Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: An individual participant data meta-analysis.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGCs) of the pancreas is a rare neoplasm that accounts for less than 1% of all pancreatic malignancies. The aim of this study was to review the literature regarding UC-OGC, and to highlight its biological behavior, clinicopathologic characteristics, prognosis, and therapeutic options. A systematic review of the literature in PubMed/Medline and Scopus databases was performed (last search October 31st, 2023) for articles concerning pancreatic UC-OGC in the adult population. Fifty-seven studies met the inclusion criteria, involving 69 patients with a male-to-female ratio of 1.1:1 and a mean age of 62.96. Main symptoms included abdominal pain (33.3%), jaundice (14.5%), weight loss (8.7%), while fourteen patients (20.3%) were asymptomatic. Surgical resection was performed in 88.4% of cases. Survival rates at one, three, and five years were 58%, 44.7%, and 37.3% respectively. Sex, age, size (cut-off of 4 cm), location, and adjuvant treatment did not significantly affect patient survival. UC-OGC of the pancreas is a rare subtype of undifferentiated pancreatic carcinoma with a better prognosis than conventional pancreatic ductal adenocarcinoma or undifferentiated carcinoma without giant cells. The establishment of a dedicated patient registry is imperative to further delineate the optimal treatment for this uncommon clinical entity.

The Immunohistochemical Expression of REV-7 in Various Human Cancer Pathology Specimens: A Systematic Review.

The purpose of this systematic review is to summarize all existing evidence, regarding the immunohistochemical expression of REV-7 in different human cancer pathology specimens. Moreover, the association of REV-7 expression with disease severity (clinical course), patients' survival, prognosis, and response to various treatments, such as chemotherapy and irradiation, was investigated. Three databases (PubMed, Scopus, and Cochrane) were systematically screened, from inception to September 2, 2023, as suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies using immunohistochemical staining for REV-7 in paraffin-embedded cancer tissues were included. Nine studies met the inclusion criteria and were included in the final qualitative synthesis. All nine studies were retrospective and non-comparative ones. Selected studies reported immunohistochemical expression of REV-7 in different types of cancer, including testicular cancer, ovarian cancer, esophagus squamous cell carcinoma, prostate cancer, colorectal cancer, diffuse large B-cell lymphoma, breast cancer, lung cancer, and skin cancer. High REV-7 expression was associated with faster disease progression, resistance to available treatment options, and worse prognosis in the majority of included studies. These results indicate that immunohistochemical staining of REV-7 protein could potentially be used as a predictive tissue marker in certain cases. Promising results, arising from REV-7 inactivation experiments, render REV-7 targeting a potential therapeutic strategy for future cancer management, especially in the cases of chemoresistant or radioresistant disease.

Predictive tissue markers in testicular germ cell tumors: Immunohistochemical expression of MLH1 and REV-7 proteins.

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.

Gender disparity trends in genitourinary oncology academic publishing over the past 3 decades: A bibliometric analysis.

OBJECTIVES: To examine gender disparities in genitourinary (GU) oncology academic publishing over the past three decades. MATERIALS AND METHODS: We performed a bibliometric analysis of eight academic journals featuring GU oncology research articles: Journal of Clinical Oncology, Cancer, European Journal of Cancer, European Urology, Journal of Urology, BJU International, Prostate Cancer and Prostatic Diseases, and Urologic Oncology: Seminars and Original Investigations. After selecting four time points (1990, 2000, 2010, 2020), we recorded the gender of the first and senior authors and investigated their association with independent variables including publication year, research field, and geographic continent. Results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 14,786 articles were included in our analyses. Females comprised 25.7% of first and 18.1% of senior authors. Compared to 1990, there was a trend of progressively higher female first author (OR 1.47 [95% CI 1.27-1.69] in 2000; 2.28 [95% CI 2.00-2.59] in 2010; 3.10 [95% CI 2.71-3.55] in 2020) and senior author positions (OR 1.23 [95% CI 1.05-1.45] in 2000; 1.67 [95% CI 1.45-1.93] in 2010; 2.55 [95% CI 2.20-2.96] in 2020). Compared to GU oncology, non-GU oncology articles were more likely to have female first (OR 2.61, 95% CI 2.38-2.86) or senior authors (OR 2.61, 95% CI 2.35-2.91). Articles from Asia (OR 0.45, 95% CI 0.38-0.51), Africa (OR 0.45, 95% CI 0.22-0.91), and international collaborations (OR 0.62, 95% CI 0.50-0.76) had a lower proportion of female first authors compared to North America. First authors were significantly more likely to be female when senior authors were also female (OR 2.45, 95% CI 2.23-2.69). CONCLUSIONS: Despite the bridging trend demonstrated, GU oncology remains a male-predominant discipline. Female leadership and mentorship are pivotal in achieving gender parity in the academic medicine community.

Endometriosis-Associated Ovarian Carcinomas: How PI3K/AKT/mTOR Pathway Affects Their Pathogenesis.

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.

Effects of Incretin Pathway Elements on Bone Properties.

Introduction The effects of incretin-based drugs, such as receptor agonists of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4, on bone metabolism are not completely clear yet. The aim of this study is to compare the effects of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4 on the bone to see how different elements of the incretin pathway affect bone quality in terms of biomechanical properties, bone turnover, and mineral properties. Materials and methods Forty 10-week-old Wistar rats were divided into four groups: a control group, a control diabetic group, a diabetic group treated with sitagliptin, and a diabetic group treated with exenatide. Type 2 diabetes was simulated by dietary manipulation in addition to low-dose streptozotocin, and then two different incretin-based drugs were administered. The rats were sacrificed after five weeks of therapeutic treatment. Their serum was analyzed with the enzyme-linked immunosorbent assay (ELISA) method for basic bone turnover markers, and their right femur was subjected to a three-point bending test. Finally, Hematoxylin & Eosin staining, in addition to Raman spectroscopy, were employed to access the collagen and mineral properties of the bone. Results Both incretin-based drugs reduced osteoclast function; however, they were not able to restore osteoblastic function to normal. The net effect on bone strength was surprising: bone elasticity was restored by the antidiabetic treatment, but bone strength deteriorated. Exenatide had a slightly more pronounced effect, which, although not significant, points to the direction that dipeptidyl peptidase-4 (DPP4) may be a linking factor between reduced osteoclastic function and reduced bone formation, as suggested by the literature. Conclusion DPP4 receptors seem to be one of the links between reduced osteoclast function and reduced bone remodeling, so DPP4 inhibition can be more detrimental to the bone than glucagon-like peptide-1 (GLP-1) receptor agonists.

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases.

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.