In anovulatory women with PCOS and obesity undergoing a lifestyle program, RO+ women lose more body weight and abdominal fat on DEXA than RO- women. In addition, this study shows that early and consistent loss of IAF is associated with resumption of ovulation. Future studies should address the mechanisms behind these changes and should assess interventions aimed at loss of IAF to facilitate resumption of ovulation.
Pregnancy in patients with VHL disease induces cerebellar hemangioblastoma progression and causes a high VHL disease-related pregnancy complication rate. We recommend intensified surveillance of patients with VHL disease, especially of cerebellar hemangioblastomas during preconception care and pregnancy.
Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients. Methods: Patients with advanced progressive well-differentiated NETs underwent 89 Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. 89 Zr-bevacizumab uptake was quantified by the maximum standardized uptake value (SUV max ). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly). Results: In 4 of the 14 patients entered, no tumor lesions were visualized with 89 Zr-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUV max decreased during everolimus treatment, with a median of −7% at 2 wk (P 5 0.09) and a median of −35% at 12 wk (P , 0.001). The difference in SUV max at 2 and 12 wk with respect to SUV max at baseline correlated with percentage change on CT at 6 mo (r 2 5 0.51, P , 0.05, and r 2 5 0.61, P , 0.01, respectively). Conclusion: This study demonstrates variable 89 Zr-bevacizumab PET tumor uptake in NET patients. 89 Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial 89 Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGFdirected treatment in NET patients.
Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL) disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL). VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.
Background: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a headto-head comparison, we evaluated endoscopic ultrasound (EUS) and 11 C-5-hydroxytryptophan positron emission
Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with 89 Zr-bevacizumab PET and to explore whether 89 Zr-bevacizumab PET can differentiate progressive from nonprogressive lesions. Methods: VHL patients with at least 1 measurable hemangioblastoma were eligible. 89 Zrbevacizumab (37 MBq) was administered intravenously 4 d before the scan. Maximum standardized uptake values were calculated. PET scans were fused with routine MRI of the central nervous system and abdominal MRI or CT. Progressive lesions were defined as new lesions, lesions that became symptomatic, and lesions $ 10 mm that increased $ 10% and $ 4 mm on repeated anatomic imaging within 12 mo. Results: Twenty-two patients were enrolled. At baseline, anatomic imaging showed 311 lesions. 89 Zr-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient. The median of maximum standardized uptake values was 8.5 (range, 1.3-35.8). The detection rate for lesions $ 10 mm was 30.8%. Seven additional hotspots without substrate on baseline anatomic imaging were found; 2 were also detected with anatomic imaging during follow-up. Nine of 25 progressive lesions were visible on PET and 27 of 175 nonprogressive lesions, corresponding to a positive predictive value of 25% and a negative predictive value of 90%. SUV max was similar in progressive and nonprogressive lesions (median, 4.8; range, 0.9-8.9 vs. median, 6.7; range, 1.3-35.8, P 5 0.14). Conclusion: VHL manifestations can be visualized with 89 Zrbevacizumab PET with a striking heterogeneity in tracer accumulation. 89 Zr-bevacizumab uptake does not predict progression within 12 mo. In one third of the lesions, the drug target VEGF is available and accessible. 89 Zr-bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.