Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

Urgent one-stage endoscopic treatment for choledocholithiasis related moderate to severe acute cholangitis: A propensity scorematched analysis

BACKGROUND During emergency endoscopic retrograde cholangiopancreatography(ERCP),the safety and feasibility of performing one-stage endoscopic treatment for patients with acute cholangitis(AC)due to choledocholithiasis are unclear.AIM To investigate the safety and feasibility of one-stage endoscopic treatment for moderate to severe AC.METHODS We enrolled all patients diagnosed with moderate to severe cholangitis due to common bile duct stones from January 2019 to July 2023.The outcomes were compared in this study between patients who underwent ERCP within 24 h and those who underwent ERCP 24 h later,employing a propensity score(PS)frame-work.Our primary outcomes were intensive care unit(ICU)admission rates,ICU length of stay,and duration of antibiotic use.RESULTS In total,we included 254 patients and categorized them into two groups based on the time elapsed between admission and intervention:The urgent group(≤24 h,n=102)and the elective group(>24 h,n=152).Ninety-three pairs of patients with similar characteristics were selected by PS matching.The urgent ERCP group had more ICU admissions(34.4%vs 21.5%,P=0.05),shorter ICU stays(3 d vs 9 d,P<0.001),fewer antibiotic use(6 d vs 9 d,P<0.001),and shorter hospital stays(9 d vs 18.5 d,P<0.001).There were no significant differences observed in adverse events,in-hospital mortality,recurrent cholangitis occurrence,30-d readmission rate or 30-d mortality.CONCLUSION Urgent one-stage ERCP provides the advantages of a shorter ICU stay,a shorter duration of antibiotic use,and a shorter hospital stay.

Short vs long-course antibiotic therapy in adults with acute cholangitis:A systematic review,meta-analysis,and evidence quality assessment

BACKGROUND Acute cholangitis(AC)constitutes an infection with increased mortality rates in the past.Due to new diagnostic tools and therapeutic methods,the mortality of AC has been significantly reduced nowadays.The initial antibiotic treatment of AC has been oriented to the most common pathogens connected to this infection.However,the optimal duration of the antibiotic treatment of AC is still debatable.AIM To investigate if shorter-course antibiotic treatments could be similarly effective to long-course treatments in adults with AC.METHODS This study constitutes a systematic review and meta-analysis of the existing literature concerning the duration of antibiotic therapy of AC and an assessment of the quality of the evidence.The study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses.Fifteen studies were included in the systematic review,and eight were eligible for meta-analysis.Due to heterogeneous duration cutoffs,three study-analysis groups were formed,with a cutoff of 2-3,6-7,and 14 d.RESULTS A total of 2763 patients were included in the systematic review,and 1313 were accounted for the meta-analysis.The mean age was 73.66±14.67 years,and the male and female ratio was 1:08.No significant differences were observed in the mortality rates of antibiotic treatment of 2-3 d,compared to longer treatments(odds ratio=0.78,95% confidence interval:0.23-2.67,I2=9%)and the recurrence rates and hospitalization length were also not different in all study groups.CONCLUSION Short-and long-course antibiotic treatments may be similarly effective concerning the mortality and recurrence rates of AC.Safe conclusions cannot be extracted concerning the hospitalization duration.

Predictive value of presepsin and acylcarnitines for severity and biliary drainage in acute cholangitis

BACKGROUND Bacteremia,which is a major cause of mortality in patients with acute cholangitis,induces hyperactive immune response and mitochondrial dysfunction.Presepsin is responsible for pathogen recognition by innate immunity.Acylcarnitines are established mitochondrial biomarkers.AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage.METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018.Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry,respectively.RESULTS The concentrations of presepsin,procalcitonin,short-and medium-chain acylcarnitines increased,while long-chain acylcarnitines decreased with the severity of acute cholangitis.The areas under the receiver operating characteristic curves(AUC)of presepsin for diagnosing moderate/severe and severe cholangitis(0.823 and 0.801,respectively)were greater than those of conventional markers.The combination of presepsin,direct bilirubin,alanine aminotransferase,temperature,and butyryl-L-carnitine showed good predictive ability for biliary drainage(AUC:0.723).Presepsin,procalcitonin,acetyl-L-carnitine,hydroxydodecenoyl-Lcarnitine,and temperature were independent predictors of bloodstream infection.After adjusting for severity classification,acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality(hazard ratio 14.396;P<0.001)(AUC:0.880).Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine.CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage.Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis.Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.

