High-Grade Esophageal Dysplasia: Long-Term Survival and Quality of Life After Esophagectomy

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1 ORIGINAL ARTICLES: GENERAL THORACIC High-Grade Esophageal Dysplasia: Long-Term Survival and Quality of Life After Esophagectomy James R. Headrick, MD, Francis C. Nichols III, MD, Daniel L. Miller, MD, Mark S. Allen, MD, Victor F. Trastek, MD, Claude Deschamps, MD, Cathy D. Schleck, BS, Ann M. Thompson, RN, and Peter C. Pairolero, MD Division of General Thoracic Surgery and Section of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota Background. Esophagectomy for high-grade dysplasia in Barrett s esophagus has been advocated. Although long-term survival data exist, little is known about functional outcome and quality of life in this particular subset of patients. Methods. The records of all patients who underwent esophageal resection for high-grade dysplasia from June 1991 through July 1997 were reviewed. Long-term functional outcome and quality of life were assessed using a two-part written survey. Results. There were 54 patients (48 men, 6 women). Median age was 64 years (range, 36 to 83 years). Ivor Lewis esophagogastrectomy was performed in 34 patients (63%), transhiatal esophagectomy in 10 (18%), extended esophagectomy in 8 (15%), and other in 2 (4%). Invasive carcinoma was found in 19 patients (35%). Five patients (9%) were stage 0, 7 (13%) stage I, 3 (6%) stage IIA, 1 (2%) stage IIB, and 3 patients (6%) stage III. There was one operative death (1.8%). Complications occurred in 31 patients (57%). Median hospitalization was 13 days (range, 11 to 44 days). Follow-up was complete in all patients and ranged from 6 months to 9 years (median, 63 months). Overall 5-year survival was 86% and did not differ significantly from a population matched for age and gender. Five-year survival for patients with only high-grade dysplasia was 96% and 68% for patients with cancer (p 0.017). Quality of life was measured by the Medical Outcomes Study 36-Item Short-Form Health Survey. For patients with only high-grade dysplasia, the role-physical and role-emotional scores were better than for the control population (p < 0.03). For patients with cancer, the health perception score was worse than for the control population (p < 0.03). Scores measuring physicalfunction, social function, mental health, bodily pain, and energy/fatigue were similar. Conclusions. Although perioperative morbidity is significant, surgical resection of high-grade dysplasia in Barrett s esophagus provides excellent long-term survival with acceptable function and quality of life. (Ann Thorac Surg 2002;73: ) 2002 by The Society of Thoracic Surgeons The incidence of carcinoma of the esophagus is increasing faster than any other type of solid tumor [1]. Long-term survival is unlikely unless this cancer is treated at an early stage. A precursor to esophageal cancer is often Barrett s metaplasia. If high-grade dysplasia (HGD) is demonstrated in the Barrett s epithelium, invasive carcinoma already may be present in up to 50% of patients [2 5]. Controversy exists regarding the optimal management of Barrett s esophagus (BE) with HGD. Some investigators believe that HGD can be safely observed with frequent endoscopy, whereas others offer various forms of endoscopic ablative therapy [6, 7]. Still other researchers, particularly in the surgical community, advocate esophagectomy as appropriate management [2 5, 8, 9]. Although data on long-term survival exist, very little is published on functional outcome and quality of life after esophageal resection for HGD. This information will be important as the enthusiasm for less invasive Presented at the Thirty-seventh Annual Meeting of the Society of Thoracic Surgeons, New Orleans, LA, Jan 29 31, Address reprint requests to Dr Nichols, Division of General Thoracic Surgery, Mayo Clinic and Mayo Foundation, 200 First St, SW, Rochester, MN 55905; nichols.francis@mayo.edu. means of treating HGD grows. The purpose of this study is to review our recent experience with esophagectomy for HGD in BE and to examine long-term survival, functional outcome, and quality of life. Material and Methods Approval for this study was granted by the Mayo Foundation s Institutional Review Board. All patients who underwent esophageal resection for BE from June 1991 through July 1997 were reviewed. None of these patients had previously been reported on. Patients with a preoperative biopsy demonstrating carcinoma were excluded. In addition, patients with HGD in whom the pathologists thought the specimens were suspicious for but not diagnostic of carcinoma were excluded. Thus, our final study population was believed to have solely HGD before esophagectomy. The records of these patients were reviewed for age, gender, presenting signs and symptoms, endoscopic findings, length of surveillance, operative procedure, postsurgical stage, operative morbidity and mortality, survival, functional outcome, and quality of life. All cancers were staged by the 2002 by The Society of Thoracic Surgeons /02/$22.00 Published by Elsevier Science Inc PII S (02)

