Camilo Jimenez

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (76)313.28 Total impact

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    ABSTRACT: Mestastatic pheochromocytoma and paraganglioma (MPP) present clinicians with three major challenges: scarcity, complexity of characterization, and heterogeneous behavior and prognosis. As with the treatment of all neuroendocrine tumors, the control of hormonal symptoms and tumor growth are the main therapeutic objectives in MPP patients. A significant number of MPP patients still die from uncontrolled hormone secretion. In addition, the management of MPP remains palliative. Steps forward include proper characterization of MPP patients at large cancer referral centers with multidisciplinary teams; improved strategies to stratify patients prognostically; and implementation of trials within national and international networks. Progress in the molecular characterization and staging of MPP constitutes the basis for significant treatment breakthroughs.
    European journal of endocrinology / European Federation of Endocrine Societies. 06/2014;
  • Mimi I Hu, Anita K Ying, Camilo Jimenez
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    ABSTRACT: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer, demonstrating variable behavior from indolent disease to highly aggressive, progressive disease. There are distinguishing phenotypic features of sporadic and hereditary MTC. Activation or overexpression of cell surface receptors and up-regulation of intracellular signaling pathways in hereditary and sporadic MTC are involved in the disease pathogenesis. There has been an exponential rise in clinical trials with investigational agents, leading to approval of 2 medications for progressive, advanced MTC. Developments in understanding the pathogenesis of MTC will hopefully lead to more effective and less toxic treatments of this rare but difficult to treat cancer.
    Endocrinology and metabolism clinics of North America. 06/2014; 43(2):423-442.
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    ABSTRACT: Sorafenib has proven efficacy in advanced differentiated thyroid cancer (DTC), but many patients must reduce the dose or discontinue treatment because of toxicity. The tolerability and efficacy of lower starting doses of sorafenib for DTC remain largely unstudied.Methods.We retrospectively examined overall survival, time to treatment failure, time to progression, discontinuation rates, and dose-reduction and interruption rates in patients with metastatic DTC treated with first-line sorafenib outside of a clinical trial. Two patient groups were compared; group 1 received the standard starting dose of 800 mg/day, and group 2 received any dose lower than 800 mg/day.Results.We included 75 adult patients, with 51 in group 1 and 24 in group 2. Mean age at diagnosis was 54 years, and 56% were male. The most common histologies included 43% papillary thyroid cancer of the conventional type, 15% papillary thyroid cancer of the follicular variant, and 15% Hürthle cell carcinoma. Time to treatment failure was 10 months (95% confidence interval [CI]: 5.6-14.3) in group 1 and 8 months (95% CI: 3.4-12.5) in group 2 (p = .56). Median overall survival was 56 months (95% CI: 30.6-81.3) in group 1 and 30 months (95% CI: 16.1-43.8) in group 2 (p = .08). Rates of discontinuation due to disease progression were 79% in group 1 and 91% in group 2, and 21% in group 1 and 9% in group 2 (p = .304) stopped treatment because of toxicity. Dose-reduction rates were 59% and 43% (p = .29), and interruption rates were 65% and 67% (p = .908) in group 1 and group 2, respectively.Conclusion.Efficacy and tolerability of sorafenib in treatment-naïve DTC patients does not appear to be negatively influenced by lower starting daily doses.
    The Oncologist 04/2014; · 4.10 Impact Factor
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    ABSTRACT: Objective: To describe and compare the clinical, biochemical, radiologic, and pathologic features of adrenal pheochromocytoma-ganglioneuroma (PC-GN) composites with the features of isolated pheochromocytomas (PCs) and adrenal ganglioneuromas (AGNs).Methods: We reviewed data for PC-GN composite cases seen at a single tertiary center between 1993 and 2012 and compared them with isolated AGN and relatively similar median-size PC.Results: Nine PC-GN composites were included. Median age at diagnosis was 52 yr (range, 28-83 yr) for PC-GN compared with 55 yr (range, 24-78) for PC patients and 40 yr (range 18-64) for AGN. Similar to PCs, all PC-GNs composites were associated with catecholamine overproduction while AGNs were non-functioning. On pathology, the median tumor sizes were 7 cm (range, 2.5-13 cm) for PC-GN tumors, 6.5 cm (range, 3.5-7 cm) for PCs, and 8 cm (range, 3.2-20) for AGNs. On CT imaging, PC-GN composites and PCs were heterogeneous, with both having significantly higher post-contrast density values than did AGNs, which typically looked homogeneous and had a progressive enhancement pattern without contrast washout in most cases.Conclusions: The presence of a PC component significantly increased tumor heterogeneity and post-contrast density values. CT imaging could be very helpful in distinguishing AGNs from both PC-GN and PC tumors, but only pathologic examination can yield the diagnosis. Clinically and radiologically, PC-GN composites were indistinguishable from PCs and need to be managed similarly.
