DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences.

90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL-1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure.

Buried bumper syndrome: low incidence and safe endoscopic management.

AIMS: Buried bumper syndrome (BBS) is a rare long-term complication of percutaneous endoscopic gastrostomy (PEG) and consists of a progressive impaction of the inner bumper of the tube in the mucosa of gastric wall. The aim of our study was to report our own experience with BBS, focusing on its incidence and endoscopic management. PATIENTS AND METHODS: Medical records of a large group of 879 patients having undergone PEG insertion (2002-2009) were retrospectively reviewed. All PEG's were followed by our special Nutrition Support Team. Patients presenting with BBS during their follow-up were included in the study. RESULTS: Only eight patients (8/879; 0.9%) developed BBS, which was confirmed during gastroscopy. Median time between PEG insertion and BBS diagnosis was 22.0+/-22.28 months. Five patients underwent successful treatment with: 1) flexible guide wire insertion through the internal orifice of the PEG to define its anatomical settings, 2) cruciform incisions of the gastric mucosa with a needle-knife starting at the center of the mucosal dome covering the internal bumper, and reaching its edges, 3) extrusion and complete extraction of the inner bumper through the gastric tract. No complications were observed. Median hospital stay related to BBS lasted 4.0+/-3.67 days. In two patients with peristomal abscess and deeply migrated bumper surgery was needed. CONCLUSIONS: Cruciform mucosal incisions with needle-knife is a safe endoscopic technique to treat the BBS that could avoid surgery in most of the cases. Preventive measures applied after PEG insertion and continued during the follow-up may result in a distinctly lower prevalence of BBS.

Chromogranin A as a useful neuroendocrine marker in patients with autoimmune Addison's disease.

BACKGROUND: Antiparietal cells antibodies (APC-Ab) are commonly found in patients with autoimmune Addison's disease (AAD), usually pointing to autoimmune atrophic gastritis and pernicious anemia. The autoaggression to the gastric proton pumpmay result in a long-term hypergastrinemia, which predisposes to enterochromaffin-like cell hyper/dysplasia and gastric carcinoids. AIM: We evaluated the clinical utility of assessing serum chromogranin A levels in patients with AAD. MATERIAL AND METHODS: Serum chromogranin A, gastrin, and gastric APC-Ab levels were determined in 40 patients with AAD using commercially available kits. RESULTS: Serum chromogranin A and gastrin levels were found to be elevated in 27.5 and 22.5% of patients with AAD, respectively. The Addison's patients with elevated APC-Ab had significantly higher chromogranin A and gastrin levels, as compared to individuals with normal APC-Ab (chromogranin A: 128.00+/-123.08 vs 57.68+/-36.50 ng/ml, p=0.0036; gastrin: 141.38+/-191.43 vs 49.50+/-75.36 muU/ml, p=0.003). Additionally, the patients with AAD and coexisting elevated serum APC-Ab, contrary to those with normal levels, showed a significant correlation between the chromogranin A and gastrin concentrations (r=0.52, p=0.0092 vs r=0.211, p=0.43). Serum chromogranin A appeared also significantly correlated with APC-Ab levels (r=0.431, p=0.005). CONCLUSIONS: In patients with autoimmune Addison's disease hyperchromograninemia and hypergastrinemia occur with a prevalence of 27.5 and 22.5%, respectively. Addison's patients with coexisting elevated gastric APC-Ab, particularly with elevated gastrin levels, are at risk of enterochromaffin-like cells hyper/dysplasia. Serum chromogranin A assessment may complement histology for the early diagnosis of gastric carcinoid in these patients.

Single brain metastasis from a minute, well differentiated, but invading beyond the tunica muscularis mucosa rectal carcinoid.

We report the case of a 48-year-old woman with small-sized (< 10 mm), highly differentiated, aggressive rectal carcinoid, who developed a solitary distant metastasis to the brain. The primary lesion, initially removed by conventional polypectomy, invaded the mucosa/tunica muscularis mucosa and had positive resection margins. Afterwards, an assessment of 5-hydroxyindoloacetic acid (5-HIAA) 24 h urine excretion revealed a significantly increased level. Thus, a partial rectal resection was performed. Because of constantly elevated carcinoid markers: serum chromogranin A (CGA) and 5-HIAA, a somatostatin receptor scintigraphy was performed, which disclosed a focus of pathological marker accumulation in the left frontal area. The pathological finding after neurosurgical excision was meningioma. An unexpected normalization of the biochemical markers prompted us to verify this diagnosis. The final histopathological report was a well-differentiated neuroendocrine brain metastasis. Our case shows that in well differentiated, of diameter < 10 mm rectal carcinoids, an invasion even beyond the mucosa/tunica muscularis mucosa seems to be an independent factor predicting a malignant metastatic potential of these tumors. Hence, in such cases, behind the endoscopic submucosal resection with ligation device a more radical surgery should be considered. Additionally, a systematic CGA and 5-HIAA follow-up assessment and whole body somatostatin receptor scintigraphy, if necessary, are required.