ERCP management of acute cholangitis caused by rupture of Echinococcus hepaticus into the biliary tract

Abstract

Background:

Hepatic cystic echinococcosis (HCE) rupture into the biliary tract, one of the most common and refractory complications, is treated by laparotomy to remove hydatid lesions. The aim of this article was to investigate the role of endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of this particular disease.

Patients and Methods:

This was is a retrospective analysis of 40 patients with HCE ruptured into the biliary tract in our hospital from September 2014 to October 2019. They were divided into two groups, ERCP group (group A, n = 14) and conventional surgery group (group B, n = 26). Group A was treated with ERCP first to control infection and improve the general condition before undergoing laparotomy at an optional stage while group B was treated with laparotomy directly. First, the infection parameters and liver, kidney and coagulation functions of group A patients before and after ERCP were compared to evaluate treatment effectiveness. Second, the intraoperative and post-operative parameters during the laparotomy of group A were compared with group B to evaluate the impact of ERCP treatment on laparotomy.

Results and Conclusions:

White blood cell, NE%, platelet, procalcitonin, C-reactive protein, interleukin-6, Total bilirubin (TBIL), alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, alanine transaminase (ALT), ALT and Cr in group A significantly improved by ERCP (P < 0.05); during laparotomy, the bleeding amount and hospital stay in group A were better (P < 0.05); moreover, concerning the post-operative complications, the incidence of acute renal failure and coagulation dysfunction in group A was significantly less (P < 0.05). ERCP, which not only quickly and effectively controls infection and improves the patient’s systemic condition but also provides good support for subsequent radical surgery, enjoys good prospects for clinical application.

INTRODUCTION

Echinococcosis is a near-cosmopolitan zoonosis caused by adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major species of medical and public health importance are Echinococcus granulosus and Echinococcus multilocularis, which cause cystic echinococcosis and alveolar echinococcosis, respectively, with cyst echinococcosis being the most common type. Hepatic cystic Echinococcosis (HCE) has no obvious clinical symptoms in its early stages and is only brought to the attention of patients because of its complications.[1-5] At this point, the difficulty of treatment and the prognostic risk increase substantially. HCE ruptured into the biliary tract is one of the most common and intractable complications with an incidence rate of 1%25%.[6-9] If not treated promptly, it may further develop into acute obstructive septic cholangitis with an extremely poor prognosis.[7,9-11] In order to remove hydatid lesions from the liver and biliary tract simultaneously, and the lack of ERCP technology in some medical units, the traditional treatment modality remains open surgery.[4,9,12-15] However, patients often face a high rate of post-operative complications such as severe systemic infections and even multi-organ dysfunction.[16] ERCP for this disease has been reported only rarely.[15,17-20] Given that the ERCP technique is minimally invasive and functions to safely and effectively control biliary tract infection by effectively draining the bile duct, we have adopted a staged treatment strategy utilising the technique over the past few years. ERCP was first used to control the patient’s infection and improve general condition, followed by laparotomy to remove the liver hydatid lesions, which achieved good results. In this article, we investigated the efficacy of ERCP in the improvement of infection and general condition of patients with HCE ruptured into the biliary tract, and its effect on subsequent laparotomy was observed.

PATIENTS AND METHODS

All surgeries were performed at the Department of Digestive and Vascular Surgery of the First Affiliated Hospital of Xinjiang Medical University.

The study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (No. K202109-13). All methods were carried out in accordance with relevant guidelines and regulations. The requirement for individual consent was waived by the committee because of the retrospective nature of the study.

Patients

This study was a retrospective analysis of 40 patients with HCE ruptured into the biliary tract in our hospital from September 2014 to October 2019. According to different treatment strategies, they were divided into two groups: ERCP group (group A) (14 cases) and conventional operation group (group B) (26 cases).

Diagnostic criteria of HCE ruptured into the biliary tract: intrahepatic hydatid lesions and typical Charcot triad, manifested as chills, high fever, epigastric pain and jaundice. All patients were graded greater than or equal to grade II according to the Tokyo Guidelines for acute cholangitis.

