A case of insulin-like growth factor 2-producing gastrointestinal stromal tumor with severe hypoglycemia.

BACKGROUND: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome that secretes incompletely processed high molecular weight insulin growth factor 2 (big-IGF2), which results in stimulation of the insulin receptor and subsequently induces hypoglycemia. Gastrointestinal stromal tumor (GIST) is a common intestinal mesenchymal neoplasm of the gastrointestinal tract. The most frequent site of GIST is the stomach; NICTH induced by IGF2-producing stomach GISTs is rare. CASE PRESENTATION: An 84-year-old man was admitted to the hospital due to impaired consciousness (JCS II-10) in the morning. At the time of admission, his serum glucose was 44 mg/dL; his consciousness was restored with 20 ml of 50% glucose. To avoid hypoglycemia, a continuous intravenous infusion of glucose as well as dietary intervention was required. At the time of hypoglycemia, the levels of insulin and C-peptide were suppressed. Additionally, IGF1 levels were below the normal range. Abdominal computed tomography revealed that he had a large lobulated mass (116 × 70 × 72 mm) around the gastric corpus. Pathological analysis of biopsy specimens identified disarray of spindle cells and positivity for c-kit as well as strong positivity for DOG-1. Further analysis revealed high levels of Ki-67 (Mib-1 index: 15.5%) and mitotic index (7/50HPF); the tumor was diagnosed as high-risk GIST, and complete surgical resection was performed. Hypoglycemia resolved immediately after tumor resection. The resected tumor specimen was positive for IGF2 staining, and big-IGF2 (11-18 kDa) was detected in preoperative serum and tumor samples; the patient was diagnosed with NICTH due to an IGF2-producing tumor. CONCLUSIONS: NICTH is rare in GIST of the stomach; however, the large GIST could produce big-IGF2 and subsequently cause severe hypoglycemia, requiring prompt evaluation and complete tumor resection.

Mechanical properties of epithelial cells in domes investigated using atomic force microscopy.

As epithelial cells in vitro reach a highly confluent state, the cells often form a microscale dome-like architecture that encloses a fluid-filled lumen. The domes are stabilized by mechanical stress and luminal pressure. However, the mechanical properties of cells that form epithelial domes remain poorly characterized at the single-cell level. In this study, we used atomic force microscopy (AFM) to measure the mechanical properties of cells forming epithelial domes. AFM showed that the apparent Young's modulus of cells in domes was significantly higher when compared with that in the surrounding monolayer. AFM also showed that the stiffness and tension of cells in domes were positively correlated with the apical cell area, depending on the degree of cell stretching. This correlation disappeared when actin filaments were depolymerized or when the ATPase activity of myosin II was inhibited, which often led to a large fluctuation in dome formation. The results indicated that heterogeneous actomyosin structures organized by stretching single cells played a crucial role in stabilizing dome formation. Our findings provide new insights into the mechanical properties of three-dimensional deformable tissue explored using AFM at the single-cell level.

Misleading Focal Clinical, Neurophysiologic, and Imaging Features in 2 Children With Generalized Epilepsy Who Underwent Invasive Electroencephalographic (EEG) Monitoring.

Children and adults with genetic generalized epilepsy may have focal clinical seizure symptoms as well as electroencephalographic (EEG) findings. This may pose a diagnostic challenge to clinicians, especially when concomitant focal neuroimaging findings exist and the epilepsy is medically refractory. We sought to highlight the challenges that clinicians may face through the description of 2 children with suspected genetic generalized epilepsy who had both focal seizure symptoms and EEG/neuroimaging findings and underwent invasive EEG monitoring. Ultimately, invasive monitoring failed to demonstrate a focal origin for the seizures in both cases, and instead confirmed the presence of genetic generalized epilepsy. We demonstrate that ≥3-Hz generalized monomorphic spike and waves are less likely to represent secondary bilateral synchrony, that focal neuroimaging findings may not always be causal and that repeated hyperventilation is an essential activation procedure for genetic generalized epilepsy.