2 1698 HEADRICK ET AL Ann Thorac Surg BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 2002;73: TNM classification system of the American Joint Committee for Cancer Staging [10]. Follow-up data were obtained from both the patients clinical record and a two-part survey that was mailed to all survivors known to be alive in August Part one of the survey used the Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF 36) [11]. This survey allows for a statistical comparison of patients with chronic health problems with people sampled from the general population. This nationally standardized questionnaire is a self-administered health assessment tool that permits group comparisons in eight different conceptual areas. The areas included are general health (health perception), daily activities (physical functioning), work performance (role-physical), emotional problems (role-emotional), social activities (social functioning), nervousness/depression (mental health), pain (bodily pain), and vitality (energy/fatigue). A numeric score was calculated for each of the answers and from the scores a mean and standard deviation derived. The mean and standard deviation were then compared to age- and gender-matched national norms [12]. Part two of the survey consisted of a four-page questionnaire subjectively evaluating digestive functional outcome. Specifically addressed were the qualitative and quantitative estimates of dysphagia, the need for esophageal dilatation, the presence of heartburn and its treatment, the presence of dumping syndrome, and weight change. Questions related to shortness of breath and hoarseness were also asked. If the results of the subjective questionnaire were inconclusive, the medical record was used to supplement the functional outcome information where possible. Operative mortality was defined as death within 30 days of operation or during the same hospitalization if longer. Survival using the date of operation as the starting time was calculated using the Kaplan-Meier method [13]. The relationship between variables was assessed using 2 tests for discrete factors and Wilcoxon rank sum tests for continuous factors [14]. Evaluation of the MOS SF-36 Health Status Questionnaire relative to a matched population was done using the sign test or signed-rank test [15]. A p value of less than 0.05 was considered significant. Clinical Findings Fifty-four consecutive patients underwent esophageal resection for BE with HGD at the Mayo Clinic in Rochester, Minnesota. Forty-eight were men (89%) and 6 women (11%). Median age at the time of esophagectomy was 64 years and ranged from 36 to 83 years. Preoperative signs or symptoms were present in 53 patients. The most common symptoms were heartburn in 45 patients (83%) and dysphagia in 19 (35%). Other presenting symptoms included gastrointestinal bleeding in 13 patients (24%), chronic anemia in 3 (6%), and chest pain in 3 (6%). Fifty-one patients (94%) were taking medications for their reflux disease; most common was a proton pump inhibitor. Forty-one patients (76%) were smokers or had a history of prior tobacco abuse and 16 (30%) chronically used alcohol. Nine patients (17%) had undergone previous antireflux procedures; 7 had a single procedure, 1 had 2 and 1 had 3. Three patients (6%) had other prior gastric or esophageal resections, which included a limited esophagogastrectomy in 1 patient, antrectomy and gastrojejunostomy in 1, and an aborted esophagogastrectomy in 1 patient. Two patients were treated with photodynamic therapy and surveillance before finally undergoing esophagectomy. Thirty-two patients (59%) were in an endoscopic surveillance program for BE. None of these patients initially had HGD. The median length of surveillance before the detection of HGD was 22 months (range, 4 to 240 months). The median number of endoscopies was 4 (range, 2 to 24). The median number of days between the diagnosis of BE and operation was 512 (range, 1 day to 20.6 years). The median number of days between the diagnosis of HGD and operation was 42 (range, 1 to 2.8 years). Preoperatively, all patients had endoscopic evidence of BE. Thirty-three patients (61%) had other endoscopic findings in addition to the Barrett s mucosa. These findings included nodularity in 12 (22%), ulceration in 8 (15%), strictures in 5 (9%), ulceration and nodularity in 4 (7%), nodularity and stricture in 2 (4%), and esophageal polyps in 2 (4%). Twenty-one patients (39%) had no other endoscopic finding other than the Barrett s mucosa. Endoscopic ultrasound (EUS) was done in 23 patients; 8 had normal findings, 14 had esophageal wall thickening, and 1 had both wall thickening and enlarged periesophageal lymph nodes. The median length of BE on endoscopy was 8 cm (range, 2 to 20 cm). All patients had biopsy proven HGD without evidence of cancer at the time of operation. The operation performed was an Ivor Lewis esophagogastrectomy in 34 patients (63%), transhiatal esophagogastrectomy in 10 (18%), extended esophagectomy in 8 (15%), completion gastrectomy and Roux-en-Y esophagojejunostomy in 1, and completion gastrectomy with isoperistaltic left colon interposition in 1 patient. Extended esophagectomy includes an initial right thoracotomy for mobilization of the esophagus. The actual resection and reconstruction are then carried out with the patient supine and through separate abdominal and left cervical incisions [16]. Excluding the two completion gastrectomies, a pyloromyotomy was performed in 46 patients and a pyloroplasty in 3 patients. Three patients had no gastric drainage procedure performed. Thirty-five patients (65%) had an intrathoracic anastomosis and 19 (35%) had a cervical anastomosis. For the patients who had an Ivor Lewis esophagogastrectomy, the anastomosis was always completed above the level of the azygos vein. Concomitant procedures were performed in 10 patients. These included pulmonary wedge excision in 4, cholecystectomy in 2, and pulmonary lobectomy, splenectomy, salpingo-oophorectomy, and cystoscopy with urethral dilatation in 1 patient each. Ten patients had a feeding jejunostomy. Pathologic examination of the resected specimen revealed the median length of BE was 7 cm (range, 2 to

