Surgery for advanced neuroendocrine tumours of the small bowel: recommendations based on a consensus meeting of the European Society of Endocrine Surgeons (ESES).

BACKGROUND: Small bowel neuroendocrine tumours often present with locally advanced or metastatic disease. The aim of this paper is to provide evidence-based recommendations regarding (controversial) topics in the surgical management of advanced small bowel neuroendocrine tumours. METHODS: A working group of experts was formed by the European Society of Endocrine Surgeons. The group addressed 11 clinically relevant questions regarding surgery for advanced disease, including the benefit of primary tumour resection, the role of cytoreduction, the extent of lymph node clearance, and the management of an unknown primary tumour. A systematic literature search was performed in MEDLINE to identify papers addressing the research questions. Final recommendations were presented and voted upon by European Society of Endocrine Surgeons members at the European Society of Endocrine Surgeons Conference in Mainz in 2023. RESULTS: The literature review yielded 1223 papers, of which 84 were included. There were no randomized controlled trials to address any of the research questions and therefore conclusions were based on the available case series, cohort studies, and systematic reviews/meta-analyses of the available non-randomized studies. The proposed recommendations were scored by 38-51 members and rated 'strongly agree' or 'agree' by 64-96% of participants. CONCLUSION: This paper provides recommendations based on the best available evidence and expert opinion on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours.

Assessing Outcomes After Adrenalectomy for Primary Aldosteronism - Early is Accurate: Retrospective Cohort Study.

OBJECTIVE: We aimed to investigate the postoperative trend in blood pressure (BP)-related outcomes [BP and antihypertensive (AHT) drug use] during the year following adrenalectomy for primary aldosteronism (PA) to determine the optimal timing for outcome assessment and to determine the necessary follow-up length. BACKGROUND: Since the course of BP-related outcomes after adrenalectomy is unknown, the optimal timing of outcome assessment and follow-up duration are not clear. METHODS: In this retrospective single center cohort study, we used a prospectively collected database with all patients referred for difficult-to-control-hypertension-analysis. All patients diagnosed with PA who underwent adrenalectomy were included. AHT drug use [in defined daily dose (DDD)] and home blood pressure measurements (HBPMs) during the first postoperative year were collected. A mixed-effects model was developed to assess the stability of DDD and HBPM over time and adjust for potential confounders. RESULTS: In total 1784 patients were assessed for difficult-to-control-hypertension of whom 41 were included. Both the DDD and HBPM showed the strongest decrease in the first postoperative month (mean 1.6DDD; mean 140/85 mm Hg) compared with preoperative values (4.5DDD; 153/92 mm Hg). Thereafter, both outcomes showed a stable course from 4 to 6 months (1.6DDD; 136/86 mm Hg) up to 12 months postoperatively (2.0DDD; 136/83 mm Hg). CONCLUSIONS: This study showed that AHT drug use and HBPM decreased substantially within the first month after adrenalectomy for PA and afterwards generally remained stable during the year following adrenalectomy. We propose that BP-related outcomes can be assessed reliably early after adrenalectomy and question the need for routine long-term follow-up in referral centers.

Complications After Major Surgery for Duodenopancreatic Neuroendocrine Tumors in Patients with MEN1: Results from a Nationwide Cohort.

