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BACKGROUND - Endoscopic therapy has emerged as an alternative to surgical esophagectomy for the management of Barrett's esophagus (BE)-associated neoplasia. Accurate pretreatment staging is essential to ensure an appropriate choice of therapy and optimal long-term outcomes. This study aimed to assess the frequency with which expert histopathologic review of biopsies combined with endoscopic mucosal resection (EMR) would alter the pretreatment diagnosis of BE-associated neoplasia.
METHODS - Patients referred to the Vanderbilt Barrett's Esophagus Endoscopic Treatment Program (V-BEET) were retrospectively identified. Demographic, histopathologic, and endoscopic data were extracted from the medical record.
RESULTS - For this study, 29 subjects referred for endoscopic staging of BE fulfilled the entry criteria. The referral diagnosis was low-grade dysplasia (LGD) in 3 % (1/29), high-grade dysplasia (HGD) in 62 % (18/29), intramucosal adenocarcinoma (T1a) adenocarcinoma in 17 % (5/29), and invasive adenocarcinoma in 17 % (5/29) of the subjects. Expert histopathologic review of available referral biopsy specimens altered the diagnosis in 33 % (5/15) of the cases. Further diagnostic staging with EMR showed BE without dysplasia in 10 % (3/29), LGD in 14 % (4/29), HGD in 34 % (10/29), T1a adenocarcinoma in 28 % (8/29), and invasive adenocarcinoma in 14 % (4/29) of the patients. The combination of expert histopathologic review and EMR altered the initial diagnosis for 55 % (16/29) of the subjects, with 56 % (9/16) upstaged to more advanced disease and 44 % (7/16) downstaged to less advanced disease.
CONCLUSIONS - The practice of combined expert histopathologic review and EMR alters the pretreatment diagnosis for the majority of patients with BE-associated neoplasia. Caution is advised for those embarking on endoscopic or surgical treatment for BE-associated neoplasia in the absence of these staging methods.
Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at an alarming rate. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor, vascular endothelial growth factor, v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinase pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.
BACKGROUND - The American Joint Committee on Cancer staging of esophageal cancer has been criticized for not establishing a minimum standard for lymphadenectomy, and for relying on location of nodes involved rather than their number. The objective of this study was to review the current practice of American surgeons with regard to lymph node assessment during esophageal resection.
METHODS - The operative and pathology reports of patients who underwent staging by computed tomography and fluorodeoxyglucose-positron emission tomography and subsequent resection for esophageal cancer (multiinstitutional American College of Surgeons Oncology Group Z0060 trial) were analyzed.
RESULTS - One hundred forty-five patients underwent resection. Operative and pathology reports were unavailable in 11 patients. The results of the remaining 134 resections (Ivor-Lewis, n = 64; transhiatal, n = 59; other, n = 11) were reviewed. Overall, 13 +/- 9 (mean +/- standard deviation) lymph nodes were evaluated per patient. More lymph nodes were evaluated in patients undergoing Ivor-Lewis (15 +/- 9) than transhiatal esophagectomy (9 +/- 7; p < 0.001). The mean number of distinct lymph node stations analyzed per patient was 3 +/- 2. In 38% (51 of 134) of patients the nodes attached to the specimen were evaluated without any distinction among nodal stations. The practice of submitting named packets of nodal material resulted in 16 +/- 9 nodes per case, as opposed to the practice of submitting an entire specimen for the pathologists to dissect, which yielded 10 +/- 8 nodes (p < 0.001).
CONCLUSIONS - There is considerable variability and room to improve in the extent of resection and pathologic evaluation of esophagectomy specimens. A uniform standard for esophageal cancer resection is warranted to improve the precision and value of pathologic staging.
OBJECTIVES - The American College of Surgeons Oncology Group trial Z0060 is a prospective multi-institutional trial with a primary objective to evaluate whether positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) detects evidence of metastastic disease that precludes esophagectomy in patients with esophageal cancer who are surgical candidates after routine staging.
METHODS - Patients with resectable, biopsy-proven carcinoma were enrolled after computed tomography of chest and abdomen demonstrated no evidence of metastasis. FDG-PET was performed according to specified standards. FDG-PET findings suggesting metastases required confirmation and patients without metastases on PET were expected to proceed to surgery.
RESULTS - A total of 262 patients were registered. Of these, 199 were deemed eligible and of these, 189 patients were evaluable. Seventy-three patients were ineligible or unevaluable. Reasons for ineligibility included nonresectable disease by routine staging (39), missing or outdated staging procedures (12), PET technical protocol violations (10), no cancer (4), pre-PET induction therapy (3), claustrophobia (1), and other causes (4). There were 145 (78%) patients who went on to have surgery, 42 (22%) who did not, and 2 patients for whom the surgical status was not determined. The reasons for no resection included the following: M1 disease found by PET and confirmed (9), M1 disease found by PET and not confirmed (2), M1 disease at exploration not found by PET (7), decline or death before surgery (10), patient refusal of surgery (7), unresectable local tumor at exploration (5), and extensive N1 disease precluding operation (2). Eight (4.2%) patients undergoing resection had a recurrence in the first 6 months.
