Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs. Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in emergency surgical units worldwide.The cornerstone of effective treatment of IAIs includes early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using intravenous fluid therapy in critically ill patients.Results from published clinical trials often may not be representative of the true morbidity and mortality rates of such severe infections. Firstly, patients who have perforated appendicitis are usually over-represented in clinical trials. Secondly, patients with IAIs enrolled in clinical trials have often an increased likelihood of cure and survival. This is due to the fact that selective trial eligibility criteria usually exclude patients with comorbid diseases and other factors which are associated with death from IAI . AffectiIAIs respect the principles of egalitarianism, as they remain a potential threat to the health of all humans of all age groups, race, and socioeconomics. Globally, the burden of IAIs is tremendous . PatientA wide variety of organizations have published guidelines outlining the clinical management of IAIs –11; howeIn hospitals worldwide, non-acceptance of or non-compliance with or lack of access to evidence-based practices and guidelines in hospitals result in the overall poorer outcome of patients suffering from IAIs. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), The World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries worldwide with varying backgrounds.Adequate detection and treatment are essential to minimize complications of IAIs , 13. DiaPatients with IAIs typically present with rapid-onset abdominal pain and signs of local and systemic inflammation . Hypotension and signs of hypoperfusion such as oliguria, acute alteration of mental status, and lactic acidosis are indicative of ongoing organ failure.Physical evaluation may limit the differential diagnoses to better direct decisions regarding a proper management plan including the selection of appropriate diagnostic testing, the need for initiation of antibiotic therapy, and whether emergent intervention is required .The value of physical findings in the diagnostic work-up for IAIs has been studied in relation to acute appendicitis where signs and symptoms are helpful in diagnosing or excluding appendicitis , 13.Inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT) have been evaluated in the diagnosis of bacterial infection. CRP is an acute-phase protein promptly released during an inflammation. Since systemic bacterial infection is often associated with an inflammatory reaction, it represents an indirect marker of infection and inflammation .Conversely, PCT rapidly increases in the presence of bacterial and fungal infections but not viral infections or noninfectious inflammation .PCT has been evaluated in the management of IAIs, both for diagnosis and for guiding antibiotic therapy. However, it is important to take into account the limitations of biomarkers to ensure the appropriate use of them. Importantly, as with any diagnostic tool, PCT and CRP should be used embedded in clinical algorithms adapted to the type of infection and the clinical context and setting . MoreoveProposals of staged algorithms using a step-up approach with CT performed after an inconclusive or negative US have been proposed in the setting of acute appendicitis and acute diverticulitis –23.In order to identify an optimal imaging strategy for the accurate detection of urgent conditions in patients with acute abdominal pain, a multicenter diagnostic accuracy study using prospective data collection has been published . In thisMagnetic resonance imaging (MRI) is not routinely available in most hospitals in the emergency setting. Its use has been proposed in pregnant patients with abdominal pain when US is inconclusive , 23.Once the diagnosis is made, initial management of IAI includes an appropriate control of the source of the infection, adequate antibiotic therapy directed against the likely pathogens, and the prompt physiologic stabilization of the patient using intravenous fluid therapy Fig. .Fig. 1PThe term “source control” encompasses all those physical measures used to control a focus of invasive infection and to restore the optimal function of the affected area .Intra-abdominal infections along with soft tissues infections are the sites where a source control is more feasible and more impactful.Appropriate source control is of utmost importance in the management of IAIs. In these settings, appropriate source control can improve patients’ outcomes. Even though not definitively tested by randomized control trials, the magnitude of the increase in death and other adverse outcomes associated with inadequate source control makes it clear that it is of prime importance in treating most patients with IAIs. Moreover, an adequate source control can also shorten the course of antibiotic therapy. The impact of source control seems to be unrelated to the administration of appropriate antibiotics. Several studies found that both are independent predictors of mortality , but theSource control assumes a comprehensive knowledge of biologic principles, the complexities of the infection response, the range of surgical and nonsurgical options, and a combination of therapeutic aggressiveness and judicious caution in the clinician charged with making the decision. Appropriate source-control intervention can rapidly alter the course of intra-abdominal infections to a more favorable direction, and suboptimal decision-making can change a difficult clinical challenge into a clinical burden .The rules of source control are the following: (First) Time, Totalization, Technique, and (Second) Time.The first time is related to the starting time of the treatment. Each hour in delaying represents a negative factor in the outcome.The goal of the procedure is the totally  removing of any infective source and damaged tissues, opening spaces and compartment, evacuating pus or other fluids, deriving or resecting of any intestinal critical ischemic tracts also without immediate continuity restoration, and washing out the abdominal cavity. The surgical technique should be always correct and adequate.The second time is related to the timing of further surgical control that may be either “on demand” or planned aimed to avoid a more dangerous surgical trauma in a critical patient.The level of urgency of treatment is determined by the affected organ(s), the relative speed at which clinical symptoms progress and worsen, and the underlying physiological stability of the patient.Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock recommend that a specific anatomic diagnosis of infection requiring emergent source control be identified or excluded as rapidly as possible in patients with sepsis or septic shock, and that any required source control intervention be implemented as soon as medically and logistically practical after the diagnosis is made. Studies of septic patients undergoing source control for IAIs suggest that delays of only 3–6 h were associated with an increased mortality –27. AlthThe control of the source of infection can be achieved using both operative and non-operative techniques. An operative intervention remains the most viable therapeutic strategy for managing surgical infections in critically ill patients .The selection of a specific source control procedure for a patient should be predicated both on the characteristics of the infection and the patient, as well as the availability of technical expertise at the local institution.Non-operative interventional procedures include percutaneous drainages of abscesses. Ultrasound-and CT-guided percutaneous drainage of abdominal and extraperitoneal abscesses in selected patients are safe and effective. The principal cause for failure of percutaneous drainage is the misdiagnosis of the magnitude, extent, complexity, and location of the abscess.Surgery is the most important therapeutic measure to control surgical infections. In the setting of IAIs the primary objectives of surgical intervention include a) determining the cause of the infection, b) draining fluid collections, and c) controlling the origin of the infection. In patients with IAIs, surgical source control entails resection or suture of a diseased or perforated viscus , removal of the infected organ , debridement of necrotic tissue, resection of ischemic bowel, and repair/resection of traumatic perforations with primary anastomosis or creation of stomas.p = 0.001) and shorter median hospital stays . Direct medical costs per patient were reduced by 23% using the on-demand strategy.Traditionally, extensive lavage of the peritoneal cavity is used in the management of IAIs. Several recent series and one prospective trial of patients with perforated appendicitis likewise have found that aspiration and limited irrigation to remove gross contamination were as effective as lavage –31. SurgThe open abdomen (OA) may seem a viable option to some for treating physiologically deranged patients with ongoing sepsis, facilitating subsequent exploration and control of abdominal contents, and preventing abdominal compartment syndrome. The OA concept is closely linked to damage control surgery. However, the OA principle is the complete opposite of the on-demand relaparotomy strategy; the latter being a level 1 evidence proven beneficial strategy. Abdominal compartment syndrome in non-trauma patients can be mainly prevented by modern ICU techniques and fluid management. Deliberately leaving an abdomen open, which could otherwise be closed primarily, introduces risks of excessive fluid and electrolyte loss, undirected explorations, and intestinal fistula .Every day an abdomen is left open, the risk of intestinal fistula increases. When closure is not possible at index laparotomy due to visceral edema, a negative pressure-based temporary closure device for progressive secondary fascial closure is used.Open abdomen combined with negative pressure therapy is a different and more recent concept of abdominal sepsis treatment. In an open abdomen, the use of a  negative pressure device reduces mortality. Unclear is whether the benefits of this strategy are a reason to leave an abdomen open that could otherwise be closed. In order to define the role of OA with negative pressure therapy for improved biomediator clearance and mitigated systemic sepsis in patients with severe peritonitis the results of ongoing prospectively randomized trials, such as the COOL Trial, are needed .Open abdomen combined with negative pressure therapy and fluid instillation is taking this therapeutic concept one step further, and results are promising , 36. SevAntibiotics should be used after a treatable infection has been recognized or if there is a high degree of suspicion of an infection. The prolonged and inappropriate use of antibiotics appears a key factor in the rapid rise of antimicrobial resistance worldwide over the past decade. A rational and appropriate use of antibiotics is particularly important both to optimize quality clinical care and to reduce selection pressure on resistant pathogens.In the setting of uncomplicated IAIs, such as uncomplicated appendicitis or cholecystitis, single doses have the same impact as multiple doses and post-operative antimicrobial therapy is not necessary if source control is adequate .In the setting of complicated IAIs, a short course of antibiotic therapy after adequate source control is a reasonable option. The recent prospective trial by Sawyer et al.  demonstrShort-course antibiotics were demonstrated also in patients with post-operative IAIs .p < 0.0001) . Equivalence was established in terms of 45-day mortality . Treatments did not differ in terms of ICU and hospital length of stay, emergence of multi-drug-resistant (MDR) bacteria, or reoperation rate.A multicenter prospective randomized trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with post-operative IAIs. Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days versus 12 days, respectively; Short-course antibiotic therapy in critically ill ICU patients with post-operative IAIs reduced antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit.However, in patients with evidence of an ongoing infection, an individualized approach should be mandatory and the patient’s inflammatory response should be monitored regularly and decisions to continue, narrow, or stop antibiotic therapy must be made on the basis of clinician judgment and laboratory (such as CRP or PCT levels) investigations.Patients who have ongoing signs of infection or systemic illness beyond 5–7 days of antibiotic treatment normally warrant a diagnostic investigation to determine whether additional surgical intervention or percutaneous drainage is necessary to address an ongoing uncontrolled source of infection or antibiotic treatment failure .Initial antibiotic therapy for IAIs is typically empiric in nature because a patient with abdominal sepsis needs immediate treatment, and microbiological data (culture and susceptibility results) can require up to 48–72 h before they are available for a more detailed analysis.Obtaining microbiological results from peritoneal fluid cultures from the site of infection has two advantages: (a) it provides an opportunity to expand the antimicrobial regimen if the initial choice was too narrow, and (b) it also allows de-escalation of antimicrobial therapy if the empirical regimen was too broad. Intraperitoneal specimens for microbiological evaluation from the site of infection are always recommended for patients with hospital-acquired IAIs or with community-acquired IAIs at risk for resistant pathogens and in critically ill patients. Obtaining cultures in all patients with IAIs for epidemiologic purposes if adequate resources are available can also allow aggregation and analysis of the data and the information can be used to guide institutional empiric antibiotic therapy policies. The choice of empiric antibiotic regimens in patients with IAI should be based on the local resistance epidemiology, the individual risk for infection by resistant pathogens, and the clinical condition of the patients .Candida spp., may be warranted in selected conditions. Generally, the most important factors in predicting the presence of resistant pathogens in IAIs is acquisition in a healthcare setting , corticosteroid use, organ transplantation, baseline pulmonary or hepatic disease, and previous antimicrobial therapy  occurs rarely in patients with suspected appendicitis. The diagnosis of appendicitis can be challenging even in the most experienced hands and is predominantly clinical.Abdominal pain: it usually has a gradual onset and increases intensity over time. It is usually relieved in the supine position and aggravated by coughing or abdominal movements. Typically, there may be a short history (1 to 3 days) of migration of the pain from the peri-umbilical region to the RLQ.Nausea and/or vomiting soon after abdominal pain beginsFeverTenderness localized in the RLQ (often in complicated acute appendicitis)Increased white blood cell countLeucocyte shift to left (>75%)Increased C-reactive protein) useful in predicting the risk of complicated acute appendicitisUnfortunately, the clinical presentation of AA is often inconsistent. While the clinical diagnosis may be clear in patients presenting with classic signs and symptoms, atypical presentations may result in the delay in treatment. Therefore, diagnostic scoring systems have been described with the aim to provide clinical probabilities that a patient has acute appendicitis. The development of these scores may contribute to diagnosis and by easily applying clinical criteria and simple laboratory tests, a score estimating the probability of diagnosis may be attributed to the patient. The most common used scores are the Alvarado score Table , the AndAlthough the Alvarado score is not sufficiently specific in diagnosing AA, a cutoff score of < 5 is sufficiently sensitive to exclude AA (sensitivity of 99%). The Alvarado score could, therefore, be used to reduce emergency department length of stay and radiation exposure in patients with suspected AA .The Alvarado score is not able to differentiate complicated from uncomplicated AA in elderly patients . Severalp < 0.001), fewer admissions , fewer negative explorations , and fewer surgical operations for non-perforated AA . Intermediate-risk patients randomized to the imaging and observation strategies had the same proportion of negative appendectomies , number of hospital admissions, rates of perforation, and length of hospital stay, but routine imaging was associated with an increased proportion of patients treated for AA  [The RCT by Andersson et al. demonstrated that, in low-risk patients, the use of an AIR (Appendicitis Inflammatory Response) score-based algorithm resulted in less imaging  .The Adult Appendicitis Score (AAS) stratifies patients into three groups: high, intermediate, and low risk of AA . The scoIn the validation study by Sammalkorpi et al. , the AASUSCTMRIEstimating pre-image likelihood of AA is important in tailoring the diagnostic workup and using scoring systems to guide imaging can be helpful: low-risk adult patients according to the AIR/AAS/Alvarado scores could be discharged with appropriate safety netting. In patients younger than 40 years old, a high-probability score for acute appendicitis  may be used to select patients in whom imaging, such is as CT is not needed before deciding for appendectomy, whereas the high-risk patients are likely to require surgery rather than diagnostic imaging . For difA positive US would lead to a discussion of appendectomy and a negative test to either CT or further clinical observation with repeated US. A conditional CT strategy, where CT is performed after the negative US, is preferable, as it reduces the number of CT scans by 50% and will correctly identify as many patients with AA as an immediate CT strategy.Diameter of the appendix > 6 mmSingle wall thickness ≥ 3 mmIncreased echogenicity of local mesenteric fatAppendicolith: hyperechoic with posterior shadowingFree fluid surrounding appendixLocal abscess formationEnlarged local mesenteric lymph nodesThickening of the peritoneumCT is the most accurate imaging study for evaluating suspected AA and alternative etiologies of right lower quadrant pain.Recent studies from the Finnish group led by Sippola et al.  demonstrIt should also be remembered that in many parts of the world mainly in LMICs, non-enhanced CT becomes the only option and that according to the review from Xiong et al., non-enhanced CT has a high diagnostic accuracy in detecting AA, which is adequate for clinical decision-making .In pregnant women, ultrasound is initially preferred, with MRI as a second imaging examination in inconclusive cases.Laparoscopic appendectomy  or open appendectomy. Post-operative antibiotics are unnecessary if source control is adequate.Antibiotic therapy without surgery (in selected patients).Although the standard treatment for acute appendicitis has historically been appendectomy and it is the goal standard, the medical community has recently seen a notable increase in the use of antibiotic therapy as a primary means of treatment. Antibiotic therapy is a safe means of primary treatment for patients with uncomplicated acute appendicitis, without an appendicolith, but it is less effective in the long-term due to significant recurrence rates, requires a CT proven diagnosis of uncomplicated appendicitis , 83, andLaparoscopic appendectomy  or open appendectomy, and antibiotic therapy for 4 days if source control is adequate (immunocompetent patients).The advent of laparoscopy has changed the surgical treatment of AA in high-income countries. In contrast, in many areas of the world, the challenges posed by the burden of primary healthcare concerns have limited support for the development of modern tertiary healthcare facilities, and laparoscopic surgery is practiced in only a few tertiary hospitals. In the last years, several prospective randomized studies, meta-analyses, and systematic critical reviews have been published on the topic of laparoscopic appendectomy. Laparoscopic appendectomy is safe and effective, but open surgery still confers benefits, in particular with regard to the likelihood of postoperative intra-abdominal abscess. Sauerland et al.  have perHowever, in the cumulative meta-analysis by Ukai et al. , with reIn the setting of complicated appendicitis, a short course of antibiotic therapy after adequate source control is a reasonable option. The prospective trial by Sawyer et al. demonstrated that in patients with complicated IAIs undergoing an adequate source control, the outcomes after approximately 4 days of fixed-duration antibiotic therapy were similar to those after a longer course of antibiotics that extended until after the resolution of physiological abnormalities .Patients who have ongoing signs of infection or systemic illness beyond 5 to 7 days of antibiotic treatment warrant a diagnostic investigation.In Table Empiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 6–8 h +/− gentamicin 5–7 mg/Kg every 24 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised the clinical utility of this agent for empirical therapy of serious Gram-negative infections, and therefore, it should be used based on local rates of resistance. Avoid its use if local Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion +/− Gentamicin 5-7 mg/Kg every 24 h Cefuroxime 1.5 g every 8 h + metronidazole 500 every 8 hCeftriaxone 2 g 24-hourly + metronidazole 500 mg every 8 hCefotaxime 2g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8/12 h + metronidazole 500 mg every 8 horAn aminoglycoside-based regimenAmikacin 15–20 mg/kg every 24 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeErtapenem 1 g every 24 hTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy).Cholelithiasis is a common disease worldwide , 87. ItsAcute cholecystitis develops in 1–3% of patients with symptomatic gallstones .The pathogenesis of cholecystitis most commonly involves the impaction of gallstones in the bladder neck, or the cystic duct; gallstones are not always present in cholecystitis, however. Pressure on the gallbladder increases, the organ becomes enlarged, the walls thicken, the blood supply decreases, and an exudate may form. The gallbladder can become infected and can undergo necrosis and gangrene. If left untreated, it may result in perforation of the gallbladder, a rare but life-threatening phenomenon.In 2020, the WSES guidelines for the management of acute calculous cholecystitis (AAC) were published .Abdominal pain in the right upper quadrant of the abdomen. The pain is characteristically worst when palpating the upper right quadrant of the abdomen during deep inspiration by the patient (Murphy’s sign)FeverAbdominal tenderness, palpable gallbladder lump (sign of complicated acute cholecystitis)Increased white blood cell countLeucocyte shift to left (> 75%)C-reactive proteinUSCTMRIPericholecystic fluid Distended gallbladder, edematous gallbladder wallGallstones (impacted in cystic duct)Murphy’s sign can be elicited on ultrasound examinationUS is the investigation of choice in patients suspected of having acute cholecystitis.A meta-analysis by Kiewiet et al. included studies on CT, MRI, and hepatobiliary iminodiacetic acid (HIDA) scan in addition to those on US . Data onEarly (within 7–10 days) laparoscopic/open cholecystectomy (early treatment). Post-operative antibiotics are unnecessary if source control is adequate.Antibiotic therapy and planned delayed laparoscopic/open cholecystectomy (delayed treatment) (second option).Treatment is predominantly surgical, although the timing of surgery without evidence of gangrene or perforation has been under debate in recent years. Two approaches are available for the treatment of acute cholecystitis: the early option, generally within 7 days of onset of symptoms, includes laparoscopic/open cholecystectomy to provide immediate, definitive surgical treatment after establishing the diagnosis and surgical fitness of the patient in the same hospital admission while the delayed treatment option is performed in a second hospital admission after an interval of 6–12 weeks during which time the acute inflammation settles , 95.Multiple prospective trials have demonstrated that laparoscopic cholecystectomy is a safe and effective treatment for acute cholecystitis –99. In aAs a result, immediate laparoscopic cholecystectomy has largely become the therapy of choice for acute cholecystitis in patients who are good surgical candidates.In a recent systematic review and meta-analysis by Lyu et al.  includinp = 0.005), sex (p < 0.001), indication for surgery (p < 0.001), ASA (p < 0.001), thick-walled gallbladder (p = 0.040), and CBD diameter (p = 0.004) which allows surgeons to predict a sixfold increase in the need for open surgery [While the laparoscopic approach is common, several risk factors predicting the need to convert to an open approach are reported. In the large CholeS study of 8820 patients, a prediction score was developed of six significant predictors: age  with or without delayed laparoscopic cholecystectomy appears to be the correct clinical approach .Cholecystostomy should be used for critically ill patients who are not fit for surgery, or for those who fail to improve after 2–3 days of antibiotic treatment . In TablEmpiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/ 2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or 12 h + metronidazole 500 mg every 8 horAn aminoglycoside-based regimenAmikacin 15–20 mg/kg every 24 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeOne of the following antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy)Ertapenem 1 g every 24 hMeropenem 1 g every 8 h (only in patients with septic shock)Doripenem 500 mg every 8 h (only in patients with septic shock)Imipenem/cilastatin 500 mg every 6 h (only in patients with septic shock)In patients at high risk for infection from enterococci including immunocompromised patients or patients with recent antibiotic exposure, consider the use of ampicillin 2 g every 6 h if patients are not being treated with piperacillin/tazobactam or imipenem/cilastatin (active against ampicillin-susceptible enterococci) or tigecycline.Acute cholangitis is an infectious disease characterized by acute inflammation and infection in the bile ducts resulting from a combination of biliary obstruction and bacterial growth in bile.Bacteria reach the biliary system either by ascent from the intestine or by the portal venous system . The mosIntermittent fever with rigorsJaundiceRight upper quadrant abdominal painIncreased white blood cell countC-reactive proteinTotal bilirubinDirect bilirubinAlkaline phosphataseGamma-glutamyl transpeptidaseAspartate aminotransferaseAlanine aminotransferaseUSCTMRIEndoscopic ultrasound (EUS)ERCPDilatation of intra- and extrahepatic bile ductsThickening of the bile duct wallIntraluminal stones or sludgeHistorically, US has been the initial modality for evaluating biliary obstruction in the setting of suspected cholangitis. However, research and recommendations published over the last decade have challenged this approach, and data have become increasingly supportive of the use of computed tomography (CT) as the initial imaging study of choice to confirm biliary obstruction and identify its source. In case the cause of biliary obstruction presenting with cholangitis is not identified on US and CT, EUS is very helpful in diagnosing occult choledocholithiasis. EUS is more sensitive than both CT and MRI in these settings. ERCP has similar sensitivity to EUS and it has therapeutic potential. Documentation of pus during ERCP is the gold standard for diagnosis of cholangitis but ERCP can worsen cholangitis if there is inadvertent contrast injection into an undrained segment.Biliary drainage and antibiotic therapy for 3–5 daysThe key elements of therapy in acute cholangitis are adequate antimicrobial treatment to avoid or manage the septic complications and biliary decompression to restore biliary drainage in case of obstruction . The cliIn severe cholangitis, an early interventional approach is absolutely essential for survival.Endoscopic retrograde cholangiopancreatography (ERCP) plays a central role in the management of biliary obstruction in patients with acute cholangitis and is the treatment of choice for biliary decompression in patients with moderate/severe acute cholangitis. Biliary endoscopic sphincterotomy with stone extraction continues to be a therapeutic choice and the reference standard in the treatment of symptomatic choledocholithiasis, especially for the solitary common bile duct stones up to 10–12 mm in diameter. It has been shown that biliary endoscopic sphincterotomy reduces hospital stay and duration of cholangitis but does not prevent recurrent cholangitis. Biliary sphincterotomy in acute cholangitis as a result of common bile duct stones can allow definitive therapy or placement of a large-bore biliary stent which can drain the thick infected bile more efficiently. Endoscopic drainage can be carried out either by external drainage using a nasobiliary tube or internal drainage using biliary stenting. Both the modalities of internal and external drainage have their own advantages and disadvantages. Both have similar technical and clinical success rates.Percutaneous transhepatic biliary drainage (PTBD) should be reserved for patients in whom ERCP fails. PTBD can lead to significant complications, including biliary peritonitis, haemobilia, pneumothorax, hematoma, liver abscesses, and patient discomfort related to the catheter.Open drainage may be indicated for patients who cannot undergo non-invasive drainage procedures, for anatomical and structural reasons, including patients after Roux-en-Y choledochojejunostomy or patients with a propensity for hemorrhage. In open drainage, the goal is to decompress the biliary system. Simple procedures such as T-tube placement without choledocholithotomy should be recommended as a temporary solution in unstable patients, because prolonged operations should be avoided in such ill patients. Whenever possible, definitive elimination of the biliary obstruction should be the goal of surgery.The type and timing of biliary drainage should be based on the severity of the clinical presentation, and the availability and feasibility of drainage techniques, such as endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC), and open surgical drainage.Endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice for biliary decompression in patients with moderate/severe acute cholangitis.n = 41) were significantly lower than those of T-tube drainage under laparotomy (n = 41).A randomized controlled trial (RCT)  was condThere are various endoscopic transpapillary options available, including biliary stent or nasobiliary drain placement above the obstruction site ± sphincterotomy, all of which with appropriate indications corresponding to disease severity and clinical context .Endoscopic biliary decompression by nasobiliary catheter or indwelling stent was equally effective for patients with acute suppurative cholangitis caused by bile duct stones in a prospective randomized trial published in 2002 . The indPercutaneous transhepatic biliary drainage (PTBD) should be reserved for patients in whom ERCP fails either due to cannulation, or an inaccessible papilla.However, PTBD can lead to significant complications, including biliary peritonitis, hemobilia, pneumothorax, hematoma, liver abscesses, and patient discomfort related to the catheter .In 2012, a retrospective study comparing the safety and effectiveness of endoscopic and percutaneous transhepatic biliary drainage in the treatment of acute obstructive suppurative cholangitis was reported. It confirmed the clinical efficacy of endoscopic drainage as well as its ability to facilitate subsequent endoscopic or surgical intervention . SurgicaAlthough there are no clinical data to support the use of antibiotics with biliary penetration for these patients, the efficacy of antibiotics in the treatment of biliary infections may also depend on effective biliary antibiotic concentrations . ObviousAntibiotics commonly used to treat biliary tract infections and their biliary penetration ability are illustrated in Table In Table Empiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%. Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2 g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or 12 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy)Pseudomonas aeruginosa)Ertapenem 1 g every 24 h (not active against Meropenem 1 g every 8 h (only in patients with septic shock)Doripenem 500 mg every 8 h (only in patients with septic shock)Imipenem/cilastatin 500 mg every 6 h (only patients with septic shock)In patients at high risk for infection from enterococci including immunocompromised patients or patients with recent antibiotic exposure, consider the use of ampicillin 2 g every 6 h if patients are not being treated with piperacillin/tazobactam or imipenem/cilastatin (active against ampicillin-susceptible enterococci) or tigecycline.Acute left colonic diverticulitis (ALCD) is a common problem encountered by surgeons in the acute setting. It encompasses a variety of conditions, ranging from localized diverticular inflammation to perforation and fecal peritonitis. Decisions in the diagnosis and treatment of acute diverticulitis often depend on clinicians’ personal preferences rather than evidence-based medicine.In 2020, WSES guidelines for the management of ALCD were updated .ALCD ranges in severity from uncomplicated inflammatory diverticulitis to complicated diverticulitis (abscess formation or perforation). For the past three decades, the Hinchey classification has been the most commonly used classification for complicated ALCD in the international literature.Based on the surgical findings of abscesses and peritonitis, Hinchey classified the severity of acute diverticulitis into four grades , but thiThe management of ALCD has recently changed dramatically, due to better radiological imaging and the availability of non-surgical treatment options. Computer tomography (CT) imaging has become the primary diagnostic tool in the diagnosis and staging of patients with acute diverticulitis and more detailed information provided by CT scans led to several modifications of the Hinchey classification.In 2002, Ambrosetti et al.  classifiLocalized sigmoid wall thickeningPericolic fat strandingModerate diverticulitisAbscessExtraluminal airExtraluminal contrastSevere diverticulitisStage 0 mild clinical diverticulitis.Stage 1a confined pericolic inflammation.Stage 1b confined pericolic abscess.Stage 2 pelvic or distant intra-abdominal abscess.Stage 3 generalized purulent peritonitis.Stage 4 fecal peritonitis at presentation.In 2005, Kaiser et al.  modifiedStage 1 Uncomplicated diverticulitis.Stage 2 Complicated diverticulitis with small abscess (<6 cm).Stage 3 Complicated diverticulitis with large abscess (≥6 cm) or distant intraperitoneal or retroperitoneal air.Stage 4 Generalized peritonitis without organ dysfunction.Stage 5 Generalized peritonitis with organ dysfunction.In 2015, Sallinen et al.  publisheA proposal for a CT-guided classification of left colon acute diverticulitis was published in 2015 by the WSES acute diverticulitis working group. It is a simple classification system of acute diverticulitis based on CT scan findings . It may Stage 0 Diverticula, thickening of the colonic wall or increased density of the pericolic fat.Uncomplicated:Stage 1a Pericolic air bubbles or little pericolic fluid without abscess (within 5 cm from inflamed bowel segment).Stage 1b Abscess ≤ 4 cm.Stage 2a Abscess > 4 cm.Stage 2b Distant air (>5 cm from inflamed bowel segment).Stage 3 Diffuse fluid without distant free air (no hole in colon).Stage 4 Diffuse fluid with distant free air (persistent hole in colon).Complicated:Abdominal pain in the left lower quadrant of the abdomen without vomitingElevated temperatureTenderness localized in the left lower quadrantIncreased white blood cell countLeucocyte shift to left (>75%)C-reactive proteinUSCTIntestinal wall thickening.Signs of inflammation in the pericolonic fat and thickening of the lateroconal fascia.Signs of intestinal perforation .Pericolonic or distant abscess.Patients who fulfill the triad of criteria CRP > 50 mg/L, absence of vomiting, and tenderness in the left lower quadrant are highly likely to have acute diverticulitis. The positive predictive value of this triad is very high in the emergency department development cohort (97%) and excellent in an independent validation cohort (100%) .Radiological imaging techniques that are used for diagnosing ALCD in the emergency setting are US and CT . CurrentCT findings in patients with ALCD may include diverticulosis with associated colon wall thickening, fat stranding, phlegmon, extraluminal gas, abscess formation, or intra-abdominal free fluid . CT imagp = 0.86). Summary specificity estimates for US were 90% (95% CI 86–94%) versus 96% (95% CI 90–100%) for CT (p = 0.04).A systematic review and meta-analysis of studies  that repAlthough CT is the most sensitive imaging modality for patients with suspected acute diverticulitis, a step-up approach with CT performed after an inconclusive or negative US has been proposed as a safe and alternative approach for patients with suspected acute diverticulitis , 203.Conservative treatment without antibiotics in patients with CT diagnosis of uncomplicated acute diverticulitis.Antibiotic therapy for 5–7 days in patients with CT diagnosis of uncomplicated acute diverticulitis is reserved for immunocompromised patients and patients with signs of sepsis.The definition of uncomplicated acute diverticulitis is often vague and poorly defined. Uncomplicated acute diverticulitis is defined as localized diverticular inflammation without any abscess or perforation. A universally accepted classification divides IAIs into complicated and uncomplicated . In uncoUncomplicated acute diverticulitis is an anatomically confined inflammatory process. CT findings include diverticula, thickening of the wall, and increased density of the pericolic fat. Patients with uncomplicated diverticulitis usually have an indolent course with a low incidence of subsequent complications.The utility of antibiotics in acute uncomplicated acute diverticulitis has been a point of controversy. In recent years, several studies demonstrated that antimicrobial treatment was not superior to withholding antibiotic therapy, in terms of clinical resolution, in patients with mild unperforated diverticulitis . The curA multicenter randomized trial was published in 2012 by Chabok et al. involving ten surgical departments in Sweden and one in Iceland recruiting 623 patients with computed tomography-confirmed acute uncomplicated left-sided diverticulitis . PatientA recent Dutch randomized controlled trial of observational versus systemic antibiotic treatment   for a fiLong-term follow-up of the AVOD and DIABOLO trials on omitting antibiotic treatment in uncomplicated diverticulitis have confirmed that routine antibiotics are not beneficial. A recently published individual patient data meta-analysis (IPDMA) of both RCTs shows that observational management of acute uncomplicated diverticulitis is safe . Some stOutpatient management is suggested for patients with uncomplicated acute diverticulitis, with no comorbidities. These patients should be clinically monitored as outpatients and re-evaluated within 7 days to assess for resolution of the inflammatory processes. Earlier revaluation is necessary if the clinical condition deteriorates.p = 0.62). The overall health care cost per episode was 3 times less in the outpatient treated group, with significant costs savings of €1124.70 per patient. No differences were observed between the groups in terms of quality of life.The DIVER trial  has demoA systematic review including 21 studies  with 1781 patients with ALCD managed in the outpatient setting was recently published . The metAntibiotic therapy alone in patients with small diverticular abscesses.Percutaneous drainage combined with antibiotic therapy for 3–5 days in large diverticular abscesses. Whenever percutaneous drainage of the abscess is not feasible or not available, based on the clinical conditions, unless emergency surgery is needed, antibiotics could be considered the primary treatment.The size of 4–5 cm may be a reasonable limit between antibiotic treatment alone, versus percutaneous drainage combined with antibiotic treatment in the management of diverticular abscesses –139.Whenever percutaneous drainage of the abscess is not feasible or not available, based on the clinical conditions, patients with large abscesses can be initially treated with antibiotic therapy alone. However, careful clinical monitoring is mandatory.Primary resection and anastomosis with or without a diverting stoma Hartmann’s procedure (HP) .Laparoscopic peritoneal lavage and drainage suitable only for patients with purulent  peritonitis due to complicated diverticulitis. Very controversial.+Antibiotic therapy for 4 days (immunocompetent and stable patients) (more days if there are signs of ongoing infection).HP has been considered the procedure of choice in patients with generalized peritonitis and remains a safe technique for emergency colectomy in diverticular peritonitis. It is especially useful in critically ill patients and in patients with multiple comorbidities. However, restoration of bowel continuity after a HP is associated with significant morbidity and resource utilization . As a reIn recent years, some authors have reported the role of primary resection and anastomosis with or without a diverting stoma, in the treatment of acute diverticulitis, even in the presence of diffuse peritonitis . The decp < 0.0001). There were no significant differences in short-term morbidity and mortality after the index procedure for Hartmann’s procedure compared with primary anastomosis .The results of a multicenter, randomized, open-label, superiority trial which was done in eight academic hospitals and 34 teaching hospitals in Belgium, Italy, and the Netherlands were published in 2019 . PatientA minimally invasive approach using laparoscopic peritoneal lavage and drainage has been proposed in recent years as an alternative to colonic resection. It can potentially avoid a stoma in patients with diffuse peritonitis. It consists of the laparoscopic aspiration of pus followed by abdominal lavage and the placement of abdominal drains, which remain for many days after the procedure.Laparoscopic lavage reduces the risk for colostomy at one- and two-year follow-up, but may in the short-term result in intraabdominal abscesses and overlooked free or tumor perforations requiring reoperation. Laparoscopic lavage consists of the laparoscopic aspiration of pus followed by abdominal lavage and optional the placement of abdominal drains that, which remain for many days after the procedure.Great debate is still open on this topic, mainly due to the discrepancy and sometimes disappointing results of the latest prospective trials such as SCANDIV, Ladies, and DILALA trials –152, butIn Table Empiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 h +/− gentamicinIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2 g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or 12 h + metronidazole 500 mg every 8 horAn aminoglycoside-based regimenAmikacin 15–20 mg/kg every 24 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy)Ertapenem 1 g every 24 hMeropenem 1 g every 8 h (only in patients with septic shock)Doripenem 500 mg every 8 h (only in patients with septic shock)Imipenem/cilastatin 500 mg every 6 h (only in patients with septic shock)Empiric antibiotic regimens. Normal renal functionIn patients at high risk for infection from Enterococci including immunocompromised patients or patients with recent antibiotic exposure, consider the use of ampicillin 2 g every 6 h if patients are not being treated with piperacillin/tazobactam or imipenem/cilastatin (active against ampicillin-susceptible enterococci) or tigecycline.Source control by resection of the affected segment of the colon, usually the sigmoid, followed by primary fascial closure is standard treatment. If primary fascial closure is not possible due to visceral edema, a negative pressure-based temporary closure device should be used for progressive closure steps over the next days. A damage control surgical strategy may be useful for patients in physiological extremis from abdominal sepsis . The iniAcute colonic diverticulitis is a common condition affecting the adult population. Traditionally, the sigmoid colon is considered the most commonly involved part, and ARCD is much rarer . HoweverARCD generally occurs in middle-aged men, and its incidence does not increase with age. ARCD located in the cecum is difficult to distinguish from acute appendicitis because of their similar symptoms and signs. CT appears to be the best overall imaging modality in the diagnosis of possible ARCD , 161. HoUS features, including diverticular wall thickening, surrounding echogenic fat, and intra-diverticular