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barrett's esophagus in SOT patients [1440].pptx
- 1. NEOPLASTIC PROGRESSION OF BARRETT’S ESOPHAGUS AMONG ORGAN TRANSPLANT RECIPIENTS Dr. Vidhi Patel, Research Fellow, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio May 6, 2023 Digestive Disease Week 2023
- 2. BACKGROUND: High risk of neoplastic progression in Barrett’s esophagus patients who undergo solid organ transplantation (SOT) and immunosuppressants. Case series Case reports Lack of control population
- 3. AIMS: Rates of neoplastic progression in BE patients with h/o SOT Compare it to controls Identify predictors of progression
- 4. METHODS: Retrospective study Adult patients with a confirmed diagnosis of BE (2000- 2022) Three groups of BE patients- Group I- underwent SOT Group II- no SOT but with immunosuppressants Group III- no SOT and without immunosuppressants
- 5. Variables: Demographics immunosuppressants use H/o fundoplication, SOT Endoscopic and histological findings Follow up time from the index EGD to development of HGD/EAC or death or to the latest EGD in patients who did not progress.
- 6. GROUP I SOT N=115 • Lung= 35 • Liver= 34 • Kidney= 32 • Heart= 14 • Pancreas= 2 RESULTS: GROUP II No SOT, with IS N= 704 No SOT, without IS N= 2647 GROUP II GROUP III BE N= 3466
- 7. Factor Group I (SOT+) (N= 115) Group II (SOT-,IS+) (N=704) Group III (SOT-,IS-) (N=2,647) Group I vs. Group II Group I vs. Group III Age (years) 57.7 ± 11.1 61.1 ± 12.0 60.4 ± 13.0 0.005 0.011 Male sex 102 (88.7) 484 (68.8) 1,876 (70.9) <0.001 <0.001 Race - White 109 (98.2) 677 (96.2) 2,512 (94.9) 0.37 0.17 BMI (kg/m2) 27.5 ± 4.6 29.6 ± 5.7 29.5 ± 5.7 <0.001 <0.001 H/o alcohol use 45 (40.2) 385 (59.6) 1,288 (59.4) <0.001 <0.001 H/o tobacco use 77 (66.9) 430 (65.0) 1427 (62.9) 0.056 0.007 Immunosuppressant use: -Calcineurin inhibitors 102 (88.7) 214 (30.4) 0 (0.00) <0.001 -- -m-TOR inhibitors 22 (19.1) 27 (3.8) 0 (0.00) <0.001 -- -Anti-proliferative drugs 95 (82.6) 333 (47.3) 0 (0.00) <0.001 -- -Glucocorticoids 111 (96.5) 259 (36.8) 0 (0.00) <0.001 -- -Biological agents 26 (22.6) 99 (14.1) 0 (0.00) 0.018 -- Demographics and Immunosuppressant Use:
- 8. Factor Group I (SOT+) (N= 115) Group II (SOT-, IS+) (N=704) Group III (SOT-, IS+) (N=2,647) Group I vs. Group II Group I vs. Group III No. of EGDs 2.0 (2.0, 3.0) 3.0 (2.0, 6.0) 3.0 (1.00, 5.0) <0.001 <0.001 Presence of HH 51 (44.3) 444 (63.1) 1,703 (64.3) <0.001 <0.001 BE length (cm) 1.00 (0.90, 2.9) 2.0 (1.00, 4.0) 2.0 (1.00, 5.0) <0.001 <0.001 Visible lesions: 0.012 0.002 -None 95 (82.6) 612 (86.9) 2,300 (86.9) -Erosive Esophagitis 18 (15.7) 47 (6.7) 169 (6.4) -Stricture 0 (0.00) 15 (2.1) 52 (2.0) -Nodularity 2 (1.7) 23 (3.3) 108 (4.1) -Plaque 0 (0.00) 2 (0.28) 6 (0.23) -Mass 0 (0.00) 5 (0.71) 12 (0.45) Histology: 0.23 0.18 -NDBE 97 (84.3) 559 (79.4) 2,092 (79.0) -IND 5 (4.3) 36 (5.1) 129 (4.9) -LGD 6 (5.2) 46 (6.5) 188 (7.1) -HGD 4 (3.5) 49 (7.0) 190 (7.2) -EAC 2 (1.7) 13 (1.8) 40 (1.5) -Invasive Cancer 1 (0.87) 1 (0.14) 8 (0.30) Endoscopic and Histologic Characteristics
