- Email: [email protected]
Cholangitis and Liver Abscess after Percutaneous Ablation Therapy for Liver Tumors: Incidence and Risk Factors
Cholangitis and Liver Abscess after Percutaneous Ablation Therapy for Liver Tumors: Incidence and Risk Factors Toshiya Shibata, MD, Yuzo Yamamoto, MD, Naritaka Yamamoto, MD, Yoji Maetani, MD, Toyomichi Shibata, MD, Iwao Ikai, MD, Hiroaki Terajima, MD, Etsuro Hatano, MD, Takeshi Kubo, MD, Kyo Itoh, MD, and Masahiro Hiraoka, MD
PURPOSE: To determine the risk factors of cholangitis and liver abscess occurring after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS: Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total of 683 ablation procedures, such as percutaneous ethanol injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency (RF) ablation therapy. With a retrospective review of medical records, the rates and outcomes of cholangitis and/or liver abscess occurring after ablation therapy were evaluated. The relationship between cholangitis and/or liver abscess and multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotics administration) were statistically analyzed. RESULTS: Cholangitis and/or liver abscess occurred in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions after PMC, and one session after RF ablation. Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. On stepwise regression analysis, bilioenteric anastomosis was the sole significant predictor of cholangitis and/or liver abscess formation (P < .001; odds ratio ⴝ 36.4; 95% CI ⴝ 9.67–136.9). CONCLUSION: Bilioenteric anastomosis strongly correlated with the development of cholangitis and/or liver abscess after percutaneous ablation therapy. Close posttreatment attention should be paid to this subgroup of patients. J Vasc Interv Radiol 2003; 14:1535–1542 Abbreviations:
HCC ⫽ hepatocellular carcinoma, PEI ⫽ percutaneous ethanol injection, PMC ⫽ percutaneous microwave coagulation, RF ⫽ radiofrequency
PERCUTANEOUS ablation therapy, such as percutaneous ethanol injection (PEI), percutaneous microwave coag-
From the Departments of Diagnostic Imaging and Radiology (T.S., Y.M., T.S., T.K., K.I., M.H.) and Gastroenterological Surgery (Y.Y., N.Y., I.I., H.T., E.H.), Kyoto University Graduate School of Medicine, Shogoin, Sakyoku, Kyoto, 606-8507, Japan. Received April 22, 2003; revision requested June 5; revision received July 29; accepted July 31. From the 2003 SIR Annual Meeting. Address correspondence to Toshiya Shibata; E-mail: [email protected] None of the authors have identified a potential conflict of interest. © SIR, 2003 DOI: 10.1097/01.RVI.0000099532.29957.4F
ulation (PMC), radiofrequency (RF) ablation therapy, and interstitial laser photocoagulation, is an effective, minimally invasive treatment for small liver tumors (1–12). The most common complications of percutaneous ablation therapy are abdominal pain and low-grade fever that last only a few days. The ablation techniques are considered safe: major complications have been reported, but only rarely (1–12). Infections such as cholangitis and liver abscess are rare complications but may be severe sometimes, necessitating interventional procedures (13,14). Conversely, several studies have suggested that bilioenteric anastomosis is a possible risk factor for liver abscess
formation after transcatheter arterial embolization (15–17). Another study (18) has suggested that biliary abnormality prone to ascending biliary infection, such as endoscopic papillotomy, bilioenteric anastomosis, bilioenteric fistula, external biliary drainage, and pneumobilia, is the most important predisposing factor to the development of liver abscess after transcatheter arterial embolization. A few case studies have shown that liver abscess occurs after percutaneous ablation therapies in patients with bilioenteric anastomosis (14,19). In establishing a safety guideline, it is important to know the risk factors of cholangitis and liver abscess after per-
1535
1536
•
Cholangitis and Liver Abscess after Ablation Therapy
cutaneous ablation therapy. The purpose of our study is to evaluate outcomes of cholangitis and liver abscess after percutaneous ablation therapy and to determine the risk factors.
MATERIALS AND METHODS Patients Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total 683 sessions of percutaneous ablation therapy. The study population included 275 men and 83 women aged 14 – 83 years. Three hundred five patients had hepatocellular carcinoma (HCC) and 53 patients had metastatic liver tumor. Primary lesions were colorectal carcinoma in 34, cholangiocarcinoma in four, gallbladder carcinoma in four, breast carcinoma in three, gastric carcinoma in two, esophageal carcinoma in two, lung carcinoma in two, pancreatic carcinoma in one, and gastrointestinal stromal tumor in one. Our standard criteria used for selection of patients for percutaneous ablation therapy included the presence of no more than three nodules measuring no more than 5 cm in diameter (3). Patients with platelet counts less than 40 ⫻ 109/L, prothrombin activity less than 40%, moderate ascites, or preexisting biliary obstruction were considered unsuitable for ablation therapy (7). The human subjects research review boards at our institution approved our study. Before treatment, informed consent was obtained from all patients, who were provided a comprehensive description of the procedure. Pretreatment imaging studies performed were abdominal ultrasonography (US) and dynamic computed tomography (CT). Abdominal US was performed with a real-time scanner with use of a 3.5-MHz transducer (SSD-550; Aloka, Tokyo, Japan). Dynamic CT was performed with a helical CT scanner (W-3000; Hitachi, Tokyo, Japan). Triple-phase contiguous 7-mm-thick CT scans were obtained. Initially, noncontrast CT scans were obtained. Then, early-phase CT scans were obtained 30 seconds after initiation of bolus injection of 100 mL of 65% iopamidol (Iopamiron 300; Nihon Schering, Osaka, Japan), and latephase CT scans were obtained 120 sec-
onds after the initiation of the injection of contrast media. Ablation Technique One author (Toshiya Shibata) performed ablation therapies. PEI has been performed in 205 patients with 261 liver tumors since October 1995, primarily for HCC. Of the 205 patients who underwent PEI, 198 had 254 HCC nodules and seven patients had seven metastatic nodules. Pentazocine (15 mg Sosegon; Yamanouchi, Tokyo, Japan) was intramuscularly injected 10 minutes before therapy as premedication for sedation. After disinfection of the skin surface and induction of local anesthesia with 1% lidocaine (Xylocaine; AstraZenca Japan, Osaka, Japan), a 21-gauge needle designed for injection therapy (PEIT needle; Hakko, Tokyo, Japan) was introduced into the liver nodule under US or CT guidance. Two to three needles were introduced into larger nodules (⬎3 cm in diameter). Absolute ethanol (1–25 mL) was injected in each session. One to eight sessions of treatment were performed in each nodule, and a total of 441 sessions of PEI were performed. PMC was performed for 70 patients with 90 liver tumors between January 1996 and December 2000. PMC was initially performed for metastatic nodules and later for HCC nodules as well as metastatic nodules. Of 70 patients, 40 patients had 49 HCC nodules and 30 patients had 41 metastatic nodules. The microwave delivery system consisted of a microwave generator, which emits a 2450-MHz microwave, and a microwave electrode (diameter, 1.6 mm; length, 25 cm; Microtaze; Nippon Shoji, Osaka, Japan) (9). Premedication, disinfection, and local anesthesia were performed in the same manner as in PEI. A 14-gauge guide needle (PMCT NSP; Hakko) was introduced into the nodule under US or CT guidance. The inner needle was removed and the electrode was introduced through the outer needle of the guide. Microwave ablation was performed in the same manner as in our group’s previous report (20). One to five sessions of treatment were performed in each nodule, and 145 sessions of PMC were performed in total. RF ablation was introduced in March 1999, and it has been used in
December 2003
JVIR
