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Prophylactic antibiotic therapy in the prevention of stent blockage
April 1995
•
Biliary Disorders A413
THE ROLE OF ANTIOXIDANT ENZYMES IN THE CONTROL OF SPHINCTER OF ODDI MOTILITY. J.J. Cullen*, R.M.Thomas, S. Fang, J.A. Murray, A. Ledlow, I. Christensen, J.L. Conldin. Departments of Surgery* and Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, Superoxide (02-') rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus inhibiting NO-mediated smooth muscle relaxation. Superoxide dismutase (SOD) prevents this reaction by converting 02.- to H202. AIM: To localize and determine the function ofantioxidant enzymes in the enteric neurons of the sphincter of Oddi (SO). METHODS: Adult opossums were sacrificed and the SO removed for either immunostaining or physiological studies. Immunostaining was performed usingthe avidin-biotin complex method aider inenbation with the following primary rabbit antisera: anti-copper-zinc SOD (CuZn SOD), anti-manganese SOD (Mn SOD) or anti-catalase (CAT)at dilutions of 1:100-1:300. In physiologic experiments, the SO was placed in a tissue bath containing oxygenated Krebs solution at 37°C and force transducers recorded tension in a transverse orientation at two sites. 02." was generated by the addition of xanthine (X) 10-4 M with xanthine oxidase (XO) 3x10 -3 M while 02.- radicals were scavenged by the addition of SOD 100 U/ml. RESULTS: lmmunostaining demonstrated CuZn SOD, CAT, and Mn SOD immunoreactivity in plexuses external to the muscularis propria and plexuses in the lamina propria of the mucosa. Addition of X/XO, but not X alone, (Table, Group I) increased the frequency of contractions. SOD decreased contractile frequency after X/XO (Group II). SOD alone had no affect but inhibited the effect of X/XO on contractile frequency (Group liD. CONCLUSIONS: 02." alters SO motor function. The presence of 02-" scavenging enzymes in enteric neurons suggests that they may regulate SO neuromuscular function by clearing endogenous 02.group I cycles/min group II cgcles/min control 3.1_+0.8 control 3.0+1.2 X 2.8L,-'0.7 X/XO 6.4_+0.8* X/XO 4.2_+0.9* SOD 2.9+0.4 Means+SEM. *p<0.05 vs control.
~,roupIII cyclcs/min control 5.4+1.1 SOD 5.6_+0.9 X/XO 5.4-+1.2
@ S u c c e s s f u l T r e a t m e n t o f S y m p t o m a t i c Hepatic Cysts b y S i n g l e - S h o t Instillation of M i n o c y c l i n e Chloride. DESLANDES P.(1), CELLIER C.(2), C U E N O D C.A.(1), L A N D I B.(2), BELY N.(1), REVEL M.P.(1), BARBIER J.P.(2), FRIIA G.(1). Depts of Radiology(I) and Gastroenterology(2), HSpital La~nnec 75007 Paris FRANCE. Hepatic cysts are common and usually asymptomatic, However, large cysts may induce clinical manifestations. Simple percutaneons drainages are followed by recurrence and therapy w i t h alcohool instillation requires several procedures. We report o u r experience on single-shot instillation of minocycline chloride in large hepatic cyst treatment. Patients and Methods : From November 1992 to March 1994, 7 patients (2M, 5W, mean age : 52 years) ~:ith large symptomatic (reccurent abdominal pain or GI tract obstruction) hepatic cysts (mean diameter:. 8.5 cm; range 5.5 to 16 cm) have been treated by intracystic injection in a ambulatory procedure without any anesthesia. Five patients had a solitary cyst and two patients had polycystic liver disease. The target cyst was punctured by a 22 gauge fine needle u n d e r u l t r a s o u n d guidance. T h e n the cyst was first opacified under fluoroscopy to test for the absence of communication between the cyst and the bfliary tree. Half of the cyst content was removed by aspiration, and 250 to 500 m g of minocycline chloride diluted in 10 ml of saline with 10 ml of 1% xylocaine were instillated inside the deflated cyst. Results : After the procedure, only two patients encountered transient pain. In one case, pain was associated with a mild fever. After a mean evolution period of 12 m o n t h s (6 to 24 ) : a) S y m p t o m s diseappeared in all patients with solitary cyst. The volume of the cyst always decreased by at least 50% with total regression in three cases, b) The 2 patients with m u l t i p l e hepatic cysts experienced only transient clinical
improvment and the initial volume of the treated cyst recurred fastly in one case. C o n c l u s i o n : Single-shot instillation of Minocycline chloride is a p r o m i s i n g technique for s y m p t o m a t i c solitary hepatic cyst treatment.
