Salemis, Nikolaos S. MD, PhD; Tsohataridis, Efstathios MD
Although surgical excision is the gold standard of treatment of patients with colorectal liver metastases, only 10% to 20% are eligible for resection as most of them have an advanced disease at the time of presentation.1 Criteria of a nonresectable disease may include multifocal deposits with bilobar distribution, proximity of the tumor to great vessels, extrahepatic spread, inadequate hepatic reserve and various comorbidities.2,3 For the local control of the disease in patients with unresectable metastatic liver tumors, a variety of ablative techniques have been developed in recent years. These include percutaneous ethanol injection, cryosurgical ablation, interstitial laser photocoagulation, microwave coagulation, and radiofrequency ablation (RFA).4 Regarding RFA, many published series have verified its effectiveness in achieving local control of metastatic liver disease, with acceptable mortality and morbidity rates.5-7
A 69-year-old man with a history of heart failure and diabetes mellitus was admitted with a prediagnosed ascending colon adenocarcinoma with liver deposits. During surgery, 3 metastases measuring 3, 2.5, and 5 cm were found in liver segments 2, 3, and 8, respectively. The patient underwent a right hemicolectomy with simultaneous wedge resection of the metastases of the left liver lobe. Because of the patient's poor general condition and the size and location of the metastasis in the liver segment 8, we decided to use RFA. The Radionics Cooltip radiofrequency system (Radionics/Tyco Hellas) was used for the ablation. There were no intraoperative complications. Ultrasonography performed the following day was normal. On the fifth postoperative day, the patient had a sudden onset of high-grade fever, malaise, and right-sided abdominal and chest pain. On clinical examination, a right upper abdominal tenderness was apparent. He had a temperature of 39°C, blood pressure of 105/55 mm Hg, and a respiratory rate of 17 breaths per minute. There were no clinical findings of biliary obstruction.
Laboratory evaluation showed left shift with a leukocytosis of 18 × 103 cells/dL, 89% neutrophils, hemoglobin level of 13 g/dL, aspartate transaminase of 48 U/L, alanine transaminase of 75 U/L, alkaline phosphatase of 260 IU/L, and total bilirubin level of 1.4 mg/dL.
Computerized tomography scans and ultrasonography revealed the presence of a 6 × 7-cm collection with air-fluid level at the site of RFA in the right liver lobe (Fig. 1) and a right pleural effusion. As soon as the diagnosis of liver abscess was established, the patient started broad-spectrum antibiotics and underwent percutaneous computed tomography (CT)-guided drainage of the collection. Blood cultures and cultures of the collection fluid were positive for Escherichia coli. The patient was administered with ciprofloxacin, and the symptoms were gradually resolved. The drain catheter was left in place for 10 days, and the repeat imaging scans revealed an almost complete resolution of the abscess cavity. The patient was discharged on the 13th postoperative day. The pathological examination revealed a T3N1M1 tumor, whereas one of the 23 resected lymph nodes was found to contain metastases Adjuvant chemotherapy followed. Follow-up examinations performed 3 and 6 months after RFA did not reveal tumor recurrence or other pathological findings.
