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Lack of complications following short-term stent therapy for extrahepatic bile
duct strictures in primary sclerosing cholangitis
van Milligen de Wit, A.W.M.; Rauws, E.A.J.; van Bracht, J.; Mulder, C.J.J.; Jones, E.A.;
Tytgat, G.N.J.; Huibregtse, K.
Publication date
1997
Published in
Gastrointestinal endoscopy
Link to publication
Citation for published version (APA):
van Milligen de Wit, A. W. M., Rauws, E. A. J., van Bracht, J., Mulder, C. J. J., Jones, E. A.,
Tytgat, G. N. J., & Huibregtse, K. (1997). Lack of complications following short-term stent
therapy for extrahepatic bile duct strictures in primary sclerosing cholangitis. Gastrointestinal
endoscopy, 46, 344-347.
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Lack of complications following short-term stent
therapy for extrahepatic bile duct strictures in
primary sclerosing cholangitis
A.W. Marc van Milligen de Wit, MD, Erik A.J. Rauws, MD, PhD, Jeroen van Bracht, MD Chris J.J. Mulder, MD, PhD, E. Anthony Jones, FRCP, Guido N.J. Tytgat, MD, PhD Kees Huibregtse, MD, PhD
Amsterdam, The Netherlands
Background: In 10% to 20% of patients with primary sclerosing cholangitis,
a dominant stricture of an extrahepatic bile duct is responsible for symp- toms and an exacerbation of cholestasis. The complications of a dominant stricture can usually be relieved by endoscopic placement of a stent through the stricture. The conventional policy of leaving stents in situ for 2 to 3 months is associated with a high incidence (e.g., 50%) of clinical deteriora- tion due to stent occlusion. We have attempted to overcome this problem by substantially reducing the duration of stent placement.
Methods: Sixteen patients with symptomatic primary sclerosing cholangitis
and dominant extrahepatic bile duct strictures were treated by stent place- ment for a median interval of only 9 days.
Results: In all patients endoscopic stent therapy was technically successful
with a 7% incidence of transient procedure-related complications. During median follow-up of 19 months (range 7 to 27 months) serum biochemical evidence of cholestasis decreased substantially and 13 (81%) of the 16 patients became asymptomatic. No patient had a recurrence or exacerba- tion of either symptoms or biochemical evidence of cholestasis that could be attributed to stent occlusion.
Conclusions: Short-term endoscopic stent therapy is a safe and effective
treatment for symptomatic dominant extrahepatic bile duct strictures in patients with primary sclerosing cholangitis. (Gastrointest Endosc 1997;46: 344-7.)
P r i m a r y sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of u n k n o w n cause charac- terized by patchy fibroproliferative inflammation of the intrahepatic and extrahepatic bile ducts. Dis- ease progression leads to secondary biliary cirrhosis and sometimes cholangiocarcinoma. 1 In 10% to 20% Received October 24, 1996. For revision January 30, 1997. Accepted May 23, 1997
From the Departments of Gastroenterology and Hepatology, Aca- demic Medical Center, Amsterdam, and Rijnstate Hospital, Arn- hem, The Netherlands.
Presented in part at United European Gastroenterology Week, 1995, Berlin, Germany (Endoscopy 1995;27:$73); and at the Annual Spring Meeting of the Dutch Society of Gastroenterology 1995, Veldhoven, The Netherlands (Neth J Med 1995;47:A22). Reprint requests: A. W. Marc van Milligen de Wit, MD, Gastroen- terology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Copyright © 1997 by the American Society for Gastrointestinal Endoscopy
0016-5107/97/$5.00 + 0 37/1/83438
of patients a dominant stricture of an extrahepatic bile duct develops and is responsible for the precip- itation or an exacerbation of symptoms and an increase in cholestasis. 2, 3 Surgery for this complica- tion is associated with substantial morbidity and mortality and m a y increase the technical difficulty and risk of possible future liver transplantation. 4 P e r c u t a n e o u s trans-hepatic dilation and stenting of dominant strictures have been reported in small n u m b e r s of patients with P S C g ' 5 However, this approach carries a substantial risk of infection and is technically difficult because the intrahepatic bile ducts are usually not dilated.
