Background-Simvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. However, the effect of simvastatin on cholangiocarcinoma has not been evaluated.

Secretin plays a key role in the regulation of normal cholangiocyte physiology via secretin receptor (SCTR). SCTR expression is upregulated during extrahepatic cholestasis induced by bile duct ligation and closely associated with cholangiocyte proliferative responses. Although well studied in normal cholangiocytes, the role of secretin and the expression of SCTR in the regulation of cholangiocarcinoma proliferation are unknown. In vitro, secretin (10 27 M) displayed differential effects on normal cholangiocyte [H-69 and human intrahepatic biliary epithelial cell line (HIBEpiC)] and cholangiocarcinoma (Mz-ChA-1, HuH-28, TFK-1, SG231, CCLP1 and HuCC-T1) cell lines as such secretin is mitogenic for normal cholangiocytes and antiproliferative for cholangiocarcinoma. As expected in normal cholangiocytes (HIBEpiC), secretin increased intracellular cyclic adenosine monophosphate (cAMP) levels. However, the effect of secretin on intracellular cAMP levels was suppressed in MzChA-1 cells. Secretin-stimulated intracellular cAMP levels in Mz-ChA-1 were restored by pretreatment with pertussis toxin, suggesting that the receptor coupled to Ga i rather than Ga s . SCTR expression was found to be downregulated in 4 of the 6 cholangiocarcinoma cell lines evaluated and in human cholangiocarcinoma biopsy samples. In vivo, secretin significantly inhibited the tumor size and more than doubled tumor latency, which was associated with a decrease in proliferating cell nuclear antigen and an increase in cleaved-caspase 3 expression levels. Our results demonstrate that secretin and/or the modulation of SCTR expression might have potential as a therapeutic tool in the treatment of cholangiocarcinoma.Cholangiocytes are simple epithelia, which line the intrahepatic and extrahepatic ducts and are the target of chronic cholestatic liver diseases, that are characterized biliary inflammation and by the dysregulation of the balance between cell growth and apoptosis.

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Anterior cervical discectomy and fusion (ACDF) is a common treatment modality that has shown good clinical results in patients with cervical degenerative disc disease. ACDF remains the procedure of choice for most patients given its satisfactory clinical outcomes and proven radiological fusion ranging from 90-100%. Five-level ACDF is a very rare type of surgery, even in large spine centers. This type of procedure is unique because, beyond three or four levels, the surgeon needs to switch from a transverse incision to a longitudinal incision along the medial sternocleidomastoid (SCM) muscle border, which is less preferred for cosmetic reasons. Another reason why this procedure is seldom performed is that extreme multilevel ACDF is associated with higher complication and failure rates. Literature covers one, two, and three-level anterior surgeries, but there are few studies reporting the outcomes of five-level ACDF. In the few studies that do report five-level ACDF, the data is controversial. Some studies show the risk of adjacent-segment disease increasing with a higher number of fused levels and increasing incidences of reoperation. Other studies show no changes in the risk of adjacent segment disease in multilevel ACDF in comparison with single-level ACDF. One study even showed a decreased level of adjacent-segment disease and reoperation rates in multilevel ACDF when compared to single-level ACDF. To contribute to current knowledge, we share our experience with five-level ACDF. We report the case of a 63-year-old female who presented with complaints of progressively worsening weakness in the upper extremities. MRI of her cervical spine demonstrated multilevel degenerative disc disease throughout C3-T1 with reversal of normal lordosis and a kyphotic deformity. We performed a successful ACDF at C3-T1 as well as partial corpectomy of the C5 and C6 vertebrae. We did it through a standard transverse incision from the midline to the medial border of the SCM within a preexisting neck crease, demonstrating that in select patients, extreme multilevel ACDF can be performed with proper anatomical dissection and without the need for multiple or longitudinal incisions.

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