Validation of the standardization framework SSTR-RADS 1.0 for neuroendocrine tumors using the novel SSTR­targeting peptide [18F]SiTATE.

OBJECTIVES: Somatostatin receptor positron emission tomography/computed tomography (SSTR-PET/CT) using [68Ga]-labeled tracers is a widely used imaging modality for neuroendocrine tumors (NET). Recently, [18F]SiTATE, a SiFAlin tagged [Tyr3]-octreotate (TATE) PET tracer, has shown great potential due to favorable clinical characteristics. We aimed to evaluate the reproducibility of Somatostatin Receptor-Reporting and Data System 1.0 (SSTR-RADS 1.0) for structured interpretation and treatment planning of NET using [18F]SiTATE. METHODS: Four readers assessed [18F]SiTATE-PET/CT of 95 patients according to the SSTR-RADS 1.0 criteria at two different time points. Each reader evaluated up to five target lesions per scan. The overall scan score and the decision on peptide receptor radionuclide therapy (PRRT) were considered. Inter- and intra-reader agreement was determined using the intraclass correlation coefficient (ICC). RESULTS: The ICC analysis on the inter-reader agreement using SSTR-RADS 1.0 for identical target lesions (ICC ≥ 85%), overall scan score (ICC ≥ 90%), and the decision to recommend PRRT (ICC ≥ 85%) showed excellent agreement. However, significant differences were observed in recommending PRRT among experienced readers (ER) (p = 0.020) and inexperienced readers (IR) (p = 0.004). Compartment-based analysis demonstrated good to excellent inter-reader agreement for most organs (ICC ≥ 74%), except for lymph nodes (ICC ≥ 53%). CONCLUSION: SSTR-RADS 1.0 represents a highly reproducible and consistent framework system for stratifying SSTR-targeted PET/CT scans, even using the novel SSTR-ligand [18F]SiTATE. Some inter-reader variability was observed regarding the evaluation of uptake intensity prior to PRRT as well as compartment scoring of lymph nodes, indicating that those categories require special attention during further clinical validation and might be refined in a future SSTR-RADS version 1.1. CLINICAL RELEVANCE STATEMENT: SSTR-RADS 1.0 is a consistent framework for categorizing somatostatin receptor-targeted PET/CT scans when using [18F]SiTATE. The framework serves as a valuable tool for facilitating and improving the management of patients with NET. KEY POINTS: SSTR-RADS 1.0 is a valuable tool for managing patients with NET. SSTR-RADS 1.0 categorizes patients with showing strong agreement across diverse reader expertise. As an alternative to [68Ga]-labeled PET/CT in neuroendocrine tumor imaging, SSTR-RADS 1.0 reliably classifies [18F]SiTATE-PET/CT.

Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses.

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Gabapentin for post-operative pain management - a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: Perioperative pain treatment often consist of combinations of non-opioid and opioid analgesics, 'multimodal analgesia', in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment. METHODS: Randomized clinical trials comparing gabapentin vs. placebo or active placebo in adult surgical patients receiving gabapentin perioperatively were included. This review was conducted using Cochrane standards, trial sequential analysis (TSA), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The primary outcomes were 24-h opioid consumption and incidence of serious adverse events (SAE). RESULTS: One hundred and thirty-two trials with 9498 patients were included. Thirteen trials with low risk of bias reported a reduction in 24-h opioid consumption of 3.1 mg [0.5, 5.6] [corrected]. In the analysis of gabapentin as add-on analgesic to another non-opioid analgesic regimen found a mean reduction in 24-h morphine consumption of 1.2 mg [-0.3, 2.6; TSA-adjusted CI: -0.3, 2.6] in trials with low risk of bias. [corrected]. Nine trials with low risk of bias reported a risk ratio of SAEs of 1.61 [0.91; 2.86; TSA-adjusted CI: 0.57, 4.57]. CONCLUSION: Based on GRADE assessment of the primary outcomes in trials with low risk of bias, the results are low or very low quality of evidence due to imprecision, inconsistency, and in some outcomes indirectness. Firm evidence for use of gabapentin is lacking as clinically relevant beneficial effect of gabapentin may be absent and harm is imminent, especially when added to multimodal analgesia.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

Valproate release from polycaprolactone implants prepared by 3D-bioplotting.

