Yuji Toh

Pattern of Recurrence after Extended Radical Esophagectomy with Three-Field Lymph Node Dissection for Squamous Cell Carcinoma in the Thoracic Esophagus

Abstract. Factors responsible for recurrence of esophageal cancer were investigated in 90 patients who underwent extended radical esophagectomy with three-field dissection for a squamous cell carcinoma in the thoracic esophagus. The initial tumor recurrence was grouped as either locoregional (site of the primary tumor, anastomotic site, or lymph nodes) or as distant (distant organs, pleura, or peritoneum). Nineteen patients (21%) developed a locoregional recurrence, and 19 (21%) developed a distant recurrence. One (1%) developed both recurrences simultaneously and was classified as a distant recurrence. The locoregional recurrence was correlated with the stage factors, particularly the number of metastasis-positive nodes. For the distant recurrence, vascular invasion was found to have been the most important prognostic factor. Our findings suggested that locoregional recurrence was due to tumor progress related to the extent of lymph node metastasis, whereas distant recurrence was due to the oncologic behavior of the tumor. Locoregional recurrence in patients with limited disease may be reduced by extended radical esophagectomy with three-field dissection. Distant recurrence cannot be controlled by surgery. Adopted postoperative adjuvant therapies showed no effect on recurrence.

Endosonography for Preoperative Staging of Specific Nodal Groups Associated with Esophageal Cancer

Abstract. The results of endoscopic ultrasonography (EUS), used preoperatively in 74 endoscopically evaluable patients, were compared with the histopathology after subsequent total esophagectomy with radical lymphadenectomy involving a three-field dissection of the lower cervical, mediastinal, and abdominal nodes. Patients with obstruction to endoscopy were excluded from this study. Overall accuracy, specificity, and sensitivity were 87%, 90%, and 37%, respectively. EUS has an accuracy of more than 80% for detecting metastatic nodes in the cervical paraesophageal, supraclavicular, right recurrent laryngeal, left paratracheal, upper and lower paraesophageal, infraaortic, infracarinal, and lower posterior mediastinal regions. Its sensitivity is highest for cervical and upper thoracic paraesophageal, infracarinal, left paratracheal, and recurrent laryngeal nodes. Accuracy is maximum for periesophageal nodes and varies inversely with the axial distance of the nodes from the esophageal axis. We recommend that EUS be used routinely for preoperative assessment of the cervical and mediastinal nodal status.

Gastropericardial and gastrobrachiocephalic vein fistulae caused by penetrating ulcers in a gastric pedicle following esophageal cancer resection: A case report

The gastric pedicle is commonly used for reconstruction following resection of esophageal cancer. However, we recently experienced a case in which two gastric tube ulcers occurred three months postoperatively; one penetrating into the pericardial cavity and the other into the left brachiocephalic vein. To our knowledge, no other such a case has ever been reported and we therefore report and discuss its etiology and management.

Expression of MAGE-1 Gene by Esophageal Carcinomas

Expression of the MAGE genes encoding tumor‐rejection antigens on HLA‐A1 and ‐Cwl601 recognized by cytotoxic T lymphocytes was investigated in esophageal carcinomas at the mRNA level by the semiquantitative reverse transcription‐polymerase chain reaction method. MAGE‐1 and ‐2 genes, but not MAGE‐3, ‐3/‐6 and ‐4a/‐4b genes, were expressed in substantial proportions of the primary esophageal carcinomas and their metastatic lymph nodes. The proportion of MAGE‐positive samples in the primary esophageal carcinomas correlated with the T factor of the TNM classification (pT1: 2 of 12 tumors, pT2: 1 of 6, pT3: 12 of 29, and pT4: 7 of 18). These results have important implications for specific immunotherapy of esophageal carcinomas using MAGE‐1 gene product.

DEVELOPMENT OF CANCER VACCINE BY TUMOR REJECTION ANTIGENS

Identification of the MAGE genes allowed us the molecular approach to identify genes encoding tumor rejection antigens expressed on human cancer cells. MAGE-1 proteins are normal tissue antigens compartmentalized in the particular testicular cells playing an important role in the early phase of the spermatogenesis. The MAGE-1, -2, -3, -4 and -6 genes are preferentially expressed in many different cancers at both the mRNA and protein levels. The MAGE genes, particularly MAGE-1, became positive in relatively advanced stages of cancers and recurrent cancers. Approximately one-third to half of human cancers except for myelo-monocytic leukemia expressed at least one of these MAGE genes. The MAGE gene products shall be appropriate target molecules for development of new cancer vaccine.

A MONOCLONAL ANTIBODY KIS-1 RECOGNIZING A NEW MEMBRANE ANTIGEN ON HUMAN SQUAMOUS-CELL CARCINOMA

A KIS‐1 monoclonal antibody (MAb) (IgG1, K) recognizing a membrane antigen on human squamous‐cell carcinomas (SCC) was developed to understand their antigenicity using an esophageal SCC as an immunogen. The KIS‐1 MAb recognized a membrane antigen on a majority of esophageal, lung, and oral‐cavity SCC by immunofluorescent and by immunohistochemical analyses. In contrast, it showed little reactivity to adenocarcinomas from different organs, and none to keratinocyte cell lines. This MAb showed reactivity to the cells in the basal layer of normal esophageal epithelium adjacent to the esophageal SCC, but none of the other normal tissues, including esophageal epithelium far from the SCC and that from patients with non‐malignant disease. The KIS‐1 MAb immunoprecipitated a 46‐kDa membrane protein of the esophageal SCC in non‐reducing and in reducing conditions. It recognized the 46‐ and the 40‐kDa proteins of the esophageal SCC by immunoblot analysis. These results suggest that the KIS‐1 MAb recognizes a new membrane antigen preferentially expressed on SCC, and that this antigenicity is shared only by the cells in the basal layer of the esophageal epithelium adjacent to SCC. The KIS‐1 MAb may be a new tool for understanding the antigenicity of SCC.