Timing of biliary decompression for acute cholangitis

Severe acute cholangitis(AC)exacerbates the risk of death because of the rapid progression of the disease.The optimal timing of biliary decompression(BD)as a necessary intervention in patients with severe AC is controversial.A recently report titled“Timing of endoscopic retrograde cholangiopancreatography in the treatment of acute cholangitis of different severity”in the World Journal of Gastroenterology that the optimal time of endoscopic retrograde cholangiopancreatography for treating patients with severe AC is≤48 but not≤24 h,providing clinical evidence for selecting the optimal time for implementation of BD.Here,we discuss the controversy over the optimal timing of BD for AC based on guidelines and clinical evidence,and consider that more high-level clinical researches are urgent needed to benefit the management of patients with different severity of AC.

Response letter to “Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the outcomes?” with imaging aspects

Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.

Efficacy and safety of emergency endoscopic retrograde cholangiopancreatography for acute cholangitis in the elderly

AIM To investigate the efficacy and safety of emergency endoscopic retrograde cholangiopancreatography(ERCP) in elderly patients with acute cholangitis. METHODS From June 2008 to May 2016, emergency ERCPs were performed in 207 cases of acute cholangitis at our institution. Patients were classified as elderly if they were aged 80 years and older(n = 102); controls were under the age of 80 years(n = 105). The patients' medical records were retrospectively reviewed for comorbidities, laboratory data, etiology of cholangitis(presence of biliary stones, biliary stricture and malignancy), details of the ERCP(therapeutic approaches, technical success rates, procedure duration), ERCP-related complications and mortality. RESULTS The frequency of comorbidities was higher in the elderly group than the control group(91.2% vs 67.6%). Periampullary diverticulum was observed in the elderly group at a higher frequency than the control group(24.5% vs 13.3%). Between the groups, there was no significant difference in the technical success rates(95.1% vs 95.2%) or endoscopicprocedure durations. With regard to the frequency of ERCP-related complications, there was no significant difference between the two groups(6.9% vs 6.7%), except for a lower rate of post-ERCP pancreatitis in the elderly group than in the control group(1.0% vs 3.8%). Neither angiographic nor surgical intervention was required in any of the cases with ERCP-related complications. There was no mortality during the observational periods. CONCLUSION Emergency ERCP for acute cholangitis can be performed safely even in elderly patients aged 80 years and older.

Diagnostic value of elevated serum carbohydrate antigen 199 level in acute cholangitis secondary to choledocholithiasis

AIM To investigate the diagnostic value of abnormal serum carbohydrate antigen 199(CA199) level in acute cholangitis secondary to choledocholithiasis.METHODS In this retrospective cohort study, the clinical data of 727 patients with choledocholithiasis admitted to the Third Affiliated Hospital of Zunyi Medical College from June 2011 to June 2017 were collected. Among these patients, 258 patients had secondary acute cholangitis and served as observation group, and the remaining 569 choledocholithiasis patients served as the control group. Serum liver function indexes and tumor markers were detected in both groups, and the receiver operating characteristic(ROC) curves were constructed for markers showing statistical significances. The cutoff value, sensitivity, and specificity of each marker were calculated according to the ROC curves. RESULTS The results of liver function tests showed no significant differences between the two groups(P > 0.05). Tumor markers including serum CA125, CA153, carcinoembryonic antigen, and alpha fetoprotein levels were also not significantly different(P > 0.05); however, the serum CA199 level was significantly higher in the observation group than in the control group(P < 0.05). The ROC curve analysis showed that the area under the curve was 0.885(95%CI: 0.841-0.929) for CA199, and the cutoff value of 52.5 kU/L had the highest diagnostic accuracy, with a sensitivity of 86.8% and a specificity of 81.6%.CONCLUSION Abnormally elevated serum CA199 level has an important value in the diagnosis of acute cholangitis secondary to choledocholithiasis. It may be a specific inflammatory marker for acute cholangitis.