echogenic material, can provide clear information for making the correct preoperative diagnosis. However, US is operator dependent. Ambiguous US studies should be complemented with a contrast-enhanced CT .Currently, the management of ARCD is not well defined, and no guidelines have been proposed.Although previous studies have shown that the percentage of complications requiring surgery is higher in patients with ALCD than in patients with ARCD , the priCompared to LMIC, small bowel perforations are a less common source of peritonitis in Western countries, where most small bowel perforations are due to unrecognized intestinal ischemia (mesenteric or strangulation) or inflammatory bowel disease such as Crohn’s disease. This pattern of disease is quite different in LMICs, where small bowel perforations are usually due to typhoid fever (TF). TF remains endemic in Asia, Africa, Latin America, the Caribbean, and Oceania . Ileal pIntestinal perforation is the most serious complication of typhoid fever estimated to be solely responsible for 25% of deaths . In mostTyphoid ileal perforations have a mortality rate up to 60% . TyphoidIn the CIAOW study, according to stepwise multivariate analysis, the presence of small bowel perforation was an independent variable predictive of mortality . The mosThe preoperative diagnosis of perforation usually is based on findings of peritonitis in a patient with a history of prolonged febrile illness. In a prospective study, 53 consecutive patients with typhoid perforation were surgically treated; the morbidity rate in this series was 49.1%, and the most common post-operative complications included wound infection, wound dehiscence, burst abdomen, residual intra-abdominal abscesses, and entero-cutaneous fistulae. The mortality rate was 15.1% and it was significantly affected by the presence of multiple perforations, severe peritoneal contamination, and burst abdomen .• Severe, sudden-onset periumbilical pain, which can become generalized• Abdominal tenderness• Fever• Increased white blood cell• Leucocyte shift to left (> 75%)• C-reactive proteinUSCTAngiography (if there is suspicion of acute mesenteric ischemia)The sonographic findings suggestive of small bowel perforation are presence of extra-luminal air, a fluid collections and inflammatory changes adjacent to a thickened small bowel segment. In hemodynamically stable patients, triple contrast CT  using water-soluble contrast is the imaging modality of choice for suspected small bowel perforation. It gives anatomical details of the intestinal wall, detects secondary signs of underlying bowel pathology and surrounding mesentery, and picks up even small amounts of extra-luminal air or oral contrast leakage into the peritoneal cavity. In septic and unstable patients in the ICU with uncertain preoperative diagnosis, bedside diagnostic laparoscopy is being used in diagnosis and decision-making thus shortening the observation period.In patients with sepsis-induced tissue hypoperfusion or septic shock prompt administration of 30 mL/kg intravenous crystalloid fluid. If blood pressure is not restored after initial fluid resuscitation vasopressors should be commenced.Open or laparoscopic small bowel segmental resection and primary anastomosis.In the setting of perforation due to small bowel ischemia, resection and delayed anastomoses at a second look are usually needed. Also, open or endovascular mesenteric vessel reconstruction may be needed.Open or laparoscopic resection and stoma creation or exteriorization of the perforation as a stoma .In the setting of typhoidal perforation, although closure in two layers of single perforation with relatively healthy tissue after refreshment of the edge seems an acceptable option, resection of the unhealthy tissue segment with primary anastomosis of healthy edges about 10 cm on each side of the perforation is recommended.+Antibiotic therapy for 4 days (immunocompetent and stable patients) (more days if there are signs of ongoing infection).There are many methods of surgical treatment of small bowel perforation, including wedge resection and closure, resection and primary anastomosis, and exteriorization of the perforation as a stoma. Primary repair is only rarely an option, in the occasional patient with minimal peritoneal contamination of the peritoneal cavity and a small puncture hole –175.In delayed cases with diffuse peritonitis, there can be severe inflammation and edema of the bowel, resulting in friable tissue which precludes anastomosis after resection, and therefore, an ileostomy should be performed as a life saving measure .Damage control surgery can be an alternative option deferring the definitive surgical management via anastomosis .Laparoscopic management of small bowel perforations has been reported, but there are no comparative studies with open surgery . In TablEmpiric antibiotic regimens suggested. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam loading dose 6 g/0.75 g then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2 g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or 12 h + metronidazole 500 mg every 8 horAn aminoglycoside-based regimenAmikacin 15–20 mg/kg every 24 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy)Ertapenem 1 g every 24 hMeropenem 1 g every 8 h (only in patients with septic shock)Doripenem 500 mg every 8 h (only in patients with septic shock)Imipenem/cilastatin 500 mg every 6 h (only in patients with septic shock)In patients at high risk for infection from enterococci including immunocompromised patients or patients with recent antibiotic exposure, consider the use of ampicillin 2 g every 6 h if patients are not being treated with piperacillin/tazobactam or imipenem/cilastatin (active against ampicillin-susceptible enterococci) or tigecycline.Helicobacter pylori, so apart from simple closure, definitive surgery is not usually required. Perforated peptic ulcer is an indication for operation in nearly all cases except when the patient is unfit for surgery.Gastroduodenal perforations may be spontaneous or traumatic and most of the spontaneous perforations are due to peptic ulcer disease. Improved medical management of peptic ulceration has reduced the incidence of perforation, but still remains a common cause of peritonitis. Chichom-Mefire et al. in 2016 reported gastroduodenal perforations as the leading cause of peritonitis in the tropics . The majHelicobacter pylori infection in Western countries. However, ulcer disease is still a common emergency condition worldwide and is associated with mortality rates of up to 30% [Helicobacter pylori, and a diet high in salt. All these factors have in common that they affect acid secretion and impairment of the gastric mucosal protection [Gastroduodenal ulcer perforations have decreased in frequency in the last few years, largely due to the widespread adoption of medical therapies for peptic ulcer disease and decreasing incidence of p to 30% . The maiotection . Stress Severe, sudden-onset epigastric pain, which can become generalizedAbdominal tendernessFeverAbdominal distension, tenderness, and rigidity with masked liver dullness and absent bowel soundsWhite blood cell countLeucocyte left shift (>75%)C-reactive proteinCTPlain abdominal x-rayUSSigns of gastrointestinal perforation Air pockets around the stomach and duodenum and thick reactive intestinal wallLaparoscopic/open simple or double-layer suture with or without an omental patch is a safe and effective procedure to address small perforated ulcers (standard procedure).Distal gastrectomy .+Antibiotic therapy for 4 days (immunocompetent and stable patients) (more days if there are signs of ongoing sepsis).Surgery is the most effective means of source control in patients with gastroduodenal perforation . A perfoIn 2010, Lo et al. conducted a study to determine if an omental patch offers any clinical benefit that is not offered by simple closure alone . The stuScoring systems to predict disease severity or outcome in patients with gastroduodenal perforations are unreliable and not accurate and cannot be generalized from one population to another . The cloLaparoscopic repair of PPU is a safe and effective procedure in experienced hands. The literature was summarized in a recent systematic review . The autConservative treatment for PPU is seldom reported and restricted mostly to case reports and series of patients that are critically ill and unsuitable for operative intervention .In Table Empiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2 g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or 12 h + metronidazole 500 mg every 8 horAn aminoglycoside-based regimenAmikacin 15–20 mg/kg every 24 h + metronidazole 500 mg every 8 hPost-operative peritonitis (PP) is a life-threatening hospital-acquired intra-abdominal infection with high mortality rates , 190. ThSeveral recent studies have investigated the role of CRP as an early marker of anastomotic leakage following colorectal surgery. A systematic literature search to identify studies evaluating the diagnostic accuracy of postoperative CRP for anastomotic leakage following colorectal surgery was published by Singh et al. . CRP res• Fever• Abdominal pain• Abdominal tenderness• Increased white blood cell count• C-reactive protein• PCTImaging• CTSigns of intestinal perforation such as extraluminal air bubbles, intra-abdominal fluidPost-operative abscessPercutaneous drainage and antibiotic therapy.Antibiotics and drainage may be the optimal means of treating post-operative localized intra-abdominal abscesses in stable patients when there are no signs of generalized peritonitis. Several retrospective studies in the fields of surgery and radiology have documented the effectiveness of percutaneous drainage in the treatment of post-operative localized intra-abdominal abscesses .Early surgical source control and antibiotic therapy.The inability to control the septic source is associated with an intolerably high mortality rate. Organ failure and/or delay in subsequent re-laparotomies which have been delayed for more than 24 h, both result in higher mortality rates in patients affected by post-operative IAIs . Early rIn 2009, a retrospective study by Chichom-Mefire et al.  analyzedIn Table Empiric antibiotic regimens. Normal renal functionIn patients with no risk for multidrug-resistant organismOne of the following intravenous antibioticsPiperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2g by continuous infusionTigecycline 100 mg initial dose, then 50 mg every 12 h (carbapenem-sparing strategy)Meropenem 1 g every 8 h +/− ampicillin 2 g every 6 h Doripenem 500 mg every 8 h +/− ampicillin 2 g every 6 h Imipenem/cilastatin 500 mg every 6 h +/−In patients at high risk for invasive candidiasisFluconazole 800 mg LD then 400 mg every 24 hIn patients with documented beta-lactam allergy, consider the use of antibiotic combinations with Amikacin 15–20 mg/kg every 24 hIn patients with high risk for multidrug-resistant organismOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (not active against Pseudomonas aeruginosa)Eravacycline 1 mg/kg every 12 h (not active against Pseudomonas aeruginosa)+Piperacillin/tazobactam 4.5 every 6 horIn critically ill patientsone of the following intravenous antibioticsMeropenem 1 g every 8 hDoripenem 500 mg every 8 hImipenem/cilastatin 500 mg every 6 h+One of the