Acute obstructive suppurative cholangitis (AOSC) is a severe infectious disease characterized by acute suppurative infection and pus in the biliary system that is caused by biliary obstruction, which results in hepatobiliary system damage. This condition leads to the release of a large quantity of bacteria and toxins into the bloodstream, causing biliary hypertension and systemic damage to multiple organs. AOSC is considered to be a serious form of acute cholangitis (AC) (1). It is the predominant cause of mortality in patients with benign biliary disease. The clinical presentation of AOSC commonly includes abdominal pain, fever, jaundice and in severe cases it may be accompanied by septic shock characterized by shock and symptoms of nervous system suppression. AOSC can lead to multiple organ failure if not promptly detected and treated, resulting in a morbidity and mortality rate ranging from 13-88% (2). There are numerous factors associated with biliary tract infections, including bacterial infections, gallstones and trauma. When there are gallstones in the biliary tract, these can lead to biliary obstruction and, subsequently, enteric pathogens can retrogradely migrate into the bile duct, causing biliary tract infections. Systemic infections derived from bacteria in the bloodstream may also enter the bile duct. Moreover, in cases of severe trauma, burns or shock, the biliary system is prone to local vascular disturbances, which can also result in biliary tract infections (3).

In recent years, significant and rapid advances have been made in terms of the development of minimally invasive endoscopic intervention techniques. Endoscopic retrograde cholangiopancreatography (ERCP) is used more and more often in the clinic for the treatment of AOSC, due to its advantages of simple operation and high safety. Especially in Europe and the United States, with the development of endoscopic technology, the safety and effectiveness of ERCP have been widely studied and established in the treatment of biliary tract diseases (4,5). However, current clinical studies on ERCP in China mainly focus on patients with AC and there is still no conclusion on the efficacy and safety of ERCP in the treatment of AOSC patients, especially elderly patients (2,6). The present study therefore investigated an effective minimally invasive treatment approach that holds promise for improving treatment outcomes for patients with AOSC, with the goals of alleviating suffering and reducing complications, thereby offering a beneficial therapeutic option for both physicians and patients. These findings should prove to be beneficial for enhancing quality of life of patients and optimizing the utilization of medical resources.

Charcot's triad, shock and central nervous system depression were observed in 14 of 47 patients with AOSC. A total of 33 patients were found to have between two and four features of Charcot's pentalogy, including one patient with coma. After having performed clinical and endoscopic minimally invasive treatments, purulent bile outflow was observed in 47 patients with AOSC (Figs. 1 and 2), including 41 cases of common bile duct stones (Figs. 3 and 4). The end-stage tumors included bile duct malignancy in four cases and pancreatic cancer in two cases and the clinical symptoms were significantly improved. In this group, on day 7 after endoscopic treatment, blood inflammatory indexes and liver function were found to be significantly improved the most of the group compared with the measured values at admission: The level of PCT decreased from 8.95±15.26 to 0.42±0.37 ng/ml, the level of CA-199 was reduced from 635.04±907.76 to 164.68±475.78 kU/l and that of ALT was decreased from 190.96±105.91 to 50.56±20.33 µmol/l. The value of the direct bilirubin test was decreased from 62.21±36.23 to 30.64±15.40 µmol/l and these differences were found to be statistically significant (P<0.05 or P<0.01), as shown in Table VII. Out of the total of 47 patients, 16 cases involved the use of ERCP and ENBD, 17 cases included the use of ERCP, EST and ENBD, 14 cases included the use of ERCP and ERBD, and 28 cases included the use of ERCP for stone extraction. During ERCP examination, purulent bile was discharged from the bile duct. A total of three patients underwent secondary ERCP (Table VI). Out of the total cases, 35 (74.5%) showed positive results in the bile culture. The predominant bacterium species identified were Gram-negative bacteria, with Escherichia coli being the most frequently observed in 11 instances (31.4%). Klebsiella pneumoniae was detected in seven instances, accounting for 20% of the cases. Pseudomonas faecium was identified in five cases (14.3%), Enterococcus faecium in four cases (11.4%), Pseudomonas aeruginosa in four cases (11.4%), Staphylococcus aureus in three cases (8.6%) and Enterococcus casselifavus in two cases (5.7%). There was one case of both E. faecium and E. coli (2.9%), two cases of K. pneumoniae and Candida albicans (5.7%), one case of E. faecalis, K. pneumoniae and Enterococcus casselifavus (2.9%), one case of Aeromonas hydrophila (strain found in guinea pigs) and E. faecalis (2.9%), and two cases of E. faecalis and E. coli (5.7%). There were two cases of Citrobacter freundii and Stenotrophomonas maltophilia, accounting for 5.7% of the cases. Additionally, there was one case of E. faecium and C. albicans, which made up 2.9% of the cases. Within 1 to 7 days after treatment, the high fever of 45 of the patients disappeared and their body temperature returned to normal. It was difficult to completely control the infection in the remaining two patients after 7 days of ERCP treatment. One of these patients was an elderly patient (≥80 years old) with a secondary tumor and stenosis of bilioenteric anastomosis complicated with AOSC. Even though the infection was not entirely treated while the patient was in the hospital, the family members requested that the patient be discharged. Another patient with multiple common bile duct stones complicated with sepsis underwent some improvements after a second line of ERCP was performed and was discharged. Within 7 days of treatment, the abdominal pain of 27 patients, and jaundice experienced by 29 patients, were resolved. Hyperamylasemia or acute pancreatitis (mild) occurred in three patients following ERCP, which itself improved after conservative treatments. The average hospital stay per patient was 11.9±4.6 days. Finally, no severe complications, including perforation, bleeding, severe pancreatitis or mortality, were identified for any of the patients.

