Putative role of circulating human papillomavirus DNA in the development of primary squamous cell carcinoma of the middle rectum: a case report

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines. In the stroma nearby the tumor mass we were able to demonstrate the presence of virus DNA in the stromal compartment, supporting its potential to be transferred from epithelial cells to the stromal ones. Thus, this case report favors the notion that human papillomavirus DNA can be vehiculated by exosomes in the blood of neoplastic patients and that it can be transferred, at least in vitro, to normal and neoplastic cells. Furthermore, we showed the presence of viral DNA and RNA in pluripotent stem cells of non-tumor tissue, suggesting that after viral integration (as demonstrated by p16 and RNA in situ hybridization positivity), stem cells might have been activated into cancer stem cells inducing neoplastic transformation of normal tissue through the inactivation of p53, p21, and Rb. It is conceivable that the virus has elicited its oncogenic effect in this specific site and not elsewhere, despite its wide anatomical distribution in the patient, for a local condition of immune suppression, as demonstrated by the increase of T-regulatory (CD4/CD25/FOXP3 positive) and T-exhausted (CD8/PD-1positive) lymphocytes and the M2 polarization (high CD163/CD68 ratio) of macrophages in the neoplastic microenvironment. It is noteworthy that our findings depicted a static picture of a long-lasting dynamic process that might evolve in the development of tumors in other anatomical sites. Copyright © 2019 Ambrosio, Vernillo, De Carolis, Carducci, Mundo, Ginori, Rocca, Nardone, Lucenti Fei, Carfagno, Lazzi, Cricca and Tosi

Diffusion-weighted MR volumetry for assessing the response of rectal cancer to combined radiation therapy with chemotherapy

Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imagin

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report [La volumetria con risonanza magnetica pesata in diffusione nella valutazione della risposta alla chemio-radioterapia nel tumore del retto: studio preliminare]

Purpose: This study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (V DWI) and compared it with conventional T2-weighted volumetry (V C) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT). Materials and methods: Fourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate V C. A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm 2 and volume (V DWI) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen. Results: Interobserver agreement was 0.977 [(95% confidence interval (CI) 0.954-0.989) and 0.956 (95% CI 0.905-0.980) for V C and V DWI and 0.964 (95% CI 0.896-0.988) and 0.271 (95% CI-0.267 to 0.686) between V C and V DWI before and after CHRT. The correlation between TRG and V C and V DWI was, respectively, rho = 0.597 (p<0.05) and r 2=0.156 (p=0.162) and rho=0.847 (p<0.001). Conclusions: V DWI seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value

Notulae to the Italian native vascular flora: 12

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1