Hiroyuki Kato

Esophageal cancer is one of the most difficult malignancies to cure. The prognosis remains unsatisfactory despite significant advances in surgical techniques and perioperative management. The optimal treatment strategy for localized esophageal cancer has not yet been established. Surgical resection remains the mainstay of treatment for esophageal cancer, and curative resection is the most important surgery. Extended esophagectomy with three-field lymphadenectomy provides the highest quality of tumor clearance and prolongation of patient survival. There has been intense effort in developing novel strategies to treat patients with resectable esophageal cancer. Various combined-modality approaches have been attempted to improve treatment outcomes. Definitive chemoradiotherapy has an impact on long-term survival in patients with resectable esophageal cancer. Accordingly, there are three main combined-modality approaches: esophagectomy with adjuvant chemotherapy or chemoradiotherapy; primary definitive chemoradiotherapy with or without salvage esophagectomy, and preoperative chemoradiotherapy followed by planned esophagectomy. Recently, owing to the remarkable advances in optical technology, minimally invasive esophagectomy using endoscopic instruments has been introduced into esophageal cancer surgery. This article reviews recent changes in the treatment of esophageal cancer surgery, and considers the role of esophagectomy.

BACKGROUND: The purpose of the current study was to assess whether [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG‐PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma.METHODS: The authors examined 149 consecutive patients with thoracic esophageal carcinoma. Eighty‐one patients underwent radical esophagectomy without pretreatment, 17 received chemoradiotherapy followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining 48 patients received definitive radiotherapy and chemotherapy. The diagnostic accuracy of FDG‐PET and CT was evaluated at the time of diagnosis.RESULTS: The primary tumor was visualized using FDG‐PET in 119 (80%) of 149 patients. Regarding lymph node metastases, FDG‐PET had 32% sensitivity, 99% specificity, and 93% accuracy for individual lymph node group evaluation and 55% sensitivity, 90% specificity, and 72% accuracy for lymph node staging evaluation. PET exhibited incremental value over CT with regard to lymph node status in 14 of 98 patients who received surgery: 6 patients with negative CT findings were eventually shown to have lymph node metastases (i.e., they had positive PET findings and a positive reference standard [RS]); 6 patients with positive CT findings were shown not to have lymph node metastases (i.e., they had negative PET findings and a negative RS); and 2 patients were shown to have cervical lymph node metastases in addition to mediastinal or abdominal lymph node metastases. Among the remaining patients, PET showed incremental value over CT with regard to distant organ metastases in six patients. The overall incremental value of PET compared with CT with regard to staging accuracy was 14% (20 of 149 patients).CONCLUSIONS: FDG‐PET provided incremental value over CT in the initial staging of esophageal carcinoma. At present, combined PET‐CT may be the most effective method available for the preoperative staging of esophageal tumors. Cancer 2005. © 2004 American Cancer Society.

Background: Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) might be useful for staging oesophageal squamous cell carcinoma (SCC). FDG-PET may be more accurate than computed tomography (CT) in diagnosing lymph node metastasis. This retrospective study compared the ability of FDG-PET and CT to diagnose recurrent oesophageal carcinoma. Methods: Fifty-five patients with thoracic oesophageal SCC who had undergone radical oesophagectomy were studied. The accuracy of FDG-PET and CT in detecting recurrence during follow-up was calculated using data from the first images generated by either modality that suggested the presence of recurrent disease. Lesions deemed to be equivocal on these scans were considered as positive for recurrence. Results: Twenty-seven of the 55 patients had recurrent disease in a total of 37 organs. Locoregional recurrence was observed in 19 patients (35 per cent). Distant recurrent disease occurred in 15 patients (27 per cent) in 18 organs. Six patients had recurrence in the liver, four in the lung, six in bone and two in distant lymph nodes. FDG-PET showed 96 per cent sensitivity, 68 per cent specificity and 82 per cent accuracy in demonstrating recurrent disease. The corresponding values for CT were 89, 79 and 84 per cent. The sensitivity of FDG-PET was higher than that of CT in detecting locoregional recurrence, but its specificity was lower because of FDG uptake in the gastric tube and thoracic lymph nodes. In distant organs the sensitivity of PET in detecting lung metastasis was lower than that of CT, but its sensitivity for bone metastasis was higher. Conclusion: FDG-PET has a larger field than CT. Combined PET–CT would appear to be an appropriate modality for the detection of recurrent oesophageal cancer.

Background: Our aim was to determine whether minichromosome maintenance protein (MCM) 2 expression is useful in predicting tumor proliferation rates and outcome after therapy in patients undergoing surgery for esophageal squamous cell carcinoma (SCC). In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki‐67, in esophageal SCC.Methods: We examined immunohistochemical expression of MCM2 and Ki‐67 in surgically resected tissues from 93 patients with esophageal SCC.Results: The mean nuclear labeling index of MCM2 was markedly higher in SCC than in normal epithelia (P < 0.0001). A comparison of MCM2 labeling index and clinicopathological characteristics in 93 patients with esophageal cancer revealed significant associations between MCM2 labeling index and tumor status (P < 0.05), lymph node status (P < 0.01), metastatic status (P < 0.01), pathologic stage (P < 0.01), histologic grade (P < 0.05), and poor prognosis (P < 0.05). A comparison of Ki‐67 labeling index and clinicopathological characteristics revealed significant associations between Ki‐67 labeling index and lymph node status (P < 0.01), metastatic status (P < 0.05), pathologic stage (P < 0.05), histologic grade (P < 0.05), and poor prognosis (P < 0.05). The relationship between MCM2 and Ki‐67 labeling indices in the primary tumor showed a significant correlation (P < 0.05), but the MCM 2 labeling index was considerably higher.Conclusions: MCM2 may be a more reliable and useful marker than Ki‐67 in assessing the growth of normal and tumor cells and in evaluating tumor aggressiveness and prognostic value in patients with esophageal SCC. J. Surg. Oncol. 2003;84:24–30.

BACKGROUND: The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium‐99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging.METHODS: The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium‐99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium‐99m injection. After surgery, the resected lymph nodes were evaluated by CK staining.RESULTS: Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false‐negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false‐negative (sentinel lymph node–negative and nonsentinel lymph node–positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23).CONCLUSIONS: Lymphatic mapping with technetium‐99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node. Cancer 2003;98:932–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11559

In our previous study, it was suggested that nitrotyrosine, a product of nitrogen species, found in esophageal squamous cell carcinoma (ESCC), may contribute to the progression of esophageal cancer. To clarify whether nitrotyrosine expression is associated with apoptosis and/or angiogenic factors in ESCC, we have analyzed the relationship between nitrotyrosine presence and the apoptosis-related proteins, Bcl-2 and Bax, or CD34, the marker of vascular endothelial cells, by an immunohistochemical approach. Nitrotyrosine was detected in 21 out of 55 esophageal cancers. The correlation between nitrotyrosine presence and Bcl-2, Bax expression or apoptotic index (AI) was not significant. In contrast, nitrotyrosine presence was significantly correlated with the microvessel density (MVD); nitrotyrosine-positive specimens tended to show a high MAD, while nitrotyrosine-negative specimens tended to be associated with a low MVD (p<0.05). Our data suggest that NO induces progression of esophageal carcinoma through its effect on angiogenesis, rather than its effect on tumor apoptosis.