Introduction

Stretta, a minimally invasive endoscopic procedure, has demonstrated efficacy in improving GERD symptoms by delivering radiofrequency energy to the lower esophageal sphincter. Despite its effectiveness, there is limited understanding of Stretta's impact on the epithelial barrier function.

Aims & Methods

This study aims to investigate changes in epithelial barrier function in GERD patients who underwent Stretta treatment. Tight junction gene expression levels, measurement of dilated intercellular spaces (DIS), and electrophysiological and permeability properties of the esophageal epithelium were investigated in order to determine the epithelial barrier function characteristics of patients treated with Stretta.
Six Stretta-treated (3 men, 38.5±4.9 years) patients and 15 (7 men, 36.2±6.3 years) healthy volunteers (HV) were included in the study. Esophageal epithelial biopsies taken during endoscopy were used as study material. In order to determine tight junction gene expressions, qRT-PCR method was used for the expression levels of 6 (E- cadherin, Zonula ocludens 1, Zonula ocludens 2, Claudin 1, Claudin 4, Occludin) genes. Ussing chamber system was used to determine the transepithelial resistance (TEER) of the esophageal epithelium and permeability properties were examined by a fluorometric method. In DIS measurements, For each patient, photographs were taken from 10 different areas without artifacts under the light microscope at 1000x magnification. Ten vertical measurements were made continuously around the single epithelial cell with the largest DIS between the upper part of the Stratum Basale and the six parts of the Stratum Spinosum. A total of 100 blind measurements were made by a single investigator for each patient.

Results

In comparing the gene expressions of tight junctions before (Pre-str) and after Stretta (Post-str), it was observed that only the expression of the Claudin 4 gene was 6.91 (p=0.02) fold higher in the Post-str group compared to the Pre-str group. Similarly compared to the HV group, the Post-str group exhibited a 6.02-fold (p=0.001) increase in Claudin 4 expression.
Comparing the TEER results between the pre-str (110.8 Ω) and post-str (151.7 Ω) groups, although there is a numerical increase, no statistically significant difference was observed. In addition, the TEER values of the HV (165,8 Ω ) group were statistically significantly higher than the Pre-str group. Upon examining the permeability results, it was determined that the Post-str (30.1 pmol) group had lower permeability compared to the Pre-str (67.3 pmol) group (p=0.043), while there was no statistically difference observed between the HV (34.4 pmol) group and the Stretta groups.
According to the study findings, the group that exhibited the largest DIS was the Post-str (0.974±0.212) group. However, no statistically significant difference was observed between the Pre-str (1.030±0.266) and Post-str groups in terms of DIS. Notably, a significant difference (p=0.03) was only observed between the HV (1.374±0.269) group and the Post-str group.

Conclusion

In summary, our findings suggest that treatment with Stretta strengthens the epithelial barrier function, as evidenced by the increase in Claudin 4 expression and the corresponding decrease in fluorescent permeability. However, the lack of support from our DIS results in terms of gene expression and electrophysiological changes suggests the need for further investigation to fully understand the effects of Stretta treatment on the epithelial barrier.

Introduction

Persistent High-Risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC). Anal cytology and HR-HPV testing are strategies used for anal SCC screening. Anal HR-HPV prevalence in HIV-negative MSM and in MSM living with HIV (MSM-HIV) is 41% and 74%, respectively. The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP (MSM-PrEP). The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytology in MSM-PrEP and MSM-HIV.

Aims & Methods

MSM-PrEP and MSM-HIV were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing.

Results

We enrolled 150 MSM-PrEP and 152 MSM-HIV. Quality of anal swabs was sufficient in respectively 96.7% (n=145) and 96.1% (n=146). HR-HPV prevalence in MSM-PrEP was comparable with HR-HPV prevalence in MSM-HIV; respectively 74.5% (n=108) and 76.6% (n=111) tested positive for at least one HR-HPV (p=0.78). No significant difference in abnormal cytology was seen; 53.1% (n=77) of the MSM-PrEP and 57.2%(n=83) of MSM-HIV had either ASCUS, ASC-H, LSIL or HSIL (p=0.56).