The most important diagnostic methods are ultrasound, computed tomography (CT) and nuclear magnetic resonance imaging, which are manifested in the expansion of intrahepatic and extrahepatic hepatic ducts. It can even be seen that the expanded bile duct is connected with hydatid, and the cyst of hydatid ruptured into the bile duct.

Operation mode

ERCP group (group A)

ERCP was first performed to control the patient’s infection and improve the systemic condition. The patient was given intravenous anaesthesia and electrocardiogram monitoring during the operation. Olympus TJF-260 electronic duodenoscope was used. Under X-ray fluoroscopy, the imaging of intrahepatic and extrahepatic bile ducts was visualised, and the structural changes of the biliary tract, the degree of biliary dilatation, the location of fistula where hydatid cyst ruptured into the biliary tract and foreign bodies in common bile duct were identified [Figure 1]. According to the location and size of the echinococcal cavity biliary fistula, suitable stent was implanted for internal drainage to ensure smooth biliary drainage. The choice of stent length was determined by the location of hydatid cavity-bile duct fistula after cholangiography. In general, the stent should be placed above the fistula to prevent re-obstruction by the contents of the hydatid cavity. Patients were discharged after the symptoms were relieved and all indexes returned to normal, and were asked to come to the hospital for re-examination 1 month later.

Figure 1.

(a) ERCP angiography showed the location of hydatid cavity, hydatid internal capsule and biliary fistula. (b) ERCP removes the hydatid cyst ruptured into the common bile duct. ERCP: Endoscopic retrograde cholangiopancreatography

About a month later, laparotomy surgery was performed to completely remove the hydatid lesions. The operation was performed in the same way as the conventional operation described below.

Conventional operation group (group B)

Laparotomy was performed directly. After the liver was protected by gauze with hypertonic saline, the outer wall of the sac was opened, and the inner sac was carefully removed to extract the sac fluid. The residual cavity was thoroughly cleaned with 20% hypertonic saline. The external capsule should be removed as much as possible. The common bile duct was thoroughly explored and the internal hydatid cysts, subcapsules and debris in the bile duct were carefully cleaned. The fistula between echinococcosis and bile duct is usually located in the secondary bile duct and can be easily detected by injection of methylene blue solution into the bile duct. The fistula can be directly sutured or T-tube can be placed at the fistula according to the size and position of the fistula. Another T-tube was placed in common bile duct for biliary decompression, and drainage tube was placed in residual cavity of the hydatid cyst. The surgical details of the two T-tubes were described in detail in the previous study [Figure 2].[21]

Figure 2.

(a) The punctured inner sac is removed from the common bile duct. (b) Methylene blue solution was injected into T-tube to explore the fistula between hydatid cavity and biliary tract. (c) T-tubes were placed in the common bile duct and biliary fistula. (d) Post-operative cholangiography showed that the T-tube at the fistula was located in the right hepatic duct

Observed items

The infection parameters, liver function, kidney function and coagulation function of group A patients within 24 h before and 1, 3 and 5 days after treatment with ERCP were compared to evaluate the effectiveness of the treatment.

The intraoperative and post-operative conditions, intraoperative blood loss, length of hospital stay and post-operative biliary fistula were compared between group A and group B. The results of liver function, kidney function, coagulation function and arterial blood gas analysis on the 3 days after operation were compared between the two groups. These results were performed to evaluate the impact of ERCP treatment on laparotomy.

Definitions

• Acute renal dysfunction: according to the Second International Consensus Conference of the Acute Dialysis Quality Initiative Group in 2004

• Coagulation disorders: The coagulation test was out of the normal range

• Respiratory failure: at rest breathing air at sea level if, because of impaired respiratory function, the arterial blood pO2 is below 60 mmHg or the pCO2 is above 49 mmHg.

Statistical methods

Statistical analyses were performed with SPSS 26.0 (SPSS Inc., Chicago, IL, USA). Non-parametric continuous variables were expressed as mean ± standard deviation or median and range. Fisher’s exact test or Chi-square test was used for univariate analysis with dichotomous variables, while unpaired t-test was used for non-parametric continuous variables. P < 0.05 was considered statistically significant.

RESULTS

There were 14 patients, including 5 males and 9 females, with an average age of 40.42 years (range, 3559 years) in group A, and there were 26 patients, including 12 males and 14 females, with an average age of 48.65 years (range, 2268 years) in group B.

