Management hepatolithiasis with operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy

Hangzhou, China

Management hepatolithiasis with operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy

Zhi-Jun Jiang, Ying Chen, Wei-Lin Wang, Yan Shen, Min Zhang, Hai-Yang Xie, Lin Zhou and Shu-Sen Zheng

Hangzhou, China

BACKGROUND:Hepatolithiasis is very common in East Asia. It is benign in nature, but has a high recurrence rate. It is likely to lead to biliary cirrhosis and increase the risk of cholangiocarcinoma. Hence, the treatment of hepatolithiasis is diff i cult but vital. In this report, we present a novel approach to manage hepatolithiasis using the choledochoscopic Frequency-Doubled Double pulse Nd:YAG (FREDDY) laser lithotripsy combined with or without hepatectomy.

METHODS:Between July 2009 and October 2012, 45 patients underwent choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy (laser lithotripsy group). Fortyeight patients underwent a traditional operation (traditional method group) from January 2009 to June 2009. Comparative analysis was made of demographic and clinical characteristics of the two groups.

RESULTS:The fi nal stone clearance rate of the laser lithotripsy group was 93.3%, whereas that of the traditional method group was 85.4% (P=0.22). In the laser lithotripsy group, 2 patients experienced hemobilia and 3 patients had acute cholangitis. In the traditional method group, 3 patients had intraoperative hemorrhage, 1 patient had bile leakage, 6 patients had acute cholangitis, and 1 patient died of liver failure. Moreover, the operative time in the traditional method group was signif i cantly longer than that in the laser lithotripsy group (P=0.01). The mean hospital stay of the patients in the traditional method group was longer than that in the laser lithotripsy group (9.8 vs8.2 days,P=0.17). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups.

CONCLUSION:Operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy may be an effective and safe treatment for hepatolithiasis.

(Hepatobiliary Pancreat Dis Int 2013;12:160-164)

hepatolithiasis; lithotripsy; frequency-doubled double pulse Nd:YAG laser; hepatectomy; choledochoscopy

Introduction

Hepatolithiasis, also known as "oriental cholangiohepatitis", is quite common in East Asia, with an incidence of 38% in China, 17.0% in Korea, and 2.1% in Japan.[1]It is characterized by the recurrent pyogenic cholangitis which leads to secondary biliary cirrhosis and liver failure,[2]and cholangiocarcinoma represents a long-term unfavorable complication of the disease.[3]The clinical progress of hepatolithiasis is hard-bitten, demanding various surgical or nonsurgical treatments because of a frequent stone recurrence. The main purpose of treatment should be complete removal of the stones, preventing from further attacks of cholangitis and controlling disease progression to biliary cirrhosis. Currently, various treatment options have been available, including liver resection, percutaneous approach, endoscopic approach and laser lithotripsy.[4-24]Usually, stones that are hard and impact or can not be extracted by traditional methods (basket catheters, forceps and irrigation) are considered refractory bile duct stones. Some surveys[7-9]showed that laser lithotripsy may offer a safe and eff i cacious optionto manage refractory intrahepatic bile duct stones. In this report, we describe the operative choledochoscopic Frequency-Doubled Double pulse Nd:YAG (FREDDY) laser lithotripsy combined with or without hepatectomy for the management of intrahepatic bile duct stones.

Methods

This retrospective review included 45 patients (19 males and 26 females), with a median age of 53 years (range 36-72), who had undergone choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy from July 2009 to October 2012 in our Hepatobiliary and Pancreatic Surgery Center. A preoperative assessment was performed for the 45 patients with regard to clinical symptoms, physical examinations, a comprehensive metabolic panel, a complete blood count with differential carcinoembryonic antigen (CEA), CA-199, and right upper quandrant ultrasound, upper abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP). Fifteen patients (33.3%) experienced jaundice at the diagnosis of bile duct obstruction. Before surgical intervention, 17 patients (37.8%) had previous hepatobiliary operation, 31 (68.9%) had fever, 30 (66.7%) had upper abdominal pain, and 8 (17.8%) suffered from biliary cirrhosis.

