Primary Hyperparathyroidism and Intraoperative Parathyroid Hormone Monitoring: Application of a Modified Interpretation in Patients With "Parathyroid Hormone Spikes".

INTRODUCTION: Intraoperative parathyroid hormone (PTH) spikes occur in up to 30% of patients during surgery for primary hyperparathyroidism. This can lead to a prolonged PTH decline and cause difficulties in using current interpretation criteria of intraoperative PTH monitoring. The aim of this study aim was to evaluate an alternative interpretation model in patients with PTH spikes during exploration. METHODS: 1035 consecutive patients underwent surgery for primary hyperparathyroidism in a single center. A subgroup of patients with intraoperative PTH spikes of >50 pg/mL were selected (n = 277; 27.0%). The prediction of cure applying the Miami and Vienna criteria was compared with a decay of ≥50% 10 min after excision of the enlarged parathyroid gland using the "visualization value" (VV; =PTH level immediately after visualization of the gland) as basal value. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated. RESULTS: Using the VV, sensitivity was 99.2% (Vienna 71.0%; Miami 97.7%), specificity was 18.2 (Vienna 63.6%; Miami 36.4%), and accuracy was 92.8 (Vienna 70.4%; Miami 92.8%). Of 255 single-gland disease patients, 72 were identified correctly as cured by applying the VV (P < 0.001), yet 10 of 22 patients with multiple-gland disease were missed compared with the Vienna Criterion (P = 0.002). The comparison with the Miami Criterion showed that six more patients were correctly identified as cured (P = 0.219), whereas four patients with multiple-gland disease were missed (P = 0.125). CONCLUSIONS: Using the VV as a baseline in patients with intraoperative PTH spikes may prove to be an alternative and therefore can be recommended. However, if the VV is higher than the preexcision value, it should not be applied.

Left Renal Vein Division for Juxtarenal Aortic Exposure: Influence on Renal Function and Role of the Communicating Lumbar Vein.

BACKGROUND: In this study, we evaluate the outcome of renal function in patients undergoing juxtarenal abdominal aortic aneurysm repair with or without division of the left renal vein with special focus on the role of the communicating lumbar vein. METHODS: A retrospective analysis of prospectively collected data of 110 patients undergoing elective juxtarenal abdominal aortic aneurysm repair between 2000 and 2018 was performed. The demographic characteristics and comorbidities were reviewed in detail and the renal function was analysed pre- and post-operatively. The cohort of patients was split into group A (left renal vein divided) and B (left renal vein mobilised). Group A was further sub-analysed regarding the presence of a communicating lumbar vein on preoperative imaging data (group A+ = vein present, group A- = no communicating lumbar vein present). RESULTS: The patients were matched well regarding their demographic characteristics and comorbidities. In the analysis of renal function, no statistically significant difference could be detected between group A and B. In the sub-analysis of group A, the group with a communicating lumber vein (group A+) turned out to have a significantly better renal function in the long term (sCrea 0.87 vs. 1.51; p = 0.016). CONCLUSION: Ligation of the left renal vein is a safe procedure in surgery of juxtarenal aortic aneurysms regarding the outcome of the renal function. A communicating lumbar vein between the left renal vein and the left ascending lumbar vein seems to play a key role to provide venous drainage after division of the left renal vein.

Papillary thyroid cancer: the value of bilateral diagnostic lymphadenectomy.

PURPOSE: Papillary thyroid carcinoma (PTC) spreads early to lymph nodes (LN). However, prophylactic central (CND) and lateral neck dissection (LND) is controversially discussed in patients with clinically negative nodes (cN0). The preoperative prediction of LN metastasis is desirable as re-operation is associated with higher morbidity and poor prognosis. The study aims to analyse possible benefits of a systemic bilateral diagnostic lateral lymphadenectomy (DLL) for intraoperative LN staging. METHODS: Preoperative prediction of LN metastasis by conventional ultrasound (US) was correlated with the results of DLL and intra-/postoperative complications in 118 consecutive patients with PTC (cN0) undergoing initial thyroidectomy and bilateral CND and DLL. RESULTS: Lateral LNs (pN1b) were positive in 43/118 (36.4%) patients, including skip lesions (n = 6; 14.0%). Preoperative US and intraoperative DLL suspected lateral LN metastasis in 19/236 (TP: 8.1%) and 54/236 (TP: 22.9%) sides at risk, which were confirmed by histology. Sixty-seven out of 236 (FN: 28.4%) and 32/236 (FN: 13.6%) sides at risk with negative preoperative US and intraoperative DLL lateral LN metastasis were documented. DLL was significantly superior compared to US regarding sensitivity (62.8% vs 22.1%; p < 0.002), positive predictive value (100% vs 76.0%), negative predictive value (82.4% vs 68.2%), and accuracy (86.4% vs 69.1%), but not specificity (100% vs 96.0%; p = 0.039). DLL-related complications (haematoma) occurred in 6/236 [2.5%] sides at risk, including chylous fistula in 2/118 [1.7%] patients. CONCLUSION: DLL can be recommended for LN staging during initial surgery in patients with PTC to detect occult lateral LN metastasis not suspected by US in order to plan lateral LN dissection.

Multiple Endocrine Neoplasia Type 1 and the Pancreas: Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement.

The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.

How to Manage Small Intestine (Jejunal and Ileal) Neuroendocrine Neoplasms Presenting with Liver Metastases?

PURPOSE OF REVIEW: Small intestinal neuroendocrine neoplasms (siNENs) are slowly growing tumours with a low malignant potential. However, more than half of the patients present with distant metastases (stage IV) and nearly all with locoregional lymph node (LN) metastases at the time of surgery. The value of locoregional treatment is discussed controversially. RECENT FINDINGS: In stage I to III disease, locoregional surgery was currently shown to be curative prolonging survival. In stage IV disease, surgery may prolong survival in selected patients with the chance to cure locoregional disease besides radical/debulking liver surgery. It may improve the quality of life and may prevent severe local complications resulting in a state of chronic malnutrition and severe intestinal ischaemia or bowel obstruction. Locoregional tumour resection offers the opportunity to be curative or to focus therapeutically on liver metastasis, facilitating various other therapeutic modalities. Risks and benefits of the surgical intervention need to be balanced individually.

Oral Ondansetron Offers Effective Antidiarrheal Activity for Carcinoid Syndrome Refractory to Somatostatin Analogs.

OBJECTIVES: Somatostatin analogs (SSAs) are standard for symptomatic patients with neuroendocrine tumors (NETs). However, most patients experience tachyphylaxis, and limited options exist for this so-called "refractory carcinoid syndrome." Recently, 5-HT3 antagonist ondansetron has been associated with reduction of bowel movement in a small series. The aim of this analysis was to assess effectiveness of ondansetron for symptomatic treatment of carcinoid syndrome. DESIGN AND PATIENTS: We have analyzed patients given ondansetron as bridging therapy for refractory carcinoid syndrome. The dose was 2 × 8 mg for 5 days, followed by reduction to 1 × 8 mg in case of benefit. RESULTS: A total of 14 patients with small bowel NETs metastatic to the liver were identified. All patients had been treated with SSAs for a median time of 18 months before aggravation of diarrhea. One patient had to be excluded because of an underlying infectious cause of diarrhea. The median number of daily bowel movements was 7 (range, 5-13) before initiation of therapy. At this time, seven patients had stable disease, whereas six patients showed radiological progression with symptomatic breakthrough. All 13 patients were scheduled for salvage therapy. Remarkably, in 85% (11/13) ondansetron resulted in a clinically relevant decrease of bowel movements to a median of 3 (1-4). The median time of ondansetron intake was 29 days (7 days to 29 months). In four patients, diarrhea recurred after initial improvement at an interval of 22-43 days, whereas the remaining seven had an ongoing benefit, including two long-term responders who refused further therapy because of pronounced decrease of symptoms (ondansetron for 14+ and 29+ months). CONCLUSION: Ondansetron offers symptomatic relief in the majority of patients. Although there was no influence on 5-HIAA levels, evidence from two patients suggests prolonged benefit. IMPLICATIONS FOR PRACTICE: Somatostatin analogs are standard treatment in patients with carcinoid syndrome and have an overall response rate of up to 50%. This symptomatic benefit, however, is lost in many patients because of the development of tachyphylaxis or tumor progression. Patients with this "refractory carcinoid syndrome" pose a therapeutic challenge and are sometimes faced with a detrimental effect on quality of life. In this article, the authors suggest the 5-HT3 receptor antagonist ondansetron as potential symptomatic therapy for patients with refractory diarrhea due to carcinoid syndrome. Although the number of patients in this retrospective series is limited, treatment was easily applicable, feasible, and safe and resulted in an ongoing symptomatic benefit in 85% of patients, including two long-term responders.