the treatment of 83 patients with 104 liver tumors. Of 83 patients, 67 had 85 HCC nodules and 16 had 19 metastatic nodules. PMC was abandoned in favor of RF ablation in January 2001 following our group’s finding that tumor ablation by RF ablation could be achieved with fewer sessions than that by PMC (20). As Livraghi et al (7) demonstrated, RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than PEI. RF ablation is currently a main ablation technique in our department. PEI is performed for nodules located on the liver surface, near large vessels, near the gallbladder, or near the hepatic hilum, in which the treatments with RF ablation were thought dangerous or ineffective. A RF 2000 generator system (RadioTherapeutics; Mountain View, CA) was used (6). This system consists of a generator, a LeVeen monopolar array needle electrode, and a dispersive electrode pad applied to the skin. Premedication, disinfection, and local anesthesia were performed in the same manner as in PEI. A 15-gauge RF electrode connected to the RF generator with a soft cable was introduced into the nodule under US or CT guidance. Then, RF ablation was performed in the same manner as in our previous report (20). One to three sessions of treatment were performed in each nodule, and a total of 97 sessions of RF ablation were performed. Prophylactic intravenous administration of antibiotics (21) has been performed since July 2000 because of the awareness of the possible risk of sepsis or abscess. The protocol was administration of 1 g cefazolin or cefmetazole 1 day before ablation therapy and 1 g every 12 hours until discharge. Dynamic CT images were obtained 1 month after RF ablation therapies to evaluate the therapeutic effects. Follow-up dynamic CT images were obtained every 3 months. Diagnosis of Cholangitis and Liver Abscess after Ablation Therapy The diagnosis of cholangitis was made according to the following criteria: (i) high fever (⬎38°C) lasting more than 3 days, (ii) doubling of the baseline serum bilirubin level or doubling of the baseline serum alkaline phosphatase level, and (iii) newly appear-
Volume 14
Number 12
ing dilation of intrahepatic bile duct on abdominal CT. The diagnosis of liver abscess was made according to the following criteria: (i) high fever (⬎38°C) lasting more than 3 days, (ii) presence of a low-density lesion on abdominal CT, and (iii) aspiration of pus or isolation of organism in patients in whom abscess drainage was performed. We evaluated the incidence and outcomes of the patients with cholangitis and/or liver abscess occurring after percutaneous ablation therapy. Statistical Analysis The percentages of cholangitis/ liver abscess were based on the 683 ablation procedures performed. Variables analyzed were patients’ age, disease (HCC or metastatic liver tumor), Child-Pugh class, size of nodules, multiplicity of nodules (solitary or multiple), history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and presence or lack of prophylactic antibiotic administration. The relationship between cholangitis/liver abscess and the five nominal variables— disease, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotic administration— was analyzed with use of the Fisher exact probability test. A P value of less than .05 was considered to indicate a statistically significant difference. Next, the relationship between cholangitis/liver abscess and all eight aforementioned variables was determined with use of logistic regression analysis. A P value of less than .05 was considered to indicate a statistically significant difference.
RESULTS Cholangitis and/or liver abscess occurred in 10 of 683 sessions (1.5%) in 10 patients: six (in six patients) among 441 PEI sessions (1.4%; Fig 1), three (in three patients) among 145 PMC sessions (2.1%; Fig 2), and one among 97 RF ablation sessions (1.0%). Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Table 1 shows the clinical findings in these 10 patients. Abscess drainage was performed in
Shibata et al
six sessions: cultured organisms included Escherichia coli (n ⫽ 2), Enterococcus species (n ⫽ 2), Enterobacter cloacae (n ⫽ 1), Klebsiella pneumoniae (n ⫽ 1), and no isolation (n ⫽ 1). Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. Of these 10 patients, five had bilioenteric anastomoses: four with metastatic nodules after surgical resection for biliary or pancreatic malignant lesions and one with recurrent HCC after surgical resection for tumor growth of HCC in the bile duct. Four of the five patients with bilioenteric anastomosis exhibited pneumobilia on pretreatment CT. On the Fisher exact probability test, presence of bilioenteric anastomosis and disease (HCC or metastatic liver tumor) were significant risk factors for cholangitis and/or liver abscess (P ⬍ .001 and P ⫽ .01, respectively), but multiplicity of nodules (solitary or multiple), history of transcatheter arterial embolization, and lack of prophylactic antibiotic administration were not significant (P ⫽ .175, P ⫽ .317, P ⫽ .310, respectively). Univariate logistic regression analysis showed that presence of bilioenteric anastomosis and disease (HCC/metastasis) were significant risk factors as well (Table 2). However, on stepwise regression analysis, the presence of bilioenteric anastomosis proved to be the sole significant predictor of cholangitis and/or liver abscess formation (P ⬍ .001; r ⫽ 0.218; odds ratio ⫽ 36.4; 95% CI ⫽ 9.671–136.9), and the other variables were not significant risk factors.
DISCUSSION In our study, infectious complications (cholangitis and/or liver abscess) occurred in 1.5% of sessions of percutaneous ablation therapy. In six sessions, cholangitis and/or liver abscess abated with suitable treatments. Of the 10 patients who had cholangitis and/or liver abscess, five had a history of bilioenteric anastomosis resulting from hepatobiliary or pancreatic malignant lesions. The presence of bilioenteric anastomosis was the sole significant predictor of cholangitis or liver abscess formation on stepwise regression analysis.
•
1537
In accordance with the complication definitions established by the Society of Interventional Radiology (22), specific complications of interventional procedures were assigned to major and minor categories. Major complications were defined as those that required therapy with hospitalization and/or involved permanent adverse sequelae including death. Major complications occurring after percutaneous ablation therapy for liver tumors are focal liver infarction, hemorrhage requiring transfusion, liver abscess, bile duct injury, pleural effusion requiring thoracentesis, tumor dissemination, and death. The study by the Korean Radiofrequency Study Group demonstrated 37 major complications (2.4%) among a total of 1,520 RF ablation procedures in 1,139 patients with hepatic tumors, among which hepatic abscess (0.66%) was the most common major complication (23). The study of the Italian Multicenter RF Study Group showed six deaths (0.3%) and 50 major complications (2.2%) in 2,320 patients, including six hepatic abscesses (0.3%) (24). These six procedure-related deaths developed from two colonic perforations, one bile duct injury, one case of peritonitis, one peritoneal hemorrhage, and one unknown cause. However, the last patient, whose cause of death was unknown, had undergone bilioenteric anastomosis for pancreatic carcinoma. Vogl et al (25) treated 899 patients with malignant liver tumors with laser-induced thermotherapy, and hepatic abscess was noted in 0.7% of sessions. Three procedure-related deaths developed from sepsis caused by bacterial cholangitis, perforation of jejunum, or rupture of esophageal varices. Conversely, we know of no study evaluating major complications of PMC procedures in a large number of patients with malignant liver tumors. In earlier studies in which samples were too small, the rates of liver abscess or cholangitis occurring after PMC were reported to be between 0% and 8% (9 –11,26). Livraghi et al (3) performed PEI in 746 patients with HCC and described one liver abscess and one episode of cholangitis. As a major complication of the ablation therapy, liver abscess or cholangitis is not uncommon. Most patients with cholangitis and/or liver abscess recover with prompt diagnosis and
1538
•
Cholangitis and Liver Abscess after Ablation Therapy
December 2003
JVIR
Figure 1. Images from patient 10, a 71-year-old man who underwent a Whipple procedure for pancreatic carcinoma, who had a metastatic nodule for which PEI was performed. (a) Transverse early-phase CT image obtained before PEI shows a metastatic nodule (arrows) in the anterosuperior segment of the right lobe and pneumobilia (arrowheads). (b) After PEI, the patient had a high fever (39°C). Transverse late-phase CT image obtained 1 month after PEI shows that the treated nodule’s density has decreased with air (white arrowheads). (c) Transverse late-phase CT image just caudal to b shows a low-density lesion. Liver abscess was confirmed by percutaneous drainage.
