenocortical carcinoma producing 11-deoxycorticosterone: a rare cause of mineralocorticoid hypertension, J Endocrinol Invest source

In the paper

“The diagnosis of hypercortisolism is usually established by a 1 mg dexamethasone suppression test (DST), midnight salivary cortisol, or elevated 24-hour urine free cortisol.”

In the paper

“This classification system has been recently challenged due to several shortcomings and the newly introduced European Network for the Study of Adrenal Tumors (ENSAT) system became widely adopted by the ACC community due to the better reflection of ENSAT stage to patient outcome (91).”

What the sources say

• Not checked yetcites [91] Fassnacht, 2009, Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification, Cancer source

In the paper

“Frequently, very high cortisol levels in ACC saturate the renal HSD11B2 system, resulting in glucocorticoid-mediated mineralocorticoid receptor activation.”

In the paper

“[18F]FDG PET/CT, however, cannot distinguish ACC from metastases, lymphoma, or pheochromocytoma, which also exhibit high metabolic activity (109).”

What the sources say

• Not checked yetcites [109] Sundin, 2012, Imaging of adrenal masses with emphasis on adrenocortical tumors, Theranostics source

In the paper

“[11C]MTO PET can distinguish tumors of adrenocortical origin from noncortical lesions (113).”

What the sources say

• Not checked yetcites [113] Khan, 2003, 11C-Metomidate PET imaging of adrenocortical cancer, Eur J Nucl Med Mol Imaging source

In the paper

“ACAs demonstrate a greater contrast washout than adrenal nonadenomas (103, 104).”

What the sources say

• Not checked yetcites [103] Caoili, 2000, Delayed enhanced CT of lipid-poor adrenal adenomas, AJR Am J Roentgenol source
• Not checked yetcites [104] Slattery, 2006, Adrenocortical carcinoma: contrast washout characteristics on CT, AJR Am J Roentgenol source

In the paper

“In a study of 77 patients with surgically proven diagnosis of ACA or ACC, [18F]FDG PET/CT had a sensitivity of 100% and specificity of 88% in distinguishing benign from malignant lesions by using cutoff value above 1.45 for adrenal to liver maximum standardized uptake value (SUV).”

What the sources say

• Not checked yetcites [108] Groussin, 2009, 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients, J Clin Endocrinol Metab source

In the paper

“Moreover, in an independent cohort, the study confirmed the diagnostic utility of 6 loci (5q, 7p, 11p, 13q, 16q, and 22q) in the differentiation of ACA and ACC (sensitivity, 100%; specificity, 83%) (188).”

What the sources say

• Not checked yetcites [188] Barreau, 2013, Identification of a CpG Island Methylator Phenotype in Adrenocortical Carcinomas, J Clin Endocrinol Metab source

In the paper

“An initial study identified elevated expression of genes involved in cell proliferation in ACCs, such as IGF2, compared with increased expression of steroidogenic genes in ACAs (steroidogenic cluster) (190).”

What the sources say

• Not checked yetcites [190] de Fraipont, 2005, Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic acid microarrays identifies several candidate genes as markers of malignancy, J Clin Endocrinol Metab source

In the paper

“A recent study of 51 ACCs and 84 ACAs revealed hypermethylation of promoters in ACCs with correlation to poor survival”

What the sources say

• Not checked yetcites [188] Barreau, 2013, Identification of a CpG Island Methylator Phenotype in Adrenocortical Carcinomas, J Clin Endocrinol Metab source

In the paper

“The study confirmed increased alterations in ACCs (44%) compared with ACAs (10%).”

What the sources say

• Not checked yetcites [188] Barreau, 2013, Identification of a CpG Island Methylator Phenotype in Adrenocortical Carcinomas, J Clin Endocrinol Metab source

In the paper

“Giordano et al (192) identified unique transcriptionally activated (12q and 5q) and repressed (11q, 1p, and 17p) chromosomal regions in 33 ACCs vs 22 ACAs in a microarray study”

What the sources say

• Not checked yetcites [192] Giordano, 2009, Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling, Clin Cancer Res source

In the paper

“ACAs and ACCs have distinct expression profiles (174, 190–192).”

What the sources say

• Not checked yetcites [174] Giordano, 2003, Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis, Am J Pathol source
• Not checked yetcites [190] de Fraipont, 2005, Gene expression profiling of human adrenocortical tumors using complementary deoxyribonucleic acid microarrays identifies several candidate genes as markers of malignancy, J Clin Endocrinol Metab source
• Not checked yetcites [191] de Reyniès, 2009, Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival, J Clin Oncol source
• Not checked yetcites [192] Giordano, 2009, Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling, Clin Cancer Res source

In the paper

“The key feature that distinguishes ACC from ACA, short of the presence of metastatic disease, is the presence of invasion.”

