Esophageal Adenocarcinoma Arising from Barrett s Epithelium in Taiwan

Transcription

1 CSE REPORT Esophageal denocarcinoma rising from arrett s Epithelium in Taiwan Chia-Hung Tu, 1,2 Ching-Tai Lee, 1 Daw-Shyong Perng, 1 Chun-Chao Chang, 3 Chih-Hung Hsu, 4 Yi-Chia Lee 5,6 * The prevalence of arrett s esophagus (E) in Eastern countries is rising to match the prevalence in the West. However, a corresponding trend of E-associated adenocarcinoma has yet to be observed in sia. Historically, adenocarcinoma complicating E has been considered a rare event in Taiwan. In the present report, we collected three Taiwanese cases of esophageal adenocarcinoma arising from E. The first case was a 37-year-old man with an advanced cancer that developed on pre-existing E after a 3-year interval without endoscopic surveillance. The second case was a 63-year-old man who presented with odynophagia and was found to have an ulcerative tumor centered on the characteristic arrett s mucosa. The final case was a 44-year-old man who presented with gradual-onset dysphagia and weight loss, without typical reflux symptom. Our report emphasizes the need for an updated epidemiologic study to determine the incidence of E-associated adenocarcinoma in Taiwan. [J Formos Med ssoc 2007;106(8): ] Key Words: arrett s esophagus, esophageal adenocarcinoma, gastroesophageal reflux disease arrett s esophagus (E) is a premalignant condition that leads to esophageal adenocarcinoma. The incidence of arrett s adenocarcinoma in Western countries has increased dramatically over the last three decades. 1,2 lthough E and associated adenocarcinoma have been considered to be less common in Eastern populations, recent studies have demonstrated a rising incidence of gastroesophageal reflux disease (GERD) and E in sia. 3,4 However, a corresponding increase in the incidence of arrett s adenocarcinoma has not been reported in our region. 5,6 In this report, we describe three cases who were diagnosed in a northern city of Taiwan in order to raise awareness of this disease entity in Taiwan. Case Reports Case 1 37-year-old man who did not smoke or drink alcohol presented with gradual-onset dysphagia. Three years earlier, he had undergone esophagogastroduodenoscopy (EGD) at National Taiwan University Hospital because of typical GERD symptoms. t that time, the squamocolumnar junction was located 4 cm proximal to the upper ends of the gastric mucosa and had an appearance typical of E (Figure 1). biopsy specimen proved the presence of intestinal metaplasia. For unknown reasons, the patient failed to receive regular endoscopic surveillance afterwards. The EGD performed 2007 Elsevier & Formosan Medical ssociation Department of Internal Medicine, I-Shou University Hospital, Kaohsiung; 2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 3 Department of Internal Medicine, Taipei Medical University Hospital, Taipei; Departments of 4 Oncology and 5 Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei; 6 Division of iostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. Received: pril 10, 2006 Revised: May 9, 2006 ccepted: February 6, 2007 *Correspondence to: Dr Yi-Chia Lee, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. yichialee@ntu.edu.tw 664 J Formos Med ssoc 2007 Vol 106 No 8

2 arrett s esophageal adenocarcinoma in Taiwan Figure 1. Case 1: () esophagogastroduodenoscopy reveals a proximal extension of the squamocolumnar junction (arrow), typical of arrett s esophagus; () 3 years later, a repeat examination shows that an irregular exophyting tumor had developed on the territory of arrett s mucosa. 3 years later showed a nodular creeping tumor of the lower esophagus arising from the pre-existing arrett s territory (Figure 1). Pathology proved adenocarcinoma. fter multiple liver, bone and brain metastases were identified, the patient underwent intensive systemic chemotherapy with palliative irradiation. Case 2 63-year-old man with chronic GERD symptoms for 6 months visited Taipei Medical University Hospital with gradual-onset odynophagia of roughly 1 month s duration. He denied the habits of alcohol, tobacco, and betel quid consumption. EGD found a bulging tumor with central ulceration at the lower esophagus, cm below the incisors (Figure 2). The squamocolumnar junction was displaced 4 cm proximal to the esophagogastric junction; velvety pink mucosa with wave-like projections coursed across the ulcerated tumor. iopsies confirmed adenocarcinoma arising from E. The patient was treated with radical esophagectomy and proximal gastrectomy with esophagogastric anastomosis. Examination of the surgical specimen showed that the malignant ulcer was located near the proximal end of the distinctive arrett s mucosa (Figure 2). Microscopically, the tumor was moderately to poorly differentiated adenocarcinoma in glandular structures, infiltrating as solid nests into the desmoplastic stroma. The surrounding arrett s mucosa contained intestinal metaplasia. Eight months after surgery, the patient was free of recurrent disease, but he has since undergone two endoscopic dilation procedures for anastomotic stricture. Case 3 44-year-old man without a history of reflux symptoms visited National Taiwan University Hospital because of a 6-week history of progressive dysphagia and weight loss. He did not smoke, but had limited amount of alcoholic beverages. arium swallow examination revealed an irregular narrowing of the lower esophagus (7 cm in length) that was continuous with the gastroesophageal junction (Figure 3). subsequent EGD showed an eccentric tumor of the lower esophagus that extended longitudinally from the gastroesophageal junction to the level of 33 cm below the incisors. The tumor was nodular, with a friable surface (Figure 3). The gastric cardia was partially involved. The underlying mucosa surrounding the tumor was composed of pink velvety-like epithelium that extended to the upper end of the tumor, a typical picture of E. iopsies confirmed an adenocarcinoma and surrounding E (Figure 3C). Endoscopic ultrasound J Formos Med ssoc 2007 Vol 106 No 8 665

