Biliothoracic Fistula after Microwave Ablation of Liver Metastasis : Literature Review

Microwave ablation is a safe and effective interventional approach, widely used in the treatment of unresectable primary or metastatic hepatic lesions. Thoracobiliary fistula is a rare postablation complication that can be treated with a conservative or surgical approach. We reviewed aetiology, pathogenesis, clinical picture, diagnostic possibilities, and therapeutic options for biliothoracic fistula developed after microwave ablation of liver metastasis. Furthermore, we reported our experience of successful conservative management of a nonhealing thoracobiliary fistula occurred after percutaneous thermal ablation of colorectal cancer liver metastasis. Our case supports a conservative approach based on percutaneous biliary system decompression and synthetic glue embolization for the treatment of combined biliopleural and biliobronchial fistula.


Biliothoracic Fistula
Almost 30% of patients with metastatic colorectal cancer (CRC) present with liver metastases only. Although surgical resection is the most effective treatment, patients with isolated CRC liver lesions, deemed to be unresectable, may benefit from thermal ablation (Radiofrequency Ablation, RA, and Microwave Ablation, MWA) or Trans-Arterial Chemoembolization (TACE) [1][2][3].
We report our experience on combined BPF and BBF treated conservatively in a patient with CRC single liver metastasis undergone MWA.

Our Experience
In January 2020, a 73-year-old man with a history of metachronous and unresectable CRC liver metastasis ( Figure 1) was admitted to our center because of fatigue and shortness of breath. Since March 2016, the patient has been treated with a multidisciplinary approach characterized by chemotherapy plus targeted therapy and MWA. In particular, MWA of the single hepatic lesion at segment V was performed twice: in October 2016 and November 2019.
At the time of admission, the chest X-rays showed rightside pleural effusion (Figure 2(a)) and the thoracentesis revealed bilious fluid; thus, a chest drainage was inserted. A chest and abdomen CT scan confirmed the pleural effusion and revealed postablation liver damage (Figure 2(b)). e clinical hypothesis of BPF was demonstrated by means of ERCP with contrast extravasation from the liver towards the pleural cavity (Figure 2(c)). After sphincterotomy, a bilioduodenal endoprosthesis and multiple biliary stents (AdvanixBiliary stent-Boston Scientific ® 10 Fr x 12 cm) were placed to decompress the intrahepatic biliary system adjacent the ablated lesion (Figure 3(a)-3(c)). After this procedure, the amount of biliary fluid from the chest tube progressively decreased and chest X-rays demonstrated the reduction of pleural effusion; thus, the chest tube was removed after two weeks, and the patient was discharged home. Ten days later, he was readmitted at our hospital with fever, dyspnea, and productive cough with greenish sputum. Blood examination showed elevated value of white blood cells count and C-reactive protein. Bacteria culture of blood revealed Enterococcus faecium. e chest and abdomen CT scan showed a large lung abscess of the middle lobe communicating with a bilioma of the hepatic segments V-VIII by means of a long and thin BBF (Figure 4(a)). e aforementioned findings were confirmed by the percutaneous cholangiography. is exam revealed a "Y"-shaped fistula originating from the intrahepatic bilioma and dividing in two arms which reached separately the pleural space (BPF) and the middle lobe abscess up to one segmental bronchus (BBF). Moreover, bilioduodenal endoprosthesis obstruction was observed (Figure 4(b)). Immediately, the pleural space and the middle lobe abscess were drained by two chest tubes (10Fr pigtails) and appropriate antibiotic therapy was started. In order to minimize the pressure in the biliary tree and prevent the bile flow through the TBF, we drained the bilioma with a 10Fr pigtail catheter and we introduced a percutaneous transhepatic biliary drainage (10Fr pigtail) with a percutaneous transhepatic approach. Regarding the BBF and BPF, we decided to treat them with percutaneous synthetic glue embolization (Glubran mixed with Lipiodol 1 : 3). Sixteen days after, there was no evidence of BBF and BPF at percutaneous cholangiography ( Figure 5(a)). Consequently, we decided to remove both chest and abdomen drainages. Presently, the patient is alive and free from cancer recurrence 14 months after the last liver metastasis MWA and almost 5 years after the diagnosis of CRC (Figures 5(b) and 5(c)).
Written informed consent was obtained from the patient. All procedures were in accordance with the ethical standards of the institutional and national research committees and with the Helsinki Declaration, as revised in 2013.

Discussion and Literature Review
For patients not eligible for surgery, MWA can be offered as a valid alternative option for liver metastasis from CRC [1][2][3]. Despite its safe profile, MWA may have several complications including vascular injury, biliary damage, and infections [4]. e incidence of biliary tract thermal ablation complications (e.g., biliary strictures, bilomas, and bile leaks) ranges between 0.1% and 12% of cases, and TBF are exceedingly rare [5,7,9]. Postablation tissue inflammation can be considered the main trigger process causing adhesion between the liver and diaphragm. Furthermore, the biliary stricture and the intrapleural pressure lower than abdominal pressure play a role in the fistula formation and favor the flow of bile toward the pleural space. Consequently, the risk of this complication is higher when treating voluminous lesions located near the diaphragm (i.e., lesions in hepatic segments VII or VIII) [10][11][12][13].
Despite the diffusion of thermal ablation for the treatment of liver metastases, the literature reports higher rates of postablative TBF in patients with primary hepatic tumor than in patients with secondary liver lesions [8,12,14]. We speculate that hepatocarcinoma and intrahepatic cholangiocarcinoma are often voluminous and subdiaphragmatic lesions with consequently high risk of bile leaks. e diagnosis of TBF is based on radiologic imaging. CT scan and magnetic resonance, indeed, can show indirect signs of biliopleural communication as pleural effusion, intrahepatic bile duct dilatation, and postprocedure liver damage close to the diaphragm. Conversely, cholangiography is the procedure of choice to identify the biliary leak.
e combination of pathognomonic clinical symptoms, a history of recent locoregional liver procedure, and radiological imaging, guide the diagnosis [10,15,16]. e optimal treatment for TBF is far to be defined [7,16]. Although the surgical approach based on debridement and ductal repair has been long advocated [6,12], less-invasive treatments have recently developed [16][17][18]. None of the patients with postablative TBF for liver metastasis described in the literature underwent surgery (Table 1) [14,[16][17][18][19][20]. e conservative approach is aimed to decrease the pressure in the biliary tree and to prevent the flow of bile through the TBF, enhancing its closure [7]. Biliary drainage can be performed by ERCP with endoprosthesis or stent placement or by means of the PT approach [17][18][19][20]. e synthetic glue treatment is a minimally invasive and safe technique, already used for endoscopic cure of gastrointestinal fistula and as an embolizing agent in interventional radiology and vascular neuroradiology. e successful use of Glubran ® glue to seal the TBF is described in few reports [16].

Conclusions
TBF is a rare postablation complication characterized by relevant mortality and morbidity rates. e diagnosis of TBF requires a high index of suspicion. Indeed, early detection and conservative management with biliary drainage may prevent severe sequelae. e current case highlights the successful management of an iatrogenic, nonhealing TBF. We initially decided to decompress the biliary system with endoscopic stent placement. However, this method offered a short-term benefit followed by pleural effusion recurrence complicated by BBF. Percutaneous drainages, biliary decompression, and the injection of glue in both BBF and PBF resulted in prompt resolution of biloptysis and pleural effusion. Glubran ® glue embolization of the TBF is effective, safe, and should be considered for the treatment of TBF before recourse to surgery.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.