Precision Oncology: Circulating Microvesicles as New Biomarkers in a Very Early Stage of Colorectal Cancer.

BACKGROUND: The release of microvesicles (MVs) is an essential phenomenon for inter-cellular signaling in health and disease. The role of MVs in cancer is multidimensional and includes cancer cell survival, proliferation, and invasion. In this prospective study, we analyzed MV levels in colorectal cancer patients and assessed the importance of MV release in early-stage colorectal cancer and survival. METHODS: This study included 98 patients and 15 controls. The characterization of MVs from human plasma was performed by flow cytometry using monoclonal antibodies. RESULTS: The levels of total MVs and MUC-1-positive, tissue factor (TF)-positive, and endothelial cell-derived MVs (EMVs) were statistically significantly higher in the colon cancer patients than in the controls (p < 0.001). Furthermore, the subgroup of patients with very early-stage colorectal cancer also had statistically significant differences in the levels of the abovementioned MVs compared to the controls (p < 0.01). Highly differentiated tumors had lower levels of MUC-1-positive MVs (p < 0.02), EMVs (p < 0.002), and EMV/TF combinations (p < 0.001) versus those with tumors with low/intermediate differentiation. CONCLUSIONS: Our data demonstrate that the analysis of circulating MV levels in plasma could possibly become a tool for the early diagnosis of colon cancer at a very early stage of the disease.

Giant Basal Cell Carcinoma in a Renal Transplant Recipient: A Case Report.

Basal cell carcinoma is a skin cancer with a more benign clinical course, compared to other skin cancers. However, when left neglected, it can cause serious morbidity and mortality. A basal cell carcinoma larger than 5 cm is defined as giant. Common causes of these carcinomas are negligence, immunosuppression, low socioeconomic status, physical or mental dysfunction, light exposure, exposure to radiation, existence of a previous lesion, recurrence after treatment, and aggressive histologic pattern. In some cases, giant basal cell carcinoma has been described to infiltrate multiple intracranial structures and to be associated with distant metastasis. Herein, we present a case of a giant basal cell carcinoma on the temporary scalp of a renal transplant recipient with depression.

The Impact of Periodontal Disease on Preterm Birth and Preeclampsia.

This review delves into the possible connection between periodontitis and negative pregnancy outcomes, such as preeclampsia and preterm birth. It highlights the potential influence of an unidentified microbial factor on preeclampsia and the effects of inflammatory responses on the rate of preterm births. Furthermore, it underscores the prevalent occurrence of oral ailments within the populace and their significant repercussions on quality of life. Hormonal fluctuations during pregnancy may exacerbate oral conditions such as pregnancy gingivitis and periodontitis, necessitating bespoke therapeutic approaches that take into account potential fetal ramifications. Periodontal disease, characterized by microbial attack and inflammatory response, results in tissue destruction and tooth loss. The oral cavity's susceptibility to bacterial colonization, which is primarily due to its role as a site for food intake, is highlighted. Furthermore, research indicates a correlation between inflammatory responses and factors such as prostaglandin E2 and IL-1ß, and preterm birth. Therapeutic interventions are a focus of international research, with efforts being aimed at optimizing outcomes through larger studies involving pregnant women.

Primary Omental Torsion in Children in the Laparoscopy Era: What Have we Learned so far?

BACKGROUND/AIM: Primary omental torsion is uncommon, mimicking appendicitis and other acute abdominal pathologies. It often escapes diagnosis on imaging investigation or conventional open laparotomy. This study aimed to evaluate the effect of laparoscopy on the various parameters of this entity, including incidence, diagnosis, and treatment. MATERIALS AND METHODS: A systematic review was performed, including PubMed and Scopus databases, without a time limit, following the PRISMA principles. A total of 16 articles from January 2000 to December 2023, corresponding to 56 children with primary omental torsion, complied with the research criteria. RESULTS: Primary omental torsion was associated with obesity. Symptoms were right abdomen oriented, often compared to those of acute appendicitis. Preoperative ultrasound displayed low diagnostic accuracy, whereas computerized tomography diagnosed only two thirds of cases. In all patients, the vermiform appendix was normal. CONCLUSION: Laparoscopy affected both diagnosis and treatment of primary omental torsion in children. Easy peritoneal cavity access rendered possible the diagnosis of cases previously discharged as abdominal pain of unknown etiology. Combined with the increased pediatric obesity, it also affected primary omental torsion incidence. The recent pathogenetic theories may be better supported today, as laparoscopy provides a detailed view in situ, and facilitates harvesting of fat tissue from the omentum for molecular investigation. The diagnostic efficiency of laparoscopy is superior to ultrasonography and computerized tomography. Finally, the removal of the ischemic omentum is technically easier compared to the open laparotomy alternative with all the technical difficulties of traction of a vulnerable hemorrhagic tissue through a small incision.