following intravenous antibioticsVancomycin 25–30 mg/kg LD then 15–20 mg/kg/dose every 8 hTeicoplanin 12 mg/kg every 12 h 3 LDs then 12 mg/kg every 24 h+/−In patients with high risk for invasive candidiasisIn stable patientsFluconazole 800 mg LD then 400 mg every 24 hIn unstable patientsone of the following antifungal agentsCaspofungin 70 mg LD, then 50 mg dailyAnidulafungin 200 mg LD, then 100 mg dailyMicafungin 100 mg dailyAmphotericin B Liposomal 3 mg/kg daily Pseudomonas aeruginosa, consider the use of antibiotic combinations with ceftolozane/tazobactam.In patients with suspected or proven infection with MDR  Klebsiella pneumoniae and MDR  Pseudomonas aeruginosa, consider the use of antibiotic combinations with Ceftazidime/Avibactam.In patients with suspected or proven infection with carbapenemase-producing In patients with suspected or proven infection with vancomycin-resistant enterococci (VRE) including patients with previous enterococcal infection or colonization, immunocompromised patients, patients with long ICU stay, or recent Vancomycin exposureOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 hLinezolid 600 mg every 12 hIn patients with documented beta-lactam allergy, consider the use of antibiotic combinations with Amikacin 15–20 mg/kg daily.Trauma continues to be a major public health problem worldwide, and it is associated with high morbidity and mortality regardless of the socioeconomic status . Both blHollow viscus injury (HVI) has a more insidious presentation in this setting, often resulting in delayed diagnosis. Clinical signs may take time to develop, and imaging investigations are not completely sensitive. In addition, other distracting injuries may affect an accurate and timely diagnosis. Improved outcome is reported in settings where, availability of advanced imaging modalities, patient monitoring capabilities, and prompt intervention are possible, whereas limited diagnostic capabilities, late presentation, and late intervention adversely affect outcomes , 202. Se• Fever• Abdominal pain• Abdominal tenderness• Increased of white blood cell count• C-reactive protein• PCT• CT• USSigns of intestinal perforation Focused Assessment with Sonography in Trauma (FAST) is an initial step in assessment of hemodynamically unstable patients with blunt abdominal injury. It primarily detects the presence of free fluid but identifies free air only in 8% of the cases with traumatic bowel perforation. Abdominal CT scan is performed in hemodynamically stable patients and the findings considered diagnostic for bowel perforation are contrast extravasation and/or extra-luminal air. Fluid between the mesentery, thickening of bowel wall are also common CT signs.More subtle but important concerns for injury is the presence of thickened segments of bowel wall, associated mesenteric hematomas and free fluid in the pelvis without evidence of a solid organ injury consistent with a bleeding source. In the current approach of non-operative management (NOM) of stable patients with solid organ injury, the presence of fluid without solid organ injury should warrant consideration for laparotomy/laparoscopy to evaluate for possible visceral perforation.Open/laparoscopic surgical repair. Use of laparoscopy in blunt trauma is highly debatable.Resection and primary anastomosis.Stoma .+Perioperative antibiotics. If hollow viscus injury is repaired within 12 h, antibiotics should be continued for ≤ 24 hEarly clinical recognition and surgical intervention is important in case of HVI , 205.Repair or anastomosis of intestinal injuries should be considered in all patients. A complete diversion of the fecal stream should be considered in colorectal injuries involving all layers in the setting of multiple injuries and resultant physiological compromise, unfavorable comorbid conditions, and perhaps in the setting of delayed diagnoses . Damage If hollow viscus injury is repaired within 12 h, antibiotics should be continued for ≤ 24 h .In Table Empiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsAmoxicillin/clavulanate 2.2 g every 8 hIncreasing rates of antimicrobial resistance to amoxicillin/clavulanate among E. coli and other Enterobacteriaceae worldwide, during the last decade, has compromised clinical utility of this agent for empirical therapy of serious Gram-negative infections and therefore it should be used based on local rates of resistance. Avoid its use if Enterobacteriaceae resistances > 20%.Piperacillin/tazobactam 6 g/0.75 g LD then 4 g/0.5 g every 6 h or 16 g/2 g by continuous infusion, Ceftriaxone 2 g every 24 h + metronidazole 500 mg every 8 hCefotaxime 2 g every 8 h + metronidazole 500 mg every 8 horIn patients with beta-lactam allergyA fluoroquinolone-based regimenCiprofloxacin 400 mg every 8 or12 h + metronidazole 500 mg every 8 horAn aminoglycoside regimenAmikacin 15-20 mg/kg every 24 h + metronidazole 500 mg every 8 horIn patients at high risk for infection with community-acquired ESBL-producing EnterobacteriaceaeOne of the following antibioticsTigecycline 100 mg LD, then 50 mg every 12 h (carbapenem-sparing strategy)Ertapenem 1 g every 24 hMeropenem 1 g every 8 h (only in patients with septic shock)Doripenem 500 mg every 8 h (only in patients with septic shock)Imipenem/cilastatin 500 mg every 6 h (only in patients with septic shock)In patients at high risk for infection with Enterococci including immunocompromised patients or patients with recent antibiotic exposure, consider the use of ampicillin 2 g every 6 h if patients are being treated with ertapenem/ meropenem or doripenem.Tertiary peritonitis is an infection of the peritoneal cavity that occurs after seemingly successful surgical source control of secondary peritonitis. Actually, complete recovery from secondary peritonitis, however, has not been achieved. It is more common among critically ill or immunocompromised patients and often associated with multidrug-resistant organisms (MDROs). It is typically associated with high morbidity and mortality. Tertiary peritonitis was previously seen as a distinct entity, but essentially it represents an evolution and complication of secondary peritonitis , 209. ThIncreased of white blood cell countC-reactive proteinPCTCTOn-demand re-laparotomy and/or antibiotic therapyIn patients who are prone to persistent infections regardless of eradication of the source of infection timely relaparotomy provides the only surgical option that significantly improves outcome. In these cases, single operation may not be sufficient to achieve source control; thus, relaparotomy may become necessary , 213. ReThe benefits and potential harms of an OA has been discussed in the ‘principles of source control’.Candida spp. in surgical samples and inadequate source control have been seen the major risk factors for persistent peritonitis. Montravers et al. [Initial severity, the presence of s et al.  demonstrEmpiric antibiotic regimens. Normal renal functionOne of the following intravenous antibioticsPseudomonas aeruginosa)Tigecycline 100 mg LD, then 50 mg every 12 h (not active against Pseudomonas aeruginosa)Eravacycline 1 mg/kg every 12 h Eravacycline 1 mg/kg every 12 h (No active against Pseudomonas aeruginosa)+Piperacillin/tazobactam 4.5 every 6 horIn critically ill patientsone of the following intravenous antibioticsMeropenem 1 g every 8 hDoripenem 500 mg every 8 hImipenem/cilastatin 500 mg every 6 h+One of the following intravenous antibioticsVancomycin 25–30 mg/kg loading dose then 15–20 mg/kg/dose every 8 hTeicoplanin 12 mg/kg every 12 h times 3 loading doses then 12 mg/kg every 24 h+/−In patients with high risk for invasive candidiasisIn stable patientsFluconazole 800 mg LD then 400 mg every 24 hIn unstable patientsone of the following antifungal agentsCaspofungin 70 mg LD, then 50 mg dailyAnidulafungin 200 mg LD, then 100 mg dailyMicafungin 100 mg dailyAmphotericin B Liposomal 3 mg/kg daily Pseudomonas aeruginosa, consider the use of antibiotic combinations with ceftolozane/tazobactam.In patients with suspected or proven infection with MDR  Klebsiella pneumoniae and MDR  Pseudomonas aeruginosa, consider the use of antibiotic combinations with Ceftazidime/Avibactam.In patients with suspected or proven infection with carbapenemase-producing In patients with suspected or proven infection with vancomycin-resistant enterococci (VRE) including patients with previous enterococcal infection or colonization, immunocompromised patients, patients with long ICU stay, or recent Vancomycin exposureOne of the following intravenous antibioticsTigecycline 100 mg LD, then 50 mg every 12 hLinezolid 600 mg every 12 hIn patients with documented beta-lactam allergy, consider the use of antibiotic combinations with Amikacin 15–20 mg/kg daily.IAIs are common surgical emergencies and have been reported as major contributors to non-trauma deaths in emergency departments worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization in critically ill patients. Affecting both high-income and low and middle-income countries, IAIs are a tremendous source of lost life, livelihood, and resources.This document is presented in light of the aim to facilitate clinical management of IAIs worldwide building evidence-based clinical pathways for the most common IAIs.


Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for palliative treatment of peritoneal surface malignancies (PSM) and is currently tested also in the neoadjuvant and prophylactic setting. The aim was therefore to compare safety and tolerance of staging laparoscopy with or without PIPAC.This retrospective analysis compared consecutive patients undergoing staging laparoscopy alone for oesogastric cancer with patients having PIPAC for suspected PSM of various origins from January 2015 until January 2020. Safety was assessed by use of the Clavien classification for complications and CTCAE for capturing of adverse events. Pain and nausea were documented by use of a visual analogue scale .Overall, 25 PIPAC procedures were compared to 24 staging laparoscopies. PIPAC procedures took a median of 35 min (IQR: 25–67) longer. Four patients experienced at least one complication in either group (p = 0.741). No differences were noted for postoperative nausea (p = 0.961) and pain levels (p = 0.156). Median hospital stay was 2 (IQR: 1–3) for PIPAC and 1 (IQR: 1–2) for the laparoscopy group (p = 0.104).The addition of PIPAC did not jeopardize safety and postoperative outcomes of staging laparoscopy alone. Further studies need to clarify its oncological benefits. Treatment of peritoneal metastases (PM) remains an oncological and surgical challenge –4. PressThe aim of this study was to assess safety and tolerance of the addition of PIPAC to baseline staging laparoscopy, for patients with high-risk features for PSM.This single centre retrospective comparative study included all consecutive patients admitted for staging laparoscopy, during workup of intra-abdominal neoplasia of various origin . Indications for adding PIPAC were either suspected PSM on baseline imaging or a high-risk constellation. Indications for the procedure were decided in the multidisciplinary tumor board and all patients signed informed consent. The study period lasted from January 2015 (start of PIPAC program in our department) to January 2020. Patients in the PIPAC group were compared to all consecutive patients with laparoscopic