Compared with the condition before ERCP, the aspartate transaminase, alanine transaminase and ALB at the 1^st day after ERCP, interleukin-6 and Cr at the 3^rd day and white blood cell, NE%, procalcitonin, C-reactive protein, platelet, TBIL, alkaline phosphatase and gamma-glutamyl transpeptidase at the 5^th day were improved dramatically (P < 0.05), but there were no significant differences in coagulation function (prothrombin time [PT], international normalised ratio, Fibrinogen (FIB), activated partial thromboplastin time, thrombin time and PT%) before and after ERCP (P > 0.05) [Tables 1 and 2].

Table 1.

Comparison of infection parameters before and after endoscopic retrograde cholangiography in Group A patients

	Within 24 h before ERCP	1 day after ERCP	3 days after ERCP	5 days after ERCP	P
WBC (109/L)	13.71±8.31	13.34±5.88	11.90±6.10	8.70±3.72	5 days=0.039
NE (%)	84.60±8.53	82.21±10.00	81.69±9.51	76.33±9.96	5 days=0.026
PCT (ng/mL)	18.54±28.71	19.89±30.52	6.52±10.62	1.91±2.44	5 days=0.044
CRP (mg/L)	89.89±67.22	93.57±72.17	70.52±52.40	47.15±33.67	5 days=0.031
IL-6 (pg/mL)	1191.27±2232.28	720.90±1462.62	50.19±69.58	50.27±75.44	3 days=0.028
PLT (/L)	146.67±70.90	136.06±66.15	125.85±58.60	178.61±74.41	5 days=0.271

ERCP: Endoscopic retrograde cholangiography, WBC: White blood cell, PCT: Procalcitonin, CRP: C-reactive protein, PLT: Platelet, IL-6: Interleukin-6, NE: Neutrophilicgranulocyte

Table 2.

Comparison of changes in serum biochemical tests before and after endoscopic retrograde cholangiography treatment in Group A patients

	Within 24 h before ERCP	1 days after ERCP	3 days after ERCP	5 days after ERCP	P
TBIL (µmol/L)	131.48±87.26	101.40±68.20	84.32±76.63	60.38±51.87	5 days=0.008
AST (U/L)	238.22±284.06	207.23±272.81	148.63±217.76	51.43±29.89	1 days=0.045
ALT (U/L)	252.63±293.76	205.22±241.92	157.86±229.62	67.01±48.81	1 days=0.045
ALP (U/L)	322.05±335.20	245.48±247.11	288.62±344.30	165.25±209.29	5 days=0.024
GGT (U/L)	495.54±429.20	355.14±295.46	307.99±278.75	203.83±152.50	5 days=0.032
Albumin (g/L)	37.19±8.30	29.19±6.01	29.89±4.22	27.93±5.32	1 days=0.000
Creatinine (µmol/L)	109.49±73.89	87.96±44.18	79.11±42.21	65.44±37.79	3 days=0.025
PT (s)	16.59±6.74	16.12±3.94	14.28±2.76	19.37±12.40	5 days=0.519
INR	1.51±0.78	1.41±0.35	1.24±0.24	1.69±1.07	5 days=0.676
FIB (g/L)	6.18±6.29	3.77±1.63	4.15±1.59	4.34±1.87	5 days=0.463
APTT (s)	34.17±6.79	36.38±9.87	34.38±5.39	34.97±7.25	5 days=0.808
TT (s)	18.24±2.54	19.69±3.53	19.43±3.17	19.59±4.68	5 days=0.410
PT (%)	62.01±30.50	56.79±20.41	70.47±27.65	58.22±29.99	5 days=0.793
BUN (mmol/L)	10.05±7.40	7.64±5.61	7.22±4.88	6.43±3.27	5 days=0.380

ERCP: Endoscopic retrograde cholangiography, AST: Aspartate transaminase, ALT: Alanine transaminase, ALP: Alkaline phosphatase, GGT: Gamma-glutamyl transpeptidase, PT: Prothrombin time, INR: International normalised ratio, APTT: Activated partial thromboplastin time, TT: Thrombin time, BUN: Blood urea nitrogen, FIB: Fibrinogen, TBIL: Total bilirubin

The general information of group A before ERCP and group B before operation was compared. The results showed that there was no significant difference in general information (P > 0.05) [Table 3].

