Πειραματική μελέτη της συμμετοχής της απορογοννοποίησης στην πρώιμη επούλωση των εντερικών αναστομώσεων

ΕΙΣΑΓΩΓΗ Η αναστομωτική διαφυγή παραμένει καίριο ζήτημα για τους χειρουργούς του γαστρεντερικού σωλήνα. Το ποσοστό των αναστομωτικών διαφυγών, στα χέρια έμπειρων χειρουργών, παραμένει σε σχετικά υψηλά επίπεδα (2-7%). Τις τελευταίες δεκαετίες, η προοδευτική κατανόηση των πολύπλοκων παθολογοανατομικών μηχανισμών της επούλωσης, προσέφερε στους επιστήμονες ένα ευρύ φάσμα εργαλείων, προς περαιτέρω μελέτη και πειραματισμό. Στα πλαίσια αυτά δοκιμάστηκαν πολλές διαφορετικές χειρουργικές τεχνικές, υλικά και φαρμακευτικοί παράγοντες με σκοπό την ενίσχυση της επουλωτικής διαδικασίας, με αντικρουόμενα αποτελέσματα. ΣΚΟΠΟΣ Σκοπός της παρούσας μελέτης είναι η αξιολόγηση της συμμετοχής της απορρογονοποίησης στην επούλωση των εντεροεντερικών αναστομώσεων, και η επίδραση της στη μηχανική αντοχή και το σχηματισμό κολλαγόνου. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΣ Επτά οικόσιτοι χοίροι άρρενες τύπου Landrace, υποβλήθηκαν σε λαπαροτομία και διενέργεια 3 διαφορετικών τύπων πλαγιο- πλάγιας αναστόμωσης λεπτού εντέρου, σε απόσταση ~ 1,5 μέτρο από το σύνδεσμο του Treitz και με απόσταση 20 εκ. μεταξύ τους. Η πρώτη ομάδα αναστομώσεων (Ομάδα Α ή Ομάδα ελέγχου) περιελάμβανε τις αναστομώσεις χωρίς απορογοννοποίηση των αναστομωτικών επιφανειών. Στην Ομάδα Β αφαιρείτο ο ορογόννος από τη μία πλευρά της αναστομωτικής επιφάνειας, ενώ στην Ομάδα Γ διενεργείτο απορρογονοποίηση και των 2 πλεύρων της αναστόμωσης. Σε κάθε πειραματόζωο, πραγματοποιούνταν σε ίσες αποστάσεις μεταξύ τους, 2 αναστομώσεις από κάθε ομάδα. Όλα τα πειραματόζωα θυσιάζονταν την 7η μετεγχειρητική ημέρα. Η μηχανική αντοχή της αναστόμωσης ελέγχθηκε με τη μέτρηση της πίεσης διάσπασης (BP) εντός της κοιλιακής χώρας (in vivo). Η επούλωση αξιολογήθηκε και βαθμονομήθηκε σε ιστολογικό επίπεδο με ημιποσοτική κλίμακα για τον βαθμό επιθηλιοποίησης, τον βαθμό διήθησης από ουδετερόφιλα, την παρουσία και έκταση εξιδρώματος και αιμορραγίας, τη νέκρωση, καθώς επίσης τον πολλαπλασιασμό των ινοβλαστών, την εναπόθεση κολλαγόνου και την νεοαγγείωση. Στη συνέχεια, υπολογίστηκε το ιστολογικό σκορ επούλωσης [Histologic Repair Score System (HRS 0-9)] και το ιστολογικό σκορ αξιολόγησης της φλεγμονής [Histologic Assesment Inflammation System (HAIS 0-12)]. Η περιεκτικότητα σε κολλαγόνο αξιολογήθηκε μέσω των μετρήσεων της συγκέντρωσης υδροξυπρολίνης για κάθε δείγμα της αναστόμωσης, με τη χρήση της μεθόδου ELISA (BlueGene Hyp Kit). ΑΠΟΤΕΛΕΣΜΑΤΑ Η μακροσκοπική εξέταση των αναστομωτικών περιοχών δεν ανέδειξε σημεία διαφυγής, συλλογές ή αποστήματα σε κανένα από τα πειραματόζωα. Η ιστολογική αξιολόγηση της επούλωσης με τη χρήση της χρώσης αιματοξυλίνη- ιωσίνη και της τριχρωμίας Masson, ήταν συγκρίσιμη στις 3 ομάδες, χωρίς στατιστικά σημαντικές διαφορές. Η διάμεση BP διαμορφώθηκε για τις 3 ομάδες ώς εξής: oμάδα 1 (ομάδα ελέγχου) 59 