The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

New molecular biomarkers for the prevention and early detection of precancerous or cancerous colorectal lesions during screening for colorectal cancer

Our aim was to perform a comparison study of the mutation rate of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-Raf murine sarcoma viral oncogene homolog-B (BRAF) genes between blood-based cell-free DNA (cfDNA), and tissue sample biopsies in individuals undergoing screening colonoscopy. Materials and Methods: All specimens were collected from January 2015 to January 2016. A total of 92 blood samples and colonic biopsy specimens were collected from healthy individuals with no polyps undergoing screening colonoscopy (group A, n=35), patients with colorectal cancer (group B, n=27), and patients with neoplastic intestinal polyps (group C, n=30). Peripheral blood was collected from each patient and a focal tissue biopsy was conducted. Results: We only found a limited statistically significant difference (p=0.046) in the mutation analysis for codon 12 of the KRAS gene when we compared tissue biopsies from patients in group B to those from group C. In the blood samples, only the rate of mutation in codon 12 of the KRAS gene in samples of group B was significantly higher than that in group A (p=0.013). Conclusion: Blood cfDNA may be a promising tool in CRC screening as it may discriminate patients with CRC compared to healthy individuals and those with colonic polyps, even though it does not appear useful in predicting the presence of colonic polyps.Σκοπός μας ήταν να πραγματοποιήσουμε μια μελέτη σύγκρισης του ρυθμού μετάλλαξης των V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) και v-Raf murine sarcoma viral oncogene homolog-B (BRAF) γονιδίων μεταξύ του κυκλοφορούντος DNA (cfDNA) σε δείγμα αίματος και στα ιστοτεμάχια από βιοψία παχέος εντέρου σε άτομα που υποβάλλονται σε προληπτική κολοσκόπηση. Υλικά και μέθοδοι: όλα τα δείγματα συλλέχθηκαν μεταξύ Ιανουαρίου 2015 έως τον Ιανουάριο 2016. Συνολικά 92 δείγματα αίματος και δείγματα βιοψίας από υγιή άτομα χωρίς πολύποδες που υποβάλλονται σε προληπτική κολοσκόπηση (ομάδα A, ν=35), ασθενών με καρκίνο του παχέος εντέρου (ΚΠΕ) (ομάδα Β, ν=27), και ασθενείς με νεοπλασματικούς εντερικούς πολύποδες (Ομάδα Γ, ν=30). Μικρή ποσότητα περιφερικού αίματος και ιστοτεμάχιο βιοψίας συλλέχθηκαν από κάθε ασθενή. Αποτελέσματα: βρήκαμε μόνο μια περιορισμένη στατιστικά σημαντική διαφορά (p=0.046) στην ανάλυση μετάλλαξης για το κωδικόνιο 12 του KRAS γονιδίου όταν συγκρίναμε βιοψίες ιστού παχέος εντέρου από ασθενείς της ομάδας Β με εκείνους της ομάδας Γ. Στα δείγματα αίματος, μόνο η συχνότητα μετάλλαξης στο κωδικόνιο 12 του γονιδίου KRAS σε δείγματα της ομάδας Β ήταν σημαντικά υψηλότερη από εκείνην της ομάδας Α (p=0.013). Συμπέρασμα: το cfDNA του αίματος μπορεί να είναι ένα ελπιδοφόρο εργαλείο στον προληπτικό έλεγχο για ΚΠΕ, καθώς μπορεί να διακρίνει ασθενείς με ΚΠΕ σε σύγκριση με υγιή άτομα και άτομα με πολύποδες κόλου, παρόλο που δεν φαίνεται χρήσιμο στην πρόβλεψη της παρουσίας πολυπόδων παχέος εντέρου

Ανεύρεση νέων μοριακών βιοδεικτών για την πρόληψη και έγκαιρη διάγνωση προκαρκινικών ή καρκινικών βλαβών παχέος εντέρου κατά την διάρκεια προληπτικού ελέγχου για καρκίνο παχέος εντέρου