Volume 14
Number 12
Shibata et al
•
1539
Figure 2. Images from patient 4, a 61-year-old man with previous left lobectomy and hepaticojejunostomy for hilar cholangiocarcinoma, who had three metastatic nodules in the anteroinferior and posteroinferior segments of the right lobe for which PMC was performed. (a) Transverse early-phase CT image obtained before PMC shows a metastatic nodule (arrow) in the anteroinferior segment. (b) Transverse late-phase CT image obtained 1 week after PMC shows intrahepatic high- and low-density fluid (arrowheads) and air (white arrowhead). (c) Transverse noncontrast CT image obtained 10 days after PMC shows huge fluid collection in the liver and subcapsular region. Two drainage catheters were percutaneously introduced, and pus and hemorrhage were aspirated. Percutaneous drainage was not effective, so surgical abscess drainage was performed successfully.
1540
•
December 2003
Cholangitis and Liver Abscess after Ablation Therapy
JVIR
Table 1 Clinical Findings of 10 Patients with Cholangitis and/or Liver Abscess Child-Pugh Class
Size of Nodules (cm)/ Multiplicity
Bilioenteric Anastomosis
HCC
B
3.3/Multiple
Yes
Yes
Yes
72/M
HCC
A
2.0/Single
No
No
No
3
52/M
HCC
B
1.5/Single
No
No
Yes
4 5
61/M 72/M
Liver metastasis of cholangiocarcinoma Liver metastasis of cholangiocarcinoma
A A
3.8/Multiple 2.3/Single
Yes Yes
Yes No
No No
6 7 8
54/F 61/M 45/F
A A A
4.0/Single 4.0/Multiple 2.4/Multiple
No No Yes
No No Yes
No No No
9
70/M
HCC Liver metastasis of lung carcinoma Liver metastasis of gallbladder carcinoma HCC
A
3.0/Single
No
No
No
10
71/M
Liver metastasis of pancreatic carcinoma
A
1.8/Single
Yes
Yes
No
Pt. No.
Age (y)/ Sex
1
60/M
2
Disease
Pneumobilia on CT
History of TAE
Note.—TAE ⫽ transcatheter arterial embolization.
treatment, such as percutaneous drainage in combination with systemic antibiotics. However, as shown in the previous studies as well as our study, infectious complications are likely to be fatal in some cases, or permanent biliary drainage may be sometimes necessary as a result of a nonhealing biliary fistula (13,14,17,24). The mechanism of abscess development after percutaneous ablation therapy is not established, but subsequent bacterial contamination of the ablated necrotic lesions may lead to abscess formation (23). In interventional procedures, aseptic technique to prevent skin contamination is required. In our study, no skin flora was noted in cultured organisms. Analyzing our 10 cases of cholangitis/liver abscess, multiple treatments by PMC or RF ablation for the larger nodules might have been related to the development of abscess in two sessions (patients 6 and 7), even though the size of nodules was not a significant risk factor. In one session (patient 3; HCC nodule near the hepatic hilum), we suppose the direct damage of ethanol might have led to stenosis of hilar biliary tracts and cholangitis. In two cases (patients 2 and 9), the etiology of cholangitis/liver abscess was unknown. In the other five cases (patients 1, 4, 5, 8, and 10), previous bil-
ioenteric anastomosis is likely responsible for the development of cholangitis/abscess formation. Several processes related to ablation therapy and bilioenteric anastomosis may enhance the development of cholangitis and abscess formation. First, bilioenteric anastomosis is associated with retrograde enteric bacterial contamination of the biliary tract in as many as 90% of patients (21). In tumor ablation therapies, the traffic between necrotic tissues produced by ablation therapy and biliary tracts is likely to enhance abscess formation by contaminated enteric bacteria. Of the five patients with bilioenteric anastomosis in whom cholangitis/liver abscess occurred after ablation therapies, four patients exhibited pneumobilia on pretreatment CT. In the three patients treated with abscess drainage, cultured organisms were from an enteric source: E coli, Enterococcus species, and E cloacae (Table 1). Second, bilioenteric anastomosis is required after excision of lymph nodes in the hepatoduodenal ligament and removal of peribiliary arterial plexus. Direct damage by ablation to the ischemic biliary tracts may enhance the development of cholangitis. In the study of the Italian Multicenter RF Study Group (24), two of the six patients with abscesses had pneumobilia resulting from previous gas-
trointestinal surgery. Vogl et al (25) demonstrated that patients with liver metastasis from pancreatic carcinoma who had undergone Whipple procedures had significantly more abscesses than patients with metastases from other primary tumors undergoing laser-induced thermotherapy. Our study showed that chemical ablation with ethanol, as well as thermal ablation with microwave or RF energy, is likely to induce cholangitis/liver abscess in patients with bilioenteric anastomoses. Bilioenteric anastomoses are created not only in patients with pancreatic and biliary malignant lesions, but also in those with intrabile tumor growth of HCC (27,28). The rate of cholangitis/liver abscess in our study (1.5%) was higher than those in previous reports (0.3%– 0.7%) (23–25), which may be because more patients with bilioenteric anastomoses were included in our study. The rate of occurrence of cholangitis and/or liver abscess in patients with metastases (five of 105) was five times greater than that in patients with HCC (five of 578). On Fisher exact probability test and univariate logistic regression, disease (HCC/metastasis) was found to be a significant predictor, but stepwise regression analysis showed presence of bilioenteric anastomosis to be the sole significant predictor of cholangitis/
Volume 14
Number 12
Type of Ablation
Prophylactic Antibiotics
Shibata et al
Cholangitis and/or Abscess
Treatment
Organism from Abscess
PEI
No
Both
Conservative therapy
–
PEI
No
Cholangitis
Conservative therapy
–
PEI
No
Both
Conservative therapy
–
PMC PMC
No No
Both Both
Surgical abscess drainage Percutaneous abscess drainage
PMC RF PEI
No No Yes
Abscess Both Cholangitis
Percutaneous abscess drainage Percutaneous abscess drainage Conservative therapy
PEI
No
Both
Percutaneous abscess drainage
PEI
Yes
Both
Percutaneous abscess drainage
liver abscess formation (Table 2). These results were obtained because some patients with bilioenteric anastomosis caused by pancreatic or biliary malignant lesions were included among those with metastasis, and patients with HCC rarely underwent creation of bilioenteric anastomoses. Prophylactic antibiotic administration was reported to be effective to prevent infectious complications in interventional procedure (21). However, two patients with bilioenteric anastomosis (patients 8 and 10) in whom cholangitis/liver abscess occurred after PEI had prophylactic antibiotic ad-
•
1541
Prognosis of Cholangitis and/or Abscess