staging alone (laparoscopy group)) for gastro oesophageal junction (GOJ) adenocarcinoma (Siewert II and III) classified uT3 or uT4 . BaselinSafety, tolerance and potential chemotherapy-related adverse events were assessed by documentation of postoperative complications according to the Clavien classification and by use of CTCAE v5.0 , 17. NauDemographics, oncological and surgical data were retrieved from a prospectively maintained institutional database and entered in an a priori defined anonymized data base. The following variables were extracted: age, gender, primary tumour origin, body mass index, ASA class, Charslon Comorbidity Index (CCI) , intra-a2 and 2.1 mg/m2) was used for ovarian, gastric, and other malignancies [PIPAC procedure has been detailed previously and was applied according to current recommendations and safety protocols . Oxaliplgnancies . Aerosolgnancies .Continuous variables were presented as mean with standard deviation (SD) or median with interquartile range (IQR) according to their distribution. Categorical variables were reported as frequencies (%) and compared with chi-square test. Student t-test or Mann–Whitney test were used to compare continuous variables. A linear mixed-effect model to assess the effect of surgery type on VAS scores, when correcting for time. All statistical tests were two-sided and a level of 0.05 was used to indicate statistical significance. Statistical analyses were performed with GraphPad Prism 8 .www.strobe-statement.org) [The study was approved by local Commission on Ethics in Human Research (CER-VD 2019–00747) and was conducted in compliance with the current version of the STROBE statement (ent.org) .Forty-nine patients  underwent during the study period either laparoscopy alone (LA) (n = 24) or laparoscopy + PIPAC (LP) (n = 25) group. LP group included 10 patients with colorectal primary (42%), 6 gastric (22%), 5 ovarian (20%) and 4 appendicular (16%). Median PCI in the LP group was 10 (Range: 0–22). Five patients (20%) in the LP had no macroscopic disease (PCI = 0), one of these five patients had positive cytology. No patient had concomitant IV chemotherapy during PIPAC procedure. All patients in the LA group had GOJ adenocarcinoma (16 uT3 (66%) and 8 uT4 (34%)), 3 of them had PC (13%) two with a PCI 3 one PCI 15 and one patient had positive cytology with a PCI of 0. Median surgical time (p = 0.001) and number of trocars were significantly different between the two groups (p = 0.011). There were no intraoperative complications in any of the 49 procedures. Baseline demographics and surgical details are displayed in Table vs. LP regarding length of stay, postoperative nausea and overall complications , oesogastric 14%), and colorectal tumors (5%) 4%, and c, 4. Stag6%, oesogPrognosis of patients with advanced PM is dismal and depends mainly on disease extent and response to therapy . ResistaComplete abdominal surgical exploration in high-risk patients with PM has been described and evaluated in prospective non-randomised studies –40. SimiPressurised intraperitoneal aerosol chemotherapy (PIPAC) has been proposed as an alternative mode for intraperitoneal drug delivery in certain situations, claiming improved distribution, enhanced tissue uptake, better tolerance, and repeatability using minimally invasive access , 6, 8. FAdjuvant PIPAC for high-risk patients is an intriguing concept which entails a risk of overtreatment. Added PIPAC in this study did not increase the risk or tolerance of staging laparosocopy alone. On the other hand, the risk of missed opportunities (no PIPAC with patients with positive cytology) is to consider and might favour local spread. Three prospective randomized trials are currently recruiting to assess PIPAC as adjuvant treatment: the GASPACCO  and PIPAFollowing the principles of the IDEAL framework allowing standardized approach, future prospective studies are needed to confirm the efficacy and oncologic benefits of PIPAC . FurtherThe current study has some limitations which are mainly related to its retrospective nature and limited patient number and heterogeneity of groups. Differences between the comparative groups might have passed undetected due to type II error. Although baseline characteristics of patients were comparable there was no random allocation for the two groups with a consequent risk for selection bias. Arguably, patients in the PIPAC group might have been a higher risk for complications due to more advanced peritoneal disease (higher PCI) and prior treatments. This report could therefore be interpreted as indirect confirmation of the safety of PIPAC (i.e. same complication rates in "worse" patients). Even if the number of patients was low in both arms with heterogeneous patients, the groups were comparable for ASA score and only slightly different regarding the Charlson Comorbidity Index score. Furthermore, both comparative groups were treated by the same surgical team in the same hospital and with the same perioperative care strategies.In conclusion, neoadjuvant and prophylactic PIPAC could be proposed to patients undergoing staging laparosocopy for suspected or confirmed PSM with minimal increase in surgery time, but no increase in risk and tolerance of the procedure. Its oncological efficacy in this context is currently investigated under controlled conditions. Until then, PIPAC should only be performed in expert centers under standardized conditions and with and prospective monitoring and systematic patient follow-up.


P = 0.26), allergy history , platinum free interval , dexamethasone premedication dose  were significantly correlated to oxaliplatin hypersensitivity reactions. Gender, age, metastasis, combination with bevacizumab, XELOX regimen and cancer types were detected to have no statistically significant effect on oxaliplatin hypersensitivity reactions. Platinum exposure history, allergy history and long platinum-free interval are risk factors of oxaliplatin hypersensitivity reactions. High dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity reactions.This study aimed to investigate risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients through a meta-analysis. A comprehensive retrieve of Chinese databases China National Knowledge Infrastructure, Wanfang Data, VIP Database and English databases PubMed, ScienceDirect, Embase and Cochrane library was conducted. The studies that meet the requirements for meta-analysis according to inclusion and exclusion criteria were screened and assessed for eligibility. Odds ratio (OR) / Weighted mean difference (WMD) and 95% confidence intervals (95% CIs) or calculable dichotomous and continuous raw data were extracted to perform meta-analysis using random effect model or fixed effect model on the basis of heterogeneity between studies through Review Manager 5.4 software. A total of 14 cross-sectional studies and 3367 cancer patients were included. Meta-analysis results showed that platinum exposure history (OR value 3.13, 95% CI 2.19–4.48, heterogeneity  Cancer has been a public health problem and the main cause of death in patients worldwide. In 2018 there were about 18 million new cancer cases worldwide and 9.6 million patients died . HyperseThis meta-analysis was conducted on the basis of the meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines . The litEligible studies needed to meet the following inclusion criteria: (1) the study population was cancer patients; (2) the study contained risk factors of oxaliplatin hypersensitivity reactions; (3) the study design was observational study; (4) the study reported odds ratio (OR) / weighted mean difference (WMD) with 95% confidence interval (CI) or raw data which can calculate these values; (5) oxaliplatin hypersensitivity reactions needed to be graded according to severity; (6) the study published language was Chinese or English. Exclusion criteria were the following: (1) review or comment; (2) case report; (3) abstract without full text; (4) the study with incomplete or incorrect data; (5) repetitive study or same population; (6) the study did not contain outcome related with risk factors of oxaliplatin hypersensitivity.The following data were extracted from each study: (1) the first author’s name and year of publication; (2) country; (3) study design; (4) study population; (5) number of cancer patients; (5) mean age of population; (6) number of men; (7) chemotherapy drugs; (8) median cycle; (9) median oxaliplatin cumulative dose; (10) involved risk factors; (11) incidence of oxaliplatin hypersensitivity reactions; (12) study quality score. OR/WMD value and 95% confidence interval with multivariate analysis would be directly extracted from each study  or calculated based on the incidence of oxaliplatin hypersensitivity reactions in risk factors group and control group.The Newcastle–Ottawa Quality Assessment Scale (NOS) was used to assess case–control studies and cohort studies . The risI2 value were calculated to assess heterogeneity between studies [P < 0.1 and I2 > 50% was considered high heterogeneity among studies and random effect model would be used to perform the analysis. P ≥ 0.1 and I2 ≤ 50% was regarded low heterogeneity among studies and fixed effect model would be used to perform the analysis. Dichotomous outcomes were expressed as OR and 95% CI and continuous outcome were expressed as WMD and 95% CI with P < 0.05 considered to be statistically significant. Forest plots were applied to display outcomes graphically and the funnel plot was used to examine the potential publication bias [Review Manager 5.4 software was applied to conduct this meta-analysis of all included studies. The Q statistic test and  studies , 15. P <ion bias . SensitiThe literature search yielded a total of 141 potentially relevant articles, 35 of which were duplicate literatures. Sixty-four studies were excluded due to irrelevant research topics with oxaliplatin hypersensitivity reactions through primary screening on title and abstract of each literature. Of the remains, 28 literatures not meeting inclusion criteria were removed out and 14 studies which contained investigation of oxaliplatin hypersensitivity reactions were included, 4 of which were published in Chinese from China National Knowledge Infrastructure, Wanfang Data and VIP Database. The flowchart of the process on literature search and study selection was shown in Fig. N = 3367), with number of men patients from 35 to 481 and mean age from 51 to 66. Eight of the included studies were conducted in colorectal cancer patients, one was in gastrointestinal and urinary cancer patients and the other four were in all cancer patients with no restriction on cancer types. All studies were assessed for methodological quality with AHRQ Cross-Sectional/Prevalence Study Quality, 12 of which were moderate quality study and 2 of which were high-quality study. There were no studies with low-quality rating. Table FU, capecitabine, gemcitabine, S-1, docetaxel, etoposide, epirubicin, vindesine, raltitrexed, irinotecan, endostatin, bevacizumab, cetuximab, sunitinib and panitumumab. Oxaliplatin hypersensitivity reactions median chemotherapy cycle ranged from 5 to 9 with four studies no mention, while median cumulative oxaliplatin dose varied from 775.0 to 895.0 mg and from 400.9 to 625.7 mg/m2 with seven studies no mention. Risk factors associated with