Japanese Journal of Clinical Oncology 31:270-274 (2001)
© 2001 Foundation for Promotion of Cancer Research
Self-expandable Metallic Stents for Patients with Recurrent Esophageal Carcinoma After Failure of Primary Chemoradiotherapy
1Department of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba and Departments of 2Gastroenterology and 3Radiology, Ibaraki Prefectural Central Hospital, Tomobe, Ibaraki, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed.
Methods: Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula.
Results: The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38°C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications.
Conclusion: Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Recent advances in the non-surgical treatment of esophageal carcinoma have demonstrated an improvement in patient survival (1–4). Cisplatin and fluorouracil (FU) infusion along with radiation has been accepted as a standard regimen for chemoradiotherapy (3,4). We recently reported that this combined modality had curative potential, even in cases with clinical T4 and/or M1 LYM according to the TNM classification (5). Furthermore, we reported that even in patients with malignant fistula due to esophageal carcinoma, this regimen is not contraindicated and should be instituted since it may provide the best chance for survival and the improvement of oral alimentation (6).
However, even for chemoradiotherapy with curative intent, the 2-year local recurrence rate is 45% (3). Dysphagia is still the most common symptom in patients with recurrent esophageal carcinoma, and also in those with non-treated esophageal carcinoma at presentation. The main goal of treatment for such patients is usually palliative to relieve the dysphagia. Several self-expandable metallic stents (7) are now available and have been used widely to provide immediate symptomatic relief of dysphagia. However, the safety and efficacy of self-expandable metallic stents for the patients with recurrent esophageal carcinoma after failure of prior chemotherapy and/or radiotherapy have been controversial (8–10).
Therefore, it is important to evaluate whether placement of self-expandable metallic stents provides such patients with a better quality of life. To the best of our knowledge, there have been no studies on the placement of self-expandable metallic stents for patients with recurrent esophageal carcinoma where a single regimen of definitive chemoradiotherapy with curative intent has failed. Furthermore, it is difficult to conduct a prospective randomized trial for these patients because all of them require immediate relief from dysphagia. The aim of this retrospective study was to determine the safety and efficacy of self-expandable metallic stent placement in such patients.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients and Materials
From September 1994 to July 1999, self-expandable metallic stents were deployed in 13 consecutive patients with recurrent esophageal squamous cell carcinoma following failure of definitive chemoradiotherapy. All patients had been treated with the same regimen of chemoradiotherapy with curative intent. Details of the treatment schedule for chemoradiotherapy were reported previously (5,6). Eleven patients were men and two were women; the age range was 40–73 years (mean: 60 years). Recurrence of esophageal carcinoma was confirmed by both endoscopy and histological examination using biopsy specimens.
Patients’ characteristics and the types of self-expandable metallic stents deployed are summarized in Table 1. All patients had symptoms of recurrent dysphagia due to recurrent esophageal stenosis. Four patients had a malignant fistula. The types of self-expandable metallic stents used were Gianturco-Rosch Z-stent (Cook, Bloomington, IN) for two patients, Wall stent (Schneider, Blanch, Switzerland) for two patients and Ultraflex (Boston Scientific, Watertown, MA) for nine patients. Eight stents were covered and the others were uncovered. Details of these stents and their methods of release have been described elsewhere (7).
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Assessment for Status of Oral Alimentation
We assessed and categorized the oral alimentation status as follows, according to the ability to swallow: 1) solid food, 2) semisolid food, 3) only liquids or 4) no food or liquids. The best alimentation status achieved by the patient, before and after stent placement, was recorded for analysis.
Assessment of Stent-related Complications
We assessed all stent-related complications, including high fever (>38°C), chest pain requiring analgesics and esophageal perforation. Using computed tomography (CT) and X-rays of the chest, we evaluated the incidence of mediastinitis and pneumonia. If, after stent placement, a patient developed mediastinitis or pneumonia that was not observed beforehand, then this was classified as a stent-related complication. Obstruction and migration of the stent were also assessed.
Statistical Analysis
Survival was measured from the date of self-expandable metallic stent placement to death or the most recent follow-up visit. Survival data were assessed by the Kaplan–Meier method.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Oral Alimentation Status
The changes in the oral alimentation status of the patients are summarized in Fig. 1. The oral alimentation status improved in 69% (9/13) of the patients and no patient experienced a deterioration in their status. In particular, six patients who could not take even liquids before stent placement were able to take something to eat or drink. Since two patients could not take anything even after stent placement, they required intravenous hyperalimentation by a central line. In addition, two patients required percutaneus endoscopic gastrostomy (PEG) to support their inadequate nutrition.
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Complications
Complications following metallic stent placement are summarized in Table 2. High fever (>38°C) within 1 week after self-expandable metallic stent placement was observed in 85% (11/13) of patients. This fever could be controlled unless the patients had severe inflammation such as mediastinitis and pneumonia. C-reactive protein and white blood cell counts were elevated within 1 week in all patients who were examined (data not shown). Also 85% (11/13) of patients complained of severe chest pain that required analgesics, although they did not have this symptom before stent placement. In these patients, eight required morphine and the remaining three required non-steroid anti-inflammatory drugs to control the pain. No stent movement occurred. Obstruction of the stent due to re-growth of the tumor occurred in two patients.
