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Lack of hemodynamic response to long-acting octreotide (Sandostatin LAR) in patients with cirrhosis
13
Results
GI GII
follow-up bleeding ascites death months n (%) n (%) n (%)
%*
21-+15 23±18
-11.5±14 1.6__.1.5 61_+48 -16-+12 4.4±2.4, 232±169,
7(14) 3 (6)
13(25) 7 (14)
3(6) 1 (2)
HVPG
Computed Tomography(CT) Enteroclysis in Comparisonto Ileo-Colonoscopyin Patients with Crohn's Disease (CD) Cesare Hassan, Paoia Cerro, Angelo Zullo, Carmelo Spina, Sergio Morini, Dept Gastroenterologyand Radiology, Nuovo Regina Margherita Hosp, Rome Italy
PRA PA ng/ml.h pg/ml
BACKGROUND:Enteroclysisand CT scanning are widely used in CD patientsto assessluminal and extraluminal features of the disease. Recently,these techniques have been successfully combined in CT enteroclysis with promising results in preliminary studies. However, CT enteroclysis has never been compared to endoscopy.Aim of this study was to compare the accuracy of CT enteroclysis to that of endoscopy in detecting bowel watt alterations in CD patients, and to assess whether postcontrast wall density at CT enteroclysis was related to clinical activity of CD. METHODS:Overall,24 patients (Mean age:47years;M/F:16/11;previous surgery:lO patients) referred for radiological assessment of CD were consecutivelyenrolled. CD diagnosis was performed by ileo-colonoscopywith histological assessmentin all patients, and clinical activity was measured by the Crohn's diseaseactivity index(CDAI). Five patients without CD were also included as controls. Spiral CT was performed after distension of the small bowel loops with a transparent enema of methylcellulose. Radiologists were unaware of endoscopicfindings. RESULTS:At endoscopy,CD was localizedto the ileum in 16 patients, to both the ileum and the colon in 5, and only to the colon in 3 cases. CT enteroclysis was successfully performed in all patients. CD involvement of the bowel wall, defined as wall thickness greater than 4 mm with a muitilayeredappearance,was detected in 15 out of the 16 cases of CD ileitis, in 4 out of the 5 cases of iteo-colifis, and in 2 of the 3 cases of colitis, with an overall sensitivity of 87%. In detail, two early post-surgical recurrencesat the neoterminal ileum, and one case of segmental colitis were missed at CT enteroclysis. No false-positive cases were observed in the control group. Postcontrast wall density value was significantly higher in the 16 patients with active disease (CDAI>150) than in the remaining 8 cases with inactive CD(115_+25 vs 32_+20;p<0.01). Furthemore, extraluminal features of CD were detected in 13 patients (3 fistulas,3 abscessesand 7 cases ot 1ibrotattyproliferation of the mesenteric tissue). CONCLUSIONS:CTenteroclysis proved to be highly sensitive and specific in assessing bowel wall alterations in CD patients with the possible exceptionof early post-surgical recurrences. The degree of postcontrast wall enhancement may provide an imaging model to assess diseaseactivity. Its ability to evaluateboth intra- and extra-luminal features makes its use tempting in selected cases of CD.
