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Morbidity and mortality after self-expandable metallic stent placement in patients with progressive or recurrent esophageal cancer after chemoradiotherapy
Morbidity and mortality after self-expandable metallic stent placement in patients with progressive or recurrent esophageal cancer after chemoradiotherapy Tetsuya Sumiyoshi, MD, Takuji Gotoda, MD, Kei Muro, MD, Bjorn Rembacken, MD, Masahiro Goto, MD, Yoko Sumiyoshi, MD, Hiroyuki Ono, MD, Daizo Saito, MD Tokyo, Japan
Background: Placement of self-expandable metallic stents in patients with advanced esophageal cancer improves dysphagia and occludes tracheoesophageal fistulas. However, the safety of selfexpandable metallic stents for patients who have undergone chemoradiotherapy is controversial. This study evaluated the morbidity and modality after self-expandable metallic stent placement in patients with progressive or recurrent esophageal cancer after chemoradiotherapy. Methods: A total of 22 patients in whom self-expandable metallic stents were placed because of progressive or recurrent esophageal cancer after chemoradiotherapy were studied. Results: All 22 patients had dysphagia, and 13 had a tracheoesophageal fistula. After self-expandable metallic stent placement, the mean dysphagia grade improved from 3.5 to 0.9, and tracheoesophageal fistula was successfully managed in all cases. Seventeen patients had T4 stage disease, and among 8 of them with invasion to the aorta, 6 (75%) died of sudden massive hemorrhage. Median survival for these 6 patients was 31 days (range 13-63 days) compared with 67 days (range 4-262 days) for all patients after self-expandable metallic stent placement. Conclusion: Self-expandable metallic stent placement improved dysphagia and was useful for treatment of tracheoesophageal fistula. However, for patients with T4 lesions that invade to the aorta, self-expandable metallic stent placement after chemoradiotherapy should be considered carefully. (Gastrointest Endosc 2003;57:882-5.)
Although surgery is the standard therapy for localized esophageal cancer, the results with surgery alone remain poor, with 5-year survival rates of 6% to 24%.1 Studies have found, however, that chemoradiotherapy may be curative in locally advanced esophageal cancer, with results comparable with those of radical surgery.2-4 Therefore, chemoradiotherapy may become the standard therapy for patients with advanced esophageal cancer. However, local recurrence develops in nearly half of the patients treated with chemoradiotherapy.2 Dysphagia and tracheoesophageal fistulas are common complications of advanced esophageal cancer. Fatalities have been reported after placement of plastic esophageal stents.5-9 Successful self-expandable metallic stent (SEMS) placement was first reported by Domschke et al.10 in 1990. Subsequent trials found Received January 31, 2002. For revision May 1, 2002. Accepted February 10, 2003. Current affiliations: Department of Endoscopy, National Cancer Center Hospital, Tokyo, Japan, Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan, Centre for Digestive Diseases, The General Infirmary at Leeds, United Kingdom. Reprint requests: Takuji Gotoda MD, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. Copyright © 2003 by the American Society for Gastrointestinal Endoscopy 0016-5107/2003/$30.00 + 0 doi:10.1067/mge.2003.234 882
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this type of stent to be effective and safe for treatment of patients with malignant dysphagia and tracheoesophageal fistulas.11-19 However, whether SEMS placement is safe for patients who have undergone chemoradiotherapy is a matter of debate.20-23 Thermal ablative therapy, (e.g., Nd:YAG laser photoablation or argon plasma coagulation) also is used widely for palliation of patients with malignant dysphagia. However, such therapy requires multiple treatments, is costly, and re-occlusion requiring retreatment is common.21,24 In addition, thermal ablative therapy is of no benefit in the