Conclusion

The risk of HR-HPV infection and abnormal anal cytology in MSM-PrEP is comparable to that in MSM-HIV, both of which are higher than observed in HIV-negative MSM not using PrEP. This heightened prevalence of HPV in MSM-PrEP poses an increased risk for HSIL. Recent guidelines on anal screening from International Anal Neoplasia Society recommend screening for anal cancer in both MSM-HIV and HIV-negative MSM, reflecting respective anal cancer incidence rates of 70-100 per 100,000 person-years and 18-34 per 100,000 person-years. Our findings suggest that MSM-PrEP constitutes a distinct risk group for anal SCC positioned between MSM-HIV and HIV-negative MSM not using PrEP.

References

Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
Stier E, Clarke M, Deshmukh A et al. International Anal Neoplasia Society's consensus guidelines for anal cancer screening.Int.J.Cancer.2024;154:1694-1702.

Introduction

Differentiating between colorectal serrated polyps (SPs) on endoscopy can be challenging since sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) tend to have a similar appearance^1-4. Furthermore, the endoscopic differences between the two subtypes of HPs, namely microvesicular HP (MVHP) and goblet cell-rich HP (GCHP), are not well understood^5,6. Therefore, we compared the endoscopic features of SSL, MVHP, and GCHP.

Aims & Methods

This retrospective, cross-sectional study was conducted at the Toyoshima Endoscopy Clinic. We examined the polyp size, location, Paris classification type, mucus cap, indistinct border, expanded crypt opening, varicose microvascular vessels (VMV), and Japan NBI expert team (JNET) classification type. Multivariable analysis was performed to determine the endoscopic finding that predicted SP histology using a binomial logistic regression model. We constructed endoscopic microvesicular goblet (MG) score for differentiating SPs using the endoscopic findings associated with SP histology in the multivariable analysis, and calculated the area under the receiver operating characteristic curve (AUC) and diagnostic accuracy.

Results

A total of 1366 SPs were eligible for this study, including 321 SSLs, 718 MVHPs, and 327 GCHPs. The mean polyp size was 6.24 mm. SPs in the proximal colon accounted for 70.7%. In the comparison between MVHP and GCHP, a mucus cap (partial regression coefficient 1.44, 95% confidence interval [CI] 1.06-1.82), expanded crypt opening (1.92, 1.44-2.40), and VMV (1.04, 0.58-1.49) were more often found in MVHP in contrast to GCHP (Table). comparison of SSL and MVHP showed that SSLs were located in the proximal colon (0.70, 0.30-1.10), were larger (0.21, 0.16-0.25), and had mucus cap (0.54, 0.16-0.93) compared to MVHPs. On comparing the SSL plus MVHP group and GCHP group, larger size (0.12, 0.06-0.19), a mucus cap (1.76, 1.39-2.14), expanded crypt opening (2.04, 1.57-2.52), VMV (1.21, 0.75-1.68), and JNET type 2A (1.17, 0.73-1.61) were more often observed in SSL + MVHP group compared with GCHP. Mucus cap, expanded crypt opening, and VMV were each assigned 1 point and the sum of the points was defined as the endoscopic MG score. In the examination of MVHPs and GCHPs, the AUC of the endoscopic MG score for predicting MVHP was 0.78 (95% CI 0.76-0.81) and the optimal cut-off value was 1; the sensitivity, specificity, and positive predictive value (PPV) were 74.7%, 75.5%, 87.0%, respectively. In the assessment of SSLs, MVHPs, and GCHPs, the AUC of the endoscopic MG score for predicting SSL plus MVHP group was 0.82 (0.79-0.84) and the optimal cut-off value was 1; the sensitivity, specificity, and PPV were 79.4%, 75.5%, and 91.2%, respectively.