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With respect to life-threatening complications, esophageal perforation is one of the most critical complications. Three patients developed esophageal perforations, despite the fact that they had no malignant fistula before stent placement (Table 3). The perforation was confirmed by CT of the chest and these patients developed mediastinitis. Furthermore, pneumonia occurred in one of them. In total, six patients developed stent-related mediastinitis and three patients developed stent-related pneumonia. The latency for the development of stent-related mediastinitis and stent-related pneumonia ranged from 2 to 78 days (median: 12.5 days) and from 6 to 78 days (median: 31 days), respectively.
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Survival
Five patients died of respiratory failure. Of these patients, three died from perforation-induced mediastinitis and two succumbed to worsened airway obstruction caused by the stent. Three patients died of pneumonia, which was apparently associated with stent placement since we could not detect any abnormalities on the chest X-ray before placement. Finally, seven patients (54%) died apparently of stent-related pulmonary complications. Patient survival data are summarized in Table 3. The median survival time for all patients was 69 days, ranging from 22 to 399 days. One patient survived for more than 300 days, even after stent placement.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We have recently reported that definitive chemoradiotherapy, consisting of cisplatin and 5FU with radiation, had curative potential for locally advanced esophageal carcinoma, with a complete remission rate of 33% and a 3-year survival rate of 23% (5). A separate study made by the Radiation Therapy Oncology Group, comparing chemoradiotherapy with radiation alone, demonstrated that chemoradiotherapy was superior to standard radiation-alone therapy, with a 5-year survival rate of 27% (3). These results seem to be comparable to the results from extensive surgery (11). Therefore, definitive chemoradiotherapy has the potential to become the preferred treatment for locally advanced esophageal carcinoma.
Despite advances in the control of and survival from locally advanced esophageal carcinoma with chemoradiotherapy, local recurrence occurred in nearly half of the patients treated (3) and dysphagia was the most common and distressing symptom in such cases as well as in non-treated patients. Rigid plastic endoprostheses and self-expandable metallic stents are now available to provide symptomatic relief from dysphagia. A controlled trial in the treatment of esophageal obstruction due to inoperable cancer showed that the use of the self-expandable metallic stent was a safe and cost-effective alternative to the use of conventional plastic endoprostheses (12).
However, the use of the self-expandable metallic stent for recurrent esophageal carcinoma after failure of radiotherapy and/or chemotherapy has been controversial. Kinsman et al. (8) and Bethge et al. (9) reported that patients with prior radiation and/or chemotherapy have an increased risk of severe complications following placement of self-expandable metallic stents. In contrast, no relationship between prior radiotherapy and/or chemotherapy and severe complications was observed by Raijman et al. (13). Therefore, the role of the self-expandable metallic stent in the palliative treatment of recurrent dysphagia should be capable of elucidation.
In our study, there is no doubt that this method provided symptomatic relief of dysphagia, since placement of a self-expandable metallic stent obviously improved the oral alimentation status, as reported previously (12). In spite of this merit, high fever (>38°C) and severe chest pain were frequently observed just after placement of the stent. Since the level of C-reactive protein and the white blood cell count were also increased, inflammation might be responsible for these effects. Furthermore, many patients complained of severe chest pain requiring analgesics. Bethge et al. (9) also reported similar chest pain which was thought to be device related; and those patients were effectively treated with acetaminophen with codeine. Although we cannot be certain as to why severe chest pain occurred frequently in our study compared with other reports (8,13), it is possible that radiation-induced esophageal damage is potentiated by chemotherapy and that structural damage occurs even in the neuronal elements (14).
The most critical problem is that placement of a self-expandable metallic stent increases the risk of life-threatening complications, especially esophageal perforation. In general, the development of a malignant fistula is one of the life-threatening complications that can arise during the natural course of esophageal carcinoma. However, it is unknown whether this event was stent-related or due to a natural progression of the disease. Esophageal necrosis after placement of a stent has been reported in patients with recurrent esophageal carcinoma after failure of prior radiotherapy or chemotherapy (8). Furthermore, it is well known that radiation and chemotherapy (e.g. 5FU) induce esophageal injury including esophagitis and ulceration. Based on this evidence, we think that it is more likely that perforation of the esophageal wall is potentially related to the device itself and prior chemoradiotherapy. Likewise, mediastinitis and pneumonia might also be associated with the above reasons, because these complications were infrequent during the natural course of esophageal carcinoma (15).
In conclusion, the placement of a self-expandable stent can improve the oral alimentation status. However, we should recognize the fact that life-threatening complications can occur frequently in patients with recurrent esophageal carcinoma following failure of definite chemoradiotherapy, although this study was not randomized and prospective. Further investigation is now required to elucidate whether other methods (e.g. PEG) are capable of providing a better quality of life with fewer life-threatening complications for such patients.
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FOOTNOTES |
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+ For reprints and all correspondence: Manabu Muto, Department of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, 5–1 Kashiwanoha 6-chome, Kashiwa 277-8577, Japan. E-mail: mmuto@east.ncc.go.jp
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REFERENCES |
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Received November 28, 2000; accepted February 9, 2001.
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