In the paper

“Expression levels of BUB1B and PINK1 alone identified subgroups of ACCs with different overall survival, regardless of tumor stage.”

What the sources say

• Not checked yetcites [191] de Reyniès, 2009, Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival, J Clin Oncol source

In the paper

“In another study, cluster analysis of ACCs again revealed 2 distinct groups with different genetic signatures and concomitant distinct clinical outcomes.”

What the sources say

• Not checked yetcites [191] de Reyniès, 2009, Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival, J Clin Oncol source

In the paper

“Similarly, the expression levels of DLG7 and PINK1 identified subgroups of ACCs with distinct disease-free survival, regardless of tumor grade (191).”

What the sources say

• Not checked yetcites [191] de Reyniès, 2009, Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival, J Clin Oncol source

In the paper

“A recent study of 55 adrenal samples (6 normal tissues, 22 ACAs, and 27 ACCs) similarly determined an miRNA expression signature unique to ACC (198). The investigation identified 14 upregulated miRNAs and 9 downregulated miRNAs unique to ACC.”

What the sources say

• Not checked yetcites [198] Soon, 2009, miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer, Clin Cancer Res source

In the paper

“These findings were later validated in a separate cohort of adult patients (193).”

What the sources say

• Not checked yetcites [193] Fragoso, 2012, Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients, Eur J Endocrinol source

In the paper

“Levels of miR-184, miR-503, and miR-511 alone were able to distinguish benign from malignant adrenal tumors (specificity, 80%–97%; sensitivity, 100%) (197).”

What the sources say

• Not checked yetcites [197] Tömböl, 2009, Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA, tissue-specific target prediction, and pathway analysis, Endocr Relat Cancer source

In the paper

“LOH in the gene encoding p16ink/p14arf, CDKN2A is observed in a subset of ACCs.”

What the sources say

• Not checked yetcites [205] Pilon, 1999, Inactivation of the p16 tumor suppressor gene in adrenocortical tumors, J Clin Endocrinol Metab

In the paper

“Examination of TP53 in 89 adrenal tumors revealed loss of heterozygosity (LOH) at the 17p13 in 11 of 13 ACCs and 23 of 76 ACAs (203).”

What the sources say

• Not checked yetcites [203] Gicquel, 1997, Molecular markers for malignancy in adrenocortical tumors, Horm Res source

In the paper

“80% to 90% of all ACCs show very high IGF2 expression (∼100-fold over normal and ACA) (174, 218–220).”

What the sources say

• Not checked yetcites [174] Giordano, 2003, Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis, Am J Pathol source
• Not checked yetcites [218] Ilvesmäki, 1993, Insulin-like growth factors (IGFs) and their receptors in adrenal tumors: high IGF-II expression in functional adrenocortical carcinomas, J Clin Endocrinol Metab
• Not checked yetcites [219] De Fraipont, 2002, Transcription profiling of benign and malignant adrenal tumors by cDNA macro-array analysis, Endocr Res source
• Not checked yetcites [220] Erickson, 2001, Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms, Endocr Pathol source

In the paper

“Furthermore, the combined treatment of NCI-H295 cells with IGF-1R antagonists and mitotane resulted in a synergistic antiproliferative effect in vitro and in vivo in tumor xenografts (223, 227).”

What the sources say

• Not checked yetcites [223] Almeida, 2008, Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors, J Clin Endocrinol Metab source
• Not checked yetcites [227] Barlaskar, 2009, Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“However, simple overexpression of IGF2 was insufficient to initiate adrenocortical tumorigenesis.”

In the paper

“Perturbation of the IGF2 locus, with upregulation of maternally imprinted genes (IGF2), and downregulation of paternally imprinted genes (H19 and CDKN1C), is frequently observed in ACCs (226).”

What the sources say

• Not checked yetcites [226] Libé, 2005, Molecular genetics of adrenocortical tumours, from familial to sporadic diseases, Eur J Endocrinol source

In the paper

“In the hepatocarcinoma cell line HepG2, observational studies revealed the oncogenic potential of miR-483 through inhibition of apoptotic regulatory genes PUMA/BBC3 (201).”

