1
A706 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4 • EFFECT OF BISHYDROXY-PHENYL-PYRIDYL-METHAN (BI-IPM) ON RAT COLON MOTILITY IN VITRO. W.A. Voderholzer, V. Ncumann, N.E. Schindlbeck, K. Loeschke, S.A. M011er-Lissner*. Med. Klinik, Klinikum Innenstadt, University of Munich, Stadt. Krankenhaus Berlin-WeiBensee, Germany. Background: There is evidence that bisacodyl affects colonic motility inde- pendently of its antiabsorptive/seeretagoguc effects. Therefore, the influence of its active metabolite (BI-IPM) on rat colon in vitro was investigated. Methods: Isolated smooth muscle strips of ascending and descending rat colo~t were mounted in an organ bath containing modified Krebs buffer solu- tion (37" C, basal resting tension 20 raN). Contraction force was measured by force transducers and monitored by a computerized system. Muscle strips were stimulated using carbachol (CCH, 10-5 M) or substance P (SP, 10-5 M) in the presence of atropine (10"~M) and guanethidine (10"6M). Two mi- nutes after application of CCH or SP, BHPM (7,5 pg/ml and 150 pg/mi) was added Using standardized sottware, areas under the curve (AUC) after CCH/SP-stimulation with and without BHPM were evaluated. The ve- hicle of BI--IPM (DMSO)served as control. Data represent areas under the curve three minutes after adding BHPM in relation to control values. Results: a) CCH-stimulation: Application of BHPM 7.5 pg/ml to cell- stimulated strips did neither affect longitudinal nor circular muscle. However, BI-tPM 150 pg/ml reduced AUC of longitudinal muscle by 36%_+9.8 (p=0.03, Wilcoxon-test) in ascending colon and by 20%_+4.0 (p=0.001) in descending colon. BHPM 150pg/ml increased AUC of circular descending colon by 37%_+9.7 (p=0.01). Tetrodotoxin (=TTX,10 "6 M) did not influence BHPM-effect on longitudinal muscle (reduction by 41%_+7.1. p=0.03 and 23%_+4.9, p=0.01 for ascending and descending colon) but abolished BHPM-stimulation of circular muscle, b) SP-stimulation: Application of BI-IPM 7,5pg/ml did not affect SP-stimulation. BHPM 150 pg/ml reduced AUC of longitudinal muscles but did not affect circular muscle. Conclusions: By inhibiting longitudinal muscle and stimulating circular muscle, bisacodyl may reinforce the peristaltic reflex in descending rat colon. The effect on longitudinal muscle may not be mediated by cholinergic mechanisms. Since the effect on circular muscle is abolished by TTX or atropine/guanethidine the effect of bisacodyl may be neuronally mediated by a cholinergic or adrenergic mechanism. Friedrich-Baur-Stiflung grant #6/94. • NON-INVASIVE ASSESSMENT OF COLONIC MOTILITY IN PATIENTS WITH SLOW TRANSIT CONSTIPATION (STC) BY VIDEO TRANSABDOMINAL HYDROCOLONIC ULTRA- SONOGRAPHY, M.R. yon d¢r Ohe, H:P. B6ck, H. Goebell, P. Layer. Div. Gastroenterology, Un!versity of Essen, Germany. For clinical purpose assessment of human colonic motor function by intralu- minal techniques (e.g. manometry) may not always be the optimal approach since they require bowel cleansing and invasive placement of recording de~'!- ces and have yielded inconsistent results. Aim; to non-invc~ively evaluate the unprepared colon's motor response to eating in health and patients with STC. Methods: 6 healthy volunteers (age range: 26-33 yr; 4M, 2F) and 4 patients with STC (22-46 yr; 4F) were studied after an overnight fast. Patients met clinical criteria of severe constipation and showed a significant delay in col0- nic transit by scintigraphy. After instillation of IL water into the unprepared colon a real-time uhrasonography scanning transducer (3:5MHz, Toshiba) was placed constantly in the left abdominal flank with the kidney as orienta- tion landmark: Sonomgrphologic structures of the descending colonic wall Were identified and continuously recorded on video-tape in the fasting state (J 5min) and postprandially (30rain; 1,000kcaI meal). The colonic diameter (D) was defined as the rectangular distance between mucosal layers on: op- posite sides of the colonic lumen and was measured lcrn distal to the caudad renal pole at 3sec intervals by planimetry (Hewlett Packard). For analyses of fasting and fed states, the following parameters were defined: mean colonic. diameter (MD) = ~D/# of observations [mm]; motility index (MI) = Y.IMD-DI [mrn/min]; movement = duration of unidirectional consecutive movement of intraluminal contents > 6sec [% of time]; quality of movement = turbulence vs. laminar flow [% of time]. Results: Orthotopic visualization of colonic wall structures was possible in >95% of time points in all subjects. In contrast to controls, STC had greater fasting MD and lacked meal induced de- crease in MD; conversely, they had only a minimal postprandial increase in MI~ moreover postprandial induction of luminal movement and turbulence Was abolished in STC (mean_+SEM; * p < 0.01 vs. fasting, ~" p < 0.01 vs. hedlth). Grouo MD [mm] MI [ram/mini movement 1%] turbulence [%1 Fast Fed Fast Fed Fast Fed Fast Fed Health 30-2_2 27+_1" 21+2 50+5* 15-+2 67+2* 0 49+6* STC 37_+6"~ 34_+2"I" 21_+3 27+3"t (It 10-+8t 0 0+. Conclusion: Patients with slow transit constipation have a significantly ira-- paired colonic motor response to eating compared with controls. Our data suggest that video transabdominal hydrocolonic uhrasonography could be a reliable non-invasive techniqne to detect and quantify motor disturbances