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![ESCC Possible Risk Factors
Low-Risk Populations
• Tobacco
• Alcohol
• Low SES
High-Risk Populations
• [Tobacco, alcohol]
• Diet (low selenium)
• Tobacco carcinogens from
other sources:
• PAHs
• Nitrosamines
• Acetaldehyde
• Poor oral health
• Hot drinks
• Low SES
• Family history](https://image.slidesharecdn.com/studyoftenwekesophagealsquamousdysplasiaprevalencebymichaelmwachiro-steveburgert-141214232715-conversion-gate01/75/Study-of-tenwek-esophageal-squamous-dysplasia-prevalence-by-michael-mwachiro-steve-burgert-28-2048.jpg)
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Study of tenwek esophageal squamous dysplasia prevalence by michael mwachiro steve burgert
- 1. Study of TenwekEsophageal Squamous Dysplasia Prevalence: The STEP study KESHO Conference 29th November 2014 ∞ Principal Investigator, Michael Mwachiro MBChB Presented by Co-Investigator, Stephen L. Burgert, MD Tenwek Hospital – Bomet, Kenya
- 2. TENWEK STEP STUDYTEAM • Michael M Mwachiro MBChB1, Principal Investigator • Stephen L Burgert MD1, • Wairimu Waweru MBChB, MMED2, • Russell E White MD, MPH, FACS1, • Collins Bett1 • Robert Chepkwony, KRCHN1 • Jessie Githanga MBChB, MMED2, • Sanford M Dawsey MD3 • Mark Topazian, MD4 1Tenwek Hospital, Bomet, Kenya; 2Department of Pathology, University of Nairobi School of Medicine, Nairobi, Kenya; 3National Cancer Institute, Bethesda, MD, USA. 4Mayo Clinic, Rochester, MN, USA.
- 4. Esophageal Cancer -Worldwide • Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related death in the world, with an estimated 482,000 new cases and 407,000 deaths in 2008 (1) • High rates of esophageal cancer are found along geographic belts, one following the ancient Silk Road from north central China through the central Asian republics to northern Iran, and one from eastern to southern Africa 1. Jemal A, Bray F, CenterMM,Ferlay J, Ward E, FormanD. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.
- 5. Geographic Variation ofEsophageal Cancer Low-Risk High-Risk Rates <10 50 -100+ M:F 3 - 4:1 1 - 1.5:1 % ESCC 40-50% 90%
- 6. Nairobi Cancer RegistryReport 2004-2008 MEN: Esophageal Cancer is the second most common cancer (after Prostate Cancer) WOMEN: Esophageal Cancer is the third most common cancer (after Breast and Cervical Cancer) A. Korir, N. Okerosi, DM Parkin 14th May 2014
- 7. Squamous Cell EsophagealCancer vs. Adenocarcinoma of the Esophagus Worldwide in developing countries the vast majority of esophageal cancers are of squamous cell pathology.
- 10. Tenwek Hospital EndoscopyServices - 2012 • 2,030 endoscopy cases • 484 patients with esophageal cancer • 145 patients with gastric/duodenal cancer • 319 esophageal stents placed
- 11. White RE, AbnetCC, Mungatana CZ, Dawsey SM. Oesophageal cancer: A common malignancy in young people of Bomet District, Kenya. Lancet 2002; 36(9331): 462-63.
- 12. Parker RK, DawseySM, Abnet CC, White RE. Frequent occurrence of esophageal cancer in young people in western Kenya. Diseases of the Esophagus 2010 (20): 128-135.