Effectiveness of anti-osteoporotic treatment after successful parathyroidectomy for primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial.

PURPOSE: After successful surgery for primary hyperparathyroidism, bone mineral density (BMD) does not improve equally in all patients. As no trial has so far aimed to influence normalization of BMD, it was the goal of this investigation to determine whether pharmacological treatment is effective in improving regain of BMD after successful parathyroidectomy in patients with preoperatively diagnosed osteoporosis or osteopenia and to evaluate when treatment may be indicated. METHODS: In this randomized, placebo-controlled, double-blind trial, 52 patients were treated with strontium ranelate 2 g daily + 1000 mg calcium + 800 IU vitamin D (strontium group; SG) or with 1000 mg calcium + 800 IU vitamin D alone (placebo group; PG) for 1 year. The main outcome measures were BMD (lumbar spine, femoral neck, radius) and bone turnover markers. RESULTS: The baseline characteristics were similar in both groups. Absolute BMD (1.007 ± 0.197 vs. 0.897 ± 0.137 g/cm2; p = 0.024) and both relative (9.94 vs. 3.94%; p < 0.001) and absolute (0.09 ± 0.06 vs. 0.03 ± 0.04 g/cm2; p < 0.001) changes in lumbar-spine BMD were significantly higher in the SG than in the PG. Compared to baseline, BMD significantly increased in both groups at the lumbar spine (p < 0.001 and p = 0.001, respectively) and femoral neck (both p < 0.001), whereas radius BMD only changed significantly in the SG. However, the proportion of patients with osteoporosis/osteopenia significantly declined only at the lumbar spine in the SG (from 69.0 to 37.9%; p = 0.034), whereas no decrease was found in the PG. No severe adverse events occurred. CONCLUSIONS: Postoperative anti-osteoporotic treatment can positively influence regain of BMD mainly in the lumbar spine and should be considered. Without treatment, most patients and especially those with low preoperative markers of bone turnover remained osteoporotic/osteopenic 1 year after surgery.

Medullary Thyroid Carcinoma: Do Ultrasonography and F-DOPA-PET-CT Influence the Initial Surgical Strategy?

BACKGROUND: At the time of diagnosis, one-third of medullary thyroid carcinoma (MTC) patients show lymph node (LN) or distant metastasis. A metastasized MTC requires different surgical strategies. OBJECTIVE: This study aimed to determine the value of ultrasound and [18F]fluoro-dihydroxyphenylalanine positron emission tomography with computed tomography (F-DOPA-PET-CT) in localizing MTC, as well as LN and distant metastasis. METHODS: The study included 50 patients (24 males/26 females) with preoperative ultrasound, F-DOPA-PET-CT, and histologically proven MTC. Imaging results were correlated with both preoperative basal calcitonin (bCt) levels and final histology. RESULTS: Tumors were classified as pT1a:17 (diameter, mean ± standard deviation: 5.8 ± 3.0 mm), pT1b:15 (15.0 ± 3.2 mm), pT2:9 (27.3 ± 7.0 mm), and pT3:9 (38.3 ± 24.2 mm). The median bCt level was 202 pg/mL (lower/upper quartile: 82/1074 pg/mL). Ultrasound was positive for tumor in 45/50 (92%) patients (20.0 ± 16.0 mm) and negative in 5 patients (3.2 ± 2.2 mm). Overall, 43/50 (86%) patients had positive F-DOPA local scans (20.0 ± 16.4 mm), while 7 (14%) patients were negative (7.7 ± 8.1 mm). Lastly, 21/50 (42%) patients had LN metastasis; 8/21 (38%) patients had positive LNs suspected with ultrasound, and 12/21 (57%) patients had positive LNs suspected with F-DOPA. Tumor and LN sensitivity of ultrasound was 92% and 43%, respectively, and 86% and 57% of F-DOPA-PET-CT, respectively. In 3/50 (6%) patients and 3/50 (6%) patients, mediastinal LN metastasis and distant metastasis, respectively, were diagnosed only by F-DOPA-PET-CT. CONCLUSION: Ultrasound and F-DOPA-PET-CT are sensitive for the localization of MTC but not for the presence and location of LN metastasis (limitations: size/number). Only F-DOPA ensures the diagnosis of distant metastasis and influences the extent of LN surgery. Surgical strategy cannot be predicted based on neither ultrasound nor F-DOPA-PET-CT.

