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Epithelial E-cadherin expression in coeliac disease
Rbstracto
7
5 EPITHELIAL E-CADHERTN EXPRESSION IN COELIAC DISEASE Di SabatinoA. Morem R Ciwociamo R Ricewti L. Luinetti 0, Comza GR. GasWentmlogy Unit endDept ofathology, IRCCS Peliclinico S. Mattea,University of Pavia, Italy. Policlinico S.MaReo Background& Aims: E-cadherinis a calcium dependentcell adhesionreceptor expressedby epithelialcells. Normal E-cadherin expressionandfunction are essentialfor the establishmentof cell polarity anddifferentiation,and for the maintenanceof intestinalarchitecti by regulahng entemcytepmlifemtion, migration and apoptosis.Sinceit har beenshown that in untreatedcoeliac disease(CD) enterccyte apoptosisis increased,we investigatedthe distribution of E-cadherinin c0clis.cduodenaltnucosa to determinewhether its expressionis changedin this condition.Patients & MethodszEndosMpic biopsy specimenswere obtained from thesecond part of the duodenum fmm IO untreatedcceliac patients(meanage38.9 years, range 19-61), from 10 coeliacpatients (meanage39.8years, range25-62) on a gluten-freediet for at least 12 months, andfmm 10 consenting.subiects underaoiw wrner aastmintestinalendoscopyfor functional dyspepsia(mean age55.3&ars;range 33-73). &&y s&cimens were pmcesseh-for immunohist&h~&&try with the mousemonoclond anti-humanEcadhti antibody (Zymed LaboratoriesInc., SanFrancisco, CA) at I:400 dilution. As positive contml, normal gastric tissuewas used and,as negativecontrol, e sectionwas incubatedwithout theprimary antibody. The intensity of stainingwas calculatedusing ancxdinal scale (0 to * 0 to 3): +3 = sfmngly positive staining,+2 = moderatelypesltive staining,+I = weak dining, and0 = absenceof staining.Results: In normal duodenumE-cadherin positivity manifestedascrisp b&sol&ml stainingof epithelialcells. This stainingwas strong (+++) throughoutthe @helium without significantchangeain intensity b-stweensurface and crypt level. A similar mttern was seenin treatedcoeliacoatients.In untrated coeliac mtients. the intensitv of epithelial&ieing was weakly (+). Conclusi&: E-z&tin is strongly ani ever& expresseddy epithclium in normal small intestine.The tinding ofreduced membranousE-cadherinexpression in theepithelium of untreatedweliac patientssupports for the view thatE-cadherin down-regulation would panit increasedenterwyle apoptosisin active CD.
NATURAL
HISTORY OF DIGIWTIW NEIJROENDOCRINE TUMORS. Panzuto F Naxmi S. Ciardi S, Moretti A, Cassetta S, Turriziani V, Annelatis. F’emi P*, Corkto VD, DeIle Fave 0.
