HIPEC στον καρκίνο του στομάχου

Ο καρκίνος του στομάχου αποτελεί την τρίτη συνηθέστερη κακοήθεια παγκοσμίως και την τρίτη αιτία θανάτου από κακοήθη νόσο και συχνά συνοδεύεται από συγχρονη ή μετάχρονη περιτοναϊκή νόσο. Εμφανίζει δε διαφορετικά επιδημιολογικά χαρακτηριστικά ανάλογα με την περιοχή, τη φυλή και το φύλο και συνδέεται με καλά τεκμηριωμένους παράγοντες κινδύνου. Το στάδιο της νόσου είναι αυτό που καθορίζει την πρόγνωση και τις θεραπευτικές επιλογές. Οι ασθενείς με περιτοναϊκή νόσο από καρκίνο του στομάχου αντιμετωπίζονται παραδοσιακά αποκλειστικά με συστηματική χημειοθεραπεία. Ωστόσο, λόγω των ανατομικών και φυσιολογικών ιδιαιτεροτήτων του περιτοναίου, οι περιτοναϊκές εμφυτεύσεις δεν ανταποκρίνονται καλώς στη συστηματική χημειοθεραπεία. Έτσι, τις τελευταίες δεκαετίες έχει προταθεί μια διαφορετική θεραπευτική προσέγγιση για επιλεγμένους ασθενείς, η οποία αποτελείται από κυτταρομειωτική χειρουργική και ενδοπεριτοναϊκή χορήγηση χημειοθεραπείας. Τόσο η κυτταρομειωτική χειρουργική όσο και η ενδοπεριτοναϊκή χημειοθεραπεία διέπονται από συγκεκριμένες αρχές και απαιτούν η καθεμία συγκεκριμένο σχεδασμό. Ο σκοπός της εργασίας αυτής είναι να μελετήσει την προσέγγιση αυτή με αφετηρία κλινικές μελέτες που έχουν διεξαχθεί την τελευταία δεκαετία με ιδιαίτερη επικέντρωση στο όφελος που προσφέρει στην επιβίωση ο συνδυασμός κυτταρομείωσης και διεγχειρητικής χορήγησης υπέρθερμης ενδοπεριτοναϊκής χημειοθεραπείας (HIPEC). Φαίνεται ότι ο επιθετικότερος θεραπευτικός σχεδιασμός μπορεί να βελτιώσει την ολική και την ελεύθερη νόσου επιβίωση σε επιλεγμένες ομάδες ασθενών. Βασικούς προγνωστικούς παράγοντες αποτελούν η έκταση της περιτοναϊκής νόσου (PCI score) και η παραμονή υπολλειμματικής νόσου μετά την κυτταρομείωση (CC score). Οι παράγοντες αυτοί επηρεάζουν την πρόγνωση των ασθενών και καθοδηγούν το σχεδιασμό των θεραπευτικών πρωτοκόλλων στις κλινικές μελέτες. Έχουν προταθεί εκτεταμένα θεραπευτικά πρωτόκολλα αντιμετώπισης της περιτοναϊκής νόσου από γαστρικό καρκίνο, στα οποία εντάσσονται συνδυαστικά η νεοεπικουρική θεραπεία, η κυτταρομείωση, οι διάφορες μορφες ενδοπεριτοναϊκής θεραπείας και η επικουρική χημειοθεραπεία. Οι αναδυόμενες αυτές τεχνικές αποτελούν αντικείμενο εν εξελίξει τυχαιοποιημένων κλινικών μελετών, όπως είναι η GASTRICHIP, η GASTRIPEC, η DRAGON II και η PERISCOPE II. Η περιτοναϊκή νόσος πρέπει πλέον να αντιμετωπίζεται εξατομικευμένα από πολυτομεακές ομάδες σε εξειδικευμένα κέντρα.Gastric cancer constitutes the third most common malignancy worldwide and the third most common cause of death due to malignancy. The incidence of the disease differs depending on the area, the race and the gender. The prognosis as well as the treatment options depend largely on the stage of the disease. Patients with peritoneal carcinomatosis due to gastric cancer were traditionally treated solely with systemic chemotherapy. However, the cancer deposits in the peritoneal cavity do not respond well to systemic chemotherapy. This traces back to the cavity not being readily accessible to the systemically administered chemotherapeutic agents, due to its anatomical and physiological characteristics. Experts proposed during the last few decades a different approach consisting of cytoreductive surgery and intraperitoneal chemotherapy. Both the cytoreductive surgery and the intraperitoneal chemotherapy have their own unique principles and require specific design. The purpose of this study is to contemplate this approach, using the clinical studies conducted in the last decade as a starting point. It especially focuses on the survival benefit of the combination of cytoreductive surgery and intraoperative administration of Hyperthermic Intraperitoneal Chemotherapy (HIPEC). As it seems, this more aggressive therapeutic design may have a positive impact on survival, when considering carefully chosen subgroups of patients. The extent of the peritoneal disesase (PCI score) and the completeness of cytoreduction (CC score) constitute the most important prognostic factors and guide clinical decisions and the design of the treatment protocols. Such protocols for combating peritoneal disease in patients with gastric cancer have been proposed by many experts. They incorporate neoadjuvant chemotherapy, cytoreduction, different forms of intraperitoneal chemotherapy and advuvant therapy. These emerging therapeutic approaches are being investigated in evolving randomized clinical trials, such as GASTRICHIP, GASTRIPEC, DRAGON II and PERISCOPE II trials. Peritoneal disease should be individualized according to the patient characteristics by multidisciplinary teams in specialized centres

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism

Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner.

The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology

The Impact of Mechanical Bowel Preparation and Oral Antibiotics in Colorectal Cancer Surgery (MECCA Study): A Prospective Randomized Clinical Trial

Background: Colorectal cancer surgery has been associated with surgical site infections (SSIs), leading to an increase in postoperative morbidity, length of stay and total cost. The aim of the present randomized study was to investigate the relationship between the preoperative administration of oral antibiotic therapy and SSI rate, as well as other postoperative outcomes in patients undergoing colorectal cancer surgery. Material and Methods: Patients who underwent colorectal cancer surgery in a university surgical department were included in the present study. Patients were randomized into two groups using the “block randomization” method. The intervention group received three doses of 400 mg rifaximin and one dose of 500 mg metronidazole per os, as well as mechanical bowel preparation the day before surgery. The control group underwent only mechanical bowel preparation the day before surgery. The study has been registered in ClinicalTrials.gov (NCT03563586). Results: Two hundred and five patients were finally included in the present study, 97 of whom received preoperative antibiotic therapy per os (intervention group). Patients of this group demonstrated a significantly lower SSI rate compared with patients who did not receive preoperative antibiotic therapy (7% vs. 16%, p = 0.049). However, preoperative antibiotic administration was not correlated with any other postoperative outcome (anastomotic leak, overall complications, readmissions, length of stay). Conclusions: Preoperative antibiotic therapy in combination with mechanical bowel preparation seemed to be correlated with a lower SSI rate after colorectal cancer surgery