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Abstract Background The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. Methods This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99mTc-MIBI scintigraphy-Intraoperative iPTH monitoring was routinely done. Results Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99mTc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. Conclusion Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99mTc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.

Purpose: Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides Y or Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. Methods: In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [Y-DOTA]-TOC or [Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Results: Overall, 910 patients underwent 1,804 cycles of [Y-DOTA]-TOC and 141 patients underwent 259 cycles of [Lu-DOTA]-TOC. The median survival after [Lu-DOTA]-TOC and after [Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [Lu-DOTA]-TOC over [Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). Conclusion: The present results revealed no difference in median overall survival after [Lu-DOTA]-TOC and [Y-DOTA]-TOC. Furthermore, [Lu-DOTA]-TOC was less haematotoxic than [Y-DOTA]-TOC. [ABSTRACT FROM AUTHOR]

Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting 90Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of 90Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide 213Bi with a mean tissue range of 81 µm may have a more favourable toxicity profile. Therefore, we evaluated locally injected 213Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. In a pilot study, we included five patients with critically located gliomas (WHO grades II–IV). After diagnosis by biopsy, 213Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. Targeted radiopeptide therapy using 213Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. 213Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. This study provides proof of concept that targeted local radiotherapy using 213Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis. [ABSTRACT FROM AUTHOR]

Demonstration of ischaemic left ventricular dysfunction in the absence of chest pain should provide important confirmation of silent myocardial ischaemia in patients with asymptomatic ST segment changes. For this purpose, a new portable scintillation probe (VEST) similar to a miniaturized nuclear stethoscope combined with a Hotter ECG was evaluated. After standard equilibrium radionuclide angiocardiography with technetium-99m labelled red blood cells, the VEST was positioned under gamma-camera control and data were recorded from 1–12 h in 61 unselected patients. Ejection fraction (LVEF), relative changes in volumes, heart rate and ST segment changes were determined. Reproducibility of LVEF at rest (r = 0.91; variability 3.8 ± 3%, N = 19) and during exercise (r = 0.98; variability 3.2 ± 2%, N = 19) was good. In 15 asymptomatic exercise tests four different patterns of LVEF and ST segment responses were identified: (1) decrease in LVEF followed by significant ST depression (five times); (2) ST depression followed by decrease in LVEF (three times); (3) decrease in LVEF without significant ST changes (three times); and (4) ST depression without significant LVEF change (four times). In this still small series, patterns (1) to (3) corresponded to patients with documented coronary artery disease, which was not the case for pattern (4). For detection of silent ischaemia at rest, a decrease in LVEF of >5% lasting for >1 min was defined as ischaemic LV dysfunction. Using this definition, four spontaneous episodes of silent LV dysfunction could be demonstrated in two of three CCU patients with unstable angina during 160–680 min of data recordings without simultaneous ST changes. Based on this initial experience, we conclude that VEST is a reproducible method to detect transient global LV dysfunction and will be useful to confirm silent ischaemia in otherwise uncertain ST segment changes. [ABSTRACT FROM PUBLISHER]

Chronic diarrhea and weight loss are common in patients with AIDS. We report on an AIDS patient with chronic diarrhea, steatorrhea, and marked weight loss. A 75SeHCAT test demonstrated that the diarrhea was mainly due to bile acid malabsorption. Therapy with cholestyramine dramatically reduced bowel movements and led to significant reversal of weight loss. [ABSTRACT FROM AUTHOR]

Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

The hypothesis that addition of mental stress to physical exercise would modify the circulation response to stress and improve noninvasive detection of myocardial ischemia was tested in a randomized, crossover radionuclide angiocardiographic study. Compared with physical exercise or mental stress alone, combined stress led to higher heart rates and rate-pressure products in early stress stages, to more pronounced symptoms, and to a better discrimination of subjects with and without coronary artery disease by radionuclide angiography. [ABSTRACT FROM AUTHOR]