Risk factors and incidence of acute pyogenic cholangitis

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis. METHODS: We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC. RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%) Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariateanalysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC. CONCLUSIONS: This study demonstrates that advanced age, hypotension, abnormal WBC, high CRP, and long duration of antibiotic therapy are significantly associated with ASC. We recommend decompression by ERCP should be carried out in patients as early as possible.

Urgent ERCP for acute cholangitis reduces mortality and hospital stay in elderly and very elderly patients

BACKGROUND： Acute cholangitis in old people is a cause of mortality and prolonged hospital stay. We evaluated the effects of methods and timing of biliary drainage on the outcomes of acute cholangitis in elderly and very elderly patients. METHODS： We analyzed 331 patients who were older than 75 years and were diagnosed with acute calculous cholangitis. They were admitted to our hospital from 2009 to 2014. Patients＇ demographics, severity grading, methods and timing of biliary drainage, mortality, and hospital stay were retrospectively obtained from medical records. Clinical parameters and outcomes were compared between elderly （75-80 years, n= 156） and very elderly （≥81 years, n=175） patients. We analyzed the effects of methods [none, endoscopic retrograde cholangio- pancreatography （ERCP）, percutaneous transhepatic biliary drainage, or failure] and timing （urgent or early） of biliary drainage on mortality and hospital stay in these patients. RESULTS： Acute cholangitis in older patients manifested as atypical symptoms characterized as infrequent Charcot＇s triad （4.2%） and comorbidity in one-third of the patients. Patients were graded as mild, moderate, and severe cholangitis in 104 （31.4%）, 175 （52.9%）, and 52 （15.7%）, respectively. Urgent bili-ary drainage （≤24 hours） was performed for 80.5% （247/307） of patients. Very elderly patients tended to have more severe grades and were treated with sequential procedures of transient hiliary drainage and stone removal at different sessions. Hospital stay was related to methods and timing of biliary drainage. Mortality was very low （1.5%） and not related to patient age but rather to the success or failure of biliary drainage and severity grading of the acute cholangitis. CONCLUSIONS： The methods and timing used for biliary drainage and severity of cholangitis are the major determinants of mortality and hospital stay in elderly and very elderly patients with acute cholangitis. Urgent successful ERCP is mandatory for favorable prognosis in these patients.

Safety of immediate endoscopic sphincterotomy in acutesuppurative cholangitis caused by choledocholithiasis

AIM: To examine the safety of immediate endoscopic sphincterotomy(EST) in patients with acute suppurative cholangitis(ASC) caused by choledocholithiasis, as compared with elective EST.METHODS: Patients with ASC due to choledocholithiasis were allocated to two groups: Those who underwent EST immediately and those who underwent EBD followed by EST 1 wk later because they were under anticoagulant therapy, had a coagulopathy(international normalized ratio > 1.3, partial thromboplastin time greater than twice that of control), or had a platelet count < 50000 × 103/μL. One of four trainees [200-400 cases of endoscopic retrograde cholangiopancreatography(ERCP)] supervised by a specialist(> 10000 cases of ERCP) performed the procedures. The success and complication rates associated with EST in each group were examined.RESULTS: Of the 87 patients with ASC, 59 were in the immediate EST group and 28 in the elective EST group. EST was successful in all patients in both groups. There were no complications associated with EST in either group of patients, although white blood cell count, C-reactiveprotein, total bilirubin, and serum concentrations of liver enzymes just before EST were significantly higher in the immediate EST group than in the elective EST group.CONCLUSION: Immediate EST can be as safe as elective EST for patients with ASC associated with choledocholithiasis provided they are not under anticoagulant therapy, or do not have a coagulopathy or a platelet count < 50000 × 103/μL. Moreover, the procedure was safely performed by a trainee under the supervision of an experienced specialist.