Current endoscopic t h e r a p y consists of sphincter- otomy, g r a d u a t e d catheter or balloon dilation, place- m e n t of endoprostheses, and/or nasobiliary catheter drainage. 6s These endoscopic t r e a t m e n t modalities are often used in combination and are all aimed at relieving the large bile duct obstruction.
Short-term stent therapy for extrahepatic bile duct strictures A van Milligen de Wit, E Rauws, J van Bracht, et at. I n a r e c e n t r e t r o s p e c t i v e s t u d y we e v a l u a t e d t h e r e s u l t s of e n d o s c o p i c s t e n t t h e r a p y for s y m p t o m a t i c d o m i n a n t e x t r a h e p a t i c bile d u c t s t r i c t u r e s in p a - t i e n t s w i t h P S C . T h e m e d i a n p e r i o d of s t e n t t h e r a p y w a s 3 m o n t h s a n d a l t h o u g h o u r policy w a s to r e m o v e or e x c h a n g e s t e n t s e l e c t i v e l y a f t e r 2 to 3 m o n t h s , n o n e l e c t i v e i n d i c a t i o n s for t h i s p r o c e d u r e w e r e j a u n - dice a n d / o r c h o l a n g i t i s a t t r i b u t a b l e to s t e n t occlu- sion in 50% of i n s t a n c e s , s T h e o p t i m a l t i m e to l e a v e s t e n t s in s i t u to a c h i e v e a d e q u a t e s t r i c t u r e d i l a t i o n w i t h m i n i m a l c o m p l i c a t i o n s d u e to s t e n t occlusion is u n k n o w n . W e h a v e t e s t e d t h e h y p o t h e s i s t h a t s h o r t - t e r m (1 w e e k ) s t e n t i n t e r v e n t i o n m i g h t n o t o n l y be efficacious in r e l i e v i n g t h e c o n s e q u e n c e s of d o m i - n a n t s t r i c t u r e s b u t also a v o i d t h e c o m p l i c a t i o n s of s t e n t occlusion.
PATIENTS AND METHODS
From J a n u a r y 1994 until October 1995, 16 patients with PSC (8 men and 8 women) were selected for short- t e r m stent t h e r a p y because of clinical and serum biochem- ical findings putatively related to dominant extrahepatic bile duct strictures. The patients studied had not previ- ously been treated with endoscopic therapy. Their median age was 43 years (range 17 to 69 years). One patient had clinical signs compatible with cirrhosis at the time of stent therapy. Associated inflammatory bowel disease was present in 10 (63%) of the 16 patients for a median of 9 years (range 0 to 16 years). Twelve patients complained of fatigue, 10 complained of pruritus, 7 had right upper quadrant pain, 5 were jaundiced, and fever was present in 2 of the 16 patients.
The diagnosis of PSC was established by peroperative cho!angiography after cholecystectomy in 2 patients and by ERCP in 3 patients, with a median interval of 37 months (range 5 to 108 months) before stenting. At t h a t time a dominant extrahepatic bile duct stricture was already present in 4 of these patients. In the remaining 11 patients, the diagnosis of PSC was made by ERCP at presentation for stent therapy. Dominant extrahepatic bile duct strictures were defined as proximal, mid, or distal, when located in the main hepatic ducts, common hepatic duct, or common bile duct, respectively.
Six patients had been treated with ursodeoxycholic acid (UDCA) for a median interval of 36 months (range 5 to 60 months) before stenting, and in another 5 patients UDCA was started within 2 months of stent therapy. In these 11 patients UDCA was continued during follow-up after stenting.
Patients received antibiotics (intravenous gentamycin 2 mg/kg b.i.d, and amoxycillin i g q.i.d.) before and for 24 hours after each ERCP procedure. A brush cytology spec- imen (GCB-200-3-3.5, Wilson-Cook, Winston-Salem, N.C.) of the stricture was obtained before stent insertion.