Association of Anti-Ro/SSA and Anti-La/SSB Autoantibodies With Pregnancy Outcome in the General Population.

Background: Autoimmune diseases encompass a diverse array of disorders that disturb the optimal functioning of the immune system, which is to eliminate the 'foreign or/and dangerous' to mistakenly target the body's own tissues. Objective: The aim of this research is to evaluate the most effective approach to managing autoimmune diseases within the framework of pregnancy. Methods: The exact causes and etiologies of these diseases are multifactorial and mostly still unclear. Ro/SSA autoantibodies and La/SSB, could be found in Sjögren's disease (SJ), systemic lupus (SLE) and other autoimmune disorders. Smoking, stress, UV exposure, vitamin D deficiency, and other genetic and environmental factors have been identified as risk factors for rheumatic diseases. Results: Over the years, an ever-increasing incidence of these diseases has been observed in the general population, with the female sex being at increased risk for their occurrence. This fact raises the question of what should be the management of these pathological entities during pregnancy. Taking into account the very significant impact on the quality of paitients'daily life and the seemingly augmented prevalence of autoimmune diseases, as well as their preference in the female population, the reasonable question arises as to what should be the optimal management of these diseases in the context of pregnancy. Conclusion: Given the limited data of the global medical community regarding the etiological factors and mechanisms that trigger the onset of rheumatic diseases, the management of pregnant women is a complex conundrum that health professionals are challenged to face and solve.

Programmed Death Ligand 1: Unveiling its Impact on Endometrial Carcinogenesis.

Endometrial cancer is a commonly diagnosed gynecological malignancy presenting an increasing incidence worldwide. The immune response plays a crucial role in the mechanisms underlying carcinogenesis and the progression of tumors. In recent times, there has been a discernible surge in the acknowledgment of the importance of programmed death ligand 1 (PDL1) in evading the immunological response of the host and promoting the growth of malignancies. The primary aim of this review is to consolidate the existing corpus of evidence pertaining to the role of PDL1 in the etiology and progression of endometrial cancer and investigate the molecular mechanisms involved in the expression of PDL1 in cells impacted by endometrial cancer. Finally, the association between PDL1 expression and clinical outcomes, as well as the potential therapeutic uses of targeting the PDL1 pathway are being analyzed.

The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers.

Gynecological cancers (GC) represent some of the most frequently diagnosed malignancies in women worldwide. Long-non-coding RNAs (lncRNAs) are regulatory RNAs increasingly being recognized for their role in tumor progression and metastasis in various cancers. Urothelial cancer-associated 1 (UCA1) is a lncRNA, first found deregulated in bladder cancer, and many studies have exposed its oncogenic effects in more tumors since. However, the role of UCA1 in gynecological malignancies is still unclear. This review aims to analyze and define the role of UCA1 in GC, in order to identify its potential use as a diagnostic, prognostic, or therapeutic biomarker of GC. By employing the search terms "UCA1", "breast cancer", "endometrial cancer", "ovarian cancer", "cervical cancer", "vaginal cancer", and "vulvar cancer" in the PubMed database for the literature review, we identified a total of sixty-three relevant research articles published between 2014 and 2024. Although there were some opposing results, UCA1 was predominantly found to be upregulated in most of the breast, endometrial, ovarian, cervical, and vulvar cancer cells, tissue samples, and mouse xenograft models. UCA1 overexpression mainly accounts for enhanced tumor proliferation and increased drug resistance, while also being associated with some clinicopathological features, such as a high histological grade or poor prognosis. Nonetheless, no reviews were identified about the involvement of UCA1 in vaginal carcinogenesis. Therefore, further clinical trials are required to explore the role of UCA1 in these malignancies and, additionally, examine its possible application as a target for upcoming treatments, or as a novel biomarker for GC diagnosis and prognosis.