- 14. Challenges in aDeveloping Country • Inadequate Reporting System • Fatalistic Attitude • Late Presentation • Inconsistent Referral Patterns • Traditional Healers/Treatment • Chemotherapy and Radiation Therapy Usually Not Available • Financial Constraints
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- 18. Esophageal CA –post-dilation
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- 21. After esophageal stentplacement – drinking from the “Ceremonial Cup”
- 22. Survival Following Treatmentat Tenwek Hospital • Stenting alone – Median Survival 9 months – Dysphagia score 0-2 at time of death • Surgery alone – Median survival 24 months stage I and II – Median survival 14 months stage III and IV
- 23. Esophageal Dysplasia •Dysplasia has been shown to be an important element along the pathway leading to development of Esophageal Carcinoma- both for Adenocarcinoma and Squamous Cell carcinoma • Interventions at eradicating the dysplasia would be useful in stopping the progression to carcinoma
- 24. Esophageal Squamous dysplasia- Histology
- 25. Dysplasia – HistologyCriteria • Squamous dysplasia requires – the presence of nuclear atypia (enlargement, pleomorphism, and hyperchromasia) – loss of normal cell polarity, – and abnormal tissue maturation without invasion of epithelial cells through the basement membrane
- 26. Grading of EsophagealSquamous Dysplasia • Mild dysplasia - these abnormalities are confined to the lower third of the epithelium • Moderate dysplasia - they are present in the lower two thirds of the epithelium • Severe dysplasia - they also involve the upper third of the epithelium. • Full thickness involvement of the epithelium, called carcinoma in situ by some, is considered synonymous with severe dysplasia based on their similar histologic appearance
- 27. Esophageal Squamous Dysplasia Progression in China Over a total of 13.5 years for the Linxian cohort Esophageal Squamous Cell Carcinoma developed in: 8% of participants with normal histology (baseline positive cytology sample) 24% with mild dysplasia 50% with moderate dysplasia 74% with severe dysplasia 58% with dysplasia NOS (not otherwise specified) and 75% with carcinoma in situ Wang et al Gut 2005
- 28. ESCC Possible RiskFactors Low-Risk Populations • Tobacco • Alcohol • Low SES High-Risk Populations • [Tobacco, alcohol] • Diet (low selenium) • Tobacco carcinogens from other sources: • PAHs • Nitrosamines • Acetaldehyde • Poor oral health • Hot drinks • Low SES • Family history
- 29. OVERALL OBJECTIVES •Esophageal squamous cell cancer (ESCC) is a common malignancy in the developing world and is the leading cancer diagnosis at Tenwek Hospital, a referral hospital in western Kenya. • Our long-term goal is to understand the pathogenesis and risk factors for ESCC in Kenya, and to establish effective screening and prevention programs. • To provide effective treatment options for patients identified with esophageal squamous dysplasia.
- 30. Study of TenwekEsophageal Squamous Dysplasia Prevalence: The STEP study
- 31. STEP study •Study of • Tenwek • Esophageal Squamous Dysplasia • Prevalence
- 32. OBJECTIVE – STEPStudy • We hypothesized that asymptomatic esophageal squamous dysplasia (ESD), the precursor lesion of ESCC, is common in our region, raising the possibility of screening for ESD to prevent ESCC. • This study aimed to determine the prevalence of ESD in adult residents in the traditional Tenwek Hospital catchment area and to explore the impact of demographic data and environmental exposures on the prevalence of ESD.
- 33. METHODS: • 305**asymptomatic adult residents of villages within 50 km of Tenwek Hospital completed a detailed survey and underwent trans-oral videoendoscopy of the esophagus with Lugol’s chromoendoscopy, mapping of identified lesions, and biopsy. • Each subject was classified by their worst biopsy diagnosis, and the overall prevalence of ESD, the age-adjusted prevalence of ESD and the sex- and age-specific prevalence of ESD by decade will be calculated. • The association between potential risk factors and ESD was analyzed by univariate and multivariate logistic regression.
- 34. Inclusion Criteria •Residence within 50 kms of Tenwek Hospital • Age between 20-79 years • Exclusion of the following symptoms and allergies • Dysphagia • Odynophagia • Haematemsis • Weight loss • Allergy to iodine • Allergy to lidocaine • Exclusion of significant health problems such as: • Bleeding disorders • Heart arrhythmias • Diabetes • Lung disease or breathing problems • Stroke • Subject should be fasting/NPO (Nil Per Oral) from previous night
- 35. Recruitment Model Administrators Community level Tenwek Hospital
- 36. Zone A ZoneC Zone B
- 38. Meeting at thevillage
- 39. Going through the consent form and questionnaire
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- 41. Making up ofLugol’s iodine solution • Lugol’s iodine stain: 12g I2 + 24g KI in 1L H2O • Make it up yourself: right formula, fresh • Iodine reversibly stains glycogen (abundant in normal superficial squamous cells, absent in rapidly dividing cells); → normal epithelium is brown, dysplasia is unstained
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- 43. Esophageal dysplasia –before Lugol’s stain
- 44. Esophageal dysplasia –after Lugol’s stain
- 45. Extracting biopsy fromforceps
- 46.
