Metal stents placement for refractory pancreatic duct stricture in children

AIM To evaluate the use of fully covered self-expandable metal stents(FCSEMSs) for pancreatic duct strictures in children with chronic pancreatitis.METHODS Eight patients with refractory benign dominant stricture of the main pancreatic duct(MPD) were enrolled through chart reviews between December 2014 and June 2017 in a single center. Endoscopic retrograde cholangiopancreatography(ERCP) with placement of a 6-mm FCSEMS with dual flaps was performed. Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. All procedures were performed by a pediatric gastroenterologist. For the assessment of outcomes, technical and clinical success, adverse events, and stent patency were evaluated retrospectively.RESULTS The placement and removal of the FCSEMSs were successful in all 8 patients. Five patients were boys and 3 were girls. The median age at initial FCSEMS placement was 12 years(range, 5-18 years). The diameters of all the inserted stents were 6 mm, and the lengths were 4-7 cm. The median indwelling time was 6 mo(range, 3-10 mo). No pancreatic sepsis, pancreatitis, cholestasis, or mortality occurred. There was no proximal and distal migration. All subjects showed a patent stent. On follow-up ERCP, the mean diameter of the stricture improved from 1.1 mm to 2.8 mm(P < 0.05), whereas that of upstream dilation improved from 8.4 mm to 6.3 mm(P < 0.05).CONCLUSION This initial experience showed that temporary FCSEMS placement is feasible and safe for the management of refractory benign MPD stricture in children.

Proinflammatory cytokine TNFα promotes HPV-associated oral carcinogenesis by increasing cancer stemness

High-risk human papillomaviruses(HPVs) are involved in the development of several human cancers, including oropharyngeal squamous cell carcinomas. However, many studies have demonstrated that HPV alone is not sufficient for the oncogenic transformation of normal human epithelial cells, indicating that additional cofactors are required for the oncogenic conversion of HPV-infected cells. Inasmuch as chronic inflammation is also closely associated with carcinogenesis, we investigated the effect of chronic exposure to tumor necrosis factor α(TNFα), the major proinflammatory cytokine, on oncogenesis in two immortalized oral keratinocyte cell lines, namely, HPV16-immortalized and human telomerase reverse transcriptase(h TERT)-immortalized cells. TNFαtreatment led to the acquisition of malignant growth properties in HPV16-immortalized cells, such as(1) calcium resistance,(2)anchorage independence, and(3) increased cell proliferation in vivo. Moreover, TNFα increased the cancer stem cell-like population and stemness phenotype in HPV16-immortalized cells. However, such transforming effects were not observed in h TERTimmortalized cells, suggesting an HPV-specific role in TNFα-promoted oncogenesis. We also generated h TERT-immortalized cells that express HPV16 E6 and E7. Chronic TNFα exposure successfully induced the malignant growth and stemness phenotype in the E6-expressing cells but not in the control and E7-expressing cells. We further demonstrated that HPV16 E6 played a key role in TNFα-induced cancer stemness via suppression of the stemness-inhibiting micro RNAs mi R-203 and mi R-200 c. Overexpression of mi R-203 and mi R-200 c suppressed cancer stemness in TNFα-treated HPV16-immortalized cells. Overall, our study suggests that chronic inflammation promotes cancer stemness in HPV-infected cells, thereby promoting HPV-associated oral carcinogenesis.