Endoscopic t r e a t m e n t consisted of placement of a 10F endoprosthesis (straight polyethylene A m s t e r d a m type) through the dominant stricture and leaving it in situ for 1 week. I f necessary, pre-cut sphincterotomy was performed
to achieve deep cannulation of the bile ducts or to facilitate stent placement. If a stricture was very tight, placement of a 10F stent was preceded by dilation with wire-guided dilator catheters (Soehendra) or balloons (Rigiflex), short- t e r m placement o f a nasobiliary drain, and/or placement of a 7F stent for i week. Stents (7F and/or 10F) were inserted over a guidewire using a video duodenoscope (Olympus TJF100, Olympus, Hamburg, Germany) with a 4.2 m m instrumentation channel. Adverse events occurring within 30 days of each ERCP were considered procedure- related complications and were graded according to estab- lished criteria. 9
During follow-up, patients were seen every 2 months on an outpatient basis for assessment of clinical status and serum biochemical liver tests. Mean values for serum biochemical liver tests and prevalence of symptoms before stent placement and at the last clinic visit were compared using the Wilcoxon matched-pairs signed-ranks test and the Sign test, respectively. The m e a n improvements of serum biochemical liver tests after stent therapy were compared between patients either receiving or not receiv- ing UDCA therapy using the two-tailed t test for indepen- dent samples. P values < 0.05 generated by the two-tailed test were considered significant. Statistical analysis was performed using the SPSS statistical software package (SPSS Inc., USA). R E S U L T S A t o t a l of 42 E R C P s w e r e p e r f o r m e d for s h o r t - t e r m ( m e d i a n 9 d a y s ) s t e n t t h e r a p y in 16 p a t i e n t s . All p a t i e n t s r e c e i v e d a n t i b i o t i c s ( i n t r a v e n o u s g e n t a - m y c i n 2 m g / k g b.i.d, a n d a m o x y c i l l i n 1 g q.i.d.) b e f o r e a n d for 24 h o u r s a f t e r e a c h E R C P p r o c e d u r e a n d 6 p a t i e n t s also r e c e i v e d a n t i b i o t i c s (oral cipro- itoxacin 500 m g b.i.d.) for t h e t o t a l p e r i o d of s t e n t p l a c e m e n t . M e d i a n follow-up a f t e r s t e n t r e m o v a l w a s 19 m o n t h s ( r a n g e 7 to 27 m o n t h s ) . S t e n t occlu- sion did n o t occur.
L o c a t i o n s of d o m i n a n t e x t r a h e p a t i c bile d u c t stric- t u r e s w e r e d i s t a l in 8, m i d in 2, p r o x i m a l in 1, a n d b o t h p r o x i m a l a n d d i s t a l in 5 p a t i e n t s . B r u s h cytol- ogy, p e r f o r m e d in 14 of t h e 16 p a t i e n t s , did n o t r e v e a l e v i d e n c e of m a l i g n a n c y . P r e - c u t s p h i n c t e r o t - o m y h a d to be p e r f o r m e d to a c h i e v e d e e p c a n n u l a - t i o n of t h e bile d u c t s in 4 p a t i e n t s a n d to f a c i l i t a t e s t e n t p l a c e m e n t in 3 p a t i e n t s ; all of t h e s e 7 p a t i e n t s h a d d i s t a l s t r i c t u r e s . F u r t h e r m o r e , to f a c i l i t a t e s t e n t p l a c e m e n t , p r e d i l a t i o n of t h e s t r i c t u r e w a s p e r f o r m e d w i t h w i r e - g u i d e d d i l a t o r c a t h e t e r s in 5 p a t i e n t s ( w i t h b a l l o o n d i l a t i o n in 1) a n d w i t h place- m e n t of a n a s o b i l i a r y d r a i n for a m e d i a n of 4 d a y s ( r a n g e 1 to 4 d a y s ) in 3 p a t i e n t s ; in 5 p a t i e n t s p l a c e m e n t of a 10F s t e n t w a s p r e c e d e d b y p l a c e m e n t of a 7F s t e n t for a m e d i a n of 7 d a y s ( r a n g e 3 to 15 days). F o u r t e e n p a t i e n t s w e r e t r e a t e d w i t h place- m e n t of a 10F s t e n t t h r o u g h t h e d o m i n a n t stric- t u r e ( s ) for a m e d i a n i n t e r v a l of 7 d a y s ( r a n g e 6 to 9 V O L U M E 46, NO. 4, 1997 G A S T R O I N T E S T I N A L E N D O S C O P Y 345
A van Milligen de Wit, E Rauws, J van Bracht, et al. Short-term stent therapy for extrahepatic bile duct strictures
Figure 1. A, Cholangiogram of a patient with PSC showing a dominant stricture in the common bile duct. B, A 10F biliary endoprosthesis is inserted through the stricture. C, After removal of the endoprosthesis 1 week later a clear dilation of the stricture is apparent.