3 C.H. Tu, et al Figure 2. Case 2: () esophagogastroduodenoscopy shows arrett s mucosa appearing as a velvety pink surface with wave-like projections coursing across the ulcerated esophageal cancer; () the surgical specimen shows a distinct area between the esophagogastric junction (arrow) and the squamocolumnar junction (arrowhead), indicating arrett s mucosa. The central ulcer of the tumor is within the arrett s territory. Figure 3. Case 3. () arium swallow imaging study reveals an irregular narrowing at the lower esophagus that was continuous with the gastroesophageal junction. () Esophagogastroduodenoscopy shows an eccentric exophyting tumor at the lower esophagus. The surrounding darker mucosa is extended as several tongues proximal to the upper end of the tumor (arrow), indicating arrett s esophagus. (C) iopsy of the tumor margin shows malignant cells in a glandular pattern and necrotic debris (arrows), while the mucosal surface shows intestinal metaplasia (arrowhead) (hematoxylin & eosin, 400 ). C showed that tumor depth was limited to the adventitia and that there was regional lymphadenopathy (disease stage T3N1M0). The patient was referred for concurrent cisplatin-based chemoradiotherapy. Discussion This report has described three Taiwanese men of middle to old age (range, years) with lower esophageal adenocarcinoma. Each of the three 666 J Formos Med ssoc 2007 Vol 106 No 8

4 arrett s esophageal adenocarcinoma in Taiwan malignant tumors was morphologically proven to have concomitant E. ll three patients came to medical attention only after developing symptoms of an advanced lesion due to lack of surveillance or adequate follow-up. E is an incomplete form of intestinal metaplasia resulting from chronic GERD, in which the normal squamous epithelium of the esophagus is replaced by intestinal-type epithelium. In Western countries, it is found in approximately 6 12% of patients with reflux symptoms who have undergone endoscopy. It generally affects older people, with a peak incidence at around years, and has a male-to-female ratio of 7:1. 7,8 lthough approximately 50% of cases of esophageal adenocarcinoma arise from E, reflux symptoms alone can be associated with an increased risk. In a Swedish study, Lagergren et al 9 reported that 60% of 189 patients with esophageal adenocarcinoma had previous histories of heartburn or acid regurgitation. Other putative risk factors include duration of GERD symptoms, presence of nocturnal reflux symptoms, hiatus hernia, and the absence of Helicobacter pylori infection. 10 lthough a causal relationship between E and esophageal adenocarcinoma is well-established, the precise mechanism of progression remains elusive. It is believed that carcinogenesis may progress through the sequence of metaplasia-dysplasiaadenocarcinoma, with possible pathogenic roles for repeated exposure to acid and cyclooxygenase (COX)-2 related pathway activity. 11 Chemoprevention with proton-pump inhibitors, COX-2 inhibitors, and aspirin has been proposed to arrest or delay progression to adenocarcinoma. 12,13 However, available regimens have not convincingly decreased the likelihood of developing cancer. Current efforts are emphasizing endoscopic detection of small cancer foci by using magnification, chromoendoscopy, and/or optical devices to identify or delineate the margin. 14,15 Long-segment E, defined as a length of intestinal epithelium 3 cm, deserves intensive endoscopic surveillance because it is associated with higher esophageal acid exposure and subsequent rate of malignant transformation. 16,17 In our report, all three patients had long-segment E; two of them had typical reflux symptoms. ased on the recently validated Prague C & M criteria, 18 all of their Es can be described as C2-3 M4-7, which confirm the clinical utility of measurement of circumferential and maximum extents. relatively young age of onset (mean age, 48 years) in our series deserves special attention. Liou et al 19 reviewed 17,894 dyspeptic patients screened by upper endoscopy in Taiwan and found that 13.7% and 7.6% of patients were aged less than 45 and 40 years old, respectively. They suggested that 40 years might be an optimal age threshold for screening endoscopy for uninvestigated dyspepsia in Taiwan. Our report may strengthen their findings in making the optimal screening strategy specific for Taiwanese patients with functional gastrointestinal disorder. We assumed that there may be an increase in E-associated adenocarcinoma in Taiwan, corresponding to the 18.4% prevalence of endoscopic esophagitis reported from a cross-sectional survey. 4 Other supportive evidence is the 2% prevalence of E among a Taiwanese population of 464 selfreferred subjects, a rate that potentially matches up with the range of rates (5 10%) reported in Western countries. 3 However, the reported incidence of E-associated adenocarcinoma may be difficult to distinguish with cardiac gastric cancer, especially when the tumors are disclosed in advanced stages. The misclassification can be substantial when we estimate the incidence based on the crude database of the National Cancer Registry. In fact, the World Health Organization classification uses the proximal end of gastric folds to define distal esophageal tumor, junctional tumor, and cardiac tumor. 20 El-Rifai et al 21 also detected specific genetic alterations that may be helpful in distinguishing E-associated adenocarcinoma from cardiac gastric cancer. Further validation of morphologic and histopathologic diagnoses is a worthwhile endeavor. In summary, we report three Taiwanese men with advanced esophageal adenocarcinoma with concomitant E. In discordance to the common thought of disease rarity in Eastern countries, these J Formos Med ssoc 2007 Vol 106 No 8 667