    Endocrine Practice 03/2014; · 2.49 Impact Factor
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    ABSTRACT: Context: Sorafenib, a tyrosine kinase inhibitor, is a common first line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. Objective: To determine the efficacy of salvage therapy after first-line sorafenib failure. Design: Retrospective review at MD Anderson Cancer Center from January 2005 to May 2013. Patients: Patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). Patients who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). Outcome Measures: Progression-free survival (PFS), best response, and median OS. Results: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients was 37 months; median OS was significantly longer with salvage therapy compared to sorafenib alone (58 vs. 28 months, p = 0.013). In group 2, 17 patients were evaluable for best response, although 2 patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response (PR) in 2/15 (13%), stable disease (SD) in 10/15 (67%), and progressive disease (PD) in 3/15 (20%) patients. With salvage therapy, PRs were seen in 7/17 (41%) and SD in 10/17 (59%) patients. Median PFS was 7.4 months with first-line sorafenib only and 11.4 months with salvage therapy. Salvage therapy included sunitinib (4), pazopanib (3), cabozantinib (4), lenvatinib (3), and vemurafenib (3). Conclusions: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.
    The Journal of clinical endocrinology and metabolism 03/2014; · 6.50 Impact Factor
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    ABSTRACT: Background: Age-related risk of MTC development in presymptomatic carriers of lower risk germline RET mutations is uncertain; such data may aid counseling patients regarding timing of thyroidectomy. Methods: From an institutional database and an exhaustive literature review, we identified 679 patients with American Thyroid Association level A or B mutations who were identified due to family screening (index cases of MTC were excluded to minimize selection bias). We evaluated age at thyroidectomy or last evaluation if no thyroidectomy, preoperative calcitonin level (elevated or not), codon mutated and outcome (MTC vs. no MTC after thyroidectomy or no clinical evidence of MTC if thyroid intact). Data were used to estimate the cumulative prevalence of MTC and/or assess likelihood of MTC stratified by codon. After exclusion of cases with missing data or small representation, 503 patients were analyzed consisting of codons 533, 609, 611, 618, 620, 791, and 804. Results: 236 patients had MTC. Cumulative prevalence and median time to MTC varied by codon and within ATA risk levels (p<0.0001). Patients with a codon 620 mutation were 2.8-6.9 times more likely to have MTC than other level B mutation carriers, and 5.1-21.7 times more likely than level A mutation carriers included in our focus population. The youngest median time to MTC was 19 years for codon 620 and the oldest was 56 years for codon 611. Cumulative prevalence of MTC by age 20 was 10% or lower for codons 533, 609, 611, 791, and 804. By age 50, it varied from 18% for codon 791 to 95% for codon 620. An elevated preoperative calcitonin level strongly predicted MTC on final pathology, though false negative rates varied by codon (p<0.0001). Positive predictive values ranged from 76% to 100% by codon with an overall positive predictive value of 87% across codons Conclusions: This study offers a better understanding of the age-related development of MTC in lower risk RET mutation carriers, provides evidence of further distinctions between lower risk mutations within ATA subgroups, and clarifies the clinical significance of codon 791 mutations. The data support individualized "codon-based" management approaches coupled with clinical data such as calcitonin levels.