Malignant liver tumors, either primary or metastatic, are very common.2 Hepatocellular carcinoma is one of the most common primaries, although the liver can be the metastatic site of other malignancies like colorectal cancer, breast cancer, neuroendocrine tumors, and sarcomas. Although radical surgical excision is the treatment of choice with a 5-year survival rate of 20% to 35%, most of the patients are not eligible candidates as they present with an advanced disease.2,4
In recent years, RFA is increasingly used in the management of patients with unresectable liver tumors. Radiofrequency ablation uses a high-frequency alterating current that is applied from a radiofrequency generator through a needle electrode placed directly into the tumor. This current causes ionic agitation and results in tumor cell death because of localized frictional heating and thermal coagulative necrosis.1,7
Radiofrequency ablation can be performed percutaneously or during laparotomy or laparoscopy.4,8 The percutaneous approach is less invasive but has many limitations such as the location of the lesions, the inability to deal with small undetected lesions, and the potential for iatrogenic injuries to the surrounding structures. Although laparotomy requires general anesthesia, it has the advantages of a thorough exploration of the abdomen because of its potential combination with resection or locoregional chemotherapy.7,8 Laparotomy permits the discovery and treatment of unsuspected lesions in 30% of the patients, resulting in an increase of their survival.9
Although RFA of unresectable liver tumors is a relatively safe technique characterized by low mortality (0%-1.4%) and morbidity (2.2%-14%) rates, a variety of complications have been reported. The most common are liver abscess, intraperitoneal bleeding, injury of the major bile ducts, biloma, ground pad burns, and injury to the adjacent vulnerable structures like diaphragm, duodenum, and colon.5-7,10,11 Less frequently, cardiopulmonary complications and tumor seeding along the course of the electrode track have been reported.6,11
Liver abscess formation after RFA has a reported incidence of 0% to 2.2%5,6,10-18 (Table 1). Its most common symptoms are high-grade fever (>38°C) lasting more than 3 to 5 days, chills, and right upper quadrant pain accompanied by elevated white blood cell count.12 Although in some cases, the patients are asymptomatic, and the abscess is diagnosed at a scheduled follow-up CT.11,12
Although the mechanism of abscess formation after RFA is not clearly established, biliary abnormalities, immunocompromising conditions like diabetes mellitus and cirrhosis, and breaks in the sterile technique have been defined as risk factors.18 Biliary abnormalities can be divided into 2 major groups.12 On the first group, the ablated hepatic parenchyma may get ascendingly infected through a communication between the nonsterile gastrointestinal tract and the biliary tree, such as bilioenteric anastomosis, endoscopic papillotomy, bilioenteric fistula, or external biliary drainage. Bilioenteric anastomosis is related to retrograde enteric bacterial contamination in 90% of patients with abscess after interventional procedures.12 On the second group, the intrahepatic bile ducts are dilated as a result of a tumor invasion, extrinsic compression, strictures, or Clonorchis sinensis infections. Mulier et al,19 in a review, reported 34 (0.9%) hepatic abscesses among 3670 patients who were treated with percutaneous, laparoscopic, or open RFA. At least 8 of the patients who developed an abscess had a history of biliary tract intervention: 4 had a biliary stent, 3 had a biliary anastomosis, and 1 had a biliary stricture. Decadt and Siriwardena,20 in another study, reviewed 1931 patients with 3870 unresectable tumors and reported 15 hepatic abscesses (0.77%).
Livraghi et al6 reported a 0.3% incidence of liver abscess among 2320 patients with 3554 tumors and who underwent percutaneous RFA. Two of 6 patients had pneumobilia caused by a previous bilioenteric anastomosis, whereas 3 had diabetes mellitus. Shibata et al18 reported a 1.5% incidence of infectious complications, cholangitis or liver abscesses after RFA, percutaneous ethanol injection, and percutaneous microwave coagulation. Five of 10 patients who developed these complications had a history of a bilioenteric anastomosis, whereas in 4 of them, pneumobilia was apparent on CT before ablation.
De Baere et al11 reported 7 cases of liver abscess among 350 sessions of percutaneous and open RFA. All abscesses occurred in the group of patients who underwent the percutaneous procedure. A high significant difference concerning the rate of abscess was found between patients with (3/3) and without (4/223) bilioenteric anastomosis in a total of 226 patients who underwent the percutaneous procedure.