100
•
Before Stent Therapy ~ After Stent Therapy 80(D
E (D 60
N 40
20
Fatigue Pruritus R.U.Q.-pain Jaundice
__!
Fever Figure 2. Comparison of the prevalence of fatigue (/3 = 0.0039), pruritus (p = 0.0039), right upper quadrant pain 0o = 0.0156), jaundice (/3 = 0.0625), and fever (p =1) in 16 patients with PSC before and during follow-up after short- term endoscopic stent therapy.days) (Fig. 1) and 2 patients were treated with a 7F stent only, 1 for 7 days and the other for 13 days. The median period of (7F and/or 10F) stent place- m e n t in all patients was 9 days (range 7 to 23 days). After stent therapy, 13 (81%) of the 16 patients became a s y m p t o m a t i c and remained so t h r o u g h o u t follow-up (Fig. 2). Comparison of the m e a n s e r u m
500
•
Before Stent Therapy [ ] After Stent Therapy 400 +3°° i
200 i
100
Bilirubin AIk. P h o s . gamma-GT Figure 3. During follow-up after short-term endoscopic stent therapy in 16 patients with PSC, significant de- creases in serum levels of total bilirubin (p = 0.0004) (~mol/L), alkaline phosphatase (/9 = 0.0005) (U/L), and gamma-glutamyltransferase (p = 0.0011) (U/L) occurred (serum biochemical liver tests are expressed as mean val- ues; error bars represent standard error of the mean).
levels of total bilirubin, alkaline phosphatase, and g a m m a - g l u t a m y l t r a n s f e r a s e before stenting to cor- responding values at the last clinic visit showed significant decreases of these s e r u m biochemical liver tests in all patients (Fig. 3). There were no significant differences in the m e a n improvement of s e r u m biochemical liver tests after stent t h e r a p y b e t w e e n patients either receiving or not receiving UDCA t h e r a p y (Fig. 4). All 3 patients with recurrent or persisting symptoms after stent t h e r a p y were receiving UDCA treatment.
There were three (7%) procedure-related compli- cations. Two patients had a small perforation at the stricture site (graded as a mild complication) and one patient developed moderately severe pancreati- tis. 9 No sphincterotomy had been performed in these patients.
D I S C U S S I O N
Because our prospective study was uncontrolled, it is not possible to conclude t h a t short-term stent t h e r a p y is unequivocally beneficial for symptomatic dominant extrahepatic bile duct strictures in pa- tients with PSC. However, the results obtained in this s t u d y are striking and gratifying. Endoscopic stent t h e r a p y for a median period of 9 days was technically successful in all patients. During median follow-up of 19 months (range 7 to 27 months) after stent removal, 13 (81%) of 16 patients became asymptomatic with substantial decreases of serum
Short-term stent therapy for extrahepatic bile duct strictures A van Milligen de Wit, E Rauws, J van Bracht, et al. 100 ] g0 80 E 7O dO E 60 dO > £ 5O O.. E 4O 3O 20 10 : • No UDCA ~ UDCA
T
Bilirubin AIk. P h o s . garnma-GT Figure 4. During follow-up after short-term endoscopic stent therapy, there were no significant differences in the percentage of improvement of serum levels of total bilirubin (p = 0.5) (t~mol/L), alkaline phosphatase (p = 0.2) (U/L), and gamma-glutamyltransferase (p = 0.4) (U/L) between pa- tients either receiving or not receiving UDCA treatment (percentages of improvement of serum biochemical liver tests are expressed as mean values; error bars represent standard error of the mean).