Valuesare givenas mean±SD.* p~O.Otvs baselinel ,, % of decreasevs baseline 11 Lock of Hemodynamic Responseto Long-ActingOctreotide (Sandostatin LAR) in Patients with Cirrhosis P S. Kamath, Mayo CUn, Rochester, MN; K ~nner, OHSU, Portland, OR; A Blei, Northwestern Memorial Hosp, Chicago, IL; J Bosch, Hosp Clin I Provincial, Barcelona Spain; W Carey, ClevelandClin, Cleveland,OH; N Grace, Faulkner Hosp, Jamaica Plain, MA; K Kowdley, Univ of Washington, Seattle, WA; K Sizer, Novartis PharmaceuticalsCorp, East Hanover, NJ; R Groszmann, VA Medical Ctr, West Haven,VA BACKGROUND:Octreotlde, the short-acting synthetic analogue of somatostatin, is useful in the control of variceal bleeding (NEJM 1995;33:55). It is not known whether a long-acting derivativeof octreotide (LAO-sandostatinLAR) may be effectivein preventingvaricealbleeding. AIM: To study the fasting and postprandial hemodynamic response as measured by hepatic vein pressure gradient (HVPG), portal blood flow (PBF), and superior mesenteric artery pulsatility index (SMA-PI) in responseto two different doses of LAO. METHODS:A multicenter randomized double-blind placebo-controlledstudy was carried out in 39 patients deemedto be at low risk for variceal bleeding, namely patients with Child-Pugh Class A or B cirrhosis with small varices and standardizedexclusion criteria. HVPG measurementswere carried out at baseline and day 84 following the first administration of the study drug. Patients were randomized to LAO 10 mg (n= 15), LAO 30 mg (n= 10), or saline (N =14). Blood samples were collected over 24 hours, and again at days 14, 28, 56 and 84. Additional injections of the study drug were given on day 28 and day 56, while Doppler uifrasound studiesto measure PBF and SMA-PI were carried out at baseline and on days 28, 56 and 84. The effect of treatment was measured by change from baseline in HVPG, PBF and SMA-PI. RESULTS: There was no significant decrease(p = 0.26 by ANOVA)in HVPGat day 84 as compared with baseline with LAD 30 mg (11.6_+2.3 mm Hg vs 14.1_+3.2) or LAO 10 mg (15.3_+4.8 mm Hg vs 15.1_+3.8); saline (13.3_+3.8 mm Hg vs 15.1_+4.3). P8F did not change significantly (-97 ml/min LAO 10 mg, +27 ml/min LAO 30 mg; +4,7 ml/min saline), p=0.8, while SMAPI was almost identical. Octreotlde levels reached a plateau between days 28 and 56. Four patients in the LAO 30 mg group dropped out of the study becauseof side affects. CONCLUSION: Octreotide levels were adequately maintained with administration of LAO. However, there was no significant decrease in either hepatic vein pressure gradient, portal blood flow or superior mesenteric artery pulsatile index with either dose of LAO. These results do not support the use of long-acting octreotide in the prevention of variceal bleeding in patients of portal hypertension.
14 Galactase-Dased IntravenousSonographic Contrast Agent (Levovist) In Crahn's Disease Antonio Oi S~hatlno, GastroenterologyUnit, Univ of Pavia, Pavia italy; llada Fufle, Dept o1 Radiology, Univ of Pavia, Pavia Italy; Lodovica Po:~i, RacheleCiccocioppo, Laura Ricevuti, Gastroenterology Unit, Univ of Pavia, Pavia Italy; FrancescoPaolo Tinozzi, Stefano Tinozzi, Dept of Surg, Univ of Pavia, Pavia Italy; Rodolfo Campani, Dept of Radiology, Univ of Pavia, Pavia Italy; Gino Roberto Cor~a, GastroenterologyUnit, Univ of Pavia, Pavia Italy Background & Aims: Abdominal ultrasound (US) has been proposed as a reliable tool to assess increasedbowel wall thickness (BWT), the most common sign in patientswith Crohn's disease (CD). Neverthless its sensitivity is not satisfactory. Therefore, we tried to assess whether the use in color power Doppler (CPD) of Levovist, a galactose-hasedintravenous sonographiccontrast agent able to enhancearterial Dopplersignal, increasesthe US accuracy. Patients & Methods: Twenty-two patients with ileal CD, .diagnosed by lower endoscopy and enteroclisis (mean age 36.1 yrs, range 18-63) and 20 control subjects (mean age 38.3 yrs, range 20-65) were examinetedwith conventional US (Aloka SSD-1700; convex probe 5 MHz). BWT up to 4 mm was consideredas normal. Afterwards, CPD of the intramural enteric vessels was performed (7.5 MHz, ATL HDI 3000) before and after intravenous injection of 5-10 ml of Levovist at the concentration of 300 mg/ml. Disease activity was assessed by Crohn's disease activity index (CDAI). None of the CD patients were previously operated due to complications of IBD. Results: Fifteen CD patients with ileal (n=9) or ileocolonic (n=6) lesions had a BWT>4. Nine of these 15 patients presented an active disease (CDAI>150). The remaining 7 CD patients, all with BWT<4, had ileal (n = 3), ileocolonic (n = 3) and gastroileo-colonic (n = 1) lesions, and 2 of them presentedan active disease.All the control subjects had a normal BWT. CPD showed an increased intramural flow in 16 CD patients in basal conditions, and in 20 CD patients after Levovist injection. Two of the 4 patients identified only by CPD after Levovist injection, all with quiescent CO, underwent to relapse within two months. In our hands, sensitivity and specificity were respectively 68% and 100% in US, 72% and 100% in basal CPD, 90% and 100% after Levovist injection. Conclusions: The use of Levovist in CPD showed an higher accuracy in CD diagnosis and follow-up compared to basal CPD and US. In addition, our data support that an increased intramural flow evaluated by CPD after Levovist injection representsa predictivefactor of impending relapse in patients with quiescent CD.