AOSC is one of the most common biliary tract infections encountered in clinical practice and has the characteristics of rapid onset and rapid progress. If it is not diagnosed and treated in time, it may pose a serious threat to the lives of patients (7), especially those patients who have multiple comorbidities, including coronary heart disease, hypertension, diabetes, pulmonary heart disease, liver cirrhosis, renal insufficiency and a personal history of cerebral infarction. AOSC is characterized by severe biliary tract infection and empyema on the basis of biliary obstruction, resulting in biliary hypertension, the leakage of bacterial endotoxins into the blood and severe infectious diseases, including multiple organ damage. The initial clinical manifestations of AOSC are mild. Subsequently, as the pressure in the bile duct increases, the septic substances in the bile duct flow back into the hepatic bloodstream, leading to hyperbilirubinemia and sepsis. This may result in symptoms such as chilliness, high fever, abdominal pain, jaundice, shock and mental changes (all symptoms of Reynolds pentalogy).

Biliary obstruction and bile infection are the two major factors leading to the onset of AC. There are numerous causes of biliary obstruction, the most common one being biliary stone obstruction, as mediated by bile duct stones and gallstones. Compression by malignant tumors of the biliary system, liver and pancreatic head can also cause biliary obstruction and, if accompanied by severe infection, this may also lead to cholangitis (7). In a healthy state, there are no bacteria present in the bile. The biliary tract, with its tubular structure, is not conducive to bacterial presence. However, due to its anatomical location, structure and physiological characteristics, there is a high risk of infection when stone diseases such as choledocholithiasis, cholelithiasis and biliary ascariasis occur. These conditions can also disrupt the circulatory system of the body, affect bile excretion and lead to bacterial growth, resulting in infections (8). The biliary tract is connected to the intestinal tract, and retrograde infection from intestinal bacteria is the primary pathogenic cause of biliary tract infections. Therefore, the isolated pathogens from bile are generally consistent with the intestinal bacterial profile. The Gram-positive bacteria we identified to be present were mainly Enterococcus, whereas Gram-negative bacterial rods mainly included Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, findings that were in agreement with the those of a similar study (9). In some patients, the bacteria that remain in the gallbladder due to recurrent gallstone attacks are able to alter both the gallbladder's environment and the physicochemical properties of bile. This alteration makes it conducive for bacteria to proliferate within the biliary tract (10). Certain independent risk factors, including diabetes, lead to deficiencies in the mechanisms of immune defense in patients. In addition, high levels of blood sugar negatively affect the functions of neutrophils and T-lymphocytes, including their impaired migration, phagocytosis, intracellular killing and chemotaxis (11,12). This, in turn, leads to microvascular damage, compromising local biliary circulation, leading to a reduction in blood supply, worsening metabolic disorders and delaying the response to infections, allowing the infection to spread. Additionally, it causes autonomic nervous system dysregulation, resulting in dysfunction of the Oddi sphincter and gallbladder contraction and relaxation, leading to increased resting tension in the fasting state, the promotion of bile stasis, and increasing the risk of biliary tract infection (13). In recent years, some researchers have also proposed that the development of AC may be associated with an increase in vagal nerve excitability (11-13). However, due to the relatively limited research in this area, further investigations are required for an improved understanding of the role of the vagal nerve in AC.