treatment of tracheoesophageal fistulas. To the investigators’ knowledge, there is no previous study that addresses the association between tumor stage and life-threatening complications related to SEMS placement in patients who have had chemoradiotherapy. This study retrospectively evaluated post–SEMS-placement morbidity and modality for patients with progressive or recurrent esophageal cancer after initiation of chemoradiotherapy. PATIENTS AND METHODS At the National Cancer Center Hospital, 172 patients with advanced esophageal cancer, seen from October 1998 to September 2001, received chemoradiotherapy. In 22 of these patients, an SEMS was placed because of recurrent esophageal cancer or esophageal cancer that VOLUME 57, NO. 7, 2003
Esophageal cancer chemoradiotherapy: morbidity, mortality after SEMS placement
Table 1. Characteristics of patients with advanced esophageal cancer Patient gender Male Female Median age (range) Histopathology of tumor Squamous cell carcinoma Location of tumor Proximal third Middle third Distal third Mean length of tumor (range) Depth of tumor invasion T2 T3 T4 Invasion to aorta Invasion to bronchus Obstruction before placement of SEMS Present Absent Fistula before placement of SEMS Present Absent Mean dysphagia grade before placement of SEMS Primary therapy Chemoradiotherapy Radiation alone
19 3 66 y (49-82) 22 3 16 3 6.8 cm (3.5-10) 1 4 17 8 10 19 3 13 9 3.5
20 2
had progressed after chemoradiotherapy. Endoscopy and/or contrast esophagography were performed to determine the location and length of the tumor and to confirm the level of obstruction and identify tracheoesophageal fistulas. The diagnosis of esophageal cancer was made by histopathologic evaluation of endoscopic biopsy specimens. The extent of tumor invasion (T factor) was evaluated by CT of the chest and/or EUS with either 7.5 or 20 MHz frequencies, using the standard TNM classification system.25 Dysphagia was assessed before and after SEMS placement and graded as follows: grade 0, normal swallowing; grade 1, unable to swallow solids; grade 2, unable to swallow semisolids; grade 3, unable to swallow liquids; and grade 4, unable to swallow saliva.26 All stents were placed over a guidewire endoscopically with fluoroscopic monitoring; these procedures were performed under sedation during hospitalization. Morbidity and mortality were evaluated after SEMS placement for the 22 patients with recurrent or progressive tumor after receiving chemoradiotherapy. Post– SEMS complications were defined as any new adverse event after placement, including high fever, chest pain, food impaction, stent migration, and bleeding within the first week after the procedure. Survival was measured from SEMS placement to death or most recent follow-up. Survival rates were calculated using the Kaplan-Meier method. An inclusive consent, including consent for review of medical records, was obtained from each patient at the first examination. VOLUME 57, NO. 7, 2003
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Table 2. Post–SEMS-placement complications High fever (>38°C) Chest pain Food impaction Stent migration Bleeding
77.3% 81.8% 9.1% 9.1% 9.1%
(17/22) (18/22) (2/22) (2/22) (2/22)
RESULTS Patient characteristics Characteristics for the 22 patients (19 men, 3 women; median age 66, range 49 to 82 years) are shown in Table 1. Three tumors were located in the proximal esophagus, 16 in the mid esophagus, and 3 in the distal esophagus. Mean tumor length was 6.8 cm (range 3.5-10 cm). Histopathologically, all tumors were squamous cell carcinoma. The extent of tumor invasion was T2 in 1 patient, T3 in 4 patients, and T4 in 17 patients before chemoradiotherapy. Eight of the 17 patients with clinical T4 cancers had invasion to the aorta; 10 had invasion to a bronchus. In one patient, the cancer invaded to both aorta and bronchus. All 22 patients had dysphagia and 13 had a tracheoesophageal fistula at initial evaluation. The mean dysphagia grade was 3.5 before SEMS placement. Twenty patients previously had undergone chemoradiotherapy