1. Esophageal Cancer Victor Ghobrial, MD Hira Koul, MD Temple University Conemaugh Memorial Hospital

2. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 HPI z47 yrs W M was seen cause of worsening symptoms of ‘ rifting, belching, burping, epigastric distress. zPt has progressive recurrent solid food dysphagia. zAlso, had rifting up blood

3. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 PMH zGERD since 1992 zHad hiatal hernia w’ required Nissen Funduplication (1992) zIntermittent heartburn, indigestion. zSpontaneous retinal detachment. zNo CAD, HTN, DM or cancer

4. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 ROS zPt lost 30 lbs over the past few months. zGI symptoms complex of hematemesis, dysphagia, burping and significant weight loss.

5. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Physical Exam zAppears cachectic in distress cause of epigastric pain. zVital WNL zHt & Lungs clinically free zAbdomen soft no organomegally, epigastric tenderness.

6. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 EGD zBarrette’s mucosa in the distal esophagus. zLarge ulcerating GE junctional area with active bleeding from a Mallory-Weiss tear zBleeding was stopped by BICAP electro- coagulation. zNo other pathology was revealed in gastric mucosa.

7. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Barrett's esophagus zA condition in which an abnormal columnar epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus. zIt is the most severe histologic consequence of chronic gastroesophageal reflux and predisposes to the development of adenocarcinoma of the esophagus

8. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 CLINICAL FEATURES yDiscovered during endoscopic examinations of middle-aged and older adults 55 years. yIt rarely occurs before the age of five. yIs an acquired condition, not a congenital one. yBarrett's esophagus appears to be uncommon in blacks and Asians. The prevalence in Hispanics is similar to Caucasians

9. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Symptomatology zThe columnar metaplasia in Barrett's esophagus causes no symptoms. zPatients are seen initially for symptoms of the associated GERD such as heartburn, regurgitation, and dysphagia.

10. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Difficulties of Dx zDifferent identifications of GE junction by anatomists, radilogists, physiologists and endoscopists. zAssociated hiatal hernia hides Barrette’s. zColumnar epithelium, reddish and velvet- like texture, distinguished from the pale, glossy squamous epithelium of the esophagus.

11. Gastroesophageal Junction Schematic representation of the relationship between the gastroesophageal junction, Z-line and hiatus hernia in patients with Barrett’sesophagus. The Barrett’s mucosa and appear as the confluent area (left picture), as tongues arising from the distal esophagus (middle picture), or as patches containing islands of squamous mucosa or squamous mucosa containing islands of Barrett’s mucosa (right panel). Armed Forces Institute of Pathology

12. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Barrett’s Esophagus Esophagectomy specimen in a patient found to have high grade dysplasia during endoscopic surveillance. Salmon-colored Barrett’s mucosa has replaced the squamous mucosa circumferentially. Scattered erosions are visible (  ). (From Lwein, KJ; Appelman, HD. Tumors of the Esophagus and Stomach. Atlas of Tumor Pathology (electronic fascicle), Third series, fascicle 18, 1996, Washington, DC. Armed Forces Institute of pathology.)

13. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Back to our pt. zBleeding from Mallory-Weiss was stopped. zPt admitted to hosp and started on IVFs, antirelux meds. zPt was rescoped 48 h later with Bx of the ulcer.

14. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 The 2nd EGD zFungating mass at GE junction highly suggestive of malignancy. zBarrette’s mucosa starting 30 cm from upper incisor & border of mass at 35 cm. zBx was done.

15. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Ulcerating malignant esophageal mass in distal esophagus seen on endoscopy. Courtesy of William Brugge, MD.

16. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Pathology Moderate to poorly differentiated adenocarcinoma

17. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Esophageal Cancer zSq cell carcinoma and adenocarcinoma account for more than 95 % of tumors. zFor most of the twentieth century, SCC comprised the vast majority of cancers. z In the 1960s, SCC 90%. zFor the past two decades the two tumors now occur with almost equal prevalence

18. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Epidemiology of Esophageal Cancer in the United States Squamous Adeno New cases per year60006000 Male-to-female ratio3:17:1 Black-to-white ratio6:11:4 Most common locationsmiddledistal Major risk factorssmokingBarrett’s alcohol esophagus

19. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Squamous Cell Carcinoma zThe highest rates are found in Asia (particularly in China and Singapore), Africa, and Iran. zLower socioeconomic status was associated with esophageal SCC in a large population-based study.

20. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Risk Factors zSmoking and alcohol zDietary factors * N-nitroso compounds (animal carcinogens) *Pickled vegetables and other food-products *Toxin-producing fungi *Betel nut chewing *Ingestion of very hot foods and beverages (such as tea) zUnderlying esophageal disease (such as achalasia and caustic strictures)

21. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Risk Factors y Human papilloma virus HPV serotype 16 was identified in 9 percent of resection specimens from 70 Chinese patients with esophageal SCC. yTylosis rare disease associated with hyperkeratosis of the palms of the hands and soles of the feet and a high rate of esophageal SCC

22. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Adenocarcinoma yAC is largely a disease of Caucasians and males yAlcohol is probably not an important risk factor yObesity has been associated with AC but not SCC ySmoking probably increases the risk of AC

23. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Risk Factors zIncreased esophageal acid exposure (such as Zollinger-Ellison syndrome) zHelicobacter pylori infection Probable protective role from chronic infection.

24. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 DIAGNOSTIC TESTING yThe diagnosis of esophageal cancer is usually established by endoscopy yEarly esophageal cancer may appear as a superficial plaque or ulceration yAdvanced lesions may appear as a stricture an ulcerated mass or circumferential mass or a large ulceration.

25. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Early, superficial esophageal cancer on endoscopy. Courtesy of William Brugge, MD

26. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Circumferential ulceration esophageal cancer seen on endoscopy. Courtesy of William Brugge, MD

27. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Malignant stricture of esophagus The tumor mass is not readily evident because it is predominantly infiltrating the esophageal wall. Courtesy of William Brugge, MD.

28. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Biopsy yConfirm the diagnosis in more than 90% yIn a series of 202 consecutive patients, 47 of whom had gastric or esophageal carcinoma, the percentage of correct diagnoses of esophageal carcinoma were as follows yFirst biopsy – 93 percent yFour biopsies – 95 percent ySeven biopsies – 98 percent

29. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Bx... yThe addition of brush cytology specimens to seven biopsies increased the accuracy to 100%. y Seventeen percent of lesions thought to be benign endoscopically were subsequently proven to be malignant.

30. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 In vivo staining??! (chromoendoscopy) yLugol's iodide reacts with the glycogen components of normal squamous mucosa to produce a greenish brown color, while neoplastic tissue is depleted of glycogen and remains unstained.

31. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 study... y158 patients at high risk of SCC;12 had cancerous lesions identified before Lugol's staining, while 13 patients had 17 esophageal cancers noted after staining. yStaining also found that endoscopy underestimated the extent of tumor.

32. Temple University/Conemaugh Memorial Hospital Esophageal CA VG/2000 Take home message zSurgical repair for symptoms of GERD did not prevent development of AC on top of Barrette’s esophageous in this pt. zPeriodic endoscopy in Barrette’s is needed zNo single modality is known to reverse the mucosal dysplasia in Barrette’s as of yet. (Argon LASER Rx still under trial)