    Thyroid: official journal of the American Thyroid Association 03/2014; · 2.60 Impact Factor
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    ABSTRACT: Subdiaphragmatic paraganglioma is a rare neuroendocrine tumor for which scarce data exist regarding long-term patient outcome following resection. The aim of this study was to determine the association of surgical resection with survival. A retrospective study at a tertiary care center was performed. Demographics, genetics, histology, and operative details were reviewed. Patients were grouped according to margin status (R0, R1, or R2) and survival calculated. A total of 50 patients with subdiaphragmatic paragangliomas underwent primary resection from 1999 to 2012. Median age at operation was 46 years, with a median tumor size of 6.0 cm. Of these patients, 30 (60 %) had a R0 resection, 11 (22 %) had a R1 resection, and 9 (18 %) had a R2 resection. There was no operative mortality, and 17 (34 %) patients had metastatic disease. Six (12 %) patients died, four (8 %) of whom had metastatic disease. Univariate analysis identified that age >50 years (p = 0.02) and undergoing a R2 resection (p = 0.03) were associated with a shorter overall survival (OS). Those with metastases at some point after their initial diagnosis had a shorter disease-free survival (DFS) than those without metastases (p = 0.04). Of 27 patients tested, 12 (44 %) had a germline succinyl dehydrogenase B (SDHB) mutation. SDHB immunohistochemistry identified 18 patients (of 27 who underwent staining) who had loss of SDHB expression in which 7 of 11 patients (63 %) who underwent genetic testing had a genetic mutation. Surgical resection of subdiaphragmatic paraganglioma is safe. Survival was longest in patients who were younger, with no metastases, or had a R0 or R1 resection. Patients who test negative for a germline mutation should undergo SDHB immunostaining to identify potential hereditary carriers missed by current genetic testing.
    World Journal of Surgery 01/2014; · 2.23 Impact Factor
  • Mimi I. Hu, Anita K. Ying, Camilo Jimenez
    Endocrinology and Metabolism Clinics of North America. 01/2014; 43(2):423–442.
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    ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients [45 at MD Anderson (16.4%)]. For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P= 0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV, respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.
    European Journal of Endocrinology 10/2013; · 3.14 Impact Factor
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    ABSTRACT: Context:Pheochromocytoma (PHEO) occurs in 50% of patients with multiple endocrine neoplasia type 2 (MEN2). It is unknown if association with PHEO is associated with more aggressive medullary thyroid cancer (MTC).Objective:To present our experience with MEN2 PHEO and evaluate whether PHEO impacts MTC overall survival in patients with RET codon 634 mutations.Design:We performed a retrospective chart review of MEN2 patients at MD Anderson Cancer Center from 1960 through 2012.Patients:The study group comprised of 85 patients (group 1) with MEN2 associated PHEO. Of these, 59 patients (subgroup 1) with RET codon 634 mutations were compared to 48 patients (group 2) with RET codon 634 mutations, but without MEN 2-associated PHEO.Main Outcome Measures:Of 85 patients with MEN2 and PHEO, 70 had MEN2A and 15 had MEN2B. Median age at PHEO diagnosis was 32 years. The initial manifestation of MEN2 was MTC in 60% of patients, synchronous MTC and PHEO in 34%, and PHEO in 6% of patients. 72% of patients had bilateral PHEO, and most tumors were synchronous (82%). Subgroup analysis of MEN2 patients with and without PHEO, who were carriers of RET codon 634, the most common mutation with PHEO, showed no significant differences in the stage of MTC at initial diagnosis. The median follow-up time for patients with PHEO was 249 months and without PHEO was 67 months (p<.01). Survival analyses among RET 634 carriers didn't show shorter survival for patients with PHEO. The median survival time for patients with PHEO was 499 months and without PHEO was 444 months (p<.05).Conclusions:PHEO in MEN2 patients are usually bilateral and unlikely to be metastatic. Subgroup analysis of patients RET 634 mutations with and without PHEO, showed that PHEO was not associated with a more advanced stage of MTC at diagnosis or a shorter survival.
