Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice

Abstract

BACKGROUND

Percutaneous transhepatic cholangiodrainage (PTCD) and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice, yet the safety and effect of endobiliary radiofrequency ablation (EB-RFA) combined PTCD is rarely reported, in this article, we report our experience of EB-RFA combined PTCD in such patients.

AIM

To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.

METHODS

Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected, the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases. The general conditions of all patients, preoperative tumour markers, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB), alkaline phosphatase (ALP), and glutamyl transferase (GGT) before and on the 7^th day after the procedure, as well as perioperative complications, stent patency time and patient survival were recorded.

RESULTS

All patients successfully completed the operation, TBIL and DBIL decreased significantly in all patients at the 7^th postoperative day (P = 0.009 and 0.006, respectively); the values of ALB, ALP and GGT also decreased compared with the preoperative period, but the difference was not statistically significant. Perioperative biliary bleeding occurred in 2 patients, which was improved after transfusion of blood and other conservative treatments, pancreatitis appeared in 1 patient after the operation, no serious complication and death happened after operation. Except for 3 patients with loss of visits, the stent patency rate of the remaining 14 patients was 100% 71% and 29% at the 1^st, 3^rd, and 6^th postoperative months respectively, with a median survival of 4 months.

CONCLUSION

EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety, which is worthy of further clinical practice.

Key Words: Biliary tract tumour; Malignant obstructive jaundice; Percutaneous transhepatic cholangiodrainage; Endoluminal radiofrequency ablation; Biliary radiofrequency ablation

Core Tip: Studied the efficacy and safety of endobiliary radiofrequency ablation using percutaneous transhepatic cholangiodrainage in 17 patients with malignant obstructive jaundice, all patients successfully completed the operation, total bilirubin and direct bilirubin decreased significantly after operation; perioperative biliary bleeding occurred in 2 patients, which was improved after transfusion of blood and other conservative treatments, pancreatitis appeared in 1 patient after the operation, and was improved by medication; during follow-up, the stent patency rate was 100% 71% and 29% at the 1^st, 3^rd, and 6^th postoperative months respectively, with a median survival of 4 months.

INTRODUCTION

Biliary and pancreatic malignant tumors are the most aggressive types of digestive malignancies. Despite the rapid development of comprehensive treatment in recent years, surgery remains the only effective curative treatment for these tumors. Due to the insidious onset of these tumors in the early stage, most patients may no longer be eligible for surgery due to vascular invasion and distant metastasis during diagnosis, and studies have shown that < 30% of these patients can undergo radical surgery[1]. Symptomatic supportive and comprehensive drug therapies are equally important for patients who cannot undergo surgery. Most patients commonly present with obstructive jaundice, and timely reduction of jaundice is crucial for improving patient prognosis and ensuring that follow-up comprehensive therapy is available.

Percutaneous transhepatic cholangiodrainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic nasobiliary drainage are the most common clinical procedures to control jaundice. For inoperable patients, a biliary stent is often placed during external drainage to ensure the internal circulation of bile. However, because the tumor is not treated, tumor tissues can easily pass through the grid structure of the stent to enter into the biliary tract postoperatively and cause obstruction again, resulting in a short stent patency time[2]. In this case, endobiliary radiofrequency ablation (EB-RFA) has emerged, and EB-RFA can achieve a certain effect of tumor inactivation and prolong the stent patency time concurrently. Reports on EB-RFA under PTCD in clinical practice are limited. After reviewing the clinical outcome of EB-RFA in patients with malignant obstructive jaundice in our department in recent years, we explored its safety and effectiveness.

MATERIALS AND METHODS

General information

We retrospectively selected patients with malignant obstructive jaundice who underwent EB-RFA under PTCD in the general surgery department of our hospital from January 2019 to December 2022. The inclusion criteria were the following: (1) Malignant tumor confirmed by imaging or pathology; (2) Presence of local invasion or distant metastasis, with no chance of radical surgery; (3) Presence of clear main bile duct obstructive dilatation on imaging and total bilirubin (TBIL) > 50 µmol/L; and (4) The patient can cooperate with the treatment and has provided informed consent.

Processes

We used EMcision’s Habib EndoHPB radiofrequency catheter with Ahgiodynamics’ RITA radiofrequency generator.