Died of septic shock 12 days after PEI Recurrent cholangitis and abscess
E. coli Enterococcus species No isolation E. coli – Recurrent cholangitis and abscess
K. pneumoniae, Enterococcus species E. cloacae
ministration. In our study, lack of prophylactic antibiotic administration was not a risk factor. Kim et al (17) described a prophylactic regimen that failed to prevent abscess formation after hepatic chemoembolization for patients with earlier bilioenteric anastomosis. However, Geschwind et al (29) showed that aggressive antibiotic prophylaxis with bowel preparation may provide protection against intrahepatic abscesses after chemoembolization in patients who have a history of biliary reconstructive surgery. Further evaluation seems necessary to determine the effectiveness of aggressive
Complicated lung abscess
antibiotic prophylaxis and bowel preparation when tumor ablation therapy is performed in patients with bilioenteric anastomoses. The presence of bilioenteric anastomosis may not be a contraindication to ablation therapy because cholangitis/liver abscess do not always occur in these patients, but utmost care should be taken when ablation therapy is selected for these patients. In conclusion, the presence of bilioenteric anastomosis was a risk factor for cholangitis and/or liver abscess after tumor ablation therapies. Careful posttreatment attention should be
Table 2 Relationship between Variables and Cholangitis/Liver Abscess in 683 Sessions of Ablation Therapy According to Univariate Logistic Regression Analysis Variables Age (y): mean ⫾ SD (range) Disease (HCC/metastatic liver tumor) Child-Pugh class (A/B) Size of nodules (cm): mean ⫾ SD (range) Multiplicity of nodules (solitary/multiple) History of TAE (yes/no) Presence of bilioenteric anastomosis (yes/no) Prophylactic antibiotic administration (no/yes) Note.—TAE ⫽ transcatheter arterial embolization
64 ⫾ 11 (14–83) 578/105 578/105 2.6 ⫾ 1.1 (0.8–5.0) 527/156 222/461 23/660 459/224
P Value
r2
Odds Ratio
95% CI
.441 .007 .684 .618 .205 .404 ⬍.001 .394
.005 .069 .002 .002 .015 .008 .218 .008
1.02 0.175 0.723 0.869 0.438 0.515 36.39 1.968
0.97–1.07 0.05–0.61 0.15–3.45 0.50–1.51 0.12–1.57 0.11–2.45 9.67–136.9 0.42–9.34
1542
•
December 2003
Cholangitis and Liver Abscess after Ablation Therapy
paid after ablation therapies in patients with bilioenteric anastomoses. References 1. Shiina S, Tagawa K, Niwa Y, et al. Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients. AJR Am J Roentgenol 1993; 160:1023–1028. 2. Kotoh K, Sakai H, Sakamoto S, et al. The effect of percutaneous ethanol injection therapy on small solitary hepatocellular carcinoma is comparable to that of hepatectomy. Am J Gastroenterol 1994; 89:194 –198. 3. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995; 197:101–108. 4. Livraghi T, Benedini V, Lazzaroni S, et al. Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma. Cancer 1998; 83:48 –57. 5. Solbiati L, Ierace T, Goldberg SN, et al. Percutaneous US-guided RF tissue ablation of liver metastasis: results of treatment and follow-up in 16 patients. Radiology 1997; 202:195–203. 6. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies. Ann Surg 1999; 230:1– 8. 7. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210:655– 661. 8. De Baere T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 2000; 175:1619 –1625. 9. Sato M, Watanabe Y, Ueda S, et al. Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 1996; 110:1507–1514. 10. Seki T, Wakabayashi M, Nakagawa T, et al. Percutaneous microwave coag-
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
ulation therapy for solitary metastatic liver tumors from colorectal cancer: a pilot clinical study. Am J Gastroenterol 1999; 94:322–327. Lu MD, Chen JW, Xie XY, et al. Hepatocellular carcinoma: US-guided percutaneous microwave coagulation therapy. Radiology 2001; 221:167–172. Vogl TJ, Mack MG, Roggan A, et al. Internally cooled power laser for MRguided interstitial laser-induced thermotherapy of liver lesions: initial clinical results. Radiology 1998; 209:381– 385. Zagoria RJ, Chen MY, Shen P, et al. Complications from radiofrequency ablation of liver metastases. Am Surg 2002; 68:204 –209. Shibata T, Yamamoto N, Ikai I, et al. Choledochojejunostomy: possible risk factor for septic complications after percutaneous hepatic tumor ablation. AJR Am J Roentgenol 2000; 174:985– 986. Okajima K, Kohno S, Tamaki M, et al. Bilio-enteric anastomosis as a risk factor for postembolic hepatic abscesses. Cardiovasc Intervent Radiol 1989; 12: 128 –130. De Baere T, Roche A, Amenabar JM, et al. Liver abscess formation after local treatment of liver tumors. Hepatology 1996; 23:1436 –1440. Kim W, Clark TW, Baum RA, et al. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 2001; 12:965–968. Young SS, Jin WC, Joon KH, et al. Liver abscess after transcatheter oil chemoembolization for hepatic tumors. J Vasc Interv Radiol 2001; 12:313–320. Okada S, Aoki K, Okazaki N, et al. Liver abscess after percutaneous ethanol injection (PEI) therapy for hepatocellular carcinoma: a case report. Hepatogastroenterology 1993; 40:496 – 498. Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagula-
21.
22.
23.
24.
25.
26.
27.
28.
29.
JVIR
tion therapy. Radiology 2002; 223:331– 337. Spies JB, Rosen RJ, Lebowitz AS. Antibiotic prophylaxis in vascular and interventional radiology: a rational approach. Radiology 1988; 166:381–387. Leoni CJ, Potter JE, Rosen MP, et al. Classifying complications of interventional procedures: a survey of practicing radiologists. J Vasc Interv Radiol 2001; 12:55–59. Rhim H, Yoon KH, Lee JM, et al. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics 2003; 23:123–134. Livraghi T, Solbiati L, Meloni MF, et al. Treatment of focal liver tumors with percutaneous radiofrequency ablation: complications encountered in a multicenter study. Radiology 2003; 226:441– 451. Vogl TJ, Straub R, Eichler K, et al. Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: experience with complications in 899 patients (2520 lesions). Radiology 2002; 225:367–377. Shimada S, Hirota M, Beppu T, et al. Complications and management of microwave coagulation therapy for primary and metastatic liver tumors. Surg Today 1998; 28:1130 –1137. Kojiro M, Kawabata K, Kawano Y, et al. Hepatocellular carcinoma presenting as intrabile duct tumor growth: a clinicopathologic study of 24 cases. Cancer 1982; 49:2144 –2147. Tanoue K, Kanematsu T, Matsumata T, et al. Successful surgical treatment of hepatocellular carcinoma invading into biliary tree. HPB Surg 1991; 4:237–244. Geschwind JF, Kaushik S, Ramsey DE, et al. Influence of a new prophylactic antibiotic therapy on the incidence of liver abscesses after chemoembolization treatment of liver tumors. J Vasc Interv Radiol 2002; 13:1163–1166.