BACKGROUND: Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore, the incidence and severity of complications after major surgery for MEN1-related dpNETs were assessed. METHODS: Patients were selected from the population-based Dutch MEN1 database if they had undergone a Whipple procedure or total pancreatectomy from 2003 to 2017. Complications were graded according to the Clavien-Dindo classification (grade III or higher complications were considered a severe complication) and definitions from the International Study Group of Pancreatic Surgery. The Cumulative Complication Index (CCI®) was calculated as the sum of all complications weighted for their severity. Univariable logistic regression was performed to assess potential associations between predictor candidates and a severe complication. RESULTS: Twenty-seven patients (median age 43 years) underwent a major duodenopancreatic resection, including 14 Whipple procedures and 13 total pancreatectomies. Morbidity and mortality were 100% (27/27) and 4% (1/27), respectively. A severe complication occurred in 17/27 (63%) patients. The median CCI® was 47.8 [range 8.7-100]. Grade B/C pancreatic fistulas, delayed gastric emptying, bile leakage, hemorrhage, and chyle leakage occurred in 7/14 (50%), 10/27 (37%), 1/27 (4%), 7/27 (26%), 3/27 (11%) patients, respectively. Patients with a severe complication had longer operative time and higher blood loss. After Whipple, new-onset endocrine and exocrine insufficiency occurred in 1/13 and 9/14 patients, respectively. CONCLUSIONS: Major duodenopancreatic surgery in MEN1 is associated with a very high risk of severe complications and cumulative burden of complications and should therefore be reserved for a select subgroup of patients with MEN1-related dpNETs.

Reliability and Agreement of Radiological and Pathological Tumor Size in Patients with Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors: Results from a Population-Based Cohort.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still regarded as the main prognostic factor and therefore used for surgical decision-making. We assessed reliability and agreement of radiological and pathological tumor size in a population-based cohort of patients with MEN1-related pNETs. METHODS: Patients were selected from the Dutch MEN1 database if they had undergone a resection for a pNET between 2003 and 2018. Radiological (MRI, CT, and endoscopic ultrasonography [EUS]) and pathological tumor size were collected from patient records. Measures of agreement (Bland-Altman plots with limits of agreement [LoA] and absolute agreement) and reliability (intraclass correlation coefficients [ICC] and unweighted kappa) were calculated for continuous and categorized (< or ≥2 cm) pNET size. RESULTS: In 73 included patients, the median radiological and pathological tumor sizes measured were 22 (3-160) and 21 (4-200) mm, respectively. Mean bias between radiological and pathological tumor size was -0.2 mm and LoA ranged from -12.9 to 12.6 mm. For the subgroups of MRI, CT, and EUS, LoA of radiological and pathological tumor size ranged from -9.6 to 10.9, -15.9 to 15.8, and -13.9 to 11.0, respectively. ICCs for the overall cohort, MRI, CT, and EUS were 0.80, 0.86, 0.75, and 0.76, respectively. Based on the 2 cm criterion, agreement was 81.5%; hence, 12 patients (18.5%) were classified differently between imaging and pathology. Absolute agreement and kappa values of MRI, CT, and EUS were 88.6, 85.7, and 75.0%, and 0.77, 0.71, and 0.50, respectively. CONCLUSION: Within a population-based cohort, MEN1-related pNET size was not systematically over- or underestimated on preoperative imaging. Based on agreement and reliability measures, MRI is the preferred imaging modality.

Correction to: Validation of the Aldosteronoma Resolution Score Within Current Clinical Practice.

In the original article, two of the International CONNsortium Study Group collaborator's names are spelled wrong: Anton F. Engelsman and Els J.M. Nieveen van Dijkum. The spellings are correct as reflected here.

Adrenalectomy for Primary Aldosteronism: Significant Variability in Work-Up Strategies and Low Guideline Adherence in Worldwide Daily Clinical Practice.