The procedure was performed using digital subtraction angiography, and the needle was inserted from the tenth to twelfth intercostal space in the right axillary midline, and the bile ducts of the right posterior lobe were selected as the target in all cases. After imaging confirmed the entrance of the needle into the dilated intrahepatic bile ducts, a wire guided the contrast tube into the distal end of the obstructed duct. After imaging clarified the obstruction location, a stiffer wire was used to pass through the obstructing segment and place the radiofrequency ablation catheter, and the working segment of the catheter was placed in the lesions for ablation treatment, using an ablation power of 8 W and duration of 120 s. The number of radiofrequency times should be determined based on lesion length, and in principle, the same lesion should receive only one radiofrequency, ensuring that the radiofrequency range covers all lesions. After the treatment, the obstruction was observed using imaging, and one to two biliary stents were placed in the lesion segment, and a drainage tube was placed in the intrahepatic biliary tract. Figure 1 shows the procedure.

Figure 1 Endobiliary radiofrequency ablation procedure under percutaneous transhepatic cholangiodrainage. A: Cholangiography showing obstruction of the lower bile duct; B: Placement of a radiofrequency ablation catheter in the stenotic segment and completion of ablation; C: Placement of a biliary stent in the stenotic segment.

Postoperative management

Intravenous pain management and hepatoprotective treatment were provided postoperatively. Blood routine, liver and kidney function, and ion and amylase indexes were reviewed on the first, third, and seventh days postoperatively. The amount and character of drainage fluid from the external drainage tube were observed, and the general condition and laboratory tests of the patient preoperatively and on the seventh postoperative day were recorded. Additionally, postoperative complications, such as bleeding and perforation, were recorded.

Follow-up

In the form of outpatient or telephone follow-up, the patients were re-examined at the 1^st, 3^rd, 6^th, and 9^th postoperative months, and laboratory tests and imaging examinations, such as abdominal ultrasound and computed tomography were performed. The stent patency time was recorded as the time between the treatment and beginning of the first rise in jaundice, and the stent patency time of patients who died of causes other than jaundice was recorded as the postoperative survival period. Moreover, postoperative patient survival and stent patency time were recorded.

Statistical methods

Data were processed using the SPSS 22.0 statistical software. Measurement data were tested for normality, and data conforming to the normal part were expressed as mean ± SD, and a t-test was used for comparison between groups. Data not normally distributed were expressed as median and interquartile spacing, and a rank-sum test was used for comparison between groups. Stent patency and survival rates at each postoperative time point were expressed as percentages.

RESULTS

General information

We included 17 patients, with 6 males and 11 females, aged 69.2 ± 11.1 years. The primary lesions were found in the pancreatic head, biliary tract, and gallbladder in 7, 6, and 2 patients, respectively, as well as the liver and duodenum in 1 patient each. The preoperative glucose-chain antigen 19-9 and methemoglobin levels were 10032 ± 28435.3 U/mL and 13.8 ± 44.7 ng/mL, respectively. Combined distant metastases were present in 21 Locations in 9 patients, of which 7 were liver metastases, 6 were retroperitoneal lymph node metastases, 2 were hilar lymph node metastases, 2 were portal vein invasions, 1 was splenic vein invasion, and 1 gallbladder, colon, and adrenal gland metastases each.

Treatment

All patients were successfully treated with EB-RFA under PTCD, with a 100% treatment success rate. All patients underwent single ablation, wherein one biliary stent was placed in 11 patients and two in 6, none of them was dilated with a balloon, and the radiofrequency catheter and biliary stent passed through the duodenal papilla in 13 patients.

Changes in biochemical indexes

All patients had different degrees of obstructive jaundice preoperatively, but the TBIL and direct bilirubin levels significantly decreased by the seventh postoperative day. However, the bilirubin levels of 3 patients remained at > 100 µmol/L on the seventh postoperative day, which was considered to be related to the late tumor stage and poor liver function. Compared with the preoperative period, albumin (ALB), alkaline phosphatase, and glutamyl transferase levels also decreased, but the difference was not statistically significant. Table 1 shows the changes in the biochemical indexes of the patients pre- and postoperatively.

Table 1 Changes in biochemical indices in all patients preoperatively and on postoperative day 7.