PURPOSE: To determine the risk factors of cholangitis and liver abscess occurring after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS: Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total of 683 ablation procedures, such as percutaneous ethanol injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency (RF) ablation therapy. With a retrospective review of medical records, the rates and outcomes of cholangitis and/or liver abscess occurring after ablation therapy were evaluated. The relationship between cholangitis and/or liver abscess and multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotics administration) were statistically analyzed. RESULTS: Cholangitis and/or liver abscess occurred in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions after PMC, and one session after RF ablation. Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. On stepwise regression analysis, bilioenteric anastomosis was the sole significant predictor of cholangitis and/or liver abscess formation (P < .001; odds ratio ⴝ 36.4; 95% CI ⴝ 9.67–136.9). CONCLUSION: Bilioenteric anastomosis strongly correlated with the development of cholangitis and/or liver abscess after percutaneous ablation therapy. Close posttreatment attention should be paid to this subgroup of patients. J Vasc Interv Radiol 2003; 14:1535–1542 Abbreviations:
HCC ⫽ hepatocellular carcinoma, PEI ⫽ percutaneous ethanol injection, PMC ⫽ percutaneous microwave coagulation, RF ⫽ radiofrequency
PERCUTANEOUS ablation therapy, such as percutaneous ethanol injection (PEI), percutaneous microwave coag-
From the Departments of Diagnostic Imaging and Radiology (T.S., Y.M., T.S., T.K., K.I., M.H.) and Gastroenterological Surgery (Y.Y., N.Y., I.I., H.T., E.H.), Kyoto University Graduate School of Medicine, Shogoin, Sakyoku, Kyoto, 606-8507, Japan. Received April 22, 2003; revision requested June 5; revision received July 29; accepted July 31. From the 2003 SIR Annual Meeting. Address correspondence to Toshiya Shibata; E-mail: [email protected] None of the authors have identified a potential conflict of interest. © SIR, 2003 DOI: 10.1097/01.RVI.0000099532.29957.4F
ulation (PMC), radiofrequency (RF) ablation therapy, and interstitial laser photocoagulation, is an effective, minimally invasive treatment for small liver tumors (1–12). The most common complications of percutaneous ablation therapy are abdominal pain and low-grade fever that last only a few days. The ablation techniques are considered safe: major complications have been reported, but only rarely (1–12). Infections such as cholangitis and liver abscess are rare complications but may be severe sometimes, necessitating interventional procedures (13,14). Conversely, several studies have suggested that bilioenteric anastomosis is a possible risk factor for liver abscess
formation after transcatheter arterial embolization (15–17). Another study (18) has suggested that biliary abnormality prone to ascending biliary infection, such as endoscopic papillotomy, bilioenteric anastomosis, bilioenteric fistula, external biliary drainage, and pneumobilia, is the most important predisposing factor to the development of liver abscess after transcatheter arterial embolization. A few case studies have shown that liver abscess occurs after percutaneous ablation therapies in patients with bilioenteric anastomosis (14,19). In establishing a safety guideline, it is important to know the risk factors of cholangitis and liver abscess after per-
1535
1536
•
Cholangitis and Liver Abscess after Ablation Therapy
cutaneous ablation therapy. The purpose of our study is to evaluate outcomes of cholangitis and liver abscess after percutaneous ablation therapy and to determine the risk factors.
MATERIALS AND METHODS Patients Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total 683 sessions of percutaneous ablation therapy. The study population included 275 men and 83 women aged 14 – 83 years. Three hundred five patients had hepatocellular carcinoma (HCC) and 53 patients had metastatic liver tumor. Primary lesions were colorectal carcinoma in 34, cholangiocarcinoma in four, gallbladder carcinoma in four, breast carcinoma in three, gastric carcinoma in two, esophageal carcinoma in two, lung carcinoma in two, pancreatic carcinoma in one, and gastrointestinal stromal tumor in one. Our standard criteria used for selection of patients for percutaneous ablation therapy included the presence of no more than three nodules measuring no more than 5 cm in diameter (3). Patients with platelet counts less than 40 ⫻ 109/L, prothrombin activity less than 40%, moderate ascites, or preexisting biliary obstruction were considered unsuitable for ablation therapy (7). The human subjects research review boards at our institution approved our study. Before treatment, informed consent was obtained from all patients, who were provided a comprehensive description of the procedure. Pretreatment imaging studies performed were abdominal ultrasonography (US) and dynamic computed tomography (CT). Abdominal US was performed with a real-time scanner with use of a 3.5-MHz transducer (SSD-550; Aloka, Tokyo, Japan). Dynamic CT was performed with a helical CT scanner (W-3000; Hitachi, Tokyo, Japan). Triple-phase contiguous 7-mm-thick CT scans were obtained. Initially, noncontrast CT scans were obtained. Then, early-phase CT scans were obtained 30 seconds after initiation of bolus injection of 100 mL of 65% iopamidol (Iopamiron 300; Nihon Schering, Osaka, Japan), and latephase CT scans were obtained 120 sec-
onds after the initiation of the injection of contrast media. Ablation Technique One author (Toshiya Shibata) performed ablation therapies. PEI has been performed in 205 patients with 261 liver tumors since October 1995, primarily for HCC. Of the 205 patients who underwent PEI, 198 had 254 HCC nodules and seven patients had seven metastatic nodules. Pentazocine (15 mg Sosegon; Yamanouchi, Tokyo, Japan) was intramuscularly injected 10 minutes before therapy as premedication for sedation. After disinfection of the skin surface and induction of local anesthesia with 1% lidocaine (Xylocaine; AstraZenca Japan, Osaka, Japan), a 21-gauge needle designed for injection therapy (PEIT needle; Hakko, Tokyo, Japan) was introduced into the liver nodule under US or CT guidance. Two to three needles were introduced into larger nodules (⬎3 cm in diameter). Absolute ethanol (1–25 mL) was injected in each session. One to eight sessions of treatment were performed in each nodule, and a total of 441 sessions of PEI were performed. PMC was performed for 70 patients with 90 liver tumors between January 1996 and December 2000. PMC was initially performed for metastatic nodules and later for HCC nodules as well as metastatic nodules. Of 70 patients, 40 patients had 49 HCC nodules and 30 patients had 41 metastatic nodules. The microwave delivery system consisted of a microwave generator, which emits a 2450-MHz microwave, and a microwave electrode (diameter, 1.6 mm; length, 25 cm; Microtaze; Nippon Shoji, Osaka, Japan) (9). Premedication, disinfection, and local anesthesia were performed in the same manner as in PEI. A 14-gauge guide needle (PMCT NSP; Hakko) was introduced into the nodule under US or CT guidance. The inner needle was removed and the electrode was introduced through the outer needle of the guide. Microwave ablation was performed in the same manner as in our group’s previous report (20). One to five sessions of treatment were performed in each nodule, and 145 sessions of PMC were performed in total. RF ablation was introduced in March 1999, and it has been used in
December 2003
JVIR