Activation of TLR-4 and liver injury via NF-kappa B in rat with acute cholangitis

BACKGROUND: Toll-like receptors (TLRs) are a family of type 1 transmembrane receptors, which can recognize different pathogen-associated molecular patterns. Among them, TLR-4 is specific to lipopolysaccharide. It transfers the infection signal into the cell and promotes the translocation of nuclear factor kappa B (NF-kappa B) to the nucleus and the subsequent transcriptional activation of genes encoding pro- and anti-inflammatory cytokines and chemokines. Acute cholangitis (AC) is a common biliary tract infection in oriental countries, and often leads to liver injury. The activation of TLR-4 and its significance in liver injury in rats with AC remain unclear. METHODS: Rat models of AC (biliary tract obstruction+E. coli injection, n=36) and control models (biliary tract obstruction+saline, n=18) were made. Liver tissue injury was investigated by pathological examination. The levels of serum TNF-alpha and IL-10 were measured by enzyme-linked immunosorbent assay, and the expressions of TLR-4, NF-kappa B mRNAs and proteins in the liver were detected by RT-PCR, immunohistochemical staining and Western blotting, respectively. RESULTS: Severe liver tissue injury in rats with AC was evident as shown by pathological examination. TLR-4 and NF-kappa B were strongly expressed in the cytoplasm of hepatocytes in the AC group. They were negative or slightly positive in the control group. TLR-4 mRNA and protein in the liver of rats with AC increased 1 hour after biliary tract ligation and E. coli injection, and peaked at 6 hours after surgery. Twenty-four hours later, they began to decrease. The expression of TLR-4 was paralleled by that of NF-kappa B in the liver and TNF-alpha in serum. CONCLUSION: The higher expression of TLR-4 in the liver of rats with AC may be involved in liver injury through the activation of NF-kappa B and release of cytokines such as TNF-alpha.

Early vs late endoscopic retrograde cholangiopancreatography in patients with acute cholangitis: A nationwide analysis

AIM To assess the effect of early vs late endoscopic retrograde cholangiopancreatography(ERCP) on mortality and readmissions in acute cholangitis, using a nationally representative sample.METHODS We used the 2014 National Readmissions Database to identify adult patients hospitalized with acute cholangitis who underwent therapeutic ERCP within one week of admission. Early ERCP was defined as ERCP performed on the same day of admission or the next day(days 0 or 1, < 48 h), and late ERCP was performed on days 2 to 7 of admission. Patients with severe cholangitis had any of the following additional diagnoses: Severe sepsis, septic shock, acute renal failure,acute respiratory failure, or thrombocytopenia. Multivariate logistic regression was used to calculate the adjusted odds of association of ERCP timing with inhospital mortality, 30-d mortality, and 30-d readmissions, controlling for age, sex,severe disease and comorbidities.RESULTS Four thousand five hundred and seventy patients satisfied the inclusion criteria;with a mean age of 64.1 years. Of these, 66.6% had early ERCP, while 33.4% had late ERCP. Early ERCP was associated with lower in-hospital mortality [1.2% vs2.4%, adjusted odds ratio(aOR) = 0.50, 95%CI: 0.76-0.83, P = 0.001] and lower 30-d mortality(1.5% vs 3.3%, aOR = 0.48, 95%CI: 0.33-0.69, P < 0.0001) compared to the late ERCP group. Similarly, early ERCP was associated with lower 30-d readmissions(9.7% vs 15.1%, aOR = 0.58, 95%CI: 0.49-0.7, P < 0.0001). When stratified by severity of cholangitis, there was a similar benefit of early ERCP on all outcomes in those with and without severe cholangitis. The mean length of stay was higher in the late ERCP group compared to the early ERCP group(6.9 d vs 4.5 d, P < 0.0001). The mean hospitalization cost was higher in the late ERCP group($21459 vs $16939, P < 0.0001).CONCLUSION Early ERCP is associated with lower in-hospital and 30-d mortality in those with or without severe cholangitis. Regardless of severity, we suggest performing early ERCP.