3 Ann Thorac Surg HEADRICK ET AL 2002;73: BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 1699 Fig 1. Estimated survival (death due to any cause) of 53 patients undergoing esophagectomy for high-grade dysplasia. Zero time on the abscissa is date of operation. 15 cm). HGD alone was found in 35 patients (65%), adenocarcinoma in 18 (33%), and squamous cell carcinoma in 1 (2%). Of the 21 patients who had no additional endoscopic findings except for BE, 2 (10%) patients had cancer. Seventeen (52%) of the 33 patients with additional endoscopic findings (nodularity, ulceration, strictures) had cancer. Eight (53%) of the 15 patients with an abnormal EUS had cancer. The tumor was classified as Tis (in situ carcinoma) in 5 patients, T1 in 7, T2 in 2, and T3 in 5. Lymph node metastases were found in 4 patients. The postsurgical stage was stage 0 in 5 patients (9%), stage I in 7 (13%), stage IIA in 3 (6%), stage IIB in 1 (2%), and stage III in 3 (6%). Two patients subsequently underwent adjuvant chemotherapy and radiation therapy. Results Intraoperative complications occurred in 1 patient (1.8%). This patient previously had undergone an aborted esophagogastrectomy elsewhere and required a splenectomy at the time of esophageal resection for splenic bleeding. Postoperative complications occurred in 31 patients (57%). Thirteen patients (24%) had respiratory complications, which included pneumonia in 9, parapneumonic empyema in 2, and retained secretions in 2 patients. Both patients with empyema required thoracotomy and decortication. One patient with respiratory complications required tracheostomy. Other complications included atrial arrhythmias in 5 patients (9%), superficial wound infection in 4 (7%) and transient ischemic attack, small cerebral infarct, and chest wall dehiscence requiring reclosure in 1 patient each (6%). Both of the patients with cerebral events recovered completely by the time of discharge. Anastomotic leaks occurred in 7 patients (13%). There were five cervical and two intrathoracic leaks. The two intrathoracic leaks were radiographically contained and found at the time of the routine postoperative esophagogram. Both patients were asymptomatic. Three of the cervical leaks occurred in patients who had undergone prior esophageal or gastric procedures. All leaks were treated conservatively. There was one operative death (1.8%), which occurred from rupture of a pulmonary artery secondary to manipulation of a Swan-Ganz catheter. Follow-up was complete in all 53 operative survivors and ranged from 6 months to 9 years (median, 5.3 years). Thirty-three patients had follow-up endoscopy, and no patient had evidence of recurrent Barrett s mucosa. At time of last follow-up, 43 patients (80%) were alive and without evidence of recurrent disease. Cause of death in the 10 patients who died included metastatic esophageal cancer in 4, other metastatic cancer (lung, pancreas, and bladder) in 3, and noncancer in 3 patients. Thirteen of the 19 patients found to have cancer at the time of esophagectomy were alive at follow-up. Overall actuarial 5-year survival was 86% and did not differ significantly from an expected survival of 87% (95% confidence interval, 75.7% to 95.7%) (Fig 1). The presence of invasive cancer with HGD significantly affected survival. Five-year survival for patients with cancer was 68% (95% confidence interval, 45.7% to 92.9%) as compared to 96% (95% confidence interval, 87.7% to 100%) for patients with HGD only (Fig 2) (p 0.017). Functional Outcome Patients who died within 2 years of esophagectomy were excluded from the analysis of functional outcome and quality of life. Long-term functional outcome was available for 48 patients. Seven patients (13%) were entirely asymptomatic. Thirty-one patients lost weight (median 9 kg; range, 3 to 50 kg) and 7 gained weight (median 2 kg; range, 1 to 5 kg). Ten patients had no change in weight. Thirty patients had no dysphagia. Mild, moderate, and severe dysphagia were reported in 15, 1, and 2 patients, respectively. Dilatation of the esophageal anastomosis was required in 27 patients (51%). The median number of dilatations was three and ranged from 1 to 20. Gastroesophageal reflux was present in 36 patients (68%), but the majority had minimal symptoms with medical management. Dumping was present in 8 patients (15%). Fig 2. Estimated survival of 34 patients with high-grade dysplasia only undergoing esophagectomy as compared with the survival of 19 patients with cancer. Zero time on the abscissa is date of operation.

4 1700 HEADRICK ET AL Ann Thorac Surg BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 2002;73: Table 1. Results of Quality of Life Survey All Patients a Category All Patients Normal Physical functioning 74.1 (25.7) 79.0 (10.4) Role-physical 75.0 (37.8) b 72.8 (14.8) Role-emotional 85.6 (26.3) b 85.2 (7.6) Social functioning 81.5 (26.5) 87.3 (5.3) Mental health 77.8 (16.1) 78.3 (1.4) Bodily pain 78.7 (21.9) 75.4 (5.6) Energy/fatigue 56.4 (20.4) 62.1 (4.7) Health perception 60.3 (22.9) c 68.6 (6.3) a Scores are shown as the mean with the standard deviation in parentheses. b Significance: p 0.01 compared with normal population matched for age and gender (sign test). c Significance: p 0.02 compared with normal population matched for age and gender (signedrank test). Long-term functional outcome was significantly affected by the level of the anastomosis. Patients with a cervical anastomosis had significantly (p 0.04) more dumping than those with an intrathoracic anastomosis (33.3% versus 6.7%). The level of the anastomosis did not significantly affect the incidence of dysphagia and reflux. No significant difference was observed in dysphagia, reflux, or dumping with regard to age, gender, or postoperative leaks. Quality of Life Information from the MOS SF-36 Health Status Questionnaire was available from 44 patients (82%). For our overall population, the role-physical and role-emotional scores were better than the national norm (p 0.01), whereas the health perception score was lower (p 0.02) (Table 1). Patients with only HGD differed significantly from the national norm in that they scored better in the role-physical and role-emotional categories (p 0.03) (Table 2). Patients with cancer, however, were similar to the national norm in all categories except for health perception, which was less than the norm (p 0.03) (Table 3). Table 2. Results of Quality of Life Survey High-Grade Dysplasia Patients a Category HGD Patients Normal Physical functioning 76.0 (27.0) 80.7 (10.0) Role-physical 76.7 (38.2) b 75.4 (13.9) Role-emotional 86.0 (25.5) c 86.5 (6.7) Social functioning 83.9 (26.4) 88.1 (4.9) Mental health 76.9 (17.1) 78.5 (1.2) Bodily pain 79.6 (20.3) 76.4 (5.5) Energy/fatigue 58.2 (19.6) 63.0 (4.4) Health perception 62.8 (24.9) 69.6 (6.0) a Scores are shown as the mean with the standard deviation in parentheses. b Significance: p 0.02 compared with normal population matched for age and gender (sign test). c Significance: p 0.03 compared with normal population matched for age and gender (sign test). HGD high-grade dysplasia. Table 3. Results of Quality of Life Survey Cancer Patients a Category When factors affecting quality of life were analyzed, the occurrence of an anastomotic leak adversely affected the social functioning scores in our population (p 0.02). Age was significantly correlated with physical functioning (p ) and role-physical (p 0.03). As our patients became older, their physical function and physical performance at work were less than the norm. Time from operation was also significantly correlated with social functioning (p 0.02). The further our patient population was beyond operation, the better was their social function. No difference was detected in the categories of bodily pain, health perception, energy/fatigue, role-emotional, and mental health with regard to age, gender, time from operation, anastomotic leak, reflux, or dumping. Comment Cancer Normal Physical functioning 69.6 (22.6) 74.8 (10.6) Role-physical 71.2 (38.0) 66.7 (15.6) Role-emotional 84.6 (29.2) 81.9 (8.9) Social functioning 76.0 (26.7) 85.2 (5.8) Mental health 80.0 (13.6) 77.9 (1.6) Bodily pain 76.5 (26.2) 73.1 (5.4) Energy/fatigue 51.9 (22.2) 59.9 (5.0) Health perception 54.5 (17.0) b 66.2 (6.5) a Scores are shown as the mean with the standard deviation in parentheses. b Significance: p 0.03 compared with normal population matched for age and gender (signed-rank test). Patients with BE have a 30 to 125 times increased risk of developing esophageal cancer [17]. With the incidence of adenocarcinoma of the esophagus rising at an alarming rate, considerable attention has been focused on the role of BE in the development of this cancer. Guidelines exist for the management of BE and vary depending on the presence and grade of dysplasia [18]. The management of HGD remains controversial. Esophagectomy is commonly believed to be the treatment of choice within the surgical community [2 5, 8, 9]. Justification for this recommendation comes from the high rate, up to 50%, of associated invasive cancer and the improved 5-year survival when resection is performed at an early stage. Figure 2 clearly shows the improved survival in HGD-only patients when compared to patients with cancer. Our postoperative mortality of 1.8% confirms along with other series that esophagectomy for HGD can be performed safely [8]. However, this view is not universally shared. In the nonsurgical community esophagectomy has been referred to as a complex and perilous surgical procedure with an alarming 10% mortality [19]. Some physicians favor close endoscopic surveillance as an alternative to esophagectomy. Worrisome, however, is a survey by Gross and colleagues [20] that showed the