Aims: Evaluation of predictors of silent coronary artery disease (SCAD) in high-risk asymptomatic diabetic patients and to evaluate their two-year outcome., Methods and Results: Four hundred diabetic patients without prior CAD but at high CAD risk underwent myocardial perfusion scintigraphy (MPS) in this prospective multicentre outcome trial. MPS were abnormal in 22% of patients. Male sex (OR 2.223, 1.152-4.290; p=0.017), diabetes duration (OR 1.049,1.015-1.085; p=0·005), peripheral artery disease (OR 2.134, 1·150-3.961; p=0.016), smoking (OR 2.064, 1.109-3.839; p=0·022), systolic blood pressure (OR 1.014, 1.00-1.03, p=0·056), brain natriuretic peptide (OR 1.002, 1.001-1.004, p=0·005) independently predicted an abnormal MPS: if <2 and >3 predictors were present, 3.2% and 47% patients had an abnormal MPS, respectively (p<0·001). Two-year major adverse cardiac event rates increased from 2·9% to 14·6%, cardiac death rates from 0·6% to 4·1% in patients with summed stress scores ≤10 and >10%, respectively (each p<0.045)., Conclusions: Male sex, diabetes duration, peripheral artery disease, smoking, elevated systolic blood pressure and increased brain-natriuretic peptides independently predicted SCAD. In presence of >3 predictors, almost 50% of patients had an abnormal MPS. They may benefit from screening by MPS since the extent of the MPS abnormality discriminated clearly between a favourable compared to a bad 2-year outcome. However, even highest risk patients without objective evidence of CAD had a benign prognosis without need for specific evaluation or therapy., Trial Registration Number: ISRCTN87953632., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr 2 ) in neuroendocrine tumors (NETs)., Methods: We established a tissue microarray and imaging database from NET patients that received sstr 2 -targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr 2 -imaging and sstr 2 -immunohistochemistry., Results: We included a total of 279 patients. In these patients, sstr 2 -immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr 2 -expression on immunohistochemistry correlated with tumor uptake on sstr 2 -imaging (n = 170, p < 0.001); however, sstr 2 -imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 - 56 %, p = 0.025). Sstr 2 -expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93)., Conclusions: Our results suggest sstr 2 as an independent prognostic marker in NETs. Sstr 2 -immunohistochemistry correlates with sstr 2 -imaging; however, sstr 2 -imaging is more accurate for determining the individual prognosis.

Objectives: The objective of this study was to describe the outcomes of patients in the University of Iowa Neuroendocrine Tumor (NET) Database treated with peptide receptor radionuclide therapy (PRRT)., Methods: One hundred thirty-five patients from the University of Iowa NET Database who received PRRT were analyzed, their characteristics were described, and survival was calculated., Results: The median age at diagnosis was 51 years, and 64% were men. The primary tumor was located in the small bowel (SBNET) in 37.8%, in the pancreas (PNET) in 26.0%, in the lung in 13.3%, in unknown primary in 9.6%, and in other sites in 13.3%. A radiographic response of any magnitude was observed in 65.8%, 11.1% had a mixed response, and 15.4% showed progression. The overall survival (OS) from the first PRRT was 40 months, and the median time to progression was 23.9 months. Higher pretreatment chromogranin A and pancreastatin levels predicted inferior OS., Conclusions: Peptide receptor radionuclide therapy resulted in a relatively long OS and time to progression in heavily pretreated North American patients with advanced NETs. Elevated pretreatment chromogranin A and pancreastatin predicted shorter OS after therapy. Peptide receptor radionuclide therapy is a valuable treatment option in patients with advanced NETs, especially SBNETS.

We aimed to assess the risk of developing diabetes mellitus and its effects on all-cause mortality after radiopeptide therapy for neuroendocrine tumors (NETs)., Methods: NET patients received somatostatin radiopeptide therapy with 90 Y-DOTATOC or 177 Lu-DOTATOC. The incidence of diabetes mellitus and its mortality were assessed using univariate and multivariate regression., Results: Overall, 1,535 NET patients were enrolled and received 3,807 treatment cycles. After treatment, 72 patients developed diabetes mellitus, including 47 cases after 90 Y-DOTATOC and 25 cases after combined treatment. The diabetes mellitus risk was higher before than after DOTATOC (estimate, 0.0032; P < 0.001), and overall survival was similar in patients with and without diabetes mellitus (hazard ratio, 1.13; 95% confidence interval, 0.91-1.39; n = 1,535; P = 0.27)., Conclusion: Radiopeptide therapy does not appear to increase the risk of developing diabetes mellitus in NET patients, whereas diabetes mellitus does not appear to increase the mortality of NET patients undergoing receptor-targeted radiopeptide therapy., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor., Methods: Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination., Results: (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments., Conclusions: Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.