- 9. Group I (SOT+) (N=78) Group II (SOT-, IS+) (N=480) Group III (SOT-, IS-) (N=1,526) P-value Progression to HGD/EAC, n (%) 2 (2.6) 30 (6.3) 80 (5.2) 0.37 Outcomes, n (%) 0.22 -to LGD 1 (1.3) 24 (5.0) 94 (6.2) -to HGD 1 (1.3) 11 (2.3) 46 (3.0) -to EAC 1 (1.3) 13 (2.7) 25 (1.6) -to Invasive cancer 0 (0.00) 6 (1.3) 9 (0.59) Median duration of f/u (years), 2.9 (1.1, 6.7) 2,3 5.4 (2.8, 9.5) 1 5.1 (2.6, 9.1) <0.001 Progression rate per 100 years (95%CI) 0.61(0.15,2.44) 0.94(0.66,1.35) 0.82(0.66,1.02) 0.72 Incidence Cohort (NDBE + > 1 EGD) median follow-up of 5.1 years
- 10. Factor OR P-value Age (for every 5 year increment) 1.26 (1.19, 1.33) <0.001 Male Sex 3.36 (2.43, 4.66) <0.001 Race -African American vs. Caucasian 0.39 (0.12, 1.30) 0.12 -Other vs. Caucasian 1.17 (0.58, 2.37) 0.66 BE length (for every 1 cm increment) 1.15 (1.11, 1.19) <0.001 Presence of Hiatal hernia 1.51 (1.16, 1.95) 0.002 BMI (for every 5kg/m2 increment) 1.26 (1.13, 1.41) <0.001 H/o alcohol use 0.82 (0.65, 1.05) 0.12 H/o immunosuppressant use 1.38 (1.04, 1.82) 0.025 H/o SOT 0.39 (0.15, 1.01) 0.053 Fundoplication before HGD/EAC 0.04 (0.01, 0.30) 0.002 Predictors associated with HGD/EAC: Multivariate analysis
- 11. CONCLUSION: Immunosuppression is a risk factor for HGD/EAC in BE patients. No differences in progression rates in BE pts after SOT compared to general BE population. Studies with longer f/u required Further exploratory studies on the risk of BE progression with immunosuppressants warranted.
Editor's Notes
- Good Morning everyone. I am Vidhi Patel, Research Fellow at Department of Gastroenterology and Hepatology, Cleveland Clinic, Ohio. Thank you to all my co-authors and also all the Moderators for inviting me at DDW. Today, I am going to present on Neoplastic progression of Barrett’s esophagus among organ transplant recipients,
- There are few studies reporting SOT and associated immunosuppression as risk factors for BE and EAC. There are mainly case reports/case series showing high rates of neoplastic progression of BE in such patients. However, a lack of control group in these studies prevents from drawing meaningful conclusions. Whether the higher rates of progression are due to transplant status or due to immunosuppression or observer bias remains unanswered by these studies.
- Therefore, in this study of BE patients, we aimed to 1) determine the rates of neoplastic progression in those who underwent SOT, 2) compare the rates of progression to controls and 3) also assess the predictors associated with neoplastic progression.
- This retrospective study included patients with BE seen in Cleveland Clinic and affiliated hospitals between January 2000 and August 2022. BE patients underwent surveillance EGD based on prevailing guidelines from major societies. BE patients were classified into three groups: Group I- underwent SOT, Group II- patients who did not undergo SOT but were on chronic immunosuppressants and Group III- patients who did not undergo SOT and also were not on any immunosuppressants.