Conclusion

MVHP and GCHP, while belonging to the same HP category, exhibited different endoscopic appearances such as mucus cap, expanded crypt opening, and VMV. Conversely, SSL and MVHP despite belonging to different histopathological categories, showed similar endoscopic appearances except for mucus cap. Moreover, SSL plus MVHP showed distinct endoscopic appearances compared to GCHP group. Considering MVHP and GCHP as separate entities can aid in the endoscopic diagnosis of SPs.

References

1. Ijspeert JEG, de Wit K, van der Vlugt M, et al. Prevalence, distribution and risk of sessile serrated adenomas/polyps at a center with a high adenoma detection rate and experienced pathologists. Endoscopy. 2016;48(08):740-746.
2. Turner KO, Genta RM, Sonnenberg A. Lesions of All Types Exist in Colon Polyps of All Sizes. Am J Gastroenterol. 2018;113(2):303-306.
3. Zessner-Spitzenberg J, Waldmann E, Jiricka L, et al. Comparison of adenoma detection rate and proximal serrated polyp detection rate and their effect on post-colonoscopy colorectal cancer mortality in screening patients. Endoscopy. 2023;55(5):434-441.
4. Nishizawa T, Yoshida S, Toyoshima A, et al. Endoscopic diagnosis for colorectal sessile serrated lesions. World J Gastroenterol. 2021;27(13):1321-1329.
5. Qazi TM, O'Brien MJ, Farraye FA, et al, 3rd. Epidemiology of goblet cell and microvesicular hyperplastic polyps. Am J Gastroenterol. 2014;109(12):1922-1932.
6. Crockett SD, Barry EL, Mott LA, et l. Predictors of Incident Serrated Polyps: Results from a Large Multicenter Clinical Trial. Cancer Epidemiol Biomarkers Prev. 2022;31(5):1058-1067.

Disclosure

The authors have no COI.

Introduction

Persistent high-risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC).
HR-HPV prevalence is higher in men who have sex with men living with HIV (MSMLWH) than in HIV-negative MSM, respectively 74% and 37-41% (1,2). The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP. The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytohistology in MSM using PrEP and MSMLWH. Preliminary data are reported here and final results are expected in coming months.

Aims & Methods

MSM using PrEP and MSMLWH were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing. Patients with HR-HPV infection, abnormal cytology or both were subsequently sent for High Resolution Anoscopy (HRA).

Results

At present, we enrolled 150 MSM using PrEP and 107 MSMLWH. Quality of anal swabs was sufficient in respectively 95% (n=143) and 81% (n=87). HR-HPV prevalence in MSM using PrEP was comparable with HR-HPV prevalence in MSMLWH; respectively 74% (n=106) and 75% (n=65) tested positive for at least one HR-HPV (p=1.000). No significant difference in abnormal cytology was seen; 53% (n=76) of MSM using PrEP and 58% (n=51) of MSMLWH had either ASC-US, ASC-H, LSIL or HSIL (p=0.6). Until today, 58 MSM using PrEP and 31 MSMLWH underwent HRA. Biopsies were performed in 43 MSM using PrEP and 25 MSMLWH. Preliminary results on histology of lesions show presence of anal HSIL in 19% (n=11) and 32% (n=10) respectively (p= 0.706).

Conclusion

MSM using PrEP have a similar risk of HR-HPV infection and abnormal anal cytohistology as MSMLWH, which is higher than what has been reported in HIV-negative MSM not using PrEP (1). ANCHOR showed that treating anal HSIL reduces the incidence of anal SCC in people living with HIV (3), but the risk of progression to anal cancer and thus the need for screening and treatment is to be investigated in this immunocompetent population of MSM using PrEP.

References

1. Wei F, Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
2. Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
3. Palefsky J, Lee J, Jay N et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 202;386(24):2273-82.