What the sources say

• Not checked yetcites [201] Veronese, 2010, Oncogenic role of miR-483-3p at the IGF2/483 locus, Cancer Res source

In the paper

“In an NCI-H295 xenograft mouse model, IGF pathway inhibition by the small-molecule inhibitor NVP-AEW541 and the monoclonal IGF-1R antibody IMCA12 showed an antitumor effect.”

What the sources say

• Not checked yetcites [223] Almeida, 2008, Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors, J Clin Endocrinol Metab source
• Not checked yetcites [227] Barlaskar, 2009, Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“Of note, there was no overlap of LOH and mutations in the same tumors.”

What the sources say

• Not checked yetcites [203] Gicquel, 1997, Molecular markers for malignancy in adrenocortical tumors, Horm Res source

In the paper

“Pediatric ACCs reveal an ∼20-fold overexpression of IGF2.”

In the paper

“Moreover, miR-483 is located in an intron of IGF2.”

What the sources say

• Not checked yetcites [198] Soon, 2009, miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer, Clin Cancer Res source
• Not checked yetcites [200] Patterson, 2011, MicroRNA profiling of adrenocortical tumors reveals miR-483 as a marker of malignancy, Cancer source

In the paper

“However, 11p15 LOH has been shown to be a stronger predictor for shorter disease-free survival than simple levels of IGF2 overexpression (184).”

What the sources say

• Not checked yetcites [184] Gicquel, 2001, Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors, Cancer Res

In the paper

“This is in contrast with LOH of 11q13, which has been identified in ∼83% of samples (185).”

What the sources say

• Not checked yetcites [185] Kjellman, 1999, Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16, J Clin Endocrinol Metab

In the paper

“mutational analysis of the effector of the canonical Wnt pathway, the β-catenin gene, CTNNB1, has identified activating point mutations in over 25% of both ACAs and ACCs in children and adults (149, 206–208).”

What the sources say

• Not checked yetcites [149] Tissier, 2005, Mutations of β-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors, Cancer Res source
• Not checked yetcites [206] Gaujoux, 2008, Wnt/β-catenin and 3′,5′-cyclic adenosine 5′-monophosphate/protein kinase A signaling pathways alterations and somatic β-catenin gene mutations in the progression of adrenocortical tumors, J Clin Endocrinol Metab source
• Not checked yetcites [207] Tadjine, 2008, Detection of somatic β-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD), Clin Endocrinol (Oxf) source
• Not checked yetcites [208] Tadjine, 2008, Frequent mutations of β-catenin gene in sporadic secreting adrenocortical adenomas, Clin Endocrinol (Oxf) source

In the paper

“MEN1 (located on 11q13) somatic mutations are unusual in sporadic ACC.”

In the paper

“Conditional knockout of β-catenin in a transgenic mouse resulted in the absence of the adrenal gland at embryonic day 18.5.”

What the sources say

• Not checked yetcites [228] Kim, 2008, Targeted disruption of β-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex, Development source

In the paper

“Thirty to 40 LAs are generally sufficient to reach some level of proficiency with the technique (252).”

What the sources say

• Not checked yetcites [252] Guerrieri, 2008, The learning curve in laparoscopic adrenalectomy, J Endocrinol Invest source

In the paper

“However, an earlier clinical trial using bevacizumab, an anti-VEGF monoclonal antibody, proved to be ineffective (239).”

What the sources say

• Not checked yetcites [239] Wortmann, 2010, Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma, Eur J Endocrinol source

In the paper

“Moreover, inactivating mutations of AXIN2 (a component of the β-catenin destruction complex) have also been described in some adrenocortical tumors (231).”

What the sources say

• Not checked yetcites [231] Chapman, 2011, Identification of genetic alterations of AXIN2 gene in adrenocortical tumors, J Clin Endocrinol Metab source

In the paper

“High tumor grade (>20 mitoses per HPF) is also an unfavorable prognostic indicator (245).”

What the sources say

• Not checked yetcites [245] Miller, 2010, Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade, Langenbecks Arch Surg source

In the paper

“some recent studies identified cortisol production as an adverse prognostic factor (12, 85, 244).”

What the sources say

• Not checked yetcites [12] Wajchenberg, 2000, Adrenocortical carcinoma: clinical and laboratory observations, Cancer source
• Not checked yetcites [85] Abiven, 2006, Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients, J Clin Endocrinol Metab source
• Not checked yetcites [244] Gonzalez, 2007, Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma, Surgery source

In the paper

“Furthermore, mutational analysis of the β-catenin gene CTNNB1 identified activating point mutations in both ACAs and ACCs (149, 206–208).”