Primary hyperparathyroidism: Dynamic postoperative metabolic changes.

OBJECTIVE: Little is known about the natural changes in parathyroid function after successful parathyroid surgery for primary hyperparathyroidism. The association of intact parathyroid hormone (iPTH) and calcium (Ca) with "temporary hypoparathyroidism" and "hungry bone syndrome" (HBS) was evaluated. DESIGN: Potential risk factors for temporary hypoparathyroidism and HBS were evaluated by taking blood samples before surgery, intra-operatively, at postoperative day (POD) 1, at POD 5 to 7, in postoperative week (POW) 8 and in postoperative month (POM) 6. PATIENTS: Of 425 patients, 43 (10.1%) had temporary hypoparathyroidism and 36 (8.5%) had HBS. MEASUREMENTS: The discriminative ability of iPTH and Ca on POD 1 for temporary hypoparathyroidism and HBS. RESULTS: Intact parathyroid hormone (IPTH) on POD 1 showed the highest discriminative ability for temporary hypoparathyroidism (C-index = 0.952), but not for HBS. IPTH was helpful in diagnosing HBS between POD 5 and 7 (C-index = 0.708). Extending the model by including Ca resulted in little improvement of the discriminative ability for temporary hypoparathyroidism (C-index = 0.964) and a decreased discriminative ability for HBS (C-index = 0.705). Normal parathyroid metabolism was documented in 139 (32.7%) patients on POD 1 and in 423 (99.5%) 6 months postoperatively, while 2 (0.5%) patients had persistent hyperparathyroidism, one diagnosed between POD 5 and 7 and another at POW 8. No patients suffered from permanent hypoparathyroidism. CONCLUSIONS: The necessity for Ca and vitamin D3 substitution cannot be predicted with certainty before POD 5 to 7 without serial laboratory measurements. Based on the results, a routine 8-week course of Ca and vitamin D3 treatment seems reasonable and its necessity should be evaluated in a follow-up study.

How radical is total parathyroidectomy in patients with renal hyperparathyroidism?

PURPOSE: Total parathyroidectomy (tPTX) in patients with renal hyperparathyroidism (RHPT) aims at the complete removal of all hyperfunctioning parathyroid tissue. Whenever parathyroidectomy is termed "total," undetectable postoperative parathyroid hormone (PTH) levels within the first postoperative week are expected. The aim of this study was to evaluate if tPTX is technically possible using a radical surgical procedure. METHODS: In 109 consecutive patients with RHPT (on hemodialysis: n = 50; after kidney grafting n = 59), removal of all visible parathyroid tissue, bilateral thymectomy, bilateral central neck dissection (level VI), and immediate autotransplantation (AT) was performed. Intact PTH (iPTH) levels were measured in the first postoperative week. PTX was classified "total" when iPTH dropped below 10 pg/ml, "subtotal" between 10 and 65 pg/ml, and "insufficient" where levels stayed above 65 pg/ml. RESULTS: According to the postoperative PTH value, tPTX was achieved in 80 of 109 (73.4%) patients (hemodialysis n = 27, normal kidney function: n = 43, restricted: n = 10). PTX was "subtotal" in 25 patients (22.9%), 19 on hemodialysis, 2 had normal, and 4 had restricted kidney graft function. PTX turned out to be insufficient in four patients (3.7%); all of them were on hemodialysis. Insufficient PTX was not observed in kidney-grafted patients. Postoperative temporary laryngeal nerve morbidity was 1.8% (no permanent paresis). CONCLUSIONS: Although applying a very radical concept in patients with RHPT, PTX was "total" in only 73.4%. Persistence of disease was avoided in 91.7%, and low morbidity was documented. In conclusion, it seems difficult to remove all parathyroid tissue from the neck which has to be considered when choosing the surgical procedure.