Σκοπός: σκοπός μας ήταν να πραγματοποιήσουμε μια μελέτη σύγκρισης του ρυθμού μετάλλαξης των V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) και v-Raf murine sarcoma viral oncogene homolog-B (BRAF) γονιδίων μεταξύ του κυκλοφορούντος DNA (cfDNA) σε δείγμα αίματος και στα ιστοτεμάχια από βιοψία παχέος εντέρου σε άτομα που υποβάλλονται σε προληπτική κολοσκόπηση. Υλικά και μέθοδοι: όλα τα δείγματα συλλέχθηκαν μεταξύ Ιανουαρίου 2015 έως τον Ιανουάριο 2016. Συνολικά 92 δείγματα αίματος και δείγματα βιοψίας από υγιή άτομα χωρίς πολύποδες που υποβάλλονται σε προληπτική κολοσκόπηση (ομάδα A, ν=35), ασθενών με καρκίνο του παχέος εντέρου (ΚΠΕ) (ομάδα Β, ν=27), και ασθενείς με νεοπλασματικούς εντερικούς πολύποδες (Ομάδα Γ, ν=30). Μικρή ποσότητα περιφερικού αίματος και ιστοτεμάχιο βιοψίας συλλέχθηκαν από κάθε ασθενή. Αποτελέσματα: βρήκαμε μόνο μια περιορισμένη στατιστικά σημαντική διαφορά (p=0.046) στην ανάλυση μετάλλαξης για το κωδικόνιο 12 του KRAS γονιδίου όταν συγκρίναμε βιοψίες ιστού παχέος εντέρου από ασθενείς της ομάδας Β με εκείνους της ομάδας Γ. Στα δείγματα αίματος, μόνο η συχνότητα μετάλλαξης στο κωδικόνιο 12 του γονιδίου KRAS σε δείγματα της ομάδας Β ήταν σημαντικά υψηλότερη από εκείνην της ομάδας Α (p=0.013). Συμπέρασμα: το cfDNA του αίματος μπορεί να είναι ένα ελπιδοφόρο εργαλείο στον προληπτικό έλεγχο για ΚΠΕ, καθώς μπορεί να διακρίνει ασθενείς με ΚΠΕ σε σύγκριση με υγιή άτομα και άτομα με πολύποδες κόλου, παρόλο που δεν φαίνεται χρήσιμο στην πρόβλεψη της παρουσίας πολυπόδων παχέος εντέρου.Aim: Our aim was to perform a comparison study of the mutation rate of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-Raf murine sarcoma viral oncogene homolog-B (BRAF) genes between blood-based cell-free DNA (cfDNA), and tissue sample biopsies in individuals undergoing screening colonoscopy. Materials and Methods: All specimens were collected from January 2015 to January 2016. A total of 92 blood samples and colonic biopsy specimens were collected from healthy individuals with no polyps undergoing screening colonoscopy (group A, n=35), patients with colorectal cancer (group B, n=27), and patients with neoplastic intestinal polyps (group C, n=30). Peripheral blood was collected from each patient and a focal tissue biopsy was conducted. Results: We only found a limited statistically significant difference (p=0.046) in the mutation analysis for codon 12 of the KRAS gene when we compared tissue biopsies from patients in group B to those from group C. In the blood samples, only the rate of mutation in codon 12 of the KRAS gene in samples of group B was significantly higher than that in group A (p=0.013). Conclusion: Blood cfDNA may be a promising tool in CRC screening as it may discriminate patients with CRC compared to healthy individuals and those with colonic polyps, even though it does not appear useful in predicting the presence of colonic polyps

Impact of occupational stress on irritable bowel syndrome pathophysiology and potential management in active duty noncombat Greek military personnel: a multicenter prospective survey.

INTRODUCTION Irritable bowel syndrome (IBS) is one of the gut-brain axis interaction disorders. It has global distribution with varying prevalence and particular financial and psychological consequences. IBS has been associated with stress and anxiety, conditions that are usually prevalent in the army. There are scarce data investigating the impact of IBS on noncombat active duty military without reports of Greek military or stress in the occupational environment. MATERIALS AND METHODS The main exclusion criteria in our noncombat military multicenter prospective survey were gastrointestinal pathologies, malignancies, hematochezia, recent infections and antibiotics prescription, and pregnancy. Questionnaires included a synthesis of baseline information, lifestyle, and diet, psychological and stress-investigating scales and the IBS diagnosis checklist. Hospital Anxiety and Depression Scale and Rome IV criteria were utilized. RESULTS Among 1605 participants included finally, the prevalence of IBS was 8% and 131 cases were identified. Women were more vulnerable to IBS, although male sex was prevalent at a ratio of 3.5 : 1 (male:female) in the entire sample. The mean age of all participants was 23.85 years; most of the IBS patients were older than thirty. Abnormal anxiety scores and high levels of occupational stress were related to an IBS diagnosis. DISCUSSION This prospective multicenter survey showed, for the first time, the potential impact of occupational stress on IBS in active duty noncombat Greek Military personnel. The diagnosis of IBS by questionnaire is a quick, affordable way that can upgrade, by its management, the quality of life and relieve from the military burden. Our results are comparable with previous studies, although large-scale epidemiological studies are required for the confirmation of a possible causative relationship