What the sources say

• Not checked yetcites [149] Tissier, 2005, Mutations of β-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors, Cancer Res source
• Not checked yetcites [206] Gaujoux, 2008, Wnt/β-catenin and 3′,5′-cyclic adenosine 5′-monophosphate/protein kinase A signaling pathways alterations and somatic β-catenin gene mutations in the progression of adrenocortical tumors, J Clin Endocrinol Metab source
• Not checked yetcites [207] Tadjine, 2008, Detection of somatic β-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD), Clin Endocrinol (Oxf) source
• Not checked yetcites [208] Tadjine, 2008, Frequent mutations of β-catenin gene in sporadic secreting adrenocortical adenomas, Clin Endocrinol (Oxf) source

In the paper

“Naturally, age at diagnosis is correlated with decreased overall survival (243).”

What the sources say

• Not checked yetcites [243] Assié, 2007, Prognostic parameters of metastatic adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“Mariniello et al (240) reported marked growth inhibition using sorafenib and everolimus, for VEGFR1–2 and mammalian target of rapamycin inhibition, respectively, suggesting potential antiangiogenic and antitumor effects.”

What the sources say

• Not checked yetcites [240] Mariniello, 2012, Combination of sorafenib and everolimus impacts therapeutically on adrenocortical tumor models, Endocr Relat Cancer source

In the paper

“The fact that both nuclear β-catenin accumulation and activating CTNNB1 mutations are present in ACAs as well as in ACCs suggests that WNT activation may be an early step in adrenocortical tumorigenesis, which precedes malignant transformation.”

In the paper

“Elevated VEGF levels were identified in blood samples from ACC patients (237, 238).”

What the sources say

• Not checked yetcites [237] de Fraipont, 2000, Expression of the angiogenesis markers vascular endothelial growth factor-A, thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations, J Clin Endocrinol Metab
• Not checked yetcites [238] Kolomecki, 2001, Usefulness of VEGF, MMP-2, MMP-3 and TIMP-2 serum level evaluation in patients with adrenal tumours, Endocr Regul

In the paper

“Despite preoperative diagnostics, approximately 25% of stage 3 cases are initially suspected to be stage 2 ACC but ultimately found to have microscopic extension through the adrenal capsule.”

What the sources say

• Not checked yetcites [246] Miller, 2012, Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy, Surgery source

In the paper

“Furthermore, activation of β-catenin as well as TP53 inactivation predicted poor outcome in one study of 51 samples (232).”

What the sources say

• Not checked yetcites [232] Ragazzon, 2010, Transcriptome analysis reveals that p53 and β-catenin alterations occur in a group of aggressive adrenocortical cancers, Cancer Res source

In the paper

“In addition, overexpression of VEGFR type 2 in ACC samples was observed by immunohistochemistry (239).”

What the sources say

• Not checked yetcites [239] Wortmann, 2010, Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma, Eur J Endocrinol source

In the paper

“Moreover, gene expression profiling studies revealed overexpression of β-catenin target genes such as ENC1, suggesting a role of active β-catenin signaling in ACCs (174).”

What the sources say

• Not checked yetcites [174] Giordano, 2003, Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis, Am J Pathol source

In the paper

“The increased expression of VEGF correlates with the expression of IGF2 (192).”

What the sources say

• Not checked yetcites [192] Giordano, 2009, Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling, Clin Cancer Res source

In the paper

“Immunohistochemical analysis of 39 adrenal tumors revealed accumulation of β-catenin in 10 of 26 ACAs and in 11 of 13 ACCs, consistent with stabilized and hence activated β-catenin (149).”

What the sources say

• Not checked yetcites [149] Tissier, 2005, Mutations of β-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors, Cancer Res source

In the paper

“Mice with constitutive activation of the Wnt signaling pathway obtained by adrenal-specific Apc knockout develop adrenal hyperplasia and adenomas by 30 weeks of life.”

What the sources say

• Not checked yetcites [143] Heaton, 2012, Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and β-catenin, Am J Pathol source

In the paper

“Tumor extent (eg, stage), specifically the presence of distant metastasis and number of organs involved in metastatic disease, confers a worse prognosis (243, 244).”

What the sources say

• Not checked yetcites [243] Assié, 2007, Prognostic parameters of metastatic adrenocortical carcinoma, J Clin Endocrinol Metab source
• Not checked yetcites [244] Gonzalez, 2007, Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma, Surgery source

In the paper

“Unfortunately, most ACCs are removed by low-volume and less experienced adrenal surgeons (253).”

