Effect of experimental acalculous cholecystitis on gallbladder smooth muscle contractility

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A536 AGA ABSTRACTS G2189 COMPARISON OF TREATMENTS FOR HEPATOLITHIASIS: HEPATIC RESECTION VS CHOLANGIOSCOPIC LITHOTOMY. K. Otani, S. Shimizu, K. Chijiiwa, K. Yamaguchi, S. Kuroki, M. Tanaka. Dept. of Surg. 1, Kyushu Univ., Fukuoka, Japan. [Backgrounds] Hepatolithiasis, a benign disease in nature, is frequently associated with recurrence, leading to cirrhosis and liver failure due to long- standing cholangitis. The aim of the present study is to compare the long-term results of two main procedures, hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCS-L). [Methods] Between 1980 and 1996, 86 patients with hepatolithiasis were admitted. Hepatic resections were performed in 26 patients (combined with PTCS-L in 4) and PTCS-L in 29 patients. Operations included 16 lateral segmentectomies, 5 left lobectomies and 5 others. Six times of PTCS-L were required on average (range: 1-20) in each patient. There was no difference between the two groups in terms of sex, age, and the distribution of intrahepatic stones. Recurrence ram and long-term prognosis were analyzed by the Kaplan-Meier's method and other factors listed below were statistically compared. [Results] Hepatic resection PTCS-L P Complete removal of stones (%) 96.2 (25/26) 96.6 (28/29) N.S. Remaining bile duct stricture (%) 12.5 (3/24) 50.0 (14/28) < 0.01 Complications (%) 38.5 (10/29) 20.7 (6/29) N.S. Hospital stay (days) 115 (40-400) 79 (24-223) < 0.05 5-year recurrence rate (%) 5.6 31.2 < 0.05 5-year survivalrate (%) 78.6 96.3 N.S. Complications included bile leaks (n=3), liver failure (n=2) and sepsis (n=2) in the surgery group, and impaired liver function (n=2), cholangitis (n=2) and hemobilia (n=2) in PTCS-L. Causes of death were cholangiocellular carcinoma (n=2), hepatocellular carcinoma (n=l), liver failure (n=2), operative death (n=l) in the former, and liver failure (n=l), rupture of esophageal varices (n=l) and unrelated diseases (n=2) in the latter. [Conclusions] The rate of complete removal of stones was similarly high in both groups. Rate of complications and 5-year survival rate were comparable. Recurrence rate was statistically high in the PTCS-L group, which was partly ascribed to the remaining bile duct stricture. We conclude that hepatic resection is a better treatment when complete removal of both stones and stricture can be achieved by surgery. • G2190 LAPAROSCOPIC BILE DUCT STONES MANAGEMENT IN TIlE FIRST 100 OF 216 CONSECUTIVE UNSELECTED PATIENTS. A.MPaganini, M.Guerrieri, F.Feliciotti, A.Tamburini, R.Campagnacci, E.Lezoche. Istituto di Scienze Chirurgiche, University of Ancona, Ancona. The introduction of laparoscopic cholecystectomy (LC) has modified the treatment of gallstones and common bile duct (CBD) stones. Aim of this prospective study was to evaluate the feasibility, safety and efficacy of single stage laparoscopic management of gallstones and CBD stones. Common bile duct stones were present at routine intraoperative cholangiography in 216 patients (140 females, 76 males, mean age 52.3 years, age range 12-94 years) out of 2290 with gallstones undergoing laparoscopic cholecystectomy (9.4%) from January 1991 to November 1997. In the first 100 patients (64 female, 36 male, mean age 58.1, range 12-94) CBD stones were unsuspected in 45 (45%) and suspected in 55 patients (55%) (in 15 after failed endoscopic sphincterotomy, ERCP/ES). Laparoscopic trans-cystic (TC) duct CBD exploration was the procedure of choice, followed by laparoscopic cboledochotomy when the former was not feasible. Use of biliary drainages was liberal and completion cholangiograms were obtained in all patients. LC and TC-CBD exploration was successful in 68 cases (with no biliary drainage in 30) and after choledochotomy in 28 (with a biliary drainage in 27). Four cases were converted to open surgery at the beginning of our experience (4%). Retained stones in 5 patients (5%), were treated mainly by percutaneous endoscopic/fluoroscopic stone removal (3 cases) and by ERCP/ES in 1 case. Spontaneus stone passage was observed in another case awaiting percutaneous treatment. Cystic duct bile leakage in 3 cases (3%) was due to clips (2) and biliary drainage displacement (1). Hyperamylasemia (2), biloma (1), and umbilical haematoma (1) were observed. An 81 years old, high risk patient, referred after failed ES, died from cardiogenic shock 3 days after successful laparoscopic surgery. Clinical follow-up (F-U) was available in 95 cases out of 95 (100%) (mean F-U 55.5 months, range 42-94 months), with yearly laboratory exams and ultrasound (US) in asymptomatic patients, and with ERCP or Cholangio Magnetic Resonance when symptoms of biliary origin were present. Seventy patients are presently asymptomatic (70%) and 20 have unrelated symptoms (irritable bowel syndrome 7, 7.3%, dyspepsia ! 