Feasibility of initial endoscopic common bile duct stone removal in patients with acute cholangitis

AIM To investigate the feasibility of initial endoscopic common bile duct(CBD) stone removal in patients with acute cholangitis(AC).METHODS A single-center,retrospective study was conducted between April 2013 and December 2014 and was approved by the Medical Ethics Committee at our institution.Written informed consent was obtained from each patient prior to the procedure.The cohort comprised 31 AC patients with CBD stones who underwent endoscopic biliary drainage(EBD) for na?ve papilla within 48 h after AC onset.We retrospectively divided the participants into two groups: 19 patients with initial endoscopic CBD stone removal(initial group) and 12 patients with delayed endoscopic CBD stone removal(delayed group).We evaluated the feasibility of initial endoscopic CBD stone removal in patients with AC.RESULTS We observed no significant differences between the groups regarding patient characteristics.According to the assessments based on the Tokyo Guidelines,the AC severity of patients with initial endoscopic CBD stone removal was mild to moderate.The use of antithrombotic agents before EBD was less frequent in the initial group than in the delayed group(11% vs 58%,respectively; P = 0.004).All the patients underwent successful endoscopic CBD stone removaland adverse events did not differ significantly between the groups.The number of endoscopic retrograde cholangiopancreatography procedures was significantly lower in the initial group than in the delayed group [median(interquartile range) 1(1-1) vs 2(2-2),respectively; P < 0.001].The length of hospital stay was significantly shorter for the initial group than for the delayed group [10(9-15) vs 17(14-20),respectively; P = 0.010].CONCLUSION Initial endoscopic CBD stone removal in patients with AC may be feasible when AC severity and the use of antithrombotic agents are carefully considered.

Factors predicting adverse short-term outcomes in patients with acute cholangitis undergoing ERCP: A single center experience

AIM: To identify potential factors that can predict adverse short-term outcomes in patients with acute cholangitis undergoing endoscopic retrograde cholangiopancreatography(ERCP). METHODS: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and underwent ERCP from 2001 to 2012. Involvement of two or more organ systems was termed as organ failure(OF). Cardiovascular failure was defined based on a systolic blood pressure of < 90 mmHg despite fluid replacement and/or requiring vasopressor treatment; respiratory failure if the Pa02 /Fi02 ratio was < 300 mmHg and/or required mechanical ventilation; coagulopathy if the platelet count was < 80; and renal insufficiency if serum creatinine was > 1.9 mg/dL. Variables associated with short term adverse clinical outcomes defined as persistent OF and/or 30-d mortality was determined. RESULTS: A total of 172 patients(median age 62 years, 56.4% female) were included. The median door to ERCP time was 17 h. Bile duct stones were the most common etiology(n = 67, 39.2%). In multivariate analysis, factors that were independently associated with persistent OF and/or 30-d mortality included American Society of Anesthesiology(ASA) physical classification score > 3(OR = 7.70; 95%CI: 2.73-24.40), presence of systemic inflammatory response syndrome(OR = 3.67; 95%CI: 1.34-10.3) and door to ERCP time greater than 72 h(OR = 3.36; 95%CI: 1.12-10.20). Door to ERCP time greater than 72 h was also associated with 70% increase in the mean length of stay(P < 0.001). Every one point increase in the ASA physical classification and every 1 mg/dL increase in the preERCP bilirubin level was associated with a 34% and 2% increase in the mean length of hospital stay, respectively. Transfer status did not impact clinical outcomes. CONCLUSION: Higher ASA physical classification and delays in ERCP are associated with adverse clinical outcomes and prolonged length of hospital stay in patients with acute cholangitis undergoing ERCP.