The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review

Colorectal carcinoma (colon and rectum) is currently considered among the most prevalent malignancies of Western societies. The pathogenesis and etiological mechanisms underlying colorectal cancer (CRC) development remain complex and heterogeneous. The homeostasis and function of normal human intestinal cells is highly regulated by microRNAs. Therefore, it is not surprising that mutations and inactivation of these molecules appear to be linked with progression of colorectal tumors. Recent studies have reported significant alterations of microRNA expression in adenomas and CRCs compared with adjacent normal tissues. This observed deviation has been proposed to correlate with the progression and survival of disease as well as with choice of optimal treatment and drug resistance. MicroRNAs can adopt either oncogenic or tumor-suppressive roles during regulation of pathways that drive carcinogenesis. Typically, oncogenic microRNAs termed oncomirs, target and silence endogenous tumor-suppressor genes. On the other hand, tumor-suppressive microRNAs are critical in downregulating genes associated with cell growth and malignant capabilities. By extensively evaluating robust studies, we have emphasized and distinguished a discrete set of microRNAs that can modulate tumor progression by silencing specific driver genes crucial in signaling pathways including Wnt/b-catenin, epidermal growth factor receptor, P53, mismatch repair DNA repair, and transforming-growth factor beta

Helicobacter pylori eradication regimens in an antibiotic high-resistance European area: a cost-effectiveness analysis

INTRODUCTION: Helicobacter pylori infection (H pylori-I) affects more than half of the global population and consists an important burden to public health and healthcare expenditures, by contributing to many diseases' pathogenesis. AIM: This study aimed to evaluate the current nonbismuth quadruple eradication regimens in a high antibiotic resistance area, such as Greece, concerning their cost-effectiveness, especially during financial crisis period. MATERIALS AND METHODS: Eight hundred and nine patients who received eradication treatment against H pylori-I were included to evaluate five different regimens, using amoxicillin, clarithromycin, and metronidazole as antibiotics and one proton-pump inhibitor, based on their current eradication rates. Regimes compared 10-day concomitant use of (a) pantoprazole or (b) esomeprazole; 10-day sequential use of (c) pantoprazole or (d) esomeprazole; and 14-day hybrid using esomeprazole. Cost-effectiveness analysis ratio (CEAR) and incremental cost-effectiveness ratios were calculated taking into account all direct costs and cases who needed second-line treatment. Additionally, sensitivity analysis was performed to predict all potential combinations. RESULTS: Ten-day concomitant regimen with esomeprazole was characterized by the lowest CEAR (179.17€) followed by the same regimen using pantoprazole (183.27€). Hybrid regimen, although equivalent in eradication rates, was found to have higher CEAR (187.42€), whereas sequential regimens were not cost-effective (CEAR: 204.12€ and 216.02€ respectively). DISCUSSION: This is the first study evaluating the cost-effectiveness of H pylori-I treatment regimens in a high clarithromycin-resistance (≈26.5%) European area, suggesting the 10-day concomitant regimen with generics using esomeprazole 40 mg as the most appropriate one. National and regional guidelines should include cost-effectiveness in their statements, and further studies are required to clarify the necessity of a wide "test and treat" policy for H pylori-I

Evaluation of the direct economic cost per eradication treatment regimen against helicobacter pylori infection in Greece: Do national health policy-makers need to care?

Helicobacter pylori (Hp) management has undoubtedly resulted in a notable economic burden on healthcare systems globally, including Greece. Its cost has never been estimated so far, especially during the recent 10-year unprecedented financial crisis. Direct medical and procedural costs for one attempt "outpatient" Hp eradication treatment were estimated as the following: (I) first-line regimens: 10 and 14 days standard triple, 10 and 14 days sequential, 10 and 14 days concomitant non-bismuth quadruple, 14 days hybrid, (II) second-line salvage regimens: 10 and 14 days levofloxacin-containing triple regimens. Treatment costs using prototypes and/or generic drugs were calculated. Drug prices were collected and confirmed from two official online medical databases including all medicines approved by the Greek National Organization for Medicines. Regimens based on generics were more affordable than prototypes and those including pantoprazole yielded the lowest prices (mean: 27.84 €). Paradoxically, 10-day concomitant and 14-day hybrid regimens (currently providing good (90-94%) first-line eradication rates in Greece) cost the same (mean: 34.76 €). The expenditures for Hp eradication treatment regimens were estimated thoroughly for the first time in Greece. These data should be taken into account by Public Health policymakers both in Greece and the European Union, aiming for a better and less expensive therapeutic approach