and 2 had received radiotherapy alone because of liver cirrhosis in one and the advanced age of the other (82 years). Post–SEMS-placement complications Stents were successfully placed in all patients; a single stent was placed in 21 patients and 2 stents in 1 patient. An Ultraflex stent (Boston Scientific, Watertown, Mass.) was used in 19 patients and a Wallstent (Schnider, Blanch, Switzerland) in 4 patients. Post–SEMS-placement complications are shown in Table 2. High fever (>38°C) and severe chest pain that required administration of analgesic medication were common. Minor hemorrhage, not requiring transfusion, developed in 2 cases after stent placement. There were no deaths post SEMS placement. Post–SEMS-placement morbidity and mortality Outcomes after SEMS placement are shown in Table 3. Dysphagia improved in 21 of 22 patients (95.5%); mean grade decreased from 3.5 to 0.9. All tracheoesophageal fistulas were successfully occluded as assessed radiographically and endoscopically. Nine patients could not be discharged because of post–SEMS-placement complications or tumor progression after placement. Twenty patients died of post–SEMS-placement complications or tumor progression. The early death (4 days after stent placement) was that of a patient who previously had GASTROINTESTINAL ENDOSCOPY
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Esophageal cancer chemoradiotherapy: morbidity, mortality after SEMS placement
Table 3. Outcome after SEMS placement Dysphagia relief 95.5% (21/22) Mean dysphagia grade after placement of SEMS 0.9 Fistula closure 100% Patients who could be discharged 59.1% (13/22) Patients who could not be discharged 40.9% (9/22) Patient state Dead 20 Alive 2 Median survival for all patients (d) (range) 67 (4-262) Median survival for patients with sudden 31 (13-63) massive hemorrhage (d) (range)
developed a tracheoesophageal fistula complicated by a severe pneumonia. The fistula was successfully managed by emergent SEMS placement, but the patient succumbed to the pneumonia. Sudden massive hemorrhage developed in 6 patients, all of whom died. Clinically, all 6 patients had T4 tumors before chemoradiotherapy commenced. Among the 17 patients with T4 tumors, 8 had invasion to the aorta, and 6 (75%) of these patients died suddenly. For the 6 patients who developed sudden massive hemorrhage, tumor location, length of lesion, and dysphagia grade were not significantly associated with bleeding. Invasion to both aorta and bronchus was found in one patient. In contrast, there was no instance of sudden death among the 9 patients with T4 tumors with invasion to the bronchus. Median survival for the 6 patients who died of sudden massive hemorrhage was 31 days (range 13-63 days) compared with 67 days (range 4-262 days) for all patients after SEMS placement. DISCUSSION Many studies have shown that SEMS placement provides effective palliation for patients with advanced esophageal cancer.11-19 However, most studies did not include patients who had received chemoradiotherapy, and the safety of SEMS placement in such patients is uncertain.20-23 In general, it is difficult to distinguish clearly whether the lifethreatening events after SEMS placement were stent-related or caused by tumor progression. However, radiation can cause esophageal injury with esophagitis and ulceration, and esophageal perforation and tracheoesophageal fistulas may also occur because of radiation-induced vasculitis.27,28 Furthermore, chemotherapy is known to potentiate radiation-induced esophageal injury.29-31 In addition, an SEMS can cause pressure necrosis in patients previously treated with chemoradiotherapy.21 Thus, it is thought that SEMS placement in the setting of chemoradiotherapy may be associated with esophageal perforation. 884
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Kinsman et al.21 found that life-threatening complications occurred after SEMS placement in 36.4% (8/22) of patients who had prior radiation and/or chemotherapy compared with 2.5% (1/37) of those with no prior therapy. Moreover, the stent-related mortality rate was 23% (5/22) among patients with prior therapy, whereas there were no deaths among the 37 patients without prior therapy. Furthermore, these investigators observed that life-threatening complications were not associated with tumor location, histopathologic tumor type, length of obstructing lesion, dysphagia grade, or previous surgical resection. Bethge et al.22 also found that prior radiotherapy increased the risk of complications after SEMS placement. In contrast, Raijman et al.23 found no association between prior chemoradiotherapy and complications. The most realistic goal of any palliative therapy is maximal relief of symptoms with minimal risk. In the present study, SEMS placement was obviously effective in the treatment of malignant dysphagia and tracheoesophageal fistula. However, post–SEMSplacement complications were common and often life threatening. In particular, 6 patients died of sudden hemorrhage. Thus, it is essential to clarify which patients are eligible for SEMS placement. All 6 patients in whom massive hemorrhage developed suddenly in the present study had T4 cancers clinically with invasion to the aorta before chemoradiotherapy was initiated. These 6 patients were among the group of 8 with aortic invasion; the other 2 patients died of progression of the cancer. It is likely that T4 cancers are susceptible to pressure necrosis from an SEMS, with a consequent increase in the risk of perforation into adjacent structures. However, the mean dysphagia grade improved from 3.8 to 0.7 in patients with aortic invasion compared with an improvement from 3.4 to 1.0 after SEMS placement in patients without aortic invasion. Therefore, other modalities should be selected to improve quality of life with fewer complications for patients with T4 cancers and aortic invasion with tumor progression or recurrence despite chemoradiotherapy. For example, the investigators performed PEG procedures in 3 patients with recurrent esophageal cancer after chemoradiotherapy. They did not have tracheoesophageal fistulas and preferred PEG instead of SEMS placement after they were informed of the increased risk of severe stent-related complications. In conclusion, the investigators suggest that patients under consideration for placement of an SEMS after chemoradiotherapy, especially those with tumor invasion to the aorta, should be advised that while their ability to swallow will most likely improve, the risk of dying from sudden bleeding is substantial. VOLUME 57, NO. 7, 2003
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REFERENCES 1. Roth JA, Putnam JB Jr. Surgery of cancer of the esophagus. Semin Oncol 1994;21:453-61. 2. Al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 1997;15: 277-84. 3. Ohtu A, Boku N, Muro K, Chin K, Muto M, Yoshida S, et al. Definitive chemoradiotherapy for T4 and/or M1-LYM squamous cell carcinoma of the esophagus. J Clin Oncol 1999;17: 2915-21. 4. Kato H, Tachimori Y, Watanabe H, Iizuka T. Evaluation of the new (1987) TNM classification for thoracic esophageal tumors. Int J Cancer 1993;53:220-3. 5. den Hartog Jager FC, Bartelsman JF, Tytgat GN. Palliative treatment of obstructing esophageal malignancy by endoscopic positioning of a plastic prosthesis. Gastroenterology 1979;77:1008-14. 6. Ogilvie AL, Dronfield MW, Percuson R, Atkinson M. Palliative intubation of oesophagogastric neoplasms at fiberoptic endoscopy. Gut 1982;23:1060-7. 7. Liakakos TK, Ohri SK, Townsend ER, Fountain SW. Palliative intubation for dysphagia in patients with carcinoma of the esophagus. Ann Thorac Surg 1992;53:460-3. 8. Spinelli P, Cerrai FG, Ciuffi M, Ignomirelli O, Meroni E, Pizzetti P. Endoscopic stent placement for cancer of the lower esophagus and gastric cardia. Gastrointest Endosc 1994;40:455-7. 9. Wilton A, Smith PM. Endoscopic intubation of oesophagogastric malignancy. Eur J Gastroenterol Hepatol 1995;7:559-62. 10. Domschke W, Foerster EC, Matek W, Rodl W. Self-expanding mesh stent for esophageal cancer stenosis. Endoscopy 1990; 22:134-6. 11. Cwikiel W, Stridbeck H, Tranberg KG, Stael von Holstein C, Hambraeus G, Lillo-Gil R, et al. Malignant esophageal strictures: treatment with a self-expanding nitinol stent. Radiology 1993;187:661-5. 12. Raijman I, Walden D, Kortan P, Haber GB, Fuchs E, Siemens M, et al. Expandable esophageal stents: initial experience with a new nitinol stent. Gastrointest Endosc 1994;40:614-21. 13. Wagner HJ, Stinner B, Schwerk WB, Hoppe M, Klose KJ. Nitinol prostheses for the treatment of inoperable malignant esophageal obstruction. J Vasc Interv Radiol 1994;5:899-904. 14. Ellul JP, Watkinson A, Khan RJ, Adam A, Mason RC. Selfexpanding metal stents for the palliation of dysphagia due to inoperable oesophageal carcinoma. Br J Surg 1995;82:1678-81. 15. Grund KE, Storec D, Becker HD. Highly flexible self-expanding meshed metal stents for palliation of malignant esophagogastric obstruction. Endoscopy 1995;27:486-94. 16. May A, Selmajer M, Hochberger J, Gossner L, Muhldorfer S, Hahn EG, et al. Memory metal stents for palliation of malignant obstruction of the oesophagus and cardia. Gut 1995;37: 309-13. 17. De Palma GD, Galloro G, Sivero L, Di Matteo E, Labianca O,
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Siciliano S, et al. Self-expanding metal stents for palliation of inoperable carcinoma of the esophagus and gastroesophageal junction. Am J Gastroenterol 1995;90:2140-2. Neuhaus H, Hoffman W, Dittler HJ, Niedermeyer HP, Classen M. Implantation of self-expanding stents for palliation of malignant dysphagia. Endoscopy 1992;24:405-10. Winkelbauer FW, Schofl R, Niederle B, Wildling R, Thurnher S, Lammer J. Palliative treatment of obstructing cancer with nitinol stents: value, safety, and long-term results. AJR Am J Roentgenol 1996;166:79-84. Siersema PD, Hop WC, Dees J, Tilanus HW, Blankenstein M. Coated self-expanding metal stents versus latex prostheses for esophagogastric cancer with special reference to prior radiation and chemotherapy: a controlled, prospective study. Gastrointest Endosc 1998;47:113-20. Kinsman KJ, DeGregrio BT, Katon RM, Morrison K, Saxon RR, Keller FS, et al. Prior radiation and chemotherapy increase the risk of life-threatening complications after insertion of metallic stents for esophagogastric malignancy. Gastrointest Endosc 1996;43:196-203. Bethge N, Sommer A, Kleist D, Vakil N. A prospective trial of self-expanding metal stents in the palliation of malignant esophageal obstruction after failure of primary curative therapy. Gastrointest Endosc 1996;44:283-6. Raijman I, Siddique I, Ajani J, Lynch P. Palliation of malignant dysphagia and fistulae with coated expandable metal stents: experience with 101 patients. Gastrointest Endosc 1998;48:172-9. Dallal HJ, Smith GD, Grieve DC, Ghosh S, Penman ID, Palmer KR. A randomized trial of thermal ablative therapy versus expandable metal stents in the palliative treatment of patients with esophageal carcinoma. Gastrointest Endosc 2001;54:549-57. Sobin LH, Wittkind CH, editors. UICC TNM classification of malignant tumors. 5th ed. New York: Wiley-Liss; 1997. p. 54-8. Mellow MH, Pinkas H. Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction: analysis of technical and functional efficacy. Arch Intern Med 1985;145:1443-6. Seaman EB, Ackerman LV. The effect of radiation on the esophagus. A clinical and histologic study of the effects produced by the betatron. Radiology 1957;68:534-41. Vanagunas A, Jacob P, Olinger E. Radiation-induced esophageal injury: a spectrum from esophagitis to cancer. Am J Gastroenterol 1990;85:808-12. Feld R. Complications in the treatment of small cell carcinoma of the lung. Cancer Treat Rev 1981;8:5-25. Umsawasdi T, Valdivieso M, Barkley HT, Booser DJ, Chiuten DF, Murphy WK, et al. Esophageal complications from combined chemoradiotherapy (cyclophosphamide + Adriamycin + cisplatin + XRT) in the treatment of non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1985;11:511-9. Newburger PE, Cassady JR, Jaffe N. Esophagitis due to adriamycin and radiation therapy for childhood malignancy. Cancer 1978;42:417-23.
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Background: Placement of self-expandable metallic stents in patients with advanced esophageal cancer improves dysphagia and occludes tracheoesophageal fistulas. However, the safety of selfexpandable metallic stents for patients who have undergone chemoradiotherapy is controversial. This study evaluated the morbidity and modality after self-expandable metallic stent placement in patients with progressive or recurrent esophageal cancer after chemoradiotherapy. Methods: A total of 22 patients in whom self-expandable metallic stents were placed because of progressive or recurrent esophageal cancer after chemoradiotherapy were studied. Results: All 22 patients had dysphagia, and 13 had a tracheoesophageal fistula. After self-expandable metallic stent placement, the mean dysphagia grade improved from 3.5 to 0.9, and tracheoesophageal fistula was successfully managed in all cases. Seventeen patients had T4 stage disease, and among 8 of them with invasion to the aorta, 6 (75%) died of sudden massive hemorrhage. Median survival for these 6 patients was 31 days (range 13-63 days) compared with 67 days (range 4-262 days) for all patients after self-expandable metallic stent placement. Conclusion: Self-expandable metallic stent placement improved dysphagia and was useful for treatment of tracheoesophageal fistula. However, for patients with T4 lesions that invade to the aorta, self-expandable metallic stent placement after chemoradiotherapy should be considered carefully. (Gastrointest Endosc 2003;57:882-5.)
Although surgery is the standard therapy for localized esophageal cancer, the results with surgery alone remain poor, with 5-year survival rates of 6% to 24%.1 Studies have found, however, that chemoradiotherapy may be curative in locally advanced esophageal cancer, with results comparable with those of radical surgery.2-4 Therefore, chemoradiotherapy may become the standard therapy for patients with advanced esophageal cancer. However, local recurrence develops in nearly half of the patients treated with chemoradiotherapy.2 Dysphagia and tracheoesophageal fistulas are common complications of advanced esophageal cancer. Fatalities have been reported after placement of plastic esophageal stents.5-9 Successful self-expandable metallic stent (SEMS) placement was first reported by Domschke et al.10 in 1990. Subsequent trials found Received January 31, 2002. For revision May 1, 2002. Accepted February 10, 2003. Current affiliations: Department of Endoscopy, National Cancer Center Hospital, Tokyo, Japan, Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan, Centre for Digestive Diseases, The General Infirmary at Leeds, United Kingdom. Reprint requests: Takuji Gotoda MD, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. Copyright © 2003 by the American Society for Gastrointestinal Endoscopy 0016-5107/2003/$30.00 + 0 doi:10.1067/mge.2003.234 882
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this type of stent to be effective and safe for treatment of patients with malignant dysphagia and tracheoesophageal fistulas.11-19 However, whether SEMS placement is safe for patients who have undergone chemoradiotherapy is a matter of debate.20-23 Thermal ablative therapy, (e.g., Nd:YAG laser photoablation or argon plasma coagulation) also is used widely for palliation of patients with malignant dysphagia. However, such therapy requires multiple treatments, is costly, and re-occlusion requiring retreatment is common.21,24 In addition, thermal ablative therapy is of no benefit in the treatment of tracheoesophageal fistulas. To the investigators’ knowledge, there is no previous study that addresses the association between tumor stage and life-threatening complications related to SEMS placement in patients who have had chemoradiotherapy. This study retrospectively evaluated post–SEMS-placement morbidity and modality for patients with progressive or recurrent esophageal cancer after initiation of chemoradiotherapy. PATIENTS AND METHODS At the National Cancer Center Hospital, 172 patients with advanced esophageal cancer, seen from October 1998 to September 2001, received chemoradiotherapy. In 22 of these patients, an SEMS was placed because of recurrent esophageal cancer or esophageal cancer that VOLUME 57, NO. 7, 2003
Esophageal cancer chemoradiotherapy: morbidity, mortality after SEMS placement
Table 1. Characteristics of patients with advanced esophageal cancer Patient gender Male Female Median age (range) Histopathology of tumor Squamous cell carcinoma Location of tumor Proximal third Middle third Distal third Mean length of tumor (range) Depth of tumor invasion T2 T3 T4 Invasion to aorta Invasion to bronchus Obstruction before placement of SEMS Present Absent Fistula before placement of SEMS Present Absent Mean dysphagia grade before placement of SEMS Primary therapy Chemoradiotherapy Radiation alone
19 3 66 y (49-82) 22 3 16 3 6.8 cm (3.5-10) 1 4 17 8 10 19 3 13 9 3.5
20 2
had progressed after chemoradiotherapy. Endoscopy and/or contrast esophagography were performed to determine the location and length of the tumor and to confirm the level of obstruction and identify tracheoesophageal fistulas. The diagnosis of esophageal cancer was made by histopathologic evaluation of endoscopic biopsy specimens. The extent of tumor invasion (T factor) was evaluated by CT of the chest and/or EUS with either 7.5 or 20 MHz frequencies, using the standard TNM classification system.25 Dysphagia was assessed before and after SEMS placement and graded as follows: grade 0, normal swallowing; grade 1, unable to swallow solids; grade 2, unable to swallow semisolids; grade 3, unable to swallow liquids; and grade 4, unable to swallow saliva.26 All stents were placed over a guidewire endoscopically with fluoroscopic monitoring; these procedures were performed under sedation during hospitalization. Morbidity and mortality were evaluated after SEMS placement for the 22 patients with recurrent or progressive tumor after receiving chemoradiotherapy. Post– SEMS complications were defined as any new adverse event after placement, including high fever, chest pain, food impaction, stent migration, and bleeding within the first week after the procedure. Survival was measured from SEMS placement to death or most recent follow-up. Survival rates were calculated using the Kaplan-Meier method. An inclusive consent, including consent for review of medical records, was obtained from each patient at the first examination. VOLUME 57, NO. 7, 2003
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Table 2. Post–SEMS-placement complications High fever (>38°C) Chest pain Food impaction Stent migration Bleeding
77.3% 81.8% 9.1% 9.1% 9.1%
(17/22) (18/22) (2/22) (2/22) (2/22)
RESULTS Patient characteristics Characteristics for the 22 patients (19 men, 3 women; median age 66, range 49 to 82 years) are shown in Table 1. Three tumors were located in the proximal esophagus, 16 in the mid esophagus, and 3 in the distal esophagus. Mean tumor length was 6.8 cm (range 3.5-10 cm). Histopathologically, all tumors were squamous cell carcinoma. The extent of tumor invasion was T2 in 1 patient, T3 in 4 patients, and T4 in 17 patients before chemoradiotherapy. Eight of the 17 patients with clinical T4 cancers had invasion to the aorta; 10 had invasion to a bronchus. In one patient, the cancer invaded to both aorta and bronchus. All 22 patients had dysphagia and 13 had a tracheoesophageal fistula at initial evaluation. The mean dysphagia grade was 3.5 before SEMS placement. Twenty patients previously had undergone chemoradiotherapy and 2 had received radiotherapy alone because of liver cirrhosis in one and the advanced age of the other (82 years). Post–SEMS-placement complications Stents were successfully placed in all patients; a single stent was placed in 21 patients and 2 stents in 1 patient. An Ultraflex stent (Boston Scientific, Watertown, Mass.) was used in 19 patients and a Wallstent (Schnider, Blanch, Switzerland) in 4 patients. Post–SEMS-placement complications are shown in Table 2. High fever (>38°C) and severe chest pain that required administration of analgesic medication were common. Minor hemorrhage, not requiring transfusion, developed in 2 cases after stent placement. There were no deaths post SEMS placement. Post–SEMS-placement morbidity and mortality Outcomes after SEMS placement are shown in Table 3. Dysphagia improved in 21 of 22 patients (95.5%); mean grade decreased from 3.5 to 0.9. All tracheoesophageal fistulas were successfully occluded as assessed radiographically and endoscopically. Nine patients could not be discharged because of post–SEMS-placement complications or tumor progression after placement. Twenty patients died of post–SEMS-placement complications or tumor progression. The early death (4 days after stent placement) was that of a patient who previously had GASTROINTESTINAL ENDOSCOPY
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Esophageal cancer chemoradiotherapy: morbidity, mortality after SEMS placement
Table 3. Outcome after SEMS placement Dysphagia relief 95.5% (21/22) Mean dysphagia grade after placement of SEMS 0.9 Fistula closure 100% Patients who could be discharged 59.1% (13/22) Patients who could not be discharged 40.9% (9/22) Patient state Dead 20 Alive 2 Median survival for all patients (d) (range) 67 (4-262) Median survival for patients with sudden 31 (13-63) massive hemorrhage (d) (range)