BACKGROUND: Various diagnostic tests are available to establish the primary aldosteronism (PA) diagnosis and to determine the disease laterality. Combined with the controversies in the literature, unawareness of guidelines and technical demands and high costs of some of these diagnostics, this could lead to significant differences in work-up strategies worldwide. Therefore, we investigated the work-up before surgery for PA in daily clinical practice within a multicenter study. METHODS: Patients who underwent unilateral adrenalectomy for PA within 16 centers in Europe, Canada, Australia and the USA between 2010 and 2016 were included. We did not exclude patients based on the performed diagnostic tests during work-up to make our data representative for current clinical practice. Adherence to the Endocrine Society Guideline and variables associated with not performing adrenal venous sampling (AVS) were analyzed. RESULTS: In total, 435 patients were eligible. An aldosterone-to-renin ratio, confirmatory test, computed tomography (CT), magnetic resonance imaging and AVS were performed in 82.9%, 32.9%, 86.9%, 17.0% and 65.3% of patients, respectively. A complete work-up, as recommended by the guideline, was performed in 13.1% of patients. Bilateral disease or normal adrenal anatomy on CT (OR 16.19; CI 3.50-74.99), smaller tumor size on CT (OR 0.06; CI 0.04-0.08) and presence of hypokalemia (OR 2.00; CI 1.19-3.32) were independently associated with performing AVS. CONCLUSIONS: This study is the first to examine the daily clinical practice work-up of PA within a worldwide cohort of surgical patients. The results demonstrate significant variability in work-up strategies and low adherence to The Endocrine Society guideline.

Prognostic factors and survival in MEN1 patients with gastrinomas: Results from the DutchMEN study group (DMSG).

BACKGROUND AND OBJECTIVES: Gastrinomas are the most prevalent functioning neuroendocrine tumors (NET) in multiple endocrine neoplasia type 1 (MEN1). Guidelines suggest medical therapy in most patients, but surgery may be considered in a subgroup. Currently, factors to guide management are necessary. This population-based cohort study assessed prognostic factors of survival in patients with MEN1-related gastrinomas. METHODS: Patients with MEN1 having gastrinomas were identified in the Dutch MEN1 database from 1990 to 2014 based on fasting serum gastrin (FSG) levels and/or pathology. Predictors of overall survival were assessed using Cox regression. RESULTS: Sixty-three patients with gastrinoma (16% of the MEN1 population) were identified. Five- and 10-year overall survival rates were 83% and 65%, respectively. Prognostic factors associated with overall survival were initial FSG levels ≥20x upper limit of normal (ULN) (hazard ratio [HR], 6.2 [95% confidence interval, 1.7-23.0]), pancreatic NET ≥2 cm (HR 4.5; [1.5-13.1]), synchronous liver metastases (HR 8.9; [2.1-36.7]), gastroduodenoscopy suspicious for gastric NETs (HR 12.7; [1.4-115.6]), and multiple concurrent NETs (HR 5.9; [1.2-27.7]). CONCLUSION: Life expectancy of patients with MEN1 gastrinoma is reduced. FSG levels and pancreatic NETs ≥2 cm are prognostic factors. FSG levels might guide surveillance intensity, step-up to additional diagnostics, or provide arguments in selecting patients who might benefit from surgery.

Validation of the Aldosteronoma Resolution Score Within Current Clinical Practice.

INTRODUCTION: Complete resolution of hypertension after adrenalectomy for primary aldosteronism is far from a certainty. This stresses the importance of adequate preoperative patient counseling. The aldosteronoma resolution score (ARS) is a simple and easy to use prediction model only including four variables: ≤ 2 antihypertensive medications, body mass index ≤ 25 kg/m2, duration of hypertension ≤ 6 years and female sex. However, because the model was developed and validated within the USA over a decade ago, the applicability in modern practice and outside of the USA is questionable. Therefore, we aimed to validate the ARS in current clinical practice within an international cohort. MATERIALS AND METHOD: Patients who underwent unilateral adrenalectomy, between 2010 and 2016, in 16 medical centers from the USA, Europe (EU), Canada (CA) and Australia (AU) were included. Resolution of hypertension was defined as normotension without antihypertensive medications. RESULTS: In total, 514 patients underwent adrenalectomy and 435 (85%) patients were eligible. Resolution of hypertension was achieved in 27% patients within the total cohort and in 22%, 30%, 40% and 38% of patients within USA, EU, CA and AU, respectively (p = 0.015). The area under the curve (AUC) for the complete cohort was 0.751. Geographic validation displayed a AUC within the USA, EU, CA and AU of 0.782, 0.681, 0.811 and 0.667, respectively. DISCUSSION: The ARS is an easy to use prediction model with a moderate to good predictive performance within current clinical practice. The model showed the highest predictive performance within North America but potentially has less predictive performance in EU and AU.