    The Journal of clinical endocrinology and metabolism 09/2013; · 6.50 Impact Factor
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    ABSTRACT: Adrenal ganglioneuroma (AGN) is a rare neurogenic tumor that can mimic other adrenal neoplasms. Limited information, mostly derived from small cases series, is available for AGN. A retrospective review for AGNs seen at a tertiary referral center describing important features to distinguish AGN from other adrenal neoplasms. Out of 53 ganglioneuromas, 27 were AGNs. Median age was 31yr (range, 1.7-64 yr) and median tumor size was 8 cm (range, 1.5-20 cm). Seventeen AGNs (63 %) were detected incidentally and 9 patients (33%) presented with abdominal/ back discomfort. Catecholamine levels, available for 21 patients, were normal. On computed tomography (CT), most AGNs were homogenous and well-circumscribed with a median density of 32.5 Hounsfield Units (HU) on unenhanced CT; 40 HU on post- contrast venous phase; and 66.5 HU on delayed post-contrast phase. On magnetic resonance imaging (MRI), AGNs had hypointense signal on T1-weighted images with heterogeneous hyperintense signal on T2-weighted images. In 4 patients, there was no tumor growth during median follow-up of 48 months (range, 21-60 months). One patient had malignant peripheral nerve sheath tumor arising from AGN. Thirteen patients with resected AGN had no recurrence during a median follow-up of 50 months (range, 2-135 months). We herein describe the largest AGN series reported to date. Isolated AGNs do not produce catecholamines and have CT imaging characteristics that can help in distinguishing them from other adrenal and para-adrenal neoplasms. The natural history of AGNs is usually benign, although local extra-adrenal extension or malignant transformation can rarely occur. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2013; · 3.40 Impact Factor
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    ABSTRACT: Background Genetic testing in head and neck paragangliomas (HNPG) can have profound implications in patient and family counseling. Methods Retrospective review was performed of patients with HNPG at a cancer care center from 1970 to present. Patient demographics, disease patterns, outcomes, and genetic mutations were analyzed. Results We identified 26 patients with available genetic testing results. Sixteen had mutations. Succinate dehydrogenase gene, sub unit D (SDHD) accounted for 75% of mutations, of which P81L accounted for 75%. The remainder had SDHB mutations. Patients with mutations were younger (average age 39.5 years versus 48.4 years), 63% (versus 40%) had multiple tumors, 94% (60%) had at least one carotid body tumor, and family history was positive in 38% (20%). Conclusion Patients suspected of heritable HNPG should undergo testing first at the SDHD and SDHB loci, and those with younger age, multiple tumors, carotid body tumors, and positive family history are more likely to have mutations.
    Journal of neurological surgery. Part B, Skull base. 08/2013; 74(4):236-40.
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    ABSTRACT: Pheochromocytomas (PHs) and sympathetic paragangliomas (SPGs) are rare neuroendocrine tumors. Approximately 17 % of these tumors are malignant, but because no molecular or histologic markers for malignancy exist, patients are often diagnosed with malignant PHs or SPGs after unresectable disease has formed. Patients with progressive metastatic tumors and overwhelming symptoms are currently treated with systemic chemotherapy and radiopharmaceutical agents such as metaiodobenzylguanidine. These therapies lead to partial radiographic response, disease stabilization, and symptomatic improvement in approximately 40 % of patients, and systemic chemotherapy is associated with a modest improvement in overall survival duration. However, over the past decade, substantial progress has been made in clinical, biochemical, and radiographic diagnosis of PHs and SPGs. Approximately 50 % of patients with malignant PHs and SPGs have been found to carry hereditary germline mutations in the succinate dehydrogenase subunit B gene (SDHB), and anti-angiogenic agents such as sunitinib have been found to potentially play a role in the treatment of malignant disease, especially in patients with SDHB mutations. In some patients, treatment with sunitinib has been associated with partial radiographic response, disease stabilization, decreased fluorodeoxyglucose uptake on positron emission tomography, and improved blood pressure control. These findings have led to the development of prospective clinical trials of new targeted therapies for metastatic disease. Here, we provide an updated review of the clinical and genetic predictors of malignant disease, radiographic diagnosis of malignant disease, and information from the most relevant studies of systemic therapies, as well as proposed treatment guidelines for patients with metastatic or potentially malignant PHs and SPGs.
    Current Oncology Reports 05/2013; · 3.33 Impact Factor
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    ABSTRACT: Context:Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and reduced survival. There is limited information on the clinical effects of BM and SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL).Objectives:We studied the prevalence and clinical characteristics of BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE development.Design:Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011.Results:Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001).Conclusions:BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.