Previous studies have also shown that the initial basic factor for its occurrence is bile duct obstruction, which, as explained above, causes an increase in intraluminal pressure, leads to retrograde bacteria from the biliary tract into the blood and biliary drainage disorders lead to infection. If there is no biliary obstruction, even simple injection of bacteria into the gallbladder or biliary tract will not cause biliary tract infection. Ligation of the cystic duct or common bile duct at the same time, resulting in cholestasis or obstruction of the blood supply of the biliary tract, will induce severe infection, and this has been borne out in the clinical results of a couple of previously published studies (14,15). In the present group of cases, the clinical manifestations of patients were not completely consistent with bile duct empyema (i.e., the most severe complication of acute cholangitis). Certain patients exhibited atypical clinical symptoms, although their blood tests revealed significantly elevated inflammatory markers, indicating the presence of severe sepsis. ERCP aspiration of bile revealed a large amount of pus in the bile duct, which is mainly associated with the delayed response of elderly patients. Collectively, the results suggested that the culture of aspirated bile is helpful to guide clinical medication according to the drug-sensitivity test, and to promote the recovery of patients.

Elderly patients, especially, are subjected to weakened levels of immunity; moreover, they are often afflicted with multiple diseases, and their condition occasionally deteriorates rapidly, leading to mortality. Qin et al (16) found that advanced age is an independent risk factor for AOSC, and that the occurrence and development of sepsis was positively correlated with an advanced age. One of the explanations that may account for this is that early manifestations of patients are not typically identified, and Charcot's triad is rarely encountered in the early stage (17). It is often necessary to combine the patient's medical history, imaging examination and various laboratory indicators to evaluate the severity of AC in patients.

Previous studies have also demonstrated that early intervention with AOSC is crucial in terms of alleviating biliary obstruction and facilitating the drainage of infected bile within a 24-h timeframe. Failure to do so can result in the development of severe infections resulting from biliary obstruction and cholestasis. An elevated pressure in the bile duct can cause the contaminated bile to flow back into the bloodstream, leading to the onset of sepsis, shock, and even mortality (18,19). It has also been reported that hypoproteinemia is one of the factors that affects the poor prognosis of patients with sepsis (20). In severe infection, due to the increases in body catabolism and capillary permeability, the level of albumin (ALB) may be decreased. In addition, ischemia, hypoxia and oxidative damage may occur in severe infection and ALB is the main target of extracellular oxidative stress (21). Schneider et al (22) and Gravito-Soares et al (23) found that ALB at a concentration of 30 g/dl was an important risk predictor of in-hospital mortality in patients with AC. Cozma et al (13) showed that ALB is a protective factor for severe cholangitis, and the lower the level of ALB, the higher the incidence of severe cholangitis. There were 19 very elderly patients (≥80 years old) in the present group of cases, and 15 patients had hypoproteinemia. Among the 15 patients with hypoproteinemia, nine patients developed sepsis and three patients exhibited poor therapeutic effects following the first ERCP, although their condition improved significantly after the second ERCP. The explanation for this was closely associated with obstruction drainage after ERCP. Therefore, the key to the treatment of AOSC is to relieve the biliary obstruction in a timely manner, effectively reducing the biliary pressure, and then to drain the purulent bile, block the liver-intestinal circulation of bilirubin so as to reduce the level of jaundice and relieve its injurious symptoms and gradually restore the function of the damaged bilirubin transporters and microvilli. Conjugated bilirubin in the blood is secreted into the biliary system and, as a consequence, the jaundice is gradually decreased and its symptoms are improved (24). Implementing this strategy should enable the body's recovery. In addition to the improvements in symptoms, the parameters of blood routine, TBil, PCT and CA199 were found to be significantly decreased at 3 days after operation. Previous studies (25,26) demonstrated that the success rate of ENBD treatment for AOSC was 97%, which marks a significant improvement compared with that of surgical drainage. ERCP minimally invasive endoscopic treatment can therefore be used as the first-choice treatment for AOSC (27-29).

