Histone deacetylase inhibitors as a novel therapeutic approach for pheochromocytomas and paragangliomas.

Epigenetic mechanisms, such as DNA methylation and histone modifications (e.g., acetylation and deacetylation), are strongly implicated in the carcinogenesis of various malignancies. During transcription, the expression and functionality of coding gene products are altered following the histone acetylation and deacetylation. These processes are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. HDAC inhibitors (HDACis) have been developed as promising therapeutic agents, to limit exposure to traditional and toxic chemotherapies and offer more alternatives for some specific malignant diseases with limited options. Mechanistically, these agents affect many intracellular pathways, including cell cycle arrest, apoptosis and differentiation, and their mechanism of action mainly depends on the type of cancer. Currently, five HDACis have been approved for the treatment of several hematological malignancies (e.g., T-cell lymphoma subtypes and multiple myeloma); while, many of them are tested for further therapeutic indications in solid tumors (e.g., colorectal, thyroid, breast, lung and pancreatic cancer). Herein, we review the literature and gather all available evidence, from in vitro and in vivo data to clinical trial results, that recognizes the antitumor activity of HDACis on pheochromocytomas and paragangliomas; and supports their clinical implementation in the treatment of these rare neuroendocrine tumors at metastatic setting.

Implementing Change in Neuroanatomy Education: Organization, Evolution, and Assessment of a Near-Peer Teaching Program in an Undergraduate Medical School in Greece.

In light of the current shifts in medical education from traditional lectures to more active teaching modalities, a peer-teaching program was introduced to a compulsory, second-year neuroanatomy course. A cross-sectional survey of 527 medical students in the six-year medical program of the National and Kapodistrian University of Athens was administered. The primary aim of the survey, which was distributed to second- through sixth-year medical students, who had completed the neuroanatomy course, was to assess student perception of peer teachers (PTs). Across the five years assessed, students increasingly acknowledged the contribution of PTs to their learning (P < 0.001). Attributes of PTs (e.g., contribution to learning, motivation, effective usage of material, and team environment) were significantly related to the student's opinion of the importance of laboratory activities (P < 0.001). Students who received "average" final grades scored the importance of laboratory exercises, and by inference PTs, significantly lower than students who received "excellent" final grades (P < 0.05). The amount of training that PTs had received was also significantly related to student perceptions of a PT's contribution. Better trained PTs were associated with significantly higher scores regarding learning, motivation, and positive environment compared to less trained PTs (P < 0.05). The results of the present study show that peer-teaching was well received by students attending the neuroanatomy course. While the results express the evolution of the program across the years, the findings also show that learners believed that PTs and the laboratory program contributed significantly to their understanding of neuroanatomy.

Monitoring of colonoscopy quality indicators in an academic endoscopy facility reveals adherence to international recommendations.

BACKGROUND: We monitor colonoscopy service quality biannually, by measuring sedation administration, colonoscopy completion, adenoma detection and early complications rates (CR). We herein present our audit results for the years 2013 and 2015. METHODS: In our endoscopy facility, five rotating senior gastroenterologists perform colonoscopies, on a daily basis. We measured the quality indicators in three cohorts: A, intention for total colonoscopy cases; B, cohort A excluding bowel obstruction cases; C, colorectal cancer (CRC) screening cases. RESULTS: In 2015, overall sedation administration rate (SAR) was 93.0% (91.6-94.4%), achieving our target to give conscious sedation to >90% of patients undergoing colonoscopy in all three cohorts. Colonoscopy completion rate (CCR) increased significantly (P<0.0001) from 94.8% (93.4-96.2%) to 98.1% (97.3-98.9%) in cohort B and numerically from 96.6% (94.4-98.8%) to 98.6% (97.4-99.7%) in cohort C, at the same periods. In cohort C, adenoma detection rates (ADR) were similar-27.1% (21.7-32.5%) and 27% (22.7-31.3%)-in the two periods. There were only two serious early complications: one cardiorespiratory event and one perforation in 2013 and 2015, respectively. While significant variability regarding SAR (ranging from 80% to 100%) was detected among the participating endoscopists, all but one of them constantly achieved [judged by the lower confidence interval (CI) of the quality indicator] CCRs higher than the recommended by international guidelines. On the contrary ADR was variable among endoscopists during the studied periods. CONCLUSIONS: Although there is certain variability in endoscopists' performance, the overall colonoscopy quality indicators meet or exceed the internationally recommended standards, in our endoscopy facility.