3, 13.6%). Recurrent stones were observed in 1 case (1.05%), 18 months after T-tube removal, and was treated by ERCP/ES. Four patients died from unrelated causes. On the basis of our experience LC and CBD exploration was feasible, safe and highly successful with good results both in the short and in the long term. GASTROENTEROLOGY Vol. 114, No. 4 G2191 CHOLEDOCHODUODENAL FISTULA IN KOREA: A CLINICAL ANALYSIS OF 97 PATIENTS DIAGNOSED BY ERCP. Ioon~won Park, Hyung Joon Kim, Jae Gyu Kim, Byung Chul Yoo, and Sill Moo Park. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea. Background: Choledochoduodenal fistula(CDF) is occasionally found during endoscopic retrograde cholangiopancreatography(ERCP). Cholelithiasis is suspected to be the leading cause of CDF in some endemic areas like Korea but there were only a few data of small cases of CDF. Therefore, we analyzed clinical characteristics of 97 cases of CDF diagnosed by ERCP. Methods: In 1148 ERCP studies of our hospital from 1993 to 1996, we observed 97 CDF found on the papilla of Vater or in the upper portion O f that. The records of 97 patients with CDF were retrospectively reviewed. Their clinical features and ERCP findings were analyzed and compared in the aspect of CDF types(I,II,III) which were classified by location of fistula. Results: The prevalence of CDF was 8.4% and the mean age was 55.1 +-. 12.1 years. Sixty- two patients(27 male, 35 female) were type I CDF on the longitudinal fold of the papilla, 32 patients(12 male, 20 female) were type II CDF at the oral edge of the papilla, and 3 patients(1 male, 2 female) were type III CDF on the proximal duodenum. The most common chief-complaints of 97 patients was epigastric pain(86.6%) and 56 patients(57.7%) had a history of acute cholangitis. Only 17(17.5%) had a history of common bile duct(CBD) exploration, and a history of which exerted no influence on the type of CDF statistically(p>0.05). There was no significant difference of blood chemistry results between type I, 1I, and Ili CDF. Fifty-seven(58.8%) patients had intrahepatic bile duct stones, 39(40.2%) had CBD stones, and 7(7.2%) had gallbladder stones; only 4 cases were not associated with gallstone diseases. Two cases of type III CDF were associated with both duodenal ulcer disease and gallstone diseases. The location of biliary stones, and the diameter of CBD did not influence the type of CDF(p>0.05). Type II CDF had prominent pneumobilia, and less biliary stones than type I CDF(p<0.05). Conclusions: The incidence of CDF in Korea is higher than in the West. Most of CDF cases serve as a chronic sequelae of cholelithiasis, especially intrahepatic bile duct stones, but about half of cases has no history of acute cholangitis. Two different clinical features between type I and II CDF are the pneumobilia and the amount of biliary stones. G2192 EFFECT OF EXPERIMENTAL ACALCULOUS CHOLECYSTITIS ON GALLBLADDER SMOOTH MUSCLE CONTRACTILITY, HP Parkman, L Bogar, L Bartula, AP Pagano, RM Thomas, SI Myers. Departments of Medicine, Pathology, & Surgery. Temple University. Philadelphia, PA. Acute inflammation of the gallbladder occurs in both calculous and acalculous cholecystitis. Although gallbladder motility has been studied in animal models of chronic cholelithiasis, gallbladder contractility in acute acalculous gallbladder inflammation has not been studied. The purpose of this study was to determine the effects of acute acalculous inflammation on gallbladder muscle contractility using the common bile duct ligation (CBDL) technique in guinea pigs. METHODS: Gallbladder muscle contractility was studied in normal, CBDL, and sham operated male guinea pigs. Upon sacrifice at 1, 2, or 3 days after CBDL or sham surgery, blood was obtained and the gallbladder was removed. Gallbladder dimensions were measured, and four muscle strips were prepared from each gallbladder: 3 for in vitro contractility studies in response to potassium and bethanechol, and 1 for histology. Hematoxylin and eosin stained slides were scored for inflammatory changes with a scale from 0 to 17 based on the presence of an infiltrate of inflammatory cells, hemorrhage, edema, surface ulceration, fibroblast proliferation, vascular dilation, and Rokitansky-Aschoff sinus formation. RESULTS: Expressed in table as mean _+ SEM; *: p<0.05 vs control. Muscle Tension(kg/cm2) GB Volume S e r u m lnflamm Potassium Bethanechol Groops (¢ra3) Bilirubin Store 80 mM 100 nM Normals 1.0 ± 0.1 0.0 ± 0.0 2.0 - 0.4 0.56 -+ 0.04 0.62 ± 0.04 Sham-I day 0.9-+0.3 0.0 ± 0.0 3.0-+1.0 0.50±0.05 0.52-+0.06 Sham-2day 1.5 ± 0.3 0.0 -+ 0.0 2.3 ± 0.3 0.57 -+ 0.04 0.59 ± 0.05 Sham-3day 1.0 ± 0.8 0.0 ± 0.0 N/A 0.59 ± 0.15 0.67 -+ 0.15 CBDL-1 day 2.6 ± 0.2* 3.3 -+ 0.3* 6.0 ± 0.0" 0.25 -+ 0.03* 0.33 ± 0.05* CBDL-2day 3.7 ± 0.3* 5.4 ± 0.3* 5.0 ± 0.7* 0.23 ± 0.02* 0.28 ± 0.03* CBDL-3 day 4.8±0.3* 5.1±0.9" 6.8-+1.9" 0.10-+0.02 * 0.12-+0.02" CONCLUSIONS: CBDL in the guinea pig produces both acute inflammation of the gallbladder and marked decrease in smooth muscle contractility. Direct inhibition of smooth muscle function is indicated by the impaired response to potassium depolarization and bethanechol stimulation. Thus, impaired smooth muscle contractility secondary to inflammation may play a role in the pathophysiology of acalculous cholecystitis. This study was funded by NIH K08-DK02080 and R01-DK 38342.

