Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report.

For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.

Clinical and Pathological Predictors of Death for Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority presented as European Network for the Study of Adrenal Tumors (ENSAT) III or IV (22.9% and 31.2%, respectively), and the overall mortality rate was 54.6%. Independent predictors of death were elevated secretion of cortisol (HR = 2.0), androstenedione (HR = 2.2), estradiol (HR = 2.8), 17-OH progesterone (HR = 2.0), and 11-deoxycortisol (HR = 5.1), higher Weiss (HR = 4.3), modified Weiss (HR = 4.4), and Helsinki scores (HR = 12.0), advanced ENSAT stage (HR = 27.1), larger tumor size (HR = 2.7), higher Ki-67 percentage (HR = 2.3), and incomplete surgical resection (HR = 2.5). Mitosis greater than 5/50 high-power field (HR = 5.6), atypical mitosis (HR = 2.3), confluent necrosis (HR = 15.4), venous invasion (HR = 2.8), and capsular invasion (HR = 2.4) were also identified as independent predictors of death. Knowing the risk factors for ACC's mortality may help determine the best treatment option.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

The effect of hormonal secretion on survival in adrenocortical carcinoma: A multi-center study.

BACKGROUND: Current evidence suggests that cortisol secreting adrenocortical carcinoma has worse prognosis compared to non-secreting adrenocortical carcinoma. However, the effect of other secretory subtypes is unknown. METHODS: This multicenter study within the American-Australian-Asian Adrenal Alliance included adults with adrenocortical carcinoma (1997-2020). We compared overall survival and disease-free survival among cortisol secreting, mixed cortisol/androgen secreting, androgen secreting, and non-secreting adrenocortical carcinoma. RESULTS: Of the 807 patients (mean age 50), 719 included in the secretory subtype analysis: 24.5% were cortisol secreting, 13% androgen secreting, 28% mixed cortisol/androgen, 32.5% non-secreting, and 2% were mineralocorticoid secreting. Median overall survival and disease-free survival for the entire cohort were 60 and 9 months, respectively. Median overall survival was 36 months for cortisol, 30 for mixed, 60 for androgen secreting, and 115 for non-secreting adrenocortical carcinoma, P < .01. Median disease-free survival was 7 months for cortisol, 8 for mixed, 10 for androgen, and 12 for non-secreting adrenocortical carcinoma, P = .06. On multivariable analysis of age, sex, Ki67%, secretory subtype, stage, resection, and adjuvant therapy, predictors of worse overall survival were older age, higher Ki67%, stage IV, mixed secreting, R1, and no adjuvant therapy, P < .05. On subgroup analysis of R0 resection, predictors of worse overall survival included older age and higher Ki67%. Ki67% ≥40, stage III and cortisol secretion were associated with worse disease-free survival. CONCLUSION: Mixed cortisol/androgen secreting adrenocortical carcinoma was associated with worse overall survival, while cortisol or androgen secreting alone were not. Notably, among patients after R0 resection, secretory subtype did not affect overall survival. Cortisol secreting adrenocortical carcinoma demonstrated worse disease-free survival. Ki67% remained a strong predictor of worse overall survival and disease-free survival independent of stage.

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.

CONTEXT: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. OBJECTIVE: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. METHODS: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

Cytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival.

CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.

Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas.

OBJECTIVE: Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. PATIENTS AND METHODS: This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. RESULTS: Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. CONCLUSIONS: Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.

Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism.

Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.

Internal validation and decision curve analysis of a preoperative nomogram predicting a postoperative complication in pheochromocytoma surgery: An international study.

OBJECTIVES: To develop a preoperative nomogram that would predict the risk of a postoperative complication for pheochromocytoma patients undergoing adrenalectomy using an international database. METHODS: We retrospectively analyzed preoperative variables and postoperative outcomes in patients who underwent adrenalectomy for pheochromocytoma in three institutions from 2000 to 2017. Internal validation of a generated nomogram was carried out with receiver operating characteristics, calibration plots, and decision curve analyses. RESULTS: A total of 153 patients who had undergone 166 adrenalectomies were included in the study. Overall, post-adrenalectomy complications were seen in 30% of patients, whereas 9.6% of patients sustained a Clavien ≥3a complication. Independent predictors of a complication were a history of hypertension, body mass index, tumor size, and Charlson Comorbidity Index score. On internal validation, the multivariable model generated a nomogram that predicted a postoperative complication or clinically hemodynamic event with an area under the curve of 0.86, showed good calibration and had an overall net benefit. CONCLUSIONS: An internally validated nomogram combining body mass index, Charlson Comorbidity Index score and tumor size can predict the probability of a post-adrenalectomy complication in those with and without hypertension. The model, the first of its kind in pheochromocytoma surgery, identifies patients at risk of a postoperative complication at the time of their presentation with pheochromocytoma.

