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Anal endosonographic evaluation of infliximba treatment for perianal fistulizing Crohn's disease
Colon
11
9 APOPTOSIS AND PROLIFERATION OF COLONIC EPITHELIAL CELLS DEXTRAN SULPHATE SODIUM-INDUCED COLITIS IN RATS. G. Latella A. Vetuschi. R. Sfern, MT. Pimpo, R. Captilli”, E. Gaudio’ Cat&&a -I Gastroenterologia e Catledra di Anatomia Umana, Universiti de L’Aquila; “Cattedra Gastroenterdogia I e ‘Caltedra di Anatomia Umana. UnlversitP “La Sapienza” Roma.
IN di di di
Background. A model of experimental acute and chronic colitis and cdorectal carcinoma induced in rodents by feeding of de&an sulphate sodium (DSS) has been extensively described. However, the mechanisms by which DSS induce both cdonic inflammation and cancer are still unknown, in particular limited data concenning colonic epithelial cell apoptosis and proliferation are available. Disruption in the balance between cell apoptosis and proliferation could be implicated both in cdonic inflammation and carclnogenesis. Aim. To evaluate morphologic alterations and eoithelial cell apootosis and ordiferatlon of cdonic mucosa in acute and chronic phase oi DSS-induceb &lilis. Methoda. Colitis was induced in SpragueDawley rati by 7 davs of 4% DSS oral administration foIlowed bv 7 davs of tao water for 1, 2, and 3 cycles. Control rats receved tap water only. Mo&hologjc chanjles of mucosa of distal, mid-, and proximal colon were evaluated and scored by light and scanning electron microscope. Apoptosis was evaluated by the TUNEL assay and proliferation by ki-67 immunohistochemisby. The expression both of pm-apoptotic (Fas. FasL, Bax, ~53) adn anti-apoptollc (Bcl2) cellular proteins was determined by immunohistochemistry. Reeulb. In DSS treated rats morphologic assasmant showed the most severe colonic epithelial lesions and inflammatin in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats epithelial apoptotlc index increased 20 fdd after the first cyde and 120 fold after the second and third cycle compared with tile controls. paralleiy a drammatic increase in the expression of pm apoptotic proteins (Fas, FasL. Bax. ~53) was observed. Proliferative index increased about 40-60 fold compared to controls, without differences behveen the three DSS cycles. COtlcluaions. DSS-induced colitis in rats, which share most structural and ultrastructural features with human ulcerative mll@r. r+ltes to be associated with increased epithelial apoptosis and pmliferatlon. Increased apoptosis may lead to a breackdovm of the epithelial barrier function faclh?abig the mucosal invasion of intraluminal microflora and/or antigens, an important event for the chronization of the mucosal inflammation. Abnormal and persistent epithelial hype~pmliferd6on could be mvolved in the high frequency rate of coloractal cancer which occurs in such experimental model of colitis.
ENDORECTAL ULTRASONOGBAPHY FOR STAGING AND EVALUATION OF OUTCOME AFTBR PREOPERATIVE TREATMENT OF RECTAL CANCER: A SINGLE INSTITUTION EXPERIENCE G. Bonanno,S. Cordio,, P. Naso, G .Giannone and A. Russo SurgicalEndoscopy Unit Univewty of Catania;᠋ l;Oncology Department.S.Luigi-SC& Hospital CataniaItaly ENDOKECTAL ULTKASONOGRAPHY FOR STAGING AND EVALUATION OF OUTCOME AFTER PREOPERATIVE TREATMENT OF RECTAL CANCER: A SINGLE INSTITUTION EXPERIENCE G. Bonanno,S. Cordio,, P. Naso, G .Giannone᠋l; and A. Russo SurgicalEndoscopy Unit University of Catania;᠋I;Oncalagy Department.S.Luigi-S.Cw& HospitalCataniaItaly Polictico di Catania EndoscopicUltmsonogmpby (EUS) is consideredthe most accuratemethodfor stagmgof primary rectal cancer (PRC). Aims: to assessthe accuracy of EUS in the stagingof rectal cancer andin restagingit aI& neo-adjuvanttherapy. Methods: We pcrfonned an EUS evaluationfollowing the TNM classification m two different gmups ofpts: -sixty-four pts were stagedbefore surgery (Gmup A) and specimenswere comparedwith EUS results. -thirty-four pts (Group B), T3 and T4 at baselineEUS, were treatedwith peltic radiotherapy associati with infusion of chemotherapy with J-Fluomuracil; surgery was performed a&r aninterval of six to eight weeks. In tbis group, all patientsunderwenta secondEUS evalua!ionandthis stagewas comparedwith the specimenTNM staee.Results: -Gram A: EUS was able to oredict T staeein 67% of&s (43/64) with an overa&g in 20% (13164)andunder-stagingin 13% (8/64).The evaluatibndf nodal diseasewas correct in 51% of pts (33/64) with overestimationin 31% (20&t) and underestimationin 18% (I l/64). -Group B: the EUS accuracy to predict the wall invasionwas correcl in 53% of pts (18/34) with overestimationin 26% (P/34) andunderestimationin 21% (7134).Moreover lymph-node involvementwas correctly assessedin 50% ofpts (17/34) with an overestimationin 38% (13/34) andunderestimationin 12% (4/34). EUS evaluationofresponse to radio-chemotherapyshoweda s~goificantsize reduction of tumor lesionin 68% of pts (23/34). Conclusion: in OUTexperience the accuracy of EUS u1mutine preoperativestagingof PRC is in the lower range of thepublished da&. As regard as the B group we can underlinethatthe baselineEUS allows to selectthe pts to submit to neo-adjuvmt therapy (T3-T4) and at sametime it assesthe efficacy of ibis therapy. On the contrary the EUS performed at the endof radio-chemotherapyshows a very low diagnostic accuracy and for this reason can not representa standardpractice in this setting.EUS results could be improved using SD-EndosonographyandFNA (Fine Needle Aspiration).
10 HOW DOES COLORECTAL CANCER PRESENT TO PRIMARY CARE PHYSICIANS IN A GENERAL POPULATION IN ITALY? Panzuto F’ Chiriatti A”, Bevilacqua S#, Giovsnnetti P”, Russo CC”, -3 lmpinna S”, Pistilli F”. Capurso G’. Annibale 8’. Delle Fave G’. ‘Digesrivc and Ltver Drscasc Dpr, Ii School of Medicine, Universiry “Lo Sopienzo”. Ronm n FIMMG (Fed R Med Medicina Generole) # SIMG fSoc It Medicina Gcner&/ Background: Prevention rather than cure is the most efficacious approach to Cola-Rectal Cancer (CRC). which is one of the most freauent causes of death in western count&s, including Italy. In general, mosipts with CRC firstly refer to their Primary Care Physician (PCP), whose role is crucial for the early diagnosis of this disease. Aim: to investigate the prevalence and presentation symptoms of CRC in patients in whom PCP felt the need to perform colonoscopy (CS) after consultation. Patients and methods: During a period of 8 weeks between December 1999 and April 2000, 159 PCP of Lazio recruited 331 pts (185 female/l46 male, median age 58 yrs). Symptoms and CS findings were evaluated by PCP and then collected in a database. Results. Endoscopic investigation was negative in I21 pts (36%). CRC was found in 44 Dts (13%). and colonic WIVDS >I cm in 23 , ~ I, . ,r~~~ (7%). 12 CRC (27%) were located in the right colon or cecum. Independently from symptoms, patients aged>50 had an higher risk of having CRC (OR 8.3, 95%Cl 2-37). In pts with and without CRC there ws no difference regarding the observed prevalence of lower abdominal pain (68% and 74% respectively), meteorism (55% and 62%), constipation (48 and Sl%), diarrhea (34% and 35%), upper abdominal pain (27% and 35%) and rectal bleeding (27% and 17%). In patients with and without CRC, the prevalence of iron deficiency anemia (IDA) and weight loss were 71 vs. 22% and 52 vs. 21% resoectivelv (o50.
Anal endosonombic evaluationof -ab treatmentfor perk& fistulizing Cmhn’sd&case S. Anlizmne. S. Bollani. E. Colombo. G. Maconi. V. Imbesi. G. Man&ma. G. Bianchi Porn, chair of Gas&entemlogy, L. Sacw &ivashy H&dta.l - M&n - Italy Luigi SacM Background: Intliximab is an effective treatmenffor perianalfistulizing Cmbn’s disease(PFCD). However, early fist&w reopeningis very frequent, suggestingthepersistence of deepfistulous tracks dwite su0erfxia.I healing. Aim: To assessthe efficacv of Infliximab in the trealmentof PFCD &~to~t~ convention therapy, cm&ding clinicairesponse with rmatendosonogmpbic tidings of internal tracks and me of perimal fishlla. Patisntsand methods:23 patientswith refractory PFCD enteredthe study (M/F 14/P,mean age36,range 21-71), and&ived Intliximab 5 n&g, administeredin!mvenously at weeks 0,2 and6. Clinically, fistulae were consideredclosed when they no longer draineddespiteg&e finger compRssicm.Before the first infusion anda!?.~ the last one, anal endosonographyusing B&K system was performedby the sameopaator. The post-infusion examinationswere wfomxd blindly fo theclinical results. Active fish&aswere &nwapbically defined as a h&zchoic track vii& hypxchoic content,and were &cd accordii to the Cadiff classification.Resulw -ad anal endosonograpbyshowed24 fistulas in 23 patients(IO law per&al i&P). 2 intexsphincteric(IF), 5 b&b complex (HC), 2 anowlval, and5 bigb rectovaginal fist&z?). By the end of the tre@mentregjmen,lack of cutaneous drainagewas observed in 12 of 24 fistulas (9 LP, 3 HO. Endosonouraubicdisamxaace of hyperechoiccontent was obsewed in 6 of these I2 fist&s (all w&L+). In 3 &ents with clinically and eadosonograpbicallyhealedLP &hda setonbad ban positioned, andin I a faecal diversion hadbeenperformed. Two patientswith clinically but no endosonograpbicallyhealedHC fishda developeda pelvic abscess.None of thepatientswith anovnlval andrecwaginal fistulas showeda significant clinical andendosonograpbic-me. Conclusions: These datasuggestthat: 1) tie type of fishda may be a predictive factor for clinical responseto Infliximab: 2) despite closure of draining fistulas,in most cases patientscontinuedto show an internsI track with hypnechoic content; 3) ibe associationwith setonor faecal diversion can pate&de the effectivenessof Inflixbnab; 4) closure of the cutanwus orifice with thepersistence of hyperechoic contentmay lead to pelvic abscessin patientswtb bigb complex fistulas.
A41
11
9 APOPTOSIS AND PROLIFERATION OF COLONIC EPITHELIAL CELLS DEXTRAN SULPHATE SODIUM-INDUCED COLITIS IN RATS. G. Latella A. Vetuschi. R. Sfern, MT. Pimpo, R. Captilli”, E. Gaudio’ Cat&&a -I Gastroenterologia e Catledra di Anatomia Umana, Universiti de L’Aquila; “Cattedra Gastroenterdogia I e ‘Caltedra di Anatomia Umana. UnlversitP “La Sapienza” Roma.
IN di di di
Background. A model of experimental acute and chronic colitis and cdorectal carcinoma induced in rodents by feeding of de&an sulphate sodium (DSS) has been extensively described. However, the mechanisms by which DSS induce both cdonic inflammation and cancer are still unknown, in particular limited data concenning colonic epithelial cell apoptosis and proliferation are available. Disruption in the balance between cell apoptosis and proliferation could be implicated both in cdonic inflammation and carclnogenesis. Aim. To evaluate morphologic alterations and eoithelial cell apootosis and ordiferatlon of cdonic mucosa in acute and chronic phase oi DSS-induceb &lilis. Methoda. Colitis was induced in SpragueDawley rati by 7 davs of 4% DSS oral administration foIlowed bv 7 davs of tao water for 1, 2, and 3 cycles. Control rats receved tap water only. Mo&hologjc chanjles of mucosa of distal, mid-, and proximal colon were evaluated and scored by light and scanning electron microscope. Apoptosis was evaluated by the TUNEL assay and proliferation by ki-67 immunohistochemisby. The expression both of pm-apoptotic (Fas. FasL, Bax, ~53) adn anti-apoptollc (Bcl2) cellular proteins was determined by immunohistochemistry. Reeulb. In DSS treated rats morphologic assasmant showed the most severe colonic epithelial lesions and inflammatin in the distal colon with a trend to increasing severity from the first to the third DSS cycle. In DSS rats epithelial apoptotlc index increased 20 fdd after the first cyde and 120 fold after the second and third cycle compared with tile controls. paralleiy a drammatic increase in the expression of pm apoptotic proteins (Fas, FasL. Bax. ~53) was observed. Proliferative index increased about 40-60 fold compared to controls, without differences behveen the three DSS cycles. COtlcluaions. DSS-induced colitis in rats, which share most structural and ultrastructural features with human ulcerative mll@r. r+ltes to be associated with increased epithelial apoptosis and pmliferatlon. Increased apoptosis may lead to a breackdovm of the epithelial barrier function faclh?abig the mucosal invasion of intraluminal microflora and/or antigens, an important event for the chronization of the mucosal inflammation. Abnormal and persistent epithelial hype~pmliferd6on could be mvolved in the high frequency rate of coloractal cancer which occurs in such experimental model of colitis.
ENDORECTAL ULTRASONOGBAPHY FOR STAGING AND EVALUATION OF OUTCOME AFTBR PREOPERATIVE TREATMENT OF RECTAL CANCER: A SINGLE INSTITUTION EXPERIENCE G. Bonanno,S. Cordio,, P. Naso, G .Giannone and A. Russo SurgicalEndoscopy Unit Univewty of Catania;᠋ l;Oncology Department.S.Luigi-SC& Hospital CataniaItaly ENDOKECTAL ULTKASONOGRAPHY FOR STAGING AND EVALUATION OF OUTCOME AFTER PREOPERATIVE TREATMENT OF RECTAL CANCER: A SINGLE INSTITUTION EXPERIENCE G. Bonanno,S. Cordio,, P. Naso, G .Giannone᠋l; and A. Russo SurgicalEndoscopy Unit University of Catania;᠋I;Oncalagy Department.S.Luigi-S.Cw& HospitalCataniaItaly Polictico di Catania EndoscopicUltmsonogmpby (EUS) is consideredthe most accuratemethodfor stagmgof primary rectal cancer (PRC). Aims: to assessthe accuracy of EUS in the stagingof rectal cancer andin restagingit aI& neo-adjuvanttherapy. Methods: We pcrfonned an EUS evaluationfollowing the TNM classification m two different gmups ofpts: -sixty-four pts were stagedbefore surgery (Gmup A) and specimenswere comparedwith EUS results. -thirty-four pts (Group B), T3 and T4 at baselineEUS, were treatedwith peltic radiotherapy associati with infusion of chemotherapy with J-Fluomuracil; surgery was performed a&r aninterval of six to eight weeks. In tbis group, all patientsunderwenta secondEUS evalua!ionandthis stagewas comparedwith the specimenTNM staee.Results: -Gram A: EUS was able to oredict T staeein 67% of&s (43/64) with an overa&g in 20% (13164)andunder-stagingin 13% (8/64).The evaluatibndf nodal diseasewas correct in 51% of pts (33/64) with overestimationin 31% (20&t) and underestimationin 18% (I l/64). -Group B: the EUS accuracy to predict the wall invasionwas correcl in 53% of pts (18/34) with overestimationin 26% (P/34) andunderestimationin 21% (7134).Moreover lymph-node involvementwas correctly assessedin 50% ofpts (17/34) with an overestimationin 38% (13/34) andunderestimationin 12% (4/34). EUS evaluationofresponse to radio-chemotherapyshoweda s~goificantsize reduction of tumor lesionin 68% of pts (23/34). Conclusion: in OUTexperience the accuracy of EUS u1mutine preoperativestagingof PRC is in the lower range of thepublished da&. As regard as the B group we can underlinethatthe baselineEUS allows to selectthe pts to submit to neo-adjuvmt therapy (T3-T4) and at sametime it assesthe efficacy of ibis therapy. On the contrary the EUS performed at the endof radio-chemotherapyshows a very low diagnostic accuracy and for this reason can not representa standardpractice in this setting.EUS results could be improved using SD-EndosonographyandFNA (Fine Needle Aspiration).
10 HOW DOES COLORECTAL CANCER PRESENT TO PRIMARY CARE PHYSICIANS IN A GENERAL POPULATION IN ITALY? Panzuto F’ Chiriatti A”, Bevilacqua S#, Giovsnnetti P”, Russo CC”, -3 lmpinna S”, Pistilli F”. Capurso G’. Annibale 8’. Delle Fave G’. ‘Digesrivc and Ltver Drscasc Dpr, Ii School of Medicine, Universiry “Lo Sopienzo”. Ronm n FIMMG (Fed R Med Medicina Generole) # SIMG fSoc It Medicina Gcner&/ Background: Prevention rather than cure is the most efficacious approach to Cola-Rectal Cancer (CRC). which is one of the most freauent causes of death in western count&s, including Italy. In general, mosipts with CRC firstly refer to their Primary Care Physician (PCP), whose role is crucial for the early diagnosis of this disease. Aim: to investigate the prevalence and presentation symptoms of CRC in patients in whom PCP felt the need to perform colonoscopy (CS) after consultation. Patients and methods: During a period of 8 weeks between December 1999 and April 2000, 159 PCP of Lazio recruited 331 pts (185 female/l46 male, median age 58 yrs). Symptoms and CS findings were evaluated by PCP and then collected in a database. Results. Endoscopic investigation was negative in I21 pts (36%). CRC was found in 44 Dts (13%). and colonic WIVDS >I cm in 23 , ~ I, . ,r~~~ (7%). 12 CRC (27%) were located in the right colon or cecum. Independently from symptoms, patients aged>50 had an higher risk of having CRC (OR 8.3, 95%Cl 2-37). In pts with and without CRC there ws no difference regarding the observed prevalence of lower abdominal pain (68% and 74% respectively), meteorism (55% and 62%), constipation (48 and Sl%), diarrhea (34% and 35%), upper abdominal pain (27% and 35%) and rectal bleeding (27% and 17%). In patients with and without CRC, the prevalence of iron deficiency anemia (IDA) and weight loss were 71 vs. 22% and 52 vs. 21% resoectivelv (o
Anal endosonombic evaluationof -ab treatmentfor perk& fistulizing Cmhn’sd&case S. Anlizmne. S. Bollani. E. Colombo. G. Maconi. V. Imbesi. G. Man&ma. G. Bianchi Porn, chair of Gas&entemlogy, L. Sacw &ivashy H&dta.l - M&n - Italy Luigi SacM Background: Intliximab is an effective treatmenffor perianalfistulizing Cmbn’s disease(PFCD). However, early fist&w reopeningis very frequent, suggestingthepersistence of deepfistulous tracks dwite su0erfxia.I healing. Aim: To assessthe efficacv of Infliximab in the trealmentof PFCD &~to~t~ convention therapy, cm&ding clinicairesponse with rmatendosonogmpbic tidings of internal tracks and me of perimal fishlla. Patisntsand methods:23 patientswith refractory PFCD enteredthe study (M/F 14/P,mean age36,range 21-71), and&ived Intliximab 5 n&g, administeredin!mvenously at weeks 0,2 and6. Clinically, fistulae were consideredclosed when they no longer draineddespiteg&e finger compRssicm.Before the first infusion anda!?.~ the last one, anal endosonographyusing B&K system was performedby the sameopaator. The post-infusion examinationswere wfomxd blindly fo theclinical results. Active fish&aswere &nwapbically defined as a h&zchoic track vii& hypxchoic content,and were &cd accordii to the Cadiff classification.Resulw -ad anal endosonograpbyshowed24 fistulas in 23 patients(IO law per&al i&P). 2 intexsphincteric(IF), 5 b&b complex (HC), 2 anowlval, and5 bigb rectovaginal fist&z?). By the end of the tre@mentregjmen,lack of cutaneous drainagewas observed in 12 of 24 fistulas (9 LP, 3 HO. Endosonouraubicdisamxaace of hyperechoiccontent was obsewed in 6 of these I2 fist&s (all w&L+). In 3 &ents with clinically and eadosonograpbicallyhealedLP &hda setonbad ban positioned, andin I a faecal diversion hadbeenperformed. Two patientswith clinically but no endosonograpbicallyhealedHC fishda developeda pelvic abscess.None of thepatientswith anovnlval andrecwaginal fistulas showeda significant clinical andendosonograpbic-me. Conclusions: These datasuggestthat: 1) tie type of fishda may be a predictive factor for clinical responseto Infliximab: 2) despite closure of draining fistulas,in most cases patientscontinuedto show an internsI track with hypnechoic content; 3) ibe associationwith setonor faecal diversion can pate&de the effectivenessof Inflixbnab; 4) closure of the cutanwus orifice with thepersistence of hyperechoic contentmay lead to pelvic abscessin patientswtb bigb complex fistulas.
A41