	Preoperative	Postoperative day 7	P value	t
TBIL (µmol/L)	285.4 ± 188.1	134.6 ± 127.1	0.009a	5.09
DBIL (µmol/L)	211.9 ± 134.4	96.4 ± 92.2	0.006a	5.44
ALB (g/L)	37.3 ± 18.6	33.3 ± 3.7	0.387	1.67
ALP (U/L)	491 ± 342.2	330.5 ± 241.9	0.124	2.95
GGT (U/L)	684.1 ± 448.2	439.5 ± 264.1	0.061	3.58

^aP < 0.05, differences are statistically significant.

TBIL: Total bilirubin; DBIL: Direct bilirubin; ALB: Albumin; ALP: Alkaline phosphatase; GGT: Glutamyl transferase.

Complications

The external drainage of all patients was clamped at 3–5 d postoperatively. Bile retransfusion, perioperative death, and secondary surgery were not reported. However, 2 patients (11.7%) had biliary bleeding, which improved after blood transfusion and other conservative treatments, and 1 patient (5.8%) had pancreatitis postoperatively, which improved with medication. The overall complication rate was 17.6%, and no serious complications, such as gastrointestinal perforation, biliary perforation, pancreatic leakage, liver failure, and other serious complications, occurred.

Stent patency and survival rates

Jaundice did not recur during the postoperative follow-up period. Except for 3 patients who were lost to follow-up, the stent patency rate of the remaining 14 patients was 100%, 71%, and 29% in the first, third, and sixth postoperative months, respectively. In terms of survival, 1 patient died due to cardiorespiratory failure, and 1 patient had toxic shock due to infection in the first postoperative month. Moreover, 6 and 3 patients died due to tumor progression and nontumor-related causes, respectively; 3 patients were still alive at the end of the study. Of the 11 patients followed up until death, the median survival was 4 months.

DISCUSSION

Malignant obstructive jaundice is one of the most common clinical symptoms in hepatobiliary and pancreatic tumors, and it requires immediate treatment. Although the commonly used biliary stent + drainage treatment can effectively reduce jaundice, it has no therapeutic effect on the tumor and is prone to early reinfarction within the stent caused by the progression or detachment of tumor tissues. However, subsequent jaundice is managed with external drainage, resulting in significant bile loss often requiring bile transfusion, which seriously affects the quality of life of patients. By contrast, the role of radiofrequency ablation technology in malignant tumors of the liver, kidney, and other substantial organs has been widely recognized worldwide, but its role in the treatment of biliary intraluminal tumors has been controversial due to concerns regarding postoperative biliary fistula and biliary stenosis[3].

Since the 21^st century, several animal experiments have confirmed that biliary radiofrequency ablation with a power of < 10 W and ablation time of < 120 s is safe and effective[4]. In 2011, Steel et al[5] reported the first case of human EB-RFA, and the study was completed under ERCP for 21 patients with malignant biliary obstruction treated with EB-RFA + biliary stenting, with no perioperative deaths. Biliary patency was 100% at 30 d postoperatively, and restenosis was noted in 3 patients at 90 d.

In 2013, the first case of EB-RFA + biliary stent placement under PTCD was reported[6]. The study enrolled 39 patients with unresectable biliary malignancies, who had a median postoperative stent patency time and survival of 84.5 and 89.5 d, respectively, with no significant perioperative complications.

Compared with ERCP, PTCD has a shorter operating path, a higher success rate, and a lower risk of postoperative pancreatitis and biliary tract infection. Moreover, compared with nasobiliary ducts, the external biliary drainage left by PTCD is more comfortable and hidden; therefore, the quality of life of patients is improved. For patients with biliary obstruction close to the hilar, the operational advantages of PTCD are much greater than those of ERCP. In our study, all the patients were successfully treated with PTCD, and no serious bleeding, infection, or pancreatitis occurred postoperatively. Although some studies showed a certain risk of tumor implantation and metastasis in the puncture path of PTCD[7], this phenomenon has not been observed in this study and other related reports, and the safety of EB-RFA + biliary stent placement under PTCD is satisfactory at this stage.

Our study showed that 17 patients had significantly decreased bilirubin levels at 7 d postoperatively, and liver function improved compared with the preoperative period. Although ALB also decreased, the difference was not statistically significant. Three patients had decreased bilirubin levels postoperatively, but it was significantly higher than normal levels. However, these patients had multiple distant metastases, and liver dysfunction may have caused jaundice, but they did not have irreversible liver failure postoperatively, indicating that EB-RFA + biliary stenting under PTCD can effectively reduce bilirubin levels and improve liver function in patients with malignant obstruction, without causing liver failure and other serious complications.

