Expression and clinical significance of concomitant FAK/SRC and p-Paxillin in mobile tongue squamous cell carcinoma.

Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reservedBACKGROUND/AIM: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: FAK, SRC and phospho-paxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival. RESULTS: Concomitant high FAK/SRC expression was significantly associated with high grade of tumor differentiation (p=0.048) and longer disease-free patient survival (log-rank test, p=0.019). High p-paxillin expression was significantly associated with greater depth of invasion (p=0.002), lymph node metastasis (p=0.048) and poorer disease-free patient survival (log-rank test, p=0.021; Cox-regression analysis, p=0.031). CONCLUSION: The present study provides evidence that FAK/SRC and paxillin play a role in the pathophysiological aspects of mobile tongue SCC and could constitute therapeutic targets.Final Accepted Versio

Association of Mediterranean Diet Adherence with Disease Progression Characteristics, Lifestyle Factors and Overall Survival in Gastric Cancer Patients

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/BACKGROUND: The Mediterranean diet (MD) exerts a protective effect against cancer development and progression; however, the evaluation of its impact on gastric cancer still remains quite scarce. The present study aims to evaluate the association of MD adherence during the lifespan with disease progression characteristics, lifestyle factors and overall survival in gastric carcinoma patients. METHODS: This is an observational, cross-sectional study conducted on 186 gastric cancer patients followed up for a median time interval of 57 months or until death due to cancer disease. Tumor histopathological characteristics were retrieved from patients' medical records, while validated questionnaires assessing, immediately after the time of diagnosis, health-related quality of life, physical activity levels, sleep quality, depression, anxiety and MD adherence during the lifespan were used. RESULTS: Higher MD adherence during the lifespan was significantly associated with younger patients (p = 0.0106), regular smoking (p < 0.0001), abnormal BMI status (p < 0.0001), intestinal-type gastric carcinoma (p = 0.0111), high tumor histopathological grade (p < 0.0001) and earlier disease stage (p < 0.0001). Moreover, patients with elevated MD adherence during their lifespan showed significantly better health-related quality of life (p < 0.0001), higher physical activity levels (p < 0.0001), more adequate sleep quality (p < 0.0001) and lower prevalence of depression (p = 0.0003) and anxiety (p = 0.0006) compared to those with reduced MD adherence. In multiple regression analysis, elevated MD compliance during the lifespan was independently correlated with longer overall patient survival after adjustment for several confounders (Cox regression analysis, p = 0.0001). CONCLUSIONS: Higher MD adherence during the lifespan was associated with less advanced tumor histopathology characteristics and favorable mental and physical lifestyle factors. Moreover, higher MD adherence during the lifespan was also independently correlated with longer overall survival in gastric carcinoma patients. Thus, adopting a healthy dietary pattern like the MD during the lifespan may act as a preventive agent in combination with a healthy lifestyle against gastric cancer development and progression.Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia

Histone deacetylases (HDACs) have long been implicated in tumorigenesis and tumor progression demonstrating their important participation in neoplasia. Therefore, numerous studies have been performed, highlighting the mechanism of HDACs action in tumor cells and demonstrating the potential role of HDAC inhibitors in the treatment of different cancer types. The outcome of these studies further delineated and strengthened the solid role that HDACs and epigenetic modifications exert in neoplasia. These results have spread promise regarding the potential use of HDACs as prospective therapeutic targets. Nevertheless, the clinical significance of HDAC expression and their use as biomarkers in cancer has not been extensively elucidated. The aim of our study is to emphasize the clinical significance of HDAC isoforms expression in different tumor types and the correlations noted between the clinicopathological parameters of tumors and patient outcomes. We further discuss the obstacles that the next generation HDAC inhibitors need to overcome, for them to become more potent

Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia

Histone deacetylases (HDACs) have long been implicated in tumorigenesis and tumor progression demonstrating their important participation in neoplasia. Therefore, numerous studies have been performed, highlighting the mechanism of HDACs action in tumor cells and demonstrating the potential role of HDAC inhibitors in the treatment of different cancer types. The outcome of these studies further delineated and strengthened the solid role that HDACs and epigenetic modifications exert in neoplasia. These results have spread promise regarding the potential use of HDACs as prospective therapeutic targets. Nevertheless, the clinical significance of HDAC expression and their use as biomarkers in cancer has not been extensively elucidated. The aim of our study is to emphasize the clinical significance of HDAC isoforms expression in different tumor types and the correlations noted between the clinicopathological parameters of tumors and patient outcomes. We further discuss the obstacles that the next generation HDAC inhibitors need to overcome, for them to become more potent

