International Histopathology Consensus for Unilateral Primary Aldosteronism.

OBJECTIVE: Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). CONTEXT: Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. PATIENTS AND METHODS: Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. RESULTS: Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. CONCLUSION: The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines.

PURPOSE: Adrenal incidentalomas are being discovered with increasing frequency, and their discovery poses a challenge to clinicians. Despite the 2002 National Institutes of Health consensus statement, there are still discrepancies in the most recent guidelines from organizations representing endocrinology, endocrine surgery, urology and radiology. We review recent guidelines across the specialties involved in diagnosing and treating adrenal incidentalomas, and discuss points of agreement as well as controversy among guidelines. MATERIALS AND METHODS: PubMed®, Scopus®, Embase™ and Web of Science™ databases were searched systematically in November 2019 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to identify the most recently updated committee produced clinical guidelines in each of the 4 specialties. Five articles met the inclusion criteria. RESULTS: There is little debate among the reviewed guidelines as to the initial evaluation of an adrenal incidentaloma. All patients with a newly discovered adrenal incidentaloma should receive an unenhanced computerized tomogram and hormone screen. The most significant points of divergence among the guidelines regard reimaging an initially benign appearing mass, repeat hormone testing and management of an adrenal incidentaloma that is not easily characterized as benign or malignant on computerized tomography. The guidelines range from actively recommending against any repeat imaging and hormone screening to recommending a repeat scan as early as in 3 to 6 months and annual hormonal screening for several years. CONCLUSIONS: After reviewing the guidelines and the evidence used to support them we posit that best practices lie at their convergence and have presented our management recommendations on how to navigate the guidelines when they are discrepant.

Adrenal-sparing surgery: current concepts on a theme from the past.

Adrenal insufficiency represents a debilitating condition which mandates lifelong steroid replacement and which is associated with significant long-term morbidity, due to either inadequate or excessive replacement. The concept of preserving healthy cortical tissue by means of partial adrenalectomy has evolved as a means of avoiding the detrimental consequences of adrenal insufficiency. The advent of advanced technology in adrenal surgery has greatly facilitated the performance of partial adrenalectomy, enabling utilization of this method in an increasing number of endocrine diseases. Hereditary pheochromocytoma, Conn's syndrome, Cushing's syndrome, and non-functional adrenal masses represent the current indications for partial adrenalectomy, although the specific circumstances under which adrenal-sparing surgery should be proposed are still debatable. Partial adrenalectomy can be achieved by all types of minimally invasive surgery. In the absence of randomized, prospective, controlled studies designed to compare laparoscopic, retroperitoneoscopic, and robot-assisted partial adrenalectomy, none of these techniques has as yet been proven to be the gold standard for adrenal-sparing surgery. Apart from indications for surgery, results of surgery, and different types of partial adrenalectomy, controversial topics addressed in this review article include technical aspects such as the volume of residual adrenal tissue needed, ligation of adrenal vein, and means of tumor identification. Discussion of these controversial topics represents an attempt to define the role of partial adrenalectomy in modern adrenal surgery.

Surgery for adrenocortical carcinoma: When and how?

Adrenocortical carcinoma (ACC) is a rare malignancy that is frequently asymptomatic at presentation, yet has a high rate of metastatic disease at the time of diagnosis. Prognosis is overall poor, particularly with cortisol-producing tumors. While the treatment of ACC is guided by stage of disease, complete surgical resection is the most important step in the management of patients with primary, recurrent, or metastatic ACC. Triphasic chest, abdomen, and pelvis computer tomography (CT) scans and 18F flourodeoxyglucose positron emission tomography CT scanning are essential for accurate staging; moreover, MRI may be helpful to identify liver metastasis and evaluate the involvement of adjacent organs for operative planning. Surgical resection with negative margins is the single most important prognostic factor for survival in patients with ACC. To achieve the highest rate of R0 resection, open adrenalectomy is the gold standard surgical approach for confirmed or highly suspected ACC. It is extremely important that the tumor capsule is not ruptured, regardless of the surgical approach used. The best post-operative outcomes (complications and oncologic) are achieved by high-volume surgeons practicing at high-volume centers.

Defining the competencies for laparoscopic transabdominal adrenalectomy: An investigation of intraoperative behaviors and decisions of experts.

BACKGROUND: Safe performance of laparoscopic transabdominal adrenalectomy requires the application of a complex body of knowledge and skills, which are difficult to define, teach, and measure. This qualitative study aims to characterize expert behaviors, decisions, and other cognitive processes required to perform laparoscopic transabdominal adrenalectomy. METHOD: Hierarchical and cognitive task analyses for right and left laparoscopic transabdominal adrenalectomy were performed using semi-structured interviews and field observations of experts. Verbal data was supplemented with published literature, coded and thematically analyzed using constructivist grounded-theory by 2 independent reviewers. RESULTS: A conceptual framework was synthesized. Sixty-eight tasks, 46 cognitive behaviors, and 52 potential errors were identified and categorized into 8 procedural steps and 8 fundamental principles: anticipation, exposure, teamwork or communication, physiology, dissection techniques, oncologic margins, tactical modification, and error recovery. Experts emphasized the importance of creating a 3-dimensional mental model of the anatomy or pathology (eg, aberrant vessels, tumor location) that is consistently fine-tuned throughout the operation, with conscious awareness of danger zones (eg, medial arc). Despite variations in dissection techniques, experts highlighted 2 themes: macrodissection and microdissection, with emphasis on nonlinear motions and effective transitions between the 2 when appropriate. CONCLUSION: This study defines behaviors and competencies that are essential to performing laparoscopic transabdominal adrenalectomy effectively and safely.