5 Ann Thorac Surg HEADRICK ET AL 2002;73: BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 1701 vast majority of respondents who performed surveillance failed to use the rigorous methods suggested in the literature. Of note in our study is the 52% incidence of cancer in patients who besides BE with HGD had additional endoscopic abnormalities (nodularity, ulceration, strictures). If the endoscopy was normal except for BE and HGD, there was still a 10% incidence of cancer. Less than half of our patients had EUS; however, of the 15 patients with an abnormal EUS, 8 (53%) did have cancer. EUS does have a role in the staging of esophageal cancer; however, its role in the management of HGD is doubtful. Falk and associates [21] found EUS to be unreliable in distinguishing benign from malignant changes in BE with HGD. The functional outcome after esophagectomy for patients with benign and malignant esophageal disease has been addressed in two previous reports by us [12, 22]. Patients with HGD were excluded from the review by Young and colleagues [22]. Although the review by McLarty and co-workers [12] also addressed long-term quality of life, that review dealt exclusively with esophageal cancer patients. In reality, little is known about the long-term functional outcome and quality of life in patients with HGD undergoing esophagectomy. This large study represents our current experience. The review by Heitmiller and Hamilton [4] included 30 patients during a 12-year period and did not address either functional outcome or quality of life. Similarly, the review by Ferguson and Naunheim [8] contained only 15 patients from two institutions during a 12-year period. Their review of the English literature resulted in 104 additional patients. The meta-analysis performed did not address either functional outcome or quality of life [8]. Similar to other series, we used a variety of surgical techniques. The particular technique used in each patient was based on surgical preference and was occasionally necessitated by the unique circumstances of the patient. Sixty-two percent of patients had no dysphagia and 31% had mild dysphagia on long-term follow-up. Likewise, gastroesophageal reflux and dumping were present in 68% and 15% of our patients, respectively. Most of these symptoms were well controlled with diet and medication. Unlike other series, reflux was not significantly related to the level of the anastomosis. Interestingly, dumping was significantly greater in our patients when a cervical anastomosis was performed. Most of our patients had functional outcomes that were acceptable but perhaps less than ideal. It is understandable that our cancer patients perceived their health to be worse than the normal population. Also understandable is a postoperative leak adversely affecting the social function score and that score improving with time. Not as easy to explain is why the overall patient population and specifically patients with HGD only performed better at work both physically and emotionally. The distribution of the differences between the patients role-physical and role-emotional scores and their age- and gender-specific normal scores was markedly nongaussian. Consequently, two nonparametric tests were used on these scores. The signed-rank test was not significant but the sign test was very significant. Because of the unique nature of these distributions, caution must be exercised in their interpretation. Although there may be statistically significant differences, these differences may be of no clinical importance. Despite the less than ideal long-term functional results, with the exception of a health perception worse than a normal matched population, esophagectomy had no significant negative impact on quality of life. With the current trend toward minimally invasive procedures, it is not surprising that newer alternative therapeutic approaches for the management of HGD are being popularized. Such alternatives include endoscopic thermal and photochemical mucosal ablation. Although the less invasive alternative treatments may be promising, long-term results are not yet