Neuroendocrine neoplasms of the gallbladder: early detection and surgery is key to improved outcome.

PURPOSE: Neuroendocrine neoplasms (NENs) of the gallbladder are very rare. As a result, the classification of pathologic specimens from gallbladder NENs, currently classified as gallbladder neuroendocrine tumors (GB-NETs) and carcinomas (GB-NECs), is inconsistent and makes nomenclature, classification, and management difficult. Our study aims to evaluate the epidemiological trend, tumor biology, and outcomes of GB-NET and GB-NEC over the last 5 decades. METHODS: This is a retrospective analysis of the SEER database from 1973 to 2016. The epidemiological trend was analyzed using the age-adjusted Joinpoint regression analysis. Survival was assessed with Kaplan-Meier analysis and Cox regression was used to assess predictors of poor survival. RESULTS: A total of 482 patients with GB-NEN were identified. Mean age at diagnosis was 65.2 ± 14.3 years. Females outnumbered males (65.6% vs. 34.4%). The Joinpoint nationwide trend analysis showed a 7% increase per year from 1973 to 2016. The mean survival time after diagnosis of GB-NEN was 37.11 ± 55.3 months. The most common pattern of nodal distribution was N0 (50.2%) followed by N1 (30.9%) and N2 (19.2%). Advanced tumor spread (into the liver, regional, and distant metastasis) was seen in 60.3% of patients. Patients who underwent surgery had a significant survival advantage (111.0 ± 8.3 vs. 8.3 ± 1.2 months, p < 0.01). Cox regression analysis showed advanced age (p < 0.01), tumor stage (P < 0.01), tumor extension (p < 0.01), and histopathologic grade (p < 0.01) were associated with higher mortality. CONCLUSION: Gallbladder NENs are a rare histopathological variant of gallbladder cancer that is showing a rising incidence in the USA. In addition to tumor staging, surgical resection significantly impacts patient survival, when patients are able to undergo surgery irrespective of tumor staging. Advanced age, tumor extension, and histopathological grade of the tumor were associated with higher mortality.

Combined treatment with Cinnamaldehyde and ß-TCP had an additive effect on bone formation and angiogenesis in critical size calvarial defect in ovariectomized rats.

Accumulating evidence suggests that improvements in osteogenesis and angiogenesis play an important role in repairing osteoporotic bone defects. Cinnamomum cassia (C. cassia), a traditional Chinese medicinal herb, is reported to show anabolic effects on osteoblasts. However, whether C. cassia could actually repair bone defects in osteoporotic conditions remains unknown. The purpose of this study was to evaluate the effect of combined treatment with Cinnamaldehyde (main oil isolated from the C. cassia) and ß-tricalcium phosphate (ß-TCP) on bone formation and angiogenesis in critical size calvarial defects in ovariectomized (OVX) rats. Using a previously established OVX model, 5 mm critical size calvarial defect was established in OVX rats. All OVX rats were then randomly divided into OVX group (OVX rats + empty defect), TCP group (OVX rats + ß-TCP), and CTCP group (Cinnamaldehyde 75 mg/kg/day for 12 weeks + ß-TCP). Twelve weeks after treatment, according to Micro-CT and HE staining, combination of Cinnamaldehyde and ß-TCP had an additive effect on bone regeneration compared with other groups (p < 0.05). Based on dynamic fluorochrome-labelling analysis, Cinnamaldehyde+ß-TCP continuously promoted new bone mineralization compared with other groups at each time point (p < 0.05). Microfil perfusion suggested that CTCP group showed more neovascularization compared with other groups (p < 0.05). Immunohistochemical assay supported the findings that Cinnamaldehyde+ß-TCP enhanced expression of OCN, VEGF and CD31. The present study demonstrated that combined treatment with Cinnamaldehyde and ß-TCP promoted bone formation and angiogenesis in osteoporotic bone defects, which provides a promising new strategy for repairing bone defects in osteoporotic conditions.