New Energy Devices in the Treatment of Cystic Echinococcosis

Treatment of cystic echinococcosis of the liver still remains a debatable subject. The method of choice should aim for the total elimination of the parasite with minimum morbidity and mortality. Different approaches have been proposed. Medical treatment as a monotherapy has been abandoned due to the high chances of recurrence and is mostly used as an adjuvant to surgery or minimally invasive methods. Surgical methods are divided into conservative ones, which include cystectomy and partial pericystectomy, and radical ones, total pericystectomy and hepatectomy. Radical procedures are correlated with lower complication and recurrence rates and, therefore, should be attempted when indications are present. On the other hand, conservative surgery can be the first option in endemic areas, performed by non-specialized general surgeons. The development of laparoscopic techniques made their use a possible alternative approach in selected cases. The use of percutaneous treatments is also quite widespread due to their minimally invasive nature. New energy devices seem to play a significant role in the treatment of cystic echinococcosis, although more studies are needed to establish their efficacy. Observation without intervention is an option for inactive uncomplicated cysts

Valve Type and Operative Risks in Surgical Explantation of Transcatheter Aortic Valves: A Systematic Review and Meta-Analysis

Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients with longer life expectancy. We proposed to perform a systematic review and meta-analysis with metaregression to identify potential factors that can determine an increase in the high mortality and morbidity that characterize these surgical procedures. MEDLINE and Embase were searched for relevant studies. Twelve studies were eligible according to our inclusion criteria. TAVR explantation was confirmed as a procedure with high 30-day mortality (0.17; 95% CI, 0.14–0.21) and morbidity (stroke incidence 5%; 95% CI, 0.04–0.07; kidney injury incidence 16%; 95% CI, 0.11–0.24). The type of transcatheter valve implanted during the index procedure did not influence the outcomes after surgical explantation. The role of these high-risk operations is growing, and it will likely expand in the coming years. Specific tools for risk stratification are required

Validation of the Surgical Outcome Risk Tool (SORT) and SORT v2 for Predicting Postoperative Mortality in Patients with Pancreatic Cancer Undergoing Surgery

BACKGROUND: Pancreatic cancer surgery is related to significant mortality, thus necessitating the accurate assessment of perioperative risk to enhance treatment decision making. A Surgical Outcome Risk Tool (SORT) and SORT v2 have been developed to provide enhanced risk stratification. Our aim was to validate the accuracy of SORT and SORT v2 in pancreatic cancer surgery. METHOD: Two hundred and twelve patients were included and underwent pancreatic surgery for cancer. The surgeries were performed by a single surgical team in a single tertiary hospital (2016-2022). We assessed a total of four risk models: SORT, SORT v2, POSSUM (Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity), and P-POSSUM (Portsmouth-POSSUM). The accuracy of the model was evaluated using an observed-to-expected (O:E) ratio and the area under the curve (AUC). RESULTS: The 30-day mortality rate was 3.3% (7 patients). Both SORT and SORT v2 demonstrated excellent discrimination traits (AUC: 0.98 and AUC: 0.98, respectively) and provided the best-performing calibration in the total analysis. However, both tools underestimated the 30-day mortality. Furthermore, both reported a high level of calibration and discrimination in the subgroup of patients undergoing pancreaticoduodenectomy, with previous ERCP, and CA19-9 ≥ 500 U/mL. CONCLUSIONS: SORT and SORT v2 are efficient risk-assessment tools that should be adopted in the perioperative pathway, shared decision-making (SDM) process, and counseling of patients with pancreatic cancer undergoing surgery

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting

Background: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. Methods: A systematic database search with meta‐analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single‐photon emission computed tomography (SPECT), and positron emission tomography (PET). Results: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post‐CABG was reduced in patients with versus without viability (random‐effects model: odds ratio: 0.42; 95% confidence interval: 0.29–0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. Conclusion: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount

The Surgical Treatment of Infective Endocarditis: A Comprehensive Review

Infective endocarditis (IE) is a severe cardiac complication with high mortality rates, especially when surgical intervention is delayed or absent. This review addresses the expanding role of surgery in managing IE, focusing on the variation in surgical treatment rates, the impact of patient demographics, and the effectiveness of different surgical approaches. Despite varying global data, a notable increase in surgical interventions for IE is evident, with over 50% of patients undergoing surgery in tertiary centres. This review synthesizes information from focused literature searches up to July 2023, covering preoperative to postoperative considerations and surgical strategies for IE. Key preoperative concerns include accurate diagnosis, appropriate antimicrobial treatment, and the timing of surgery, which is particularly crucial for patients with heart failure or at risk of embolism. Surgical approaches vary based on valve involvement, with mitral valve repair showing promising outcomes compared to replacement. Aortic valve surgery, traditionally favouring replacement, now includes repair as a viable option. Emerging techniques such as sutureless valves and aortic homografts are explored, highlighting their potential advantages in specific IE cases. The review also delves into high-risk groups like intravenous drug users and the elderly, emphasizing the need for tailored surgical strategies. With an increasing number of patients presenting with prosthetic valve endocarditis and device-related IE, the review underscores the importance of comprehensive management strategies encompassing surgical and medical interventions. Overall, this review provides a comprehensive overview of current evidence in the surgical management of IE, highlighting the necessity of a multidisciplinary approach and ongoing research to optimize patient outcomes

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Development and characterization of patient-derived xenografts (PDX) as preclinical models for pancreatic cancer