Status of Surveillance and Nonsurgical Therapy for Small Nonfunctioning Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine tumors (PNETs) occur in < 1/100,000 patients and most are nonfunctioning (NF). Approximately 5% occur as part of multiple endocrine neoplasia type 1. Anatomic and molecular imaging have a pivotal role in the diagnosis, staging and active surveillance. Surgery is generally recommended for nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) >2 cm to prevent metastases. For tumors ≤2 cm, active surveillance is a viable alternative. Tumor size and grade are important factors to guide management. Assessment of death domain-associated protein 6/alpha-thalassemia/mental retardation X-linked and alternative lengthening of telomeres are promising novel prognostic markers. This review summarizes the status of surveillance and nonsurgical management for small NF-PNETs, including factors that can guide management.

Use of intraoperative parathyroid hormone measurements during parathyroidectomy to predict postoperative parathyroid hormone levels in patients with renal hyperparathyroidism: meta-analysis.

BACKGROUND: Several studies have reported on the use of intraoperative parathyroid hormone (ioPTH) measurements during parathyroidectomy (PTX) for renal hyperparathyroidism (rHPT), but there is no consensus on whether it is helpful and, if so, what protocol should be used. Therefore, the literature was systematically reviewed to assess a correlation between ioPTH and early postoperative parathyroid hormone (PTH) levels in patients undergoing PTX for rHPT, separately for those on dialysis and those with a functioning renal transplant. METHODS: A systematic literature search was performed in electronic databases. Quality assessment was performed using the Quality In Prognosis Studies tool. Mean ioPTH values were calculated at different time points and correlated to the postoperative PTH levels within 1 month. Fixed-effect and random-effects models were performed to assess the mean ioPTH levels at 10 or 20 min after resection (T10 and T20). Stratified analyses were performed for patients on dialysis and those with a functioning renal transplant. RESULTS: Of the 3087 records screened, 14 studies were included, including some 1177 patients; 1091 were on dialysis and 86 had a functioning kidney transplant. Risk of bias was moderate for most studies. For patients on dialysis, T10 and T20 mean ioPTH levels were 32.1 (95 per cent c.i. 24.3 to 39.9) pmol/l and 15.4 (95 per cent c.i. 7.8 to 22.9) pmol/l) in the random effects meta-analysis. Between individual studies, ioPTH ranged from 4.0-65.1 pmol/l at T10 and 8.6-25.7 pmol/l at T20. T10 and T20 ioPTH were 9.6 and 4.1 times the postoperative PTH-after T20 ioPTH stabilized in those on dialysis. In patients with a functioning renal transplant, ioPTH levels seemed to plateau after 10 min and measured 2.6 times the postoperative PTH. CONCLUSION: There is a strong correlation between ioPTH and early postoperative PTH levels, indicating that ioPTH is potentially a useful instrument during PTX in patients with rHPT. For patients on dialysis, at T20 ioPTH levels have stabilized and are approximately four times the postoperative PTH. Therefore, it is recommended to use ioPTH 20 min after resection in patients on dialysis, which might be longer than necessary for those with a kidney transplant.

Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice.

