Daigo Ozawa

High stathmin 1 expression is associated with poor prognosis and chemoradiation resistance in esophageal squamous cell carcinoma

Stathmin 1 (STMN1) is a major cytosolic phosphoprotein regulating microtubule dynamics, thereby playing an important role in cancer progression and resistance to microtubule-binding anticancer agents. We assessed the prognostic significance of STMN1 expression and STMN1-associated resistance to docetaxel and radiation in esophageal squamous cell carcinoma (ESCC) patients. STMN1 expression was evaluated by immunohistochemistry in 172 surgical specimens. The association of STMN1 expression with chemoradiation resistance using docetaxel was examined by comparing expression in 15 biopsy specimens obtained before neoadjuvant therapy to histological grades of post-therapy surgically resected tumors. We also evaluated the effects of STMN1 on sensitivity to docetaxel and radiation in ESCC cell lines. High STMN1 immunoexpression was significantly associated with tumor depth, lymph node metastasis, lymphatic invasion and venous invasion. Survival rates were significantly lower in ESCC patients with high STMN1 expression than in those with low STMN1 expression. Multivariable analysis showed that high STMN1 expression was an independent factor for poor survival. High STMN1 expression was also associated with poor response to neoadjuvant chemoradiotherapy using docetaxel. Knockdown of STMN1 expression enhanced ESCC cell line sensitivity to docetaxel and radiation. STMN1 appears critical for ESCC invasiveness and predicts an unfavorable prognosis in ESCC.

18F-FAMT-PET is useful for judging clinical complete response in advanced esophageal cancer patients who have received definitive chemoradiotherapy

Abstract Background: We developed 18F-FAMT as an amino acid tracer for PET imaging. In esophageal cancer, 18F-FAMT PET was significantly higher than that of 18F-FDG PET and CT in the evaluation of individual lymph node groups. Definitive CRT has been considered to be a potentially curative treatment for locoregional esophageal cancer and may achieve the same survival benefits as surgical resection. Clinical evaluation of complete response (CR) is important using several modalities. Patients and Methods: We evaluated 6 patients who had been diagnosed with clinical CR by FAMT-PET following definitive CRT for esophageal SCC between June 2008 and July 2012. Treatment evaluation of 18F-FAMT was performed following CRT, and approximately 1 month later. Results: In primary tumors, 66.7% of patients (4/6) showed FDG uptake following CRT, whereas that of FAMT was 33.3% (2/6). In lymph node metastases, 50% of patients (3/6) showed FDG uptake following CRT, whereas that of FAMT was 0% (0/6). In the present study, FA...

18F-FAMT PET Is Useful to Distinguish between Specific Uptake and Nonspecific Uptake Compared to 18F-Flourodeoxyglucose Position Emission Tomography in Esophageal Cancer Patients

Background: L-[3-¹⁸F]-α-methyltyrosine (¹⁸F-FAMT) solely accumulates in tumor cells via an amino acid transport system. This selective uptake pattern results in a very high tumor-to-background ratio, enabling clear delineation of the tumor. The purpose of the present study was to assess the significance of ¹⁸F-FAMT PET, which shows little nonspecific uptake compared to ¹⁸F-flourodeoxyglucose position emission tomography (FDG PET) in esophageal cancer patients. Methodology: PET-CT studies with ¹⁸F-FAMT and ¹⁸F-FDG were performed as part of pretreatment work-up in 82 patients with histologically confirmed esophageal cancer. We evaluated nonspecific uptakes of ¹⁸F-FDG and ¹⁸F-FAMT PET. Results: The nonspecific uptake of ¹⁸F-FAMT PET was lower than that of ¹⁸F-FDG PET (p = 0.282). In the operation group, 26.1% demonstrated nonspecific uptake in ¹⁸F-FDG PET, whereas only 2.38% (1 case) demonstrated nonspecific uptake in ¹⁸F-FAMT PET (p = 0.433). In the inoperable group, 47.5% showed nonspecific uptake in ¹⁸F-FDG PET, whereas 5.0% showed nonspecific uptake in ¹⁸F-FAMT PET (p = 0.079). Conclusion: A crucial point for the diagnostic value of PET is distinguishing specific and nonspecific uptake. ¹⁸F-FAMT-PET is a very superior modality with regard to the lower rate of nonspecific uptake in esophageal cancer.

Intestinal epithelial culture under an air‐liquid interface: a tool for studying human and mouse esophagi

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.

Novel Procedure of Circular Stapler-Guided Nasogastric Tube Insertion during Esophageal Reconstruction

Received August 3, 2011; Revised September 7, 2011; Accepted September 12, 2011. From the Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan (Tanaka, Miyazaki, Ozawa, Suzuki, Yokobori, Inose, Sohda, Asao, Kuwano) and Department of Surgical Oncology, Dokkyo Medical University, Mibu-machi, Japan (Kato). Correspondence address: Naritaka Tanaka, MD, PhD, Department of General Surgical Science, Gunma University, Graduate School of Medicine, 3-39-22, Figure 1. (A) Silk suture is threaded through the frontal holes of the (C) Schema of A. (D) Schema of B.