Sjoerd Nell

Qualitative elastography can replace thyroid nodule fine-needle aspiration in patients with soft thyroid nodules. A systematic review and meta-analysis

CONTEXT Only a minority of thyroid nodules is malignant; nevertheless, many invasive diagnostic procedures are performed to distinguish between benign and malignant nodules. Qualitative ultrasound elastography is a non-invasive technique to evaluate thyroid nodules. OBJECTIVE To investigate the diagnostic value of qualitative elastography in distinguishing benign from malignant thyroid nodules in patients referred for fine-needle aspiration (FNA). DATA SOURCES A systematic literature search (PubMed, Embase and Cochrane Library) was performed. STUDY SELECTION Included studies reported thyroid nodule elastography color scores and the related cytologic or histologic findings in patients with a thyroid nodule referred for FNA. DATA EXTRACTION Two independent reviewers extracted study data and assessed study quality. Pooled sensitivities and specificities of different populations were calculated using a bivariate Bayesian framework. DATA SYNTHESIS Twenty studies including thyroid nodules were analyzed. Pooled results of elastography indicate a summary sensitivity of 85% (95% confidence interval [CI], 79-90%) and specificity of 80% (95% CI, 73-86%). The respective pooled negative predictive and positive predictive values were 97% (95% CI, 94-98%) and 40% (95% CI, 34-48%). The pretest probability of a benign nodule was 82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma. A pooled negative predictive value of 99% (95% CI, 97-100%) was found when only complete soft nodules (Asteria elastography 1) were classified as benign, which included 14% of the studied population. CONCLUSIONS Elastography has a fair specificity and sensitivity for diagnostic accuracy. Its major strength entails the detection of benignity, especially when only completely soft nodules are qualified as benign. The outcomes of our analysis show that FNA could safely be omitted in patients referred for analysis of their thyroid nodule when elastography shows it to be completely soft (Asteria elastography 1). This could prevent unnecessary invasive diagnostic procedures in a substantial portion of patients.

Management of MEN1 Related Nonfunctioning Pancreatic NETs : A Shifting Paradigm: Results From the DutchMEN1 Study Group

Objective:To assess if surgery for Multiple Endocrine Neoplasia type 1 (MEN1) related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) is effective for improving overall survival and preventing liver metastasis. Background:MEN1 leads to multiple early-onset NF-pNETs. The evidence base for guiding the difficult decision who and when to operate is meager. Methods:MEN1 patients diagnosed with NF-pNETs between 1990 and 2014 were selected from the DutchMEN1 Study Group database, including > 90% of the Dutch MEN1 population. The effect of surgery was estimated using time-dependent Cox analysis with propensity score restriction and adjustment. Results:Of the 152 patients, 53 underwent surgery and 99 were managed by watchful waiting. In the surgery group, tumors were larger and faster-growing, patients were younger, more often male, and were more often treated in centers that operated more frequently. Surgery for NF-pNETs was not associated with a significantly lower risk of liver metastases or death, [adjusted hazard ratio (HR) = 0.73 (0.25–2.11)]. Adjusted HRs after stratification by tumor size were: NF-pNETs <2 cm = 2.04 (0.31–13.59) and NF-pNETs 2–3 cm = 1.38 (0.09–20.31). Five out of the 6 patients with NF-pNETs >3 cm managed by watchful waiting developed liver metastases or died compared with 6 out of the 16 patients who underwent surgery. Conclusions:MEN1 patients with NF-pNETs <2 cm can be managed by watchful waiting, hereby avoiding major surgery without loss of oncological safety. The beneficial effect of a surgery in NF-pNETs 2 to 3 cm requires further research. In patients with NF-pNETs >3 cm, watchful waiting seems not advisable.

Early and Late Complications After Surgery For MEN1-related Nonfunctioning Pancreatic Neuroendocrine Tumors

Objective: To estimate short and long-term morbidity after pancreatic surgery for multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs). Background: Fifty percent of the MEN1 patients harbor multiple NF-pNETs. The decision to proceed to NF-pNET surgery is a balance between the risk of disease progression versus the risk of surgery-related morbidity. Currently, there are insufficient data on the surgical complications after MEN1 NF-pNET surgery. Methods: MEN1 patients diagnosed with a NF-pNET who underwent surgery were selected from the DutchMEN1 study group database, including >90% of the Dutch MEN1 population. Early postoperative complications, new-onset diabetes mellitus, and exocrine pancreatic insufficiency were captured. Results: Sixty-one patients underwent NF-pNET surgery at 1 of the 8 Dutch academic centers. Patients were young (median age 41 years) with low American Society of Anesthesiologists scores. Median NF-pNET size on imaging was 22 mm (3–157). Thirty-three percent (19/58) of the patients developed major early—Clavien-Dindo grade III to IV—complications mainly consisting International Study Group of Pancreatic Surgery grade B/C pancreatic fistulas. Twenty-three percent of the patients (14/61) developed endocrine or exocrine pancreas insufficiency. The development of major early postoperative complications was independent of the NF-pNET tumor size. Twenty-one percent of the patients (12/58) developed multiple major early complications. Conclusions: MEN1 NF-pNET surgery is associated with high rates of major short and long-term complications. Current findings should be taken into account in the shared decision-making process when MEN1 NF-pNET surgery is considered.