Evaluation of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

BACKGROUND/AIM: Triple negative breast cancer belongs to the most aggressive breast cancer forms. Histone deacetylases (HDACs) constitute a class of enzymes that exhibit a significant role in breast cancer genesis and progression. In this study, we aimed at assessing the clinical importance of HDAC-2 in triple negative breast cancer. MATERIALS AND METHODS: A total of 138 breast cancer specimens were examined on an immunohistochemical basis. A statistical analysis was performed in order to examine the association between HDAC-2 and the survival and clinicopathological features of the patients. RESULTS: Increased HDAC-2 expression was observed in every fourth case of triple negative breast cancer with positive HDAC-2 staining, whereas only 12 out of 98 non-triple negative breast cancer samples showed high HDAC-2 expression. HDAC-2 overexpression correlated with prolonged overall survival (OS) and disease-free survival (DFS) in triple negative breast cancer. CONCLUSIONS: High HDAC-2 levels in triple negative breast cancer seem to positively influence patient survival, disease stage and recurrence.

Synchronous Insulinoma and Glucagonoma: A Review of the Literature.

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS: A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS: A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION: Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.

Ovarian Torsion in Polycystic Ovary Syndrome: A Potential Threat?

Polycystic ovary syndrome (PCOS) constitutes the most prevalent endocrine disorder in women of reproductive age worldwide. Given the increased risk of ovarian torsion in the presence of large ovarian cysts, polycystic ovarian syndrome could be regarded as one of the most significant risk factors for ovarian and/or adnexal torsion in cases of significantly enlarged ovaries. The aim of the present review is to investigate, for the first time, the association between polycystic ovarian syndrome and ovarian torsion. We performed a review of the literature using the MEDLINE and LIVIVO databases in order to find relevant studies. By using the search terms "polycystic ovarian syndrome" and "ovarian torsion", we were able to identify 14 studies published between 1995 and 2019. The present work constitutes the most up-to-date, comprehensive literature review focusing on the risk of ovarian/adnexal torsion in patients with polycystic ovaries. Ovarian/adnexal torsion seems to be a feared complication in patients with polycystic ovary syndrome. Acute lower abdominal pain in patients with known polycystic ovaries represents the most common symptom, while diagnostic assessment almost always incorporates transvaginal ultrasound and computer tomography or magnetic resonance tomography scans. In case of suspected torsion, emergency laparoscopy with ovarian or adnexal detorsion seems to be the standard therapeutic approach with a view to restitute the interrupted blood supply. In cases of repeated ovarian/adnexal torsions, ovariopexy or ovariectomy/adnexectomy had to be discussed with the patient in the context of risk recurrence minimization.

A Proposed Cytodiagnosistic Approach for Breast Lesions.

In clinical practice, the diagnosis of breast lesions is achieved by the triple approach of the specialized surgeon, radiologist and pathologist. The recommended approach to breast lesions should always include a detailed history, along with a thorough clinical examination, mammography and/or ultrasound, as well as preoperative cytodiagnosis. In this context, fine needle aspiration cytology and core needle biopsy are the methods of choice for histological diagnosis. Herein, we aim to explain why these procedures seem to be superior compared to open biopsy and we propose a cytodiagnostic algorithm for breast lesions.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy.

Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "hyperthermic intraperitoneal chemotherapy", "uterine cancer", "endometrial cancer", and/or "uterine sarcoma", we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.

Liver Cancer and Pregnancy: A Review of the Literature.

BACKGROUND/AIM: Liver cancer constitutes one of the leading cancers globally. During pregnancy, however, liver cancer is an absolute rarity, with very few cases reported in the international literature. The aim of the present review was to provide a useful update and summarize all case studies of liver cancer in pregnancy published between 2012-2023. MATERIALS AND METHODS: A literature review was conducted using the MEDLINE, LIVIVO, and Google Scholar databases. Solely case reports and case studies written in the English language that explicitly reported on the presence of histologically confirmed HCC or intrahepatic cholangiocarcinoma during pregnancy were included in the data analysis. RESULTS: After detailed evaluation, a total of 35 reported cases of liver cancer during pregnancy were identified, hence bringing the total number of reported cases globally to 83. Oncological challenges during pregnancy call for an interdisciplinary approach. Although the desire to preserve the pregnancy should be taken into consideration, specialists need to evaluate maternal and fetal well-being and choose the optimal oncological treatment with the least dangers for both the maternal and fetal safety. CONCLUSION: The present review proves that, despite its scarcity, liver cancer may always occur during pregnancy and clinicians should, therefore, remain vigilant and endeavor to detect and evaluate any hepatic mass or symptoms of liver cancer promptly and exhaustively.

Is There an Association Between Circulating Kisspeptin Levels and Ovarian Reserve in Women of Reproductive Age?

