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.

Is Precision Surgery Applicable to Colorectal Liver Metastases? A Systematic Review and Meta-analysis of Studies that Investigate the Association of Surgical Technique with Outcomes in the Context of Distinct Tumor Biology.

BACKGROUND: Although some data suggest that patients with mutRAS colorectal liver metastases (CRLM) may benefit from anatomic hepatectomy, this topic remains controversial. We performed a systematic review and meta-analysis to determine whether RAS mutation status was associated with prognosis relative to surgical technique [anatomic resection (AR) vs. nonanatomic resection (NAR)] among patients with CRLM. PATIENTS AND METHODS: A systematic review and meta-analysis of studies were performed to investigate the association of AR versus NAR with overall and liver-specific disease-free survival (DFS and liver-specific DFS, respectively) in the context of RAS mutation status. RESULTS: Overall, 2018 patients (831 mutRAS vs. 1187 wtRAS) were included from five eligible studies. AR was associated with a 40% improvement in liver-specific DFS [hazard ratio (HR) = 0.6, 95% confidence interval (CI) 0.44-0.81, p = 0.01] and a 28% improvement in overall DFS (HR = 0.72, 95% CI 0.54-0.95, p = 0.02) among patients with mutRAS tumors; in contrast, AR was not associated with any improvement in liver-specific DFS or overall DFS among wtRAS patients. These differences may have been mediated by the 40% decreased incidence in R1 resection among patients with mutRAS tumors who underwent AR versus NAR [relative risk (RR): 0.6, 95% CI 0.40-0.91, p = 0.02]. In contrast, the probability of an R1 resection was not decreased among wtRAS patients who underwent AR versus NAR (RR: 0.93, 95% CI 0.69-1.25, p = 0.62). CONCLUSIONS: The data suggest that precision surgery may be relevant to CRLM. Specifically, rather than a parenchymal sparing dogma for all patients, AR may have a role in individuals with mutRAS tumors.

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.

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.

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.

Implementation of a Sequence-to-Sequence Stacked Sparse Long Short-Term Memory Autoencoder for Anomaly Detection on Multivariate Timeseries Data of Industrial Blower Ball Bearing Units.

The advent of Industry 4.0 introduced new ways for businesses to evolve by implementing maintenance policies leading to advancements in terms of productivity, efficiency, and financial performance. In line with the growing emphasis on sustainability, industries implement predictive techniques based on Artificial Intelligence for the purpose of mitigating machine and equipment failures by predicting anomalies during their production process. In this work, a new dataset that was made publicly available, collected from an industrial blower, is presented, analyzed and modeled using a Sequence-to-Sequence Stacked Sparse Long Short-Term Memory Autoencoder. Specifically the right and left mounted ball bearing units were measured during several months of normal operational condition as well as during an encumbered operational state. An anomaly detection model was developed for the purpose of analyzing the operational behavior of the two bearing units. A stacked sparse Long Short-Term Memory Autoencoder was successfully trained on the data obtained from the left unit under normal operating conditions, learning the underlying patterns and statistical connections of the data. The model was evaluated by means of the Mean Squared Error using data from the unit's encumbered state, as well as using data collected from the right unit. The model performed satisfactorily throughout its evaluation on all collected datasets. Also, the model proved its capability for generalization along with adaptability on assessing the behavior of equipment similar to the one it was trained on.

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.

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.

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.

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC - Is it the exception to the rule?

BACKGROUND: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. METHODS: All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS. RESULTS: A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98). CONCLUSIONS: In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

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

BACKGROUND/AIM: There is a strong association between malignancy and histone deacetylases (HDACs). Histone deacetylase inhibitors (HDACIs) are now being tested as antitumor agents in various clinical trials. We aimed to assess the clinical importance of HDAC-2 in breast cancer (BC). MATERIALS AND METHODS: A total of 118 BC specimens were examined immunohistochemically. A statistical analysis was conducted in order to examine the relation between HDAC-2 and the clinicopathological features and survival of the patients. RESULTS: Higher HDAC-2 expression was related to lobular histological type of cancer, grade III, and stage III BC. In addition, the disease-free period and overall survival were curtailed and negatively related to the over-expression of HDAC-2. Other factors correlating with worse survival were histological types other than ductal or lobular, and the stage of the disease. CONCLUSIONS: This study showed a relationship between HDAC-2 and BC. Further studies are required in order to eventually potentiate the role of HDACIs as anticancer agents in BC.