PROGNOSTIC FACTORS FOR SURVIVAL OF MEN1 PATIENTS WITH DUODENOPANCREATIC TUMORS METASTATIC TO THE LIVER: RESULTS FROM THE DMSG

OBJECTIVE Duodenopancreatic neuroendocrine tumors (DP-NETs) develop in a majority of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Overall survival (OS) and prognostic factors for patients with liver metastases from DP-NETs are not known. METHODS This was a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population treated between 1990 and 2014. OS was assessed with time to event analysis, and prognostic factors were evaluated. RESULTS A total of 56% of the MEN1 patients (n = 220) were diagnosed with a DP-NET, of who 34 (15%) developed DP-NET liver metastases. Median age at liver metastases diagnosis was 53 years (range 31-74). Of those patients, 16 patients (47%) had died after a median follow-up of 4 years (range 0.3-12.3). OS at 2, 5, and 10 years were 91%, 65%, and 50%, respectively. A trend towards worse survival was seen in males compared to females (5-year OS 58% versus 75%, P = .07) and also in patients with multiple liver metastases compared to patients with solitary liver metastasis (59 versus 83%, P = .09). CONCLUSION Despite the fairly indolent course of DP-NET liver metastases in MEN1 patients, half of the population was deceased after 10 years. Sex and tumor load at diagnosis of liver metastases are possible prognostic factors for worse survival. ABBREVIATIONS DMSG = DutchMEN1 Study Group; D-NET = duodenal neuroendocrine tumor; DP-NET = duodenopancreatic neuroendocrine tumor; HPF = high-power field; Ki67 LI = Ki67 labeling index; MEN1 = multiple endocrine neoplasia type 1; NET = neuroendocrine tumor; OS = overall survival; P-NET = pancreatic neuroendocrine tumor; PPI = proton pump inhibitor; ULN = upper limit of normal; WHO = World Health Organization.

Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age.

The role of qualitative elastography in thyroid nodule evaluation: exploring its target populations

Thyroid nodules are frequently found and pose a dilemma to the clinician, as only a few harbor a malignancy, and the majority of nodules are benign. The standard work-up of thyroid nodules consists of ultrasound and fine needle aspiration (FNA), both having their limitations [1, 2]. In particular, ultrasound lacks criteria for determining whether a nodule is malignant [3]. FNA shows good sensitivities and specificities, but inconclusive and indeterminate results are frequently found, resulting in the need for a diagnostic thyroid lobectomy to obtain a final diagnosis [4]. In the long lasting search to reduce the number of invasive diagnostic procedures, real-time qualitative elastography has been proposed to fulfill this need. Elastography determines the elasticity of the thyroid nodule. Soft nodules are assumed to be benign, whereas hard nodules are considered to be malignant. Qualitative elastography represents the elasticity of the nodule in a colored image projected over the ultrasound image. Multiple elasticity scoring systems are used, which makes reviewing literature challenging. Most common is the 4-point scale developed by Asteria et al., in which elastography 1 (ES 1) is assigned to nodules with elasticity in the entire nodule, ES 2 is assigned to nodules with elasticity in a large portion of the nodule, ES 3 is assigned to nodules with stiffness in a large portion of the nodule, and ES 4 is assigned to hard nodules. A cut-off between ES 2 and ES 3 is widely accepted to discriminate benign from malignant nodules [5]. Studies on thyroid nodule elastography have focused on different target populations: (1) patients referred for FNA with the aim to reduce the number of FNAs, and (2) patients with an indeterminate FNA result (i.e., Bethesda classification III or IV), with the aim to reduce the number of futile lobectomies. Recently, we performed a meta-analysis of studies that investigated the first population: patients referred for FNA. The aim of this study was to determine whether elastography could determine the nature of thyroid nodules and thereby identify those that require further analysis by FNA [6]. In this study, analyzing twenty reports including 3908 nodules, two different cut-offs were examined. The first was the standard cut-off between ES 2 and 3. The second used a cut-off between ES 1 and 2, meaning that only the completely soft nodules were considered benign and the rest of the nodules as potentially malignant. Both cut-offs showed that elastography is an excellent tool to diagnose benignity, with a respective negative predictive value (NPV) of 97 and 99 %. Based on these outcomes, it was concluded that in these cases FNA could be omitted safely. However, considering the modest positive predictive value (PPV) of only 40 % of elastography, this implies that any nodule with an elastography score above ES 2 requires further analysis [6]. In the current issue of Endocrine, Trimboli et al. published an extensive review and meta-analysis on nodules with an indeterminate FNA [7]. Although the majority of these nodules are benign, around one in four harbors a malignancy [4]. Diagnostic lobectomies are often Jakob W. Kist and Sjoerd Nell have contributed equally to the manuscript.

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1.

CONTEXT An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood type O was proposed as an additional factor to personalize screening criteria for neuroendocrine tumors in MEN1 patients. OBJECTIVE The aim of this study was to assess the association between blood type O and the occurrence of neuroendocrine tumors in the national Dutch MEN1 cohort. DESIGN This is a cohort study using the Dutch National MEN1 database, which includes more than 90% of the Dutch MEN1 population. Demographic and clinical data were analyzed by blood type. Chi-square tests and Fisher exact tests were used to determine the association between blood type O and occurrence of neuroendocrine tumors. A cumulative incidence analysis (Grays test) was performed to assess the equality of cumulative incidence of neuroendocrine tumors in blood type groups, taking death into account as a competing risk. RESULTS The ABO blood type of 200 of 322 MEN1 patients was known. Demographic and clinical characteristics were similar among blood type O and non-O type cohorts. The occurrence of neuroendocrine tumors of the lung, thymus, pancreas, and gastrointestinal tract was equally distributed across the blood type O and non-O type cohorts (Grayss test for equality; P = 0.72). Furthermore, we found no association between blood type O and the occurrence of metastatic disease or survival. CONCLUSIONS An association between blood type O and the occurrence of neuroendocrine tumors in MEN1 patients was not confirmed. For this reason, the addition of the blood type to screening and surveillance practice seems not to be of additional value for identifying MEN1 patients at risk for the development of neuroendocrine tumors, metastatic disease, or a shortened survival.