What the sources say

• Not checked yetcites [253] Park, 2009, Outcomes from 3144 adrenalectomies in the United States: which matters more, surgeon volume or specialty?, Arch Surg source

In the paper

“Local recurrence and peritoneal carcinomatosis was more common in the LA group.”

What the sources say

• Not checked yetcites [251] Gonzalez, 2005, Laparoscopic resection of adrenal cortical carcinoma: a cautionary note, Surgery source
• Not checked yetcites [257] Grubbs, 2010, Recurrence of adrenal cortical carcinoma following resection: surgery alone can achieve results equal to surgery plus mitotane, Ann Surg Oncol source

In the paper

“On the other hand, no adrenal phenotype is observed in the adrenal-specific Igf2 overexpression mouse model.”

What the sources say

• Not checked yetcites [143] Heaton, 2012, Progression to adrenocortical tumorigenesis in mice and humans through insulin-like growth factor 2 and β-catenin, Am J Pathol source

In the paper

“Mitotane remains the only drug approved by the U.S. Food and Drug Administration and European Medicine Executive Agency for treatment of ACC (15).”

What the sources say

• Not checked yetcites [15] Schteingart, 2005, Management of patients with adrenal cancer: recommendations of an international consensus conference, Endocr Relat Cancer source

In the paper

“although LA may be technically feasible (even for large tumors) (263, 264)”

What the sources say

• Not checked yetcites [263] Castillo, 2008, Laparoscopic adrenalectomy for adrenal masses: does size matter?, Urology source
• Not checked yetcites [264] Palazzo, 2006, Long-term outcome following laparoscopic adrenalectomy for large solid adrenal cortex tumors, World J Surg source

In the paper

“In a study by Leboulleux et al (258), peritoneal carcinomatosis occurred in only 25% of patients treated by OA, as opposed to 60% of patients who underwent LA.”

What the sources say

• Not checked yetcites [258] Leboulleux, 2010, Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis?, Eur J Endocrinol source

In the paper

“The evidence that patients with ACC remain at high risk for tumor recurrence despite complete surgical tumor excision has fueled the search for adjuvant therapies.”

In the paper

“The number of organs involved by tumor at the time of the first metastasis is a predictor of survival (243, 265).”

What the sources say

• Not checked yetcites [243] Assié, 2007, Prognostic parameters of metastatic adrenocortical carcinoma, J Clin Endocrinol Metab source
• Not checked yetcites [265] Erdogan, 2013, The role of surgery in the management of recurrent adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“In summary, existing data are inconclusive and more studies are needed to better judge the equivalence of LA to OA.”

In the paper

“Mitotane leads with relative specificity to a destruction of the inner zones of the adrenal cortex, the zona fasciculata, and zona reticularis.”

In the paper

“Even with ostensibly complete resections, rates of local recurrence have typically ranged from at least 19% to 34% in those patients with no residual disease after surgery (244, 267, 270).”

What the sources say

• Not checked yetcites [244] Gonzalez, 2007, Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma, Surgery source
• Not checked yetcites [267] Bellantone, 1997, Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma, Surgery source
• Not checked yetcites [270] Icard, 1992, Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery, Surgery

In the paper

“In contrast, other studies reported evidence that LA may be comparable to OA in patients with stage 1 and 2 ACC based on no significant difference in recurrence-free survival (259, 260).”

What the sources say

• Not checked yetcites [259] Lombardi, 2012, Open versus endoscopic adrenalectomy in the treatment of localized (stage I/II) adrenocortical carcinoma: results of a multiinstitutional Italian survey, Surgery source
• Not checked yetcites [260] Porpiglia, 2001, Transperitoneal laparoscopic adrenalectomy: experience in 72 procedures, J Endourol source

In the paper

“The outcomes after surgical resection alone have remained suboptimal (11, 244, 267, 269–273).”

What the sources say

• Not checked yetcites [11] Bilimoria, 2008, Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors, Cancer source
• Not checked yetcites [244] Gonzalez, 2007, Response to mitotane predicts outcome in patients with recurrent adrenal cortical carcinoma, Surgery source
• Not checked yetcites [267] Bellantone, 1997, Role of reoperation in recurrence of adrenal cortical carcinoma: results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma, Surgery source

In the paper

“In contrast, those patients with high-grade tumors benefit less from reresection, because other sites of disease often appear quickly.”

In the paper

“High local recurrence rates after seemingly complete resections underscore the difficulty of achieving adequate margins during surgery.”

