Prognostic significance of IMP-3 expression pattern in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is one of the most malignant gastroenterological cancers. To improve the treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC), a biomarker capable of predicting the malignant potential of the cancer cells is needed. The aim of the present study was to investigate the relationship between the expression pattern of insulin-like growth factor II m-RNA-binding protein 3 (IMP3), a promising cancer testis antigen for peptide vaccine therapy, in ESCC tumors and the outcomes of patients with ESCC. METHODS: One hundred and seventy patients with ESCC who underwent a radical transthoracic esophagectomy between 2003 and 2005 at Tokai University Hospital were investigated. IMP3 expression was immunohistochemically analyzed using sections from surgically resected tumor specimens and metastatic lymph nodes. RESULTS: Of the 170 patients, 160 patients (94%) exhibited IMP3 positivity in the cytoplasm of their cancer cells (IMP3-positive group), while 10 patients (6%) were IMP3-negative (IMP3-negative group). No significant difference in the overall survival curves were observed between the IMP3-positive and IMP3-negative groups. When the survival analysis was confined to the 160 IMP3-positive patients, however, an invasive front-type IMP3 expression pattern (IF-type) was seen in 46 patients (29%) and a diffuse-type pattern (D-type) was seen in 114 patients (71%). A multivariate analysis also showed that an IF-type was a prognostic factor (HR =1.618, P=0.049). The overall survival curve for patients with an IF-type was significantly worse than that of D-type patients (P=0.001). CONCLUSIONS: An IF-type pattern of IMP3 expression might predict a poor outcome in patients with ESCC.

Thoracoscopic esophagectomy while in a prone position for esophageal cancer: a preceding anterior approach method.

BACKGROUND: In 2009, the rate of thoracoscopic esophagectomy for esophageal cancer was about 20% in Japan. This low rate may be due to the difficulty in maintaining a good surgical field and the meticulous procedures that are required. The purpose of this study was to establish and evaluate a new procedure for performing a thoracoscopic esophagectomy while the patient is in a prone position using a preceding anterior approach to make the esophagectomy easier to perform. METHODS: We have performed thoracoscopic esophagectomy using our new procedure in 60 patients with esophageal cancer. Each patient was placed in a prone position and five trocars were inserted; only the left lung was ventilated and a pneumothorax was maintained. The esophagus was mobilized from the anterior structure during the first step and from the posterior structure during the second step. The lymph nodes around the esophagus were also dissected anteriorly and posteriorly. The patients were sequentially divided into two groups and their clinical outcomes were evaluated. RESULTS: The mean operative time for the thoracoscopic procedure for the latter 30 cases (203 min) was shorter than that for the former 30 cases (260 min) (P = 0.001). Among the 52 cases without pleural adhesion, the mean blood loss in the latter 26 cases (18 mL) was also less than that in the former 26 cases (40 mL) (P = 0.027). There were no conversions to a thoracotomy and no operative deaths in this series. Postoperative complications related to the thoracoscopic procedure occurred in 8 cases (27%) in the former group and in 4 cases (13%) in the latter group. CONCLUSIONS: Thoracoscopic esophagectomy with the patient in the prone position using a preceding anterior approach is a safe and feasible procedure. As experience performing the procedure increases, the performance of the procedure stabilizes. This method seems to make the esophagectomy easier to perform.

Significant clinical response of advanced colon cancer to peptide vaccine therapy: a case report.

Partial response (PR) was obtained in a patient with advanced colon cancer following peptide vaccine therapy. A 61-year-old woman was referred to our hospital for peptide vaccine therapy. She had undergone sigmoidectomy at a nearby hospital and eventually developed multiple metastases to the lung and pelvic lymph nodes with left hydronephrosis. A ureteral stenting catheter had been inserted for left hydronephrosis, and oral opioids had been administered for relief of pain in the left pelvic region. Three tumor-antigen-derived peptides (RNF43, TOMM34, and KOC1) and two human VEGFR-derived peptides (VEGFR1 and VEGFR2) were used as a cocktail. The peptide cocktail was subcutaneously inoculated on days 1, 8, 15, and 22 and repeated at 14-day intervals. The patient's serum level of carcinoembryonic antigen was 28.9 ng/mL (N<5 ng/mL) before treatment, and it decreased promptly after the initiation of therapy to within a normal range. Evaluation of computed tomography images at week 5 revealed PR as determined by the Response Evaluation Criteria in Solid Tumor criteria. After month 3, the oral opioid was discontinued. The PR lasted for 4 months and was followed by stable disease for another 4 months. No particular adverse effects were observed. A cytotoxic T lymphocyte (CTL) response was evaluated by immunosorbent spot assay, and a positive CTL response was recognized against at least one of five peptides at each end of the six courses. Immunotherapy has been proven to slow tumor growth by inducing an active antitumor immune response; and therefore, significant tumor shrinkage is rarely observed. To our knowledge, this is the first case report of PR presented in a patient with advanced colon cancer.

[Recent advances in endoscopic resection for esophageal cancer].

The indications for endoscopic resection (ER) in esophageal cancer are limited to cases without lymph node metastasis because it is a local therapy. The relationship between cancer depth and lymph node metastasis has been clarified according to the pathologic analysis of lymph nodes removed during esophagectomy for early esophageal cancer. Cancer invasion remaining in the lamina propria mucosa rarely metastasizes to the lymph nodes, and ER is thus indicated. ER allows the esophagus to be preserved and is less invasive, enabling the specimen to be examined pathologically. Lesions extending to a large area can be resected by repeated endoscopic mucosal resection (EMR), but have recently been resected en bloc in the endoscopic submucosal dissection (ESD) procedure, which is also indicated for the treatment of gastric cancer. The selection of EMR or ESD depends on the size of the lesion, the technique of the surgeon, the time the patient can safely spend under anesthesia, and economic management. ER is now employed in T1a-MM, SM1 cases without lymph node metastasis, although some require additional treatment including surgery after pathologic examination of the resected lesions.

[Treatment of esophageal cancer in elderly patients].

During the last 30 years, the median survival time and 5-year survival rate of esophageal cancer have improved significantly. In recent years, two major factors have greatly contributed to improve the outcomes of treatment for esophageal cancer in Japan. One is the establishment of endoscopic diagnosis and treatment of superficial esophageal cancer, and another is the establishment of a standard surgical procedure, subtotal esophagectomy with dissection of three field lymph nodes. In an aging society like Japan, with the increased incidence, the diagnosis and treatment of esophageal cancer will become increasingly important in the future. The effectiveness and risk of surgical treatment, chemotherapy, radiotherapy and combination therapy for elderly patients with esophageal cancer will also become important. However, the average life expectancy has reached 79 years for Japanese men, and various evidence from clinical research on patients less than 75 years old is not longer sufficient. Care of elderly patients with esophageal cancer has relied on past experience. Now, clinical studies on elderly esophageal cancer must be improved.