the treatment of 83 patients with 104 liver tumors. Of 83 patients, 67 had 85 HCC nodules and 16 had 19 metastatic nodules. PMC was abandoned in favor of RF ablation in January 2001 following our group’s finding that tumor ablation by RF ablation could be achieved with fewer sessions than that by PMC (20). As Livraghi et al (7) demonstrated, RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than PEI. RF ablation is currently a main ablation technique in our department. PEI is performed for nodules located on the liver surface, near large vessels, near the gallbladder, or near the hepatic hilum, in which the treatments with RF ablation were thought dangerous or ineffective. A RF 2000 generator system (RadioTherapeutics; Mountain View, CA) was used (6). This system consists of a generator, a LeVeen monopolar array needle electrode, and a dispersive electrode pad applied to the skin. Premedication, disinfection, and local anesthesia were performed in the same manner as in PEI. A 15-gauge RF electrode connected to the RF generator with a soft cable was introduced into the nodule under US or CT guidance. Then, RF ablation was performed in the same manner as in our previous report (20). One to three sessions of treatment were performed in each nodule, and a total of 97 sessions of RF ablation were performed. Prophylactic intravenous administration of antibiotics (21) has been performed since July 2000 because of the awareness of the possible risk of sepsis or abscess. The protocol was administration of 1 g cefazolin or cefmetazole 1 day before ablation therapy and 1 g every 12 hours until discharge. Dynamic CT images were obtained 1 month after RF ablation therapies to evaluate the therapeutic effects. Follow-up dynamic CT images were obtained every 3 months. Diagnosis of Cholangitis and Liver Abscess after Ablation Therapy The diagnosis of cholangitis was made according to the following criteria: (i) high fever (⬎38°C) lasting more than 3 days, (ii) doubling of the baseline serum bilirubin level or doubling of the baseline serum alkaline phosphatase level, and (iii) newly appear-
Volume 14
Number 12
ing dilation of intrahepatic bile duct on abdominal CT. The diagnosis of liver abscess was made according to the following criteria: (i) high fever (⬎38°C) lasting more than 3 days, (ii) presence of a low-density lesion on abdominal CT, and (iii) aspiration of pus or isolation of organism in patients in whom abscess drainage was performed. We evaluated the incidence and outcomes of the patients with cholangitis and/or liver abscess occurring after percutaneous ablation therapy. Statistical Analysis The percentages of cholangitis/ liver abscess were based on the 683 ablation procedures performed. Variables analyzed were patients’ age, disease (HCC or metastatic liver tumor), Child-Pugh class, size of nodules, multiplicity of nodules (solitary or multiple), history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and presence or lack of prophylactic antibiotic administration. The relationship between cholangitis/liver abscess and the five nominal variables— disease, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotic administration— was analyzed with use of the Fisher exact probability test. A P value of less than .05 was considered to indicate a statistically significant difference. Next, the relationship between cholangitis/liver abscess and all eight aforementioned variables was determined with use of logistic regression analysis. A P value of less than .05 was considered to indicate a statistically significant difference.
RESULTS Cholangitis and/or liver abscess occurred in 10 of 683 sessions (1.5%) in 10 patients: six (in six patients) among 441 PEI sessions (1.4%; Fig 1), three (in three patients) among 145 PMC sessions (2.1%; Fig 2), and one among 97 RF ablation sessions (1.0%). Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Table 1 shows the clinical findings in these 10 patients. Abscess drainage was performed in
Shibata et al
six sessions: cultured organisms included Escherichia coli (n ⫽ 2), Enterococcus species (n ⫽ 2), Enterobacter cloacae (n ⫽ 1), Klebsiella pneumoniae (n ⫽ 1), and no isolation (n ⫽ 1). Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. Of these 10 patients, five had bilioenteric anastomoses: four with metastatic nodules after surgical resection for biliary or pancreatic malignant lesions and one with recurrent HCC after surgical resection for tumor growth of HCC in the bile duct. Four of the five patients with bilioenteric anastomosis exhibited pneumobilia on pretreatment CT. On the Fisher exact probability test, presence of bilioenteric anastomosis and disease (HCC or metastatic liver tumor) were significant risk factors for cholangitis and/or liver abscess (P ⬍ .001 and P ⫽ .01, respectively), but multiplicity of nodules (solitary or multiple), history of transcatheter arterial embolization, and lack of prophylactic antibiotic administration were not significant (P ⫽ .175, P ⫽ .317, P ⫽ .310, respectively). Univariate logistic regression analysis showed that presence of bilioenteric anastomosis and disease (HCC/metastasis) were significant risk factors as well (Table 2). However, on stepwise regression analysis, the presence of bilioenteric anastomosis proved to be the sole significant predictor of cholangitis and/or liver abscess formation (P ⬍ .001; r ⫽ 0.218; odds ratio ⫽ 36.4; 95% CI ⫽ 9.671–136.9), and the other variables were not significant risk factors.
DISCUSSION In our study, infectious complications (cholangitis and/or liver abscess) occurred in 1.5% of sessions of percutaneous ablation therapy. In six sessions, cholangitis and/or liver abscess abated with suitable treatments. Of the 10 patients who had cholangitis and/or liver abscess, five had a history of bilioenteric anastomosis resulting from hepatobiliary or pancreatic malignant lesions. The presence of bilioenteric anastomosis was the sole significant predictor of cholangitis or liver abscess formation on stepwise regression analysis.
•
1537
In accordance with the complication definitions established by the Society of Interventional Radiology (22), specific complications of interventional procedures were assigned to major and minor categories. Major complications were defined as those that required therapy with hospitalization and/or involved permanent adverse sequelae including death. Major complications occurring after percutaneous ablation therapy for liver tumors are focal liver infarction, hemorrhage requiring transfusion, liver abscess, bile duct injury, pleural effusion requiring thoracentesis, tumor dissemination, and death. The study by the Korean Radiofrequency Study Group demonstrated 37 major complications (2.4%) among a total of 1,520 RF ablation procedures in 1,139 patients with hepatic tumors, among which hepatic abscess (0.66%) was the most common major complication (23). The study of the Italian Multicenter RF Study Group showed six deaths (0.3%) and 50 major complications (2.2%) in 2,320 patients, including six hepatic abscesses (0.3%) (24). These six procedure-related deaths developed from two colonic perforations, one bile duct injury, one case of peritonitis, one peritoneal hemorrhage, and one unknown cause. However, the last patient, whose cause of death was unknown, had undergone bilioenteric anastomosis for pancreatic carcinoma. Vogl et al (25) treated 899 patients with malignant liver tumors with laser-induced thermotherapy, and hepatic abscess was noted in 0.7% of sessions. Three procedure-related deaths developed from sepsis caused by bacterial cholangitis, perforation of jejunum, or rupture of esophageal varices. Conversely, we know of no study evaluating major complications of PMC procedures in a large number of patients with malignant liver tumors. In earlier studies in which samples were too small, the rates of liver abscess or cholangitis occurring after PMC were reported to be between 0% and 8% (9 –11,26). Livraghi et al (3) performed PEI in 746 patients with HCC and described one liver abscess and one episode of cholangitis. As a major complication of the ablation therapy, liver abscess or cholangitis is not uncommon. Most patients with cholangitis and/or liver abscess recover with prompt diagnosis and
1538
•
Cholangitis and Liver Abscess after Ablation Therapy
December 2003
JVIR
Figure 1. Images from patient 10, a 71-year-old man who underwent a Whipple procedure for pancreatic carcinoma, who had a metastatic nodule for which PEI was performed. (a) Transverse early-phase CT image obtained before PEI shows a metastatic nodule (arrows) in the anterosuperior segment of the right lobe and pneumobilia (arrowheads). (b) After PEI, the patient had a high fever (39°C). Transverse late-phase CT image obtained 1 month after PEI shows that the treated nodule’s density has decreased with air (white arrowheads). (c) Transverse late-phase CT image just caudal to b shows a low-density lesion. Liver abscess was confirmed by percutaneous drainage.