Background: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the diagnostic accuracy of the currently used conventional pancreatic imaging techniques and the added value of fine needle aspirations (FNAs). Methods: Patients who had at least one imaging study were included from the population-based MEN1 database of the DutchMEN Study Group from 1990 to 2017. Magnetic resonance imaging (MRI), computed tomography (CT), endoscopic ultrasonography (EUS), FNA, and surgical resection specimens were obtained. The first MRI, CT, or EUS was considered as the index test. For a comparison of the diagnostic accuracy of MRI versus CT, patients with their index test taken between 2010 and 2017 were included. The reference standard consisted of surgical histopathology or radiological follow-up. Results: A total of 413 patients (92.8% of the database) underwent 3,477 imaging studies. The number of imaging studies per patient increased, and a preference for MRI was observed in the last decade. Overall diagnostic accuracy was good with a positive (PPV) and negative predictive value (NPV) of 88.9% (95% confidence interval, 76.0-95.6) and 92.8% (89.4-95.1), respectively, for PanNET in the pancreatic head and 92.0% (85.3-96.0) and 85.3% (80.5-89.1), respectively, in the body/tail. For MRI, PPV and NPV for pancreatic head tumors were 100% (76.1-100) and 87.1% (76.3-93.6) and for CT, 60.0% (22.9-88.4) and 70.4% (51.3-84.3), respectively. For body/tail tumors, PPV and NPV were 91.3% (72.0-98.8) and 87.0% (75.3-93.9), respectively, for MRI and 100% (74.9-100) and 77.8% (54.3-91.5), respectively, for CT. Pathology confirmed a PanNET in 106 out of 110 (96.4%) resection specimens. FNA was performed on 34 lesions in 33 patients and was considered PanNET in 24 [all confirmed PanNET by histology (10) or follow-up (14)], normal/cyst/unrepresentative in 6 (all confirmed PanNET by follow-up), and adenocarcinoma in 4 (2 confirmed and 2 PanNET). Three patients, all older than 60 years, had a final diagnosis of pancreatic adenocarcinoma. Conclusion: As the accuracy for diagnosing MEN1-related PanNET of MRI was higher than that of CT, MRI should be the preferred (non-invasive) imaging modality for PanNET screening/surveillance. The high diagnostic accuracy of pancreatic imaging and the sporadic occurrence of pancreatic adenocarcinoma question the need for routine (EUS-guided) FNA.

Metastatic Patterns of Duodenopancreatic Neuroendocrine Tumors in Patients With Multiple Endocrine Neoplasia Type 1.

Patients with multiple endocrine neoplasia 1 syndrome (MEN1) often develop multifocal duodenopancreatic neuroendocrine tumors (dpNETs). Nonfunctional pancreatic neuroendocrine tumors (PanNETs) and duodenal gastrinomas are the most frequent origins of metastasis. Current guidelines recommend surgery based on tumor functionality, size ≥2 cm, grade or presence of lymph node metastases. However, in case of multiple primary tumors it is often unknown which specific tumor metastasized. This study aims to unravel the relationship between primary dpNETs and metastases in patients with MEN1 by studying endocrine differentiation. First, it was shown that expression of the endocrine differentiation markers ARX and PDX1 was concordant in 18 unifocal sporadic neuroendocrine tumors (NETs) and matched metastases. Thereafter, ARX, PDX1, Ki67 and gastrin expression, and the presence of alternative lengthening of telomeres were determined in 137 microscopic and macroscopic dpNETs and 36 matched metastases in 10 patients with MEN1. ARX and PDX1 H-score clustering was performed to infer relatedness. For patients with multiple metastases, similar intrametastases transcription factor expression suggests that most metastases (29/32) originated from a single NET of origin, while few patients may have multiple metastatic primary NETs. In 6 patients with MEN1 and hypergastrinemia, periduodenopancreatic lymph node metastases expressed gastrin, and clustered with minute duodenal gastrinomas, not with larger PanNETs. PanNET metastases often clustered with high grade or alternative lengthening of telomeres-positive primary tumors. In conclusion, for patients with MEN1-related hypergastrinemia and PanNETs, a duodenal origin of periduodenopancreatic lymph node metastases should be considered, even when current conventional and functional imaging studies do not reveal duodenal tumors preoperatively.