Publication dynamics in gastroenterology and hepatology over the last decade in Greece: a SCImago-based study.

BACKGROUND: There is evidence that the financial crisis has deleteriously affected scientific output. We aimed to assess the dynamics of Greek publications in gastroenterology and hepatology over the last ten years. METHODS: Data were collected from SCImago. The average annual growth rate (AAGR) of total and citable documents published in Greece in the field of gastroenterology and hepatology was compared with that of cardiology, surgery, and radiology. In addition, it was compared with the corresponding rates in Belgium, Ireland and Portugal. RESULTS: The annual number of Greek publications (total and citable documents) remained relatively unchanged in the field of gastroenterology and hepatology from 2006-2011. During the following years, we detected a negative AAGR, with values of -12%, -3.3%, -9.5% and -5.4% for gastroenterology-hepatology, cardiology, surgery and radiology, respectively. During the same period, the AAGR of the citable documents of the respective specialties was -8.6%, -3.7%, -9.8%, and -5.1%. Comparison of the 4 European countries in the field of gastroenterology and hepatology revealed that publications from Portugal rose massively (AAGR +24.6% and +20.6% for total and citable documents, respectively), almost reaching the number of Greek publications in 2015. The number of publications from Belgium and Ireland remained essentially unchanged after 2011, with AAGR values of -0.7%, and -2.1% for total and -1.1% and -1.4% for citable documents, respectively. CONCLUSION: The publication output in the field of gastroenterology and hepatology decreased significantly after the outbreak of the financial crisis in Greece, not only in relation to other medical specialties, but also compared to the output of other European countries with or without fiscal austerity measures.

Promoting Undergraduate Surgical Education: Current Evidence and Students' Views on ESMSC International Wet Lab Course.

BACKGROUND: Undergraduate Surgical Education is becoming an essential element in the training of the future generation of safe and efficient surgeons. Essential Skills in the Management of Surgical Cases (ESMSC), is an international, joint applied surgical science and simulation-based learning wet lab course. METHODS: We performed a review of the existing literature on the topic of undergraduate surgical education. Following that, we analyzed the feedback questionnaire received 480 from 2 recent series of ESMSC courses (May 2015, n = 49 and November 2015, n = 40), in order to evaluate European Union students' (UK, Germany, Greece) views on the ESMSC course, as well as on the undergraduate surgical education. Results Using a 10 point graded scale, the overall ESMSC concept was positively evaluated, with a mean score of 9.41 ± 0.72 (range: 8-10) and 8.94 ± 1.1 (range: 7-10). The majority of delegates from both series [9.86 ± 0.43 (range: 8-10) and 9.58 ± 0.91 (range: 6-10), respectively] believed that ESMSC should be incorporated in the undergraduate surgical curriculum. Comparison of responses from the UK to the Greek Medical Student, as well as the findings from the third and fourth year versus the fifth and sixth year Medical Students, revealed no statistically significant differences pertaining to any of the questions (p > 0.05). CONCLUSIONS: Current evidence in the literature supports the enhancement of surgical education through the systematic use of various modalities that provide Simulation-Based Training (SBT) hands-on experience, starting from the early undergraduate level. The findings of the present study are in agreement with these previous reports.

Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Against Medullary Thyroid Cancer?