    The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
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    ABSTRACT: The ideal surgical management of hereditary pheochromocytomas includes planning for a potential metachronous bilateral presentation and the possibility of lifelong steroid dependence if bilateral adrenalectomy is needed. An intact and viable cortical remnant after bilateral pheochromocytoma resection can eliminate the necessity for steroid dependency, but can increase the risk of pheochromocytoma recurrence. We retrospectively reviewed outcomes of all patients with a diagnosis of hereditary pheochromocytomas treated at our tertiary cancer institution from 1962-2011, with subset analysis of patients undergoing a cortical-sparing procedure in the setting of bilateral adrenalectomy. Of the ninety-six patients who underwent adrenalectomy for hereditary pheochromocytomas, 47 presented with bilateral disease. In 15 of the 49 patients (30%) who originally underwent unilateral adrenalectomy, pheochromocytoma developed in the contralateral gland at a median of 8.2 years (range 1 to 20 years) after the initial diagnosis. There were 4 recurrences in 55 cortical-sparing remnants (7%) and 3 recurrences in the adrenal bed after 101 intended total adrenal resections (3%) (p = 0.24). Total bilateral adrenalectomy was performed in 25 patients and acute adrenal insufficiency developed in 5 (20%) of those patients. An intended cortical-sparing adrenalectomy was performed in 39 patients and acute adrenal insufficiency developed in 1 (3%). Of these patients with adequate follow-up, 21 of 27 (78%) were steroid independent at 3-year follow-up. Sex, median age, adrenal vein preservation, metachronous adrenal resection, and bilateral cortical-sparing procedures did not predict steroid independence at 3 years. Cortical-sparing adrenalectomy avoids long-term corticosteroid dependence in the majority of patients with hereditary pheochromocytoma with minimal risk of acute adrenal insufficiency. Recurrence occurs in approximately 7% of adrenal remnants.
    Journal of the American College of Surgeons 02/2013; 216(2):280-9. · 4.50 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) represent a class of small, non-coding RNAs that control gene expression by targeting mRNA and triggering either translational repression or RNA degradation. The objective of our study was to evaluate the involvement of miRNAs in human medullary thyroid carcinoma (MTC) and to identify the markers of metastatic cells and aggressive tumour behaviour. Using matched primary and metastatic tumour samples, we identified a subset of miRNAs aberrantly regulated in metastatic MTC. Deregulated miRNAs were confirmed by quantitative real-time PCR and validated by in situ hybridisation on a large independent set of primary and metastatic MTC samples. Our results uncovered ten miRNAs that were significantly expressed and deregulated in metastatic tumours: miR-10a, miR-200b/-200c, miR-7 and miR-29c were down-regulated and miR-130a, miR-138, miR-193a-3p, miR-373 and miR-498 were up-regulated. Bioinformatic approaches revealed potential miRNA targets and signals involved in metastatic MTC pathways. Migration, proliferation and invasion assays were performed in cell lines treated with miR-200 antagomirs to ascertain a direct role for this miRNA in MTC tumourigenesis. We show that the members of miR-200 family regulate the expression of E-cadherin by directly targeting ZEB1 and ZEB2 mRNA and through the enhanced expression of tumour growth factor β (TGFβ)-2 and TGFβ-1. Overall, the treated cells shifted to a mesenchymal phenotype, thereby acquiring an aggressive phenotype with increased motility and invasion. Our data identify a robust miRNA signature associated with metastatic MTC and distinct biological processes, e.g., TGFβ signalling pathway, providing new potential insights into the mechanisms of MTC metastasis.
    Endocrine Related Cancer 01/2013; 20(6):809-823. · 5.26 Impact Factor
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    ABSTRACT: Posterior retroperitoneoscopic adrenalectomy (PRA) is a minimally invasive procedure offering several advantages over a transabdominal laparoscopic operation. The three-dimensional optics and articulating instrumentation offered by current robotic surgical technology potentially improve this procedure. Robotic-assisted PRA (RA-PRA) was performed in patients meeting standard criteria for minimally invasive adrenalectomy. We prospectively collected demographic, clinical, perioperative, and pathologic data on patients undergoing RA-PRA. Thirty consecutive RA-PRAs were performed in 28 patients (26 unilateral and 2 bilateral). Indications for adrenalectomy included pheochromocytoma (8), hyperaldosteronism (3), hypercortisolism (8), oligometastases (5), and nonfunctional tumors (6). Mean tumor size was 3.8 ± 1.6 cm. Mean body mass index was 30.7 ± 6.5 kg/m(2). Mean operative time was 154 ± 43 minutes for unilateral total adrenalectomy. Four patients with multiple endocrine neoplasia Type 2A-associated pheochromocytomas underwent cortical-preserving procedures. Three patients experienced perioperative complications (one pneumothorax, one urinary retention, one required postoperative blood transfusion). No patient required conversion to an open procedure. Robotic surgical technology is an excellent complement to retroperitoneoscopic adrenalectomy. The three-dimensional view and ergonomic advantages of a robotic procedure promote better visualization and a more flexible approach to dissection. We believe these features may optimize the ability to maintain a vascularized remnant during minimally invasive cortical-sparing adrenalectomy.