Risk factors for complications after surgery for pancreatic neuroendocrine tumors.

BACKGROUND: Surgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients. This cohort study aimed to assess complications and risk factors after resections of pancreatic neuroendocrine tumors. METHODS: Patients undergoing resection of a pancreatic neuroendocrine tumor were identified within 2 centers of excellence. Complications were assessed according to the Clavien-Dindo classification and the comprehensive complication index. Logistic regression was performed to compare surgical procedures with adjustment for potential confounders (Clavien-Dindo ≥3). RESULTS: The cohort comprised 123 patients, including 12 enucleations, 50 distal pancreatectomies, 51 pancreatoduodenectomies, and 10 total/combined pancreatectomies. Mortality was 0.8%, a severe complication occurred in 41.5%, and the failure-to-rescue rate was 2.0%. The median comprehensive complication index was 22.6 (0-100); the comprehensive complication index increased after more extensive resections. After adjustment, a pancreatoduodenectomy, as compared to a distal pancreatectomy, increased the risk for a severe complication (odds ratio 3.13 [95% confidence interval 1.32-7.41]). Of the patients with multiple endocrine neoplasia type 1 or von Hippel-Lindau, 51.9% developed a severe complication vs 38.5% with sporadic disease. After major resections, morbidity was significantly higher in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau (comprehensive complication index 45.1 vs 28.9, P = .029). CONCLUSION: Surgery for pancreatic neuroendocrine tumors is associated with a high rate of complications but low failure-to-rescue in centers of excellence. Complications are procedure-specific. Major resections in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau appear to increase the risk of complications.

Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: Functionality matters.

BACKGROUND: Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis. METHODS: Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival. RESULTS: Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%-76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%-91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47-6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22-7.33]) and World Health Organization grade 2 (2.95 [1.02-8.50]) were associated with liver metastases-free survival. CONCLUSION: Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.

A simplified primary aldosteronism surgical outcome score is a useful prediction model when target organ damage is unknown - Retrospective cohort study.

BACKGROUND: Cure of hypertension after adrenalectomy for primary aldosteronism is no certainty and therefore preoperative patient counseling is essential. The Primary Aldosteronism Surgical Outcome (PASO) Score is a useful prediction model with an area under the curve (AUC) of 0.839. The PASO Score includes 'Target Organ Damage' (TOD) (i.e., left ventricular hypertrophy and/or microalbuminuria), which is often unavailable during preoperative counseling and might therefore limit its use in clinical practice. We hypothesized that the PASO score would still be useful if TOD is unknown at time of counseling. Therefore, we aimed to examine the predictive performance of the simplified PASO Score, without taking TOD into account. MATERIALS AND METHODS: In this retrospective cohort study, patients who underwent unilateral adrenalectomy between 2010 and 2016 in 16 medical centers from North America, Europe and Australia were included. TOD was unknown in our database and therefore assigned as absent. Patients were classified as complete, partial or absent clinical success using the PASO consensus criteria. RESULTS: A total of 380 (73.9%) patients were eligible for analysis. Complete, partial and absent clinical success were observed in 29.5%, 55.8% and 14.7% of patients, respectively. The simplified PASO Score had an AUC of 0.730 (95% confidence interval 0.674-0.785) in our total cohort. CONCLUSION: Without taking TOD into account, the simplified PASO Score had a lower predictive value as compared to the original derivation cohort. Ideally, the complete PASO Score should be used, but when data on TOD are not readily available, the simplified PASO Score is a useful and reasonable alternative.

Trends in blood pressure-related outcomes after adrenalectomy in patients with primary aldosteronism: A systematic review.