oxaliplatin hypersensitivity reactions in each study included gender, age, platinum exposure history, allergy history, metastasis, platinum-free interval, combination with bevacizumab, XELOX regimen, dexamethasone premedication dose and cancer types. The incidence of oxaliplatin hypersensitivity reactions remained between 4.9 and 22.2%, among which two Chinese studies reported lower hypersensitivity reactions incidence (4.9 and 6.6%) than current reviews [Table  reviews , 20.TablI2 = 52%, P = 0.02) and age  were analyzed through random effect model. Other risk factors including platinum exposure history , allergy history , metastasis , platinum-free interval , combination with bevacizumab , XELOX regimen , dexamethasone premedication dose  and cancer type (colon cancer)  were analyzed through fixed effect model.This meta-analysis investigated ten risk factors related to oxaliplatin hypersensitivity reactions. Among them, gender  to show no statistically significant differences between both groups. The forest plot was displayed in Fig. Twelve studies were involved into analysis to compare patients in female group with those in male group and the pooled OR for oxaliplatin hypersensitivity reactions was 1.40  to show no statistically significant differences between both groups. The forest plot is displayed in Fig. Five studies were involved in the analysis to compare patients in hypersensitivity reaction group with those in non-hypersensitivity reaction group and the pooled WMD for age was −1.93  to show platinum exposure history considerably increased the risk of oxaliplatin hypersensitivity reactions. The forest plot is displayed in Fig. Four studies were involved in the analysis to compare patients in platinum exposure history group with those in no platinum exposure history group and the pooled OR for oxaliplatin hypersensitivity reactions was 3.13  to show allergy history considerably increased the risk of oxaliplatin hypersensitivity reactions. The forest plot is displayed in Fig. Six studies were involved in the analysis to compare patients in allergy history group with those in no allergy history group and the pooled OR for oxaliplatin hypersensitivity reactions was 1.76  that showed no statistically significant differences between both groups. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in metastasis group with those in no metastasis group, and the pooled OR for oxaliplatin hypersensitivity reactions was 1.28  that showed long platinum-free interval considerably increased the risk of oxaliplatin hypersensitivity reactions. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in long platinum free interval group with those in short platinum free interval group and the pooled OR for oxaliplatin hypersensitivity reactions was 3.75  that showed no statistically significant differences between both groups. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in bevacizumab group with those in no combination with bevacizumab group and the pooled OR for oxaliplatin hypersensitivity reactions was 1.61  that showed no statistically significant differences between both groups. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in XELOX regimen group with those in other regimen group and the pooled OR for oxaliplatin hypersensitivity reactions was 0.83  to show high dexamethasone premedication dose considerably decreased the risk of oxaliplatin hypersensitivity reactions. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in high dose group with those in low dose group and the pooled OR for oxaliplatin hypersensitivity reactions was 0.28  to show no statistically significant differences between both groups. The forest plot is displayed in Fig. Three studies were involved in the analysis to compare patients in colon cancer group with those in other cancer types group and the pooled OR for oxaliplatin hypersensitivity reactions was 1.15 , suggesting that females may be more likely to develop oxaliplatin hypersensitivity reactions than males. (2) Age: After omitting the study by Yamauchi et al., heterogeneity I2 decreased from 82 to 46% and the result changed. The pooled WMD value was −3.42 (95% CI −6.69 to −0.16), suggesting that younger patients may be more likely to occur oxaliplatin hypersensitivity reactions than elder patients.Risk factors with high heterogeneity of more than 50% were eliminated studies one by one and pooled analysis again. (1) Gender: After omitting the study by Okayama et alSince oxaliplatin hypersensitivity reactions may interrupt basic chemotherapy of cancer patients, which puts adverse effects on disease control, it is crucial to identify risk factors of oxaliplatin hypersensitivity reactions early in clinical treatment to enhance patients’ management. Although current studies have analyzed risk factors of oxaliplatin hypersensitivity reactions, the opinions are still not unified and no unanimous conclusion can be reached. On the basis of previous studies, this meta-analysis assessed the affection of gender, age, platinum exposure history, allergy history, metastasis, platinum-free interval, combination with bevacizumab, XELOX regimen, dexamethasone premedication dose and cancer types (colon cancer) on oxaliplatin hypersensitivity reactions, among which platinum exposure history, allergy history, platinum-free interval and dexamethasone premedication dose are typical features that may have representative significance.. [. found that platinum-free interval of patients in oxaliplatin hypersensitivity group was significantly longer than that of patients in non-hypersensitivity group , but the mechanism underlying longer platinum-free interval promoting hypersensitivity reactions is still unclear [The pathophysiology of oxaliplatin hypersensitivity reactions remains not clarified yet, but most widely accepted mechanism is generally explained with IgE-mediated type I hypersensitivity. Degranulation of mast cells and basophils leading to nonimmune-mediated histamine and cytokines released arouses capillary expansion and smooth muscle contraction –7. Clini.  consider. , 22. Soh unclear . Therefo. enrolled 139 colorectal cancer patients receiving oxaliplatin treatment and investigated that among 14 patients occurring hypersensitivity reactions, 3 of 5 patients receiving premedication with steroids and antihistamines successfully rechallenged oxaliplatin regimen, and premedication with dexamethasone was a potential risk factor of oxaliplatin hypersensitivity reactions [. evaluated the efficacy of premedication for controlling oxaliplatin-related hypersensitivity reactions in patients with gastrointestinal malignancy, and of the 134 patients who were administered premedication with chlorpheniramine and hydrocortisone , 71.6% had complete or partial prevention of hypersensitivity reactions after premedication [. found that the success rate of completing oxaliplatin administration by premedication decreased as the severity of hypersensitivity reactions increased [. reached a similar conclusion through data mining of the FDA Adverse Event Reporting System that dexamethasone administration effectively reduced oxaliplatin-induced mild hypersensitivity reactions, but had less impact on severe and lethal hypersensitivity reactions, while the effects of diphenhydramine to hypersensitivity reactions were examined no signals [. concluded that simultaneous infusion of oxaliplatin and dexamethasone increased pH of the infusion solution, thereby inhibiting the release of histamine and reducing the occurrence of hypersensitivity reactions [. reported that increased doses of dexamethasone and antihistamines significantly reduced incidence of oxaliplatin hypersensitivity reactions [. and Kim et al. believed that dexamethasone doses less than 12 and 20 mg, respectively, were risk factors for oxaliplatin hypersensitivity reactions [. thought that dexamethasone premedication had nothing to do with oxaliplatin hypersensitivity [., six patients were administrated with dexamethasone premedication to reintroduce oxaliplatin, five of which still went through the same hypersensitivity reaction [Several studies report that premedication with steroids  and antihistamines  can reduce the occurrence of oxaliplatin hypersensitivity reactions to some extent , 34–36. eactions . Analogodication . Moreovencreased . Sakaedaeactions . Some steactions . In our eactions , 29. Howsitivity . In the reaction –42. Curr., which almost drew the opposite conclusion that patients with hypersensitivity reactions to oxaliplatin were 3.1 years elder than those without hypersensitivity [. which produced heterogeneity of gender indicated that men were more likely to occur oxaliplatin hypersensitivity reaction [This meta-analysis finds that age has nothing to do with oxaliplatin hypersensitivity reactions, but after excluding one study a positive conclusion is reached that younger patients are more likely to develop oxaliplatin hypersensitivity reactions. Heterogeneity among these studies attributes to the study by Yamauchi et alsitivity . Howeversitivity , but thesitivity , 43, thesitivity , while treaction . Based oThe following are the potential limitations in this study: (1) all cross-sectional studies are included with lack of case–control studies and cohort studies. Evidence level of literature keeps not high enough that may cause certain potential bias and lack of persuasiveness with the conclusion to some extent; (2) some of the risk factors analyzed involve less researches and thereby the pooled results are not reliable enough that more data are required to increase the stability of the evidence; (3) this study has a wider geographical variation with most patients included belong to Asians, of which two studies’ populations are from the United States and France, so certain publication bias exists. The individual differences in oxaliplatin hypersensitivity reactions actually remain, so big gap among the ethnicity of study population may exacerbate the clinical heterogeneity; (4) in this study only a risk factor with not less than three studies were analyzed. The remaining factors such as palliative chemotherapy, cumulative dose, eosinophils, albumin, etc. cannot be counted due to lack of data, on which some researches hold affirmative thoughts indeed with no explanation that they are irrelevant with oxaliplatin hypersensitivity reactions; (5) this study is a review of the current evidence without analyzing individual data. Based on the results, we assume that premedication is a point that is worth further exploration, so as the next step we are going to study the effect of different premedication regimens on oxaliplatin hypersensitivity in real-world settings.In summary, our meta-analysis shows that platinum exposure history, allergy history and long platinum-free interval are important risk factors of oxaliplatin hypersensitivity reactions and high dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity. The danger of hypersensitivity to oxaliplatin should not be underestimated This study may help identify patients with risk factors and conduct clinical monitoring and management so as not to affect patients’ chemotherapy process and life quality. Additional prospective studies with larger sample size and high-level evidence are needed to further investigate risk factors associated with oxaliplatin hypersensitivity reactions.