30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE): A Prospective, International Collaborative Cohort Study.

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

The ChoCO-W prospective observational global study: Does COVID-19 increase gangrenous cholecystitis?

BACKGROUND: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. METHODS: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. RESULTS: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. CONCLUSIONS: The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands.

Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE study.

OBJECTIVE: This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. DESIGN: A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. RESULTS: PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test-retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. CONCLUSION: The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. TRIAL REGISTRATION NUMBER: NCT03650062.

Pathogenic role of myeloperoxidase in acute pancreatitis.

BACKGROUND: Myeloperoxidase (MPO) has been implicated in promoting tissue damage in various inflammatory diseases. However, MPO blood levels in relation to the severity of acute pancreatitis (AP) and its time-course have not been studied. The present study aimed to determine the role of MPO in AP. METHODS: We studied 86 patients with AP (48 patients with mild and 38 with severe pancreatitis) and 18 controls (volunteers). The relations of serum MPO levels to cytokine level, severity, and time-course of pancreatitis were studied. The serum level of MPO and cytokines were measured by MPO-EIA and cytokines ELISA, respectively. RESULTS: The highest level of MPO was noted at the first day in patients with severe AP. A decrease of MPO blood level occurred during the first three days in all patients with necrotizing pancreatitis. The development of pancreatitis-associated lung injury and purulent complications was accompanied by increased MPO levels. Administration of pentoxifylline significantly reduced the MPO blood level, which was clearly correlated with the levels of proinflammatory cytokines in the two groups of patients. CONCLUSIONS: The results of the present study showed the MPO blood level is dependent on the severity of AP and on cytokine blood levels. Pentoxifylline in the complex management of severe AP may improve the results of treatment.

Pathogenic aspects of pulmonary complications in acute pancreatitis patients.

BACKGROUND: Experimental and clinical observations show that proinflammatory cytokines and oxidative stress are involved in the development of local and particularly systemic complications in acute pancreatitis (AP) patients. There are often pulmonary complications in such patients. The mechanisms through which lung injury is induced in AP are not fully clear. METHODS: In order to assess the role of activated neutrophils, pro- and anti-inflammatory cytokines and adhesion molecules at the onset and development of respiratory complications and respiratory failure, we measured the serum levels of pro-inflammatory (IL-1 beta, IL-6, IL-8, IL-18, TNF-alpha) and anti-inflammatory (IL-1 ra, IL-10) cytokines in 51 AP patients who had been diagnosed with pancreatitis-associated lung injury with and without the development of organ dysfunction. RESULTS: When admitted to the hospital, severe AP patients had increased concentrations of IL-1 beta, IL-6, IL-8, IL-18, and TNF-alpha. The concentration of IL-18 alone was considerably increased in the patients who later developed respiratory failure. The onset of acute respiratory distress syndrome in the AP patients was accompanied by an increase in the level of anti-inflammatory cytokines, especially IL-10. It was noted that in severe lung injury, myeloperoxidase activity in the blood increased significantly, but still reflected the processes taking place in the lung parenchyma. Increase in the concentrations of adhesion molecules preceded the development of pulmonary infiltration with respiratory failure symptoms, which provoked endothelial dysfunction and determined the capillary surface permeability for neutrophils and monocytes. CONCLUSIONS: In the pathogenesis of respiratory complications in AP cytokines, chemokines and adhesion molecules, in particular IL-1 eta, IL-6, IL-8, IL-18, TNF-alpha, ICAM-1, and E-selectin play major roles. At IL-18 concentrations >650 pg/ml, AP patients are likely to develop pulmonary dysfunction (sensitivity 58%, specificity 100%, LR-positive >58) which allows us to use it as a screening test.