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Our experience in restorative proctocolectomy and s-pouch procedure for ulcerative colitis
Abstracts
117
OUR EXPERIENCE IN RESTORATIVE PROCTOCOLECTOMY POUCH PROCEDURE FOR ULCERATIVE COLITIS.
1..lY AND S-
Montecamouo G, Kurihara H, Danelli PG, Sampietro GM, Vignati GA, Poliziani D and Taxhieri AM. Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacco” Universik degli Studi di Milan0 - Italia. Background and aims. Since the initial description in 1978, several modifications of restorative proctocolectomy with ileal-pouch-anal-anastomosis (IPAA), for the surgical management of ulcerative colitis (UC), have occurred. Aim of this study is to evaluate safety and efficacy of our IPAA procedure. Patients and Methods. From January 1993 to lune 1999 we treated 44 patients for UC; 33 underwent IPAA. We always performed an S-pouch with mucosectomy and hand-sewn IAA introducing several modifications in the originally described S-pouch. The central loop of the pouch is sutured on ik antimesenteric site with the mesenteric sides of the lateral loops and the length of the limbs is no longer than 9 cm. This shape increases pouch capacitance and allows a better set in lower pelvis. In order to avoid outlet obstruction due to chinking of the pouch, we limit the length of the efferent limb to two cm with preservation of the mesorectum. Mucosectomy stark just few millimetres below the dentate line and is extended for two cm along the anal canal; the IPAA is fashioned by a hand-sewn suture. Results and conclusions. We had no perioperatlve mortality with a low complication rate (12%). The patients referred good continence and an average of 4 bowel movements a day. Various pouch configurations with either two (I), three (5) or four (W) loops have been described; criteria used in choosing a pouch design include the ease of construction, the expected pouch capacity and compliance, ease of evacuation and the Occurrence of complication aRer construction. A controversial technical aspect regards mucosectomy with a hand-sewn ileo-anal anastomosis (IAA) versus stapled anastomosis.The technique we propose appears to be feasible and offers good functional results.
SHORT-TERM EFFICACY OF CHIMERIC MONOCLONAL ANTIBODY cAZ TO TUMOR NECROSIS FACTOR a FOR REFRACTORY, FIStlJLI7XNG CROHN’S DISEASE. &i&@,
Ardizzone S, Colombo E, Imbesi V and Bianchi Porro G.
Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacco” Univenik degli Studi di Milan0 - Italia. Background and Aim: Tumor necmsis factor a (TNFa) is thought to play a crucial role in the pathogenesis of Crohn’s disease (CD). Open label and controlled clinical trials have reported that Infliximab is effective in reducing signs and symptoms of active CD. Aim of this study is to report our experience in the treatment of patients suffering from refractory, fistulizing CD. Methods: Ten patients (M/F 5/5, mean age 39, range 27-69) who had inadequately responded to conventional therapy (steroids, Immunosuppressive agents, antibiotics), received Infliximab 5 mg/Kg, administered intravenously at weeks 0, 2 and 6. Four patients presented with one or more perianal flstulas, 2 with perianal and rectoveginal fistulas, 1 wRh bowel to bladder fistula, 1 with enterocutaneous flstulas, and 2 with chronically active disease. Cmhn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) were calculated in all patients and in those with perianal disease, respectively, at baseline and aRer 2 and 6 weeks of therapy. Resultr: There was a statistically significant decrease in the mean CDAI between baseline (232) and week 2 (151, p = 0.002), and 6 (133, p = 0.006). For patients with perianal disease, PDAI significantly changed from baseline (13) only after 6 weeks of treatment (5, p = 0.04). Only in one case a closure of draining fistulas was observed. Four patients had adverse events: 3 had cardiopulmonary reactions (hypotension, hypertension and chest pain), and 1 had nausea. Conclusions: These data suggest that Infliximab is effective in reducing the clinical and perianal activity indices In CD patients. However, the low rate of closure of draining perianal and enterocutaneous fistulas, stress the necessity to try further short-term regimen doses, and long-term treatment trials should be envisaged for this condition.
118*
NORMALIZATION OF BOWEL WALL AFTER St-RIClWREPLASTY MINIRESECTION FOR COMPLICATED CROHN’S DISEASE.
AND
Samoietro GM, Cristaldi M, Mawni G, Bollani S, Danelli PG and Taschleri AM. Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacw” Universik degli Studi di Milan0 - Italia. Background and aims. In the past, a number of risk factors for postoperative recurrences of CD have been proposed, but a few data are available concerning the behaviour of the intestinal wall aRer conservative surgery and ik ability to predict the recurrence of CD. The aim of this study was to assess the clinical usefulness as a prognostic factor of the bowel wall behaviour during postoperative follow-up after strlctureplastles and miniresections for Cmhn’s disease (CD). Patients and methods. Eighty-five consecutive patients undergone strictureplasty and mini-resectiins for CD. Clinical and ultrasoncgraphic bowel wall evaluations were made before and six months after surgery, as well as whenever symptoms compatible wlth recurrence occurred during the follow-up. The US evaluations included the preoperative maximum bowel wall thickness (BWT), the length of BWT and bowel wall echopattem (homogeneous, stratified was classified as px.t-surgical BWT behaviour and mixed); normalized/improved or unchanged/worsened. Results. Three years clinical and surgical recurrences occurred in 35.3% and 18.8% of cases mspeck& A slgnmcant correlation was found between a longer preoperative BWT and surgical recurrence (p=O.O4); a previous surgery and post-surgical unchanged/worsened BWT behaviour (p=O.Ol). Patients with unchanged/worsened BWT after surgery are at higher risk of clinical (HR 9.98; 95% CI 3.48-28.56) and surgical (HR 16.15; 95% CI 2.87-90.75) recurrence at the Cox’s propomona hazard model.
A34
A NOVEL ROLE FOR TEE NEUROPEPTJDE NEUROTENSIN IN CHRONIC COLITIS. Cataldi F’. Galeazzi p, Pothoulakis C’, Wang C’, Zacks J”, Carraway R4. Q&tdiuolo I ’ ‘Beth Israel DeaconessMedical Center, Harvard Medical School, Boston USA, ‘University of P&a, Padua Italy; Boston University School of Medicine, Boston USA, !University of Massachussets,Worchester USA. The neuropeptide neurotensin (NT) is a potent neuroimmunomodulator that in the gastrointestinal tract promotes acute inflammation,
In addition we recently reported that the expression of
the high &iiity NT receptor (NlXI) is up-regulated in colonic epithelial and microvaacolar endothelial cells in IBD patients. Since NT also stimulates mucosal trophism and microvascular endothelial cell proliferation we decided to investigated the role of NT during chronic colitis. We observed that colonic NT mRNA (by in situ hybridization) and peptide levels (by EIA) significantly increased during experimental TNBS (3.2-fold increaseat day 7, FO.01) or DSS (S.&fold increaseat day S,~0.01) colitis. Furthermore, within S to 7 days after the induction of colitis, Nl’Rl immunoreactivity in the colonic mucosa drastically increased.To assessthe functional significance ofNT and NTRl up-regulation during chronic colitis, we administered SR-48642, a specific non-peptide NTRl
antagonist, to
mice. Clinical signs, macroscopicand histologic damage associated with TNBS (12 d) and DSS (5 d) colitis were significantly more severe in mice receiving SR-48642 then in vehicle treated mice Furthermore, continues administration of NT by micro-in&ion pumps (for S days) significantly ameliorated clinical signs, macroscopic and histologic damage associatedwith DSS (S d) colitis. In summary NT and Nl’Rl are up-regulated during TNBS and DSS colitis and antiyonizing NT effects during chronic colitis worsen tissue damage.We propose that during the chronic phasesof inflammatory disorders NT may participate in the processof mucossl restitution following tissue injury.
