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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Objective Immune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or ...anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitis Methods retrospective analysis of 67 patients (27 anti-PD-(L)1, 6 anti-CLTA-4 and 34 anti-CTLA-4/PD-1 induced hypophysitis). Results The median time between starting ICIs and IR-hypophysitis was longer after anti-PD(L)-1) therapy (22 weeks versus 11 and 14 weeks after anti-CTLA-4 and anti-CTLA-4/PD-1 therapy, respectively). The majority of patients (>90%), presented with atypical complaints such as fatigue, nausea, and muscle complaints. Headache, TSH or LH/FSH deficiency were more common in anti-CTLA-4 and anti-CLTA-4/PD-1 versus anti-PD-(L)1 induced hypophysitis (83% and 58% versus 8%, 67% and 41% versus 11%, and 83% and 48% versus 7%, respectively). Pituitary abnormalities on MRI (hypophysitis or secondary empty sella syndrome) were only seen in patients receiving anti-CTLA-4 or anti-CTLA-4/PD-1 therapy. Recovery from TSH, LH/FSH and ACTH deficiency was described in 92%, 70% and 0% of patients after a mean period of 14 and 104 days, respectively, and did not differ between patients who did or did not receive high-dose steroids. Conclusion The clinical presentation of IR-hypophysitis varies depending on the type of ICIs. MRI abnormalities were only seen in anti-CTLA-4 or anti-CTLA-4/PD-1 induced hypophysitis. Endocrine recovery is seen for LH/FSH and TSH deficiency but not for ACTH deficiency, irrespective of the corticosteroid dose.
Context:
The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has ...never been validated for this purpose.
Objective:
The objective of the study was to assess the diagnostic accuracy of chromogranin A (CgA), pancreatic polypeptide (PP), and glucagon for pNET in MEN1.
Design:
This was a diagnostic study.
Setting:
The study was conducted at Dutch university medical centers from 2008 to 2011, representing 90% of the total Dutch MEN1 population.
Patients and Methods:
Patients for whom data on tumor markers in combination with the reference standard (ie, radiological imaging) were available between 2008 and 2011 were included. The reference standard for the presence of pNET was pathology or detection on magnetic resonance imaging, computed tomography, or endoscopic ultrasound confirmed on subsequent imaging, irrespective of modality at follow-up.
Main Outcome Measures:
The area under the receiver-operating characteristic curve (AUC), positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, sensitivity, and specificity were calculated for each marker.
Results:
For the analysis of PP, CgA, and glucagon, 73, 81, and 94 patients were available, respectively. The AUC for CgA was 0.48 95% confidence interval (CI) 0.35–0.61 with a sensitivity 0.33 and a specificity 0.73; the AUC for glucagon was 0.58 (95% CI 0.46–0.70) with a sensitivity 0.43 and a specificity 0.73; and the AUC for PP was 0.64 (95% CI 0.50–0.77) with a sensitivity 0.36 and a specificity 0.74. Age, imaging modality, tumor size, and number did not influence the outcomes.
Conclusion:
The diagnostic accuracy of the tumor markers CgA, PP, and glucagon for pNET in MEN1 is low.
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.
Multiple endocrine neoplasia type 1 is a rare autosomal inherited disorder associated with a high risk for patients to simultaneously develop tumors of the parathyroid glands, duodenopancreatic ...neuroendocrine tumors and tumors of the anterior pituitary gland. Early identification of MEN1 in patients enables presymptomatic screening of manifestations, which makes timely interventions possible with the intention to prevent morbidity and mortality. Causes of death nowadays have shifted toward local or metastatic progression of malignant neuroendocrine tumors. In early cohorts, complications like peptic ulcers in gastrinoma, renal failure in hyperparathyroidism, hypoglycemia and acute hypercalcemia were the primary causes of early mortality. Improved medical treatments of these complications led to a significantly improved life expectancy. The MEN1 landscape is still evolving, considering the finding of breast cancer as a new MEN1-related manifestation and ongoing publications on follow-up and medical care for patients with MEN1. This review aims at summarizing the most recent insights into the follow-up and medical care for patients with MEN1 and identifying the gaps for future research.
Objective To evaluate the usefulness of 18Ffluorodeoxyglucose (FDG) positron emissive tomography (PET)/CT in patients with low detectable thyroglobulin levels suspicious for persistent or recurrent ...differentiated thyroid cancer (DTC). Methods A retrospective case series study evaluating FDG PET/CT in patients with detectable thyroglobulin (Tg) levels (≥0.20 and <10.00 ng/mL) after initial treatment with total thyroidectomy and I-131 thyroid remnant ablation for pT1-3aN0-1bM0 DTC. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of FDG PET/CT were calculated. Results Twenty-seven patients underwent FDG PET/CT. Median Tg level at FDG PET/CT was 2.00 ng/mL (range 0.30–9.00). FDG PET/CT was positive in 14 patients (51.9%): lesions suspicious for lymph node metastases were depicted in 12 patients, and lung metastases in 2. DTC was confirmed in 13/14 FDG PET/CT-positive patients. In 9/13 patients with a negative FDG PET/CT, DTC was confirmed ≤3 months after FDG PET/CT. The sensitivity, PPV, specificity and NPV were 59.1, 92.9, 80.0 and 30.8%, respectively. Conclusions This case series shows that FDG PET/CT might be useful to detect persistent or recurrent DTC in patients with low detectable Tg. However, when FDG PET/CT is negative, this does not rule out DTC and further investigations are necessary.
Background
Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single ...preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, healthcare providers and/or the structure of health care are often combined (complex interventions).
Objectives
To assess the effectiveness of complex interventions in the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of health care.
Search methods
For the second update we searched the Cochrane Wounds Group Specialised Register (searched 22 May 2015), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), The Database of s of Reviews of Effects (DARE) (The Cochrane Library 2015, Issue 4), The Health Technology Assessment Database (HTA) (The Cochrane Library 2015, Issue 4), The NHS Economic Evaluation Database (NHS EED) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (1946 to 22 May 2015), Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations 21 May, 2015), Ovid EMBASE (1974 to 21 May, 2015) and EBSCO CINAHL (1982 to 22 May, 2015).
Selection criteria
Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions.
Data collection and analysis
Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria.
Main results
Only six RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education‐centred complex intervention with usual care or written instructions, only little evidence of benefit was found. Three studies compared the effect of more intensive and comprehensive complex interventions with usual care. One study found a significant and cost‐effective reduction, one of lower extremity amputations (RR 0.30, 95% CI 0.31 to 0.71). One other study found a significant reduction of both amputation and foot ulcers. The last study reported improvement of patients' self care behaviour. All six included RCTs were at high risk of bias, with hardly any of the predefined quality assessment criteria met.
Authors' conclusions
There is no high‐quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.
Pituitary adenomas (PA) are amongst the most prevalent intracranial tumors, causing complications by hormonal overproduction or deficiency and tumor mass effects, with 95% of cases occurring ...sporadically. Associated germline mutations (
) and
microduplications are increasingly identified, but the clinical consequences in sporadic PA remain unclear. This systematic review evaluates predictors of a genetic cause of sporadic PA and the consequences for treatment outcome. We undertook a sensitive MEDLINE/Pubmed, EMBASE, and Web of Science search with critical appraisal of identified studies. Thirty-seven studies on predictors of mutations and 10 studies on the influence on treatment outcome were included.
and
mutations were associated with young age of PA diagnosis.
mutations were also associated with gigantism and macroadenomas at time of diagnosis.
microduplications were associated with PA below the age of five.
and
mutation analysis is therefore recommended in young patients (≤30 years).
mutation analysis is specifically recommended for patients with PA induced gigantism and macroadenoma. Screening for
.3 microduplications is advisable in children below the age of five with increased growth velocity due to PA. There is no evidence supporting mutation analysis of other genes in sporadic PA.
mutation related prolactinoma respond well to dopamine agonists while
mutation associated somatotroph and lactotroph adenoma are frequently resistant to medical treatment. In patients harboring an
microduplication treatment is challenging, although outcome is not different from other patients with PA induced gigantism. Effective use of genetic analysis may lead to early disease identification, while knowledge of the impact of germline mutations on susceptibility to various treatment modalities helps to determine therapeutic strategies, possibly lowering disease morbidity.
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