12 Circadian Meal-Stimulated Portal Blood Flow In Patients With Liver Cirrhosis. Peter J E Schiedermaier, Lydia Koch, Tilman Sauerhruch, Dept of Gen Intemal Medicine, Univ of Bonn, Bonn Germany Introduction: The chronorisk of variceal hemorrhage was explained by a circadian variability of portal vein flow (PVF) which, however,has beenestablishedsolely under fasting conditions. Meal stimulated circadian portal blood flow, reflecting daily live, has not been investigatedin cirrhotic patients to date. Methods: 25 patients with liver cirrhosis were examined during a 24h period twice at day 1 and day 8. PVF (ml/min) was measured by Doppler ultrasound at 8:30, 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 13:00, 13:15, 13:30, 13:45, 14:00, 14:30, 15:00, 17:00, 19:00, 19:15, 19:30, 19:45, 20:00, 20:30, 21:00, 23:00, 1:00, 3:00, 8:30. 500 ml Ensure PlusTM were given at 9:00, 13:00 and 19:00. Measurementsat 9:15-11:00, 13:1515:00 and 19:15-21:00 were classified as postprandial. Areas under the curve of circadian PVF (AUC of 24h-PVF) were calculated and correlated with fasting HVPGs [mmHg] and the Child-Pugh scores. Results: Fasting PVF showed a significant circadian variability with a maximum at 13:00 (+ 3.7 +_ 25.8%; mean _+ SD) and a minimum at 3:00 ( -9.8 _+ 25.9%, MANOVA: p < 0.001). Postprandialincrease in PVF was higher in the morning than at noon or in the evening (66.6 _+ 66.7% vs. 39.3 _+ 27.8% vs, 49.7 _+ 37.4%, ANOVA: p = O.Ol). AUC of 24h-PVF varied considerably between patients (510150 to 4253100 ml. rain, mean 2086575 _+ 836476 ml • min) and did neither correlate to Child-Pugh scores nor to HVPG. AUCs at day 1 and day 8 correlated highly within individuals (r = 0.959, p < 0.001). Conclusion: Circadian meal stimulated PVF is highly reproducibleover time within individuals but shows a large interindividual variability not dependenton the severity of liver diseaseor portal hypertension. Both, fasting PVF and the postprandial increase in PVF show a circadian variability with highest values in the morning. However, circadian PVF is predominantly determined by meal ingestion.
15 Colonic Distribution of Oral and Rectal Markers in IBD. Sheila Rodriguez-Stanley,Malcolm Robinson, Philip B. Miner Jr, Oklahoma Fdn for Digest Research, OklahomaCity, OK Background: Approximately25-30% of patients with left-sided IBD complain of constipation, suggesting that left-sided disease behaves like a functional obstruction. This may influence the efficacy of drugs that work by mucosal contact (eg: mesalamine,budesonide)since orally ingested medication may be retained in the colon, proximal to the disease. Enemasgiven to normal subjects are dispersed to the rectum, sigmoid and descendingcolon with little or no dispersion proximal to the splenic flexure. Aim: To demonstrate patterns of distribution of oral and rectal markers in patients with left-sided IBD during active disease and clinical remission in order to define inflammation-releted alterations in colonic physiology that may influence drug distribution. Methods: Diseaseactivity (active or remission) and location was determined in 9 patients by flexible sigmoidoscopy within 10 days of study. Following a 60ml placeboenemacontaining 10 mCi of ~mTc sulfur colloid, abdominal imageswere obtained
A-3
Results
GI GII
follow-up bleeding ascites death months n (%) n (%) n (%)
%*
21-+15 23±18
-11.5±14 1.6__.1.5 61_+48 -16-+12 4.4±2.4, 232±169,
7(14) 3 (6)
13(25) 7 (14)
3(6) 1 (2)
HVPG
Computed Tomography(CT) Enteroclysis in Comparisonto Ileo-Colonoscopyin Patients with Crohn's Disease (CD) Cesare Hassan, Paoia Cerro, Angelo Zullo, Carmelo Spina, Sergio Morini, Dept Gastroenterologyand Radiology, Nuovo Regina Margherita Hosp, Rome Italy
PRA PA ng/ml.h pg/ml
BACKGROUND:Enteroclysisand CT scanning are widely used in CD patientsto assessluminal and extraluminal features of the disease. Recently,these techniques have been successfully combined in CT enteroclysis with promising results in preliminary studies. However, CT enteroclysis has never been compared to endoscopy.Aim of this study was to compare the accuracy of CT enteroclysis to that of endoscopy in detecting bowel watt alterations in CD patients, and to assess whether postcontrast wall density at CT enteroclysis was related to clinical activity of CD. METHODS:Overall,24 patients (Mean age:47years;M/F:16/11;previous surgery:lO patients) referred for radiological assessment of CD were consecutivelyenrolled. CD diagnosis was performed by ileo-colonoscopywith histological assessmentin all patients, and clinical activity was measured by the Crohn's diseaseactivity index(CDAI). Five patients without CD were also included as controls. Spiral CT was performed after distension of the small bowel loops with a transparent enema of methylcellulose. Radiologists were unaware of endoscopicfindings. RESULTS:At endoscopy,CD was localizedto the ileum in 16 patients, to both the ileum and the colon in 5, and only to the colon in 3 cases. CT enteroclysis was successfully performed in all patients. CD involvement of the bowel wall, defined as wall thickness greater than 4 mm with a muitilayeredappearance,was detected in 15 out of the 16 cases of CD ileitis, in 4 out of the 5 cases of iteo-colifis, and in 2 of the 3 cases of colitis, with an overall sensitivity of 87%. In detail, two early post-surgical recurrencesat the neoterminal ileum, and one case of segmental colitis were missed at CT enteroclysis. No false-positive cases were observed in the control group. Postcontrast wall density value was significantly higher in the 16 patients with active disease (CDAI>150) than in the remaining 8 cases with inactive CD(115_+25 vs 32_+20;p<0.01). Furthemore, extraluminal features of CD were detected in 13 patients (3 fistulas,3 abscessesand 7 cases ot 1ibrotattyproliferation of the mesenteric tissue). CONCLUSIONS:CTenteroclysis proved to be highly sensitive and specific in assessing bowel wall alterations in CD patients with the possible exceptionof early post-surgical recurrences. The degree of postcontrast wall enhancement may provide an imaging model to assess diseaseactivity. Its ability to evaluateboth intra- and extra-luminal features makes its use tempting in selected cases of CD.
Valuesare givenas mean±SD.* p~O.Otvs baselinel ,, % of decreasevs baseline 11 Lock of Hemodynamic Responseto Long-ActingOctreotide (Sandostatin LAR) in Patients with Cirrhosis P S. Kamath, Mayo CUn, Rochester, MN; K ~nner, OHSU, Portland, OR; A Blei, Northwestern Memorial Hosp, Chicago, IL; J Bosch, Hosp Clin I Provincial, Barcelona Spain; W Carey, ClevelandClin, Cleveland,OH; N Grace, Faulkner Hosp, Jamaica Plain, MA; K Kowdley, Univ of Washington, Seattle, WA; K Sizer, Novartis PharmaceuticalsCorp, East Hanover, NJ; R Groszmann, VA Medical Ctr, West Haven,VA BACKGROUND:Octreotlde, the short-acting synthetic analogue of somatostatin, is useful in the control of variceal bleeding (NEJM 1995;33:55). It is not known whether a long-acting derivativeof octreotide (LAO-sandostatinLAR) may be effectivein preventingvaricealbleeding. AIM: To study the fasting and postprandial hemodynamic response as measured by hepatic vein pressure gradient (HVPG), portal blood flow (PBF), and superior mesenteric artery pulsatility index (SMA-PI) in responseto two different doses of LAO. METHODS:A multicenter randomized double-blind placebo-controlledstudy was carried out in 39 patients deemedto be at low risk for variceal bleeding, namely patients with Child-Pugh Class A or B cirrhosis with small varices and standardizedexclusion criteria. HVPG measurementswere carried out at baseline and day 84 following the first administration of the study drug. Patients were randomized to LAO 10 mg (n= 15), LAO 30 mg (n= 10), or saline (N =14). Blood samples were collected over 24 hours, and again at days 14, 28, 56 and 84. Additional injections of the study drug were given on day 28 and day 56, while Doppler uifrasound studiesto measure PBF and SMA-PI were carried out at baseline and on days 28, 56 and 84. The effect of treatment was measured by change from baseline in HVPG, PBF and SMA-PI. RESULTS: There was no significant decrease(p = 0.26 by ANOVA)in HVPGat day 84 as compared with baseline with LAD 30 mg (11.6_+2.3 mm Hg vs 14.1_+3.2) or LAO 10 mg (15.3_+4.8 mm Hg vs 15.1_+3.8); saline (13.3_+3.8 mm Hg vs 15.1_+4.3). P8F did not change significantly (-97 ml/min LAO 10 mg, +27 ml/min LAO 30 mg; +4,7 ml/min saline), p=0.8, while SMAPI was almost identical. Octreotlde levels reached a plateau between days 28 and 56. Four patients in the LAO 30 mg group dropped out of the study becauseof side affects. CONCLUSION: Octreotide levels were adequately maintained with administration of LAO. However, there was no significant decrease in either hepatic vein pressure gradient, portal blood flow or superior mesenteric artery pulsatile index with either dose of LAO. These results do not support the use of long-acting octreotide in the prevention of variceal bleeding in patients of portal hypertension.
14 Galactase-Dased IntravenousSonographic Contrast Agent (Levovist) In Crahn's Disease Antonio Oi S~hatlno, GastroenterologyUnit, Univ of Pavia, Pavia italy; llada Fufle, Dept o1 Radiology, Univ of Pavia, Pavia Italy; Lodovica Po:~i, RacheleCiccocioppo, Laura Ricevuti, Gastroenterology Unit, Univ of Pavia, Pavia Italy; FrancescoPaolo Tinozzi, Stefano Tinozzi, Dept of Surg, Univ of Pavia, Pavia Italy; Rodolfo Campani, Dept of Radiology, Univ of Pavia, Pavia Italy; Gino Roberto Cor~a, GastroenterologyUnit, Univ of Pavia, Pavia Italy Background & Aims: Abdominal ultrasound (US) has been proposed as a reliable tool to assess increasedbowel wall thickness (BWT), the most common sign in patientswith Crohn's disease (CD). Neverthless its sensitivity is not satisfactory. Therefore, we tried to assess whether the use in color power Doppler (CPD) of Levovist, a galactose-hasedintravenous sonographiccontrast agent able to enhancearterial Dopplersignal, increasesthe US accuracy. Patients & Methods: Twenty-two patients with ileal CD, .diagnosed by lower endoscopy and enteroclisis (mean age 36.1 yrs, range 18-63) and 20 control subjects (mean age 38.3 yrs, range 20-65) were examinetedwith conventional US (Aloka SSD-1700; convex probe 5 MHz). BWT up to 4 mm was consideredas normal. Afterwards, CPD of the intramural enteric vessels was performed (7.5 MHz, ATL HDI 3000) before and after intravenous injection of 5-10 ml of Levovist at the concentration of 300 mg/ml. Disease activity was assessed by Crohn's disease activity index (CDAI). None of the CD patients were previously operated due to complications of IBD. Results: Fifteen CD patients with ileal (n=9) or ileocolonic (n=6) lesions had a BWT>4. Nine of these 15 patients presented an active disease (CDAI>150). The remaining 7 CD patients, all with BWT<4, had ileal (n = 3), ileocolonic (n = 3) and gastroileo-colonic (n = 1) lesions, and 2 of them presentedan active disease.All the control subjects had a normal BWT. CPD showed an increased intramural flow in 16 CD patients in basal conditions, and in 20 CD patients after Levovist injection. Two of the 4 patients identified only by CPD after Levovist injection, all with quiescent CO, underwent to relapse within two months. In our hands, sensitivity and specificity were respectively 68% and 100% in US, 72% and 100% in basal CPD, 90% and 100% after Levovist injection. Conclusions: The use of Levovist in CPD showed an higher accuracy in CD diagnosis and follow-up compared to basal CPD and US. In addition, our data support that an increased intramural flow evaluated by CPD after Levovist injection representsa predictivefactor of impending relapse in patients with quiescent CD.
12 Circadian Meal-Stimulated Portal Blood Flow In Patients With Liver Cirrhosis. Peter J E Schiedermaier, Lydia Koch, Tilman Sauerhruch, Dept of Gen Intemal Medicine, Univ of Bonn, Bonn Germany Introduction: The chronorisk of variceal hemorrhage was explained by a circadian variability of portal vein flow (PVF) which, however,has beenestablishedsolely under fasting conditions. Meal stimulated circadian portal blood flow, reflecting daily live, has not been investigatedin cirrhotic patients to date. Methods: 25 patients with liver cirrhosis were examined during a 24h period twice at day 1 and day 8. PVF (ml/min) was measured by Doppler ultrasound at 8:30, 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 13:00, 13:15, 13:30, 13:45, 14:00, 14:30, 15:00, 17:00, 19:00, 19:15, 19:30, 19:45, 20:00, 20:30, 21:00, 23:00, 1:00, 3:00, 8:30. 500 ml Ensure PlusTM were given at 9:00, 13:00 and 19:00. Measurementsat 9:15-11:00, 13:1515:00 and 19:15-21:00 were classified as postprandial. Areas under the curve of circadian PVF (AUC of 24h-PVF) were calculated and correlated with fasting HVPGs [mmHg] and the Child-Pugh scores. Results: Fasting PVF showed a significant circadian variability with a maximum at 13:00 (+ 3.7 +_ 25.8%; mean _+ SD) and a minimum at 3:00 ( -9.8 _+ 25.9%, MANOVA: p < 0.001). Postprandialincrease in PVF was higher in the morning than at noon or in the evening (66.6 _+ 66.7% vs. 39.3 _+ 27.8% vs, 49.7 _+ 37.4%, ANOVA: p = O.Ol). AUC of 24h-PVF varied considerably between patients (510150 to 4253100 ml. rain, mean 2086575 _+ 836476 ml • min) and did neither correlate to Child-Pugh scores nor to HVPG. AUCs at day 1 and day 8 correlated highly within individuals (r = 0.959, p < 0.001). Conclusion: Circadian meal stimulated PVF is highly reproducibleover time within individuals but shows a large interindividual variability not dependenton the severity of liver diseaseor portal hypertension. Both, fasting PVF and the postprandial increase in PVF show a circadian variability with highest values in the morning. However, circadian PVF is predominantly determined by meal ingestion.
15 Colonic Distribution of Oral and Rectal Markers in IBD. Sheila Rodriguez-Stanley,Malcolm Robinson, Philip B. Miner Jr, Oklahoma Fdn for Digest Research, OklahomaCity, OK Background: Approximately25-30% of patients with left-sided IBD complain of constipation, suggesting that left-sided disease behaves like a functional obstruction. This may influence the efficacy of drugs that work by mucosal contact (eg: mesalamine,budesonide)since orally ingested medication may be retained in the colon, proximal to the disease. Enemasgiven to normal subjects are dispersed to the rectum, sigmoid and descendingcolon with little or no dispersion proximal to the splenic flexure. Aim: To demonstrate patterns of distribution of oral and rectal markers in patients with left-sided IBD during active disease and clinical remission in order to define inflammation-releted alterations in colonic physiology that may influence drug distribution. Methods: Diseaseactivity (active or remission) and location was determined in 9 patients by flexible sigmoidoscopy within 10 days of study. Following a 60ml placeboenemacontaining 10 mCi of ~mTc sulfur colloid, abdominal imageswere obtained
A-3