Transcript of Effect of experimental acalculous cholecystitis on gallbladder smooth muscle contractility

A536 AGA ABSTRACTS

• G2189 COMPARISON OF TREATMENTS FOR HEPATOLITHIASIS: HEPATIC RESECTION VS CHOLANGIOSCOPIC LITHOTOMY. K. Otani, S. Shimizu, K. Chijiiwa, K. Yamaguchi, S. Kuroki, M. Tanaka. Dept. of Surg. 1, Kyushu Univ., Fukuoka, Japan.

[Backgrounds] Hepatolithiasis, a benign disease in nature, is frequently associated with recurrence, leading to cirrhosis and liver failure due to long- standing cholangitis. The aim of the present study is to compare the long-term results of two main procedures, hepatic resection and percutaneous transhepatic cholangioscopic lithotomy (PTCS-L). [Methods] Between 1980 and 1996, 86 patients with hepatolithiasis were admitted. Hepatic resections were performed in 26 patients (combined with PTCS-L in 4) and PTCS-L in 29 patients. Operations included 16 lateral segmentectomies, 5 left lobectomies and 5 others. Six times of PTCS-L were required on average (range: 1-20) in each patient. There was no difference between the two groups in terms of sex, age, and the distribution of intrahepatic stones. Recurrence ram and long-term prognosis were analyzed by the Kaplan-Meier's method and other factors listed below were statistically compared.

[Results] Hepatic resection PTCS-L P Complete removal of stones (%) 96.2 (25/26) 96.6 (28/29) N.S. Remaining bile duct stricture (%) 12.5 (3/24) 50.0 (14/28) < 0.01 Complications (%) 38.5 (10/29) 20.7 (6/29) N.S. Hospital stay (days) 115 (40-400) 79 (24-223) < 0.05 5-year recurrence rate (%) 5.6 31.2 < 0.05 5-year survival rate (%) 78.6 96.3 N.S.

Complications included bile leaks (n=3), liver failure (n=2) and sepsis (n=2) in the surgery group, and impaired liver function (n=2), cholangitis (n=2) and hemobilia (n=2) in PTCS-L. Causes of death were cholangiocellular carcinoma (n=2), hepatocellular carcinoma (n=l), liver failure (n=2), operative death (n=l) in the former, and liver failure (n=l), rupture of esophageal varices (n=l) and unrelated diseases (n=2) in the latter. [Conclusions] The rate of complete removal of stones was similarly high in both groups. Rate of complications and 5-year survival rate were comparable. Recurrence rate was statistically high in the PTCS-L group, which was partly ascribed to the remaining bile duct stricture. We conclude that hepatic resection is a better treatment when complete removal of both stones and stricture can be achieved by surgery.

• G2190 LAPAROSCOPIC BILE DUCT STONES MANAGEMENT IN TIlE FIRST 100 OF 216 CONSECUTIVE UNSELECTED PATIENTS. A.MPaganini, M.Guerrieri, F.Feliciotti, A.Tamburini, R.Campagnacci, E.Lezoche. Istituto di Scienze Chirurgiche, University of Ancona, Ancona.

The introduction of laparoscopic cholecystectomy (LC) has modified the treatment of gallstones and common bile duct (CBD) stones. Aim of this prospective study was to evaluate the feasibility, safety and efficacy of single stage laparoscopic management of gallstones and CBD stones. Common bile duct stones were present at routine intraoperative cholangiography in 216 patients (140 females, 76 males, mean age 52.3 years, age range 12-94 years) out of 2290 with gallstones undergoing laparoscopic cholecystectomy (9.4%) from January 1991 to November 1997. In the first 100 patients (64 female, 36 male, mean age 58.1, range 12-94) CBD stones were unsuspected in 45 (45%) and suspected in 55 patients (55%) (in 15 after failed endoscopic sphincterotomy, ERCP/ES). Laparoscopic trans-cystic (TC) duct CBD exploration was the procedure of choice, followed by laparoscopic cboledochotomy when the former was not feasible. Use of biliary drainages was liberal and completion cholangiograms were obtained in all patients. LC and TC-CBD exploration was successful in 68 cases (with no biliary drainage in 30) and after choledochotomy in 28 (with a biliary drainage in 27). Four cases were converted to open surgery at the beginning of our experience (4%). Retained stones in 5 patients (5%), were treated mainly by percutaneous endoscopic/fluoroscopic stone removal (3 cases) and by ERCP/ES in 1 case. Spontaneus stone passage was observed in another case awaiting percutaneous treatment. Cystic duct bile leakage in 3 cases (3%) was due to clips (2) and biliary drainage displacement (1). Hyperamylasemia (2), biloma (1), and umbilical haematoma (1) were observed. An 81 years old, high risk patient, referred after failed ES, died from cardiogenic shock 3 days after successful laparoscopic surgery. Clinical follow-up (F-U) was available in 95 cases out of 95 (100%) (mean F-U 55.5 months, range 42-94 months), with yearly laboratory exams and ultrasound (US) in asymptomatic patients, and with ERCP or Cholangio Magnetic Resonance when symptoms of biliary origin were present. Seventy patients are presently asymptomatic (70%) and 20 have unrelated symptoms (irritable bowel syndrome 7, 7.3%, dyspepsia ! 3, 13.6%). Recurrent stones were observed in 1 case (1.05%), 18 months after T-tube removal, and was treated by ERCP/ES. Four patients died from unrelated causes. On the basis of our experience LC and CBD exploration was feasible, safe and highly successful with good results both in the short and in the long term.

GASTROENTEROLOGY Vol. 114, No. 4

G2191 CHOLEDOCHODUODENAL FISTULA IN KOREA: A CLINICAL ANALYSIS OF 97 PATIENTS DIAGNOSED BY ERCP. Ioon~won Park, Hyung Joon Kim, Jae Gyu Kim, Byung Chul Yoo, and Sill Moo Park. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Background: Choledochoduodenal fistula(CDF) is occasionally found during endoscopic retrograde cholangiopancreatography(ERCP). Cholelithiasis is suspected to be the leading cause of CDF in some endemic areas like Korea but there were only a few data of small cases of CDF. Therefore, we analyzed clinical characteristics of 97 cases of CDF diagnosed by ERCP. Methods: In 1148 ERCP studies of our hospital from 1993 to 1996, we observed 97 CDF found on the papilla of Vater or in the upper portion O f that. The records of 97 patients with CDF were retrospectively reviewed. Their clinical features and ERCP findings were analyzed and compared in the aspect of CDF types(I,II,III) which were classified by location of fistula. Results: The prevalence of CDF was 8.4% and the mean age was 55.1 +-. 12.1 years. Sixty- two patients(27 male, 35 female) were type I CDF on the longitudinal fold of the papilla, 32 patients(12 male, 20 female) were type II CDF at the oral edge of the papilla, and 3 patients(1 male, 2 female) were type III CDF on the proximal duodenum. The most common chief-complaints of 97 patients was epigastric pain(86.6%) and 56 patients(57.7%) had a history of acute cholangitis. Only 17(17.5%) had a history of common bile duct(CBD) exploration, and a history of which exerted no influence on the type of CDF statistically(p>0.05). There was no significant difference of blood chemistry results between type I, 1I, and Ili CDF. Fifty-seven(58.8%) patients had intrahepatic bile duct stones, 39(40.2%) had CBD stones, and 7(7.2%) had gallbladder stones; only 4 cases were not associated with gallstone diseases. Two cases of type III CDF were associated with both duodenal ulcer disease and gallstone diseases. The location of biliary stones, and the diameter of CBD did not influence the type of CDF(p>0.05). Type II CDF had prominent pneumobilia, and less biliary stones than type I CDF(p<0.05). Conclusions: The incidence of CDF in Korea is higher than in the West. Most of CDF cases serve as a chronic sequelae of cholelithiasis, especially intrahepatic bile duct stones, but about half of cases has no history of acute cholangitis. Two different clinical features between type I and II CDF are the pneumobilia and the amount of biliary stones.

• G2192

EFFECT OF EXPERIMENTAL ACALCULOUS CHOLECYSTITIS ON GALLBLADDER SMOOTH MUSCLE CONTRACTILITY, HP Parkman, L Bogar, L Bartula, AP Pagano, RM Thomas, SI Myers. Departments of Medicine, Pathology, & Surgery. Temple University. Philadelphia, PA.

Acute inflammation of the gallbladder occurs in both calculous and acalculous cholecystitis. Although gallbladder motility has been studied in animal models of chronic cholelithiasis, gallbladder contractility in acute acalculous gallbladder inflammation has not been studied. The purpose of this study was to determine the effects of acute acalculous inflammation on gallbladder muscle contractility using the common bile duct ligation (CBDL) technique in guinea pigs. METHODS: Gallbladder muscle contractility was studied in normal, CBDL, and sham operated male guinea pigs. Upon sacrifice at 1, 2, or 3 days after CBDL or sham surgery, blood was obtained and the gallbladder was removed. Gallbladder dimensions were measured, and four muscle strips were prepared from each gallbladder: 3 for in vitro contractility studies in response to potassium and bethanechol, and 1 for histology. Hematoxylin and eosin stained slides were scored for inflammatory changes with a scale from 0 to 17 based on the presence of an infiltrate of inflammatory cells, hemorrhage, edema, surface ulceration, fibroblast proliferation, vascular dilation, and Rokitansky-Aschoff sinus formation. RESULTS: Expressed in table as mean _+ SEM; *: p<0.05 vs control.

Muscle Tension (kg/cm2) GB Volume Serum lnf lamm Potassium Bethanechol

Groops (¢ra3) Bilirubin Store 80 mM 100 nM Normals 1.0 ± 0.1 0.0 ± 0.0 2.0 - 0.4 0.56 -+ 0.04 0.62 ± 0.04 Sham-I day 0.9-+0.3 0.0 ± 0.0 3.0-+1.0 0.50±0.05 0.52-+0.06 Sham-2 day 1.5 ± 0.3 0.0 -+ 0.0 2.3 ± 0.3 0.57 -+ 0.04 0.59 ± 0.05 Sham-3 day 1.0 ± 0.8 0.0 ± 0.0 N/A 0.59 ± 0.15 0.67 -+ 0.15 CBDL-1 day 2.6 ± 0.2* 3.3 -+ 0.3* 6.0 ± 0.0" 0.25 -+ 0.03* 0.33 ± 0.05* CBDL-2 day 3.7 ± 0.3* 5.4 ± 0.3 * 5.0 ± 0.7* 0.23 ± 0.02* 0.28 ± 0.03 * CBDL-3 day 4.8±0.3* 5.1±0.9" 6.8-+1.9" 0.10-+0.02 * 0.12-+0.02"

CONCLUSIONS: CBDL in the guinea pig produces both acute inflammation of th e gallbladder and marked decrease in smooth muscle contractility. Direct inhibition of smooth muscle function is indicated by the impaired response to potassium depolarization and bethanechol stimulation. Thus, impaired smooth muscle contractility secondary to inflammation may play a role in the pathophysiology of acalculous cholecystitis. This study was funded by NIH K08-DK02080 and R01-DK 38342.