Backgmoad: an und-i of natural history of digestive Nemocndocrine Tumors (dNETs) is r&red to identify prognostic factors, define different 8xoups of patients with di&cnt prognosis, and plsn proper @eatnerd of the disease. Houwer, few dam are available, because of the rarity, the slow evolution, and the absence of definitive reliable markers of prognosis for these tumors. Aim of this study was to investigate on onset, symptoms and survival rate of dNETs. Patients and methods 104 ots with histoIoaicallv documented dNET 160 without fNF7 and 44 with’ (F) associated sy&ome (26 gastrikss, 16 e&&ids. 1 glucagonoma, 1 VIPoma)] recruited af our h5titution and followKi up for a median of 30 months (range: 4-222). Resuk At diiosis, all F pts were symptomatic, whereas 25% of NF pu had no symptoms and diagnosis was made due to the accidental identification of hmmr lesions. Most frequent onset sympmms in NF -01s were: chronic abdominal pain (30%), appendicitis-Ike (1 I%), rectal bleeding (‘X/o), dyspepsia (6%), bowel obsmtction (6%) and weight loss (5%). In F tumors: abdominal pain (43%). diica (41%), GEBD-like (27%) and flushing (16%). The mean time between onset of symptoms and cl@nosis was 5 (95%1X: 1.4-9.1) end 43 (95%Cl: 41.8-103.8) months in NF and F tumors respectively (p
6 WIRELESS CAPSULE ENDOSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL BLEEDING: PRBLIMlNARY ~KSlJ&~;OF ;;gEw.L4N MULTTCENTRE EXPERIENCE. *E.Rondonotti, *C.Abbiatl, *G.Beccari, “R Luch& “A. Dezi, “L.&apurso, *R.de Franchis and F.P. Rossim. Ga&menterolog -Gastmintestinal Endoscopy Se&e, Dept. of Oncology, ;zy~; d&o~,l, Turin. *Gastroenterology- Gastmintes@al ept of Internal Medicine, Unwersity of Milan, IRCCS &hclinico kospltal, Milan. “Dept. of Gastroentemlogy, S.Fihppo Nen Hospital, Rome, Italy. Backeround: Available techniaues 10identifi bleedme small bowel lesions are &atisfactory The Giwi video cap&e systzm (Given hnaging Ltd.,Yoqneam, Israel) IS a new system designed to ad the gastmenterologist 11,du nosmg small boyel dxases. Aim: $ro assess the uuh of the Given video capsule system m patients wth obscure sastmintesunal ?’GI) bleeding. Methods: The G&en system con&s of three elements: a disposable, swallowable M2A imaging capsule that acquires the video images dtin natural propulsion through the GI tract; a recorder which receives ant records the transmitted data: a cmn~uter workstation for mocessinz. vrewine and reporting of ima es and data ad uired through the Gf tract Between January an%May 2001, 22 patxnts (I6 men, 9 wo,nen, age range 18-62 years) wth obscure and recurrent GI bleeding, in whom previous u per and lower endoscopies were normal, were evaluatedwith this system. & ere were 13 patients with obscure-overt bleedin and I2 patients with obscure-occu!t bleedmg. Push enteroscopy was ped mmed prior to capsule exa?nnatmn m 14 at~ents Two patients were diagnosed to have jejunal angrqdysplaszas, onPy partly responsive to entemscopic treatment. In the remammg patients push entemscopy was normal. The bowel was pr ared with a 24 hour flud diet. An oral purge (polyethylene glywl-based so“p.utmn and/or sulfate purge) was additionally given to I8 patients the day before of the capsule endoscopy. The patients swallowed the capsule after signing an informed consent farm and under continuous medical suoervision. Results: The capsule exlted the body naturally in al patients and no compbcations occurred throughout the study. The capsule remained in the stomach. for an average of 56 minutes (4-240): The avera e small bowel transd time was 220 tmnutes (125.350). The Images of t e small bowel obtamedwere of good quality, especially in patients who took an oral purge. A small,bowel bleeding site was found in 12 of 25 atients: an iodysplasia (41, van~es (2), Crohn’s disease (J), ileal ulcers pI), J~JUX~ ” %,leulafoy’s lesmn (!)! actwe ileal bleeding (I), deal lymphoma (I), traces of blood clots in rbe JCJUIIU~ (I). In this last patient a subsequent push entemscopy ldentltied a jejunal turnour which was missed by the capsule. Capsule endoscopy found a distal sowce of bleeding in 7 of 12 atimts wrtb normal push enterosco ic exams. Overall, findings at capsu changes in mea~cal treatment in 8 patients. to suwcal endoscoqic therapy m J. ., . Co~clusmns: T e Gwen diagnostic imaging system is able to acquire satlsfactoly Images and to identify pathologies m parts of the small bowel which are. be ond the reach of conventional entemscopy. The information pmwded m tit.1s ongoing study was helpful in directmg further diagnostx and therapeutic options in patients with small bowel bleeding.