Polymorphous adenocarcinoma of the salivary glands: an overview of immunohistochemical features and insights on molecular pathology

Polymorphous adenocarcinoma (PAC), represents a common minor salivary gland tumor (SGT) characterized by local growth, low metastatic potential and non-aggressive biologic behavior. Due to the clinical aggressiveness noted in a subset of such tumors, the former term polymorphous low-grade adenocarcinoma (PLGA) was recently revised. PAC’s clinical features and histological diversity result in clinical overlap of this entity with several other SGTs including mainly adenoid cystic carcinoma (AdCC). Differential diagnosis among the entities is crucial, in terms of tumor management and patients’ prognosis. The aim of the present review is to summarize the histological, cytological, immunohistochemical and molecular features of PAC. Histopathological examination is usually adequate for PAC differential diagnosis from other SGTs, except of AdCC. Several immunohistochemical markers including c-Kit, S-100/ MG, Mcm-2 and Integrin β-1, -3, -4, are reported to be useful diagnostic aids in borderline cases. Limitations in sample numbers and study methodology issues of the immunohistochemical PAC studies complicate the identification and selection of appropriate markers useful in the differential diagnosis. Additionally, molecular analyses of PAC specimens indicate that the PAC spectrum phenotypes result from different genotypes (protein kinase D positive; PRKD(+) and PRKD(-) tumors). PAC pathogenesis remains to be determined in each particular genotype while the convergence issue should be addressed in future studies

Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?

Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongoing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer’s microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies

The EPH/Ephrin System in Gynecological Cancers: Focusing on the Roots of Carcinogenesis for Better Patient Management

Gynecological cancers represent some of the most common types of malignancy worldwide. Erythropoietin-producing hepatocellular receptors (EPHs) comprise the largest subfamily of receptor tyrosine kinases, binding membrane-bound proteins called ephrins. EPHs/ephrins exhibit widespread expression in different cell types, playing an important role in carcinogenesis. The aim of the current review was to examine the dysregulation of the EPH/ephrin system in gynecological cancer, clarifying its role in ovarian, endometrial, and cervical carcinogenesis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms ephrin, ephrin receptor, ovarian cancer, endometrial cancer, and cervical cancer were employed and we were able to identify 57 studies focused on gynecological cancer and published between 2001 and 2021. All researched ephrins seemed to be upregulated in gynecological cancer, whereas EPHs showed either significant overexpression or extensive loss of expression in gynecological tumors, depending on the particular receptor. EPHA2, the most extensively studied EPH in ovarian cancer, exhibited overexpression both in ovarian carcinoma cell lines and patient tissue samples, while EPHB4 was found to be upregulated in endometrial cancer in a series of studies. EPHs/ephrins were shown to exert their role in different stages of gynecological cancer and to influence various clinicopathological parameters. The analysis of patients&rsquo; gynecological cancer tissue samples, most importantly, revealed the significant role of the EPH/ephrin system in the development and progression of gynecological cancer, as well as overall patient survival. In conclusion, the EPH/ephrin system represents a large family of biomolecules with promising applications in the fields of diagnosis, prognosis, disease monitoring, and treatment of gynecological cancer, with an established important clinical impact

Impact on ovarian reserve after minimally invasive single-port laparoscopic ovarian cystectomy in patients with benign ovarian cysts: A systematic review and meta-analysis

Background/Aim The purpose of this article is to review the published literature on single-port laparoscopic (SPL) ovarian cystectomy and to assess whether the reduced port number affects the ovarian reserve in comparison with the conventional multiport laparoscopic (MPL) ovarian cystectomy. Materials and methods It has been suggested that the most accurate marker of ovarian reserve is the Serum anti-Mullerian hormone (AMH). A review of the current literature was performed based on the preoperative and postoperative AMH after SPL and MPL ovarian cystectomy in adult patients with benign ovarian cysts. Results Ovarian cystectomy causes a non-statistically significant reduction in AMH levels four weeks postoperatively in the SPL group compared to the MPL group [MD = 0.11, 95% CI (-0.01, 0.24), P =0 .07]. Operative time was significantly longer, and blood loss was significantly higher in the SPL group. No difference was reported in terms of major or overall postoperative complications between the two groups. Conclusion SPL cystectomy may be offered as a minimally invasive surgical alternative for patients who want to preserve their fertility, at the cost of higher blood loss and longer operative time