BACKGROUND: Decrease in blood pressure (BP) is the major goal of adrenalectomy for primary aldosteronism. Nevertheless, the optimal timing to assess these outcomes and the needed duration of follow-up are uncertain. We systematically reviewed the literature regarding trends in BP-related outcomes during follow-up after adrenalectomy. METHODS: A systematic literature search of medical literature from PubMed, Embase and the Cochrane Library regarding BP-related outcomes (i.e. cure of hypertension rates, BP and antihypertensives) was performed. The Quality In Prognosis Studies risk of bias tool was used. RESULTS: Of the 2057 identified records, 13 articles met the inclusion criteria. Overall study quality was low. In multiple studies, the biggest decrease in BP was shown within the first month(s) after adrenalectomy and afterwards BP often remained stable during long-term follow-up. CONCLUSIONS: Based on the available studies one might suggest that long follow-up is unnecessary, since outcomes seem to stabilize within the first months.

Clinical outcomes after surgery for primary aldosteronism: Evaluation of the PASO-investigators' consensus criteria within a worldwide cohort of patients.

BACKGROUND: In a first step toward standardization, the Primary Aldosteronism Surgical Outcomes investigators introduced consensus criteria defining the clinical outcomes after adrenalectomy for primary aldosteronism. Within this retrospective cohort study, we evaluated the use of these consensus criteria in daily clinical practice in 16 centers in Europe, Canada, Australia, and the United States. METHODS: Patients who underwent unilateral adrenalectomy for primary aldosteronism between 2010 and 2016 were included. Patients with missing data regarding preoperative or postoperative blood pressure or their defined daily dose were excluded. According to the Primary Aldosteronism Surgical Outcomes criteria, patients were classified as complete, partial, or absent clinical success. RESULTS: A total of 380 patients were eligible for analysis. Complete, partial, and absent clinical success was achieved in 30%, 48%, and 22%, respectively. Evaluation of the Primary Aldosteronism Surgical Outcomes criteria showed that in 11% and 47% of patients with partial and absent clinical success, this classification was incorrect or debatable (16% of the total cohort). This concept of a "debatable classification of success" was due mainly to the cutoff of ≥20 mmHg used to indicate a clinically relevant change in systolic blood pressure and the use of percentages instead of absolute values to indicate a change in defined daily dose. CONCLUSION: Although introduction of the Primary Aldosteronism Surgical Outcomes consensus criteria induced substantial advancement in the standardization of postoperative outcomes, our study suggests that there is room for improvement in the concept for success given the observed limitations when the criteria were tested within our international cohort. In line, determining clinical success remains challenging, especially in patients with opposing change in blood pressure and defined daily dose.

Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base.

In multiple endocrine neoplasia type 1 (MEN1), nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are the most frequently diagnosed NETs and a leading cause of MEN1-related death. The high prevalence and malignant potential of NF-pNETs outline the need for an evidence-based screening program, as early diagnosis and timely intervention could reduce morbidity and mortality. Controversies exist regarding the value of several diagnostic tests. This systematic review aims to evaluate current literature and amplify an up-to-date evidence-based approach to NF-pNET diagnosis in MEN1. Three databases were systematically searched on the diagnostic value of biomarkers and imaging modalities. Twenty-seven studies were included and critically appraised (modified Quality Assessment of Diagnostic Accuracy Studies). Another 12 studies, providing data on age-related penetrance and tumor growth, were included to assess the optimal frequency and timing of screening. Based on current literature, biomarkers should no longer play a role in the diagnostic process for NF-pNETs, as accuracies are too low. Studies evaluating the diagnostic value of imaging modalities are heterogeneous with varying risks of bias. For the detection of NF-pNETs, endoscopic ultrasound (EUS) has the highest sensitivity. A combined strategy of EUS and MRI seems to be the most useful. Gallium 68 octreotate-DOTA positron emission tomography-CT could be added if NF-pNETs are diagnosed to identify metastasis. Reported growth rates were generally low, and two distinct phenotypes were observed. Surveillance programs should focus on and be adapted to the presence of substantial growth in NF-pNETs. The optimal age to start screening must yet be determined, as insufficient evidence for an evidence-based recommendation was available.