Internal versus external biliary drainage in malignant biliary obstructions: is there a difference in the rate of infection?

Abstract

Background

Percutaneous biliary drainage is a frequently used method to provide biliary decompression in patients with biliary obstruction.

Purpose

To investigate the between drainage type and infection risk in patients treated with internal-external and external biliary drainage catheterization for malignant biliary obstruction.

Material and Methods

A total of 410 patients with malignant biliary obstruction who underwent internal-external or external biliary drainage catheterization between January 2012 and October 2016 were retrospectively evaluated. We investigated the correlation between percutaneous biliary drainage technique and infection frequency by evaluating patients with clinical findings, bile and blood cultures, complete blood counts, and blood biochemistry.

Results

There was no statistically significant difference between the selected patient groups (internal-external or external biliary drainage catheter placed) in terms of age, sex, primary diagnosis, receiving chemotherapy, catheter sizes, and outpatient-patient status. After catheterization, catheter-related infection was observed in 49 of 216 (22.7%) patients with internal-external and 18 of 127 (14.2%) patients with external biliary drainage catheters, according to the defined criteria. There was no difference in infection rate after the biliary drainage in the two groups (P > 0.05). There was also no difference concerning frequently proliferating microorganisms in bile cultures.

Conclusion

Internal-external biliary drainage catheter placement does not bring an additional infection risk for uninfected cholestatic patients whose obstruction could be passed easily in the initial drainage.

Keywords

Complication biliary drainage infection percutaneous

Introduction

Internal or external biliary drainage catheters are introduced to ensure biliary decompression, palliative or preoperatively in patients with malignant biliary obstruction (1). It is called an internal-external biliary drainage catheter (IEBDC) if the tip of the catheter is placed into the duodenal lumen through the stenotic segment and an external biliary drainage catheter (EBDC) if the stenotic segment cannot be passed and the tip is placed into biliary ducts (2).

The complication rate has been reported to be in the range of 3%–10% during and after percutaneous biliary drainage (PBD) (3). These have been classified as biliary access-related, non-vascular, vascular, bleeding-related, and catheter-related complications. Pain at the insertion site, subcapsular hematoma, and bile duct perforation can also occur. Catheter-related complications can be infective (e.g. cholangitis, bilioma, pancreatitis) or vascular (e.g. bilioarterial-biliovenous fistula, pseudoaneurysm), as well as catheter fracture or folding during the procedure (4).

Post-PBD infection is a significant cause of mortality and morbidity. Insufficient sterilization before the procedure and inappropriate prophylactic antibiotic usage can be potential underlying causes. Infection risk is probably higher in malignant biliary obstructions compared to benign obstructions (5). Multiple stenoses in intra-extrahepatic bile ducts could be the cause. Furthermore, bile leakage is an essential parameter regarding infection by being a source for bacterial proliferation and propagation (5,6).

The aim of the present study was to evaluate the relationship between drainage type and infection risk by considering bile and/or blood culture, blood biochemistry, and clinical findings in patients with IEBDC or EBDC for malignant biliary obstruction.

Material and Methods

Patient analysis and data collection

A total of 410 patients with IEBDC or EBDC for malignant biliary obstruction between January 2012 and October 2016 were retrospectively evaluated. All procedures were performed by the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. The study protocol was approved by the local ethics committee (approval no. 2016-18/11).

The following patients were excluded from the study: those with a biliary stent placement; with any operation performed, such as cholecystectomy, Whipple procedure, and tumor surgery within the previous 15 days; and/or those with an active infection during catheter placement. Finally, 343 patients were included in the study. The scanned parameters were age, sex, primary diagnosis, inpatient/outpatient status, receiving chemotherapy during the procedure, catheter type (external-internal), proliferation in bile or blood cultures, infection markers (body temperature >38 °C and fever or chills), blood leukocyte count, absolute neutrophil count, and C-reactive protein (CRP). Bile cultures were collected in patients routinely if possible, and blood cultures were collected if infection was suspected. A complete blood count was made to support catheter-related infection parameters at the same time.

Catheter-related infection was defined as significant proliferation in bile or blood cultures accompanied by fever and chills, increased blood leukocyte count (≥10,000 k/mm³), increased neutrophil count (≥75%), high CRP levels (≥0.5 mg/dL) in the 15 days after catheterization (Table 1). Cases with positive bile or blood cultures but no clinical and laboratory findings were accepted as contamination.

Table 1.

Catheter-related infection criteria.

