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Simple Summary: Hepcidin, a peptide hormone, is overexpressed in colorectal cancer, mainly in the advanced stages. This study assessed whether the pre-treatment serum levels of hepcidin are a predictive factor of the overall survival of patients with microsatellite stable metastatic colorectal cancer receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations). Our data showed that patients with metastatic colorectal cancer had higher serum levels of hepcidin than the controls, and patients with circulating levels of hepcidin greater than 40 ng/mL had a reduced overall survival as compared to those with values lower than 40 ng/mL. These data suggest that the serum level of hepcidin can help identify subgroups of microsatellite stable metastatic colorectal cancer patients with a more aggressive course. Background & Aim. Hepcidin, a key hormone in iron homeostasis, is synthesized by colorectal cancer (CRC) cells, particularly in the late stages of tumorigenesis. This study aimed to ascertain whether the serum levels of hepcidin could serve as a prognostic biomarker in microsatellite stable (MSS) metastatic CRC (mCRC). Specifically, we assessed the predictive value of baseline serum hepcidin levels for the overall survival (OS) of patients with MSS mCRC receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations). Methods. Serum samples were prospectively collected from 35 normal healthy volunteers (normal controls) and 55 patients with MSS mCRC and analyzed for their content of hepcidin by ELISA. Results. Serum hepcidin levels were significantly greater in patients with mCRC than in the normal controls. In the mCRC group, patients with baseline levels of hepcidin greater than 40 ng/mL had a significantly shorter 1-year OS rate (39%) than those with hepcidin levels lower than 40 ng/mL (80%) [hazard ratio (HR): 2.94; 95% CI: 1.27–6.84; p = 0.01]. A multivariate Cox regression analysis showed that the pre-treatment serum hepcidin levels were an independent prognostic factor for OS, not influenced by other well-known prognostic factors (i.e., CEA status, Karnofsky performance score, number of metastatic sites, RAS/BRAF mutations), and this was evident across all major patient subgroups. Conclusions. Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings. [ABSTRACT FROM AUTHOR]

Simple Summary: VaIN after hysterectomy is a rare intraepithelial neoplasia strongly associated with HR-HPV infection. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. In a retrospective study of 170 women hysterectomized due to CIN3 or due to benign uterine pathology, all cases of high-grade VaIN occurred in women with persistent HPV. The most frequent genotype was 16. All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. A vaginal wall biopsy under colposcopy is recommended to be routinely performed before surgery for patients undergoing hysterectomy due to CIN3 or stage IA cervical cancer, which will help determine the necessary extent of vaginal resection during the procedure. The data from the literature show that women undergoing a LEEP due to CIN3 have a greater risk of having subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue, and they show mixed results. This study aimed to investigate the incidence of high-grade or severe VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease and illustrate the treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent a laparoscopic hysterectomy due to high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and a diagnosis of high-grade VaIN was 18 months. Results: High-grade or severe VaIN was found in eight patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized due to CIN3 showed an eight-fold greater risk than women hysterectomized due to benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized due to benign disease. The risk of developing VaIN is greater in women with viral persistence. Conclusion: All these elements suggest that it is a history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered risk factors for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing. [ABSTRACT FROM AUTHOR]