BACKGROUND/AIM: Medullary thyroid cancer (MTC) is highly malignant, metastatic and recurrent, remaining generally incurable, and responsible for approximately 14% of all thyroid carcinoma-related deaths. MTC can metastasize to lymph nodes, trachea and distant organs, such as brain, lungs, liver and bones. MTC cells are resistant to chemotherapy and traditional external therapies are not showing definite clinical benefits. Scientists are trying to understand the molecular background of carcinogenesis and histone deacetylase (HDAC) seems to play a potential role to gene transcription. On the other hand, HDAC inhibitors (HDACI) hamper the HDAC action giving promising results as new anticancer drugs. The purpose of this review was to evaluate the current status of research considering the role of HDACIs in MTC treatment and to present the latest trends in MTC treatment protocols. MATERIALS AND METHODS: This literature review was accomplished using the MEDLINE database. The key words/phrases were; HDACI, medullary thyroid cancer, HDACI in the therapy of neuroendocrine tumors, HDACI in MTC. Forty-one articles were selected from the total number of the search's results. Only sixteen papers focus on the use of HDACIs in the treatment of MTC. In order to extract our conclusions, we took into account some studies whose main topic does not strictly refer to the MTC but they contain noteworthy and useful information. Only English articles published up to August 2016 were assessed and used for writing this review. RESULTS: Molecules, such as valproid acid (VPA), vorinostat, suberoyl bis-hydroxamic acid (SBHA), depsipeptide, belinostat, m-carboxycinnamic acid bis-hydroxamine (CBHA) and AB3 have shown promising antitumor effects against MTC. CONCLUSION: HDACIs represent a promising field for targeted therapy both for its anticancer properties, as well as for augmenting radiotherapeutic modalities. More trials are needed.

Medical students' satisfaction with the Applied Basic Clinical Seminar with Scenarios for Students, a novel simulation-based learning method in Greece.

PURPOSE: The integration of simulation-based learning (SBL) methods holds promise for improving the medical education system in Greece. The Applied Basic Clinical Seminar with Scenarios for Students (ABCS3) is a novel two-day SBL course that was designed by the Scientific Society of Hellenic Medical Students. The ABCS3 targeted undergraduate medical students and consisted of three core components: the case-based lectures, the ABCDE hands-on station, and the simulation-based clinical scenarios. The purpose of this study was to evaluate the general educational environment of the course, as well as the skills and knowledge acquired by the participants. METHODS: Two sets of questions were distributed to the participants: the Dundee Ready Educational Environment Measure (DREEM) questionnaire and an internally designed feedback questionnaire (InEv). A multiple-choice examination was also distributed prior to the course and following its completion. A total of 176 participants answered the DREEM questionnaire, 56 the InEv, and 60 the MCQs. RESULTS: The overall DREEM score was 144.61 (±28.05) out of 200. Delegates who participated in both the case-based lectures and the interactive scenarios core components scored higher than those who only completed the case-based lecture session (P=0.038). The mean overall feedback score was 4.12 (±0.56) out of 5. Students scored significantly higher on the post-test than on the pre-test (P<0.001). CONCLUSION: The ABCS3 was found to be an effective SBL program, as medical students reported positive opinions about their experiences and exhibited improvements in their clinical knowledge and skills.

Histone Deacetylase (HDAC) Inhibitors: Current Evidence for Therapeutic Activities in Pancreatic Cancer.

Pancreatic carcinoma is one of the leading causes of cancer death. Current standard treatments include surgical resection, chemotherapy and radiotherapy but patient's prognosis remains poor and present severe side-effects. Contemporary oncology found a wide variety of novel anticancer drugs that regulate the epigenetic mechanisms of tumor genesis. Histone deacetylases (HDACs) are enzymes with pleiotropic activities that control critical functions of the cell through regulation of the acetylation states of histone proteins and other non-histone protein targets. They are divided into four groups, each with different localization in the cell, role and structure. Histone deacetylase inhibitors (HDACIs) are substances, which inhibit the function of HDACs. We recognize four leading groups (hydroxamic acid, cyclic tetrapeptide, benzamide, aliphatic acid). There are many HDACIs currently in pre-clinical and two (vorinostat, romidepsin) in clinical stages of investigation for pancreatic cancer. Numerous studies argue for the use HDACIs as monotherapy, others suggest that combination of HDACIs with other antitumor drugs has better therapeutic results. This review focuses on the use of HDACIs as novel anticancer drugs and will explain the mechanisms of therapeutic effect on pancreatic cancer.