CONCLUSIONS - Although 22% of eligible patients did not undergo esophagectomy, FDG-PET after standard clinical staging for esophageal carcinoma identified confirmed M1b disease in at least 4.8% (95% confidence interval: 2.2%-8.9%) of patients before resection. Unconfirmed PET evidence of M1 disease and regional adenopathy (N1 disease) led to definitive nonsurgical or induction therapy in additional patients.
PURPOSE - Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival.
METHODS AND MATERIALS - Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m2 on Day 1 and 5-fluorouracil 350 mg/m2 and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy.
RESULTS - Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p < 0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%.
CONCLUSION - Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.
Currently surgical resection is a necessary component of treatment for esophageal cancer, although future advances might change this. Resection provides relief of dysphagia and can markedly improve patient quality of life. In addition, there is evidence that an approach of induction chemotherapy/radiation therapy followed by surgery provides better survival outcomes than surgical or nonsurgical treatments alone. Surgery may improve survival over nonsurgical approaches by enhancing control of local disease. Surgery is also associated with the benefits of detecting occult metastases and providing a direct means of assessing response to therapy. It is hoped that methods for altering the biology of esophageal cancer will ultimately permit prevention and/or cure of the disease without surgical intervention. For now, however, resection must be considered a primary option in treatment. Greater attention should be given to improving staging procedures and to measuring improvement in quality of life as a treatment outcome to determine the optimal role of resection in treatment of esophageal cancer.
BACKGROUND - Preoperative chemotherapy and radiation therapy are often administered to patients with esophageal cancer. Despite an aging population, little data exist regarding feasibility of preoperative therapy in elderly patients.
METHODS - Between January 1997 and December 2002, 312 consecutive patients underwent esophagectomy for esophageal cancer at our institution. Outcomes of patients 70 years old, who underwent preoperative therapy (n = 35; group II), were compared with those of patients who did not (n = 39; group I) and with those of patients younger than 70 years old who received preoperative therapy (n = 165; group III).
RESULTS - The median age was 75 years old for group I and 72 years for group II (p < 0.001). The patients in group II were of more advanced clinical stage (p < 0.001). There were no differences in performance status, comorbidities, or preoperative symptoms between the two groups. Similar proportions of patients in the groups I and II underwent a transhiatal approach (52.5% vs 42.8%, p = not significant [NS]). Perioperative mortality for groups I and II was 0% and 3%, respectively (p = NS). Group II received more perioperative blood transfusions (71.4% vs 48.7%, p = 0.047). There were no differences in the rates of postoperative cardiac, pulmonary, neurologic, gastrointestinal, or anastomotic complications. Compared with group III, group II patients had higher rates of postoperative atrial arrhythmias (p = 0.013) and perioperative blood transfusions (p = 0.004).
CONCLUSIONS - Elderly patients receiving preoperative therapy for esophageal cancer do not have an increased incidence of major postoperative complications. Elderly patients receiving preoperative therapy are more likely to develop postoperative atrial arrhythmias and require transfusion than younger patients.
PURPOSE - To evaluate the effect of surgical resection on the outcome of patients with clinical Stage II or III cancer of the esophagus treated with concurrent chemoradiotherapy.
METHODS AND MATERIALS - A retrospective review of 132 consecutive patients with clinical Stage II or III esophageal cancer treated with concurrent chemoradiotherapy between January 1990 and December 1998 was performed. Of the 132 patients, 60 underwent esophagectomy 6-8 weeks after chemoradiotherapy. The median radiation dose was 50 Gy (range, 30-64.8 Gy) in the definitive chemoradiation group and 45 Gy (range, 30-50.4 Gy) in the chemoradiation plus esophagectomy group.
RESULTS - Statistically significant differences were found between the two groups in median age, histologic subtype, tumor location, and number of patients with T4 disease. Patients who underwent definitive chemoradiotherapy were older (p = 0.0004) and more likely to have squamous cell carcinoma than adenocarcinoma (p <0.000), upper thoracic or cervical esophageal tumors (p <0.000), and T4 tumors (p = 0.024). Patients treated with chemoradiation plus esophagectomy had statistically significant superior 5-year loco-regional control (67.1% vs. 22.1%, p <0.000), disease-free survival (40.7% vs. 9.9%, p < 0.000), and 5-year overall survival (52.6% vs. 6.5%, p < 0.000) rates and median survival time (62 vs. 12 months) compared with patients treated with chemoradiotherapy only. However, no statistically significant difference was found in the rate of distant metastasis-free survival between the two groups (67.5% vs. 65.8%, p = 0.3). Surgical resection of the tumor was an independent predictor of improved locoregional control and overall survival in both univariate and multivariate analyses. To reduce the effect of the selection bias on the outcome, 34 patients in each group with matched pretreatment characteristics were compared. The results showed statistically significant better overall survival, disease-free survival, and locoregional control in favor of the chemoradiotherapy plus esophagectomy group. No statistically significant difference in distant metastasis-free survival was found in this subgroup analysis.
CONCLUSIONS - Locoregional control was better in clinical Stage II or III esophageal cancer patients treated with concurrent chemoradiation plus esophagectomy. An improvement in survival occurred in the chemoradiation plus esophagectomy group, although this observation may have reflected selection bias. The results from this study suggest the need for a randomized trial to compare chemoradiation with or without esophagectomy in the treatment of cancer of the esophagus.