PCT is a type of glycoprotein that lacks hormonal activity. In recent years, it has been found that PCT is closely associated with deep infections, such as liver abscess and sepsis. Bacterial infection can induce the production of inflammatory factors throughout the body, and initiate the body's neuroendocrine cells, macrophages, monocytes and other cells to secrete PCT in large quantities, such that the serum PCT level is increased (30). In addition, a previous study found that PCT detection is not affected by steroid drugs or autoimmune status (including immune diseases, HIV and liver cirrhosis) and PCT is a specific indicator for the diagnosis of bacterial infection (30). An increased level of PCT detection is often indicative of a deep infection and it is also used to distinguish bacterial infection from viral infection in clinical practice. The results obtained in the present study showed that the serum PCT level in patients with AOSC was increased, although this was decreased significantly one week after ERCP in the majority of the patients. A previous study reported that the serum PCT level in patients with AOSC changed with the severity of cholangitis, although this tended to return to normal after the inflammation had been controlled (31). Following ERCP, the peripheral blood white blood cells, ALT, bilirubin and other indicators of the patients were found to be significantly decreased, the inflammatory reaction in the body was significantly controlled and so the liver function was restored and the PCT level was also significantly improved. These findings were consistent with those reported in a previous study (32). In that study, with patients with severe infection caused by bile duct obstruction, their levels of white blood cells, liver function indexes and PCT were often increased significantly, although the majority of these indexes improved significantly after the obstruction had been relieved.

CA199 is a carbohydrate antigen that has been confirmed to be associated with tumors. A previous study confirmed that CA199 is able to regulate the migration and adhesion of white blood cells in the inflammatory area, resulting in a leukocyte aggregation reaction (33). Although CA199 is a tumor marker, its expression is closely associated with biliopancreatic duct obstruction, which has also been confirmed by clinical observations. Zeng et al (34) found that the levels of CA199 and PCT were increased in patients with severe AC. Although abnormal changes in the level of CA199 do occur in malignant biliopancreatic tumors, Zhang et al (35) demonstrated that an increase in CA199 may be associated with biliopancreatic duct obstruction. When AC occurs, the serum concentration of CA199 is significantly increased, and this increase is positively correlated with the severity of cholangitis, which can therefore be used as a predictor of AC (35); a finding that was consistent with the results of the present study. It has also been shown that CA199 has certain reference value for the diagnosis of AC when it reaches a level of 52.50 kU/l (36). In the present study, there were two cases where the CA199 values were >12,000 kU/l. Following examination, it was found that there were no tumor lesions, and the level of CA199 returned to normal after ERCP. It was recently reported by Chen et al (37) that CA199 is associated with calculous cholecystitis. The level of CA199 was found to be elevated in certain patients with calculous cholecystitis but without tumor disease, whereas the level of CA199 in these patients returned to normal following cholecystectomy. Therefore, an elevated level of CA199 is not completely representative of neoplastic diseases, and it needs to be differentiated from other types of obstructive inflammatory disease.

In conclusion, the present study showed that, compared with traditional surgical drainage methods such as common bile duct incision, decompression and drainage of pus or cholecystostomy, endoscopic minimally invasive interventional therapy has a high success rate and a low incidence of postoperative bleeding, cholangitis and bile leakage (38). It can effectively relieve bile duct obstruction, reduce the difficulty of surgical clinical treatment to a certain extent, and improve the quality of life of patients. With the continuing development of endoscopic minimally invasive treatment technologies, as a treatment method, the endoscopic treatment of AOSC has the advantages of being rapid, effective, associated with lower levels of trauma, and it enables the rapid prognosis of patients, aspects that are in line with the developmental direction of modern medical therapies.