Perioperative outcomes of laparoscopic, robotic, and open approaches to pheochromocytoma.

While multiple studies have demonstrated that minimally invasive surgical (MIS) techniques are a safe and efficacious approach to adrenalectomy for pheochromocytomas (PC), these studies have only been small comparative studies. The aim of this multi-institutional study is to compare perioperative outcomes between open and MIS, stratified by robotic and conventional laparoscopic, techniques in the surgical management of PC. We retrospectively evaluated patients who underwent adrenalectomy for PCs from 2000 to 2017 at three different institutions. Clinical, perioperative, and pathologic parameters were analyzed using t test, Chi square, and Fisher exact statistical measures. Of the 156 adrenalectomy cases performed, 26 (16.7%) were with an open approach and 130 (83.3%) using MIS techniques. Of the MIS procedures, 41 (31.5%) were performed robotically and 89 (68.5%) performed laparoscopically without robotic assistance. Demographic and clinical parameters were similar between the open and MIS groups. Patients, who underwent MIS procedure had a lower complication rate (p = 0.04), shorter hospitalization (p = 0.02), shorter operative time (p < 0.001), and less blood loss (p = 0.002) than those who underwent open surgical resection. Conventional laparoscopic and robotic operative approaches resulted in similar complication rates, length of hospitalization, and blood loss. Our study is one of the largest cohorts comparing the perioperative outcomes between conventional laparoscopic and robotic adrenalectomies in patients with PC. Our results support that MIS techniques have potentially lower morbidity compared to open techniques, while laparoscopic and robotic approaches have similar perioperative outcomes.

KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear. OBJECTIVE: To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA. METHODS: We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases. RESULTS: KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004). CONCLUSION: The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.

Predictors of complication after adrenalectomy

ABSTRACT Purpose: To investigate risk factors for complications in patients undergoing adrenalectomy. Materials and Methods: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. Results: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p<0.001) and BMI (p=0.009) were independent predictors of intra-operative complications. Pathological diagnosis (p<0.001) and Charlson score (p=0.013) were independent predictors of death. Conclusion: Diligent care is needed with older patients, with multiple comorbidities and harboring unfavorable adrenal disorders (adrenocortical carcinoma and pheocromocytoma), who have greater risk of post-operative complications. Patients with elevated BMI and larger tumors have higher risk of intra, but not of post-operative complications.

Predictors of complication after adrenalectomy.

PURPOSE: To investigate risk factors for complications in patients undergoing adrenalectomy. MATERIALS AND METHODS: A retrospective search of our institutional database was performed of patients who underwent adrenalectomy, between 2014 and 2018. Clinical parameters and adrenal disorder characteristics were assessed and correlated to intra and post-operative course. Complications were analyzed within 30-days after surgery. A logistic regression was performed in order to identify independent predictors of morbidity in patients after adrenalectomy. RESULTS: The files of 154 patients were reviewed. Median age and Body Mass Index (BMI) were 52-years and 27.8kg/m2, respectively. Mean tumor size was 4.9±4cm. Median surgery duration and estimated blood loss were 140min and 50mL, respectively. There were six conversions to open surgery. Minor and major post-operative complications occurred in 17.5% and 8.4% of the patients. Intra-operative complications occurred in 26.6% of the patients. Four patients died. Mean hospitalization duration was 4-days (Interquartile Range: 3-8). Patients age (p=0.004), comorbidities (p=0.003) and pathological diagnosis (p=0.003) were independent predictors of post-operative complications. Tumor size (p<0.001) and BMI (p=0.009) were independent predictors of intra-operative complications. Pathological diagnosis (p<0.001) and Charlson score (p=0.013) were independent predictors of death. CONCLUSION: Diligent care is needed with older patients, with multiple comorbidities and harboring unfavorable adrenal disorders (adrenocortical carcinoma and pheocromocytoma), who have greater risk of post-operative complications. Patients with elevated BMI and larger tumors have higher risk of intra, but not of post-operative complications.