BACKGROUND/AIM: To investigate the possible association of kisspeptin levels with the ovarian reserves of women of reproductive age. PATIENTS AND METHODS: Eighty women aged 19-40 participated after signing an informed consent. Of these, 74 were finally included as in 6 women the blood samples were considered inappropriate due to hemolysis. They were divided into three main groups according to their ovarian reserve patterns: women with adequate ovarian reserves (Group A - AOR) (n=30), women with increased ovarian reserves (Group B - PCOS) (n=31), and women with diminished ovarian reserves (Group C - DOR) (n=13). RESULTS: Women with diminished ovarian reserves had statistically significantly increased age and FSH compared to the other two groups. No statistically significant difference was found between the three groups for estradiol and thyroid stimulating hormone. Moreover, body mass index, luteinizing hormone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone, anti-Mullerian hormone (AMH), and antral follicle count (AFC) were increased in group B compared to the other two groups. AMH and AFC were decreased in women with diminished ovarian reserves compared to the other two groups, as expected. The comparison of kisspeptin levels between the three groups showed that kisspeptin levels were increased in women with diminished ovarian reserves, compared to the other two groups, but without a statistically significant difference. However, kisspeptin levels in group C were statistically significantly higher than those in group A. CONCLUSION: There are no strong indications that kisspeptin levels are associated with the ovarian reserve in women of reproductive age.

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy.

Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review is to study the role of HDACIs in the treatment of cervical cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms "histone deacetylase" and "cervical cancer", we managed to identify 95 studies published between 2001 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HDACIs as treatment agents for cervical cancer. Both well-established and novel HDACIs seem to represent modern, efficacious anticancer drugs, which, alone or in combination with other treatments, may successfully inhibit cervical cancer cell growth, induce cell cycle arrest, and provoke apoptosis. In summary, histone deacetylases seem to represent promising future treatment targets in cervical cancer.

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

Exploiting Autophagy-Dependent Neoantigen Presentation in Tumor Microenvironment.

Autophagy constitutes a well-known homeostatic and catabolic process that is responsible for degradation and recycling of cellular components. It is a key regulatory mechanism for several cellular functions, whereas its dysregulation is associated with tumorigenesis, tumor-stroma interactions and resistance to cancer therapy. A growing body of evidence has proven that autophagy affects the tumor microenvironment, while it is also considered a key factor for function of several immune cells, such as APCs, T-cells, and macrophages. Moreover, it is implicated in presentation of neo-antigens of tumor cells in both MHC-I and MHC-II in dendritic cells (DCs) in functional activity of immune cells by creating T-cell memory, as well as in cross-presentation of neo-antigens for MHC-I presentation and the internalization process. Currently, autophagy has a crucial role in immunotherapy. Emergence of cancer immunotherapy has already shown some remarkable results, having changed therapeutic strategy in clinical practice for several cancer types. Despite these promising long-term responses, several patients seem to lack the ability to respond to immune checkpoint inhibitors. Thus, autophagy through neo-antigen presentation is a potential target in order to strengthen or attenuate the effects of immunotherapy against different types of cancer. This review will shed light on the recent advances and future directions of autophagy-dependent neo-antigen presentation and consequently its role in immunotherapy for malignant tumors.

FDA-Approved Monoclonal Antibodies for Unresectable Hepatocellular Carcinoma: What Do We Know So Far?

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.

Association between smoking cessation and alterations in forced expiratory volume in one second (FEV1). A Follow-Up Study from a Greek Tobacco Cessation Clinic.

Background: Cigarette smoking is the most important preventable cause of several diseases such as malignancies, pulmonary and cardiovascular diseases. Smoking cessation is now supported by both behavioral counseling and medical pharmacotherapy and is the only effective approach for slowing down an accelerated decline in forced expiratory volume in one second (FEV1). Our study aims to examine changes in forced expiratory volume in one second (FEV1) after smoking cessation for smokers attending our smoking cessation clinic their correlation to smokers' demographic characteristics. Methods: 114 smokers (48 males and 66 females), with a mean age of 48.36±10.49 years, were enrolled. They were classified in 4 groups, according to their age; <40 years (Group Α), 41-50 years (Group Β), 51-60 years (Group C), >60 years (Group D) and underwent Spirometry on the 1st day of visit, one month (2nd visit) and, 3 months later (3rd visit). Findings: Statistically significant increase in FEV1 values at the 2nd and 3rd visit compared to the 1st visit was observed in smokers who quit smoking in Group Α, B and C (p<0.05). In addition, a statistically significant decrease in FEV1 values at the 2nd and 3rd visit compared to the 1st visit was noticed in smokers who continued smoking in Group B, C and D (p<0.05). Conclusion: Smoking cessation achieved through smoking cessation support led to the improvement of FEV1 values within 3 months. The greatest benefit was observed in smokers under the age of 60.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.