b i o c h e m i c a l i n d e x e s of c h o l e s t a s i s . S t e n t occlusion did n o t occur. T h e s e r e s u l t s a r e c l e a r l y s u p e r i o r to t h o s e o b t a i n e d in a r e c e n t r e t r o s p e c t i v e s t u d y b y o u r g r o u p on t h e efficacy of s t e n t t h e r a p y for s y m p t o m - a t i c d o m i n a n t s t r i c t u r e s in P S C . s T h a t r e t r o s p e c t i v e s t u d y f o u n d t h a t s t e n t t h e r a p y for a m e d i a n d u r a - t i o n of 3 m o n t h s ( r a n g e 0.5 to 3 4 m o n t h s ) w a s a s s o c i a t e d w i t h c o m p l e t e r e s o l u t i o n of s y m p t o m s a n d s i g n i f i c a n t d e c r e a s e s of s e r u m b i o c h e m i c a l in- d e x e s of c h o l e s t a s i s in 12 (57%) of 21 p a t i e n t s ; a l t h o u g h s t e n t s w e r e e l e c t i v e l y e x c h a n g e d or re- m o v e d a f t e r 2 to 3 m o n t h s , c o m p l i c a t i o n s d u e to s t e n t occlusion w e r e t h e i n d i c a t i o n for t h i s proce- d u r e in 50% of i n s t a n c e s . C o m p a r i s o n of t h e d a t a o b t a i n e d in t h e t w o s t u d i e s s u g g e s t s t h a t s u p e r i o r clinical o u t c o m e s c a n be a c h i e v e d b y s t e n t i n g for a m e d i a n p e r i o d of 9 d a y s r a t h e r t h a n 3 m o n t h s . I t a p p e a r s t h a t s t e n t t h e r a p y of s h o r t d u r a t i o n c a n be efficacious in t r e a t i n g t h e c o n s e q u e n c e s of d o m i n a n t s t r i c t u r e s w h i l e a v o i d i n g t h e c o m p l i c a t i o n s of s t e n t occlusion. F u r t h e r m o r e , t h e p r o c e d u r e - r e l a t e d com- p l i c a t i o n r a t e (7%) in t h e c u r r e n t s t u d y w a s l o w e r t h a n t h a t r e c o r d e d in p r e v i o u s s t u d i e s of e n d o s c o p i c t h e r a p y in P S C (14% t o 15%). 7, 8 To a v o i d c o m p l i c a t i o n s of s t e n t occlusion, b a l l o o n d i l a t i o n w i t h o u t s u b s e q u e n t s t e n t i n g m a y b e a n a l t e r n a t i v e for s h o r t - t e r m s t e n t t h e r a p y . H o w e v e r , m u l t i p l e s e s s i o n s of e n d o s c o p i c b a l l o o n d i l a t i o n a r e o f t e n r e q u i r e d to a c h i e v e s u s t a i n e d s t r i c t u r e d i l a t i o n . < lO U D C A t h e r a p y h a s b e e n r e p o r t e d to b e a s s o c i a t e d w i t h i m p r o v e m e n t s in a b n o r m a l s e r u m b i o c h e m i c a l l i v e r t e s t s a n d p e r i p o r t a l i n f l a m m a t i o n in t h e l i v e r in p a t i e n t s w i t h PSC. 11, 1~ H o w e v e r , in o u r s t u d y t h e r e w e r e no s i g n i f i c a n t d i f f e r e n c e s in t h e i m p r o v e - m e n t of s e r u m b i o c h e m i c a l l i v e r t e s t s a f t e r s t e n t t h e r a p y b e t w e e n p a t i e n t s e i t h e r r e c e i v i n g or n o t r e c e i v i n g U D C A t r e a t m e n t . W e c o n c l u d e t h a t s h o r t - t e r m e n d o s c o p i c s t e n t t h e r a p y is a safe a n d effective t r e a t m e n t for s y m p t o m a t i c d o m i n a n t e x t r a h e p a t i c bile d u c t s t r i c t u r e s in p a t i e n t s w i t h PSC. T h e s h o r t d u r a t i o n of s t e n t p l a c e m e n t a p p e a r s to p r e v e n t c o m p l i c a t i o n s d u e to s t e n t occlusion t h a t c o m m o n l y occur w h e n s t e n t s r e m a i n in p l a c e for l o n g e r p e r i o d s . REFERENCES
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