Factors influencing pre-operative urinary calcium excretion in primary hyperparathyroidism.

OBJECTIVE: Normal or elevated 24-hour urinary calcium (Ca) excretion is a diagnostic marker in primary hyperparathyroidism (PHPT). It is used to distinguish familial hypocalciuric hypercalcaemia (FHH) from PHPT by calculating the Ca/creatinine clearance ratio (CCCR). The variance of CCCR in patients with PHPT is considerable. The aim of this study was to analyse the parameters affecting CCCR in patients with PHPT. DESIGN: The data were collected prospectively. Patients with sporadic PHPT undergoing successful surgery were included in a retrospective analysis. PATIENTS: The analysis covered 381 patients with pre-operative workup 2 days before removal of a solitary parathyroid adenoma. MEASUREMENTS: The impact of serum Ca and 25-hydroxyvitamin D3 (25-OH D3) on CCCR. RESULTS: The coefficient of determination (R2 ) in the multivariable model for CCCR consisting of age, Ca, 25-OH D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), testosterone (separately for males and females), intact parathyroid hormone (iPTH) and osteocalcin was 25.8%. The only significant parameters in the multivariable analysis were 1,25-(OH)2 D3 and osteocalcin with a drop in R2 of 15.4% (P<.001) and 2.4% (P=.006), respectively. Bone mineral densities at the lumbar spine, distal radius and left femoral neck were not associated with CCCR (r=-.08, r=-.10 and r=-0.09). CONCLUSIONS: In multivariable analysis, 1,25-(OH)2 D3 and osteocalcin were the only factors correlating with CCCR. Vitamin D3 replacement may therefore impair the diagnostic value of CCCR and increase the importance of close monitoring of urinary Ca excretion during treatment.

"Silent" kidney stones in "asymptomatic" primary hyperparathyroidism-a comparison of multidetector computed tomography and ultrasound.

PURPOSE: The purpose of this study was to demonstrate the high number of kidney stones in primary hyperparathyroidism (PHPT) and the low number of in fact "asymptomatic" patients. METHODS: Forty patients with PHPT (28 female, 12 male; median age 58 (range 33-80) years; interquartile range 17 years [51-68]) without known symptoms of kidney stones prospectively underwent multidetector computed tomography (MDCT) and ultrasound (US) examinations of the urinary tract prior to parathyroid surgery. Images were evaluated for the presence and absence of stones, as well as for the number of stones and sizes in the long axis. The MDCT and US examinations were interpreted by two experienced radiologists who were blinded to all clinical and biochemical data. Statistical analysis was performed using the Wilcoxon signed-rank test. RESULTS: US revealed a total of 4 kidney stones in 4 (10 %) of 40 patients (median size 6.5 mm, interquartile range 11.5 mm). MDCT showed a total of 41 stones (median size was 3 mm, interquartile range 2.25 mm) in 15 (38 %) of 40 patients. The number of kidney stones detected with MDCT was significantly higher compared to US (p = 0.00124). CONCLUSIONS: MDCT is a highly sensitive method for the detection of "silent" kidney stones in patients with PHPT. By widely applying this method, the number of asymptomatic courses of PHPT may be substantially reduced. MDCT should be used primarily to detect kidney stones in PHPT and to exclude asymptomatic PHPT.

The advantages of extended subplatysmal dissection in thyroid surgery-the "mobile window" technique.