5 C.H. Tu, et al cases show similar characteristics to those reported in Western countries. lthough the evidence remains limited, our report emphasizes the importance of risk assessment and follow-up surveillance in patients with reflux symptoms. Updated epidemiologic data are therefore warranted. References 1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005;97: Fitzgerald RC. Review article: arrett s oesophagus and associated adenocarcinoma a UK perspective. liment Pharmacol Ther 2004;20: Yeh C, Hsu CT, Fass R, et al. Erosive esophagitis and arrett s esophagus in Taiwan: a higher frequency than expected. Dig Dis Sci 1997;42: Lee YC, Wang HP, Chiu HM, et al. Comparative analysis between psychological and endoscopic profiles in patients with gastroesophageal reflux disease: a prospective study based on screening endoscopy. J Gastroenterol Hepatol 2006;21: Hongo M, Shoji T. Epidemiology of reflux disease and CLE in East sia. J Gastroenterol 2003;38: Chang SS, Lu CL, Lee SD, et al. Unchanging trend of adenocarcinoma of the esophagus and gastric cardia in Taiwan: a 15-year experience in a single center. Dig Dis Sci 2002; 47: Pera M, Manterola C, Vidal O, et al. Epidemiology of esophageal adenocarcinoma. J Surg Oncol 2005;92: Kim R, Weissfeld JL, Reynalds JC, et al. Etiology of arrett s esophagus and esophageal adenocarcinoma. Cancer Epidemiol iomarks Prev 1997;6: Lagergren J, ergstrom R, Lindgren. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340: Falk GW. arrett s esophagus. Gastroenterology 2002;122: uttar NS, Wang KK, nderson M, et al. The effect of selective cyclooxygenase-2 inhibition in arrett s esophagus epithelium: an in vitro study. J Natl Cancer Inst 2002;94: Shaheen NJ. dvances in arrett s esophagus and esophageal adenocarcinoma. Gastroenterology 2005; 128: Mehta S, Johnson IT, Rhodes M. Systematic review: the chemoprevention of oesophageal adenocarcinoma. liment Pharmacol Ther 2005;22: Hamamoto Y, Endo T, Nosho K, et al. Usefulness of narrowband imaging endoscopy for diagnosis of arrett s esophagus. J Gastroenterol 2004;39: Deviere J. arrett s oesophagus: the new endoscopic modalities have a future. Gut 2005;54: Rudolph RE, Vaughan TL, Storer E, et al. Effect of segment length on risk for neoplastic progression in patients with arrett s esophagus. nn Intern Med 2000;132: vidan, Sonnenberg, Schnell TG, et al. Hiatal hernia size, arrett s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. m J Gastroenterol 2002;97: Sharma P, Dent J, rmstrong D, et al. The development and validation of an endoscopic grading system for arrett s esophagus: the Prague C & M criteria. Gastroenterology 2006;131: Liou JM, Lin JT, Wang HP, et al. The optimal age threshold for screening upper endoscopy for uninvestigated dyspepsia in Taiwan, an area with a higher prevalence of gastric cancer in young adults. Gastrointest Endosc 2005;61: Hamilton SR, altonen L. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Digestive System. Lyon: IRC Press, El-Rifai W, Frierson HF Jr, Moskaluk C, et al. Genetic differences between adenocarcinomas arising in arrett s esophagus and gastric mucosa. Gastroenterology 2001; 121: J Formos Med ssoc 2007 Vol 106 No 8