Metaplazia de tip Barrett definesteprezenta in esofagul distal, la maimult de 1 cm de margineaproximala a pliurilor de pemareacurburagastrica, a epiteliului de tip cilindricspecializat, atestatprinprezentacelulelorcaliciforme.
The incidence of esophageal adenocarcinoma has risen approximately six-fold in the U.S. and has increased in the last three decades in the Western World. It is rising faster than breast cancer, prostate cancer, or melanoma.
Endoscopic treatment of early Barrett’s neoplasia by endoscopic resection or ablative therapy has showngood short term clinical outcomes. Yet, no study answered two essential questions: 1. are they efficient for the prevention for a long time of adenocarcinoma? 2. do they allow to supress the endoscopical surveillance?
EMR is indicated for lesions with noninvasive high-grade neoplasias that include high-grade intraepithelial neoplasia(HGIN) and well- and moderately differentiated intramucosal cancers (IMC) with no evidence of local and regional lymph node metastasis on endoscopic ultrasound.There is no consensus on the maximal size, although circumferential lesions are usually avoided because of potentials for stricture formation.
The risk for lymph node metastases is 0% for cancer limited to the mucosal layer. When there is submucosalinvolvement, nodal metastases may occur in 23–69%.
Patient’s platelet counts and coagulation profile should be checked prior to EMR.
If a normal ligation device were to be used in EMRL, the endoscope would have to be withdrawn several times to allow extensive resection.EMRC is not ideal for repeat resection because the braided snare is easily deformed after single use.
Evidentierea leziunilor esofagiene dupa coloratia cu albastru de metilen prin tehnica de magnificatie: leziuni in diferite stadii de displazie.
(A) The tissue has been pinned at its periphery onto a backing with thin needles immediately after its resection. (B) After an overnight immersion in formalin, the specimen is sectioned at 2-mm intervals. All sections are analyzed and invasive cancer is localized within the entire resected specimen for accurate staging.
in order to obtain a complete eradication of the intestinal metaplasia
Substanta fotosensibila se injecteaza in organism (2mg/kg) si se acumuleaza preferential la nivelul celulelor tumoraleActivataprin expunereala lumina laser cu o anumita lungime de unda (630 nm) – dupa 48 ore.Determina trecerea oxigenului din stare normala triplet la oxigen singlet-foartereactiv, determinand moartea celulara- Reacţie chimică NU termică
History• 77 y/o man with longstanding history of reflux: ▫ Heartburn ▫ Regurgitation• April 2010: ▫ Barrett‟s esophagus without dysplasia ▫ PPI 40mg bid• Family history: negative• Medical history: ▫ Hypercolesterolemia ▫ Benign prostatic hypertrophy ▫ Lower limbs varicose disease
3Physical Exam and Laboratory• GI and systemic enquiry was negative• Physical exam was normal.• Laboratory: hypercolesterolemia• Abdominal ultrasound: ▫ liver steatosis ▫ benign prostate hypertrophy
Barrett’s Esophagus• Replacement of the lower oesophageal squamous mucosa by metaplastic glandular epithelium resulting from gastroesophageal reflux• Red (columnar) mucosa in the esophagus; variable length
• Endoscopy with biopsy is still the gold standard for making the diagnosis of Barretts esophagus, even though it is not 100%.• Endoscopy defined the Barrett‟s mucosal segment as 10 cm long; partly circumferential• Gastric antral ulcer of 9-10mm• Helicobacter pylori positive• Biopsies demonstrate goblet cells• Biopsy showed multifocal HGD
Barrett’s esophagus• 1.7% all endoscopies showed Barrett‟s 1 ▫ 9.6% GERD also had Barrett‟s• Barrett‟s patients develop adenocarcinoma at a rate of ~ 0.5% per year 2 ▫ 40 X increased incidence of cancer as compared to the general population• In the presence of high grade intraepithelial neoplasia (HGIN), disease may progress at rates >10% per year31 Phillips and Wong, Gastroenterol Clin North Am 19912 P. Sharma et al, Clinical Gastroenterol Hepatol 20063 Seewald S, Postgrad Med J 2007
Second Step Diagnosis• Barrett Esophagus with High Grade Dysplasia (HGD)• Liver Steatosis• Benign Prostate Hypertrophy• Hypercolesterolemia• Lower Limb Varicose Disease