PROSPECTIVE EVALUATION OF THE IMPACT OF E N D O S C O P I C U L T R A S O N O G R A P H Y ON D I A G N O S T I C AND T H E R A P E U T I C S T R A T E G I E S OF E X T R A H E P A T I C C H O L E S T A S I S . B.J.Denis, K. Dron, V.Denny, M.A. Bigard, P. Gaucher. Service HGE, CHU Nancy, 54511, Vandoeuvre, France. The high accuracy of endoscopic ultrasonography (EUS) for diagnosis of extrahepatic cholestasis is well documented. The clinical effectiveness of the use of EUS on the management of extrahepatic cholestasis has not been prospectively studied yet. A I M : To evaluate prospectively the impact of the use of EUS on diagnostic and therapeutic strategies of extrahepatic cholestasis. [VIETHODS : One hundred and sixty three consecutive patients having EUS (Olympus GF-UM3) for extrahepatic cholestasis were prospectively included. Investigations performed before EUS were: ultrasonography (US) n=152; computed tomography (CT) n=118; duodenoscopy n--31; ERCP n=29 (bile duct cannulation failure in 21 cases). For each patient the following parameters were recorded before EUS: suspected diagnosis; next investigation planned for diagnostic confirmation; and suggested treatment. These data were compared to final diagnoses and effective treatments. ]IESULTS : EUS couldn't be performed in 7 cases (4%) because of a stenosis. In 12 cases (7%) no EUS diagnosis was made. Final diagnoses in the remaining 144 patients were: no obstruction n=24; stone n=65; cancer n=54; Caroli n=l. EUS diagnoses were wrong 4 times (2.5%) and exact 140 times (86%). US and CI" diagnoses were exact in 19% and 46% of cases. EUS detected 65 (40%) obstacles that had not been seen previously (42 stones, 22 cancers, 1 Caroli) and corrected 33 (20%) wrong initial diagnoses: in 19 cases there was no obstruction and in 14 cases the nature of obstruction was wrong (8 stones, 5 cancers, 1 Caroli). EUS results avoided doing 20 diagnostic ERCP, led to 9 renewed ERCP attempts for stone extraction after initial cannulation failure, and modified 20 times (12%) the diagnostic strategy. Except for the 33 (20%) wrong initial diagnoses that were corrected by EUS, EUS results never had direct impact on therapeutic management, even for cancers. Neither laparotomy nor endoscopic sphincterotomy were decided or avoided owing to EUS results. (~ONCLUSlONS : Our results confirm the unequalled accuracy of EUS for the diagnosis of extrahepatic cholestasis. But, in a non-selected population, EUS use had only a low impact on therapeutic management. This impact could probably be enhanced by an earlier use (i.e. previous to CT) of EUS in the diagnostic strategy of extrahepatic cholestasis.
PROPHYLACTIC ANTIBIOTIC THERAPY IN THE PREVENTION OF STENT BLOCKAGE. T Desta. E Libby, YL Liu, K Lain and JW Leung. UCDMC, Sacramento, CA, NEMC, Boston, MA, DUMC, Durham NC. Bacterial adherence and biofilm formation is a known cause for biliary stent blockage. The incidence vary between 28% to 53%. A mixture of gram -ve and gram +re bacteria have been isolated. Previous studies with antibiotic therapy have given conflicting results. We have tested the effect of antibiotics [Ampicillin (Amp), Ceftazidime (Cfl) and Ciprofloxacin (Cip)] in an in vitro study against E.coli and Enterococci in the prevention of adherence and stent blockage. Methods: Selected strains of E.coli and Enterococci isolated from blocked stents were tested against the antibiotics given at MIC levels using a constant flow device (MP,.D). Pieces of 10Fr polyethylene stent material mounted in the MRD were perfused with infected bile containing either bacteria for up to 7 days. Segements of the stents were removed and examined daily for biofilm formation. The experiments were arranged as follows: 1. Infected bile (I]3) alone (control), 2. 113 and Amp, 3. I]3 and Cf~, 4. ]]3 and Cip. Results: Compared to the control group, Cft and Cip caused a I00 fold reduction in E coli adherence but Cf~ is ineffective against Enterocncci. Amp led to a 10 fold reduction in Enterococci adherence. =
'
~
n
t
r
o
•
l
Ceffazidine.
...........................
~o~troi
.............
~8 ~a
p
Hour
Hour
Conclusion: Timely treatment with appropriate antibotics reduce bacterial adherence and biofilm formation and may have potential benefit in prevention of stent blockage. Further studies to address the timing, duration and possible combination of antibiotics therapy are required to develop an optimal treatment strategy.