Compared with jaundice reduction, the more important role of combined EB-RFA treatment is improving the time of stent patency. In the early stage of stent placement, bilirubin levels were reduced to varying degrees regardless of concomitant radiofrequency ablation; however, patients with stenting alone may experience in-stent restenosis within a shorter period due to tumor progression, tumor debris obstruction, and other reasons. Qi et al[8] reported that patients with combined EB-RFA had lower rates of in-stent restenosis (30% vs 11.67%) and postoperative complications (25% vs 15%) at 6 months postoperatively compared with those who underwent PTCD + biliary stenting alone, but they did not mention the tumor stage of the patients. Additionally, Kinoshita et al[9] also confirmed that EB-RFA effectively controlled tumor cells from regeneration, improving treatment efficacy and delaying the onset of recurrent jaundice.

In this study, the stent patency rates of the 14 patients with follow-up data were 100%, 71%, and 29% in the first, third, and sixth postoperative months, respectively, which were lower than those reported in the previous literature. However, it should be mentioned that, due to the insidious nature of the early onset of biliary-pancreatic system malignancies, most patients clinically judged unresectable were in the terminal stage of the disease and had poor prognosis, which commonly occurs in China. Thus, some patients may die of other causes before jaundice recurs. Of the 11 patients followed up until death, only 6 died due to tumor progression, and the overall median survival was only 4 months, which was lower than that reported in other literature[8], which may be due to the late tumor staging and high number of distant metastases.

Due to the clinical characteristics of patients with end-stage tumors, the role of EB-RFA is to provide a better quality of life for patients and prolong biliary patency. Although Kadayifci et al[10] showed that re-radiofrequency ablation can unblock the obstructed biliary duct, multiple surgical procedures will significantly affect the overall condition of patients with advanced tumors. For patients who are not amenable to secondary treatment, biliary restenosis may require prolonged external drainage with bile retransfusion to maintain biliary and intestinal circulation, which can cause severe physical and psychological effects to the patient. Therefore, prolonging biliary patency through PTCD treatment with combined EB-RFA can provide a better quality of life for patients with advanced tumors to a certain extent. In this study, all patients did not require bile retransfusion during follow-up, indicating that combined EB-RFA can still be highly beneficial even for patients with a very short, expected survival period.

The EB-RFA technique was not widely promoted in the early stage because of concerns, such as the high risk of biliary tract injury. Teratani et al[11] showed that the tumor location was closely related to the incidence of biliary tract injury and concluded that the risk of injury was highest in hepatoportal cholangiocarpal malignant tumors located within a 5 mm distance from the first to second portal vein branches. Liang et al[12] reported two cases of biliary tract injury after EB-RFA with tumors between 5 and 10 mm from the hepatic hilum, but most studies[13] showed that the risk of biliary tract injury will significantly reduce with the advancement of ablation technology, assisted by strict ablation time control and timely drainage of the ablated segment. In this study, 2 patients had malignant tumors of the hilar bile ducts, 3 had high-located obstruction due to gallbladder or liver tumor invasion, and none had biliary tract injury.

Nakai et al[14] showed that 16 patients underwent ultrasound-guided ERCP combined with EB-RFA, and the overall perioperative complication rate was 19%, which was similar to the 17.6% in our study. However, Russolillo et al[15] reported acute pancreatitis in 12.5% of the 40 patients postoperatively, whereas our study only reported one cause of pancreatitis (5.8%), which may be related to the different tumor locations. Whether the ablation and stenting passed through the papilla or not, and other factors, more cases and studies are needed to summarize the specific technical points.

CONCLUSION

The technique of EB-RFA under PTCD has been performed for only 10 years, and its effect is rarely reported. Therefore, the safety and efficiency of EB-RFA is unclear. In our study, all patients underwent surgery successfully, and the postoperative jaundice reduction effect and the time of biliary patency were satisfied. Moreover, no serious postoperative complications occurred, indicating that this procedure is safe and effective, and has a high value for clinical treatment. However, further studies are needed to confirm the difference between patients who receive EB-RFA and stenting alone in terms of the speed of jaundice reduction, duration of stent patency, and onset of recurrence.