Squamocolumnar Junction

Abstract: Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection.

Abstract: BACKGROUND Hiatus hernia and lower oesophageal sphincter hypotension are often viewed as opposing hypotheses for gastro-oesophageal junction incompetence. AIMS To examine the interaction between hiatus hernia and lower oesophageal sphincter hypotension. METHODS In seven normal subjects and seven patients with hiatus hernia, the squamocolumnar junction and intragastric margin of the gastro-oesophageal junction were marked with endoscopically placed clips. Axial and radial characteristics of the gastro-oesophageal junction high pressure zone were mapped relative to the hiatus and clips during concurrent fluoroscopy and manometry. Responses to inspiration and abdominal compression were also analysed. RESULTS In normal individuals the squamocolumnar junction was 0.5 cm below the hiatus and the gastro-oesophageal junction high pressure zone extended 1.1 cm distal to that. In those with hiatus hernia, the gastro-oesophageal junction high pressure zone had two discrete segments, one proximal to the squamocolumnar junction and one distal, attributable to the extrinsic compression within the hiatal canal. Inspiration and abdominal compression mainly augmented the distal one. Simulation of hernia reduction by algebraically summing the proximal segment pressures with the hiatal canal pressures restored normal maximal pressure, radial asymmetry, and dynamic responses of the gastro-oesophageal junction. CONCLUSIONS Hiatus hernia reduces lower oesophageal sphincter pressure and alters its dynamic responsiveness by spatially separating pressure components derived from the intrinsic lower oesophageal sphincter and the extrinsic compression of the oesophagus within the hiatal canal.

Abstract: Introduction: Barrett’s oesophageal epithelium (BE) is clinically important due to the associated inflammatory and malignant complications which are unevenly distributed throughout the BE segment. As the immunoregulatory environment may influence disease manifestations, we analysed the inflammatory and cytokine responses throughout the BE mucosa. We then investigated whether the inflammatory gradient is related to the distribution of metaplastic cell subtypes, epithelial exposure to the components of refluxate, or squamocolumnar cell interactions. Methods: Fifty consecutive patients with long segment BE were recruited. The segmental degree of endoscopic and histopathological inflammation was graded, and expression of interleukin (IL)-1β, IL-8, IL-4, and IL-10 were determined by ELISA following organ culture with or without addition of acid or bile salts. Mucin staining and IL-10 immunohistochemistry were performed. The effect of squamocolumnar interactions on cytokine expression were analysed using cocultures of squamous (OE-21) and BE (TE7) carcinoma cell lines. Results: There was a histopathological inflammatory gradient in BE. Inflammation was maximal at the new squamocolumnar junction with ≥2-fold increase in proinflammatory IL-8 and IL-1β expression. The proximal proinflammatory response could not be explained by the distribution of metaplastic subtypes. Pulsatile exposure of BE to acid and bile, as well as juxtaposition of BE to squamous epithelial cells in culture, increased expression of IL-1β. In contrast, inflammation was minimal distally with a significant increase in anti-inflammatory IL-10 expression and 4/6 cancers occurred distally. Conclusions: Specific cytokine responses may contribute to the localisation of inflammatory and malignant complications within BE.