Effect of combined therapy of Yinchenhao Chengqi decoction and endoscopic sphincterotomy for endotoxemia in acute cholangitis

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Significance of MD-2 and MD-2B expression in rat liver during acute cholangitis

AIM: To investigate the expression of myeloid differentiation protein-2 (MD-2), MD-2B (a splicing isoform of MD-2 that can block Toll-like receptor 4 (TLR4)/MD-2 LPS-mediated signal transduction) and TLR4 in the liver of acute cholangitis rats. METHODS: Male Sprague-Dawley rats (SPF level) were randomly divided into four groups: (A) sham-operated group; (B) simple common bile duct ligation group; (C)acute cholangitis group; and (D) acute cholangitis anti- TLR4 intervention group (n = 25 per group). Rat liver tissue samples were used to detect TLR4, MD-2 and MD-2B mRNA expression by fluorescence quantitative PCR in parallel with pathological changes. RESULTS: In acute cholangitis, liver TLR4 and MD-2 mRNA expression levels at 6, 12, 24, 48 and 72 h were gradually up-regulated but MD-2B mRNA expression gradually down-regulated (P < 0.05). After TLR4 antibody treatment, TLR4 and MD-2 mRNA expression were lower compared with the acute cholangitis group (P < 0.05). However, MD-2B mRNA expression was higher than in the acute cholangitis group (P < 0.05). MD-2 and TLR4 mRNA expressions were positively correlated (r = 0.94981, P < 0.05) and MD-2B mRNA expression was negatively correlated with MD-2 and TLR4 mRNA (r = -0.89031, -0.88997, P< 0.05). CONCLUSION: In acute cholangitis, MD-2 plays an important role in the process of TLR4- mediated in? am- matory response to liver injury while MD-2B plays a negative regulatory role.

Mononuclear macrophages in pathogenesis of acute lung injury during acute obstructive cholangitis

Objective: To determine the role of mononuclear macrophages in the pathogenesis of acute lung injury during acute obstructive cholangitis. Methods: Sixty Wistar rats were used to study the correlation between the behavior of mononuclear macrophages and acute pulmonary injury during a- cute obstructive cholangitis (AOC). Animal model of AOC was made according to the method that the common bile duct was injected with Escherichia coli and ligated. The rats were killed at 6 h, 12 h, 24 h and 48 h after operation. The phagocytic function of Kupffer cells (KCs), the number of alveolar macro- phages (AMs) in bronchoalveolar lavage liquid, and the extravascular water content of lung tissue were measured. The levels of lipid peroxide (LPO) and supperoxide dismutase (SOD) were determined too. Pathological alterations of liver and lung tissue were observed under light and electron microscopes. Results: KCs phagocytic function was significantly el- evated at the 6th hour but markedly decreased from the 24th hour to the 48th hour in the AOC group as compared with the control (P<0. 05). From the 12th to the 48th hour, the number of AMs, the ex- travascular water content of lung tissue, and the con- tent of LPO significantly increased, but the SOD lev- el of lung tissue decreased greatly (P<0. 05). Mor- phologically, KCs proliferated diffusely in the early period in livers of the AOC group, but decreased markedly in the late period. Mitochondria of KCs were swollen or even vacuolated; focal cytoplasmic degeneration and many myeli like figures could be seen in the cytoplasm. The changes of injury such as disturbance of pulmonary capillary blood circula- tion, degeneration and/or necrosis of the lung tissue and endothelium, and inflammatory reactions could be observed. In other two groups, no evident mor- phological changes were observed. Conclusions: KCs phagocytic function is decreased, whereas AM is activated by the invading bacteria to release such inflammatory mediators as free radicals, resulting in acute pulmonary injury. It seems that there is a close relationship between the functional status of mononuclear macrophages and the develop- ment of acute lung injury. The dysfunction of mono- nuclear macrophages may play an important role in the pathogenesis of multiple organ damage, especial- ly acute pulmonary injury.

Verification of the Tokyo guidelines for acute cholangitis secondary to benign and malignant biliary obstruction:experience from a Chinese tertiary hospital