Table 3.

Comparison of general pre-operative and pre-operative data of Group A and Group B before endoscopic retrograde cholangiography and related indicators

	Group A (n=14)	Group B (n=26)	P
Gender
Male	5	12	0.504
Female	9	14
History of chronic hepatitis B	2	3	0.643
Age	49.8±7.51	48.15±8.23	0.326
WBC (109/L)	14.75±4.16	15.27±4.32	0.118
PCT (ng/mL)	10.51±2.14	11.38±1.61	0.435
AST (U/L)	216.71±57.43	186.24±64.32	0.458
ALT (U/L)	367.3±81.72	386.74±76.51	0.659
TBI (µmol/L)	178.46±62.31	162.44±43.31	0.563
ALP (U/L)	411.75±103.69	397.17±92.39	0.503
GGT (U/L)	199.34±46.59	211.48±74.62	0.792
Albumin (g/L)	33.75±5.71	35.04±4.63	0.864

WBC: White blood cell, PCT: Procalcitonin, Aspartate transaminase, ALT: Alanine transaminase, ALP: Alkaline phosphatase, GGT: Gamma-glutamyl transpeptidase, TBI: Total bilirubin

The difference between intraoperative blood loss and length of hospital stay was statistically significant (P < 0.05), but the difference of operation time was not (P > 0.05) [Table 4].

Table 4.

Comparison of conditions before and after laparotomy between the two groups

	Group A (n=14)	Group B (n=26)	Inspection value (t)	P
Operation time (min)	131.42±32.53	134.11±42.15	0.431	0.591
Intraoperative blood loss (mL)	143.73±38.25	188.24±35.47	2.519	0.018
Post-operative hospital stay (days)	6.23±2.49	11.34±2.61	2.832	0.026

In group A, complications occurred in 3 cases (21.43%), including 1 case of acute renal dysfunction (7.14%), 1 case of residual biliary fistula (7.14%) and 1 case of acute respiratory failure (7.14%). There were 24 cases of complications (92.31%), which include 8 cases of coagulation dysfunction (30.77%), 12 cases of acute renal dysfunction (46.15%), 2 cases of acute respiratory failure (7.69%) and 2 cases of residual cavity biliary fistula (7.69%) in group B. There were significant differences in acute renal failure and coagulation dysfunction between the two groups (P < 0.05). There was no significant difference in respiratory dysfunction and residual bile leakage (P > 0.05) [Table 5].

Table 5.

Comparison of complications after laparotomy between two groups

	Group A (n=14)	Group B (n=26)	χ 2	P
Acute renal dysfunction	1	12	6.313	0.012
Coagulation disorders	0	8	5.385	0.020
Respiratory failure	1	2	0.004	0.949
Biliary fistula	1	2	0.004	0.949

Follow-up

As of 1 July 2020, a total of 30 patients were followed up, with a follow-up rate of 75%. In the follow-up population, 12 patients in group A and 18 patients in group B had no long-term complications such as recurrence of hydatid cyst in situ and biliary stricture.

DISCUSSION

HCE grows expansively, stimulating the surrounding normal liver tissue to form an external capsule. In the process of gradually increasing, the external capsule compresses the adjacent intrahepatic bile duct, resulting in bile duct wall ischaemia and necrosis. The pressure in the hydatid cyst is 3080 cm H₂O, and the pressure in bile duct is 1520 cm H₂O.[15] The unbalanced pressure between hydatid cyst and bile duct makes the cysts and debris in hydatid cyst easy to rupture into the bile duct. As one of the most common complications of hydatid disease, especially in the endemic area of hepatic hydatid disease, if patients with HCE have symptoms such as abdominal pain, chills, high fever and jaundice, and imaging studies such as ultrasound, abdominal CT and magnetic resonance cholangiopancreatography suggest intrahepatic cystic occupations and varying degrees of dilatation of the common bile duct, the possibility of HCE ruptured into the biliary tract should be considered first. Due to the specific aetiology, its radical treatment was still dominated by laparotomy.