117
OUR EXPERIENCE IN RESTORATIVE PROCTOCOLECTOMY POUCH PROCEDURE FOR ULCERATIVE COLITIS.
1..lY AND S-
Montecamouo G, Kurihara H, Danelli PG, Sampietro GM, Vignati GA, Poliziani D and Taxhieri AM. Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacco” Universik degli Studi di Milan0 - Italia. Background and aims. Since the initial description in 1978, several modifications of restorative proctocolectomy with ileal-pouch-anal-anastomosis (IPAA), for the surgical management of ulcerative colitis (UC), have occurred. Aim of this study is to evaluate safety and efficacy of our IPAA procedure. Patients and Methods. From January 1993 to lune 1999 we treated 44 patients for UC; 33 underwent IPAA. We always performed an S-pouch with mucosectomy and hand-sewn IAA introducing several modifications in the originally described S-pouch. The central loop of the pouch is sutured on ik antimesenteric site with the mesenteric sides of the lateral loops and the length of the limbs is no longer than 9 cm. This shape increases pouch capacitance and allows a better set in lower pelvis. In order to avoid outlet obstruction due to chinking of the pouch, we limit the length of the efferent limb to two cm with preservation of the mesorectum. Mucosectomy stark just few millimetres below the dentate line and is extended for two cm along the anal canal; the IPAA is fashioned by a hand-sewn suture. Results and conclusions. We had no perioperatlve mortality with a low complication rate (12%). The patients referred good continence and an average of 4 bowel movements a day. Various pouch configurations with either two (I), three (5) or four (W) loops have been described; criteria used in choosing a pouch design include the ease of construction, the expected pouch capacity and compliance, ease of evacuation and the Occurrence of complication aRer construction. A controversial technical aspect regards mucosectomy with a hand-sewn ileo-anal anastomosis (IAA) versus stapled anastomosis.The technique we propose appears to be feasible and offers good functional results.
SHORT-TERM EFFICACY OF CHIMERIC MONOCLONAL ANTIBODY cAZ TO TUMOR NECROSIS FACTOR a FOR REFRACTORY, FIStlJLI7XNG CROHN’S DISEASE. &i&@,
Ardizzone S, Colombo E, Imbesi V and Bianchi Porro G.
Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacco” Univenik degli Studi di Milan0 - Italia. Background and Aim: Tumor necmsis factor a (TNFa) is thought to play a crucial role in the pathogenesis of Crohn’s disease (CD). Open label and controlled clinical trials have reported that Infliximab is effective in reducing signs and symptoms of active CD. Aim of this study is to report our experience in the treatment of patients suffering from refractory, fistulizing CD. Methods: Ten patients (M/F 5/5, mean age 39, range 27-69) who had inadequately responded to conventional therapy (steroids, Immunosuppressive agents, antibiotics), received Infliximab 5 mg/Kg, administered intravenously at weeks 0, 2 and 6. Four patients presented with one or more perianal flstulas, 2 with perianal and rectoveginal fistulas, 1 wRh bowel to bladder fistula, 1 with enterocutaneous flstulas, and 2 with chronically active disease. Cmhn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) were calculated in all patients and in those with perianal disease, respectively, at baseline and aRer 2 and 6 weeks of therapy. Resultr: There was a statistically significant decrease in the mean CDAI between baseline (232) and week 2 (151, p = 0.002), and 6 (133, p = 0.006). For patients with perianal disease, PDAI significantly changed from baseline (13) only after 6 weeks of treatment (5, p = 0.04). Only in one case a closure of draining fistulas was observed. Four patients had adverse events: 3 had cardiopulmonary reactions (hypotension, hypertension and chest pain), and 1 had nausea. Conclusions: These data suggest that Infliximab is effective in reducing the clinical and perianal activity indices In CD patients. However, the low rate of closure of draining perianal and enterocutaneous fistulas, stress the necessity to try further short-term regimen doses, and long-term treatment trials should be envisaged for this condition.