Adrenal Venous Sampling: Where Do We Stand?

Adrenal venous sampling is the gold standard test to identify surgically curable primary aldosteronism, but it is markedly underused in clinical practice being perceived as a technically challenging and invasive procedure and, moreover, as difficult to interpret. This review provides updated information on current indications to adrenal venous sampling and how to perform and interpret adrenal venous sampling.

Volume-outcome relationship in adrenal surgery: A review of existing literature.

The relationship between operative volume and perioperative outcomes after several oncologic operations is well documented. Recent studies on adrenalectomy reveal a robust association between higher surgeon volume and improved patient outcomes. Statistical analyses have demonstrated that outcomes are improved when surgeons perform at least six adrenalectomies annually; based on this threshold definition of a 'high-volume' surgeon, more than 80% of adrenalectomies in the United States are performed by 'low-volume' surgeons. When compared to low-volume surgeons, high-volume surgeons on average achieve lower rates of postoperative complications and mortality, as well as a shorter length of hospital stay, and lower cost of hospitalization. There does not appear to be a similar association between hospital adrenalectomy volume and improved patient outcomes; however, there is evidence of benefit for the subset of patients with adrenocortical carcinoma. Despite limitations of existing literature, evidence is sufficient to recommend the referral of patients with adrenal tumors to high-volume surgeons.

Pheochromocytoma and Pregnancy.

Pheochromocytoma during pregnancy, although rare, is a perilous condition. The wellbeing of mother and fetus are at stake if not diagnosed and treated antenatally and timely. The diagnosis is frequently overlooked because of the aspecific nature of signs and symptoms and confusion with pregnancy-related hypertension. Measurements of plasma or urinary free metanephrines have the highest diagnostic accuracy. MRI is preferred over ultrasonography. The optimal time for surgical removal is before 24 weeks of gestation or at/after delivery. Laparoscopic adrenalectomy should be preceded by medical pretreatment. Cesarean delivery is preferred in these patients; vaginal delivery might be considered in selected pretreated patients.

Total and partial laparoscopic adrenalectomy.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Total and partial laparoscopic adrenalectomy

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Minimally invasive approach to the adrenal gland in obese patients with Cushing's syndrome.

Introduction: The combination of Cushing's syndrome and obesity, one of the most common manifestations of the syndrome itself, may be associated with the worsening of post-operative outcomes in case of laparoscopic adrenalectomy. This study focused on the laparoscopic treatment of Cushing's syndrome with the purpose to identify any relevant difference between morbidly obese, mildly obese and non-obese patients.Material and methods: Patients were retrospectively divided into three groups according to their Body Mass Index (BMI). Demographic characteristics, operative and post-operative data were collected. Data about different hemostatic devices were also collected and compared. Differences were analyzed with the Fisher's exact test for categorical variables, and the Mann-Whitney test for continuous variables.Results: No differences were found in operative time (101.5 ± 50.9 min; p = .919), conversion rate (2.6%; p = .655) or length of stay (4.3 ± 2.9 days; p = .886). Complication rate was 3% (p = .32), without any mortality. 95% of patients showed a complete resolution of hypercotisolyism-related symptoms, and a mean BMI reduction of 5 ± 3.2 kg/m2 (follow up = 6.3 ± 4.2 years). Conclusions: Laparoscopic adrenalectomy is safe and feasible in obese patients affected with Cushing's disease and it can lead to the resolution of the related symptoms.

Perioperative Management of Endocrine Active Adrenal Tumors.

Endocrine active adrenal tumors are associated with a relevant risk of complications during surgery, either due to direct hemodynamic effects of the hormone excess or due to hormone related comorbidities. Over the last decades, careful preoperative evaluation and improved peri-interventional medical management of affected patients has resulted in a significant reduction of perioperative complications. In addition, improvement in anesthesia and surgical techniques with the feasibility of laparoscopic adrenalectomy have contributed to reduce morbidity. Nevertheless, there are still several challenges to be considered in the perioperative care of these patients. Due to the rarity of functionally active adrenal tumors, there are no prospective data available to guide clinical management. Accordingly, most recommendations are based on retrospective data analysis, expert opinion or carry weak evidence based on small series or case reports. The aim of this review is to summarize the current knowledge and to suggest practical approaches to reduce perioperative complications in endocrine active adrenal tumors. This review exclusively deals with data from adult patients with functionally active adrenal tumors.