A2
PROSPECTIVE ANALYSIS OF THE “THREE DAY RULE”. A REGIONAL INITIATIVE FOR URGENT REFERRAL OF UPPER GASTROINTESTINAL. (GI) ENDOSCOPY BY GPs. Background&aim. A new initiative, called the Three Day Rule (TDR), has been intmduced in Lombardy in order to facilitate the earlier diagnosis and treatment of cancer. It requires patients with suspected severe diseases to be seen by a specialist or have a diagnostic procedure done within 3 working days of referral by GPs. In the case of upper GI malignancies, there is little published evidence to support the use of this scheme. Aim of this study has been to assess prospectively the effectiveness and compliance with ‘kDR. Methods. A prospective audit of all referrals for upper GI symptoms under the TDR initiative was done over a 12-month period at a single hospital of Western Milan. We collected demographic data, clinical details, referral cards and final diagnoses on all patients referred for gastmscopy by means of ‘IDR as well as on all outpatients undergoing endoscopy on open access basis during the same period. The appmpriateness of the indications for each request was then reviewed by a gastmenterologist blinded to the outcome of the test. Results. 142 patients were referred for gastmscopy under the TDR scheme and all appointed within 3 working days as compared with 767 patients who were appointed between 7 and 39 working days (median 22 days) on open access basis. 6% had a final diagnosis of cesophageal/gastric cancer in the TDR group as compared to only 1% in the open assess group (p
/No
j
/
I
~, 51/o
/64%
/
“.-
< 0.01 39% of aukscopies were rated as inappropriate in the open access group as compared with 22% in the TDR grow (wO.01). Conclusions. Significantly m&e up&r GI &mcers can be seen and a diagnosis of serious upper GI diseases made within a short period to comply with the TDR scheme. However, some GPs appear to over read alarm symptoms, end this may lead to inappropriate referrals. Better awareness of appropriate urgent refenal criteria is needed in order to ensure that resources for this initiative are used efficiently. /
7
5 EPITHELIAL E-CADHERTN EXPRESSION IN COELIAC DISEASE Di SabatinoA. Morem R Ciwociamo R Ricewti L. Luinetti 0, Comza GR. GasWentmlogy Unit endDept ofathology, IRCCS Peliclinico S. Mattea,University of Pavia, Italy. Policlinico S.MaReo Background& Aims: E-cadherinis a calcium dependentcell adhesionreceptor expressedby epithelialcells. Normal E-cadherin expressionandfunction are essentialfor the establishmentof cell polarity anddifferentiation,and for the maintenanceof intestinalarchitecti by regulahng entemcytepmlifemtion, migration and apoptosis.Sinceit har beenshown that in untreatedcoeliac disease(CD) enterccyte apoptosisis increased,we investigatedthe distribution of E-cadherinin c0clis.cduodenaltnucosa to determinewhether its expressionis changedin this condition.Patients & MethodszEndosMpic biopsy specimenswere obtained from thesecond part of the duodenum fmm IO untreatedcceliac patients(meanage38.9 years, range 19-61), from 10 coeliacpatients (meanage39.8years, range25-62) on a gluten-freediet for at least 12 months, andfmm 10 consenting.subiects underaoiw wrner aastmintestinalendoscopyfor functional dyspepsia(mean age55.3&ars;range 33-73). &&y s&cimens were pmcesseh-for immunohist&h~&&try with the mousemonoclond anti-humanEcadhti antibody (Zymed LaboratoriesInc., SanFrancisco, CA) at I:400 dilution. As positive contml, normal gastric tissuewas used and,as negativecontrol, e sectionwas incubatedwithout theprimary antibody. The intensity of stainingwas calculatedusing ancxdinal scale (0 to * 0 to 3): +3 = sfmngly positive staining,+2 = moderatelypesltive staining,+I = weak dining, and0 = absenceof staining.Results: In normal duodenumE-cadherin positivity manifestedascrisp b&sol&ml stainingof epithelialcells. This stainingwas strong (+++) throughoutthe @helium without significantchangeain intensity b-stweensurface and crypt level. A similar mttern was seenin treatedcoeliacoatients.In untrated coeliac mtients. the intensitv of epithelial&ieing was weakly (+). Conclusi&: E-z&tin is strongly ani ever& expresseddy epithclium in normal small intestine.The tinding ofreduced membranousE-cadherinexpression in theepithelium of untreatedweliac patientssupports for the view thatE-cadherin down-regulation would panit increasedenterwyle apoptosisin active CD.
