Interferon-gamma regulates the levels of bone formation effectors in a stage-dependent manner.

BACKGROUND: Interferon-gamma (IFN-γ) is an immune-derived cytokines in the innate and adaptive immune responses, and functions as a major pro-inflammatory cytokine. IFNγ has previously been reported involving in the regulation of bone metabolism. However, contradictory results about the roles of IFN-γ in bone formation or bone resorption have been reported. It is possible that the functions of IFN-γ in bone formation is dose-dependent or time-dependent. In this study we examined the effect of IFN-γ on different stages of osteoblastogenesis and bone formation. MATERIALS AND METHODS: Cell proliferation, gene expression and protein levels of the critical effectors involving in different stages of differentiation were compared between differentiating preosteoblast MC3T3-E1 treated with or without IFN-γ at different stages. Cell proliferation were determined by MTT assay. Expression levels of osteoblast differentiation markers was performed by quantitative PCR assay. Also, western blot was conducted to investigate the protein levels in those effectors. CONCLUSION: IFN-γ regulates osteoblast and bone formation in a stage-dependent manner. IFN-γ did not alter and the expression of critical osteogenic transcription factors, such as Runx2 and Cbfb, suggesting that the differentiation was not disrupted by IFN-γ. The cell number and the levels of matrix proteins, including COL1A and BSP, at both early and late stage of osteoblastogenesis were downregulated by IFN-γ, indicating its negative regulating roles in early stages. In contrast, the mineralization protein ALP and OCN was upregulated at late stages. The results suggested that IFN-γ might act as a negative regulator in osteoblast differentiation and bone formation at early stages but switch into positive regulator at late stage. Our data revealed the complex features of the effects of IFN-γ on osteoblast differentiation. The detailed mechanisms of how IFN-γ influence on the bone formation and balance of bone remodeling will be further studied.

Ampullectomy versus pancreaticoduodenectomy for ampullary tumors.

BACKGROUND: Considerable controversy surrounds the treatment of ampullary neoplasms. This report describes the authors' experiences regarding the choice of either ampullectomy or pancreaticoduodenectomy for treatment of ampullary tumors. METHODS: Demographics, statistical findings concerning diagnosis, surgical risks including morbidity and mortality, and outcomes were evaluated and compared between the ampullectomy and pancreaticoduodenectomy groups for ampullary tumors retrieved from a prospectively collected computer database of 992 periampullary tumors resected during the period from 1965 to 2013. RESULTS: A total of 377 patients with ampullary tumors were included; 15 underwent ampullectomy and 362 underwent pancreaticoduodenectomy. The overall false-negative rate for diagnosis of ampullary malignancy was 11.2%, specificity was 50.0%, positive predictive value was 98.3%, negative predictive value was 12.2%, and the overall accuracy was 87.6% (77.5% by preoperative endoscopic biopsy and 83.9% by intraoperative frozen-section biopsy). Ampullectomy was associated with shorter postoperative stays and lower surgical morbidity. There was no statistical difference observed between the two groups regarding surgical mortality, pancreatic leakage, or gastric atonia. The tumor recurrence rate was lower after pancreaticoduodenectomy, but the difference between the groups was not significant. Overall, there was no difference in survival observed between the two groups. CONCLUSION: Because biopsy is not routinely reliable, pancreaticoduodenectomy is preferable to ampullectomy for an ampullary tumor of uncertain diagnosis. Ampullectomy is associated with lower surgical morbidity and should therefore remain in the armamentarium of the pancreatic surgeon when comorbidity precludes major surgery.