Criteria for catheter-related infection
After biliary drainage for 15 days
Bile or blood culture (+)
Fever (≥38.0 °C) and chills
Leukocytosis ≥10,000 k/mm³
Neutrophilia (≥75%)
C-reactive protein >0.5 mg/dL

Procedure

Patient preparation

PBD was performed in the interventional diagnosis and treatment unit. The sufficiency of procedures was checked by controlling the general health and consciousness of every patient. Preoperative coagulation parameters (platelet count >50,000, INR <1.5) were controlled in all patients. In patients receiving anticoagulants, it was recommended to stop the drug five days before the procedure. Blood pressure, oxygen saturation, pulse, and heart rhythm were monitored in all patients during the procedure. An intravenous prophylactic antibiotic was given before all procedures.

All biliary drainage catheters were placed with guided ultrasonography and fluoroscopy. Catheters were checked using fluoroscopy in all patients. A hemorrhage occurred during the procedure in only one patient (planned IEBDC), but it was completed successfully after ensuring hemodynamic balance.

After skin preparation, 2% lidocaine was injected with a 21–22-G needle and the puncture was initiated by advancing the needle through the skin into the liver. The needle was monitored with the help of ultrasound guidance. Then, a 22-G Chiba needle was introduced into the most appropriate hepatic duct branch. Under fluoroscopy guidance, a 0.018–0.020-inch guidewire was introduced through the Chiba needle into the hilum and, if possible, into the main hepatic duct (Accustick set; Medi-tech/Boston Scientific, Watertown, MA, USA). An introducer was inserted while the inner shelf and the needle were extracted. The formerly introduced guidewire was replaced with another 0.038-inch wire (Terumo Medical, Tokyo, Japan). Then, appropriate dilators were advanced through the guidewire. After that, a 7–10-F multi-hole percutaneous biliary drainage catheter was introduced (Argon Medical Devices, Athens, GA, USA).

Statistical analysis

Statistical analyses were carried out using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). A Mann–Whitney U test was used to compare two independent samples with abnormally distributed data. The categorical data were analyzed with Pearson chi-square and Fisher–Freeman–Halton tests. The level of significance was determined as P < 0.05.

Results

The mean age of 216 patients with IEBDC and 127 patients with EBDC was 68.5 years (range = 30–94 years) and 69 years (range = 29–91 years), respectively (P = 0.856). Of the 216 patients who had an IEBDC, 86 (39.8%) were women and 130 (60.2%) were men. Of the 127 patients who had an EBDC, 49 (38.6%) were women and 78 (61.4%) were men (P = 0.822). Of the 216 patients with IEBDC, the primary pathology was a periampullary tumor in 111 (51.4%), cholangiocarcinoma in 53 (24.5%), gallbladder carcinoma in 16 (7.4%), hepatocellular carcinoma in 8 (3.7%), and liver metastases in 28 (13%) patients. Of the 127 patients with EBDC, the primary pathology was a periampullary tumor in 85 (66.9%), cholangiocarcinoma in 23 (18.1%), gallbladder carcinoma in 6 (4.7%), hepatocellular carcinoma in 4 (3.1%), and liver metastases in 9 (7.1%) (Table 2). The most common tumors in both groups were similar, and no significant difference was found (P = 0.078).

Table 2.

Primary diagnosis of patients with internal-external and external drainage catheters.

Primary diagnosis	Internal-external biliary drainage catheter (N)	External biliary drainage catheter (N)
Periampullary tumor	111 (51.4)	85 (66.9)
Cholangiocarcinoma	53 (24.5)	23 (18.1)
Gallbladder tumor	16 (7.4)	6 (4.7)
Hepatocellular carcinoma	8 (3.7)	4 (3.1)
Liver metastasis	28 (13)	9 (7.1)

Values are given as n (%).

While 181 of 216 (83.8%) patients with an IEBDC were inpatients and 35 (16.2%) were outpatients, 111 of 127 (87.4%) patients with an EBDC were inpatients and 16 (12.6%) were outpatients (P = 0.365). Of the 216 patients who had an internal biliary drainage catheter, 189 (87.5%) were not receiving chemotherapy at the time of catheterization, while 27 (12.5%) patients were receiving chemotherapy; of the 127 patients who had an EBDC, 107 (84.3%) were not receiving chemotherapy and 20 (15.7%) were receiving chemotherapy. There was no significant difference between the two groups in terms of receiving chemotherapy (P = 0.348). Of the 216 patients who had an IEBDC, 187 (86.6%) had 7-F, 21 (9.7%) 8-F, and 8 (3.7%) 8.5-F catheters, while of the 127 patients who had an EBDC, 108 (85%) had 7-F, 13 (10.2%) 8-F, 5 (3.9%) 8.5-F, and 1 (0.8%) 10-F catheters (all Argon Medical Devices, Athens, GA, USA). Only one patient (with a planned IEBDC) developed bleeding complications during the procedure, and the catheter was successfully inserted after the hemodynamics were improved. Apart from this, no complications that would trigger infection were encountered.