available. Complications from these treatments do occur. Complications include the inconvenience of photosensitivity, which can last for 4 to 8 weeks, occasionally extending to 6 months, and stricture formation in up to 34% of patients. These strictures require aggressive dilatation. Various gastrointestinal complaints, such as abdominal pain in 20% of patients, constipation in 24%, diarrhea in 5%, dyspepsia in 6%, nausea in 24%, and vomiting in 17%, have also been associated with photodynamic therapy [23]. Although the various mucosal ablative techniques can alleviate the Barrett s metaplasia to varying degrees, a decrease in the cancer risk has not been demonstrated. None of these techniques has been proven to provide long-term control of BE [24]. Both patients who underwent photodynamic therapy in this series eventually required esophagectomy. Currently, photodynamic therapy and endoscopic mucosal resection should be reserved for patients with HGD who are not appropriate surgical candidates [24]. In conclusion, esophageal cancer continues to be a significant risk for patients with HGD in BE. When cancer is found, it tends to be at an earlier stage and associated with improved survival as compared to esophageal cancer in general. Patients undergoing esophagectomy for HGD have a normal life expectancy, and despite functional symptoms a positive quality of life. Esophagectomy should remain the standard therapy for surgically acceptable patients with BE and HGD. References 1. Wright TA. High-grade dysplasia in Barrett s esophagus. Br J Surg 1997;84: Pera M, Trastek VF, Carpenter HA, et al. Barrett s esophagus with high-grade dysplasia: an indication for esophagectomy? Ann Thorac Surg 1992;54: Edwards MJ, Gable DR, Lentsch AB, et al. The rational for esophagectomy as the optimal therapy for Barrett s esophagus with high-grade dysplasia. Ann Surg 1996;223: Heitmiller RF, Hamilton SR. Barrett s esophagus with highgrade dysplasia: an indication for prophylactic esophagectomy. Ann Surg 1996;224: Hagen JA. Management of Barrett s esophagus with dysplasia. Semin Thorac Cardiovasc Surg 1997;9: Pellegrini CA, Pohl D. High-grade dysplasia in Barrett s

6 1702 HEADRICK ET AL Ann Thorac Surg BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 2002;73: esophagus: surveillance or operation? J Gastrointest Surg 2000;4: Lim KN, Waring PJ, Saidi R. Therapeutic options in patients with Barrett s esophagus. Dig Dis 1999;17: Ferguson MK, Naunheim KS. Resection for Barrett s mucosa with high-grade dysplasia. Implications for prophylactic photodynamic therapy. J Thorac Cardiovasc Surg 1997;114: Rice TW, Falk GW, Achkar E, Petras RE. Surgical management of high-grade dysplasia in Barrett s esophagus. Am J Gastroenterol 1993;88: Fleming ID, Cooper JS, Henson DE, et al (eds). American Joint Committee on Cancer. Manual for staging of cancer, 5th ed. Philadelphia: Lippincott-Raven, Ware JE. SF-36 Health Survey. Manual and interpretation guide. Boston: Nimrod, McLarty AJ, Deschamps C, Trastek VF, et al. Esophageal resection for cancer of the esophagus: long-term function and quality of life. Ann Thorac Surg 1997;63: Kaplan EL, Meier P. Non-parametric estimation from incomplete observation. J Am Stat Assoc 1958;53: Dixon WJ, Massey F Jr. Introduction to statistical analysis, 3rd ed. New York: McGraw Hill, 1969:77 80,116 18,156 63,344 45, Siegel S. Non-parametric statistics for behavioral sciences, 1st ed. New York: McGraw Hill, 1956:63 83,104 11,161 72,175 79, Vigneswaran WT, Trastek VF, Pairolero PC, et al. Extended esophagectomy in the management of carcinoma of the upper thoracic esophagus. J Thorac Cardiovasc Surg 1994; 107: Cameron AJ, Carpenter HA. Barrett s esophagus, highgrade dysplasia, and early adenocarcinoma: a pathological study. Am J Gastroenterol 1997;92: Sampliner RE, and the Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines on the diagnosis, surveillance and therapy of Barrett s esophagus. Am J Gastroenterol 1998;93: Wang KK. Photodynamic therapy of Barrett s esophagus. Gastrointest Endosc Clin N Am 2000;10: Gross CP, Canto MI, Hixson J, Powe, NR. Management of Barrett s esophagus: a national study of practice patterns and their cost implications. Am J Gastroenterol 1999;94: Falk GW, Catalano MF, Sivak MV, et al. Endosonography in the evaluation of patients with Barrett s esophagus and high-grade dysplasia. Gastrointest Endosc 1994;40: Young MM, Deschamps C, Trastek VF, et al. Esophageal reconstruction for benign disease: early morbidity, mortality, and functional results. Ann Thorac Surg 2000;70: Wang KK, Nijhawan PK. Complications of photodynamic therapy in gastrointestinal disease. Gastrointest Endosc