We performed bile duct exploration, except for refractory bile duct stones, for which choledochoscopic FREDDY laser lithotripsy therapy (laser µ100plus, world of Medicine, Berlin, Germany) was feasible. In the 45 patients who received choledochoscopic FREDDY laser lithotripsy therapy, 12 underwent hepatectomy. Laser pulses of 1.2 µs were applied at a repetition rate of 10-15 Hz. As intrahepatic stones were found by a choledochoscope (CHF type P10; Olympus, Tokyo, Japan), a 280 µm fl exible fi ber was inserted into the working channel of the choledochoscope. The energy of the FREDDY laser system was transmitted by this fl exible fi ber. Laser wavelengths of 532 nm and 1064 nm as a double pulse was applied with pulse energy of 120 mJ. If bile duct stones fragmented too slowly or were hard enough, the energy was increased to 160 mJ, and there was no relationship between the size of stone and pulse energy. After the disintegration of the stones, a complete clearance of the biliary system was attempted at the same time by irrigation and basket catheters. Generally, hepatectomy is indicative if choledochoscopic insertion in the severely narrowed intrahepatic bile duct is not successful, or patients have atrophy of liver lobe, or clinically suspected cholangiocarcinoma. After bile duct exploration and choledochoscopic FREDDY laser lithotripsy, all of our patients were routinely placed a T-tube in the common bile duct. The T-tube was removed in two months later if the stones were not found in the intrahepatic bile duct.

In order to illustrate the superiority of choledochoscopic FREDDY laser lithotripsy, we made a comparative analysis between the two groups. In our study, this time period was chosen because the FREDDY laser equipment was not available at our hospital before July 2009. The traditional methods included forceps and irrigation lithotripsy, choledochoscopic basket catheter lithotomy, and hepatectomy. The demographic and clinical features of the patients in the laser lithotripsy group and the traditional method group are shown in Table 1.

All patients were followed up after treatment with FREDDY laser lithotripsy and traditional method. The follow-up examinations included T-tube cholangiography, ultrasonography and laboratory tests (hemoglobin, white blood cell count, bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine, serum urea nitrogen, CEA, CA-199), which were performed every three months. Stones detected in the intrahepatic bile duct within 3 months after therapies were considered as residual stones. The occurrence of any operative complicationwas assessed by patient visit or telephone interview.

Table 1.Demographic and clinical features of patients in laser lithotripsy group and traditional method group

Differences in the characteristics of the laser lithotripsy group and the traditional method group were analyzed by the Chi-square test and Student'sttest, using SPSS software for Windows (Statistical Product and Service Solutions, version 18.0, SPSS Inc., Chicago, IL., USA). APvalue of less than 0.05 was considered statistically signif i cant.

Results

Forty-two (93.3%) of the 45 patients in the laser lithotripsy group achieved a complete stone fragmentation and intrahepatic bile duct clearance (Figs. 1 and 2), and 3 patients failed because stones were impacted in the bilateral bile duct and associated with bile duct stricture and biliary cirrhosis. Five of the 45 patients underwent segmental hepatectomy of the right liver, and 7 patients were subjected to left lateral hepatectomy. One patient suffered from cholangiocarcinoma with negative margins, and was still alive 23 months later. In the traditional method group, the fi nal stones clearance rate was 85.4%. Six of 48 patients underwent segmental hepatectomy of the right liver, and 12 patients received left lateral hepatectomy.

The degree of complication was mild in the laser lithotripsy group. During the operation, hemobilia occurred in two patients because of mucosal damage induced by insertion of the laser fi ber and was successfully treated by bile duct irrigation of 100 mL normal saline with 8 mg epinephrine. Three patients with acute cholangitis were treated by administration of antibiotics and T-tube irrigation. In the traditional method group, 3 patients had intraoperative hemorrhage because of forceps injury and were treated by bile duct irrigation of 100 mL normal saline with 8 mg epinephrine, 1 patient with leakage was managed by intraperitoneal drainage, 6 patients with acute cholangitis were treated by administration of antibiotics and T-tube irrigation, and 1 patient died of liver failure because of liver cirrhosis and intraoperative lithotomy for a long time on the seventh day after surgery.

The operative time of the traditional method group was signif i cantly longer than that of the laser lithotripsy group (P=0.01). The mean hospital stay of the patients in the traditional method group was longer than that in the laser lithotripsy group (9.8 vs 8.2 days,P=0.17). No postoperative mortality (within 30 days) or recurrence of stones (during follow-up period) was found in the laser lithotripsy group, and the mean follow-up period of the laser lithotripsy group and the traditional method group was 19 and 43 months, respectively (Table 2).

