Stem cells are candidates, because their self-renewal and longevity facilitate the sequential accumulation Rapamycin manufacturer of oncogenic mutations.6 Two stem-cell niches have been described within the liver: canals

of Hering, containing hepatic stem cells, and intrahepatic PBGs, containing BTSCs.3, 7 The former has been involved in the pathogenesis of cholangiocarcinomas with mixed features,8 whereas the latter could be implicated in the carcinogenesis of mucin-producing cholangiocarcinomas. Mucin-producing intrahepatic cholangiocarcinoma should be considered as having a similar origin to hilar and extrahepatic cholangiocarcinomas, opening new perspectives in the classification of cholangiocarcinomas. Vincenzo Cardinale M.D.*, Yunfang Wang M.D., Ph.D.†, Guido Carpino Ph.D.‡, Lola M. Reid Ph.D.¶, Eugenio Gaudio M.D.**

§, Domenico Alvaro M.D.* **, * Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza University of Rome, Rome, Italy, † The Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China, ‡ Department of Health Sciences, University of Rome “Foro Italico”, Rome, Italy, § Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy, ¶ Department of Cell and Molecular Physiology, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, NC, ** Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy. “
“Proton beam therapy is safe and more effective than conventional radiation therapy for the local click here control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by imaging is not accurate during the early post-irradiation period. Therefore, we examined whether the histopathological study

of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response. Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound-guided percutaneous fine-needle aspiration from the center of the tumor before, 3 weeks after and 1 year post-proton therapy. The specimens were examined after staining with hematoxylin–eosin MCE (HE) and a MIB-1 antibody. MIB-1 labeling indices (LI) before treatment were 13.0 ± 8.5% (mean ± SD; range, 0.6–27.0), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% (range, 0.6–8.9) (P < 0.05). Although the tumor size was reduced, we did not observe a reduction in tumor blood flow by dynamic computed tomography or degenerative changes by HE. All lesions that displayed reduced MIB-1 LI at 3 weeks post-proton treatment were ultimately diagnosed as complete response at 1 year after treatment. In contrast, one case with increased MIB-1 LI at 3 weeks had significant tumor size progression at 1 year post-treatment.