In the paper

“because type of operative approach likely has a much smaller role in the development of distant metastases.”

In the paper

“Tumor grade influences the decision for reoperation because it correlates with survival (243, 245).”

What the sources say

• Not checked yetcites [243] Assié, 2007, Prognostic parameters of metastatic adrenocortical carcinoma, J Clin Endocrinol Metab source
• Not checked yetcites [245] Miller, 2010, Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade, Langenbecks Arch Surg source

In the paper

“Active metabolites produced by adrenal mitochondria, in turn, covalently bind to mitochondrial proteins hypothesized to inhibit mitochondrial respiration (285).”

What the sources say

• Not checked yetcites [285] Sinsheimer, 1987, Mitotane (1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane) metabolism in perfusion studies with dog adrenal glands, Drug Metab Dispos source

In the paper

“Furthermore, mitotane metabolites inhibit several enzymes in the adrenocortical steroidogenesis pathway, mainly at the level of the cholesterol side-chain cleavage enzymes CYP11A1 (which appears to be one of the covalently bound mitotane targets) and CYP11B1 (286, 287).”

What the sources say

• Not checked yetcites [286] Cai, 1997, Adrenal proteins bound by a reactive intermediate of mitotane, Cancer Chemother Pharmacol source
• Not checked yetcites [287] Lindhe, 2002, Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis, J Clin Endocrinol Metab

In the paper

“Although TSH and free T3 levels are often unchanged, free T4 levels decrease.”

In the paper

“Neurological side effects are the main limiting side effect.”

In the paper

“Due to CBG induction and increased cortisol metabolism, neither plasma level nor 24-hour urine excretion are entirely reliable for treatment monitoring.”

In the paper

“Gonadotropins are unchanged.”

In the paper

“The most important prognostic factor is the mitotane plasma level (295).”

What the sources say

• Not checked yetcites [295] Terzolo, 2013, Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection, Eur J Endocrinol source

In the paper

“Cytotoxic chemotherapy is currently a mainstay of treatment for advanced and metastasized ACC.”

In the paper

“A study using sunitinib, which is metabolized by CYP3A4, raised concerns that several of the study subjects did not reach therapeutic levels of this drug (302, 304).”

What the sources say

• Not checked yetcites [302] van Erp, 2011, Mitotane has a strong and a durable inducing effect on CYP3A4 activity, Eur J Endocrinol source
• Not checked yetcites [304] Kroiss, 2012, Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial, J Clin Endocrinol Metab source

In the paper

“Possibly due to the relative increase in SHBG as well as inhibition of 5α-reductase by mitotane, male patients might develop gynecomastia.”

In the paper

“The efficacy of mitotane therapy in the setting of not completely resectable, metastasized, or recurrent ACC is well established.”

In the paper

“Use of these parameters is limited by the effects of mitotane on cortisol levels and cortisol metabolism and need to be interpreted with caution.”

In the paper

“It has recently become clear that mitotane is a very strong inducer of the drug-metabolizing microsomal liver and gut enzyme CYP3A4 (299, 301–303).”

What the sources say

• Not checked yetcites [299] Chortis, 2013, Mitotane therapy in adrenocortical cancer induces CYP3A4 and inhibits 5α-reductase, explaining the need for personalized glucocorticoid and androgen replacement, J Clin Endocrinol Metab source
• Not checked yetcites [301] Kroiss, 2011, Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma, Clin Endocrinol (Oxf) source
• Not checked yetcites [302] van Erp, 2011, Mitotane has a strong and a durable inducing effect on CYP3A4 activity, Eur J Endocrinol source
• Not checked yetcites [303] van Herwaarden, 2007, Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism, J Clin Invest source

In the paper

“Overt adrenal insufficiency is rare under treatment with mifepristone (326).”

What the sources say

• Not checked yetcites [326] Fleseriu, 2012, Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome, J Clin Endocrinol Metab source

In the paper

“The most data for targeted therapy exist for the IGF-1R antagonists.”

In the paper

“[123I]IMTO single-photon emission CT imaging showed high tracer uptake in tissue of adrenocortical origin (110), suggesting that [131I]IMTO represents a suitable compound for targeted radionuclide therapy.”

What the sources say

• Not checked yetcites [110] Hahner, 2008, [123I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes, J Clin Endocrinol Metab source

In the paper

“Another powerful inhibitor of steroidogenesis at the level of CYP11B1 is metyrapone (321)”

What the sources say

• Not checked yetcites [321] Hartzband, 1988, Assessment of hypothalamic-pituitary-adrenal (HPA) axis dysfunction: comparison of ACTH stimulation, insulin-hypoglycemia and metyrapone, J Endocrinol Invest source

In the paper

“The reasons for these findings are induction of CYP3A4 by mitotane and metabolism of sunitinib by the same enzyme (301, 304).”

