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BACKGROUND HIV-positive individuals have high incidence of anal high-grade squamous intraepithelial lesions (HSIL) at the squamocolumnar junction (SCJ), which can progress to cancer. Focal radiofrequency ablation (RFA) treats HSIL, but metachronous recurrence remains high and may be improved with circumferential treatment. SETTING The study was performed at a single center. METHODS This was a prospective trial of circumferential anal RFA using Barrx 60 RFA focal catheters in participants with ≥1 anal SCJ HSIL. The entire SCJ was ablated by RFA. Adverse events (AEs), symptoms, including pain, and quality of life were assessed. High-resolution anoscopy assessed recurrences at 3, 6, 9, and 12 months. Lesion site biopsies occurred at month 12. Recurrences were retreated with focal RFA. RESULTS Ten male participants (9 HIV+), with a median 2 HSILs (range 2-8) each, enrolled. Median T-cell count and viral load were 730 cells/mcL and 38 copies/mL. Median duration of RFA treatment was 6.5 (5-13) minutes. Lesion persistence occurred in 4 participants (3 at 3 months, 1 at 6 months). Recurrence at a new site occurred in 1 participant at 3 months. No lesion persisted after retreatment. All participants were HSIL free and completely healed by 12 months. Two device-related mild AEs occurred in 1 participant each (thrombosed external hemorrhoid and soft anal scar; both resolved). No serious AEs occurred. CONCLUSION Circumferential anal SCJ RFA produced total HSIL eradication with no more than 2 treatments. Circumferential RFA seems to be well tolerated with minimal pain and no serious AEs in HIV+ participants. CLINICALTRIALS.GOV:: NCT02189161.

PurposeRadiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL.MethodsTwenty-one HIV-negative participants with HSIL occupying ≤half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3months for 12months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA.ResultsTwenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29%) participants had recurrent HSIL within the treated hemi-circumference within 1year. Four participants (19%) had persistence of an index lesion at 3months. One (2.9%) index HSIL persisted again at 12months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1year was 76% (95% CI 52-89%). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43% (95% CI 10-73%) and 93% (95% CI 59-99%), respectively (p=0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95% CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95% CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding.ConclusionsHemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus. In adult normal prostate tissue, the average abundance of Ck6a+ cells was 4.9%. With proliferative stimuli in the prostate organ culture model, in which the epithelial–stromal interaction was maintained, a remarkable increase of Ck 6a expression was noticed to up to 64.9%. The difference in cytokeratin 6a expression between the normal adult prostate and the prostate organ culture model was statistically significant ( p 0.0001 ). Within the prostate organ culture model the increase of cytokeratin 6a-expressing cells significantly correlated with increased proliferation index ( r = 0.7616 , p = 0.0467 ) The Ck6a+ cells were capable of differentiation as indicated by their expression of luminal cell markers such as ZO-1 and prostate specific antigen (PSA). Our data indicate that Ck6a+ cells represent a prostatic epithelial stem cell candidate possessing high potential for proliferation and differentiation. Since the development of benign prostatic hyperplasia and prostate carcinogenesis are disorders of proliferation and differentiation, the Ck6a+ cells may represent a major element in the development of these diseases.