ERCP, as an important method for the treatment of benign and malignant biliary diseases,[22,23] has the advantages of minimally invasive and rapid remission of biliary tract infection.[15,24] It is mainly used in the management of biliary leakage after surgery for echinococcosis, and there had been successful cases of treatment of HCE into the biliary tract, but the reports were mostly in the form of case report. As a medical institution in a region with a high prevalence of echinococcosis, we had also taken advantage of ERCP to adopt a staged approach to this disease, which is similar to ‘damage control surgery’. We first performed biliary drainage with endoscopic cholangiography to effectively remove biliary obstruction in a minimally invasive manner. After infection control and organ function improvement, Echinococcus excision was selected and a good therapeutic effect was achieved. Toumi et al.[25] report that the same treatment has had good results. All 12 patients were successfully treated with ERCP, which effectively alleviated infection and improved liver and kidney function without complications. Three cases after ERCP developed a transient high fever without further aggravation. There may be two reasons: (1) acute cholangitis after hepatic hydatid cyst ruptured into the biliary tract has not been completely relieved. (2) It is caused by self-stress reaction after ERCP.

Cases of complete removal of the contents of the lesions in the liver using the ERCP technique alone, while avoiding laparotomy, had been reported.[18,19,26-28] However, in our experience, complete endoscopic removal of the encapsulated cysts accounted for only a small percentage of cases due to the limitations of the large size of the encapsulated cysts, the large contents and the small diameter of the encapsulated fistula in most patients. Most patients (75%) still required laparotomy to achieve complete removal of the intrahepatic lesion and repair of the biliary fistula opening to prevent complications such as recurrence and bile accumulation in the encapsulated cavity for infection.[15] More often than not, ERCP is used as an effective means of biliary drainage to control infection. Our results also demonstrated that ERCP provides good support for the efficacy of subsequent laparotomy. By comparing the intraoperative and post-operative conditions of the two groups at the stage of laparotomy, it can be seen that the infection, systemic inflammatory response and organ dysfunction of patients after the ERCP had been corrected, which was conducive to the subsequent surgery. This staged approach reduced the amount of intraoperative bleeding, post-operative hospital stay and post-operative complications. Post-operative bile leakage is the most common complication due to the large fistulas between the hydatid cavity and biliary tract. ERCP is beneficial to the reduction of bile pressure and helps to improve the incidence of bile leakage. Most patients can self-heal even if they develop a bile leak after surgery due to the low-pressure state of the bile duct. There was no difference in the occurrence of bile leak between our two groups, probably because we routinely placed a T-tube in the common bile duct intraoperatively.

This staged treatment measure has its advantages and deficiency. Its advantages are as follows: (1) ERCP can relieve the infection and improve the overall state of the patient, which is conducive to the recovery of the second surgery. (2) The position of the common bile duct can also be indicated by the biliary stent during the operation, which is helpful to identify the anatomical relationship between the bile duct and the bile duct break, and avoid the accidental injury of the bile duct during the laparotomy. (3) The occurrence of biliary fistula after the removal of hepatic hydatid cyst is positively correlated with the pre-operative common bile duct pressure and the severity of cholestasis. ERCP indwelling biliary stent can reduce the biliary pressure. The deficiency lies in: (1) there was a time interval between the two treatments (the mean time between treatments was 25.5 days in 12 patients), and the whole treatment process will be long, which may bring a certain psychological impact on the patient. 3P has the possibility of unsuccessful intubation and ineffective biliary drainage. (3) As an invasive procedure, ERCP itself has the risk of pancreatitis, bleeding, infection and perforation. In addition, this was a retrospective study in a small number of patients from a single centre. Thus, more cases and longer follow-up time are necessary.

CONCLUSIONS

ERCP plays important role in the treatment of acute suppurative cholangitis caused by hepatic hydatid rupture into the bile duct. It not only can quickly and effectively control the infection and improve the patient’s systemic status but also can provide good support for subsequent radical surgery. Therefore, it has good prospects for clinical application.

Financial support and sponsorship

This work was supported by the Natural Science Foundation of Xinjiang Province Project: Experimental study on the role of miRNA-HNFL α in regulating the fibrosis of the outer capsule wall in hepatic cystic echinococcosis (2018D01C222).

Conflicts of interest

There are no conflicts of interest.