Recurrent hydrothorax due to diaphragmatic perforation post hepatocellular carcinoma radiofrequency ablation: A case report

1Liver Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain 3Thoracic surgery Unit, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain 4Radiology Unit, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain


Background
Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease and cirrhosis and therapeutic options are determined both by tumoral stage and the severity of the underlying liver disease.
Among ablative therapies, one of the most commonly used is radiofrequency ablation (RFA) which is considered a potentially curative therapeutic option and commonly accepted as the best alternative for patients with small HCCs (< 3 cm in diameter) who are not candidates for surgical resection or liver transplantation [2]. Although RFA is a minimally invasive procedure, well tolerated and with a low percentage of side effects, severe and potentially fatal complications can occur.
Here, we report an uncommon complication of RFA presented as a recurrent hydrothorax 6 months after the procedure due to a diaphragmatic perforation.

Case report
A 72-year-old woman was admitted because of recurrent hydrothorax ( Figure 1). The patient had liver cirrhosis secondary to Metabolic Associated Fatty Liver Disease (MAFLD) in Child-Pugh's stage B (8 points). The patient had previously presented an esophageal variceal bleeding. During follow-up, a 27 mm HCC was diagnosed in segment VI (Figure 2), that was successfully treated by RFA in May 2018. The patient was followed in the outpatient clinic  (Figure 3), hydrothorax was not present at that time. A new RFA was performed in September 2019 without complications. Six months after the procedure, the patient was admitted to the hospital for dyspnea. A right hepatic hydrothorax was observed, and a thoracentesis con irmed the presence of a pleural effusion compatible with a transudate (protein 1.9 g/dL, LDH 110 IU/L) without signs of infection and no malignant cells in the cytological extension. Despite repeated thoracocentesis and diuretic treatment, pleural effusion recurred. A thoraco-abdominal CT showed a cirrhotic liver without new lesions, moderate ascites, splenomegaly, patent portal vein with a splenorenal shunt, and moderate pleural effusion without pleural or lung lesions.
With the intention of performing a chemical pleurodesis, a video-assisted thoracoscopy surgery (VATS) was performed demonstrating the presence of a diaphragmatic perforation 4 cm in diameter ( Figure 4) which was surgically repaired. In the immediate postoperative period, a pleural drainage was required due to hydrothorax recurrence. After 10 weeks, the patient remains without pleural luid despite having abdominal ascites that has required multiple evacuating paracentesis.

Discussion
RFA provides long-term local control for most selected patients with small hepatocellular carcinoma, with the possibility of long-term disease-free survival. Complete radiographic response rates (complete necrosis) following RFA are 90% to 99% for tumors < 5 cm, with the highest and most consistent response rates for lesions ≤ 3 cm [5,6].
Although RFA is relatively well tolerated, severe and potentially fatal complications can occur. Major complications develop in 2% to 11% of procedures, and the mortality rate is 0.1% to 0.8% [4,5]. Among the most frequent complications, it is worth to mention haemorrhagic complications (intraabdominal or intra-hepatic bleeding, subcapsular hematoma or haemobilia), liver abscess, skin burns, pneumothorax or pleural effusion. Diaphragm perforation (with or without herniation) is a rare major complication [7]. The mechanism of diaphragm perforation after RFA has not been clari ied yet, although three causative factors have been described: tumor location, collateral thermal injury and advanced cirrhosis status. Similar to our case, location is one of the most important causative factors. This is especially    important in peripheral subcapsular tumors, since the risk of diaphragmatic thermal injury increases, as the visualization by the radiologist using ultrasounds is complicated due to the lung and ribs interference. Although not as well studied, the incidence of pleural effusion is about 0.1%, with a similar rate for diaphragmatic hernias [7].
Hepatic hydrothorax is the presence of pleural effusion in a patient with cirrhosis without evidence of cardiopulmonary disease. It occurs in 5% -15% of patients with cirrhotic portal hypertension and is associated with high mortality [1].
It has been proposed that the combination of positive intraabdominal pressure and negative intrathoracic pressure facilitates the movement of luid from the peritoneal cavity into the pleural space through defects in the diaphragm.
The differential diagnosis of hepatic hydrothorax in HCC patients who undergo RFA includes malignant, infectious and diaphragm injury-related pleural luid. The study of the pleural effusion after RFA should include a diagnostic thoracentesis with biochemistry, cytological extension and microbiological culture. In addition, a thoracic CT scan is mandatory to rule out the presence of a lung or pleural tumor, or any anatomical defects. Hepatic hydrothorax can occasionally be diagnosed through direct visualization of diaphragmatic defects by VATS, although this procedure is invasive and should be performed only if the diagnosis remains unclear or it is planned to repair the defect.
There are some techniques to prevent or minimize diaphragmatic thermal injury mostly related to tumor location issues, such as arti icial ascites, arti icial pleural effusion, carbon dioxide insuf lation or laparoscopy assisted ablation [2].
Approximately 50 RFA are performed per year since 2004 in our hospital. This is the irst documented case of hydrothorax secondary to a diaphragmatic defect caused by this procedure in our Liver Unit. Another case was detected years ago in our center, but we couldn't ind enough data to report it.
In conclusion, the present report presents a case of recurrent hepatic hydrothorax due to a diaphragmatic perforation after RFA. Although this complication is uncommon, clinicians should be aware of its occurrence, and keep in mind this possibility as part of the differential diagnosis in a patient with liver cirrhosis and HCC, after a RFA procedure especially in subcapsular and subphrenic locations.