Intra-arterial peptide-receptor radionuclide therapy for neuro-endocrine tumour liver metastases: an in-patient randomised controlled trial (LUTIA).

PURPOSE: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity. METHODS: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a "second-pass" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test. FINDINGS: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle. CONCLUSION: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.

Toward omitting sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with clinically node-negative breast cancer.

BACKGROUND: The nodal positivity rate after neoadjuvant chemotherapy (ypN+) in patients with clinically node-negative (cN0) breast cancer is low, especially in those with a pathological complete response of the breast. The aim of this study was to identify characteristics known before surgery that are associated with achieving ypN0 in patients with cN0 disease. These characteristics could be used to select patients in whom sentinel lymph node biopsy may be omitted after neoadjuvant chemotherapy. METHODS: This cohort study included patients with cT1-3 cN0 breast cancer treated with neoadjuvant chemotherapy followed by breast surgery and sentinel node biopsy between 2013 and 2018. cN0 was defined by the absence of suspicious nodes on ultrasound imaging and PET/CT, or absence of tumour cells at fine-needle aspiration. Univariable and multivariable logistic regression analyses were performed to determine predictors of ypN0. RESULTS: Overall, 259 of 303 patients (85.5 per cent) achieved ypN0, with high rates among those with a radiological complete response (rCR) on breast MRI (95·5 per cent). Some 82 per cent of patients with hormone receptor-positive disease, 98 per cent of those with triple-negative breast cancer (TNBC) and all patients with human epidermal growth factor receptor 2 (HER2)-positive disease who had a rCR achieved ypN0. Multivariable regression analysis showed that HER2-positive (odds ratio (OR) 5·77, 95 per cent c.i. 1·91 to 23·13) and TNBC subtype (OR 11·65, 2·86 to 106·89) were associated with ypN0 status. In addition, there was a trend toward ypN0 in patients with a breast rCR (OR 2·39, 0·95 to 6·77). CONCLUSION: The probability of nodal positivity after neoadjuvant chemotherapy was less than 3 per cent in patients with TNBC or HER2-positive disease who achieved a breast rCR on MRI. These patients could be included in trials investigating the omission of sentinel node biopsy after neoadjuvant chemotherapy.

Influence of lanreotide on uptake of 68Ga-DOTATATE in patients with neuroendocrine tumours: a prospective intra-patient evaluation.

INTRODUCTION: Somatostatin receptor imaging with PET is the standard of care for patients with a neuroendocrine tumour (NET). Since therapy and imaging with somatostatin analogues utilize the same receptor, current guidelines recommend withdrawing long-acting somatostatin analogues for 3-4 weeks prior to somatostatin receptor PET imaging. The aim of this study is to prospectively assess the effect of lanreotide use on the uptake of 68Ga-DOTATATE intra-individually 1 day prior to and 1 day post injection of lanreotide. METHODS: Thirty-four patients with metastatic and/or unresectable NET and currently on lanreotide therapy for at least 4 months were included in the study. A 68Ga-DOTATATE PET/CT scan was performed on the day before and the day after lanreotide injection. In each patient 68Ga-DOTATATE uptake (SUVmax, mean, peak) was assessed in both tumour lesions and normal tissue. All scans were assessed by two blinded nuclear medicine physicians for visual analysis. Paired T-tests were performed to determine the differences between the scans. RESULTS: Of the 34 patients included, 31 were available for analyses in which 190 tumour lesions were measured. Uptake of 68Ga-DOTATATE in tumour lesions was increased significantly after lanreotide, but decreased significantly in the liver, spleen, and thyroid gland resulting in a higher tumour-to-liver ratio. CONCLUSION: Lanreotide injection prior to 68Ga-DOTATATE PET/CT does not result in decreased tumour uptake. In contrast, tumour uptake was increased, whereas the uptake in normal organs is decreased, leading to an increased tumour-to-liver ratio. However, these differences were small and not deemed clinically relevant. These results strongly suggest that discontinuation of lanreotide injections in the weeks prior to 68Ga-DOTATATE PET examinations is unnecessary and does not compromise nuclear medicine imaging results.

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure.

BACKGROUND: Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy. METHODS: All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node. RESULTS: The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment. CONCLUSION: Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN + breast cancer patients.

18F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases.

PURPOSE: Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation 18F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). METHODS: Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline 18F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SULpeak, SULmean, SULmax, partial volume corrected SULmean (cSULmean), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. RESULTS: Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SULpeak, SULmax, SULmean , and cSULmean are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. CONCLUSION: We found no association between the metabolic parameters on pre-ablation 18F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly associated with improved NHR-FS. The clinical implication of these findings might be the identification of high-risk patients who might benefit most from adjuvant or combined treatment strategies.

Early differences in dynamic uptake of 68Ga-PSMA-11 in primary prostate cancer: A test-retest study.

INTRODUCTION: Dynamic PET/CT allows visualization of pharmacokinetics over the time, in contrast to static whole body PET/CT. The objective of this study was to assess 68Ga-PSMA-11 uptake in pathological lesions and benign tissue, within 30 minutes after injection in primary prostate cancer (PCa) patients in test-retest setting. MATERIALS AND METHODS: Five patients, with biopsy proven PCa, were scanned dynamically in list mode for 30 minutes on a digital PET/CT-scanner directly after an intravenous bolus injection of 100 MBq 68Ga-PSMA-11. Approximately 45 minutes after injection a static whole body scan was acquired, followed by a one bed position scan of the pelvic region. The scans were repeated approximately four weeks later, without any intervention in between. Semi-quantitative assessment was performed using regions-of-interest in the prostate tumor, bladder, gluteal muscle and iliac artery. Time-activity curves were extracted from the counts in these regions and the intra-patient variability between both scans was assessed. RESULTS: The uptake of the iliac artery and gluteal muscle reached a plateau after 5 and 3 minutes, respectively. The population fell apart in two groups with respect to tumor uptake: in some patients the tumor uptake reached a plateau after 5 minutes, whereas in other patients the uptake kept increasing, which correlated with larger tumor volumes on PET/CT scan. Median intra-patient variation between both scans was 12.2% for artery, 9.7% for tumor, 32.7% for the bladder and 14.1% for the gluteal muscle. CONCLUSION: Dynamic 68Ga-PSMA-11 PET/CT scans, with a time interval of four weeks, are reproducible with a 10% variation in uptake in the primary prostate tumor. An uptake plateau was reached for the iliac artery and gluteal muscle within 5 minutes post-injection. A larger tumor volume seems to be related to continued tumor uptake. This information might be relevant for both response monitoring and PSMA-based radionuclide therapies.

The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations.

Lutetium-177 [177Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([177Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [177Lu]LuCl3 cannot exceed 2% of the radioactive dose. Since no monograph is available for [177Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [177Lu]LuCl3 and [177Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [177Lu]LuCl3 were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [177Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [177Lu]Lu-HA-DOTA-TATE.

A physiologically based pharmacokinetic (PBPK) model to describe organ distribution of 68Ga-DOTATATE in patients without neuroendocrine tumors.

BACKGROUND: Physiologically based pharmacokinetic (PBPK) models combine drug-specific information with prior knowledge on the physiology and biology at the organism level. Whole-body PBPK models contain an explicit representation of the organs and tissue and are a tool to predict pharmacokinetic behavior of drugs. The aim of this study was to develop a PBPK model to describe organ distribution of 68Ga-DOTATATE in a population of patients without detectable neuroendocrine tumors (NETs). METHODS: Clinical 68Ga-DOTATATE PET/CT data from 41 patients without any detectable somatostatin receptor (SSTR) overexpressing tumors were included. Scans were performed at 45 min (range 30-60 min) after intravenous bolus injection of 68Ga-DOTATATE. Organ (spleen, liver, thyroid) and blood activity levels were derived from PET scans, and corresponding DOTATATE concentrations were calculated. A whole-body PBPK model was developed, including an internalization reaction, receptor recycling, enzymatic reaction for intracellular degradation and renal clearance. SSTR2 expression was added for several organs. Input parameters were fixed or estimated using a built-in Monte Carlo algorithm for parameter identification. RESULTS: 68Ga-DOTATATE was administered with a median peptide amount of 12.3 µg (range 8.05-16.9 µg) labeled with 92.7 MBq (range 43.4-129.9 MBq). SSTR2 amounts for spleen, liver and thyroid were estimated at 4.40, 7.80 and 0.0108 nmol, respectively. Variability in observed organ concentrations was best described by variability in SSTR2 expression and differences in administered peptide amounts. CONCLUSIONS: To conclude, biodistribution of 68Ga-DOTATATE was described with a whole-body PBPK model, where tissue distribution was mainly determined by variability in SSTR2 organ expression and differences in administered peptide amounts.

Transient ischemic dilatation ratio derived from myocardial perfusion scintigraphy: What are we looking at?

BACKGROUND: Elevated transient ischemic dilatation (TID) ratio during myocardial perfusion imaging (MPI) is described as a marker of severe CAD, even in acquisitions with normal perfusion. This was initiated to explore the effects of stressor type on the TID. Additionally the relation between the TID and other functional parameters, such as end diastolic volume (EDV), end systolic volume (ESV), and left ventricle ejection fraction (LVEF), heart rate (HR), and severity of ischemia, was evaluated. METHOD: A total of 299 consecutive patients referred for a 2-day stress/rest MPI protocol were included. Patients were stressed with either adenosine (n = 164) or exercise (n = 135). MPI data were analyzed with an automated software tool to determine TID, EDV, ESV, LVEF, SSS, and SDS. The SDS was used to quantify the degree of ischemia, with a SDS > or = 3 considered ischemic. RESULTS: Comparison of the adenosine and exercise stressed population revealed significant differences, especially in parameters derived from the poststress acquisition. Within the exercise stressed population, TID was proportional with the SDS (R(2) = .12); whereas the adenosine population did not show such a relation (R(2) = .001). Difference in HR between rest and poststress acquisitions showed high levels of linear regression with TID values of both the adenosine (R(2) = .41) and exercise (R(2) = .29) stressed population. CONCLUSION: In an exercise stressed population, TID is determined by both the degree of ischemia and the heart-rate difference between the two acquisition moments. TID within the adenosine population was found to be highly proportional with the HR, rather than with the degree of ischemia.

The success of 131I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq 131I.

OBJECTIVE: Dosimetry studies have shown that activities of 131I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative 131I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq 131I causes a lower success rate of ablation. DESIGN: retrospective chart review study. PATIENTS, METHODS: In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic 131I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq 131I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone 131I ablation between July 2002 and December 2005, and who had returned for 131I follow-up. Successful ablation was defined as absence of pathological 131I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. RESULTS: Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq 131I was an independent determinant for success of ablation (p = 0.002). CONCLUSIONS: After applying a diagnostic activity of 40 MBq 131I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of 131I for diagnostic scintigraphy or uptake measurement prior to 131I ablation is best avoided.

Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F.

BACKGROUND: Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing 68Ga to 18F. RESULTS: The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R2 = 0.99). 68Ga showed approximately 22 times more detectable Cerenkov signal compared to 18F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of 18F was 23.7 kBq/mL and 1.2 kBq/mL for 68Ga. The spatial resolution was 1.31 mm for 18F and 1.40 mm for 68Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. CONCLUSION: 68Ga was superior over 18F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for 68Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution < 2 mm, CLI for intraoperative margin assessment using 68Ga could be feasible.

Noninvasive assessment of left ventricular function prior to and 6 months after renal transplantation.

BACKGROUND: The purpose of this study was to evaluate the effect of a successful kidney transplantation on left ventricular functional parameters that can be measured with gated-single photon emission computed tomography (gated-SPECT) myocardial perfusion scintigraphy in patients with end-stage renal disease. MATERIALS AND METHODS: Thirty-two consecutive patients (22 male) who had undergone a successful kidney transplantation in whom gated-SPECT myocardial perfusion scintigraphy was performed prior to and 6 months after surgery were included. Functional parameters, such as left ventricular ejection fraction (LVEF), wall motion, and wall thickening, were calculated with quantitative gated-SPECT. RESULTS: The mean LVEF improved significantly (P<.001) from 52% (SD+/-11) before to 63% (SD+/-10) after renal transplantation. This was attributable to a significant improvement in the end-systolic volume (P=.028). Wall motion and wall thickening improved in almost all myocardial segments. We found a significant correlation between the levels of urea and creatinine and the LVEF. However, correlations between an increase in the LVEF and the improvement in urea (P=.30) and creatinine (P=.26) levels were not significant, which is probably related to the number of patients studied. CONCLUSION: The systolic left ventricular dysfunction in terms of LVEF, wall motion, and wall thickening improves significantly 6 months after kidney transplantation in patients with end-stage kidney disease. Long-term follow-up is required to establish the prognostic value of these findings.

A novel semi-robotized device for high-precision 18F-FDG-guided breast cancer biopsy.

PURPOSE: To assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high 18F-FDG uptake. MATERIALS AND METHODS: In the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm3 voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with 18F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of 18F-FDG uptake areas within the tumour. RESULTS: Needle positioning tests revealed an average accuracy of 0.5mm (range 0-1mm), 0.6mm (range 0-2mm), and 0.4mm (range 0-2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high 18F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application. CONCLUSIONS: Accuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.

PET/CT with 18F-FDG predicts short-term outcome in stage II/III breast cancer patients upstaged to N2/3 nodal disease.

INTRODUCTION: 18F-FDG PET/CT has high positive predictive value for the detection of avid lymph node metastases in breast cancer patients. We analysed the effect of upstaging lymph nodes by PET/CT on short-term outcome in stage II/III breast cancer patients. PATIENTS AND METHODS: A total of 278 stage II/III primary breast cancer patients (mean age 48.9 years, range 19-75 years) were re-staged with 18F-FDG PET/CT before start of pre-operative systemic treatment (PST). Patients were divided in three groups based on risk for local recurrence: a low - (T2N0), intermediate - (T0-2N1 and T3N0) and a high-risk group (T0-3N2-3, T3N1 and T4). Within these groups we looked at local recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS) within the first 3 years of follow-up. RESULTS: With a median follow-up (FU) of 50 months the RFS, LRFS and OS were 87%, 88% and 92% respectively for the whole group. PET/CT upstaged 43 patients from the low- and intermediate risk group to the high-risk group, based on detection of ≥4 avid axillary nodes or occult N2/3-disease. Patients upstaged with PET/CT had more events for all three analyses compared to the original risk groups, which resulted in a significantly worse RFS (69.8%; p = 0.03) a nearly significantly worse LRFS (p = 0.052) and no effect in OS (p = 0.433). DISCUSSION: Additional PET/CT staging allows breast cancer patients to be treated according to the true stage, still stage II/III breast cancer patients upstaged to N2/3 by PET/CT have worse short-term outcome, despite adjustment of treatment, than patients staged high-risk with conventional imaging.

[Intramyocardial injection of autologous bone-marrow stem cells in a 74-year-old man with untreatable angina pectoris and demonstrated myocardial ischaemia]. / Intramyocardiale injectie van autologe stamcellen bij een 74-jarige man met onbehandelbare angina pectoris en bewezen myocardischemie.

For a 74-year-old man with angina pectoris and demonstrated myocardial ischaemia, optimal medical treatment was insufficient. He was ineligible for coronary revascularization. To improve myocardial perfusion, autologous bone-marrow stem cells were injected into the ischaemic myocardium. During the months following the injection, the frequency of angina attacks decreased and myocardial perfusion and cardiac function improved.

The hidden sentinel node in breast cancer: Reevaluating the role of SPECT/CT and tracer reinjection.

INTRODUCTION: Lymphoscintigraphy with planar imaging is considered a helpful tool to depict lymph node drainage in patients with invasive breast cancer. Single Photon Emission Computed Tomography with integrated CT (SPECT/CT) is usually performed to detect sentinel nodes (SN)s in breast cancer patients showing non-visualisation on lymphoscintigraphy. Incorporation of new SN indications (recurrent surgery, previous radiotherapy, or neo-adjuvant chemotherapy) has led to an increase of non-visualisation rates. The present study evaluates the contribution of SPECT/CT and tracer reinjection for SN-visualisation in breast cancer patients without drainage on lymphoscintigraphy. METHODS: Between 1st of July 2008 and 6th of November 2014 in total 1968 patients underwent a SN breast procedure, using intra-tumoural tracer administration. SPECT/CT was performed in 284 breast cancer patients with non-visualisation of SNs on lymphoscintigraphy. If SN non-visualisation persisted, a second radiotracer injection with repeated imaging was performed when logistics allowed this. Univariate analysis was applied to evaluate SPECT/CT visualisation rates in specific subgroups. RESULTS: The SPECT/CT visualisation rate was 23.2% (66/284). Univariate analysis revealed no significant subgroups influencing SPECT/CT visualisation. In patients receiving reinjection after persistent SPECT/CT non-visualisation the SN-visualisation rate reached 62.1% (36/58). Intraoperatively, the SN-identification rate using a gamma probe and blue dye was 87.9% (175/199) and 32.9% (28/85) for, respectively, primary and recurrent surgery after non-visualisation on lymphoscintigraphy. CONCLUSION: In this evaluation including new breast cancer SN indications, SPECT/CT scored lower than reinjection to visualise SNs in patients with non-visualisation on lymphoscintigraphy. Consequently, our institutional protocol has been readjusted.

Increased prevalence of catecholamine excess and phaeochromocytomas in a well-defined Dutch population with SDHD-linked head and neck paragangliomas.