Pancreatic cancer (PC) is characterized by an increased incidence and extremely poor prognosis. Therefore, there is a great necessity to identify new biomarkers and develop personalized therapy. In this context, the Patient-Derived Xenografts (PDX) represent a novel and promising preclinical cancer model. PDXs are based on the implantation of cells from the patient's primary tumor into immunocompromised mice. With their ability to mimic the primary tumor microenvironment and highlight clonal heterogeneity, they are emerging as an innovative preclinical platform for studying cancer biology, discovering new biomarkers, and personalized testing of chemotherapeutic drug efficacy.Aquaporins (AQPs) represent a family of proteins with important channel functions, located in the cell membrane, and facilitating the translocation of water. A total of 13 proteins (AQP1-12A, B) are included in the AQP family. AQPs have been investigated for their role in the pathogenesis of various types of cancer, but the study of their role in pancreatic cancer remains limited.In the present Ph.D. thesis, we developed and standardized an orthotopic PDX model of pancreatic cancer in immunocompromised mice. The mouse strains we used were NOD/SCID, NSG, RAG-1, with different levels of immunosuppression per strain. Our results showed that the rate of successful implantation depends on the level of immunodeficiency. NSG mice, characterized by a lack of T, B, and NK cells (triple deficiency), were the most immunodeficient of the three species used in the thesis experiments. These findings highlight the important role of immune surveillance against cancer cells, which represents one of the pillars of cancer.At the same time, this thesis highlighted for the first time a unique genetic signature of 11 genes with differential expression in pancreatic cancer, which are simultaneously prognostic indicators related to patient survival. We also demonstrated the relevant molecular functions and regulatory families of miRNAs. This gene panel can be used in conjunction with existing staging systems to provide improved prognostic information. These data need further investigation and testing in PDX models to fully reveal their involvement in pancreatic cancer.As research into new therapeutic regimens and immunotherapies progresses, the orthotopic PDX models we present in this thesis allow an in-depth evaluation of new drugs in a tumor microenvironment that resembles the patient. Further studies to improve these models are already under development in our laboratory. At the same time, the identification of prognostic markers using in silico techniques allows for their further targeted study in PDX models, in a more cost-effective research approach in terms of time and resources. Finally, the identification of the prognostic role of Aquaporin 7 (AQP7) in pancreatic cancer by our group is the first and only to date recorded in the international literature.Ο καρκίνος του παγκρέατος (ΚΠ) χαρακτηρίζεται από αυξημένη επίπτωση και εξαιρετικά πτωχή πρόγνωση. Συνεπώς, η ανάγκη αναγνώρισης νέων βιοδεικτών και ανάπτυξης εξατομικευμένης θεραπείας είναι μεγάλη. Σε αυτό το πλαίσιο, τα ξενομοσχεύματα προερχόμενα από ασθενή (Patient Derived Xenografts - PDX) αποτελούν ένα νέο και πολλά υποσχόμενο προκλινικό μοντέλο καρκίνου. Τα PDX βασίζονται στην εμφύτευση κυττάρων προερχόμενων από τον πρωτοπαθή όγκο του ασθενούς σε ανοσοκατεσταλμένα ποντίκια. Με την ικανότητα που προσφέρουν να προσομοιάζουν πιστά στο μικροπεριβάλλον του πρωτοπαθούς όγκου και να αναδεικνύουν την κλωνική ετερογένεια, αναδεικνύονται σε μία καινοτόμο προκλινική πλατφόρμα για τη μελέτη της βιολογίας του καρκίνου, την ανακάλυψη νέων βιοδεικτών και την εξατομικευμένη δοκιμή της αποτελεσματικότητας χημειοθεραπευτικών φαρμάκων.Οι Ακουαπορίνες (Aquaporins – AQPs) αποτελούν μία οικογένεια πρωτεϊνών με λειτουργία διαύλων, που εντοπίζονται στην κυτταρική μεμβράνη και διευκολύνουν τη μετακίνηση ύδατος. Ένα σύνολο 13 πρωτεϊνών (AQP1-12Α, Β) συμπεριλαμβάνονται στην οικογένεια AQP. Οι AQPs έχουν διερευνηθεί για το ρόλο τους στην παθογένεση διαφόρων τύπων καρκίνου, αλλά η μελέτη του ρόλου τους στον καρκίνο του παγκρέατος παραμένει περιορισμένη.Στην παρούσα διδακτορική διατριβή αναπτύξαμε ένα ορθοτοπικό μοντέλο PDX καρκίνου παγκρέατος σε ανοσοκατεσταλμένα ποντίκια. Τα στελέχη ποντικιών που χρησιμοποιήσαμε ήταν τα NOD/SCID, NSG, RAG-1, με διαφορετικό επίπεδο ανοσοκαταστολής ανά στέλεχος. Τα αποτελέσματά μας έδειξαν ότι το ποσοστό επιτυχούς εμφύτευσης εξαρτάται από το επίπεδο ανοσοανεπάρκειας. Τα ποντίκια NSG που χαρακτηρίζονται από έλλειψη T, B, και κυττάρων φυσικών φονέων (NK cells) (τριπλή ανεπάρκεια) ήταν τα πλέον ανοσοανεπαρκή από τα τρία είδη που χρησιμοποιήθηκαν στα πειράματα της διατριβής. Αυτά τα ευρήματα αναδεικνύουν το σημαίνοντα ρόλο της ανοσολογικής επιτήρησης έναντι των καρκινικών κυττάρων, που αντιπροσωπεύει και έναν από τους πυλώνες του καρκίνου. Παράλληλα, η παρούσα διατριβή ανέδειξε για πρώτη φορά μία μοναδική γενετική υπογραφή 11 γονιδίων με διαφοροποιημένη έκφραση στον καρκίνο του παγκρέατος, που αποτελούν ταυτόχρονα προγνωστικούς δείκτες σχετιζόμενους με την επιβίωση των ασθενών. Επίσης, αναδείξαμε τις σχετικές μοριακές λειτουργίες και ρυθμιστικές οικογένειες miRNA. Αυτό το γονιδιακό πάνελ μπορεί να χρησιμοποιηθεί σε συνδυασμό με τα υπάρχοντα συστήματα σταδιοποίησης ώστε να διαθέτουμε βελτιωμένες προγνωστικές πληροφορίες. Τα συγκεκριμένα δεδομένα χρήζουν περαιτέρω έρευνας και δοκιμής σε μοντέλα PDX ώστε να αποκαλυφθεί πλήρως η εμπλοκή τους στον καρκίνο του παγκρέατος.Καθώς η έρευνα για νέα θεραπευτικά σχήματα και ανοσοθεραπείες προχωράει, τα ορθοτοπικά μοντέλα PDX που παρουσιάζουμε στην παρούσα διατριβή επιτρέπουν μία σε βάθος εκτίμηση των νέων φαρμάκων σε ένα μικροπεριβάλλον όγκου που ομοιάζει με του ασθενούς. Περαιτέρω μελέτες για τη βελτίωση αυτών των μοντέλων βρίσκονται ήδη σε στάδιο ανάπτυξης στο εργαστήριο μας. Παράλληλα, ο εντοπισμός προγνωστικών δεικτών με in silico τεχνικές επιτρέπει την περαιτέρω στοχευμένη μελέτη τους σε μοντέλα PDX, σε μία πιο αποδοτική ως προς το κόστος, το χρόνο και τους διαθέσιμους πόρους ερευνητική προσέγγιση. Τέλος, η ανάδειξη του προγνωστικού του ρόλου της AQP7 στον καρκίνο του παγκρέατος από την ομάδα μας αποτελεί την πρώτη και μοναδική μέχρι σήμερα καταγραφή στη διεθνή βιβλιογραφία