Volume 14
Number 12
Shibata et al
•
1539
Figure 2. Images from patient 4, a 61-year-old man with previous left lobectomy and hepaticojejunostomy for hilar cholangiocarcinoma, who had three metastatic nodules in the anteroinferior and posteroinferior segments of the right lobe for which PMC was performed. (a) Transverse early-phase CT image obtained before PMC shows a metastatic nodule (arrow) in the anteroinferior segment. (b) Transverse late-phase CT image obtained 1 week after PMC shows intrahepatic high- and low-density fluid (arrowheads) and air (white arrowhead). (c) Transverse noncontrast CT image obtained 10 days after PMC shows huge fluid collection in the liver and subcapsular region. Two drainage catheters were percutaneously introduced, and pus and hemorrhage were aspirated. Percutaneous drainage was not effective, so surgical abscess drainage was performed successfully.
1540
•
December 2003
Cholangitis and Liver Abscess after Ablation Therapy
JVIR
Table 1 Clinical Findings of 10 Patients with Cholangitis and/or Liver Abscess Child-Pugh Class
Size of Nodules (cm)/ Multiplicity
Bilioenteric Anastomosis
HCC
B
3.3/Multiple
Yes
Yes
Yes
72/M
HCC
A
2.0/Single
No
No
No
3
52/M
HCC
B
1.5/Single
No
No
Yes
4 5
61/M 72/M
Liver metastasis of cholangiocarcinoma Liver metastasis of cholangiocarcinoma
A A
3.8/Multiple 2.3/Single
Yes Yes
Yes No
No No
6 7 8
54/F 61/M 45/F
A A A
4.0/Single 4.0/Multiple 2.4/Multiple
No No Yes
No No Yes
No No No
9
70/M
HCC Liver metastasis of lung carcinoma Liver metastasis of gallbladder carcinoma HCC
A
3.0/Single
No
No
No
10
71/M
Liver metastasis of pancreatic carcinoma
A
1.8/Single
Yes
Yes
No
Pt. No.
Age (y)/ Sex
1
60/M
2
Disease
Pneumobilia on CT
History of TAE
Note.—TAE ⫽ transcatheter arterial embolization.
treatment, such as percutaneous drainage in combination with systemic antibiotics. However, as shown in the previous studies as well as our study, infectious complications are likely to be fatal in some cases, or permanent biliary drainage may be sometimes necessary as a result of a nonhealing biliary fistula (13,14,17,24). The mechanism of abscess development after percutaneous ablation therapy is not established, but subsequent bacterial contamination of the ablated necrotic lesions may lead to abscess formation (23). In interventional procedures, aseptic technique to prevent skin contamination is required. In our study, no skin flora was noted in cultured organisms. Analyzing our 10 cases of cholangitis/liver abscess, multiple treatments by PMC or RF ablation for the larger nodules might have been related to the development of abscess in two sessions (patients 6 and 7), even though the size of nodules was not a significant risk factor. In one session (patient 3; HCC nodule near the hepatic hilum), we suppose the direct damage of ethanol might have led to stenosis of hilar biliary tracts and cholangitis. In two cases (patients 2 and 9), the etiology of cholangitis/liver abscess was unknown. In the other five cases (patients 1, 4, 5, 8, and 10), previous bil-
ioenteric anastomosis is likely responsible for the development of cholangitis/abscess formation. Several processes related to ablation therapy and bilioenteric anastomosis may enhance the development of cholangitis and abscess formation. First, bilioenteric anastomosis is associated with retrograde enteric bacterial contamination of the biliary tract in as many as 90% of patients (21). In tumor ablation therapies, the traffic between necrotic tissues produced by ablation therapy and biliary tracts is likely to enhance abscess formation by contaminated enteric bacteria. Of the five patients with bilioenteric anastomosis in whom cholangitis/liver abscess occurred after ablation therapies, four patients exhibited pneumobilia on pretreatment CT. In the three patients treated with abscess drainage, cultured organisms were from an enteric source: E coli, Enterococcus species, and E cloacae (Table 1). Second, bilioenteric anastomosis is required after excision of lymph nodes in the hepatoduodenal ligament and removal of peribiliary arterial plexus. Direct damage by ablation to the ischemic biliary tracts may enhance the development of cholangitis. In the study of the Italian Multicenter RF Study Group (24), two of the six patients with abscesses had pneumobilia resulting from previous gas-
trointestinal surgery. Vogl et al (25) demonstrated that patients with liver metastasis from pancreatic carcinoma who had undergone Whipple procedures had significantly more abscesses than patients with metastases from other primary tumors undergoing laser-induced thermotherapy. Our study showed that chemical ablation with ethanol, as well as thermal ablation with microwave or RF energy, is likely to induce cholangitis/liver abscess in patients with bilioenteric anastomoses. Bilioenteric anastomoses are created not only in patients with pancreatic and biliary malignant lesions, but also in those with intrabile tumor growth of HCC (27,28). The rate of cholangitis/liver abscess in our study (1.5%) was higher than those in previous reports (0.3%– 0.7%) (23–25), which may be because more patients with bilioenteric anastomoses were included in our study. The rate of occurrence of cholangitis and/or liver abscess in patients with metastases (five of 105) was five times greater than that in patients with HCC (five of 578). On Fisher exact probability test and univariate logistic regression, disease (HCC/metastasis) was found to be a significant predictor, but stepwise regression analysis showed presence of bilioenteric anastomosis to be the sole significant predictor of cholangitis/
Volume 14
Number 12
Type of Ablation
Prophylactic Antibiotics
Shibata et al
Cholangitis and/or Abscess
Treatment
Organism from Abscess
PEI
No
Both
Conservative therapy
–
PEI
No
Cholangitis
Conservative therapy
–
PEI
No
Both
Conservative therapy
–
PMC PMC
No No
Both Both
Surgical abscess drainage Percutaneous abscess drainage
PMC RF PEI
No No Yes
Abscess Both Cholangitis
Percutaneous abscess drainage Percutaneous abscess drainage Conservative therapy
PEI
No
Both
Percutaneous abscess drainage
PEI
Yes
Both
Percutaneous abscess drainage
liver abscess formation (Table 2). These results were obtained because some patients with bilioenteric anastomosis caused by pancreatic or biliary malignant lesions were included among those with metastasis, and patients with HCC rarely underwent creation of bilioenteric anastomoses. Prophylactic antibiotic administration was reported to be effective to prevent infectious complications in interventional procedure (21). However, two patients with bilioenteric anastomosis (patients 8 and 10) in whom cholangitis/liver abscess occurred after PEI had prophylactic antibiotic ad-
•
1541
Prognosis of Cholangitis and/or Abscess
Died of septic shock 12 days after PEI Recurrent cholangitis and abscess
