Drug eluting biliary stents to decrease stent failure rates: A review of the literature

Table 1 Current stent failure rates

Stent type	Stent failure rates in malignant obstruction
Plastic stents	30%-70%
Self expanding metal stents	19%-46%

Adapted from Ref.[31-37].

Table 2 Causes of stent failure

Causes of stent failure	Percent of total failures
Tumor ingrowth	66%-68%
Epithelial ingrowth
Biliary clogging	17%-21%
Tumor overgrowth	2%-11%
Stent migration	0%-4%

Adapted from Ref.[31-37].

Table 3 Studies evaluating drug elution or coating to prevent internal failure

Ref.	Journal	Study design	Study results
In vitro
Rees et al[17]	Journal of Hospital Infection (1998)	In vitro	BZC and Teflon reduced the number of organisms attached to stents
		- control (polyurethane)
		- benzalkonium chloride (BZC)
		- ePTFE (Teflon)
Cetta et al[18]	The European Journal of Surgery (1999)	In vitro	Heparin and hyaluronic acid coating reduced biofilm development
		5 stents - control (polyurethane)
		5 stents - heparin + hyaluronic acid
Weickert et al[21]	Advances in Medical Sciences (2011)	In vitro	Stents coated with hydrophobin or both hydrophobin and heparin reduced clogging material scanning electron microscopy (SEM) images
		7 stents - control (polyethylene)
		4 stents - hydrophobin (H)
		3 stents - H + ampicillin/sulbactam
		3 stents - H + levofloxacin
		3 stents - H + heparin
Animals
Gwon et al[22]	Acta Radiologica (2012)	Canine model	Cefotaxime did not prevent biofilm development (gross inspection, SEM images)
		3 stents - control (ePTFE)
		3 stents - 10% wt/vol cefotaxime
		3 stents - 20% wt/vol cefotaxime
Humans
Farnbacher et al[19]	Scandinavian Journal of Gastroenterology (2012)	Randomized prospective	Heparin is effective in preventing encrustation on stents (encrustation weighed)
		13 stents - control (polyethylene)
		13 stents (same patients) - heparin

Table 4 Trials evaluating systemic treatments to prevent internal failure

Ref.	Journal	Study design	Study results
Humans
Barrioz et al[48]	Lancet (1994)	Randomized prospective	Drugs were associated with longer stent patency and shorter hospital stay
		25 - conservative treatment
		21 - ursodeoxycholic acid and norfloxacin
Coene et al[49]	Scandinavian Journal of Gastroenterology (1994)	Randomized prospective	Bile clogging did not correlate with bile viscosity. Mucolytic agents or antibiotics only effective when bile is highly viscous
		60 patients received either
		co-trimoxazole or
		N-acetylcysteine
Smit et al[50]	Gastrointestinal Endoscopy (1989)	Randomized prospective	Both doxycycline and aspirin reduced the dry weight of sludge. Doxycycline improved patient survival
		30 patients received either
		placebo or
		doxycycline or
		aspirin
Halm	Endoscopy (2001)	Randomized prospective	No difference in patient survival or stent occlusion
		26 - ursodeoxycholic acid
		26 - ursodeoxycholic acid + ofloxacin
De Lédinghen et al[51]	Digestive Diseases and Sciences (2000)	Randomized prospective	No difference in stent patency and patient survival
		29 - conservative treatment
		33 - ursodeoxycholic acid and norfloxacin
In vitro
Tsang et al[52]	Journal of Laboratory and Clinical Medicine (1997)	In vitro	Ampicillin and sulbactam inhibited biofilm formation
		4 - porcine bile
		4 - porcine bile + ampicillin + sulbactam

Table 5 Studies evaluating drug elution or coating to prevent external failure

Ref.	Journal	Study design	Study results
Animals
Lee et al[38]	Gastrointestinal Endoscopy (2005)	Porcine model	Paclitaxel-eluting stents caused mild adverse effects, but are safe to use in porcine models
		2 pigs - control (metallic)
		2 pigs - 10% wt/v Paclitaxel
		2 pigs - 20% wt/v Paclitaxel
Lee et al[40]	Gastrointestinal Endoscopy (2009)	Canine model	Paclitaxel-eluting stents caused mild adverse effects, but are safe to use in canine models
		5 dogs - control (metallic)
		6 dogs - 20% wt/v paclitaxel
Lee et al[44]	International Journal of Pharmaceutics (2012)	In vitro, murine model	Stents coated with gemcitabine reduced the size of subcutaneous tumor in vitro and in mice
		5 mice - no stenting
		5 mice - polyurethane
		5 mice - 0% wt/v gemcitabine
		5 mice - 8% wt/v gemcitabine
		5 mice - 12% wt/v gemcitabine
Chung et al[45]	Journal of Gastroenterology and Hepatology (2012)	Porcine model	Gemcitabine-eluting stents cause mild to severe inflammation, but are safe to use in porcine models
		2 pigs - 0% wt/v gemcitabine
		2 pigs - 10% wt/v gemcitabine
		2 pigs - 15% wt/v gemcitabine
		2 pigs - 20% wt/v gemcitabine
Jang et al[41]	Endoscopy (2012)	Porcine model	Greater patency observed when stents were coated with pluronic with paclitaxel. Stents are safe to use in porcine models
		2 pigs - 0% wt/v paclitaxel
		2 pigs - 0% Pluronic + 10% taxol
		2 pigs - 10% Pluronic + 10% taxol
		2 pigs - 20% Pluronic + 10% taxol
Kim do et al[46]	International Journal of Nanomedicine (2013)	In vitro, murine model	Sorafenib-loaded film inhibited the growth of human cholangiocarcinoma cells in vitro and in mice
		10 mice - control (no stenting)
		10 mice - PCL film
		10 mice - sorafenib-loaded film
Shi et al[42]	European Journal of Gastroenterology and Hepatology (2013)	Canine model	No adverse effects
		10 dogs - control (no stenting)	less granulation tissue and glandular hyperplasia in dogs with paclitaxel stents
		10 dogs - Poly-L-lactic acid coated metallic stents (PLLA)
		10 dogs - PLLA + 1 mg paclitaxel/stent
		10 dogs - PLLA + 2 mg paclitaxel/stent
Bang et al[43]	Gastroenterology Research and Practice (2015)	Murine model	Tumor angiogenesis inhibited in mice with Paclitaxel stents through multiple molecular mechanisms
		8 mice - control (polyurethane)
		8 mice - control + Pluronic
		8 mice - Pluronic + 5% paclitaxel
		8 mice - Pluronic + 10% paclitaxel
Humans
Suk et al[2]	Gastrointestinal Endoscopy (2007)	Randomized prospective	Paclitaxel-eluting stents are safe and effective. Occlusion in 9 patients, mean patency was 429 d
		21 patients - 10% wt/v paclitaxel
Jang et al[3]	Digestive Diseases and Sciences (2013)	Randomized prospective	No significant differences in stent patency or patient survival, but stents proved safe to use in humans
		46 patients - control (metallic)
		60 patients - 10% wt/v paclitaxel