Adjuvant radiotherapy for the primary treatment of adrenocortical carcinoma: are we offering the best?

ABSTRACT Purpose: To evaluate the role of ARDT after surgical resection of ACC. Materials and Methods: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. Results: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). Conclusions: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

Adjuvant radiotherapy for the primary treatment of adrenocortical carcinoma: Are we offering the best?

PURPOSE: To evaluate the role of ARDT after surgical resection of ACC. MATERIALS AND METHODS: Records of patients from our institutional ACC database were retrospectively assessed. A paired comparison analysis was used to evaluate the oncological outcomes between patients treated with surgery followed by ARDT or surgery only (control). The endpoints were LRFS, RFS, and OS. A systematic review of the literature and meta-analysis was also performed to evaluate local recurrence of ACC when ARDT was used. RESULTS: Ten patients were included in each Group. The median follow-up times were 32 months and 35 months for the ARDT and control Groups, respectively. The results for LRFS (p=0.11), RFS (p=0.92), and OS (p=0.47) were similar among subsets. The mean time to present with local recurrence was significantly longer in the ARDT group compared with the control Group (419±206 days vs. 181±86 days, respectively; p=0.03). ARDT was well tolerated by the patients; there were no reports of late toxicity. The meta-analysis, which included four retrospective series, revealed that ARDT had a protective effect on LRFS (HR=0.4; CI=0.17-0.94). CONCLUSIONS: ARDT may reduce the chance and prolong the time to ACC local recurrence. However, there were no benefits for disease recurrence control or overall survival for patients who underwent this complementary therapy.

Presentation and surgery outcomes in elderly with pheocromocytoma: a comparative analysis with Young patients.

PURPOSE: To evaluate the presentation and early surgical outcomes of elderly patients undergoing adrenalectomy for phaeochromocytoma. PATIENTS AND METHODS: A retrospective search was performed of our adrenal disorders database for patients who underwent surgery for phaeochromocytoma or paraganglioma between 2009 and 2014. Patients >60 years old were classified as elderly. The clinical manifestations, intraoperative course, and early postoperative outcomes of elderly patients were compared to those of younger individuals (<60 years old). RESULTS: The mean (±standard deviation) age in the older (n=10) and younger (n=36) groups was 69.6±5.3 years and 34.0±12.9 years. Germ-line mutations were more common in younger patients (50.0% versus 0%; p=0.004), whereas incidental lesions were more common in the elderly (40.0% versus 5.3%; p=0.003). In both groups, surgery was most commonly performed by videolaparoscopy (90% in the elderly and 82% in the younger group), with similar intraoperative anesthetic and surgical outcomes. Postoperatively, the older group more commonly received vasoactive drugs (60.0% versus 10.5%; p<0.001) and had a longer intensive care unit stay (3.1±2.8 versus 1.4±1.0 days; p=0.014), more clinical complications (60% versus 18.9%; p=0.01), and longer hospital stay (10.2±8.4 versus 5.7±4.9 days; p=0.028). CONCLUSIONS: Although all patients received the same preoperative preparation, the elderly group exhibited a slower and more complicated recovery after adrenalectomy. Meticulous perioperative care should be used in the elderly when treating phaeochromocytoma; nevertheless, adrenalectomy is a relatively safe procedure in this patient population.

