Acute pancreatitis (AP) is a severe inflammation of the pancreas presented with sudden onset and severe abdominal pain with a high morbidity and mortality rate, if accompanied by severe local and systemic complications. Numerous studies have been published about the pathogenesis of AP; however, the precise mechanism behind this pathology remains unclear. Extensive research conducted over the last decades has demonstrated that the first 24 h after symptom onset are critical for the identification of patients who are at risk of developing complications or death. The identification of these subgroups of patients is crucial in order to start an aggressive approach to prevent mortality. In this sense and to avoid unnecessary overtreatment, thereby reducing the financial implications, the proper identification of mild disease is also important and necessary. A large number of multifactorial scoring systems and biochemical markers are described to predict the severity. Despite recent progress in understanding the pathophysiology of AP, more research is needed to enable a faster and more accurate prediction of severe AP. This review provides an overview of the available multifactorial scoring systems and biochemical markers for predicting severe AP with a special focus on their advantages and limitations.
Summary Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov , NCT03471494 . Findings Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding National Institute for Health Research Global Health Research Unit.
Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that, when classified as severe, is associated with high morbidity and mortality. Promptly identifying the severity of AP is of extreme importance for improving clinical outcomes. The aim of this study was to compare the prognostic value of serological biomarkers, ratios, and multifactorial scores in patients with acute biliary pancreatitis and to identify the best predictors. In this observational and prospective study, the biomarkers, ratios and multifactorial scores were evaluated on admission and at 48 h of the symptom onset. On admission, regarding the AP severity, the white blood count (WBC) and neutrophil–lymphocyte ratio (NLR), and regarding the mortality, the WBC and the modified Marshall score (MMS) showed the best predictive values. At 48 h, regarding the AP severity, the hepcidin, NLR, systemic inflammatory response index (SIRI) and MMS and regarding the mortality, the NLR, hepcidin and the bedside index for severity in AP (BISAP) score, showed the best predictive values. The present study enabled the identification, for the first time, of SIRI as a new prognostic tool for AP severity, and validated hepcidin and the NLR as better prognostic markers than C-reactive protein (CRP) at 48 h of symptom onset.
Acute pancreatitis (AP) is a severe disease associated with high morbidity and mortality. Clinical studies can provide some data concerning the etiology, pathophysiology, and outcomes of this disease. However, the study of early events and new targeted therapies cannot be performed on humans due to ethical reasons. Experimental murine models can be used in the understanding of the pancreatic inflammation, because they are able to closely mimic the main features of human AP, namely their histologic glandular changes and distant organ failure. These models continue to be important research tools for the reproduction of the etiological, environmental, and genetic factors associated with the pathogenesis of this inflammatory pathology and the exploration of novel therapeutic options. This review provides an overview of several murine models of AP. Furthermore, special focus is made on the most frequently carried out models, the protocols used, and their advantages and limitations. Finally, examples are provided of the use of these models to improve knowledge of the mechanisms involved in the pathogenesis, identify new biomarkers of severity, and develop new targeted therapies.
Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non‐steroidal anti‐inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student‐ and trainee‐led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre‐specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non‐selective cyclo‐oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.
Introduction Transanal total mesorectal excision (TaTME) has rapidly emerged as a novel approach for rectal cancer surgery. Safety profiles are still emerging and more comparative data is urgently needed. This study aimed to compare indications and short‐term outcomes of TaTME, open, laparoscopic, and robotic TME internationally. Methods A pre‐planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients undergoing elective total mesorectal excision (TME) for malignancy between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. Results Of 2579 included patients, 76.2% (1966/2579) underwent TME with restorative anastomosis of which 19.9% (312/1966) had a minimally invasive approach (laparoscopic or robotic) which included a transanal component (TaTME). Overall, 9.0% (175/1951, 15 missing outcome data) of patients suffered an anastomotic leak. On univariate analysis both laparoscopic TaTME (OR 1.61, 1.02–2.48, P = 0.04) and robotic TaTME (OR 3.05, 1.10–7.34, P = 0.02) were associated with a higher risk of anastomotic leak than non‐transanal laparoscopic TME. However this association was lost in the mixed‐effects model controlling for patient and disease factors (OR 1.23, 0.77–1.97, P = 0.39 and OR 2.11, 0.79–5.62, P = 0.14 respectively), whilst low rectal anastomosis (OR 2.72, 1.55–4.77, P < 0.001) and male gender (OR 2.29, 1.52–3.44, P < 0.001) remained strongly associated. The overall positive circumferential margin resection rate was 4.0%, which varied between operative approaches: laparoscopic 3.2%, transanal 3.8%, open 4.7%, robotic 1%. Conclusion This contemporaneous international snapshot shows that uptake of the TaTME approach is widespread and is associated with surgically and pathologically acceptable results.
(1) Background: Acute pancreatitis (AP) is an inflammatory process of the pancreas with variable involvement of the pancreatic and peripancreatic tissues and remote organ systems. The main goal of this study was to evaluate the inflammatory biomarkers, oxidative stress (OS), and plasma metabolome of patients with different degrees of biliary AP severity to improve its prognosis. (2) Methods: Twenty-nine patients with biliary AP and 11 healthy controls were enrolled in this study. We analyzed several inflammatory biomarkers, multifactorial scores, reactive oxygen species (ROS), antioxidants defenses, and the plasma metabolome of biliary AP and healthy controls. (3) Results: Hepcidin (1.00), CRP (0.94), and SIRI (0.87) were the most accurate serological biomarkers of AP severity. OS played a pivotal role in the initial phase of AP, with significant changes in ROS and antioxidant defenses relating to AP severity. Phenylalanine (p < 0.05), threonine (p < 0.05), and lipids (p < 0.01) showed significant changes in AP severity. (4) Conclusions: The role of hepcidin and SIRI were confirmed as new prognostic biomarkers of biliary AP. OS appears to have a role in the onset and progression of the AP process. Overall, this study identified several metabolites that may predict the onset and progression of biliary AP severity, constituting the first metabonomic study in the field of biliary AP.
Introduction The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre‐operative imaging. Methods A pre‐planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post‐treatment MRI restaging (yMRI) and final pathological staging. Results Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post‐treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T‐stage, N‐stage, or AJCC status were each graded as ‘fair’ only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively). Conclusion The reported pCR rate of 10% highlights the potential for non‐operative management in selected cases. The limited strength of agreement between basic conventional post‐chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials.
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