Liver Transplantation and Budd-Chiari Syndrome: When the Cause Becomes the Solution.

Budd-Chiari syndrome consists a rare medical entity which has an estimated incidence of 0.1 to 10 people per million every year. It is defined by the obstruction of the flow in the inferior vena cava or the hepatic veins. Various classifications have been proposed. So, it can be acute or chronic and primary or secondary. Iatrogenic, a subtype of secondary Budd-Chiari syndrome, is caused by various medical interventions, including liver transplantation. On the other hand, liver transplantation is the ultimate therapeutic management of Budd-Chiari syndrome. Finally, a medical paradox and a vicious circle has been created. Liver transplantation can potentially be both the cause and treatment of Budd-Chiari syndrome. Budd-Chiari syndrome is simultaneously the cause and complication of liver transplantation. Our aim is to describe this double role of liver transplantation in Budd-Chiari syndrome and to acknowledge that a high degree of clinical suspicion is necessary for the proper recognition and management of this life-threatening condition.

The Role of SNHG15 in the Pathogenesis of Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides which cannot be translated into proteins. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA whose dysregulation has been found to have an important impact on carcinogenesis and affect the prognosis of cancer patients in various cancer types. Hepatocellular carcinoma (HCC) is one of the most common cancers with a poor long-term prognosis, while the best prognostic factor of the disease is its early diagnosis and surgery. Consequently, the investigation of the mechanisms of hepatocarcinogenesis, as well as the discovery of efficient molecular markers and therapeutic targets are of great significance. An extensive literature search was performed in MEDLINE in order to identify clinical studies that tried to reveal the role of SNHG15 in HCC. We used keywords such as 'HCC', 'hepatocellular carcinoma', 'SNHG15' and 'clinical study'. Finally, we included four studies written in English, published during the period 2016-2021. It was revealed that SNHG15 is related to the appearance of HCC via different routes and its over-expression affects the overall survival of the patients. More assays are required in order to clarify the potential role of SNHG15 as a prognostic tool and therapeutic target in HCC.

Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.

Histone Deacetylases and their Inhibitors in Colorectal Cancer Therapy: Current Evidence and Future Considerations.

Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.

Operating on Jehovah's Witnesses: A Challenging Surgical Issue.

Blood transfusion is often utilized in surgery. Greece is the second-highest consumer of blood components in Europe. It has been shown that at least half of all transfusions are unnecessary and could be avoided. Jehovah's Witnesses (JWs) are a Christian religion that do not accept transfusion of whole blood or the four primary components of blood-namely, red blood cells, white blood cells, platelets, and plasma. This a retrospective study from September of 2015 to January of 2018, analyzing all JWs who underwent an elective operation at the Second Department of Propaedeutic Surgery in Laiko University Hospital. Twenty-nine (Rogers et al. in NCCN Guidelines Version 2.2014 Cancer- and Chemotherapy-Induced Anemia. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network, Fort Washington, 2013) JW patients, 23 females (74.1%) and eight males, were operated on during the aforementioned period. The median ASA score was 1 (range 1-3), and only two of the patients needed postoperative monitoring in the ICU. Almost half of the patients (45.1%) needed iron infusion and EPO injection preoperatively. Two patients presented with postoperative complications, with no postoperative deaths. In conclusion, we found that surgery, in our small group of JW patients, was safe and successful despite the lack of blood transfusion. Techniques developed to treat JW patients should be more widely used to improve clinical outcomes and reduce costs to the healthcare system.

Mutant KRAS as a prognostic biomarker after hepatectomy for rectal cancer metastases: Does the primary disease site matter?

BACKGROUND: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. METHODS: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. RESULTS: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. CONCLUSIONS: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

Investigational Drug Treatments for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) and accounts for 10-20% of cases. Due to the lack of expression of several receptors, hormone therapy is largely ineffective for treatment purposes. Nevertheless, TNBC often responds very well to chemotherapy, which constitutes the most often recommended treatment. New beneficial targeted therapies are important to be investigated in order to achieve enhanced outcomes in patients with TNBC. This review will focus on recent therapeutic innovations for TNBC, focusing on various inhibitors such as phosphoinositide 3-kinase (PI3K) pathway inhibitors, poly-ADP-ribosyl polymerase (PARP) inhibitors, aurora kinase inhibitors, histone deacetylase inhibitors (HDACIs), and immune checkpoint inhibitors.

Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.

Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC.