Esophageal Resection for Cancer of the Esophagus: Long-Term Function and Quality of Life

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1 Esophageal Resection for Cancer of the Esophagus: Long-Term Function and Quality of Life Allison J. McLarty, MD, Claude Deschamps, MD, Victor F. Trastek, MD, Mark S. Allen, MD, Peter C. Pairolero, MD, and William S. Harmsen, MS Sections of General Thoracic Surgery and Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota Background. Information on function and quality of life of long-term survivors after esophageal resection for carcinoma is limited. Methods. Between 1972 and 1990, 359 patients underwent esophagectomy for stage I or II esophageal carcinoma at Mayo Clinic. We evaluated long-term function and quality of life in 107 of these patients (81 men and 26 women) who survived 5 or more years. Median age at operation was 62 years (range, 30 to 81 years). The operation performed was an Ivor Lewis resection in 77 patients (72%), transhiatal esophagectomy in 14 (13%), extended esophagectomy in 4 (4%), thoracoabdominal esophagectomy in 4 (4%), and other in 8 (7%). Adenocarcinoma was present in 72 patients (67%), squamous cell carcinoma in 28 (26%), and other in 7 (7%). Thirty-four patients (32%) were in postsurgical stage I, 65 (61%) in stage IIA, and 8 (8%) in stage IIB. Median survival was 10.2 years (range, 5.0 to 23.2 years). Follow-up was complete for all patients. Results. Gastroesophageal reflux was present in 64 patients (60%), symptoms of dumping in 53 (50%), and dysphagia to solid food in 27 (25%). Seventeen patients (16%) were asymptomatic. Factors affecting late functional outcome were analyzed. Patients who had a cervical anastomosis had significantly fewer reflux symptoms (p < 0.05). Dumping syndrome occurred more frequently in younger patients (p < 0.05) and women (p < 0.01). Quality of life was assessed separately by the Medical Outcomes Study 36-Item Short-Form Health Survey and compared with the national norm. Scores measuring physical functioning were decreased (p < 0.01). Scores measuring ability to work, social interaction, daily activities, emotional dysfunction, perception of health, and levels of energy were similar. Mental health scores were higher (p < 0.05). Conclusions. We conclude that long-term functional outcome after esophagectomy for esophageal carcinoma is affected by age, sex, and type of reconstruction. Quality of life as judged by the patients is similar to the national norm. (Ann Thorac Surg 1997;63: ) 1997 by The Society of Thoracic Surgeons Early detection and resection of esophageal carcinoma provides the best chance for cure [1]. Long-term survival is mostly stage dependent [2 4]. Five-year survival for resected stage I carcinoma ranges between 50% and 85% and for resected stage II carcinoma, between 20% and 50% [1 5]. Because the incidence of adenocarcinoma of the esophagus and esophagogastric junction is increasing [6], endoscopic surveillance for Barrett s disease will very likely lead to earlier cancer detection and resection and possibly improved long-term survival [7, 8]. However, little is known of the functional status and quality of life of long-term survivors after curative resection for esophageal carcinoma [9]. The purpose of this review was to analyze both esophageal function and quality of life in patients who survived more than 5 years after resection of esophageal carcinoma. Presented at the Forty-third Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 7 9, Address reprint requests to Dr Deschamps, Section of General Thoracic Surgery, Mayo Clinic and Mayo Foundation, 200 First St SW, Rochester, MN ( deschamps.claude@mayo.edu). Material and Methods Study Design Between January 1972 and December 1990, 359 patients underwent esophageal resection at the Mayo Clinic for stage I or II (A and B) carcinoma of the esophagus. One hundred seven of these patients (30%) survived 5 or more years. The records of these patients were analyzed for age, sex, signs and symptoms at presentation, type of operation, postsurgical stage, operative morbidity, adjuvant therapy, functional outcome, and quality of life. All tumors were staged by the TNM classification system of the American Joint Committee for Cancer Staging and End-Results Reporting [10]. Follow-up data were obtained from the patient s most recent clinic visit and a two-part mail survey. Part one evaluated subjective digestive function as it relates to the esophagectomy patient. It specifically addressed the qualitative and quantitative estimate of dysphagia, the need of esophageal dilation, the presence of heartburn, and the need of medication. Other queries concerned the size and number of daily meals, the presence of dumping symptoms, bowel habits, and weight change. Part two used the Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) [11]. This na by The Society of Thoracic Surgeons /97/$17.00 Published by Elsevier Science Inc PII S (97)

2 Ann Thorac Surg McLARTY ET AL 1997;63: ESOPHAGEAL RESECTION 1569 tional standardized questionnaire is a self-administered health-assessment tool that permits group comparisons in eight conceptual areas covering general health (health perception), daily activities (physical functioning), work (role-physical), emotional problems (role-emotional), social activities (social functioning), nervousness/depression (mental health), pain (bodily pain), and vitality (energy/fatigue). A numeric score is computed for the answers in each of the conceptual areas. Means and standard deviations of the numerical score were determined and compared with national norms matched for age and sex. The MOS SF-36 was constructed to measure population differences in physical and mental health status, the health burden of chronic disease, and the effect of treatments on general health status. It provides a common yardstick to compare patients with chronic health problems with people sampled from the general population. Relationship between variables was assessed using 2 tests for discrete factors and Wilcoxon rank sum tests for continuous factors [12]. Evaluation of the patients responses to the health status questionnaire relative to a matched population (national norm) was done using the signed-rank test [13]. Survival using the 5-year follow-up date as the starting time was estimated using the Kaplan- Meier method [14]. A p value of less than 0.05 was considered significant. The two-part written survey was sent to 80 patients believed to be alive at the beginning of this study. No response was obtained from 11 patients, 7 of whom were later found to have died before the survey was sent; the other 4 were lost to follow-up. Sixty-nine patients returned the survey. Five patients were excluded because of incomplete data. Thus, complete data were available on 64 patients, for a response rate of 80%. The results of part one of the written survey were combined with information obtained from our outpatient clinic to provide information on all patients. Clinical Findings There were 81 men and 26 women. At the time of esophagectomy, median age was 62 years (range, 30 to 81 years). Preoperative signs and symptoms were present in all 107 patients and included dysphagia in 65 (61%), chest pain in 28 (26%), anemia in 22 (21%), odynophagia in 13 (12%), and hoarseness in 3 (3%). Thirty-five patients (33%) were seen with a median weight loss of 9 kg (range, 2.25 to 22.5 kgs). Three patients had a prior history of achalasia and 2, of lye ingestion. Two patients received chemotherapy prior to surgical resection, and 2 had radiation therapy. The operation performed was an Ivor Lewis esophagogastrectomy in 77 patients (72%), transhiatal esophagectomy in 14 (13%), extended esophagectomy in 4 (4%), left thoracoabdominal esophagectomy in 4 (4%), partial esophagectomy and total gastrectomy in 3 (3%), and segmental esophageal resection in 5 (5%). Intestinal continuity was reestablished with the stomach in 99 patients (93%), the small bowel in 4 (4%), and the isoperistaltic left colon in 3 (3%). One patient (1%) had a primary end-toend esophageal anastomosis after a segmental resection of the cervical esophagus. Overall, 87 patients (81.3%) had an intrathoracic anastomosis and 20 patients (18.7%), a cervical anastomosis. A pyloromyotomy was done in 52 (49%) and a pyloroplasty, in 36 (34%). Forty-nine patients underwent 50 associated procedures. Splenectomy was done in 30 patients (28%), a feeding jejunostomy in 6, cholecystectomy in 5, appendectomy in 2, lung biopsy in 2, and laryngectomy and radical neck dissection, liver biopsy, left vocal cord polypectomy, excision of an ectopic focus of pancreas, and excision of an abdominal wall nevus in 1 patient each. Intraoperative complications occurred in 2 patients: a tracheal laceration in 1 and bleeding from the azygos vein in the other. Both patients required a right thoracotomy, and both recovered without sequelae. Postoperative complications occurred in 43 patients (40%). Thirteen patients (12%) had anastomotic leaks. Seven leaks were unsuspected and contained on contrast study, and all healed without further complications. The remaining 6 patients required reoperation; 3 had reexploration and drainage of the cervical area, and 3 had thoracotomy, mediastinal debridement, and drainage. Three patients bled postoperatively, and all 3 required reexploration. One patient had ischemia of a gastric conduit and required reexploration and staged reconstruction with a colon interposition. Other complications included supraventricular tachycardia in 12 patients, wound infections in 12, pneumonia or retained secretions in 9, myocardial infarction in 2, and chylothorax, left vocal cord paralysis, vaginal bleeding, and pancreatitis in 1 patient each. The tumor was located at the gastroesophageal junction in 62 patients (58%), in the middle third of the esophagus in 43 (40%), and in the cervical region in 2 (2%). Adenocarcinoma was present in 72 patients (67%), squamous cell carcinoma in 28 (26%), leiomyosarcoma in 3 (3%), and hemangiopericytoma, small cell carcinoma, undifferentiated carcinoma, and neuroendocrine carcinoma in 1 patient each. Thirty-two (44%) of the 72 patients with adenocarcinoma had histologically confirmed Barrett s mucosa. Thirty-four patients were postsurgically classified as stage I (32%), 65 as stage IIA (61%), and 8 (8%) as stage IIB. Nine patients underwent adjuvant treatment; 3 had chemotherapy, 2 had irradiation, and 4 had both. Results Survival Seventy-two patients (67%) were alive at last follow-up. Sixty-six patients (62%) were free from disease. Four patients (4%) were alive, but the status of the cancer was unknown. Two patients (2%) were alive with recurrent disease. Thirty-five patients (33%) had died. Cause of death was unrelated to esophageal carcinoma in 17 patients (16%) and unknown in 9 (8%). Nine patients (8%) died of recurrent carcinoma. Overall median survival after esophagectomy was 10.2 years (range, 5.0 to 23.2

3 1570 McLARTY ET AL Ann Thorac Surg ESOPHAGEAL RESECTION 1997;63: Fig 1. Probability of survival (death due to any cause) of 107 patients undergoing esophagectomy for stage I or II esophageal carcinoma. Starting time on the abscissa represents 5 years after esophagectomy (p 0.05). years). Overall actuarial 10-year and 15-year survival was 76.6% (95% confidence interval, 67.9% to 85.3%) and 53.6% (95% confidence interval, 40.4% to 66.8%), respectively (Fig 1). Overall, survival after 5 years was significantly less (p 0.05) than the expected survival of a normal population. Functional Outcome Information on functional esophageal outcome was available for all 107 patients. Seventeen patients (16%) were entirely asymptomatic. Twenty-seven patients (25%) had dysphagia to solid food, 10 (9%) had pain on swallowing, 10 (9%) had dysphagia to a pureed diet, and 3 (3%) had dysphagia to liquids. Forty-six patients (43%) underwent at least one postoperative dilation. Sixty-four patients (60%) had heartburn, which was intermittent in 58 and continuous in 6. Thirty-one patients (29%) required antacids for relief of heartburn. Forty patients (37%) ate smaller, more frequent meals. Fifty-two patients (49%) never regained lost weight after the operation, 27 (25%) maintained their initial preoperative weight, and 6 (6%) gained weight compared with their preoperative weight. Fifty-three patients (50%) experienced symptoms of postprandial dumping, including 26 (24%) with diarrhea, 17 (16%) with abdominal cramps, 8 (8%) with nausea, 7 (7%) with dizziness, and 6 (6%) with diaphoresis. Factors affecting late functional outcome were analyzed. Patients with a cervical anastomosis had significantly fewer symptoms of reflux (p 0.05) than those with an intrathoracic anastomosis. Dumping symptoms occurred more frequently in younger patients (p 0.05) and in women (p 0.01). Neither the type of resection (p 0.82) nor the occurrence of a postoperative leak (p 0.56) influenced the need for dilation. The time interval since operation, tumor location, histology, adjuvant therapy, anastomotic leak, and type or absence of gastric drainage did not significantly affect late functional outcome. Quality of Life Information on quality of life as assessed by the MOS SF-36 was available for 64 patients (80%). A score was computed for each patient in each of the eight conceptual areas. Data are expressed as the mean ( the standard deviation) for the group. Physical function scores were decreased significantly (p 0.01) compared with the national norm (Table 1). Ability to work, social interaction, daily activities, emotional dysfunction scores, and perception of health were similar to the national norm. Level of energy was decreased compared with the national norm, but the significance was borderline (p 0.05). Our patients had higher scores in the area of mental health (p 0.05). Factors affecting quality of life were also analyzed. The occurrence of a postoperative anastomotic leak adversely affected the physical functioning and the health perception scores in our population (p 0.05). Also, the need of postoperative dilation adversely affected the social functioning score (p 0.01). Age, sex, time interval from operation, location of lesion, histology, type of operation, and adjuvant therapy did not significantly affect any of the eight conceptual areas measured by the quality of life questionnaire. Comment Success of curative treatment of esophageal cancer has traditionally been measured with survival. Few reports on quality of life after esophageal resection for cancer have been published. A review of the literature by Gelfand and Finley [9] in 1994 revealed that of 7,569 publications on the subject of esophageal carcinoma, only 44 (0.58%) dealt with quality of life. Clearly, a better understanding of the functional outcome and quality of life of long-term survivors is needed in this new era of health care. Appropriate tools to measure outcome, however, are limited, and development of such instruments will become increasingly important in the future if surgeons are to better plan preoperative counseling, surgical approach, and postoperative care. Only a minority of our patients (16%) were completely symptom free 5 or more years after esophageal resection. More than 50% complained of reflux symptoms, 50% had some degree of dumping, and 46% had difficulty swallowing. Moreover, dumping symptoms were increased in younger patients and in women. These findings have also Table 1. Results of Quality of Life Survey a Category Patient Population Normal Population Health perception 65.3 (19.7) 69.9 (5.3) Physical functioning 70.9 (25.8) b 80.5 (9.4) Role-physical 76.2 (36.6) 75.8 (12.7) Role-emotional 87.2 (25.8) 86.4 (6.2) Social functioning 86.5 (23.6) 88.4 (4.4) Mental health 80.5 (14.8) b 78.3 (1.6) Bodily pain 79.3 (22.2) 76.2 (5.2) Energy/fatigue 56.5 (20.4) c 62.9 (3.5) a Scores are shown as the mean with the standard deviation in parentheses. b Significance: p 0.05 compared with normal population matched for age and sex. c Significance: p 0.05.

4 Ann Thorac Surg McLARTY ET AL 1997;63: ESOPHAGEAL RESECTION 1571 been reported by others [15 20]. In contrast to our functional outcome findings, however, esophagectomy for cancer did not appear to influence quality of life. Our patients were comparable to the national norm in all areas except physical functioning and actually scored significantly higher than the national norm in the area of mental health. One significant finding in our study revolves around the location of the anastomosis. The incidence of reflux is significantly reduced if the anastomosis is located in the neck. However, reduction in late reflux has to be balanced against an increased rate of fistula formation and recurrent nerve injury [3, 4] associated with the cervical anastomosis in the early postoperative period. Moreover, the occurrence of a postoperative leak had an adverse impact on quality of life scores that measure physical functioning and health perception. In addition, the need of dilation postoperatively adversely affected the social functioning score. Others [21] have also shown that complications associated with a cervical anastomosis can have long-lasting consequences. No standardized tool exists for evaluating quality of life of patients with esophageal carcinoma, and the discrepancy in the results observed in the two parts of our study points to the difficulty of developing a valid questionnaire for a specific population of patients. Others [22, 23] have reported similar findings where symptoms specific to esophageal disease correlated poorly with quality of life scores. One possible explanation for the poor correlation is that despite symptoms secondary to the operation, most patients can function at home or work and are happy to be alive and free from cancer [24]. We conclude that long-term survival after esophagectomy for stage I and II esophageal carcinoma is less than that expected in a normal population. Functional outcome after operation is affected by age, sex, and type of resection. For patients surviving 5 or more years, symptoms of reflux, dumping, and dysphagia are not uncommon. However, quality of life after resection as assessed by the patients themselves is similar to the national norm. References 1. O Rourke I, Tait N, Bull C, Gebski V, Holland M, Johnson DC. Oesophageal cancer: outcome of modern surgical management. Aust N Z J Surg 1995;65: King RM, Pairolero PC, Trastek VF, Payne WS, Bernatz PE. Ivor Lewis esophagogastrectomy for carcinoma of the esophagus: early and late functional results. Ann Thorac Surg 1987;44: Vigneswaran WT, Trastek VF, Pairolero PC, Deschamps C, Daly RC, Allen MS. Transhiatal esophagectomy for carcinoma of the esophagus. Ann Thorac Surg 1993;56: Vigneswaran WT, Trastek VF, Pairolero PC, Deschamps C, Daly RC, Allen MS. Extended esophagectomy in the management of carcinoma of the upper thoracic esophagus. J Thorac Cardiovasc Surg 1994;107: Lizuka T, Isono K, Kakegawa T, Watanabe H. Parameters linked to ten-year survival in Japan of resected esophageal carcinoma. Chest 1989;96: Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993;104: Pera M, Trastek VF, Carpenter HA, Allen MS, Deschamps C, Pairolero PC. Barrett s esophagus with high-grade dysplasia: an indication for esophagectomy? Ann Thorac Surg 1992;54: Edwards MJ, Gable DR, Lentsch AB, Richardson JD. The rationale for esophagectomy as the optimal therapy for Barrett s esophagus with high-grade dysplasia. Ann Surg 1996;223: Gelfand GAJ, Finley RJ. Quality of life with carcinoma of the esophagus. World J Surg 1994;18: Beahrs OH, Henson DE, Hutter RV, Kennedy BJ. American Joint Commission on Cancer: manual for staging of cancer. 4th ed. Philadelphia: Lippincott, 1992: Ware JE. SF-36 Health survey. Manual and interpretation guide. Boston: Nimrod, Dixon WJ, Massey FJ Jr. Introduction to statistical analysis. 3rd ed. New York: McGraw-Hill, 1969:77 80, 116 8, , 344 5, Siegel S. Nonparametric statistics for the behavioral sciences. 1st ed. New York: McGraw-Hill, 1956:63 83, , , 175 9, Kaplan EL, Meier P. Non-parametric estimation from incomplete observation. J Am Stat Assoc 1958;53: Suzuki H, Shichisaburo A, Kitamura M, Hashimoto M, Izumi K, Sato H. An evaluation of symptoms and performance status in patients after esophagectomy for esophageal cancer from the viewpoint of the patient. Am Surg 1994;60: Nishihira T, Watanabe T, Ohmori N, et al. Long-term evaluation of patients treated by radical operation for carcinoma of the thoracic esophagus. World J Surg 1984;8: Collard J-M, Otte J-B, Reynaert M, Kestens P-J. Quality of life three years or more after esophagectomy for cancer. J Thorac Cardiovasc Surg 1992;104: De Leyn P, Coosemans W, Lerut T. Early and late functional results in patients with intrathoracic gastric replacement after oesophagectomy for carcinoma. Eur J Cardio-thorac Surg 1992;6: Orringer MB, Marshall B, Stirling MC. Transhiatal esophagectomy for benign and malignant disease. J Thorac Cardiovasc Surg 1993;105: Finley RJ, Lamy A, Clifton J, Evans KG, Fradet G, Nelems B. Gastrointestinal function following esophagectomy for malignancy. Am J Surg 1995;169: Iannettoni MD, Whyte RI, Orringer MB. Catastrophic complications of the cervical esophagogastric anastomosis. J Thorac Cardiovasc Surg 1995;110: Blazeby JM, Williams MH, Brookes ST, Alderson D, Farndon JR. Quality of life measurement in patients with oesophageal cancer. Gut 1995;37: Van Knippenberg FCE, Out JJ, Tilanus HW, Mud HJ, Hop WCJ, Verhage F. Quality of life in patients with resected oesophageal cancer. Soc Sci Med 1992;35: Kuwano H, Ikebe M, Baba K, et al. Operative procedures of reconstruction after resection of esophageal cancer and the postoperative quality of life. World J Surg 1993;17:773 6.

5 1572 McLARTY ET AL Ann Thorac Surg ESOPHAGEAL RESECTION 1997;63: DISCUSSION DR KAMAL A. MANSOUR (Atlanta, GA): It is my pleasure to discuss this paper from the Mayo Clinic. It is well organized, the facts are well documented, and the conclusions are very clearly stated. This paper went beyond what we do surgically for our patients to address the quality of life for those who survive 5 or more years after esophagogastrectomy for cancer of the esophagus. Although the quality of life, as judged by your patients themselves, is similar to the national norm, there is a 60% incidence of reflux, 50% incidence of dumping symptoms, and 25% incidence of dysphagia to solid foods. Our experience at Emory is similar. We prefer the Ivor Lewis approach, as you do. We had a similar incidence of gastroesophageal reflux early in our experience when we were doing pyloroplasty or pyloromyotomy routinely, as you do. However, for the past 15 years, we have stopped doing pyloroplasty, except when the pylorus is deformed or scarred from previous peptic ulcer disease. In patients with severe bile reflux whom we encountered early in our experience, the problem was eliminated by doing a Roux-en-Y gastrojejunostomy. I believe the increased incidence of adenocarcinoma of the esophagus in your series as in ours and many others is due to the increased incidence of Barrett s esophagus, which is, in my opinion, caused by the reflux of bile rather than acid. We may have to address the question of duodenogastric reflux of bile more seriously. I have two questions. First, have you studied whether the high incidence of gastroesophageal reflux in your series is due to bile or acid, as I assume you cut both vagus nerves? Second, do you use any preoperative chemotherapy? DR LEWIS WETSTEIN (Freehold, NJ): I also commend you on your presentation and your impressive results. Dr Mansour covered most of my points. The only other question I have concerns your initial group of 359 patients. Are the percentages of each histologic group similar throughout the study and results? I ask this because the overwhelming majority of your survivors had adenocarcinoma. Although we are seeing an increasing number of esophageal adenocarcinomas, we definitely do not to that degree. In fact, we still see a preponderance of squamous cell carcinoma. Moreover, in our hands, and maybe this is unique to the North, adenocarcinoma appears to be much more aggressive. Did most of the initial 359 patients have adenocarcinoma, or did those with this histopathologic type just indeed do better? DR MCLARTY: Thank you for your comments. We did not do any studies to determine whether the nature of reflux was biliary or acid, so I do not have that information. You may not have noted it in the manuscript, but 4 patients received adjuvant therapy preoperatively. Two had chemotherapy and 2, radiation therapy. Finally, the distribution of histology was indeed superimposable. The majority of our 359 patients did have adenocarcinoma. It is unclear why. It might be secondary to the aggressive screening done for Barrett s esophagus by our gastroenterologists. Indeed, we might be picking up malignancy earlier. This could be the reason for the increased number of adenocarcinomas seen in our series.