Are Cushing's disease patients curable?

Treatment of Cushing's disease remains a challenge. Whereas pituitary surgery can "cure" the patient and restore a completely normal pituitary adrenal axis, there are immediate failures and late recurrences which ultimately require alternate therapeutic approaches. These are numerous, but so are their drawbacks, and all appear to be "default options". For the future, pituitary adenoma has to remain the "reasonable obsession" of efficient and optimistic therapists….

Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort.

BACKGROUND: Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome. METHODS: The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes. FINDINGS: Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a wide variance (range 17-62), and partial clinical success in an additional 334 (47%, range 35-66); complete biochemical success was seen in 656 (94%, 83-100) of 699 patients. Female patients had a higher likelihood of complete clinical success (odds ratio [OR] 2·25, 95% CI 1·40-3·62; p=0·001) and clinical benefit (complete plus partial clinical success; OR 2·89, 1·49-5·59; p=0·002) than male patients. Younger patients had a higher likelihood of complete clinical success (OR 0·95 per extra year, 0·93-0·98; p<0·001) and clinical benefit (OR 0·95 per extra year, 0·92-0·98; p=0·004). Higher levels of preoperative medication were associated with lower levels of complete clinical success (OR 0·80 per unit increase, 0·70-0·90; p<0·001). INTERPRETATION: These standardised outcome criteria are relevant for the assessment of the success of surgical treatment in individual patients and will allow the comparison of outcome data in future studies. The variable baseline clinical characteristics of our international cohort contributed to wide variation in clinical outcomes. Most patients derive clinical benefit from adrenalectomy, with younger patients and female patients more likely to have a favourable surgical outcome. Screening for primary aldosteronism should nonetheless be done in every individual fulfilling US Endocrine Society guideline criteria because biochemical success without clinical success is by itself clinically important and older women and men can also derive post-operative clinical benefit. FUNDING: European Research Council; European Union's Horizon 2020; Else Kröner-Fresenius Stiftung; Netherlands Organisation for Health Research and Development-Medical Sciences; Japanese Ministry of Health, Labour and Welfare; Ministry of Health, Slovenia; US National Institutes of Health; and CONICYT-FONDECYT (Chile).

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.

Endocrine surgery in present-day academia.

BACKGROUND: Endocrine surgery is a specialty that is evolving constantly. In this study, we sought to delineate the practice patterns of surgeons taking care of endocrine diseases in present-day academic centers. METHODS: A review of the Faculty Practice Solutions Center database was conducted for the years 2005, 2009, and 2013. Practice patterns were determined by International Classification of Diseases, 9th Revision and Current Procedural Terminology codes, and analyzed for practice composition, regional variability, and volume of endocrine operations. RESULTS: Of 97 national academic centers, 52 were identified to have 120 practicing American Association of Endocrine Surgeons (AAES) surgeons in the study. On average, endocrine operations comprise ∼65% of the AAES surgeon's practice, and 51% are considered high-volume surgeons for thyroidectomy, parathyroidectomy, and adrenalectomy. Most non-AAES surgeons who perform endocrine operations are otolaryngologists (24.5%) and other general surgeons (18.5%). Overall, non-AAES surgeons perform the majority of endocrine operations at academic institutions (61.6%), and low-volume surgeons perform most of these operations (55.6%). CONCLUSION: Research has shown that high-volume surgeons have improved outcomes. Even in academia, however, the majority of endocrine operations are performed by low-volume surgeons, suggesting that there is an opportunity for expanding the number of surgeons with expertise in endocrine surgery in present-day academic centers.

Reliability of laparoscopic skills assessment on video: 8-year results of the endoscopic surgical skill qualification system in Japan.

BACKGROUND AND PURPOSE: The Japanese Urological Association and Japanese Society of Endourology established a urologic laparoscopic skills qualification system called the Endoscopic Surgical Skill Qualification (ESSQ) System in Urological Laparoscopy in 2004. The reliability of video assessments by referees was evaluated. MATERIALS AND METHODS: Videos of nephrectomies or adrenalectomies performed by the applicants were assessed by two referees selected among a pool of 42 referees. From 2004 to 2011, 1308 urologists applied and 60.2% were qualified after video assessments. The results of skills assessments on 1220 videos that had fixed points by two referees were analyzed statistically. RESULTS: The average number of videos that each referee assessed was 58.1, with a range of 16 to 87. The accordance rate of the results of the video assessment, pass or fail, by the two referees was 68.9%. The scores of the video assessment by each referee averaged 62.7±2.4 (standard deviation) (full score was set at 75 points and ≥60 points was needed to pass). There was a statistically significant difference in the average video assessment score among the referees (P<0.001), and five referees showed significantly higher or lower average scores than the other referees. The percentage qualification of the final decision made by the Referee Committee on the videos originally assessed by each referee showed no significant differences among the 42 referees. The accordance rate of the results from the video assessment by each referee with the final decision by the committee showed a statistically significant positive correlation with the number of videos assessed by each referee (r=0.404, P=0.0080). CONCLUSIONS: The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.