of the human colon. NON-INVASIVE EVALUATION OF HUMAN COLONIC MOTOR FUNCTION BY VIDE() TRANSABDOMINAL HYDROCOLONIC ULTRASONOGRAPHY. M.R. yon ~lor Qh¢, H.P. B~Sck, H. Goebell, P. Layer. Div. Gastroenterology, University of Essen, Germany. Conventional assessment of human colonic motor activity in vivo necessitates bowel cleansing and invasive placement of intraluminal recording deviceS: Aim: to non-invasively identity the colon's typical motor response to eating ("gastro-colonic response") which to date is the most consistently~documen- ted motility pattern in the human colon. Methods: Six heahhy fasting volun- teers (age range: 26-33 yr; 4M, 2F) were studied. With subjects in a quiet supine position 1L of water was instilled into the unprepa~'ed colon. A real- time ultrasonography scanning device (3.5MHz, Toshiba) was placed con- stanfly in the left abdominal flank with the kidney as anatomical landmark for orientation. Sonomorphological structures of the descending colonic wall and lumen were easily identified (NEJM 1992;327:65-9). Changes of the de- scending colon were continuously monitored and recorded on video-tape for 15rain prior to and 30min after a l,(X)0kcal meal. Using an echocardiography planimetry program (Hewlett Packard) the colonic diameter (D) was defined as the rectangular distance between mucosal layers on opposite sides of the colonic lumen and was measured lcm distal to the caudad renal pole at 3sec intervals. For analyses of fasting and fed states, the following parameters were defined: mean colonic diameter (MD) = 3~D/# of observations [mm]; motility index (MI) = Y.IMD-DI [mrn/min]; movement = duration of unidirec- tional consecutive movement of intraluminal contents > 6sec [% of total ob- servation]; quality of movement (= turbulence vs. laminar flow [% of total observation]. Results: Orthotopic sonomorphologic visualization of colonic wall structures was possible in >95% of time points in all subjects. There was no significant change in any parameter during fasting. The meal caused redaction of MD, increase of MI and movement and changed the quality of intraluminal movement. There was a positive correlation between MI and mo- vement parameters during the fasting and fed state (r = 0.9, p = 0.0004). mean diameter motility index movement turbulence [mm] [mm/min] [%11 [%] Fasting 30.0-.+1,5 20.5-+2. l 14.7+2. l 0 Postprandial 26.7_+0.9* 50.2_+5.0* 67.3_+2.l* 48.7+_5.9* Data: mean_+SEM; * p <0.01 vs. fasting Conclusion: These preliminary data suggest that changes of colonic motor activity in response to a meal can reliably be detected and quantified by transabdomina! video hydrocolonie uhrasonography. This technique may of- fer a useful non-invasive tool to study colonic motor function: ILEOCECAL POOCH RECONSTRUCTION: CLINICAL OUTCOME AND ANORECTAL FUNCTION. M.von FI0e. L.Degen*, C.Beglinger*, A.Hel- wig# J.M.R0thenb0hler, F.Harder. DeptS of Surgery, *Gastroenterology, and ~Radiology, university Hospital, CH-4031 Basel, Switzerland We have I'ecently published a new technique for pouch anal reconstruction (ileocecal pouch) after total mesorectal resection(Dis Colon Rectum: Nov 1994). This approach provides a segment with intact extrinsic nerve and blood supply. The aim of this study was to evaluate the clinical outcOmeand functional aspects after this procedure. Patients and Methods: 12 consecutive patients (aged 47 to 83 years) with rectal carcinoma between 5 and 10 cm above the anal verge were operated on by total mesorectal excision: The rectum was reconstructed by an ileocecal pouch. Ooerative techniaue: A 20 cm long ileocecal segment was isolated and transected, then rotated 1807 countemlockwise, placed in the presacral space, and anastomosed with the anal canal. Postonerative evaluation: After 6 months, all patients underwent anal manometry (squeezing and resting pressure), proctometrography (threshold volume, tolerable volume, compliance), defecography, and colonic transit time measurements. A defecation quality score was defined and based on continence, frequency, imperative urge, and evacuation. A score of 8 was considered excellent, 10 was good, and 12 was unsatisfactory (modified from Paty et al: Am J Surg 1994). Pouch capacity and compliance were compared with 12 age- and sex-matched normal volunteers. B ~ are expressed as median (range). Based on the defecation quality score, all patients revealed• excellent (n=8) or good (n=4) defecation quality. The pressure of the resting anus was decreased (p<0.05). The squeezing pressure was maintained and the rectoanal inhibitory reflex remained positive in 9 out of 12 cases, In the defecography, the anorectal angle at strain was decreased (p<0.05), however, no pedneal descent was recorded. Finally, mean colonic transit t!me was 51 hours (19-70). *=p<0.05. Patients Controls Manometrv Resting pressure (mmHg) 37 (22-50)* 47 (31-64) Squeezing pressure (mmHg) 120 (82-158) 127 (89-164) Proctometroaraohv Tolerable volume iml) 289 (234-344) 311 (240,383) Threshold volume (ml) 135 (56-213) 147 (83-211) (ml/cm H20) 4.56 (2.6-6.4) 5.61 (3.2-8.02) 'Con~Jusions: The ile pc r s ~ new a misir g techniq based on an intact ileocecal segment. The present pilot data confirm that the pouch reconstruction yields an excellent clinical outcome with good defecation quality and a physiological functional result.

Non-invasive evaluation of human colonic motor function by video transabdominal hydrocolonic ultrasonography

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A 7 0 6 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 1 0 8 , No. 4

• EFFECT OF BISHYDROXY-PHENYL-PYRIDYL-METHAN (BI-IPM) ON RAT COLON MOTILITY IN VITRO. W.A. Voderholzer, V. Ncumann, N.E. Schindlbeck, K. Loeschke, S.A. M011er-Lissner*. Med. Klinik, Klinikum Innenstadt, University of Munich, Stadt. Krankenhaus Berlin-WeiBensee, Germany.

Background: There is evidence that bisacodyl affects colonic motility inde- pendently of its antiabsorptive/seeretagoguc effects. Therefore, the influence of its active metabolite (BI-IPM) on rat colon in vitro was investigated. Methods: Isolated smooth muscle strips of ascending and descending rat colo~t were mounted in an organ bath containing modified Krebs buffer solu- tion (37" C, basal resting tension 20 raN). Contraction force was measured by force transducers and monitored by a computerized system. Muscle strips were stimulated using carbachol (CCH, 10 -5 M) or substance P (SP, 10 -5 M) in the presence of atropine (10"~ M) and guanethidine (10 "6 M). Two mi- nutes after application of CCH or SP, BHPM (7,5 pg/ml and 150 pg/mi) was added Using standardized sottware, areas under the curve (AUC) after CCH/SP-stimulation with and without BHPM were evaluated. The ve- hicle of BI--IPM (DMSO)served as control. Data represent areas under the curve three minutes after adding BHPM in relation to control values. Results: a) CCH-stimulation: Application of BHPM 7.5 pg/ml to c e l l - stimulated strips did neither affect longitudinal nor circular muscle. However, BI-tPM 150 pg/ml reduced AUC of longitudinal muscle by 36%_+9.8 (p=0.03, Wilcoxon-test) in ascending colon and by 20%_+4.0 (p=0.001) in descending colon. BHPM 150pg/ml increased AUC of circular descending colon by 37%_+9.7 (p=0.01). Tetrodotoxin (=TTX,10 "6 M) did not influence BHPM-effect on longitudinal muscle (reduction by 41%_+7.1. p=0.03 and 23%_+4.9, p=0.01 for ascending and descending colon) but abolished BHPM-stimulation of circular muscle, b) SP-stimulation: Application of BI-IPM 7,5pg/ml did not affect SP-stimulation. BHPM 150 pg/ml reduced AUC of longitudinal muscles but did not affect circular muscle. Conclusions: By inhibiting longitudinal muscle and stimulating circular muscle, bisacodyl may reinforce the peristaltic reflex in descending rat colon. The effect on longitudinal muscle may not be mediated by cholinergic mechanisms. Since the effect on circular muscle is abolished by TTX or atropine/guanethidine the effect of bisacodyl may be neuronally mediated by a cholinergic or adrenergic mechanism. Friedrich-Baur-Stiflung grant #6/94.

• NON-INVASIVE ASSESSMENT OF COLONIC MOTILITY IN PATIENTS W I T H SLOW TRANSIT CONSTIPATION (STC) BY VIDEO TRANSABDOMINAL HYDROCOLONIC ULTRA- SONOGRAPHY, M.R. yon d¢r Ohe, H:P. B6ck, H. Goebell, P. Layer. Div. Gastroenterology, Un!versity of Essen, Germany. For clinical purpose assessment of human colonic motor function by intralu- minal techniques (e.g. manometry) may not always be the optimal approach since they require bowel cleansing and invasive placement of recording de~'!- ces and have yielded inconsistent results. Aim; to non-invc~ively evaluate the unprepared colon's motor response to eating in health and patients with STC. Methods: 6 healthy volunteers (age range: 26-33 yr; 4M, 2F) and 4 patients with STC (22-46 yr; 4F) were studied after an overnight fast. Patients met clinical criteria of severe constipation and showed a significant delay in col 0- nic transit by scintigraphy. After instillation of IL water into the unprepared colon a real-time uhrasonography scanning transducer (3:5MHz, Toshiba) was placed constantly in the left abdominal flank with the kidney as orienta- tion landmark: Sonomgrphologic structures of the descending colonic wall Were identified and continuously recorded on video-tape in the fasting state (J 5min) and postprandially (30rain; 1,000kcaI meal). The colonic diameter (D) was defined as the rectangular distance between mucosal layers on: op- posite sides of the colonic lumen and was measured lcrn distal to the caudad renal pole at 3sec intervals by planimetry (Hewlett Packard). For analyses of fasting and fed states, the following parameters were defined: mean colonic. diameter (MD) = ~D/# of observations [mm]; motility index (MI) = Y.IMD-DI [mrn/min]; movement = duration of unidirectional consecutive movement of intraluminal contents > 6sec [% of time]; quality of movement = turbulence vs. laminar flow [% of time]. Results: Orthotopic visualization of colonic wall structures was possible in >95% of time points in all subjects. In contrast to controls, STC had greater fasting MD and lacked meal induced de- crease in MD; conversely, they had only a minimal postprandial increase in MI~ moreover postprandial induction of luminal movement and turbulence Was abolished in STC (mean_+SEM; * p < 0.01 vs. fasting, ~" p < 0.01 vs. hedlth). Grouo MD [mm] MI [ram/mini movement 1%] turbulence [%1

Fast F e d Fast Fed Fast Fed Fast Fed Health 30-2_2 27+_1" 21+2 50+5* 15-+2 67+2* 0 49+6* STC 37_+6"~ 34_+2"I" 21_+3 27+3"t (It 10-+8t 0 0+. Conclusion: Patients with slow transit constipation have a significantly ira-- paired colonic motor response to eating compared with controls. Our data suggest that video transabdominal hydrocolonic uhrasonography could be a reliable non-invasive techniqne to detect and quantify motor disturbances of the human colon.

N O N - I N V A S I V E E V A L U A T I O N OF HUMAN C O L O N I C M O T O R F U N C T I O N BY VIDE() T R A N S A B D O M I N A L H Y D R O C O L O N I C U L T R A S O N O G R A P H Y . M.R. yon ~lor Qh¢, H.P. B~Sck, H. Goebell, P. Layer. Div. Gastroenterology, University of Essen, Germany. Conventional assessment of human colonic motor activity in vivo necessitates bowel cleansing and invasive placement of intraluminal recording deviceS: Aim: to non-invasively identity the colon's typical motor response to eating ("gastro-colonic response") which to date is the most consistently~documen- ted motility pattern in the human colon. Methods: Six heahhy fasting volun- teers (age range: 26-33 yr; 4M, 2F) were studied. With subjects in a quiet supine position 1L of water was instilled into the unprepa~'ed colon. A real- time ultrasonography scanning device (3.5MHz, Toshiba) was placed con- stanfly in the left abdominal flank with the kidney as anatomical landmark for orientation. Sonomorphological structures of the descending colonic wall and lumen were easily identified (NEJM 1992;327:65-9). Changes of the de- scending colon were continuously monitored and recorded on video-tape for 15rain prior to and 30min after a l,(X)0kcal meal. Using an echocardiography planimetry program (Hewlett Packard) the colonic diameter (D) was defined as the rectangular distance between mucosal layers on opposite sides of the colonic lumen and was measured lcm distal to the caudad renal pole at 3sec intervals. For analyses of fasting and fed states, the following parameters were defined: mean colonic diameter (MD) = 3~D/# of observations [mm]; motility index (MI) = Y.IMD-DI [mrn/min]; movement = duration of unidirec- tional consecutive movement of intraluminal contents > 6sec [% of total ob- servation]; quality of movement (= turbulence vs. laminar flow [% of total observation]. Results: Orthotopic sonomorphologic visualization of colonic wall structures was possible in >95% of time points in all subjects. There was no significant change in any parameter during fasting. The meal caused redaction of MD, increase of MI and movement and changed the quality of intraluminal movement. There was a positive correlation between MI and mo- vement parameters during the fasting and fed state (r = 0.9, p = 0.0004).

mean diameter motility index movement turbulence [mm] [mm/min] [%11 [%]

Fasting 30.0-.+1,5 20.5-+2. l 14.7+2. l 0 Postprandial 26.7_+0.9* 50.2_+5.0* 67.3_+2.l* 48.7+_5.9* Data: mean_+SEM; * p <0.01 vs. fasting Conclusion: These preliminary data suggest that changes of colonic motor activity in response to a meal can reliably be detected and quantified by transabdomina! video hydrocolonie uhrasonography. This technique may of- fer a useful non-invasive tool to study colonic motor function:

• ILEOCECAL POOCH RECONSTRUCTION: CLINICAL OUTCOME AND ANORECTAL FUNCTION. M.von FI0e. L.Degen*, C.Beglinger*, A.Hel- wig# J.M.R0thenb0hler, F.Harder. DeptS of Surgery, *Gastroenterology, and ~Radiology, university Hospital, CH-4031 Basel, Switzerland

We have I'ecently published a new technique for pouch anal reconstruction (ileocecal pouch) after total mesorectal resection(Dis Colon Rectum: Nov 1994). This approach provides a segment with intact extrinsic nerve and blood supply. The aim of this study was to evaluate the clinical outcOme and functional aspects after this procedure. Patients and Methods: 12 consecutive patients (aged 47 to 83 years) with rectal carcinoma between 5 and 10 cm above the anal verge were operated on by total mesorectal excision: The rectum was reconstructed by an ileocecal pouch. Ooerative techniaue: A 20 cm long ileocecal segment was isolated and transected, then rotated 1807 countemlockwise, placed in the presacral space, and anastomosed with the anal canal. Postonerative evaluation: After 6 months, all patients underwent anal manometry (squeezing and resting pressure), proctometrography (threshold volume, tolerable volume, compliance), defecography, and colonic transit time measurements. A defecation quality score was defined and based on continence, frequency, imperative urge, and evacuation. A score of 8 was considered excellent, 10 was good, and 12 was unsatisfactory (modified from Paty et al: Am J Surg 1994). Pouch capacity and compliance were compared with 12 age- and sex-matched normal volunteers. B ~ are expressed as median (range). Based on the defecation quality score, all patients revealed• excellent (n=8) or good (n=4) defecation quality. The pressure of the resting anus was decreased (p<0.05). The squeezing pressure was maintained and the rectoanal inhibitory reflex remained positive in 9 out of 12 cases, In the defecography, the anorectal angle at strain was decreased (p<0.05), however, no pedneal descent was recorded. Finally, mean colonic transit t!me was 51 hours (19-70). *=p<0.05.

Patients Controls Manometrv Resting pressure (mmHg) 37 (22-50)* 47 (31-64) Squeezing pressure (mmHg) 120 (82-158) 127 (89-164) Proctometroaraohv Tolerable volume iml) 289 (234-344) 311 (240,383) Threshold volume (ml) 135 (56-213) 147 (83-211)

(ml/cm H20) 4.56 (2.6-6.4) 5.61 (3.2-8.02) 'Con~Jusions: The ile pc r s ~ new a misir g techniq based on an intact ileocecal segment. The present pilot data confirm that the pouch reconstruction yields an excellent clinical outcome with good defecation quality and a physiological functional result.