118*
NORMALIZATION OF BOWEL WALL AFTER St-RIClWREPLASTY MINIRESECTION FOR COMPLICATED CROHN’S DISEASE.
AND
Samoietro GM, Cristaldi M, Mawni G, Bollani S, Danelli PG and Taschleri AM. Division of General Surgery and Gastrointestinal Unit - Ospedale “LSacw” Universik degli Studi di Milan0 - Italia. Background and aims. In the past, a number of risk factors for postoperative recurrences of CD have been proposed, but a few data are available concerning the behaviour of the intestinal wall aRer conservative surgery and ik ability to predict the recurrence of CD. The aim of this study was to assess the clinical usefulness as a prognostic factor of the bowel wall behaviour during postoperative follow-up after strlctureplastles and miniresections for Cmhn’s disease (CD). Patients and methods. Eighty-five consecutive patients undergone strictureplasty and mini-resectiins for CD. Clinical and ultrasoncgraphic bowel wall evaluations were made before and six months after surgery, as well as whenever symptoms compatible wlth recurrence occurred during the follow-up. The US evaluations included the preoperative maximum bowel wall thickness (BWT), the length of BWT and bowel wall echopattem (homogeneous, stratified was classified as px.t-surgical BWT behaviour and mixed); normalized/improved or unchanged/worsened. Results. Three years clinical and surgical recurrences occurred in 35.3% and 18.8% of cases mspeck& A slgnmcant correlation was found between a longer preoperative BWT and surgical recurrence (p=O.O4); a previous surgery and post-surgical unchanged/worsened BWT behaviour (p=O.Ol). Patients with unchanged/worsened BWT after surgery are at higher risk of clinical (HR 9.98; 95% CI 3.48-28.56) and surgical (HR 16.15; 95% CI 2.87-90.75) recurrence at the Cox’s propomona hazard model.
A34
A NOVEL ROLE FOR TEE NEUROPEPTJDE NEUROTENSIN IN CHRONIC COLITIS. Cataldi F’. Galeazzi p, Pothoulakis C’, Wang C’, Zacks J”, Carraway R4. Q&tdiuolo I ’ ‘Beth Israel DeaconessMedical Center, Harvard Medical School, Boston USA, ‘University of P&a, Padua Italy; Boston University School of Medicine, Boston USA, !University of Massachussets,Worchester USA. The neuropeptide neurotensin (NT) is a potent neuroimmunomodulator that in the gastrointestinal tract promotes acute inflammation,
In addition we recently reported that the expression of
the high &iiity NT receptor (NlXI) is up-regulated in colonic epithelial and microvaacolar endothelial cells in IBD patients. Since NT also stimulates mucosal trophism and microvascular endothelial cell proliferation we decided to investigated the role of NT during chronic colitis. We observed that colonic NT mRNA (by in situ hybridization) and peptide levels (by EIA) significantly increased during experimental TNBS (3.2-fold increaseat day 7, FO.01) or DSS (S.&fold increaseat day S,~0.01) colitis. Furthermore, within S to 7 days after the induction of colitis, Nl’Rl immunoreactivity in the colonic mucosa drastically increased.To assessthe functional significance ofNT and NTRl up-regulation during chronic colitis, we administered SR-48642, a specific non-peptide NTRl
antagonist, to
mice. Clinical signs, macroscopicand histologic damage associated with TNBS (12 d) and DSS (5 d) colitis were significantly more severe in mice receiving SR-48642 then in vehicle treated mice Furthermore, continues administration of NT by micro-in&ion pumps (for S days) significantly ameliorated clinical signs, macroscopic and histologic damage associatedwith DSS (S d) colitis. In summary NT and Nl’Rl are up-regulated during TNBS and DSS colitis and antiyonizing NT effects during chronic colitis worsen tissue damage.We propose that during the chronic phasesof inflammatory disorders NT may participate in the processof mucossl restitution following tissue injury.