    The American surgeon 01/2013; 79(1):84-9. · 0.92 Impact Factor
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    ABSTRACT: Introduction In patients with refractory adrenocorticotropic hormone−dependent Cushing’s syndrome, we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. Methods Clinical data from patients treated 1970-2012 were reviewed retrospectively by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). Results A total of 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n = 21,32%) or SI alone (n = 44,68%). Presenting M scores and source of adrenocorticotropic hormone excess (ectopic versus pituitary) were similar. Both groups improved metabolically after treatment. Over one-third of AEs in the SI+BA group occurred within 12 months of presentation. Half (n = 24, 55%) of the patients treated with SI died (median survival, 24.0 months). Steroid excess contributed to 71% of complications. Six SI+BA patients died (29%), including all 3 patients with recurrent Cushing’s syndrome after BA. Minor perioperative complications occurred in 7 patients (33%). Conclusion Posttreatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early operative intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable Cushing’s syndrome.
    Surgery 01/2013; 154(6):1174–1184. · 3.37 Impact Factor
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    ABSTRACT: Limited data are available about mitotane-nduced hyperlipidemia. We retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma (ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL-c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively. HDL-c, LDL-c, and triglyceride concentrations significantly increased with mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL (P < 0.001), a mean LDL peak of 160.1 mg/dL (P < 0.001), and a mean triglyceride peak (Tg-P) of 216.7 mg/dL (P = 0.042). HDL-P positively correlated with mitotane concentration (r = 0.52, P < 0.001), while LDL-P levels and Tg-P did not. Gender, body mass index, cortisol overproduction, baseline levels of HDL-c, and triglyceride did not predict change in HDL-c. Similar changes were noticed in subgroup analysis after excluding patients who were using lipid-lowering agents. In conclusion, in ACC patients, mitotane caused significant increases in HDL-c that may counteract the deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs.
    International Journal of Endocrinology 01/2013; 2013:624962. · 2.52 Impact Factor
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    ABSTRACT: PURPOSEThe association between oral bisphosphonate (BP) intake and colorectal cancer (CRC) risk has been investigated in several recent studies with conflicting results. We summarized the evidence from the published studies in a categorical, dose-response meta-analysis. METHODS Relevant studies were identified by a search of MEDLINE and EMBASE databases through January 15, 2012. We included studies that reported effect size estimates with 95% CIs for the association between exposure to oral BPs and risk of CRC.ResultsThree case-control studies with a total of 16,998 CRC cases and 108,197 controls and one cohort study with 94,405 individuals exposed to BPs and 283,181 unexposed to BPs were included in meta-analysis. The random effect model meta-analysis suggested reduced risk of CRC with exposure to oral BPs with pooled odds ratio (OR) of 0.87 (95% CI, 0.78 to 0.97). Significant inverse relationship was noted for 10 or more prescriptions categories, with pooled ORs of 0.71 (95% CI, 0.58 to 0.87). Similarly, the analysis for 1 to 3 years of use and more than 3 years of use of BPs suggested a significant inverse relationship, with pooled ORs of 0.76 (95% CI, 0.68 to 0.85) and 0.78 (95% CI, 0.61 to 0.99), respectively. CONCLUSION This meta-analysis suggests that the use of oral BPs at a dose of 10 or more prescriptions or 1 or more years of duration is associated with reduced risk of CRC. Further randomized controlled trials are needed to prove this association.
    Journal of Clinical Oncology 12/2012; · 18.04 Impact Factor

Publication Stats

716 Citations
313.28 Total Impact Points

Institutions

  • 2004–2014
    • University of Texas MD Anderson Cancer Center
      • • Endocrine Neoplasia and Hormonal Disorders
      • • Department of Surgical Oncology
      Houston, Texas, United States
  • 2012
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hospital San Juan de Dios de León
      León, Castille and León, Spain
  • 2005–2011
    • Baylor College of Medicine
      • • Department of Medicine
      • • Division of Diabetes, Endocrinology and Metabolism
      Houston, TX, United States
  • 2009
    • Eastern Virginia Medical School
      • Department of Surgery
      Norfolk, VA, United States
  • 2006
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia