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Markovian features in longstanding ulcerative colitis
Abstracts
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33 PAEDL4TlUC INFLAMMATORY BOWEL DISEASE IN TUSCANY, ITALY. LionettiP PallaG*, CavicchiMC, Veltroni M, SalvcstriniC, Brizzi I, Trallori -T Go,MaggioreG*. Dipartimento di Pediatria, Universti di Fircnze, ‘Istituto di Pediatria Universitidi Piss,YJ.0. Gastrocnterologia, A.O. Careggi- Firenze,Italy. Only a few epidemiological stodicson inflammatoryboweldisease(IBD) in Italy havebeenpublishedand paediatricstudiesare completelylacking.Aim of the presentstudywas lo investigatethe numberof childrenwith IBD followed in our region, to discriminatebetweensymptomsat presentationand at diagnosis,and to verify the presenceof delay in diagnosisthat is commonly reportedspeciallyin Crohn’sdisease.A questionnaire concerningpatientswith IBD: Crohn’s disease(CD), ulcerativecolitis (UC) and indeterminatecolitis (IC) with diseasepresentation5 18 year of age was sentto all paediatricand adult universitydepartmentsand hospitalunits of Tuscany.A f&I numberof 100 childrenand adolescents was recorded: 46 CD, 48 UC and 6 IC. Twenty seven(27%) patientscamefrom other Italian regionsand were followed at hospitals of Tuscany (mainly‘Florence and Pisa). Mean age at disease presentationwas 10.99 years (age range:2-18 yrs) for CD, 10.91 yn (age range:0.58-18yrs) for UC and4.84 yrs (agerange1.75-7)for IC. Meanageat diagnosiswas 12.96yrs for CD (age range:5.16-23yn), 11.81 yrs for UC (agerange2.75-26yrs) and 8.81 (age range: 1.91-20yrs) for IC. Mean time intervalbetweensymptomsat presentationand diagnosiswas 1.97yrs for CD, 0.9 yrs for UC. In childrenwith CD, diarrhceawas absentat diagnosisin 20 children (20%) and extraintestinalsymptomsalone representthe initial mainfestations in I2 (12%) children.In contrastin UC diarrhceawaspresentin 100 % of childrenat diagnosis.However3 children(3%) had liver disease beforethe onsetof diihoea and the diagnosisof UC. The numberof new diagnosisfrom 1982to 1990was22 whereasfrom 1991to 1999it was88. Evenif from this studywas not possibleto know prevalenceratesof IBD in our regionthereis a clearimpressionthat incidenceratesfor both CD and UC are increasingin the paediatricas well as in the adult populationin Tuscany. Most childrenwith IBD were diagnosed> 1I years but IBD was diagnosed evenin childrenbelow6 yearsof age.Delayin diagnosisis still very common. This is probablydueto the lack of awarenessof extraintestinalmanifestations as presentingsymptomsin CD in the childhoodagegroup.
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MARKOVIAN FEATURES IN LONGSTANDING ULCERATIVE COLITIS Armeotano R, Pirrelli M, Valentioi AM, *Penna A, CaluS ML Department of pathology and *Eodoscopy, IRCCS Cnstellanr Grotte @A)
Hktol~gkal evaluation of dysplasiarepresentsthe great effort in the management of patients with longstanding Ulcerative Colitis (UC), although is object of some criticism related to its subjectivity. The dysplasiacan be better evaluatedwith morphometricalanaIysisbased on mathematicalequationsas the Mark&m texture features. Two cases of cancer in longstanding UC were studied for the assessmentof Markovian texture features in normal, dysplastic,and neoplastic colonic epithelium with the aim to reveal their discriminatingability. An image cytometric analysis on 400 nuclei for case for detection of the 22 Markovian texture features, with the CeIh&u Analysis System (CAS 200, Be&on Dickinson), was performed. We selectedthe only three features with disximinative significance:the Entrouy, a generic measure of disorder in nuclear componentsdistribution; t&Contrast. expression of chromatin components density variation, and the Correlation expressedby nuclei with large regions of condensedchromatin. Case I: A 45 year old man with pancolitis for 20 years. No dysplastic changes around the sigmoid neoplastic stenosis, high grade dysplasia and a distant metastasiswere revealed2 years later. Case2: A 41 year old man with family history of UC with pancolitis for I2 years. Dysplastic and neoplasticchangesand local @nph node metastasiswere found. Markovian texture features were similar in both cases. Higher Entropy was found in normal mucosa. No di&ence between dysplasia and cancer was noted. The Contrast shows higher vahxs in normal than in dysplasticand neoplasticepitheliumwhile the lowest v&es were found in metastaticnuclei. Correlation value at the highest levels was obtained in both dysplasiaand cancer without notable difference among them. The Markovian features were able to differentiate normal epithelium from dysplasticand neoplastic ones. Moreover, the Contrast discriminates the neoplastic primitive from metaststic nuclei. The lymphnodal environment rather than the tumoral progression can be responsible of this nuclear change.
'6 COLITIS MIMICKING CROHN’S DISEASE IN PATIENT WITH. RHEUMATOID ARTHRITIS . . &L&M, Armentano R, *Cozzolo”go R, Valenthi AM, Mslerba MA, Caruso ML Departments of Pathology and *Medicine, lRCCS “S De Bellis” Castellana G (BA) Case history A 49 year-old female with a 17-year history of sempositive rheumatoid arthnfis (RA) treated with gold salts for many years and recently with low dose methotrexate, was admitted to our Hospital. She underwent in 1994 at right emicolectomia and segmental resection of sigmold colon for diverticular disease and at present was suffering from abdominal pain at lower quadrants with intermittent diarrhoea and blood in the stool. The Au ileo-c&c endoscopy showed mucosal ulceration in the whole colon mtewening muco~a and the rectum were almost at all normal. Serial biopsies of affected mwo~a showed angiectasia, diffuse and marked chmmc inflammation with areas of Fragments of frank ulceration, crypt abscesses in absence of architectural distortion. the spared mucusa showed minor changes or not at all. None of specimens were comprehensive of the superficial submucosa. Dmg-induced colitis (including gold enterocolitis and mfectmns methotrexatc-induced whtis), amyloidosis and vaculitis were considered as possible diagnosis but were won ruled out because of lack of the clinical correlation antior the morphological support. A diagnosis of Cmhn’s dwzase was suggested. Successively the pauent wa! readmitted because of persistence of gastrointestinal (and arthritic) symptoms. Laboratory findings dwzlosed pmtemuria An X-my of small bowel together with high value of semm creatinine and nitrogen. showed an altered transit of the barium meal with segmental luminal namwmg and mucosal ulceration thus suggesting C&n’s disease. A new set of biopsies demonstrated the same alterations already described but, in addition, large deposits of acidophilic, homogeneous glassy material m the stroma and around the vessels of the superficial submucosa were seen. A vessel wth this alterations penetmtmg the muscolaris mucmae and overcome by a cmt with features of coagulative necrosis as well as strands of necroinflammatory material stratified as pseudomembrane upon the luminal surface of the rnucosa were found. The Congo Red stain of this material showed green birefringence under polarized light and the immunohistcchenucal analysis A fmal (Dako Mab mc I) demonstrated deposition of AA type amyloid tibrils. diagnosis of amyloid colitis with ischemic features was done. The review of histological slides, either from the fmt cndoscopy either from the previous surgery, did not show any hWocheruical and immunohistochemical evidence of amyloidosis. Conclusion Gastmintcstmal amyloidosis in RA may be of s&aightfonvard importance because of a rapid worsening of prognosis. For this reasons representative biopsies comprehensive of superficial submucosa and a careful search of amyloid deposits are advisable.
CLINICAL COURSE OF FAMILIAL AND SPORADIC CASES OF CROHN’S DISEASE Orlando A, Cas& A, Oliva L, Rosselli M,Di Mitri R and Cottone M. Clinica Medica “R”, Divisione di Medicina. Ospedale“V.Cervello”. Istituto di Medicina Generalee Pneumologia,Universiti di Palermo. Background: in Crohn’s disease (CD) ileal site, fibrostenotic and perforating patternsare more frequent in familial than in sporadic cases. Therefore the clinical course of familial cases should be more aggressive. Aim: to evaluatethe natural history of familial casesof CD compared with sporadic caseshaving as end point the first operation, endoscopic and surgical recurrence. Patients and methods: 950 patients with Crohn’s disease were observedin our Department from 1973 to 1999. 139 out of them were caseswith familial occurrence. The cumulative rate of 6rst operation and the surgical recurrence rate after tirst operation of familial and sporadic cases was evaluated by Kaplan-Meier method. The comparison between the two curves was analized by Mantel-Cox test. The comparison of endoscopic recurrence after one year between familial and sporadic cases was expressed through an odds ratio. A multivariate analysis was performed by logistic regression and Cox method including the following variables: age at diagnosis, site, smoking habits, perianal fistulas, extraintestinalmanifestations. Results: The 7 year cumulative rate of tirst operation was 58% (95% CI 54-62) among sporadic cases and 55% (95% CI 46-64) among familial cases.The 7 year cumulative rate of secondoperation was 24% (95% CI 18-30) among sporadic casesand 25% (95% CI 1S-40) among familial cases.No significant differences were observed between the curves.The odds ratio for endoscopicrecurrencewas 1.02 (9S% CI OS1.8). At multivariate analysis familial occurencewas not independently associatedwith first operation, endoscopicand surgical recurrence, Conclusions: This series shows that the clinical course of CD is similar among familial and sporadic cases although fibrostenotic and perforating patternsare more frequent in the familial cases.
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33 PAEDL4TlUC INFLAMMATORY BOWEL DISEASE IN TUSCANY, ITALY. LionettiP PallaG*, CavicchiMC, Veltroni M, SalvcstriniC, Brizzi I, Trallori -T Go,MaggioreG*. Dipartimento di Pediatria, Universti di Fircnze, ‘Istituto di Pediatria Universitidi Piss,YJ.0. Gastrocnterologia, A.O. Careggi- Firenze,Italy. Only a few epidemiological stodicson inflammatoryboweldisease(IBD) in Italy havebeenpublishedand paediatricstudiesare completelylacking.Aim of the presentstudywas lo investigatethe numberof childrenwith IBD followed in our region, to discriminatebetweensymptomsat presentationand at diagnosis,and to verify the presenceof delay in diagnosisthat is commonly reportedspeciallyin Crohn’sdisease.A questionnaire concerningpatientswith IBD: Crohn’s disease(CD), ulcerativecolitis (UC) and indeterminatecolitis (IC) with diseasepresentation5 18 year of age was sentto all paediatricand adult universitydepartmentsand hospitalunits of Tuscany.A f&I numberof 100 childrenand adolescents was recorded: 46 CD, 48 UC and 6 IC. Twenty seven(27%) patientscamefrom other Italian regionsand were followed at hospitals of Tuscany (mainly‘Florence and Pisa). Mean age at disease presentationwas 10.99 years (age range:2-18 yrs) for CD, 10.91 yn (age range:0.58-18yrs) for UC and4.84 yrs (agerange1.75-7)for IC. Meanageat diagnosiswas 12.96yrs for CD (age range:5.16-23yn), 11.81 yrs for UC (agerange2.75-26yrs) and 8.81 (age range: 1.91-20yrs) for IC. Mean time intervalbetweensymptomsat presentationand diagnosiswas 1.97yrs for CD, 0.9 yrs for UC. In childrenwith CD, diarrhceawas absentat diagnosisin 20 children (20%) and extraintestinalsymptomsalone representthe initial mainfestations in I2 (12%) children.In contrastin UC diarrhceawaspresentin 100 % of childrenat diagnosis.However3 children(3%) had liver disease beforethe onsetof diihoea and the diagnosisof UC. The numberof new diagnosisfrom 1982to 1990was22 whereasfrom 1991to 1999it was88. Evenif from this studywas not possibleto know prevalenceratesof IBD in our regionthereis a clearimpressionthat incidenceratesfor both CD and UC are increasingin the paediatricas well as in the adult populationin Tuscany. Most childrenwith IBD were diagnosed> 1I years but IBD was diagnosed evenin childrenbelow6 yearsof age.Delayin diagnosisis still very common. This is probablydueto the lack of awarenessof extraintestinalmanifestations as presentingsymptomsin CD in the childhoodagegroup.
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MARKOVIAN FEATURES IN LONGSTANDING ULCERATIVE COLITIS Armeotano R, Pirrelli M, Valentioi AM, *Penna A, CaluS ML Department of pathology and *Eodoscopy, IRCCS Cnstellanr Grotte @A)
Hktol~gkal evaluation of dysplasiarepresentsthe great effort in the management of patients with longstanding Ulcerative Colitis (UC), although is object of some criticism related to its subjectivity. The dysplasiacan be better evaluatedwith morphometricalanaIysisbased on mathematicalequationsas the Mark&m texture features. Two cases of cancer in longstanding UC were studied for the assessmentof Markovian texture features in normal, dysplastic,and neoplastic colonic epithelium with the aim to reveal their discriminatingability. An image cytometric analysis on 400 nuclei for case for detection of the 22 Markovian texture features, with the CeIh&u Analysis System (CAS 200, Be&on Dickinson), was performed. We selectedthe only three features with disximinative significance:the Entrouy, a generic measure of disorder in nuclear componentsdistribution; t&Contrast. expression of chromatin components density variation, and the Correlation expressedby nuclei with large regions of condensedchromatin. Case I: A 45 year old man with pancolitis for 20 years. No dysplastic changes around the sigmoid neoplastic stenosis, high grade dysplasia and a distant metastasiswere revealed2 years later. Case2: A 41 year old man with family history of UC with pancolitis for I2 years. Dysplastic and neoplasticchangesand local @nph node metastasiswere found. Markovian texture features were similar in both cases. Higher Entropy was found in normal mucosa. No di&ence between dysplasia and cancer was noted. The Contrast shows higher vahxs in normal than in dysplasticand neoplasticepitheliumwhile the lowest v&es were found in metastaticnuclei. Correlation value at the highest levels was obtained in both dysplasiaand cancer without notable difference among them. The Markovian features were able to differentiate normal epithelium from dysplasticand neoplastic ones. Moreover, the Contrast discriminates the neoplastic primitive from metaststic nuclei. The lymphnodal environment rather than the tumoral progression can be responsible of this nuclear change.
'6 COLITIS MIMICKING CROHN’S DISEASE IN PATIENT WITH. RHEUMATOID ARTHRITIS . . &L&M, Armentano R, *Cozzolo”go R, Valenthi AM, Mslerba MA, Caruso ML Departments of Pathology and *Medicine, lRCCS “S De Bellis” Castellana G (BA) Case history A 49 year-old female with a 17-year history of sempositive rheumatoid arthnfis (RA) treated with gold salts for many years and recently with low dose methotrexate, was admitted to our Hospital. She underwent in 1994 at right emicolectomia and segmental resection of sigmold colon for diverticular disease and at present was suffering from abdominal pain at lower quadrants with intermittent diarrhoea and blood in the stool. The Au ileo-c&c endoscopy showed mucosal ulceration in the whole colon mtewening muco~a and the rectum were almost at all normal. Serial biopsies of affected mwo~a showed angiectasia, diffuse and marked chmmc inflammation with areas of Fragments of frank ulceration, crypt abscesses in absence of architectural distortion. the spared mucusa showed minor changes or not at all. None of specimens were comprehensive of the superficial submucosa. Dmg-induced colitis (including gold enterocolitis and mfectmns methotrexatc-induced whtis), amyloidosis and vaculitis were considered as possible diagnosis but were won ruled out because of lack of the clinical correlation antior the morphological support. A diagnosis of Cmhn’s dwzase was suggested. Successively the pauent wa! readmitted because of persistence of gastrointestinal (and arthritic) symptoms. Laboratory findings dwzlosed pmtemuria An X-my of small bowel together with high value of semm creatinine and nitrogen. showed an altered transit of the barium meal with segmental luminal namwmg and mucosal ulceration thus suggesting C&n’s disease. A new set of biopsies demonstrated the same alterations already described but, in addition, large deposits of acidophilic, homogeneous glassy material m the stroma and around the vessels of the superficial submucosa were seen. A vessel wth this alterations penetmtmg the muscolaris mucmae and overcome by a cmt with features of coagulative necrosis as well as strands of necroinflammatory material stratified as pseudomembrane upon the luminal surface of the rnucosa were found. The Congo Red stain of this material showed green birefringence under polarized light and the immunohistcchenucal analysis A fmal (Dako Mab mc I) demonstrated deposition of AA type amyloid tibrils. diagnosis of amyloid colitis with ischemic features was done. The review of histological slides, either from the fmt cndoscopy either from the previous surgery, did not show any hWocheruical and immunohistochemical evidence of amyloidosis. Conclusion Gastmintcstmal amyloidosis in RA may be of s&aightfonvard importance because of a rapid worsening of prognosis. For this reasons representative biopsies comprehensive of superficial submucosa and a careful search of amyloid deposits are advisable.
CLINICAL COURSE OF FAMILIAL AND SPORADIC CASES OF CROHN’S DISEASE Orlando A, Cas& A, Oliva L, Rosselli M,Di Mitri R and Cottone M. Clinica Medica “R”, Divisione di Medicina. Ospedale“V.Cervello”. Istituto di Medicina Generalee Pneumologia,Universiti di Palermo. Background: in Crohn’s disease (CD) ileal site, fibrostenotic and perforating patternsare more frequent in familial than in sporadic cases. Therefore the clinical course of familial cases should be more aggressive. Aim: to evaluatethe natural history of familial casesof CD compared with sporadic caseshaving as end point the first operation, endoscopic and surgical recurrence. Patients and methods: 950 patients with Crohn’s disease were observedin our Department from 1973 to 1999. 139 out of them were caseswith familial occurrence. The cumulative rate of 6rst operation and the surgical recurrence rate after tirst operation of familial and sporadic cases was evaluated by Kaplan-Meier method. The comparison between the two curves was analized by Mantel-Cox test. The comparison of endoscopic recurrence after one year between familial and sporadic cases was expressed through an odds ratio. A multivariate analysis was performed by logistic regression and Cox method including the following variables: age at diagnosis, site, smoking habits, perianal fistulas, extraintestinalmanifestations. Results: The 7 year cumulative rate of tirst operation was 58% (95% CI 54-62) among sporadic cases and 55% (95% CI 46-64) among familial cases.The 7 year cumulative rate of secondoperation was 24% (95% CI 18-30) among sporadic casesand 25% (95% CI 1S-40) among familial cases.No significant differences were observed between the curves.The odds ratio for endoscopicrecurrencewas 1.02 (9S% CI OS1.8). At multivariate analysis familial occurencewas not independently associatedwith first operation, endoscopicand surgical recurrence, Conclusions: This series shows that the clinical course of CD is similar among familial and sporadic cases although fibrostenotic and perforating patternsare more frequent in the familial cases.
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