In this study we examined the release kinetics of valproate from polycaprolactone (PCL) implants constructed for local antiepileptic therapy. The PCL implants were produced with a novel 3D-Bioplotting technology. Release kinetics were determined by superfusion of these implants. Valproate was measured in the superfusate fractions with high pressure liquid chromatography (HPLC). The HPLC measurements were linear over a concentration range of 10-500 microg/mL for valproate and the limit of quantification was found to be 9 microg/mL. The HPLC method used is simple, accurate and sensitive. Within the first day, valproate (10% w/w)-PCL implants released already 77% of the maximum possible liberated amount whereas (5% w/w)-PCL implants released only 53%. After four days, 88% of valproate was released from (10% w/w)-PCL implants and 94% valproate from (5% w/w)-PCL implants. When valproate was ground before the 3D-Bioplotting process, only 63% from (10% w/w)-PCL implants was released within the first day. This released amount of ground valproate was significantly lower compared to that which was not ground from the (10% w/w)-PCL implants. After three days of superfusion a total amount of 89% of ground valproate within the implants was released, corresponding to 88% of non-ground valproate after four days. The fast releasing PCL implants can be used to study acute effects of locally applied valproate on epileptogenesis in vivo after initiation of an epileptic focus in an animal model. The corresponding biocompatibility may also be analysed.

Artificial intelligence assistance improves reporting efficiency of thoracic aortic aneurysm CT follow-up.

OBJECTIVE: Follow-up of aortic aneurysms by computed tomography (CT) is crucial to balance the risks of treatment and rupture. Artificial intelligence (AI)-assisted radiology reporting promises time savings and reduced inter-reader variabilities. METHODS: The influence of AI assistance on the efficiency and accuracy of aortic aneurysm reporting according to the AHA / ESC guidelines was quantified based on 324 AI measurements and 1944 radiological measurements: 18 aortic aneurysm patients, each with two CT scans (arterial contrast phase, electrocardiogram-gated) with an interval of at least six months have been included. One board-certified radiologist and two residents (8/4/2 years of experience in vascular imaging) independently assessed aortic diameters at nine landmark positions. Aneurysm extensions were compared with original CT reports. After three weeks washout period, CTs were re-assessed, based on graphically illustrated AI measurements. RESULTS: Time-consuming guideline-compliant aortic measurements revealed additional affections of the root / arch for 80 % of aneurysms that had initially been reported to be limited to the ascending aorta. AI assistance reduced mean reporting time by 63 % from 13:01 to 04:46 min including manual corrections of AI measurements (performed for 33.6 % of all measurements with predominance at the sinuses of Vasalva). AI assistance reduced total diameter inter-reader variability by 42.5 % (0.42 / 1.16 mm with / without AI assistance, mean of all patients and landmark positions, significant reduction for 6 out of 9 measuring positions). Conventional and AI-assisted quantification aneurysm progress varied to small extent (mean of 0.75 mm over all patients / landmark positions) not significantly exceeding radiologist's inter-reader variabilities. CONCLUSIONS: Guideline-compliant aorta measurement is crucial to report detailed aneurysm extension which might affect the strategy of interventional repair. AI assistance promises improved reporting efficiency and has high potential to reduce radiologist's inter-reader variabilities that can hamper diagnostic follow-up accuracy. KEY POINT: The time-consuming guideline-compliant aorta aneurysm assessment is crucial to report aneurysm extension in detail; AI-assisted measurement reduces reporting time, improves extension evaluation and reduces inter-reader variability.

The diagnostic value of contrast-enhanced ultrasound (CEUS) for assessing hepatocellular carcinoma compared to histopathology; a retrospective single-center analysis of 119 patients1.

BACKGROUND: HCC as the 6th most common tumor entity with the fourth highest mortality and an increasing prevalence especially due to today's lifestyle acquires a high attention in the clinical setting. Beside CECT and CEMRI, CEUS depicts a dynamic, low-risk and radiation free imaging method that finds its use mainly in screening and active surveillance programs. PURPOSE: The aim of the retrospective study was to evaluate the diagnostic value of CEUS in correlation to pathologic findings. MATERIALS AND METHODS: Between 2004 and 2018 a total number of 119 patients were included in this retrospective single-center study. Every patient underwent CEUS in addition to a native B-mode and Color-Doppler scan. After given informed consent SonoVue® (Bracco, Milan, Italy), a second-generation blood-pool agent, was used as contrast medium. Every examination was performed and interpreted by a single experienced radiologist (EFSUMB level 3). A low mechanical index (MI) of <0,2 was chosen to obtain a good imaging quality. RESULTS: All 119 included patients received CEUS followed by a liver biopsy for inter-modality comparison. In correlation to the pathology results, CEUS showed a diagnostic sensitivity of 96,6%, a specificity of 63,9%, a PPV of 86,7% and a NPV of 88,5% by detecting liver lesions suspicious for HCC. According to the Cohen's Kappa coefficient (k = 0,659) CEUS shows a strong inter-modality agreement in comparison to the histopathological finding. CONCLUSION: With a high sensitivity and a strong cross-modality comparability to histopathology, the CEUS is highly effective in the detection of suspicious HCC lesions.