- 47. • So whatdid we find? Results and Discussion
- 48. RESULTS • Subjectaccrual is currently completed. Results are presented for 305 patients. (complete histologic and endoscopic data) • Enrollment up to this time had been 313 subjects • Subject drop-out rate was 3.6% and subject compliance was 97.5%
- 49. Table 1: Characteristicsof participants who were screened in the STEP study (n=305) Characteristic N (%) Total 305 Age, years (mean, SD) 46.7 (15.5) < 50 163 (53) ≥ 50 142 (47) Male 163 (53) Location A 98 (32) B 61 (20) C 145 (48) Kalenjin ethnicity 304 (99.7) Education, post-primary 105 (34) Tobacco smokers 60 (20) Alcohol drinkers 98 (32) Family history of cancer 34 (11) Family history of esophageal cancer 19 (6)
- 50. Table 2: HistologicDiagnosis Diagnosis Number N (%) Normal 115 37 Mild esophagitis 119 39 Moderate- severe esophagitis 27 9 Mild dysplasia 35 11.5 Moderate dysplasia 8 2.6 Severe dysplasia 1 0.3
- 51. Table 3: Prevalenceof esophageal squamous dysplasia, by participant characteristics, in the STEP study Worst Biopsy Diagnosis Characteristic Normal Dysplasia Dysplasia Prevalence (n=261) (n=44) (%, 95% CI) p-value Mean age (mean, SD) 46 (15) 51 (15) 0.04 Sex Male 137 26 16 (11-22) Female 124 18 13 (8-19) 0.5 Location A 79 19 19 (12-29) B 48 13 21 (12-34) C 133 12 8 (4-14) 0.01 Post primary education No 166 34 17 (12-23) Yes 95 10 10 (5-17) 0.09 Tobacco smokers No 214 31 13 (9-17) Yes 47 13 22 (12-34) 0.1 Alcohol drinkers No 185 21 10 (6-15) Yes 75 23 23 (16-33) 0.003 Family history of cancer No 232 39 14 (10-19) Yes 29 5 15 (5-31) 1.00 Family history of esophageal cancer No 243 42 15 (11-19) Yes 17 2 11 (1-33) 1.00
- 52. Table 4: Prevalenceof esophageal squamous dysplasia (ESD) by age and sex in the STEP study Characteristic Worst Biopsy Diagnosis Normal1 Dysplasia2 Dysplasia Prevalence (n= 261) (n=44) (%, 95% CI) Age <30 49 3 6 (1-16) 30-39 57 9 14 (6-24) 40-49 39 6 13 (5-27) 50-59 57 10 15 (7-26) ≥60 59 16 21 (13-32) Age: Male <30 21 2 9 (1-28) 30-39 31 4 11 (3-27) 40-49 21 3 13 (3-32) 50-59 29 8 22 (9-38) ≥60 35 9 20 (10-35) Age: Female <30 28 1 3 (0.1-18) 30-39 26 5 16 (5-34) 40-49 18 3 14 (3-36) 50-59 28 2 7 (1-22) ≥60 24 7 23 (10-41) 1 Includes normal squamous epithelium and esophagitis 2 Includes mild, moderate and severe dysplasia
- 53. Table 5: Distributionof Unstained Lesions (USLs) and Dysplasia Biopsies in the STEP Study Location USLs (%) Dysplasia Biopsies (%) Upper third 11 (3) 2 (4) Middle third 153 (44) 28 (58) Lower third 180 (52) 18 (38) Total 344 (100) 48 (100)
- 54. Table 6: ScreeningCharacteristics of Unstained Lesions (USLs) for Identifying Dysplasia in the STEP study Dysplasia + - USL + 27 175 202 - 13 200 213 40 375 415 % (95% CI) Sensitivity 27/40 68 (50-81) Specificity 200/375 53 (48-58) PPV 27/202 13 (9-19) NPV 200/213 94 (90-97)
- 55. Assuming that the305 subjects who underwent endoscopy are representative of the Bomet population: 14 % of asymptomatic adults exhibit squamous cell dysplasia of the esophagus Actual prevalence is probably higher, given 68% sensitivity of tool A previous screening study of 5760 subjects done by Tenwek with cytology balloon sampling had a dysplasia prevalence rate of 2.6% and a 56% sensitivity* *White RE, et al. Esophageal dysplasia in asymptomatic residents of western Kenya: Interim results of a cytologic and endoscopic screening program. Gastroenterology 2004; 126: A24.