There was no significant statistical difference between the two groups (IEBDC or EBDC) regarding age, sex, primary diagnosis, receiving chemotherapy, dimensions of catheters, and inpatient-outpatient status (Table 3). The absence of a statistically significant difference between these findings indicates that the groups were homogeneously distributed.

Table 3.

Statistical comparison between two groups.

	P values
Age	0.856
Sex	0.822
Primary diagnosis	0.078
Receiving chemotherapy	0.348
Size of catheters	0.698
Inpatient-outpatient	0.365
Bile culture positivity	0.44

Significant bacterial growth was detected in 96 of 168 patients whose bile cultures were performed. Bile culture was made in 108 of 216 (50%) patients with IEBDC and 60 of 127 (47%) patients with EBDC. There was no significant difference between the two groups concerning bile culture proliferation (P = 0.44).

A total of 59 patients had blood cultures performed. Growth in blood cultures was detected in 9 of 45 (20%) patients who had an IEBDC and 3 of 14 (21.4%) patients who had an EBDC. When the blood culture results of the two groups were evaluated, no significant difference was found (P = 0.06).

Significant growth was detected in 108 of 227 patients whose bile and blood cultures were performed. In addition to culture positivity, 67 of 108 patients had a fever of ≥38 °C, leukocytosis, neutrophilia, and elevated CRP, which met the criteria for infection. Although bile and/or blood culture positivity was present in 41 patients, it was not considered a catheter-related infection because there were no other accompanying infection parameters. Catheter-related infection was detected in 49 of 216 (22.7%) patients in the IEBDC group and 18 of 127 (14.2%) patients in the EBDC group. There was no significant difference between the two groups (P > 0.05).

Discussion

The aim of the present study was to evaluate the relationship between drainage type and infection risk in patients treated with IEBDC or EBDC for malignant biliary obstruction. In these patients, palliative percutaneous biliary drainage is performed when it is not possible to perform curative surgery because of co-morbid diseases, vascular invasion, distant metastasis, and so on. In this way, it can contribute to reducing jaundice and jaundice-related infectious and neurologic complications. In patients with very high blood bilirubin levels, jaundice-related surgical complications can be prevented by correcting blood bilirubin levels with preoperative PBD (5 –7).

Various complications can happen before, during, and after the PBD procedure and in the long term. The most frequently seen complications are intraabdominal hemorrhage, subcapsular hematoma, aneurysm, arteriovenous shunts/fistulas, cholangitis, fever, sepsis, septic shock, intraabdominal bile leakage, bile peritonitis, hemobilia, hemothorax, pneumothorax, subphrenic-hepatic abscess, electrolyte imbalance, hypotension, catheter dislocation, and peri-catheter bile leakage. The complication with the highest mortality and morbidity rate is infection (4,8 –11).

Ho et al. reported that high blood bilirubin levels cause damage to the intestinal mucosa and thus provide a basis for bacterial translocation (11). Yee and Ho reported cholangitis, which could be controlled with antibiotics, in 46 of 152 (30%) patients with malignancy after PBD (12). Xu et al. reported biliary infection in 83 of 193 (43%) patients with malignant biliary obstruction after PBD (13). In our study, biliary infection developed in 67 of 343 (19.5%) patients after catheterization, and it was found between the reported limits in the literature.

We investigated whether two different catheter methods in patients with performed PBD increases the risk of infection. Although inserting the catheter into the duodenum (internal type) has advantages, such as better bile physiology, catheter stability, and lower electrolyte loss, it can be concluded that it would be inappropriate because of increased cholangitic complication risk at the first procedure.

In one of the limited studies in the literature, Xu et al. reported higher infection rates in patients with IEBDC than in patients with EBDC. The infection rate was 52.4% in the IEBDC group and 27.9% in the EBDC group. They associated the increased infection rate with ascending propagation of intestinal flora into the biliary system through the catheter and approaching bacteria to the biliary system more easily because of lower pressure inside the drainage pack than the intestinal lumen (13). Despite limited literature data, in our wide-ranging study, catheter-related infection was detected in 49 of 216 (22.7%) patients with IEBDC and 18 of 127 (14.2%) patients with EBDC. There was no significant statistical difference between the two groups (P > 0.05).

Ozden et al., in their study about catheter-related infection without concerning catheter type, and Kaya et al., in their study, suggested some mechanisms in the development of biliary infections in patients with PBD. These can be aligned as direct exogenous seeding into bile ducts through PBD catheters, retrograde transportation of intestinal flora into the biliary system, and hematogenous spread (13–15). We also conclude in our study that these mechanisms could have led to biliary infection after catheterization.