E. coli Enterococcus species No isolation E. coli – Recurrent cholangitis and abscess
K. pneumoniae, Enterococcus species E. cloacae
ministration. In our study, lack of prophylactic antibiotic administration was not a risk factor. Kim et al (17) described a prophylactic regimen that failed to prevent abscess formation after hepatic chemoembolization for patients with earlier bilioenteric anastomosis. However, Geschwind et al (29) showed that aggressive antibiotic prophylaxis with bowel preparation may provide protection against intrahepatic abscesses after chemoembolization in patients who have a history of biliary reconstructive surgery. Further evaluation seems necessary to determine the effectiveness of aggressive
Complicated lung abscess
antibiotic prophylaxis and bowel preparation when tumor ablation therapy is performed in patients with bilioenteric anastomoses. The presence of bilioenteric anastomosis may not be a contraindication to ablation therapy because cholangitis/liver abscess do not always occur in these patients, but utmost care should be taken when ablation therapy is selected for these patients. In conclusion, the presence of bilioenteric anastomosis was a risk factor for cholangitis and/or liver abscess after tumor ablation therapies. Careful posttreatment attention should be
Table 2 Relationship between Variables and Cholangitis/Liver Abscess in 683 Sessions of Ablation Therapy According to Univariate Logistic Regression Analysis Variables Age (y): mean ⫾ SD (range) Disease (HCC/metastatic liver tumor) Child-Pugh class (A/B) Size of nodules (cm): mean ⫾ SD (range) Multiplicity of nodules (solitary/multiple) History of TAE (yes/no) Presence of bilioenteric anastomosis (yes/no) Prophylactic antibiotic administration (no/yes) Note.—TAE ⫽ transcatheter arterial embolization
64 ⫾ 11 (14–83) 578/105 578/105 2.6 ⫾ 1.1 (0.8–5.0) 527/156 222/461 23/660 459/224
P Value
r2
Odds Ratio
95% CI
.441 .007 .684 .618 .205 .404 ⬍.001 .394
.005 .069 .002 .002 .015 .008 .218 .008
1.02 0.175 0.723 0.869 0.438 0.515 36.39 1.968
0.97–1.07 0.05–0.61 0.15–3.45 0.50–1.51 0.12–1.57 0.11–2.45 9.67–136.9 0.42–9.34
1542
•
December 2003
Cholangitis and Liver Abscess after Ablation Therapy
paid after ablation therapies in patients with bilioenteric anastomoses. References 1. Shiina S, Tagawa K, Niwa Y, et al. Percutaneous ethanol injection therapy for hepatocellular carcinoma: results in 146 patients. AJR Am J Roentgenol 1993; 160:1023–1028. 2. Kotoh K, Sakai H, Sakamoto S, et al. The effect of percutaneous ethanol injection therapy on small solitary hepatocellular carcinoma is comparable to that of hepatectomy. Am J Gastroenterol 1994; 89:194 –198. 3. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995; 197:101–108. 4. Livraghi T, Benedini V, Lazzaroni S, et al. Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma. Cancer 1998; 83:48 –57. 5. Solbiati L, Ierace T, Goldberg SN, et al. Percutaneous US-guided RF tissue ablation of liver metastasis: results of treatment and follow-up in 16 patients. Radiology 1997; 202:195–203. 6. Curley SA, Izzo F, Delrio P, et al. Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies. Ann Surg 1999; 230:1– 8. 7. Livraghi T, Goldberg SN, Lazzaroni S, et al. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210:655– 661. 8. De Baere T, Elias D, Dromain C, et al. Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 2000; 175:1619 –1625. 9. Sato M, Watanabe Y, Ueda S, et al. Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 1996; 110:1507–1514. 10. Seki T, Wakabayashi M, Nakagawa T, et al. Percutaneous microwave coag-
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
ulation therapy for solitary metastatic liver tumors from colorectal cancer: a pilot clinical study. Am J Gastroenterol 1999; 94:322–327. Lu MD, Chen JW, Xie XY, et al. Hepatocellular carcinoma: US-guided percutaneous microwave coagulation therapy. Radiology 2001; 221:167–172. Vogl TJ, Mack MG, Roggan A, et al. Internally cooled power laser for MRguided interstitial laser-induced thermotherapy of liver lesions: initial clinical results. Radiology 1998; 209:381– 385. Zagoria RJ, Chen MY, Shen P, et al. Complications from radiofrequency ablation of liver metastases. Am Surg 2002; 68:204 –209. Shibata T, Yamamoto N, Ikai I, et al. Choledochojejunostomy: possible risk factor for septic complications after percutaneous hepatic tumor ablation. AJR Am J Roentgenol 2000; 174:985– 986. Okajima K, Kohno S, Tamaki M, et al. Bilio-enteric anastomosis as a risk factor for postembolic hepatic abscesses. Cardiovasc Intervent Radiol 1989; 12: 128 –130. De Baere T, Roche A, Amenabar JM, et al. Liver abscess formation after local treatment of liver tumors. Hepatology 1996; 23:1436 –1440. Kim W, Clark TW, Baum RA, et al. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 2001; 12:965–968. Young SS, Jin WC, Joon KH, et al. Liver abscess after transcatheter oil chemoembolization for hepatic tumors. J Vasc Interv Radiol 2001; 12:313–320. Okada S, Aoki K, Okazaki N, et al. Liver abscess after percutaneous ethanol injection (PEI) therapy for hepatocellular carcinoma: a case report. Hepatogastroenterology 1993; 40:496 – 498. Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagula-
21.
22.
23.
24.
25.
26.
27.
28.
29.
JVIR
tion therapy. Radiology 2002; 223:331– 337. Spies JB, Rosen RJ, Lebowitz AS. Antibiotic prophylaxis in vascular and interventional radiology: a rational approach. Radiology 1988; 166:381–387. Leoni CJ, Potter JE, Rosen MP, et al. Classifying complications of interventional procedures: a survey of practicing radiologists. J Vasc Interv Radiol 2001; 12:55–59. Rhim H, Yoon KH, Lee JM, et al. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics 2003; 23:123–134. Livraghi T, Solbiati L, Meloni MF, et al. Treatment of focal liver tumors with percutaneous radiofrequency ablation: complications encountered in a multicenter study. Radiology 2003; 226:441– 451. Vogl TJ, Straub R, Eichler K, et al. Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: experience with complications in 899 patients (2520 lesions). Radiology 2002; 225:367–377. Shimada S, Hirota M, Beppu T, et al. Complications and management of microwave coagulation therapy for primary and metastatic liver tumors. Surg Today 1998; 28:1130 –1137. Kojiro M, Kawabata K, Kawano Y, et al. Hepatocellular carcinoma presenting as intrabile duct tumor growth: a clinicopathologic study of 24 cases. Cancer 1982; 49:2144 –2147. Tanoue K, Kanematsu T, Matsumata T, et al. Successful surgical treatment of hepatocellular carcinoma invading into biliary tree. HPB Surg 1991; 4:237–244. Geschwind JF, Kaushik S, Ramsey DE, et al. Influence of a new prophylactic antibiotic therapy on the incidence of liver abscesses after chemoembolization treatment of liver tumors. J Vasc Interv Radiol 2002; 13:1163–1166.