NATURAL
HISTORY OF DIGIWTIW NEIJROENDOCRINE TUMORS. Panzuto F Naxmi S. Ciardi S, Moretti A, Cassetta S, Turriziani V, Annelatis. F’emi P*, Corkto VD, DeIle Fave 0.
Backgmoad: an und-i of natural history of digestive Nemocndocrine Tumors (dNETs) is r&red to identify prognostic factors, define different 8xoups of patients with di&cnt prognosis, and plsn proper @eatnerd of the disease. Houwer, few dam are available, because of the rarity, the slow evolution, and the absence of definitive reliable markers of prognosis for these tumors. Aim of this study was to investigate on onset, symptoms and survival rate of dNETs. Patients and methods 104 ots with histoIoaicallv documented dNET 160 without fNF7 and 44 with’ (F) associated sy&ome (26 gastrikss, 16 e&&ids. 1 glucagonoma, 1 VIPoma)] recruited af our h5titution and followKi up for a median of 30 months (range: 4-222). Resuk At diiosis, all F pts were symptomatic, whereas 25% of NF pu had no symptoms and diagnosis was made due to the accidental identification of hmmr lesions. Most frequent onset sympmms in NF -01s were: chronic abdominal pain (30%), appendicitis-Ike (1 I%), rectal bleeding (‘X/o), dyspepsia (6%), bowel obsmtction (6%) and weight loss (5%). In F tumors: abdominal pain (43%). diica (41%), GEBD-like (27%) and flushing (16%). The mean time between onset of symptoms and cl@nosis was 5 (95%1X: 1.4-9.1) end 43 (95%Cl: 41.8-103.8) months in NF and F tumors respectively (p
6 WIRELESS CAPSULE ENDOSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL BLEEDING: PRBLIMlNARY ~KSlJ&~;OF ;;gEw.L4N MULTTCENTRE EXPERIENCE. *E.Rondonotti, *C.Abbiatl, *G.Beccari, “R Luch& “A. Dezi, “L.&apurso, *R.de Franchis and F.P. Rossim. Ga&menterolog -Gastmintestinal Endoscopy Se&e, Dept. of Oncology, ;zy~; d&o~,l, Turin. *Gastroenterology- Gastmintes@al ept of Internal Medicine, Unwersity of Milan, IRCCS &hclinico kospltal, Milan. “Dept. of Gastroentemlogy, S.Fihppo Nen Hospital, Rome, Italy. Backeround: Available techniaues 10identifi bleedme small bowel lesions are &atisfactory The Giwi video cap&e systzm (Given hnaging Ltd.,Yoqneam, Israel) IS a new system designed to ad the gastmenterologist 11,du nosmg small boyel dxases. Aim: $ro assess the uuh of the Given video capsule system m patients wth obscure sastmintesunal ?’GI) bleeding. Methods: The G&en system con&s of three elements: a disposable, swallowable M2A imaging capsule that acquires the video images dtin natural propulsion through the GI tract; a recorder which receives ant records the transmitted data: a cmn~uter workstation for mocessinz. vrewine and reporting of ima es and data ad uired through the Gf tract Between January an%May 2001, 22 patxnts (I6 men, 9 wo,nen, age range 18-62 years) wth obscure and recurrent GI bleeding, in whom previous u per and lower endoscopies were normal, were evaluatedwith this system. & ere were 13 patients with obscure-overt bleedin and I2 patients with obscure-occu!t bleedmg. Push enteroscopy was ped mmed prior to capsule exa?nnatmn m 14 at~ents Two patients were diagnosed to have jejunal angrqdysplaszas, onPy partly responsive to entemscopic treatment. In the remammg patients push entemscopy was normal. The bowel was pr ared with a 24 hour flud diet. An oral purge (polyethylene glywl-based so“p.utmn and/or sulfate purge) was additionally given to I8 patients the day before of the capsule endoscopy. The patients swallowed the capsule after signing an informed