Kaya et al. reported that most of the bacteria found in bile cultures originate from the intestinal flora. Escherichia coli, Pseudomonas, Klebsiella, Enterococcus, and Enterobacteriaceae are the most reported microorganisms (15). Although these defined mechanisms present reasonable explanations, which mechanism is responsible for each patient is controversial. We detected on bile culture proliferation of E. coli in 18 (36%), Klebsiella pneumonia in 6 (12%) and Enterococcus faecalis in 6 (12%) of 49 patients with IEBDC, and E. coli in 6 (33%), Klebsiella pneumonia in 3 (16%), and Enterococcus faecalis in 2 (11%) of 18 patients with EBDC. The most common three agents were similar in the 12 patients with positive blood culture. Most frequently, three agents were the same in the two groups. Although bacteria-causing infections have mostly enteric origins, the fact that the same microorganisms proliferate in the EBDC group indicates that bacterial translocation is not associated only with the internal advancement of the catheter.

On the other hand, An inflammatory response caused by the forced passing of an obstructed segment can increase the risk of infection. For this reason, harsh internal passage manipulations were avoided, and an external drainage route was preferred if the first trial was difficult.

The present study has some limitations. Data reliability is more limited than a prospective method in this retrospective study because patients could not be followed one-to-one after procedures and parameters were obtained from patients’ electronic files. On the other hand, the number of patients, higher number of inpatients (which could be followed more closely) than outpatients, and indifference between the two groups with demographic characteristics can be listed as the strengths of the study.

In conclusion, PBD is the preferred treatment in patients with a malignant biliary obstruction to prevent biliary stasis in the preoperative period and inoperable cases as a palliative treatment option. We found no significant difference in the development of biliary infection between the IEBDC and EBDC groups. We conclude that IEBDC placement is more convenient if obstructed segments can be passed easily at the first attempt.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Gokhan Ongen

Omer Fatih Nas

References

Brown

Covey

. Management of malignant biliary obstruction. Tech Vasc Interv Radiol 2008;11:43–50.

Covey

Brown

. Percutaneous transhepatic biliary drainage. Tech Vasc Interv Radiol 2008;11:14–20.

Weber

Gaa

Rosca

, et al. Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts. Eur J Radiol 2009;72:412–417.

Nanda

Karthik

Apoorva

. Diagnosis and management of complications from percutaneous biliary tract interventions. Radiograp 2017;37:665–680.

Daniel

Wael

Saad

, et al. Incidence of cholangitis and sepsis associated with percutaneous transhepatic biliary drain cholangiography and exchange: a comparison between liver transplant and native liver patients. AJR Am J Roentgenol 2011;196:73–77.

Herzog

Belyaev

Hessam

. Bacteribilia with resistant microorganisms after preoperative biliary drainage the influence of bacteria on postoperative outcome. Scand J Gastroenterol 2012;47:827–835.

Lofts

Evans

Mansi

, et al. Bile duct stents: is there an increased rate of complications in patients receiving chemotherapy. Eur J Cancer 1997;33:209–213.

Saad

WEA

Wallace

Wojak

, et al. Quality improvement guidelines for percutaneous transhepatic cholangiography, biliary drainage, and percutaneous cholecystostomy. J Vasc Interv Radiol 2010;21:789–795.

Winick

Waybill

Venbrux

. Complications of percutaneous transhepatic biliary interventions. Tech Vasc Interv Radiol 2001;4:200–206.

10.

Nomura

Shıraı

Hatakeyama

. Bacteribilia and cholangitis after percutaneous transhepatic biliary drainage for malignant biliary obstruction. Dig Dis Sci 1999;44:542–546.

11.

Warkentin

. Evidence-based decompression in malignant biliary obstruction. Korean J Radiol 2013;13:56–61.

12.

Yee

. Complications of percutaneous biliary drainage: benign vs malignant diseases. AJR 1987;148:1207–1209.

13.

Huang

Wang

, et al. Comparison of infection between internal external and external percutaneous transhepatic biliary drainage in treating patients with malignant obstructive jaundice. Asian Pac J Cancer Prev 2015;16:2543–2546.

14.

Ozden

Tekant

Bilge

. Endoscopic and radiologic interventions as the leading causes of severe cholangitis in a tertiary referral center. Am J Surg 2005;189:702–706.

15.

Kaya

Bestas

Bacalan

, et al. Microbial profile and antibiotic sensitivity pattern in bile cultures from endoscopic retrograde cholangiography patients. World J Gastroenterol 2012;18:3585–3589.