Fig. 1.A: Impacted intrahepatic bile duct stones;B: FREDDY laser fragmenting the stones;C: cleared intrahepatic bile duct.

Fig. 2.A,B: abdominal CT showing a lot of stones located in the bilateral intrahepatic bile duct before laser lithotripsy;C,D: abdominal CT showing no intrahepatic bile duct stones after laser lithotripsy.

Table 2.Comparison of the treatment results between the two groups

Discussion

Hepatolithiasis is characterized by a high rate of treatment failure and recurrence. Intrahepatic bile duct stones can lead to biliary strictures, liver abscess, secondary biliary cirrhosis, liver atrophy and even cholangiocarcinoma.[10-12]To reduce the risk of recurrenceof intrahepatic bile duct stones,[13]surgeons have to remove the intrahepatic and extrahepatic stones as well as bile duct stricture, to establish adequate drainage of the intrahepatic biliary tree, and to resect the lesion of liver lobe. Currently, surgical and nonsurgical procedures are available for hepatolithiasis. The nonsurgical procedures include percutaneous approach and endoscopic approach. Percutaneous transhepatic cholangioscopic lithotomy (PTCSL) is less invasive than surgical approaches, and therefore can be conducted in patients with poor general conditions, diff i cult anatomy, and bile duct strictures.[12,14]Nd:YAG laser lithotripsy is often available for disintegrating stones that are too large to be removed using ordinary percutaneous transhepatic cholangioscopy.[7,8]However, the percutaneous approach is diff i cult to resolve hepatolithiasis completely when it occurs in both liver lobes. Moreover, PTCSL is more time-consuming and frequently induces intra-abdominal abscess, liver laceration, severe bleedings as well as bile leakage.[7,8,12,14]However, these complications can be avoided by operative laser therapy. Endoscopic retrograde cholangiopancreatography, a routine endoscopic approach, has been used to extract common bile duct stones. However, it is not so eff i cient in managing hepatolithiasis because of acute angulation of the bile duct, impacted stone or intrahepatic bile duct stricture.[15]And for multiple stones, repeated extraction may increase the risk of complications such as pancreatitis.[16]Comparatively, hepatic resection is the most effective approach for the treatment of hepatolithiasis by removal of intrahepatic stones, stenotic bile duct, and destroyed hepatic parenchyma.[17]This approach is generally considered for patients with unilateral disease, not for those with complicated diseases including stones in both lobes and factors increasing the risk of surgery.[18]Therefore, each patient should undergo preoperative CT and MRCP to demonstrate the precise location of stones, dilated segmental bile ducts, stricture of bile ducts, atrophy of affected lobes, and even concurrent cholangiocarcinoma. According to CT and MRCP, we could judge whether liver resection should be made. In addition to surgical and nonsurgical procedures for intrahepatolithiasis, operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy is a novel approach.

The technological development of FREDDY laser dates back to 1997 and has been developed for endoscopic lithotripsy to disintegrate urinary stones.[19-22]Recent studies[16,23]have shown that FREDDY laser is eff i cacious and safe for the billiary system. FREDDY laser initiates plasma formation at the stone surface utilizing the 532 nm green fraction and heats the performed plasma with the infrared portion (1064 nm).[16]The plasma rapidly expands and fi nally collapses, causing a number of physical phenomena which are responsible for the mechanical fragmentation of the stone.[16]Like the pulsed dye laser it works by generating shockwaves that mechanically break stones without adverse themal effects.[24]In vivostudies have clearly shown that direct targeting of the tissue over a prolonged period does not result in structural damage, making inadvertent perforation virtually impossible.[16,23,24]Nevertheless, the probe contacting with the bile duct wall may result in perforation or bleeding.[16,24]For instance, two patients experienced intraoperative biliary tract bleeding in the laser lithotripsy group in our center. Hence we were careful when the fl exible fi ber was inserted into the intrahepatic bile duct. The FREDDY laser system has the advantage of solid-state and pulse-dye lasers such as lower cost, good reliability, time-saving and excellent effectiveness.[16]We applied this laser on the intrahepatic bile duct stone via the working channel of a choledochoscope during the operation. Some patients underwent liver resection when bile duct stones could not be cleared only by the FREDDY laser approach or the patients had atrophy of liver segment or lobe or clinically suspected cholangiocarcinoma. In our study the fi nal stone clearance rate after choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy reached 93.3%, compared with that of the traditional method (85.4%). However, there was no signif i cant difference in the fi nal stone clearance rate between the two groups, which may be due to the small sample. The mean operation time and mean hospital stay of the patients in the traditional method group were longer than those in the laser lithotripsy group. Moreover, FREDDY laser was shown to be highly eff i cient in fragmentation of biliary stones (100%).