consent farm and under continuous medical suoervision. Results: The capsule exlted the body naturally in al patients and no compbcations occurred throughout the study. The capsule remained in the stomach. for an average of 56 minutes (4-240): The avera e small bowel transd time was 220 tmnutes (125.350). The Images of t e small bowel obtamedwere of good quality, especially in patients who took an oral purge. A small,bowel bleeding site was found in 12 of 25 atients: an iodysplasia (41, van~es (2), Crohn’s disease (J), ileal ulcers pI), J~JUX~ ” %,leulafoy’s lesmn (!)! actwe ileal bleeding (I), deal lymphoma (I), traces of blood clots in rbe JCJUIIU~ (I). In this last patient a subsequent push entemscopy ldentltied a jejunal turnour which was missed by the capsule. Capsule endoscopy found a distal sowce of bleeding in 7 of 12 atimts wrtb normal push enterosco ic exams. Overall, findings at capsu changes in mea~cal treatment in 8 patients. to suwcal endoscoqic therapy m J. ., . Co~clusmns: T e Gwen diagnostic imaging system is able to acquire satlsfactoly Images and to identify pathologies m parts of the small bowel which are. be ond the reach of conventional entemscopy. The information pmwded m tit.1s ongoing study was helpful in directmg further diagnostx and therapeutic options in patients with small bowel bleeding.
A2
PROSPECTIVE ANALYSIS OF THE “THREE DAY RULE”. A REGIONAL INITIATIVE FOR URGENT REFERRAL OF UPPER GASTROINTESTINAL. (GI) ENDOSCOPY BY GPs. Background&aim. A new initiative, called the Three Day Rule (TDR), has been intmduced in Lombardy in order to facilitate the earlier diagnosis and treatment of cancer. It requires patients with suspected severe diseases to be seen by a specialist or have a diagnostic procedure done within 3 working days of referral by GPs. In the case of upper GI malignancies, there is little published evidence to support the use of this scheme. Aim of this study has been to assess prospectively the effectiveness and compliance with ‘kDR. Methods. A prospective audit of all referrals for upper GI symptoms under the TDR initiative was done over a 12-month period at a single hospital of Western Milan. We collected demographic data, clinical details, referral cards and final diagnoses on all patients referred for gastmscopy by means of ‘IDR as well as on all outpatients undergoing endoscopy on open access basis during the same period. The appmpriateness of the indications for each request was then reviewed by a gastmenterologist blinded to the outcome of the test. Results. 142 patients were referred for gastmscopy under the TDR scheme and all appointed within 3 working days as compared with 767 patients who were appointed between 7 and 39 working days (median 22 days) on open access basis. 6% had a final diagnosis of cesophageal/gastric cancer in the TDR group as compared to only 1% in the open assess group (p
/No
j
/
I
~, 51/o
/64%
/
“.-
< 0.01 39% of aukscopies were rated as inappropriate in the open access group as compared with 22% in the TDR grow (wO.01). Conclusions. Significantly m&e up&r GI &mcers can be seen and a diagnosis of serious upper GI diseases made within a short period to comply with the TDR scheme. However, some GPs appear to over read alarm symptoms, end this may lead to inappropriate referrals. Better awareness of appropriate urgent refenal criteria is needed in order to ensure that resources for this initiative are used efficiently. /