Liver abscesses are usually diagnosed 3 to 60 days after RFA.11,12 However, a case where the abscess developed 5 months later has been reported.17 The late occurrence of an abscess indicates that there should probably be an interval between RFA and the administration of any subsequent immunodepressive treatment such as chemotherapy.17
The imaging appearance of a postablation liver abscess is similar to that of usual hepatic abscess.10 New gas bubbles not previously seen could indicate an infection,10 whereas an abscess should be strongly considered when a substantial air echogenicity is detected at sonography 1 day or more after RFA.12 In 79% of the abscesses, a substantial amount of air detected on CT appeared as gas bubbles, whereas an air fluid level appearance is less common.12 Thus, an immediate follow-up CT is a reliable modality for detecting any complications after RFA.10
Percutaneous image-guided drainage combined with adequate antibiotics is the treatment of choice for liver abscess after RFA.6,10,12 Although in some cases, an open exploration is required.6,15 Aspirate cultures are usually positive for E. coli and Enterococcus species, whereas other cultured organisms may include Klebsiella pneumoniae, Proteus vulgaris, Clostridium perfringens, Bacteroides fragilis, Streptococcus, Staphylococcus epidermidis, Morganella morganii, and Candida albicans.12,18,19,21 Antibiotic prophylaxis encompassing these large spectrum of pathogens is difficult to devise.21 A reasonable choice of antibiotics is amoxicillin plus clavulanic acid that is very active against all these organisms.19 Other antibiotics used in various series include cefazolin, cefmetazole, piperacillin/tazobactam, and ceftriaxone plus metronidazole.11,18,21 Regarding the duration of the postablation antibiotic prophylaxis, a prolonged 3-month administration of rotating oral antibiotics is recommended for patients who have biliary disease.15
Prophylactic antibiotic administration has not been effective in the prevention of abscess formation, and its use remains controversial.6,10 In a report from the Italian multicenter radiofrequency group, 3 of 6 patients who developed hepatic abscess received antibiotic prophylaxis, whereas the remaining 3 did not.6 Shibata et al18 reported that lack of antibiotic administration was not a risk factor in the abscess formation. De Baere et al11 also reported that patients with bilioenteric anastomosis developed an abscess, despite prolonged antibiotic administration. In our case, perioperative antibiotic administration also failed to prevent the abscess formation.
Further prospective evaluation is needed to determine the effectiveness of aggressive antibiotic prophylaxis after ablation therapy in patients with a history of bilioenteric procedures or other risk factors.12,18 As the type and regimen of antibiotic therapy are not uniform among the various centers, a consensus on a well-defined protocol has yet to be determined.6 Although the existence of a bilioenteric anastomoses is not a contraindication,12 great care should be taken when ablation therapy is performed in this group of patients, whereas close posttreatment attention is mandatory.18 The implementation of an aseptic technique is of great importance and should always be kept in mind during the whole procedure.10 We recommend a prolonged use of antibiotics in high-risk patients who have a biliary disease or an immunocompromising condition like diabetes or cirrhosis and in patients undergoing simultaneous RFA with colon resection.
Regarding the relation between the time of the biliary drainage construction and the risk of liver abscess after RFA, Elias et al21 reported that, when the biliary drainage procedure was performed before RFA, the risk of liver abscess formation was very high (44%), whereas when the biliary drainage was performed simultaneously with RFA, the relative risk was 0%.
The diagnosis of a liver abscess may, in some cases, be delayed because it can be misdiagnosed as a postablation syndrome.10 The latter clinical entity affects one third of the patients undergoing RFA22,23 and is characterized by low-grade fever, malaise, chills, pain, and nausea. It occurs approximately 3 days after the procedure and lasts for 5 days, with its most significant predictor being the volume of the ablated tissue. Post-RFA syndrome is self-limiting within 10 days after the procedure. Therefore, if a low-grade fever lasts for more than 10 to 14 days, the possibility of an abscess should always be considered.10,23 However, the onset of fever higher than 38.5°C any time after RFA associated with leukocytosis may indicate an abscess, and the appropriate diagnostic evaluation including ultrasonography and CT scans is mandatory.
Regarding the relation between the time of colonic resection and RFA, Berber et al14 reported, among 310 patients undergoing laparoscopic RFA for liver tumors, 16 patients who underwent RFA synchronously with a colorectal procedure. They reported no increase of the morbidity or liver abscess rates and concluded that laparoscopic RFA may be safely used synchronously with colon resections, compared with synchronous liver and colon resection that is associated with increased morbidity.
Liver abscess formation after RFA is a rare but major complication and should be considered mainly in high-risk patients with biliary abnormalities like bilioenteric anastomoses because they are prone to ascending infections of the biliary tree. Close clinical and laboratory monitoring of all patients after RFA is mandatory for the early detection and appropriate management of a liver abscess. Although antibiotic prophylaxis is especially recommended in high-risk patients, it, however, seems that it cannot prevent the liver abscess formation in all of the patients, and its use remains controversial.
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