PURPOSE: Minimal access thyroidectomy, using various techniques, is widely known, but respective data on thyroidectomy for thyroid cancer with lymphadenectomy is scarce. The present study aims to evaluate the feasability of extended subplatysmal dissection in combination with a small incision ("mobile window" technique). METHODS: A retrospective study was performed analysing data from 93 patients. All patients suffered from thyroid carcinoma and underwent (total) thyroidectomy, bilateral cervico-central (levels VI and VII) and functional lateral neck dissection (levels II to V) on the side of the malignancy. In group A, consisting of 47 patients, the operation was performed by a traditional Kocher incision (minimal range 6-7 cm), in 46 patients (group B) a mini-incision (≤4 cm) was made. Intra- and postoperative morbidity as well as oncological accuracy were assessed. RESULTS: There was no significant difference between the two groups comparing postoperative pathological diagnosis, intra- and postoperative complications and the number of removed lymph nodes. However, operating time was slightly longer in group A and thyroid weight was heavier in group B. CONCLUSIONS: Extended subplatymsal dissection allows thyroidectomy and even lateral lymphadenectomy for thyroid carcinoma via "mobile" mini-incision. The procedure is safe, of equivalent oncological accuracy compared to traditional incision and the cosmetic results are excellent.

Prophylactic "First-Step" Central Neck Dissection (Level 6) Does Not Increase Morbidity After (Total) Thyroidectomy.

BACKGROUND: In terms of morbidity, prophylactic central neck dissection (CND; level 6) in potentially malignant thyroid disease is discussed controversially. The rates of (transient and permanent) hypoparathyroidism and palsy of the recurrent laryngeal nerve (RLN) after "first-step" (FS-)CND are analyzed in this study. METHODS: Bilateral and unilateral FSCND, i.e., lymph node dissection along the RLN before (total) thyroidectomy, was performed bilaterally in 68 (group 1) and unilaterally in 44 patients (group 2), respectively. The rates of hypoparathyroidism and palsy of the RLN were documented prospectively and were compared to 237 patients of group 3 (controls) who underwent (total) thyroidectomy only. RESULTS: Fifteen of 68 patients (22 %) of group 1 developed transient and one patient had permanent hypoparathyroidism. Transient unilateral palsy of the RLN was observed in ten patients (15 %); none were permanent. Transient hypoparathyroidism was monitored in 10 of 44 patients (23 %) of group 2 and permanent hypoparathyroidism in 1 (2 %). Six patients (14 %) developed temporary palsy of the RLN; one remained permanent. Palsy was seen in 3 patients on the contralateral side of unilateral FSCND. Transient and permanent hypoparathyroidism was observed in 50 (21 %) and 2 (1 %) of 237 controls. Transient palsy of the RLN was documented in 22 (9 %) of 237 controls and permanent palsy of the RLN in 4 (2 %). CONCLUSIONS: In this single-center series, the overall permanent morbidity was low (1 %). Therefore, FSCND may be recommended (even prophylactically) for experienced high-volume surgeons in patients with thyroid nodules suspicious for malignancy.

The influence of thiazide intake on calcium and parathyroid hormone levels in patients with primary hyperparathyroidism.

OBJECTIVE: The effects of thiazide medication in patients with primary hyperparathyroidism (PHPT) have so far not been elucidated. The aim of this study was to analyse the extent to which the administration of thiazides may influence biochemical parameters and therefore the diagnosis of PHPT in a large cohort of patients. DESIGN AND PATIENTS: The biochemical parameters of 1066 patients with PHPT were analysed, and drug history was documented. Calcium (Ca)/creatinine clearance ratio (CCCR) was calculated. The results of patients given thiazides (n = 170) and those not given thiazides (n = 896) were analysed and compared. MEASUREMENTS: Twenty-four-hour urinary calcium excretion (24hU), albumin-corrected serum calcium, PTH, creatinine, 1,25OH- and 25OH-vitamin D were measured, and CCCR was calculated. RESULTS: 24hUC a and CCCR were significantly lower in patients on thiazides (P = 0·02 and P = 0·0068, resp.), and serum creatinine was significantly higher in those subjects (P < 0·0001). Serum Ca levels only proved different in an analysis of covariance among patients younger than 60 years (P = 0·003). Nevertheless, PTH was not different in both groups (P = 0·917). CONCLUSIONS: According to recently published guidelines, 24hUCa measurement is necessary to give indication for surgery in asymptomatic patients and to distinguish between PHPT and familial hypocalciuric hypercalcaemia [FHH]. Thiazides significantly decrease 24hUC a , yet neither increase serum Ca nor influence PTH levels in patients with PHPT. However, discontinuing thiazides is crucial for a correct CCCR calculation to pre-operatively rule out FHH. As a consequence, the withdrawal of thiazide medication must be recommended for the diagnosis of PHPT prior to surgery.