Presentation and surgery outcomes in elderly with pheocromocytoma: a comparative analysis with young patients

ABSTRACT Purpose: To evaluate the presentation and early surgical outcomes of elderly patients undergoing adrenalectomy for phaeochromocytoma. Patients and Methods: A retrospective search was performed of our adrenal disorders database for patients who underwent surgery for phaeochromocytoma or paraganglioma between 2009 and 2014. Patients >60 years old were classified as elderly. The clinical manifestations, intraoperative course, and early postoperative outcomes of elderly patients were compared to those of younger individuals (<60 years old). Results: The mean (±standard deviation) age in the older (n=10) and younger (n=36) groups was 69.6±5.3 years and 34.0±12.9 years. Germ-line mutations were more common in younger patients (50.0% versus 0%; p=0.004), whereas incidental lesions were more common in the elderly (40.0% versus 5.3%; p=0.003). In both groups, surgery was most commonly performed by videolaparoscopy (90% in the elderly and 82% in the younger group), with similar intraoperative anesthetic and surgical outcomes. Postoperatively, the older group more commonly received vasoactive drugs (60.0% versus 10.5%; p<0.001) and had a longer intensive care unit stay (3.1±2.8 versus 1.4±1.0 days; p=0.014), more clinical complications (60% versus 18.9%; p=0.01), and longer hospital stay (10.2±8.4 versus 5.7±4.9 days; p=0.028). Conclusions: Although all patients received the same preoperative preparation, the elderly group exhibited a slower and more complicated recovery after adrenalectomy. Meticulous perioperative care should be used in the elderly when treating phaeochromocytoma; nevertheless, adrenalectomy is a relatively safe procedure in this patient population.

The Use of Three-dimensional Printers for Partial Adrenalectomy: Estimating the Resection Limits.

OBJECTIVE: To avoid hormonal replacement after partial adrenalectomy (PA), establishing the precise limit of an adrenal gland resection is essential. Herein, we evaluated the use of three-dimensional (3D) adrenal gland printing and volumetry measurement before PA to improve the determination of the remnant gland volume. METHODS: Concomitant total adrenalectomy and a contralateral PA were performed in a patient with primary macronodular adrenal hyperplasia that exhibited mild hypercortisolism, arterial hypertension, and diabetes. Before surgery, a 3D replica of the adrenal gland to be partially resected was printed and given to the surgeon. The volumetry of the gland was measured by computed tomography 3D image reconstruction. RESULTS: No postoperative complications were noted. Immediately after the surgery, the patient initiated corticosteroid replacement, which was interrupted 52 days later. At the 6-month follow-up, the patient stopped using medications for diabetes and reduced the number of antihypertensive medications from 5 to 1. The pre- and postoperative serum cortisol levels were, respectively, 28 and 8.7 mcg/dl (n 5-25 mcg/dl). The pre- and postoperative adrenocorticotropic hormone levels were, respectively, <5 and 88 pg/ml (n 7.2-63 pg/ml). The postoperative adrenal volume was 12% of the total preoperative adrenal volume. CONCLUSION: The use of 3D printing associated with adrenal volumetry might be a useful tool for the surgeon when performing PA, enabling an estimation of the remnant gland volume.

Comparative and prospective analysis of three different approaches for live-donor nephrectomy.

PURPOSE: Living donor nephrectomy is usually performed by a retroperitoneal flank incision. Due to the significant morbidity and long recovery time for a flank incision, anterior extra peritoneal sub-costal and transperitoneal video-laparoscopic methods have been described for donor nephrectomy. We prospectively compare the long-term results of donors as well as functional recipients submitted to these three approaches. MATERIALS AND METHODS: A total of 107 live donor renal transplantations were prospectively evaluated from May 2001 to January 2004. Donors were compared with regard to operative and warm ischemia time, postoperative pain, analgesic requirements, and complications. Recipients were compared with regard to graft function, acute cellular rejection, surgical complications, and graft and recipient survival. RESULTS: The mean operative and warm ischemia times were longer in the video-laparoscopic group (p<0.001), whereas patients of the flank incision group presented more postoperative pain (p=0.035), required more analgesics (p<0.001), had longer hospital stays (p<0.001), and suffered more pain on the 90th day after surgery (p=0.006). In the sub-costal and flank incision groups, there was a larger number of paraesthesias and abdominal wall asymmetries (p<0.001). Recipient groups were demographically comparable and presented similar acute tubular necrosis incidence and delayed graft function. The incidence of acute cellular rejection was higher in the video-laparoscopic and flank incision groups (p=0.013). There was no difference in serum creatinine levels, surgical complications, or recipient or graft survival between groups. CONCLUSIONS: The video-laparoscopic and sub-costal approaches proved to be safe, and to provide donor advantages relative to the flank incision approach. Among recipients, the complication rate, graft survival, and recipient survival were similar in all groups.