mm Hg, ομάδα 2 (Ορογόνος- Υποβλεννογόνος) 73 mm Hg και ομάδα 3 (Υποβλεννογόνος- Υποβλεννογόνος) > 100 mm Hg, αναδεικνύοντας την υπεροχή της Ομάδας με την απορρογονοποίηση και στις 2 πλευρές. Επιπλέον, οι τιμές συγκέντρωσης σε υδροξυπρολίνη, ως εκφραστή της περιεκτικότητας κολλαγόνου, ήταν υψηλότερες για την εν λόγω ομάδα, με στατιστικά σημαντική διαφορά από την ομάδα χωρίς απορρογονοποίηση. Υψηλότερες τιμές υδροξυπρολίνης σημειώθηκαν και για την ομάδα με απορρογονοποίηση της μίας πλευράς [HYP]= 0.30 (± 0.05 SD), χωρίς ωστόσο στατιστικά σημαντικές διαφορές με την ομάδα της αμφοτερόπλευρης απορρογονοποίησης [HYP] = 0.38 nmol/ml ± 0.8 (SD). ΣΥΜΠΕΡΑΣΜΑ Η απορρογονοποίηση της αναστομωτικής επιφάνειας φαίνεται να έχει θετική επίδραση στην επούλωση των εντεροεντερικών αναστομώσεων, όπως αυτό διαφαίνεται από τα αποτελέσματα των πειραμάτων της παρούσας διδακτορικής διατριβής. Ειδικότερα, η απορρογονοποίηση και των δύο πλευρών των εντεροεντερικών αναστομώσεων οδηγεί σε υψηλότερες πιέσεις διάσπασης και συγκέντρωσης υδροξυπρολίνης, ως έκφραση της αύξησης της μηχανικής αντοχής και της περιεκτικότητας τους σε κολλαγόνο.Background The aim of this study is to investigate the impact of deserosalization on healing process and collagen formation in jejuno- jejunal anastomoses. Methods Seven female Landrace porcine were used. We performed three types of side to side jejuno- jejunal anastomosis. Group A anastomoses performed with no serosa removal, group B anastomoses performed after one- sided removal of jejunal serosa, and group C anastomoses were performed after serosa had been removed from both sides. Animals were survived up to 7 days before the anastomosis specimen was resected en bloc. Bursting pressure was measured in vivo as an indicator for anastomotic strength. Anastomotic collagen content was indirectly measured through Hydroxyproline (Hyp) concentration, as an indicator of the anastomotic healing. Hematoxylin- Eosin, and Mason Trichrome stained- sections were assessed by two independent histopathologists for the evaluation of cellular parameters and calculation of Histologic Repair Score System(HRS 0-9) and Histologic Assessment Inflammation System(HAIS 0-12). Results Increased Hyp concentration was observed in 6 out of 7 animals with jejuno- jejunal anastomoses lacking serosa from at least one side of the jejunal helices, compared to anastomoses that serosa remained intact (p< 0.05). Bursting pressure of the anastomosis achieved higher rates in cases of deserosalization as well. Histopathological assessment-, mechanical properties, and biochemical parameters of the three different types of anastomoses further support our findings, however, without reaching statistical significance. Conclusion Deserosalization from one or both sides of the jejunal helices in a jejuno- jejunal anastomosis seems to improve anastomotic healing in an experimental porcine model

