Kengo Takahashi

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer.

Background:Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.Methods:Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.Results:L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.Conclusions:L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Expression of ER stress markers (GRP78/BiP and PERK) in patients with tongue cancer.

The glucose-regulated protein (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK) plays a crucial role in the endoplasmic reticulum (ER) stress response. GRP78/BiP is highly elevated in various human cancers. Our study is to examine the clinicopathological significance of GRP78/BiP and PERK expression in patients with tongue cancer. A total of 85 tongue cancer patients were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP, PERK, GLUT1, Ki-67 and microvessel density (MVD) determined by CD34.GRP78/BiP and PERK were highly expressed in 47% and 35% of all patients, respectively. GRP78/BiP disclosed a significant relationship with PERK expression, lymphatic permeation, vascular invasion, glucose metabolism and cell proliferation. The expression of GRP78/BiP was significantly higher in metastatic sites than in primary sites (79% vs. 47%, p=0.003). We found that the high expression of GRP78/BiP was proven to be an independent prognostic factor for predicting poor outcome in patients with tongue cancer. In the analysis of PFS, PERK was identified as an independent predictor. The increased GRP78/BiP expression was clarified as an independent prognostic marker for predicting worse outcome. Our study suggests that the expression of GRP78/BiP as ER stress marker is important in the pathogenesis and development of tongue cancer.

Laparoscopic resection of a paraganglioma located on the border of the thoracic and abdominal cavities using a transabdominal-transdiaphragmatic approach

We treated a 64‐year‐old woman with high blood pressure. Catecholamine metabolite levels were elevated in the blood and urine. CT revealed a densely stained tumor on the right side of the descending aorta dorsal to the inferior vena cava. PET‐CT revealed abnormal accumulation of 18F‐fluorodeoxyglucose, and 123I‐meta‐iodo‐benzylguanidine uptake was apparent on scintigraphy. The tumor was determined to be a paraganglioma located on the border between the thoracic and abdominal cavities, and laparoscopic tumorectomy was performed. The patient was placed in the left lateral position. The right lobe of the liver was turned over, and we cut the diaphragm to expose the front of the tumor. We resected the straight artery flowing in from the aorta and removed the tumor safely. Herein, we describe the removal of a paravertebral paraganglioma located in the border of the thoracic and abdominal cavities with a laparoscopic transabdominal‐transdiaphragmatic approach.

High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer.

Nucleobindin 2 has been reported that its high expression is associated with poor outcome and promotes cell migration and lymph node metastasis in breast cancer, colon cancer, and prostate cancer. However, we aimed to investigate the nucleobindin 2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemical analysis. In our study, nucleobindin 2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of nucleobindin 2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and clinical stage. Furthermore, the expression level of nucleobindin 2 protein was independent predictor of progression-free survival. In summary, nucleobindin 2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. CONCLUSION Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Prognostic role of BiP/GRP78 expression as ER stress in patients with gastric adenocarcinoma

PURPOSE The glucose-regulated protein 78 (GRP78), also referred to as immunoglobulin heavy chain binding protein (BiP) (BiP/GRP78), is a major molecular chaperone in the endoplasmic reticulum (ER) and is extensively expressed in human neoplasms. Although the enhanced expression of BiP/GRP78 has been described to be associated with poor prognosis in gastric cancer (GC), details regarding its prognostic significance remain unclear. The aim of this study was to elucidate the prognostic role of BiP/GRP78 in patients with GC. METHODS Study subjects included 328 patients who underwent surgical resection. Tumor specimens of primary tumors underwent immunohistochemical staining for BiP/GRP78. RESULTS BiP/GRP78 was highly expressed in 57% (188/328) of patients. High expression of BiP/GRP78 was significantly associated with older age, male, disease staging, T factor, lymph node metastases, differentiation, lymphatic permeation, and vascular invasion. According to univariate analysis, age, disease staging, T factor, N factor, lymphatic permeation, vascular invasion, and BiP/GRP78 expression were significant prognostic factors for OS. In particular, high BiP/GRP78 expression was proven to be a significant predictor of prognosis in patients with older age, female sex, early disease stage, T1-2 factor, well or moderately differentiated tumors, and negative vascular invasion. CONCLUSION BiP/GRP78 is significantly associated with tumor aggressiveness and progression. The increased expression of BiP/GRP78 was identified as an independent factor for predicting poor OS in patients with early stage of disease, especially T1-2 factor.

Securing the surgical field in laparoscopic pancreatectomy using a Penrose drain and Endo Close.

Introduction: We adopted the use of Penrose drains and Endo Close to secure a good surgical field during laparoscopic pancreatectomy. Methods: We used a Penrose drain with threads ligated on both ends to suspend the stomach. We then pulled the threads out of the body from the side of the trocar or from besides the xiphisternum by using Endo Close. In most cases, 2 Penrose drains were used to retract the stomach. When the greater omentum on the left side of the cardia still blocks the surgical field, we sewed the posterior wall of the stomach onto the dome of the diaphragm. Results: The use of 2 Penrose drains and Endo Close were effective to retract the stomach in most cases. However, in 3 cases, we needed to additionally sew the stomach onto the diaphragm to fully open up the field. Conclusion: This is a simple and effective method to ensure a good surgical field.

Modified Pringle Maneuver Applicable for Laparoscopic Hepatectomy.

INTRODUCTION We present a widely applicable technique of the modified Pringle maneuver to reduce blood loss for laparoscopic hepatectomy. METHODS We use a drip-infusion tube and wrap it around the hepatoduodenal ligament. In the modified Pringle maneuver ① (m-Pringle ①), we use a 60 cm long tube. Both ends of the tube are led out from the side of the umbilical port, then pulled and clipped with Pean forceps to interrupt blood flow. In the modified Pringle maneuver ② (m-Pringle ②), we use a 20 cm long tube with silk threads tied at both ends. The threads were led extraperitoneally in the same manner. RESULTS Although blood flow was sufficiently interrupted, CO2 leak occurred in 14 of 60 cases in m-Pringle ①. Blood flow was interrupted and intra-abdominal pressure was kept in all 10 patients in m-Pringle ②. CONCLUSIONS These maneuvers require no extra port, and tube pulling and releasing is readily performed from outside the body.