OBJECTIVE: The aim of this study was to identify the prevalence of catecholamine excess and phaeochromocytomas in a well-defined population of people with hereditary head and neck paragangliomas. METHODS: We studied in a prospective follow-up protocol all consecutive patients referred to the Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands with documented head and neck paragangliomas and either a positive family history for paragangliomas or a proven SDHD gene mutation. Initial analysis included medical history, physical examination and the measurement of excretion of catecholamines in two 24-h urine collections. In the case of documented catecholamine excess iodinated meta-iodobenzylguanidine (123I-MIBG) scintigraphy and magnetic resonance imaging were done. RESULTS: Between 1988 and 2003, 40 consecutive patients (20 male and 20 female) with documented head and neck paragangliomas were screened. Biochemical screening revealed urinary catecholamine excess in 15 patients (37.5%). In nine of these 15 patients a lesion was found by 123I-MIBG scintigraphy. Exact localization by magnetic resonance imaging revealed phaeochromocytomas in seven of the 15 patients. One of the nine patients had an extra-adrenal paraganglioma. Histopathological examination in a subset of tumors displayed loss of heterozygosity of the wild-type SDHD allele in all cases. CONCLUSIONS: The prevalence of catecholamine excess (37.5%) and phaeochromocytomas (20.0%) is high in patients with familial head and neck paragangliomas. Therefore, patients with hereditary head and neck paragangliomas require lifelong follow up by biochemical testing for catecholamine excess.

[Utility of SPECT/CT scan for anatomical localization of pararectal and presacral sentinel nodes in prostate cancer]. / Utilidad de la SPECT-TC para la localización anatómica de los ganglios centinelas presacrales y pararrectales en el cáncer de próstata.

AIM: This study has aimed to evaluate the added value of SPECT-CT scan in the preoperative assessment of sentinel nodes of the presacral and pararectal regions localized outside the standard area of extended pelvic lymphadenectomy for the staging of the pelvis in prostate cancer. SPECT-CT scan can serve as a guide for the excision of these nodes by lymphadenectomy by open surgery or laparoscopy. MATERIAL AND METHODS: We evaluated 4 patients with prostate cancer presenting sentinel nodes in the pararectal and presacral regions on SPECT-CT scan performed in addition to lymphoscintigraphy. These patients underwent lymphadenectomy with robot-assisted laparoscopy together with prostatectomy. All of the excised lymph nodes were sent for histopathology study. RESULTS: An average of 6 sentinel nodes per patient were found on SPECT-CT scan with a mean of 2 sentinel nodes in presacral/pararectal región. Lymphadenectomy including these areas was performed. Pararectal/presacral sentinel nodes of all patients depicted by SPECT-CT scan were tumor free on histopathology study. Sentinel nodes (no pararectal/presacral) were positive for malignancy in only one patient. CONCLUSION: Preoperative SPECT-CT scan is a useful tool to localize the sentinel nodes in pararectal/presacral regions. It can be an anatomic guide for new modalities of laparoscopic surgery such as robot-assisted procedures that can access the pelvic areas visualized with SPECT-CT scan, making excision of these nodes possible.

Six months of recombinant human GH therapy in patients with ischemic cardiac failure does not influence left ventricular function and mass.

Beneficial effects of recombinant human GH on cardiac function have been reported in humans with GH deficiency and in patients with idiopathic dilated cardiomyopathy. No randomized controlled trial has been performed on the effects of recombinant human GH on cardiac function in patients with ischemic cardiac failure. We therefore randomly assigned 22 patients with ischemic cardiac failure (left ventricular ejection fraction, <40%; 19 men and 3 women; mean age, 64 yr) to receive 6 months of unblinded therapy with recombinant human GH (2.0 IU/d) or no treatment. Primary end points were left ventricular ejection fraction and left ventricular mass. Left ventricular end-diastolic volume, left ventricular end-systolic volume, and myocardial perfusion, both at rest and during exercise, were assessed as well. Cardiac imaging techniques were electrocardiographically gated single photon emission computer tomography and magnetic resonance imaging. In addition, biochemical and biometric measurements were performed. Nineteen patients completed the study (10 controls and 9 GH-treated subjects). IGF-I and IGF-binding protein-3 increased significantly after recombinant human GH treatment (+24% and +58%, respectively) compared with control values (-14% and +5%; P < 0.05). Left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular mass, and myocardial perfusion were not influenced by recombinant human GH therapy. We conclude that 6 months of recombinant human GH treatment in patients with ischemic cardiac failure had no beneficial effect on left ventricular function and mass.