37 research outputs found

    Monitoring ÎČ-cell survival after intrahepatic islet transplantation using dynamic exendin PET imaging: a proof-of-concept study in individuals with type 1 diabetes

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    Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [68Ga]Ga-NODAGA-exendin-4 (68Ga-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying ÎČ-cell mass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. ÎČ-Cell function was measured by mixed-meal tolerance test. With dynamic 68Ga-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of 68Ga-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51–0.63] vs. 0.43 [0.42–0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx. Metabolic health: pathophysiological trajectories and therap

    Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

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    Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≄7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p
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