developed a tracheoesophageal fistula complicated by a severe pneumonia. The fistula was successfully managed by emergent SEMS placement, but the patient succumbed to the pneumonia. Sudden massive hemorrhage developed in 6 patients, all of whom died. Clinically, all 6 patients had T4 tumors before chemoradiotherapy commenced. Among the 17 patients with T4 tumors, 8 had invasion to the aorta, and 6 (75%) of these patients died suddenly. For the 6 patients who developed sudden massive hemorrhage, tumor location, length of lesion, and dysphagia grade were not significantly associated with bleeding. Invasion to both aorta and bronchus was found in one patient. In contrast, there was no instance of sudden death among the 9 patients with T4 tumors with invasion to the bronchus. Median survival for the 6 patients who died of sudden massive hemorrhage was 31 days (range 13-63 days) compared with 67 days (range 4-262 days) for all patients after SEMS placement. DISCUSSION Many studies have shown that SEMS placement provides effective palliation for patients with advanced esophageal cancer.11-19 However, most studies did not include patients who had received chemoradiotherapy, and the safety of SEMS placement in such patients is uncertain.20-23 In general, it is difficult to distinguish clearly whether the lifethreatening events after SEMS placement were stent-related or caused by tumor progression. However, radiation can cause esophageal injury with esophagitis and ulceration, and esophageal perforation and tracheoesophageal fistulas may also occur because of radiation-induced vasculitis.27,28 Furthermore, chemotherapy is known to potentiate radiation-induced esophageal injury.29-31 In addition, an SEMS can cause pressure necrosis in patients previously treated with chemoradiotherapy.21 Thus, it is thought that SEMS placement in the setting of chemoradiotherapy may be associated with esophageal perforation. 884
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Kinsman et al.21 found that life-threatening complications occurred after SEMS placement in 36.4% (8/22) of patients who had prior radiation and/or chemotherapy compared with 2.5% (1/37) of those with no prior therapy. Moreover, the stent-related mortality rate was 23% (5/22) among patients with prior therapy, whereas there were no deaths among the 37 patients without prior therapy. Furthermore, these investigators observed that life-threatening complications were not associated with tumor location, histopathologic tumor type, length of obstructing lesion, dysphagia grade, or previous surgical resection. Bethge et al.22 also found that prior radiotherapy increased the risk of complications after SEMS placement. In contrast, Raijman et al.23 found no association between prior chemoradiotherapy and complications. The most realistic goal of any palliative therapy is maximal relief of symptoms with minimal risk. In the present study, SEMS placement was obviously effective in the treatment of malignant dysphagia and tracheoesophageal fistula. However, post–SEMSplacement complications were common and often life threatening. In particular, 6 patients died of sudden hemorrhage. Thus, it is essential to clarify which patients are eligible for SEMS placement. All 6 patients in whom massive hemorrhage developed suddenly in the present study had T4 cancers clinically with invasion to the aorta before chemoradiotherapy was initiated. These 6 patients were among the group of 8 with aortic invasion; the other 2 patients died of progression of the cancer. It is likely that T4 cancers are susceptible to pressure necrosis from an SEMS, with a consequent increase in the risk of perforation into adjacent structures. However, the mean dysphagia grade improved from 3.8 to 0.7 in patients with aortic invasion compared with an improvement from 3.4 to 1.0 after SEMS placement in patients without aortic invasion. Therefore, other modalities should be selected to improve quality of life with fewer complications for patients with T4 cancers and aortic invasion with tumor progression or recurrence despite chemoradiotherapy. For example, the investigators performed PEG procedures in 3 patients with recurrent esophageal cancer after chemoradiotherapy. They did not have tracheoesophageal fistulas and preferred PEG instead of SEMS placement after they were informed of the increased risk of severe stent-related complications. In conclusion, the investigators suggest that patients under consideration for placement of an SEMS after chemoradiotherapy, especially those with tumor invasion to the aorta, should be advised that while their ability to swallow will most likely improve, the risk of dying from sudden bleeding is substantial. VOLUME 57, NO. 7, 2003
Esophageal cancer chemoradiotherapy: morbidity, mortality after SEMS placement
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