BACKGROUND: The lack of widely-accepted guidelines for acute cholangitis largely lags behind the progress in medical and surgical technology and science for the management of acute cholangitis. This study aimed to verify the Tokyo guidelines for the management of acute cholangitis and cholecystitis of 2007 edition (TG07) in patients with obstructive cholangitis due to benign and malignant diseases. METHODS: The patients were retrieved from our existing ERCP database. Final diagnosis of acute cholangitis was made by detecting purulent bile during biliary drainage. We examined and compared the guidelines concerning benign and malignant obstruction. RESULTS: In 120 patients in our study, 82 and 38 had benign and malignant biliary obstruction, respectively. Guidelines based diagnosis was made in 68 (82.9%), 36 (94.7%), and 104 (86.7%) patients with benign, malignant, and overall biliary obstruction, respectively, which were significantly higher than 44 (53.7%), 17 (44.7%), and 61 (50.8%) diagnosed by Charcot’s triad (P【0.001). Treatment consistent with the guidelines was offered to 58 (70.7%) patients with benign obstruction and15 (39.5%) patients with malignant obstruction (P=0.001). No significant association was observed between clinical compliance, guidelines-based severity grades and clinical outcomes. In the multivariate model, intrahepatic obstruction (OR=11.2, 95% CI: 1.55-226.9) and hypoalbuminemia (≤25.0 g/L; OR=17.3, 95% CI: 3.5-313.6) were independent risk factors for a 30-day mortality. CONCLUSIONS: The TG07 are more reliable than Charcot’s triad for the diagnosis of acute cholangitis albeit with limited prognostic values. Intrahepatic obstruction and hypoalbuminemia are new predictors of poor prognosis and need further assessment.

Optimal timing of biliary drainage based on the severity of acute cholangitis:A single-center retrospective cohort study

BACKGROUND Biliary decompression is well known to greatly decrease the risks of mortality in acute cholangitis(AC).Although early biliary drainage is recommended by the treatment guidelines for AC,the best time for performing this procedure is yet to be established.Furthermore,since the clinical outcomes of patients with severe AC vary dramatically,screening for patients that could benefit the most from early drainage would be more beneficial than the drainage performed based on the severity grade criteria.AIM To investigate the optimal drainage timing for AC patients with each disease severity grade and organ dysfunction.METHODS In this retrospective monocenter cohort analysis,we reviewed 1305 patients who were diagnosed with AC according to the Tokyo guidelines 2018 at a Chinese tertiary hospital between July 2016 and December 2020.Demographic characteristics including age and sex,clinical and laboratory characteristics,and imaging findings of each patient were obtained from electronic medical records.We investigated the all-cause in-hospital mortality(IHM),hospital length of stay(LOS),and hospitalization costs associated with the timing of biliary drainage according to the severity grading and different dysfunctioning organs and predictors[age,white blood cell(WBC)count,total bilirubin,albumin,lactate,malignant obstruction,and Charlton comorbidity index(CCI)].RESULTS Biliary drainage within 24 or 48 h in Grade Ⅲ AC patients could dramatically decrease IHM(3.9%vs 9.0%,P=0.041;4%vs 9.9%,P=0.018,respectively),while increasing LOS and hospitalization costs.Multivariate logistic analysis revealed that neurological,respiratory,renal,and cardiovascular dysfunctions,hypoalbuminemia,and malignant obstruction were significantly associated with IHM(odds ratio=5.32,2.541,6.356,4.021,5.655,and 7.522;P<0.001,P=0.016,P<0.001,P=0.012,P<0.001,and P<0.001;respectively).Biliary decompression performed within 12 h of admission significantly decreased the IHM in AC patients with neurological dysfunction(0%vs 17.3%,P=0.041)or with serum lactate>2 mmol/L(0%vs 5.4%,P=0.016).In the subgroup of AC patients with renal dysfunction,abnormal WBC count,hyperbilirubinemia,or hypoalbuminemia,early drainage(<24 h)reduced the IHM(3.6%vs 33.3%,P=0.004;1.9%vs 5.8%,P=0.031;1.7%vs 5.0%,P=0.019;0%vs 27%,P=0.026;respectively).The IHM was lower in patients with AC combined with hepatic dysfunction,malignant obstruction,or a CCI>3 who had undergone biliary drainage within 48 h(2.6%vs 20.5%,P=0.016;3.0%vs 13.5%,P=0.006;3.4%vs 9.6%,P=0.021;respectively).CONCLUSION Biliary drainage within 12 h is beneficial for AC patients with neurological or cardiovascular dysfunction,while complete biliary decompression within 24 h of admission is recommended for treating patients with Grade Ⅲ AC.