- 56. Table 7: Univariateand multivariable adjusted odds ratios of dysplasia in STEP study Odds ratios (95% CI) Characteristic Univariate Multivariate Age 1.02 (1.00, 1.04) 1.01 (0.99-1.04) Male 1.31 (0.68-2.50) 0.87 (0.41-1.87) Location (Compared to C) A 2.67 (1.23-5.78) 2.55 (1.14-5.72) B 3.00 (1.28-7.03) 2.84 (1.19-6.78) Tobacco smokers 1.90 (0.93-3.93) 0.86 (0.34-2.19) Alcohol drinkers 2.70 (1.41- 5.17) 2.35 (1.11-6.04) Family history of cancer 1.03 (0.37-2.81) 0.90 (0.32-2.56)
- 57. Dysplasia in Chinaand Iran • in a 2002 endoscopic screening study in Linxian China (where 15% of the people die of esophageal cancer), which was restricted to asymptomatic subjects 50-64 years old, the overall prevalence of squamous dysplasia was 32% (18% high-grade, 14% low-grade)* • a similar recent endoscopic screening study of 300 adults (aged 40-75) in Iran (total dysplasia 6%, high-grade 1.4%, low-grade 4.6%).
- 58. Results of theSTEP Study in perspective Prevalence of Dysplasia and HGD, by Population Population Total Dysplasia High-Grade Dysplasia China 30 15 Iran 6 1.4 Kenya 14 3.0 • Even in China, endoscopic screening of all adults in high-risk areas, although possibly “cost-effective”, cannot screen comprehensively, so it probably cannot, by itself, significantly reduce ESCC mortality • In Iran and Kenya, endoscopic screening will be less cost-effective than in China, and in Kenya, the required infrastructure is rarely available • For this technique to reduce mortality, it must be preceded by another primary screen that can significantly and accurately stratify risk
- 59. Ongoing analysis - STEP Study • Detailed subject characteristics and risk factors • Genetic analysis of specimens • Polycyclic Aromatic Hydrocarbon (PAH) exposure levels from this subset
- 60. CONCLUSIONS – STEPSTUDY 1. Endoscopic screening as performed in the STEP study is feasible, patient acceptable, and safe in our population 2. The overall prevalence of squamous dysplasia in this population was 14.4% (2.6% high-grade and 11.5% low-grade) 3. The prevalence of dysplasia was greater in patients >50 years old, was similar in men and women, and varied significantly by location of residence
- 61. CONCLUSIONS (continued) 4.USLs were 68% sensitive and 53% specific for identifying biopsy sites containing squamous dysplasia 5. Patient risk stratification (by age, residence location, etc.) may improve the yield of dysplasia in future screening efforts and geographic location was a significant predictor of dysplasia (p 0.01).
- 62. The next Steps? • DIRECT Study - Ongoing- Study of Dysplasia In Relatives of patients with Esophageal Cancer at Tenwek • EXPECT Study - Ongoing- Endoscopic (X) Prevention of Esophageal Cancer at Tenwek Hospital by removal or ablation of esophageal squamous cell dysplasia • LEADER Study - Low grade EsophAgeal Dysplasia Evaluation Report • BOOST Study - Study of the Biomarkers Of Oesophageal Squamous Dysplasia at Tenwek Hospital
- 63. MultiMbaunldti bmauncdo Mseucctoomseycttoemchynique Graphic courtesy of SM Dawsey and Jacques Bergman
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- 65. Esophageal dysplasia –Lugol’s stain
- 66. Esophageal Endoscopic Mucosal Resection (EMR)
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- 70. Squamous Dysplasia AblationCase HALO360 Courtesy of: Jacques Bergman AMC Amsterdam Radio Frequency Ablation Pouw et al GIE 2008
- 71. Thank you foryour attention We look forward to further discussions on effective screening and prevention programs for esophageal squamous cell carcinoma in Africa.