Operative choledochoscopic FREDDY laser lithotripsy is a novel treatment of hepatolithiasis. If patients with intrahepatic stones located in the unilateral bile duct and without indications for hepatectomy, choledochoscopic FREDDY laser lithotripsy is effective treatment of choice. But how to manage intrahepatic stones which are distributed bilaterally still needs investigation. In patients with bilateral intrahepatic stones and absence of associated intrahepatic bile duct stricture and liver atrophy, only choledochoscopic FREDDY laser lithotripsy could be used to clear the stones and avoid liver resection. Moreover, choledochoscopic FREDDY laser lithotripsy combined with hepatectomy may be suitable for some patients who have bilateral multiple stones associated with unilateral stenosis of the intrahepatic duct and atrophy of the liver lobe. However,operative choledochoscopic FREDDY laser lithotripsy combined with hepatectomy is not indicated for patients with biliary cirrhosis associated with bilateral multiple stones and bilateral stenosis of the intrahepatic bile duct. Since hepatectomy may increase the risk of liver failure and a choledochoscope cannot be introduced through the narrowed intrahepatic bile duct, FREDDY laser is no longer used. For these patients, we recommend local bile duct exploration through designated liver capsule or liver transplantation.

In conclusion, given the complicated nature of the disease and various conditions of the patient, a multidisciplinary approach should be considered. The present study suggests that operative choledochoscopic FREDDY laser lithotripsy may be a safe and effective treatment of choice for intrahepatic bile duct stones.

Acknowledgment:We sincerely appreciate the self l ess support from all the doctors who participated in this survey.

Contributors:ZSS proposed the study. JZJ, WWL, SY, ZM and ZSS performed research and wrote the fi rst draft. CY, XHY and ZL collected and analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. ZSS is the guarantor.

Funding:This study was supported by grants from the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002) and Zhejiang Provincial Natural Science Foundation (Y2100498).

Ethical approval:Not needed.

Competing interest:No benef i ts in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

1 Tazuma S. Gallstone disease: Epidemiology, pathogenesis, and classif i cation of biliary stones (common bile duct and intrahepatic). Best Pract Res Clin Gastroenterol 2006;20:1075-1083.

2 Chijiiwa K, Yamashita H, Yoshida J, Kuroki S, Tanaka M. Current management and long-term prognosis of hepatolithiasis. Arch Surg 1995;130:194-197.

3 Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F. Hepatolithiasis associated with cholangiocarcinoma. Possible etiologic signif i cance. Cancer 1985;55:2826-2829.

4 Marín C, Robles R, Pastor P, Parrilla P. Liver resection in the treatment of intrahepatic lithiasis. Immediate and long-term results in a single-center series. Rev Esp Enferm Dig 2008; 100:225-229.

5 Cheung MT, Wai SH, Kwok PC. Percutaneous transhepatic choledochoscopic removal of intrahepatic stones. Br J Surg 2003;90:1409-1415.

6 Lam SK, Wong KP, Chan PK, Ngan H, Ong GB. Recurrent pyogenic cholangitis: a study by endoscopic retrograde cholangiography. Gastroenterology 1978;74:1196-1203.

7 Chen MF, Jan YY. Percutaneous transhepatic cholangioscopic lithotripsy. Br J Surg 1990;77:530-532.

8 Neuhaus H, Hoffmann W, Zillinger C, Classen M. Laser lithotripsy of diff i cult bile duct stones under direct visual control. Gut 1993;34:415-421.

9 Bark K, Gamblin TC, Zuckerman R, Geller DA. Operative choledochoscopic laser lithotripsy for impacted intrahepatic gallstones: a novel surgical approach. Surg Endosc 2009;23: 221-224.