What are the concerns with HGD?• High risk of progression to cancer,• High risk of coexisting cancer,• Difficulty in differentiating HGD from intramucosal cancer
Screening for Barrett’s• Barrett‟s most common in older white males with GERD ▫ Predictors: age > 40y, heartburn, long duration of GERD sx (> 13 years), male gender; sensitivity of heartburn is low Conio , Int J Cancer 2002;97:225-9• 85% of EAC occurs in white males ▫ 3 studies show asymptomatic cases
Surveillance: No dysplasiaDocumentation: Follow-up:• 2 EGDs with biopsy • Every 3 years within 1 year
Surveillance:Low-grade dysplasiaDocumentation: Follow-up: • Every year until no• Repeat EGD and dysplasia X 2 biopsies within 6 months• Expert pathologist confirmation
Surveillance: High Grade DysplasiaDocumentation: Follow-up:• Repeat endoscopy • Every 3 months or within 3 months treatment based on results and patient• Expert pathologist factors confirmation• EMR (endoscopic mucosal resection) of all mucosal irregularities
19Staging:• CT chest/abdomen were normal• The patient was subsequently referred for EMR
Indications for endoscopic mucosalresection in Barrett’s esophagus• High grade intraepithelial neoplasia• Well or moderately differentiated T1 m intramucosal cancer• Absence of suspicious surrounding lymph nodes by endoscopic ultrasound / CT
Depth of T1 carcinoma m1, m2, m3, and sm1 lesions could be treated endoscopically if the lesions are <30 mm, well and moderately differentiated, and without lymphangitic invasionConio M et al, Am J Gastroenterol 2006
Incidence of nodal metastasis for T1adenocarcinoma of the esophagus• M1, M2, M3, SM1: 0%• SM2: 23%• SM3: 69%Buskens et al, Gastrointest Endosc 2004
Patient preparation patient‟s platelet counts and coagulation profile ◦ EMR is contraindicated if platelet count is less than 50,000 mm3 and/or international normalized ratio (INR) more than 1.4. patients who are on aspirin (ASS) should stop taking their medication 1 wk prior to EMR. oral anticoagulation such as warfarin should be switched to low-molecular weight heparin (LMWH) injections and the injection should not be administered on the day of the procedure known gastroesophageal reflux disease should be treated with a high-dose proton pump inhibitor at least for 2 wk prior to EMR.
EMR• En bloc ▫ maximum recommended diameter for en bloc resection is 20 mm• Piece-meal resection ▫ increases the complication rate, ▫ the histologic assessment of the margins is difficult, ▫ the recurrence risk is higher
• Common EMR techniques for Barrett‟s oesophagus: A. Inject and cut technique B. Simple snare resection technique C. Cap assisted EMR D. EMR with ligation• EMR strategies used for Barrett‟s oesophagus: ▫ Localised EMR ▫ Circumferential EMR
Localised EMR Circumferential EMRthe area with HGIN and IMC is both the diseased area as well as alltargeted and resected underlying Barrett‟s mucosa is completely resectedall of the four techniques „„simple snare resection‟‟ technique, the „„inject and cut‟‟ technique, and EMRL using the Duette Multiband Mucosectomy Kit.Local recurrence- 24.4% (Lopes CV, et Local recurrence- 9.52% (Giovanini M,al Surg Endosc 2007) Endoscopy 2004)Combined with PDT and APC Piecemeal resection is unavoidable •One single setting is associated with stricture formation • Conditions for a complete resection are most optimal in the first EMR session. •In further sessions fibrosis with scar formation makes EMR more difficult
1. Identify longitudinal/circumferential extent of lesion, using chromoendoscopy if necessary (methylene blue)Chromoendoscopy (methylene blue): one flat lesion andone exulcerated lesion
2. Magnifying view: lesions with different grades of dysplasia
3. Lift the lesion (submucosal injection)4. “Suck-and-ligate” technique: the lesion has been aspirated into the variceal ligating device, then the rubber band has been released
Postprocedure• Most EMR procedures can be performed on an outpatient basis.• Patients are allowed soft diet after they are fully awake and advised to continue on soft diet for 2 wk after every EMR session.• Patients are continued on a high-dose proton pump inhibitor.
