Ovarian clear cell (OCCC) and endometrioid (EnOC) carcinomas are often subsumed under the umbrella term “endometriosis-associated ovarian cancer” (EAOC), since they frequently arise from ectopic endometrium settled in the ovaries. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is known to be aberrantly activated both in endometriosis and EAOC; however, its role in the progression of endometriosis to ovarian cancer remains unclear. In fact, cancer-associated alterations in the mTOR pathway may be found in normal uterine epithelium, likely acting as a first step towards ovarian cancer, through the intermediary stage of endometriosis. This review aims to summarize the current knowledge regarding mTOR signaling dysregulation in the uterine endometrium, endometriosis, and EAOC while focusing on the interconnections between the PI3K/AKT/mTOR pathway and other signaling molecules that give rise to synergistic molecular mechanisms triggering ovarian cancer development in the presence of endometriosis.

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

Adam Mylonakis, Tatiana S. Driva, Panagis Lykoudis, Maximos Frountzas, Nikolaos Machairas, Dimitrios Tsapralis, Konstantinos G. Toutouzas, Dimitrios Schizas. Ann Hepatobiliary Pancreat Surg -0001;0:. https://doi.org/10.14701/ahbps.23-161

Background/Objectives: In the era of precision medicine in gastric cancer, artificial intelligence has emerged as a tool in diagnosis, prognostic stratification, and clinical management. The role of big data analysis leveraging complex databases has been rapidly developing, thus challenging physicians to interpret and apply them in clinical practice. The aim of this comprehensive review is to present the current trends in the use of artificial intelligence in the field of diagnosis, histopathological evaluation, and clinical prognosis of gastric tumors. Methods: We screened the PubMed and MEDLINE databases for the latest studies with the development and evaluation of artificial intelligence algorithms in gastric cancer. Different sorts of deep learning protocols were explored, and their standardized applications are presented herein. Results: A broad spectrum of AI-based models extending from the surveillance of high-risk subepithelial lesions to the precise molecular characterization of tumors and treatment management are gaining space in clinical practice. However, all current studies are lacking a randomized design at the large-population scale, which is required to further integrate machine learning algorithms into standard clinical care. Conclusions: Despite the remaining challenges of data quality, algorithm improvement, and outcome interpretation, there is promising evidence that artificial intelligence can revolutionize gastric cancer management. There is a need to develop AI algorithms based on big data sources that must consequently be evaluated in randomized multicenter studies.

Esophageal adenocarcinoma (EAC) is an aggressive gastrointestinal (GI) malignancy with increasing incidence. Despite the recent progress in targeted therapies and surgical approaches, the survival rates of esophageal adenocarcinoma patients remain poor. The Dickkopf (DKK) proteins are secretory proteins known mainly as antagonists of the Wnt/β-catenin signaling pathway, which is considered an oncogene. However, it has been shown that in several GI cancers, including esophageal cancer, DKK1 may act as an oncogene itself through Wnt-independent signaling pathways. LRP5\6 and Kremen1/2 (Krm1/2) are transmembrane receptors to which the DKK proteins are mainly known to bind. CKAP4 (cytoskeleton-associated protein 4) is a novel receptor of DKK1, and the DKK1-CKAP4 pathway seems to be crucial in the role of DKK1 as an oncogene. The aim of this review is to feature the essential role of DKK1 and its receptors in carcinogenesis with a focus on EAC in an era of urgent need for specific biomarkers along with improved targeted therapies.

Purpose: Testicular Germ Cell Tumors (TGCTs) are the most frequent solid malignancies in young adult men. Regardless of differences in their cell of origin, all TGCTs are considered highly curable malignancies. However, approximately 3–5% of all TGCTs do not respond to platinum-based chemotherapies. The purpose of our paper is to investigate whether immunohistochemical expression of MLH1 and REV-7 can be used as predictive tissue markers for TGCTs. Material and Methods: The main demographic and clinicopathological characteristics of 64 male patients with TGCTs who underwent orchiectomy from 2007 to 2022 were retrospectively obtained from two large Oncology Clinics in Greece. Both patients with chemosensitive and chemoresistant disease were included. Immunohistochemical staining for MLH1 and REV-7 proteins was applied in specimens of these patients. Results: 31 seminomas and 33 non-seminomas were included. 48 patients had chemosensitive disease, while 16 had chemoresistant disease. 53 specimens showed preserved MLH1 expression, while 11 specimens had lost MLH1 expression. Expression of MLH1 was only significantly associated with patients’ age. 16 specimens showed positive REV-7 expression, while 48 specimens were REV-7 negative. Interestingly, 50% of patients with chemoresistant disease and 16,7% of patients with chemosensitive disease were REV-7 positive. This difference was statistically significant. Moreover, REV-7 positivity was significantly associated with chemoresistance, various clinicopathological parameters and patients’ prognosis and survival. Conclusion: Loss of MLH1 expression was only found to be significantly associated with lower patients’ age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.