Clin N Am 2000;10: Wang KK, Sampliner RE. Mucosal ablation therapy of Barrett esophagus. Mayo Clin Proc 2001;76: DISCUSSION DR JAMES D. LUKETICH (Pittsburgh, PA): I very much enjoyed your presentation. I think it s a subject that needs a lot of investigation, particularly in this area of esophagectomy. It seems that we have had some discussions through the course of the meetings about the benefits of less invasive procedures in the early outcome, such as the actual hospital stay, and there is some debate whether there are advantages. You have shown that even with open esophagectomy, by the longterm follow-up, the quality of life is actually quite good and may be better than normal. Have you applied the SF-36 in the short term, that is at 3-, 6-, 9-, 12-month intervals? It may be that intermediate outcome is important to examine, especially as we are evaluating less invasive procedures. And do you suggest any other tools specifically looking at return to work or return to daily activities in that early 6- to 12-month or even 24-month period? Thank you. Again, I enjoyed your presentation. DR HEADRICK: In this particular article we wanted to go for long-term follow-up. Our median follow-up was 5 years. So we did not pick an early point in time to acquire enough patients to have a study like this. Most of them were many years out. As we said, the median was 5 years from the follow-up. So we do not have that early data. My guess is that early on, they would not feel as good about themselves, but as they recover from the operation, and particularly any of the morbidity associated with it, they all return back to a normal lifestyle and perceive their life as a good-quality life. DR STEVE R. DEMEESTER (Los Angeles, CA): That was a very enjoyable paper, and it s nice to see some information from Mayo Clinic following the reports from our institution as well as from the Cleveland Clinic on these patients with high-grade dysplasia. I was interested in a couple things. One was the relatively few patients who had previous fundoplications. Can you identify how many actually had fundoplications and developed cancer? You lumped those together with gastric procedures. How many actually had fundoplications? What was the time interval from the fundoplication to the development or the identification of the cancer, and was there any evidence whether the fundoplication, symptomatically or otherwise, was functioning or not in the patients who developed cancer? I noticed that one of your patients had a gastrectomy and Roux-en-Y. That seems a bit unusual for someone with Barrett s. Was this a short segment of Barrett s or just a Carcinoma-in-situ or something that allowed you to resect that patient with a gastrectomy and Roux-en-Y? What were the details of that patient? In contrast to the other reported series that have demonstrated about a 50% incidence of cancer in patients thought to have high-grade dysplasia, you had a little bit lower incidence of cancer but a markedly higher incidence of advanced cancer in terms of T3 tumors. How do you explain 5 patients with T3 tumors completely undetected endoscopically in this series? That certainly should, I would think, serve as a warning against local ablative therapy, such as photodynamic therapy. If you can not identify a T3 tumor endoscopically, that certainly raises some concerns. Can you explain that? You broke it down into the lymph node stratification. Can you give us an idea of how many patients with mucosal-only tumors had lymph node involvement? DR HEADRICK: Well, in our series we saw that 17% of the patients had some prior antireflux procedure, and predominantly that was a Nissen fundoplication done through either a laparoscopic or an open approach. We do not have the specific data on those specific patients as far as the breakdown on who went on and had cancer or not, nor the time from their fundoplication to the time that we actually operated on them. Along the same lines, with 17% having some prior antireflux