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Cutaneous Metastases From Esophageal Adenocarcinoma

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30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

BACKGROUND There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates. METHODS We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020. RESULTS Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country. CONCLUSIONS BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak

Effect of BMI on safety of bariatric surgery during the COVID-19 pandemic, procedure choice, and safety protocols - An analysis from the GENEVA Study

Background: It has been suggested that patients with a Body Mass Index (BMI) of > 60 kg/m2 should be offered expedited Bariatric Surgery (BS) during the Coronavirus Disease-2019 (COVID-19) pandemic. The main objective of this study was to assess the safety of this approach. Methods: We conducted a global study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into three groups according to their preoperative BMI -Group I (BMI < 50 kg/m2), Group II (BMI 50-60 kg/m2), and Group III (BMI > 60 kg/m2). The effect of preoperative BMI on 30-day morbidity and mortality, procedure choice, COVID-19 specific safety protocols, and comorbidities was assessed. Results: This study included 7084 patients (5197;73.4 % females). The mean preoperative weight and BMI were 119.49 & PLUSMN; 24.4 Kgs and 43.03 & PLUSMN; 6.9 Kg/m2, respectively. Group I included 6024 (85 %) patients, whereas Groups II and III included 905 (13 %) and 155 (2 %) patients, respectively.The 30-day mortality rate was higher in Group III (p = 0.001). The complication rate and COVID-19 infection were not different. Comorbidities were significantly more likely in Group III (p = < 0.001). A significantly higher proportion of patients in group III received Sleeve Gastrectomy or One Anastomosis Gastric Bypass compared to other groups. Patients with a BMI of > 70 kg/m2 had a 30-day mortality of 7.7 % (2/26). None of these patients underwent a Roux-en-Y Gastric Bypass. Conclusion: The 30-day mortality rate was significantly higher in patients with BMI > 60 kg/m2. There was, however, no significant difference in complications rates in different BMI groups, probably due to differences in procedure selection

Safety of Bariatric Surgery in ≥ 65-Year-Old Patients During the COVID-19 Pandemic

Background Age >= 65 years is regarded as a relative contraindication for bariatric surgery. Advanced age is also a recognised risk factor for adverse outcomes with Coronavirus Disease-2019 (COVID-19) which continues to wreak havoc on global populations. This study aimed to assess the safety of bariatric surgery (BS) in this particular age group during the COVID-19 pandemic in comparison with the younger cohort.Methods We conducted a prospective international study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into two groups - patients >= 65-years-old (Group I) and patients < 65-years-old (Group II). The two groups were compared for 30-day morbidity and mortality.Results There were 149 patients in Group 1 and 6923 patients in Group II. The mean age, preoperative weight, and BMI were 67.6 +/- 2.5 years, 119.5 +/- 24.5 kg, and 43 +/- 7 in Group I and 39.8 +/- 11.3 years, 117.7 +/- 20.4 kg, and 43.7 +/- 7 in Group II, respectively. Approximately, 95% of patients in Group 1 had at least one co-morbidity compared to 68% of patients in Group 2 (p = < 0.001). The 30-day morbidity was significantly higher in Group I ( 11.4%) compared to Group II (6.6%) (p = 0.022). However, the 30-day mortality and COVID-19 infection rates were not significantly different between the two groups.Conclusions Bariatric surgery during the COVID-19 pandemic is associated with a higher complication rate in those >= 65 years of age compared to those < 65 years old. However, the mortality and postoperative COVID-19 infection rates are not significantly different between the two groups

30-Day morbidity and mortality of bariatric metabolic surgery in adolescence during the COVID-19 pandemic – The GENEVA study

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n = 122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7 ± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 146; 85.9%), only 42.4% (n = 72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n = 9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population