What the sources say

• Not checked yetcites [301] Kroiss, 2011, Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical management of adrenocortical carcinoma, Clin Endocrinol (Oxf) source
• Not checked yetcites [304] Kroiss, 2012, Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial, J Clin Endocrinol Metab source

In the paper

“Three other studies found radiotherapy to be ineffective on the basis of experiences in 2, 3, and 5 patients, respectively (275, 340, 341).”

What the sources say

• Not checked yetcites [275] Pommier, 1992, An eleven-year experience with adrenocortical carcinoma, Surgery
• Not checked yetcites [340] Bodie, 1989, The Cleveland Clinic experience with adrenal cortical carcinoma, J Urol source
• Not checked yetcites [341] Kasperlik-Załuska, 1995, Adrenocortical carcinoma. A clinical study and treatment results of 52 patients, Cancer source

In the paper

“The first study investigated figtilimumab, a fully human monoclonal antibody directed toward IGF-1R (316). Treatment-related toxicities were generally mild and mainly included hyperglycemia, nausea, fatigue, and anorexia.”

What the sources say

• Not checked yetcites [316] Haluska, 2010, Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma, Cancer Chemother Pharmacol source

In the paper

“Even at doses much lower than those used for anesthesia, etomidate is a powerful inhibitor of CYP11B1 and CYP11B2 (324, 325).”

What the sources say

• Not checked yetcites [324] Drake, 1998, Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing's syndrome and peritonitis, J Clin Endocrinol Metab
• Not checked yetcites [325] Schulte, 1990, Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing's syndrome and dose-response relationship in normal subjects, J Clin Endocrinol Metab source

In the paper

“The generally disappointing results of studies targeting the IGF-1R system together with a critical review of in vitro results and studies in transgenic mice have sparked a recent discussion on the contribution of IGF-2 to adrenal tumorigenesis (318).”

What the sources say

• Not checked yetcites [318] Drelon, 2013, Adrenocortical cancer and IGF2: is the game over or our experimental models limited?, J Clin Endocrinol Metab source

In the paper

“A study using the multikinase inhibitor sunitinib led to stable disease in 5 of 35 patients (304).”

What the sources say

• Not checked yetcites [304] Kroiss, 2012, Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial, J Clin Endocrinol Metab source

In the paper

“The shortcomings of such conclusions were accurately detailed by Percarpio and Knowlton (335), who described how these studies relied on poorly documented results in a low number of heterogeneous patients.”

What the sources say

• Not checked yetcites [335] Percarpio, 1976, Radiation therapy of adrenal cortical carcinoma, Acta Radiol Ther Phys Biol source

In the paper

“Eight of 14 patients had stable disease as their best response.”

What the sources say

• Not checked yetcites [316] Haluska, 2010, Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma, Cancer Chemother Pharmacol source

In the paper

“[131I]IMTO treatment in 11 patients with advanced ACC resulted in median progression-free survival for 14 months in 6 patients who responded to therapy (319).”

What the sources say

• Not checked yetcites [319] Hahner, 2012, [131I]Iodometomidate for targeted radionuclide therapy of advanced adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“Unfortunately, results of these studies have been disappointing so far (Table 11).”

In the paper

“In another study, cixutumab in combination with temsirolimus was evaluated in 10 patients with ACC. Stable disease in 4 patients, at a maximum lasting for greater than 8 months, was the best response (317).”

What the sources say

• Not checked yetcites [317] Naing, 2012, Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing's sarcoma family tumors, Clin Cancer Res source

In the paper

“They all share the criticism that they have been evaluated in heavily pretreated patients, who often have been or were on concurrent mitotane therapy, which may have blurred some of their potential effects.”

In the paper

“Although molecular targeted therapy based on basic research findings is intriguing, unfortunately, none of the studies so far have shown definitive effectiveness that would make any of the substances a good candidate for further exploration or routine use in ACC therapy.”

In the paper

“RFA has been successfully employed in the palliative setting, rendering patients free of liver metastasis (352).”

What the sources say

• Not checked yetcites [352] Ripley, 2011, Liver resection and ablation for metastatic adrenocortical carcinoma, Ann Surg Oncol source

In the paper

“For palliative cases, there are numerous although primarily anecdotal reports that radiotherapy can adequately relieve patient symptoms.”