Reccurence• 26 patients with BE and HGD/IMC• Persistent endoscopic and histologic eradication of BE at 28 months- 87.5%• 2 patients –Barrett epithelium was detected beneath the neosquamous epithelium 3 months after EMRLarghi A et al, Endoscopy 2007
Summary• EMR- first line of therapy if there is any evidence of HGD and /or an intra-mucosal ADC within a Barrett‟s mucosa.• EMR avoid the morbidity associated with esophagectomy• Patients must be carefully selected to assure early stage disease without the potential for nodal metastases• Dysplasia and invasive carcinoma may be multifocal• Even small tumors can be associated with nodal metastases, particularly once the submucosa is involved
Third Step Diagnosis• Barrett‟s Esophagus with High Grade Dysplasia (HGD) and Intramucosal Cancer treated with EMR.• Liver Steatosis• Benign Prostate Hypertrophy• Hypercolesterolemia• Lower Limb Varicose Disease
PDT• Complimentary method in order to obtain a complete eradication of the intestinal metaplasia.• Can be used as a rescue procedure if the EMR results are unsatisfactory (persistence of HGD on biopsy).• Can also be used as an alternative to EMR in case of diffuse HGD? • No data in the literature • Lack of tissue for histological assessment • crucial for determining treatment adequacy,the ablation may be incomplete, with remnant Barrett‟s mucosa post treatment • the persistent Barrett‟s oesophagus will remain at risk for progression to adenocarcinoma
• PDT treatment was given to the distal 5 cms segment in December 2010• Patient tolerated the treatment well.• Endoscopy did not reveal any areas of narrowing.• He has been continued on Esomeprazole 40 mgm bid.• Follow up - March 2011
Removal of IM may be comparable to removal ofcolon polyps in terms of cancer prevention andavoidance of esophagectomy
When is Barrett’s mucosa truly eliminated ? • 25 patients who had BE (~5cm length) eliminated by PDT were followed for a period of~23 mo • Results: ▫ 15/25 no recurrence ▫ 10/25 recurred in ~10 mo ▫ 8/10 no evidence of IM in the first set of bx, ▫ 2/10 had IM in the second sets of bx ▫ 6 pts - IM was detected in the third sets of biopsies. • Recommendation : ▫ Absence of IM should only be accepted after min 3 neg sets of biopsies.Wang KK et al. Barrett‟s esophagus after photodynamic therapy: risk of cancer development duringlong term follow-up. Gastroenterology 2004; 126 (suppl 2): A-50
PDT-complications• For all ablative methods think of the residual glands under the reepithelialised squamous epithelium (“buried glands”)
Photodynamic therapy for ablation of highgrade dysplasia in Barretts esophagus * p<0.05 PDT plus omeprazole omeprazole HGD ablated 106/138 [77%] 27/70 [39%]* Incidence of 13% (n=18) 28% (n=20) * adenocarcinoma Reduced risk of cancer by 50% (did not eliminate it) Adverse events 94% 13% * • Overholt BF et al, Gastrointest Endosc. 2005
EMR and PDT for Barrett’s Esophaguswith HGD• 115 patients – 96 with IMC – 19 with HGD• Results: – Average follow=34±10 months – Complete local remission in 98% – Complication rate:9,5% – 30% metachronous lesions in follow-up period; all but one retreated endoscopically May et al, Eur J Gastroenterol Hepatol 2002
PDT: T1 esophageal cancer• Prospective cohort• 80 (74 with EAC) patients• 10 patients required 2nd treatment• Five-year survival=97%• No cancer related death• Complete remission: ▫ PDT alone 90% ▫ PDT+EMR 95% Cahlia et al, DDW 2005
PDT• Avantages : ▫ Unifocal and multifocal lesions ▫ May be associated to other techniques ▫ Technique easy to perform ▫ Can be repeated in 48 hours• Disadvantages : ▫ Photosensibility and strictures risk patient education ▫ Pleural effusion ▫ Atrial fibrillation
Related issues - Chemoprevention• NSAIDs ▫ OR for cancer - case control studies 0.57(0.47- 0.71) ▫ RCT of celecoxib: no benefit• PPIs ▫ 2 retrospective cohort studies suggest benefit Large scale trials with aspirin and PPIs are underway
Related issues: Reflux control inBarrett’s Esophagus• PPIs or surgery should be directed to symptom control• No convincing evidence that either PPIs or surgery prevent EAC
Third Step Diagnosis• Barrett‟s Esophagus with High Grade Dysplasia (HGD) and Intramucosal Cancer treated with EMR and PDT.• Liver Steatosis• Benign Prostate Hypertrophy• Hypercolesterolemia• Lower Limb Varicose Disease
Conclusions• Screening commonly in high risk groups• Surveillance now standard of care• Dysplasia level still guides surveillance protocols• Endoscopic treatment now accepted as first line approach to HGD and T1 cancer