•
Biliary Disorders A413
THE ROLE OF ANTIOXIDANT ENZYMES IN THE CONTROL OF SPHINCTER OF ODDI MOTILITY. J.J. Cullen*, R.M.Thomas, S. Fang, J.A. Murray, A. Ledlow, I. Christensen, J.L. Conldin. Departments of Surgery* and Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, Superoxide (02-') rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus inhibiting NO-mediated smooth muscle relaxation. Superoxide dismutase (SOD) prevents this reaction by converting 02.- to H202. AIM: To localize and determine the function ofantioxidant enzymes in the enteric neurons of the sphincter of Oddi (SO). METHODS: Adult opossums were sacrificed and the SO removed for either immunostaining or physiological studies. Immunostaining was performed usingthe avidin-biotin complex method aider inenbation with the following primary rabbit antisera: anti-copper-zinc SOD (CuZn SOD), anti-manganese SOD (Mn SOD) or anti-catalase (CAT)at dilutions of 1:100-1:300. In physiologic experiments, the SO was placed in a tissue bath containing oxygenated Krebs solution at 37°C and force transducers recorded tension in a transverse orientation at two sites. 02." was generated by the addition of xanthine (X) 10-4 M with xanthine oxidase (XO) 3x10 -3 M while 02.- radicals were scavenged by the addition of SOD 100 U/ml. RESULTS: lmmunostaining demonstrated CuZn SOD, CAT, and Mn SOD immunoreactivity in plexuses external to the muscularis propria and plexuses in the lamina propria of the mucosa. Addition of X/XO, but not X alone, (Table, Group I) increased the frequency of contractions. SOD decreased contractile frequency after X/XO (Group II). SOD alone had no affect but inhibited the effect of X/XO on contractile frequency (Group liD. CONCLUSIONS: 02." alters SO motor function. The presence of 02-" scavenging enzymes in enteric neurons suggests that they may regulate SO neuromuscular function by clearing endogenous 02.group I cycles/min group II cgcles/min control 3.1_+0.8 control 3.0+1.2 X 2.8L,-'0.7 X/XO 6.4_+0.8* X/XO 4.2_+0.9* SOD 2.9+0.4 Means+SEM. *p<0.05 vs control.
~,roupIII cyclcs/min control 5.4+1.1 SOD 5.6_+0.9 X/XO 5.4-+1.2
@ S u c c e s s f u l T r e a t m e n t o f S y m p t o m a t i c Hepatic Cysts b y S i n g l e - S h o t Instillation of M i n o c y c l i n e Chloride. DESLANDES P.(1), CELLIER C.(2), C U E N O D C.A.(1), L A N D I B.(2), BELY N.(1), REVEL M.P.(1), BARBIER J.P.(2), FRIIA G.(1). Depts of Radiology(I) and Gastroenterology(2), HSpital La~nnec 75007 Paris FRANCE. Hepatic cysts are common and usually asymptomatic, However, large cysts may induce clinical manifestations. Simple percutaneons drainages are followed by recurrence and therapy w i t h alcohool instillation requires several procedures. We report o u r experience on single-shot instillation of minocycline chloride in large hepatic cyst treatment. Patients and Methods : From November 1992 to March 1994, 7 patients (2M, 5W, mean age : 52 years) ~:ith large symptomatic (reccurent abdominal pain or GI tract obstruction) hepatic cysts (mean diameter:. 8.5 cm; range 5.5 to 16 cm) have been treated by intracystic injection in a ambulatory procedure without any anesthesia. Five patients had a solitary cyst and two patients had polycystic liver disease. The target cyst was punctured by a 22 gauge fine needle u n d e r u l t r a s o u n d guidance. T h e n the cyst was first opacified under fluoroscopy to test for the absence of communication between the cyst and the bfliary tree. Half of the cyst content was removed by aspiration, and 250 to 500 m g of minocycline chloride diluted in 10 ml of saline with 10 ml of 1% xylocaine were instillated inside the deflated cyst. Results : After the procedure, only two patients encountered transient pain. In one case, pain was associated with a mild fever. After a mean evolution period of 12 m o n t h s (6 to 24 ) : a) S y m p t o m s diseappeared in all patients with solitary cyst. The volume of the cyst always decreased by at least 50% with total regression in three cases, b) The 2 patients with m u l t i p l e hepatic cysts experienced only transient clinical
improvment and the initial volume of the treated cyst recurred fastly in one case. C o n c l u s i o n : Single-shot instillation of Minocycline chloride is a p r o m i s i n g technique for s y m p t o m a t i c solitary hepatic cyst treatment.
PROSPECTIVE EVALUATION OF THE IMPACT OF E N D O S C O P I C U L T R A S O N O G R A P H Y ON D I A G N O S T I C AND T H E R A P E U T I C S T R A T E G I E S OF E X T R A H E P A T I C C H O L E S T A S I S . B.J.Denis, K. Dron, V.Denny, M.A. Bigard, P. Gaucher. Service HGE, CHU Nancy, 54511, Vandoeuvre, France. The high accuracy of endoscopic ultrasonography (EUS) for diagnosis of extrahepatic cholestasis is well documented. The clinical effectiveness of the use of EUS on the management of extrahepatic cholestasis has not been prospectively studied yet. A I M : To evaluate prospectively the impact of the use of EUS on diagnostic and therapeutic strategies of extrahepatic cholestasis. [VIETHODS : One hundred and sixty three consecutive patients having EUS (Olympus GF-UM3) for extrahepatic cholestasis were prospectively included. Investigations performed before EUS were: ultrasonography (US) n=152; computed tomography (CT) n=118; duodenoscopy n--31; ERCP n=29 (bile duct cannulation failure in 21 cases). For each patient the following parameters were recorded before EUS: suspected diagnosis; next investigation planned for diagnostic confirmation; and suggested treatment. These data were compared to final diagnoses and effective treatments. ]IESULTS : EUS couldn't be performed in 7 cases (4%) because of a stenosis. In 12 cases (7%) no EUS diagnosis was made. Final diagnoses in the remaining 144 patients were: no obstruction n=24; stone n=65; cancer n=54; Caroli n=l. EUS diagnoses were wrong 4 times (2.5%) and exact 140 times (86%). US and CI" diagnoses were exact in 19% and 46% of cases. EUS detected 65 (40%) obstacles that had not been seen previously (42 stones, 22 cancers, 1 Caroli) and corrected 33 (20%) wrong initial diagnoses: in 19 cases there was no obstruction and in 14 cases the nature of obstruction was wrong (8 stones, 5 cancers, 1 Caroli). EUS results avoided doing 20 diagnostic ERCP, led to 9 renewed ERCP attempts for stone extraction after initial cannulation failure, and modified 20 times (12%) the diagnostic strategy. Except for the 33 (20%) wrong initial diagnoses that were corrected by EUS, EUS results never had direct impact on therapeutic management, even for cancers. Neither laparotomy nor endoscopic sphincterotomy were decided or avoided owing to EUS results. (~ONCLUSlONS : Our results confirm the unequalled accuracy of EUS for the diagnosis of extrahepatic cholestasis. But, in a non-selected population, EUS use had only a low impact on therapeutic management. This impact could probably be enhanced by an earlier use (i.e. previous to CT) of EUS in the diagnostic strategy of extrahepatic cholestasis.
PROPHYLACTIC ANTIBIOTIC THERAPY IN THE PREVENTION OF STENT BLOCKAGE. T Desta. E Libby, YL Liu, K Lain and JW Leung. UCDMC, Sacramento, CA, NEMC, Boston, MA, DUMC, Durham NC. Bacterial adherence and biofilm formation is a known cause for biliary stent blockage. The incidence vary between 28% to 53%. A mixture of gram -ve and gram +re bacteria have been isolated. Previous studies with antibiotic therapy have given conflicting results. We have tested the effect of antibiotics [Ampicillin (Amp), Ceftazidime (Cfl) and Ciprofloxacin (Cip)] in an in vitro study against E.coli and Enterococci in the prevention of adherence and stent blockage. Methods: Selected strains of E.coli and Enterococci isolated from blocked stents were tested against the antibiotics given at MIC levels using a constant flow device (MP,.D). Pieces of 10Fr polyethylene stent material mounted in the MRD were perfused with infected bile containing either bacteria for up to 7 days. Segements of the stents were removed and examined daily for biofilm formation. The experiments were arranged as follows: 1. Infected bile (I]3) alone (control), 2. 113 and Amp, 3. I]3 and Cf~, 4. ]]3 and Cip. Results: Compared to the control group, Cft and Cip caused a I00 fold reduction in E coli adherence but Cf~ is ineffective against Enterocncci. Amp led to a 10 fold reduction in Enterococci adherence. =
'
~
n
t
r
o
•
l
Ceffazidine.
...........................
~o~troi
.............
~8 ~a
p
Hour
Hour
Conclusion: Timely treatment with appropriate antibotics reduce bacterial adherence and biofilm formation and may have potential benefit in prevention of stent blockage. Further studies to address the timing, duration and possible combination of antibiotics therapy are required to develop an optimal treatment strategy.