In the paper

“Furthermore, there is emerging evidence from the surgical literature that adequate lymph node dissection at the time of adrenalectomy likely improves both rates of disease recurrence and survival (249).”

What the sources say

• Not checked yetcites [249] Reibetanz, 2012, Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma, Ann Surg source

In the paper

“More modern studies have consistently shown adequate palliation in most patients treated.”

In the paper

“A study that stands in contrast to these others is that of Venkatesh et al (26), who found that palliative radiotherapy was effective in only 6 of 26 patients.”

What the sources say

• Not checked yetcites [26] Venkatesh, 1989, Adrenal cortical carcinoma, Cancer source

In the paper

“Importantly, this study also demonstrated the feasibility of treating unresectable disease with definitive radiotherapy (247).”

What the sources say

• Not checked yetcites [247] Sabolch, 2011, Adjuvant and definitive radiotherapy for adrenocortical carcinoma, Int J Radiat Oncol Biol Phys source

In the paper

“Magee et al (337) found that palliative radiotherapy was effective in 4 of 6 patients, either reducing the mass of their tumors or ameliorating symptoms of hormone excess associated with a functional tumor.”

What the sources say

• Not checked yetcites [337] Magee, 1987, Adrenal cortical carcinoma: survival after radiotherapy, Clin Radiol source

In the paper

“Henley et al (274) found that palliative radiotherapy reduced symptoms or tumor burden in 4 of 10 patients.”

What the sources say

• Not checked yetcites [274] Henley, 1983, Adrenal cortical carcinoma–a continuing challenge, Surgery

In the paper

“Patients treated with adjuvant radiotherapy after surgery had a 20% local recurrence rate.”

What the sources say

• Not checked yetcites [247] Sabolch, 2011, Adjuvant and definitive radiotherapy for adrenocortical carcinoma, Int J Radiat Oncol Biol Phys source

In the paper

“There were no significant differences found in local control or survival between these 2 groups (338).”

What the sources say

• Not checked yetcites [338] Habra, 2013, A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma, J Clin Endocrinol Metab source

In the paper

“This detailed 12 instances of palliative radiotherapy, all of which resulted in relief of symptoms or reduction in palpable tumor size, regardless of the substantial variation in the location and characteristics of their metastatic disease (335).”

What the sources say

• Not checked yetcites [335] Percarpio, 1976, Radiation therapy of adrenal cortical carcinoma, Acta Radiol Ther Phys Biol source

In the paper

“King and Lack (351) described a decrease in pain in half of the 12 patients treated”

What the sources say

• Not checked yetcites [351] King, 1979, Adrenal cortical carcinoma: a clinical and pathologic study of 49 cases, Cancer source

In the paper

“In this series, 22 patients had painful osseous metastases, and 17 patients (77%) experienced adequate palliation of pain after radiotherapy with dosages totaling 10 to 60 Gy.”

What the sources say

• Not checked yetcites [336] Polat, 2009, Radiotherapy in adrenocortical carcinoma, Cancer source

In the paper

“Similarly, in Europe, a recent analysis of the Dutch Adrenal Network Registry found that radiotherapy is employed in only 8% of patients (296).”

What the sources say

• Not checked yetcites [296] Hermsen, 2011, Plasma concentrations of o,p'DDD, o,p'DDA, and o,p'DDE as predictors of tumor response to mitotane in adrenocortical carcinoma: results of a retrospective ENS@T multicenter study, J Clin Endocrinol Metab source

In the paper

“In the United States, it is used in approximately 10% of cases, according to analyses of both the National Cancer Data Base and the SEER program (4, 11, 90).”

What the sources say

• Not checked yetcites [4] Kebebew, 2006, Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?, World J Surg source
• Not checked yetcites [11] Bilimoria, 2008, Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors, Cancer source
• Not checked yetcites [90] Paton, 2006, Outcomes of adrenal cortical carcinoma in the United States, Surgery source

In the paper

“Hermsen et al (333) found similar outcomes, as all 6 patients that they treated for bone metastases were successfully palliated.”

What the sources say

• Not checked yetcites [333] Hermsen, 2010, Response to radiation therapy in adrenocortical carcinoma, J Endocrinol Invest source

In the paper

“They reported that all 5 patients that they treated received adequate relief of their pain (334).”

What the sources say

• Not checked yetcites [334] Markoe, 1991, Radiation therapy for adjunctive treatment of adrenal cortical carcinoma, Am J Clin Oncol source