7 Ann Thorac Surg HEADRICK ET AL 2002;73: BARRETT S ESOPHAGUS: HIGH-GRADE ESOPHAGEAL DYSPLASIA 1703 procedure, those that did not have a standard transhiatal or Ivor Lewis approach got some other intervention because of the lack of being able to use the stomach as a conduit, and that was then up to the surgeon s preference, and in this one case they must have had a short segment of Barrett s and chose to do a Roux-en-Y as opposed to a colon interposition. Our incidence of cancer was 35%, and that can go up or down depending on how you look at these specimens preoperatively and include them in the study. There are lots of patients that come along that you know there is a mass, there is some finding that they likely have cancer, and on biopsy you are just seeing high-grade dysplasia, and the pathologist is telling you everything short of coming out and saying that it s cancer. Those patients we did not include in this study, and you can easily up your incidence from 35% to 50% if you include all of those patients. So we tried to select out a pure high-grade dysplasia population using the pathologist to help us. In those patients it was clearly just high-grade dysplasia, and going into it, there was no suspicion that they really had an underlying cancer. The T3 tumors, it was surprising to us also, and it shows, particularly in our earlier experience, that we were not as good at predicting. Not everybody had an endoscopic ultrasound, and those that did maybe were not as good at predicting the degree of involvement, nor could you do it from a routine endoscopic approach. So it certainly is our recommendation and our belief that in these patients a less invasive approach may be inadequate because of the significant number of people that did show up with advanced cancer. DR SCOTT J. SWANSON (Boston, MA): Because of that striking incidence of 1 in 3 cancers, have you changed your surveillance strategy for Barrett s, and what is your current Mayo Clinic surveillance strategy for Barrett s esophagus so you won t miss these cancers? DR HEADRICK: Well, the trend has actually been over the years with just simply Barrett s to go from an every year approach to initial biopsy, repeat it in a year, and if that s still showing no signs of dysplasia, then they will decrease the frequencies to 2- or 3-year intervals. If somebody is showing signs of high-grade dysplasia or low-grade dysplasia or some other concern, well, then, the frequency increases. The concern and what this article tried to address was, if somebody comes with a biopsy of high-grade dysplasia, which route should the patient go. With a lot of interest in less invasive treatments such as photodynamic therapy or mucosal resection, we wanted to set a standard for what we think should be the approach and what the long-term survival, functional outcome, and follow-up quality of life is with this type of approach. DR SWANSON: The ones that had the cancer, could you look back at your data and determine whether there was anything that predicted it? In other words, there was more moderate dysplasia in those patients, or anything that might help you find those patients before they get their cancer. DR HEADRICK: The most striking finding was that if there was any other associated finding on endoscopy, whether there was nodularity, whether there was an ulcer, whether there was stricture, then you even had a much larger suspicion that there was an underlying malignancy, and in this study it went up to 52%. Normal esophagus with just Barrett s with high-grade dysplasia, the underlying chance of having a malignancy was only 10%. Internet Discussion Forum The Annals of Thoracic Surgery Discussion Forum has resumed with a new format. Each month, we will select an article from The Annals for discussion within the Surgeon s Forum of the CTSNet Discussion Forum Section. The articles chosen will rotate among the six dilemma topics covered under the Surgeon s Forum, which include: General Thoracic Surgery, Adult Cardiac Surgery, Pediatric Cardiac Surgery, Cardiac Transplantation, Lung Transplantation, and Aortic and Vascular Surgery. Once the article selected for discussion is published in the online version of The Annals, we will post a notice on the CTSNet home page ( with a FREE LINK to the full-text article. Readers wishing to comment can post their own commentary in the discussion forum for that article, which will be informally moderated by The Annals Internet Editor. We encourage all surgeons to participate in this interesting exchange and to avail themselves of the other valuable features of the CTSNet Discussion Forum and web site. For June, the article chosen for discussion under the Adult Cardiac Surgery Dilemma Section of the Discussion Forum is: Patient Prosthesis Mismatch Is Rare After Aortic Valve Replacement: Valve Size May Be Irrelevant Naoji Hanayama, MD, George T. Christakis, MD, Hari R. Mallidi, MD, Campbell D. Joyner, MD, Stephen E. Fremes, MD, Christopher D. Morgan, MD, Peter R. R. Mitoff, and Bernard S. Goldman, MD Tom R. Karl The Annals Internet Editor UCSF Children s Hospital Pediatric Cardiac Surgical Unit 505 Parnassus Ave, Room S-549 San Francisco, CA Phone: (415) Fax: (212) karlt@surgery.ucsf.edu by The Society of Thoracic Surgeons Ann Thorac Surg 2002;73: /02/$22.00 Published by Elsevier Science Inc