Morbidity Associated with Concomitant Thyroid Surgery in Patients with Primary Hyperparathyroidism.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism are serious complications in thyroid and parathyroid surgery. The extent to which incidentally detected thyroid nodules should be treated concomitantly is a matter of debate. METHODS: This analysis was based on 1,065 patients who underwent consecutive surgery for primary hyperparathyroidism at a single institution. Together with the surgical strategy, histologic and follow-up examinations were documented prospectively and analyzed retrospectively regarding the occurrence and course of RLN palsy, hypoparathyroidism, and thyroid carcinoma. RESULTS: Altogether, RLN palsy occurred for 38 patients (3.6 %) and proved to be permanent for 1 patient (0.1 %). Postoperative calcium substitution was necessary for 191 patients (17.9 %), with 3 patients showing permanent hypoparathyroidism (0.3 %). Procedures other than open minimally invasive exploration were accompanied by a significantly increased risk for temporary RLN paresis (odds ratio [OR], 6.136) and temporary hypoparathyroidism (OR 3.306). Concomitant thyroid surgery was performed for 502 patients (47.1 %). Compared with open minimally invasive parathyroid exploration, patients undergoing unilateral exploration and hemithyroidectomy (OR 5.827) or bilateral neck exploration (BNE) and thyroidectomy (OR 8.047) had a significantly increased risk for RLN paresis. Patients administered BNE with hemithyroidectomy (OR 2.380) or thyroidectomy (OR 7.233) had a significantly increased risk for hypoparathyroidism. Thyroid malignancy was incidentally detected in 86 patients (8.1 %). CONCLUSION: Patients undergoing concomitant thyroid procedures have a significantly higher risk for temporary RLN palsy and hypoparathyroidism. However, the high rate of incidentally detected thyroid carcinoma in an iodine-replete endemic goiter area indicates hemithyroidectomy in the presence of thyroid nodules incidentally identified in preoperative ultrasounds.

Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to RECIST.

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06-3.40; p = .03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p = .91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. CLINICAL TRIAL REGISTRATION: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as "E-NETNET-L-E-CT" July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes.

BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.

Neuroendocrine liver metastasis from the small intestine: Is surgery beneficial for survival?

BACKGROUND: Neuroendocrine neoplasia of the small intestine (siNEN) are frequently diagnosed with liver metastases. The impact of the presence of liver metastases on overall survival and the necessity of surgery for liver metastasis is discussed controversially. The aim of this study is to evaluate and compare the overall long-term survival of patients with siNENs with and without liver metastasis at initial diagnosis and the possible benefit of surgical treatment as compared to active surveillance of metastases. 123 consecutive patients with siNENs were treated between 1965 and 2016. All clinical and histological records were reevaluated including analysis of the proliferation rates in all specimens. The 1-, 5-, 10- and 20-year overall survival was estimated by Kaplan-Meier analysis for patients with and without liver metastasis and according to the type of treatment (surgical vs. surveillance) of liver metastases if present. RESULTS: The 1-, 5-, 10- and 20-year overall survival rate was 89.0%, 68.4%, 52.8% and 31.0% in patients without and 89.5%, 69.5%, 33.2% and 3.6% in those with liver metastases. No statistically significant differences were observed comparing the two groups. Within the group of patients with liver metastases, the type of treatment (surgical vs. surveillance) was in favor of patients undergoing surgery. Multivariate analysis showed that the presence of liver metastases upon diagnosis was an individual risk factor associated with worse survival. CONCLUSION: The presence of liver metastasis at initial diagnosis does not have a statistically significant influence on survival. Surgery for hepatic metastasis seems to show a benefit for overall survival and may be indicated especially in patients symptomatic due to high tumor burden and serotonin hypersecretion to reduce hormone activity.