- Basic demographic data including age, sex, race, alcohol and tobacco use, BMI, duration of follow-up were collected. The total no. of EGDs underwent by each patient and also their EGD findings including hiatal hernia size, BE segment length, visible abnormalities along with the histological findings were noted. Date and type of SOT, and history of fundoplication if any was obtained. F/up was calculated from the time of the index EGD to development of HGD/EAC or death or to the latest EGD in patients who did not progress.
- A total of 3466 patients were identified to have BE with a mean age of 60.5 years. Of these, 115 patients had SOT (lung =35, liver=34, kidney=32, heart=14 and pancreas=2; multiple transplants=2) during the study period (group I). In the remaining patients, 704 were on immunosuppressants for ≥3 months (group II) and 2647 did not undergo SOT and were never on any immunosuppressants (group III).
- On comparison with Group 2 And Group 3, Group 1 was more likely to be younger in age, male sex and had lower BMI. Although both group 1and 2 were on immunosuppressants, SOT group (Group I) was more likely to be on multiple immunosuppressants compared to Group II. calcineurin inhibitors (cyclosporine, tacrolimus), mammalian target of rapamycin (m-TOR) inhibitors (sirolimus, everolimus, and temsirolimus), anti-proliferative drugs (azathioprine, methotrexate, cyclophosphamide, chlorambucil and mycophenolate mofetil); glucocorticoids (prednisone, prednisolone); and biological agents (tumor necrosis factor (TNF) alpha inhibitors- etanercept, infliximab, adalimumab; interleukin-2 receptor antagonists- basiliximab, daclizumab; anti-CD3 antibody- muromonab CD3; polyclonal antibodies- anti-thymocyte antibody (ATG), rho (D) immune globulin).
- organ transplant group also had fewer number of EGDs with shorter BE segment and lower prevalence of hiatal hernia. Erosive esophagitis was seen more in solid organ transplant group. There was no significant differences in the histologic findings on index EGD.
- After excluding the BE patients with dysplasia/EAC, 2084 pts who had NDBE and ≥1 EGD constituted the incidence cohort. During the median follow-up of 5.1 years, 2.6% in Group I, 6.3% in Group II and 5.2% in Group III progressed to HGD/EAC.
- On multivariate analysis, risk factors associated with HGD/ EAC were older age, male gender, longer BE segment, presence hiatal hernia and higher BMI. BE patients with immunosuppressants use had 38% higher risk of progression to HGD/EAC. It was interesting to note that Fundoplication showed protective role against HGD/EAC in our study. The reason we can look at those two variables separately in the model is that there are really comparing the 3 groups of patients that we have (Transplant, No Transplant w/immuno, Transplant w/out immuno). The terms in the model in Table 2.6 reflect the effect of being on immunosuppressants vs. not, and then additionally having an organ transplant (above and beyond using immunosuppressants). So we are using 2 terms to reflect the comparisons among these 3 groups. Alternatively, we could have just used the 3-level group variable as a predictor instead of the two separate variables, and would have gotten similar results. See Table 2.7 in the attached document. Here, as in 2.6 the No Transplant w/immuno effect is the same, but the effect of the Transplant group differs because it’s being compared to the No Transplant/No immuno group, rather than the No Transplant w/immuno group as it is in Table 2.6. Note that the effects of the other variables are exactly the same regardless of how we include these factors in the model.
- Based on this study, we conclude that immunosuppression is a risk factor for HGD/EAC in BE patients. Reassuringly, we have not observed any higher progression rates in BE patients after SOT compared to general BE population. Although studies with longer follow up are required, our data do not support more frequent surveillance of BE in SOT patients. Further exploratory studies on the risk of BE progression with individual class of immunosuppressive drugs are warranted.