10 Otani K, Shimizu S, Chijiiwa K, Ogawa T, Morisaki T, Sugitani A, et al. Comparison of treatments for hepatolithiasis: hepatic resection versus cholangioscopic lithotomy. J Am Coll Surg 1999;189:177-182.

11 Jan YY, Chen MF, Wang CS, Jeng LB, Hwang TL, Chen SC. Surgical treatment of hepatolithiasis: long-term results. Surgery 1996;120:509-514.

12 Huang MH, Chen CH, Yang JC, Yang CC, Yeh YH, Chou DA, et al. Long-term outcome of percutaneous transhepatic cholangioscopic lithotomy for hepatolithiasis. Am J Gastroenterol 2003;98:2655-2662.

13 Herman P, Perini MV, Pugliese V, Pereira JC, Machado MA, Saad WA, et al. Does bilioenteric anastomosis impair results of liver resection in primary intrahepatic lithiasis? World J Gastroenterol 2010;16:3423-3426.

14 Chen C, Huang M, Yang J, Yang C, Yeh Y, Wu H, et al. Reappraisal of percutaneous transhepatic cholangioscopic lithotomy for primary hepatolithiasis. Surg Endosc 2005;19: 505-509.

15 Ross AS, Kozarek RA. Cholangioscopy: where are we now? Curr Opin Gastroenterol 2009;25:245-251.

16 Kim TH, Oh HJ, Choi CS, Yeom DH, Choi SC. Clinical usefulness of transpapillary removal of common bile duct stones by frequency doubled double pulse Nd:YAG laser. World J Gastroenterol 2008;14:2863-2866.

17 Mori T, Sugiyama M, Atomi Y. Gallstone disease: Management of intrahepatic stones. Best Pract Res Clin Gastroenterol 2006;20:1117-1137.

18 Uenishi T, Hamba H, Takemura S, Oba K, Ogawa M, Yamamoto T, et al. Outcomes of hepatic resection for hepatolithiasis. Am J Surg 2009;198:199-202.

19 Hochberger J, Bayer J, Tex S, Maiss J, Tschepe J, Hahn EG. Frequency-doubled double pulse Nd:YAG laser (FREDDY) for gallstone lithotripsy--preclinical and initial clinical results. Biomed Tech (Berl) 1997;42:330.

20 Zörcher T, Hochberger J, Schrott KM, Kühn R, Schafhauser W. In vitro study concerning the eff i ciency of the frequencydoubled double-pulse Neodymium:YAG laser (FREDDY) for lithotripsy of calculi in the urinary tract. Lasers Surg Med 1999;25:38-42.

21 Yates J, Zabbo A, Pareek G. A comparison of the FREDDY and holmium lasers during ureteroscopic lithotripsy. Lasers Surg Med 2007;39:637-640.

22 Dubosq F, Pasqui F, Girard F, Beley S, Lesaux N, Gattegno B, et al. Endoscopic lithotripsy and the FREDDY laser: initial experience. J Endourol 2006;20:296-299.

23 Cho YD, Cheon YK, Moon JH, Jeong SW, Jang JY, Lee JS, et al. Clinical role of frequency-doubled double-pulsed yttrium aluminum garnet laser technology for removing diff i cult bile duct stones (with videos). Gastrointest Endosc 2009;70:684-689.

24 Delvecchio FC, Auge BK, Brizuela RM, Weizer AZ, Zhong P, Preminger GM. In vitro analysis of stone fragmentation ability of the FREDDY laser. J Endourol 2003;17:177-179.

Received July 17, 2012

Accepted after revision February 4, 2013

AuthorAff i liations:Division of Hepatobiliary Pancreatic Surgery, Department of Surgery, First Aff i liated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Jiang ZJ, Chen Y, Wang WL, Shen Y, Zhang M, Xie HY, Zhou L and Zheng SS)

Shu-Sen Zheng, MD, PhD, FACS, Division of Hepatobiliary Pancreatic Surgery, Department of Surgery, First Aff i liated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel: 86-571-87236570; Fax: 86-571-87236567; Email: shusenzheng@ zju.edu.cn)

© 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.

10.1016/S1499-3872(13)60026-0