Naritaka Tanaka

MiR‐150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1

The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR‐150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial‐mesenchymal‐transition (EMT)‐inducer, as a target gene of miR‐150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR‐150 in ESCC, and to investigate miR‐150′s EMT‐regulatory ability. Quantitative RT‐PCR was used to evaluate miR‐150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR‐150 via degradation of ZEB1. MiR‐150 expression was significantly lower in cancer tissues compared to adjacent non‐cancerous tissues (P < 0.001). Low expression of miR‐150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (P < 0.05). In vitro assays showed that EMT‐inducer‐ZEB1 is a new direct target of miR‐150. Moreover, miR‐150 induced MET‐like changes in TE‐8 cells through ZEB1 degradation (e.g., E‐cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR‐150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC. (Cancer Sci 2013; 104: 48–54)

The clinical application of 18F‐fluorodeoxyglucose positron emission tomography to predict survival in patients with operable esophageal cancer

Metabolic tumor activity using 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) was believed to have a predictive value for patient outcome in malignancies. The objective of the current study was to assess the prognostic effectiveness of the highest standardized uptake value (SUV) in the primary or regional area (peak SUV) and the number of PET‐positive lymph nodes in esophageal cancer.

Surgical Treatment for Esophageal Cancer

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.

Effect of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve to gastrointestinal function: an experimental study in conscious dogs.

Objective:To evaluate the effects of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve on gastrointestinal function. Summary Background Data:The operative procedure of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve is now in the spotlight in Japan with the goal of finding a function-preserving surgical technique. However, there has been no analysis of the effect of this type of surgery on gastrointestinal function. In this article, we describe the results of a fundamental experiment on distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve. Methods:Twenty conscious dogs were divided into 2 groups, each subdivided into 2 groups of 5: a normal intact dog group (NG) divided into 2 groups, with preservation (PNG) and resection (RNG; these dogs were truncally vagotomized including transaction of the celiac branch) of the celiac branch, and a gastrectomy dog group (GG) divided into 2 groups, with preservation (PGG) and resection (RGG) of the celiac branch. The motility of the dogs was recorded using strain gauge force transducers. The effects of the preservation of the celiac branch of the vagus nerve on gastrointestinal motility, gastric emptying, and pancreatic insulin release were evaluated. Results:The motility index of gastrointestinal motility with preservation of the celiac branch was higher than the motility index with resection of the celiac branch in fasted and fed of NG and GG. In gastric emptying, significant differences were found between the PNG and RNG but not between the PGG and RGG. In the fasted state for 80 minutes of the PNG and PGG, the serum insulin concentration reached a peak during the early phase III at 20 minutes in the gastric body and the antrum. Conclusions:This study has shown that it is effective to preserve the celiac branch of the vagus nerve for gastroduodenal motility, gastric emptying, and pancreatic insulin release after a gastrectomy.

Quantitative analysis of cisplatin sensitivity of human esophageal squamous cancer cell lines using in-air micro-PIXE

Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in‐air micro‐PIXE (particle induced X‐ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE‐2 and TE‐13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real‐time reverse transcription–polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in‐air micro‐PIXE. TE‐2 cells were more sensitive to cisplatin than TE‐13 cells (IC50: 37.5 μm and 56.3 μm, respectively). Flow cytometry analysis confirmed that more TE‐2 than TE‐13 cells were in the sub‐G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE‐13 cells was stronger than in TE‐2 cells. In‐air micro‐PIXE showed that TE‐2 cells had higher intracellular cisplatin concentrations than TE‐13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in‐air micro‐PIXE. The results of this study suggest that in‐air micro‐PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells. (Cancer Sci 2010)

Diaphragmatic Hernia with Ischemic Bowel Obstruction in Pregnancy : Report of a Case

Diaphragmatic hernia complicating pregnancy is rare and is associated with high morbidity and mortality, particularly if surgical intervention is delayed. We report a case of diaphragmatic hernia in a pregnant 25-year-old woman. The patient was referred to our hospital in respiratory distress in the 28th week of her pregnancy. Chest radiograph and computed tomography showed air-filled bowel loops in the left side of the chest, with a marked mediastinal shift. Immediately after an emergency caesarean section, the herniated abdominal viscera were reduced through the opening in the diaphragm. We resected the ischemic segment of ileum and repaired the diaphragmatic defect with interrupted sutures and a Gore-Tex sheet. She had an uneventful postoperative course and her baby boy also recovered well. We report this case to alert surgeons to the possibility of this rare surgical emergency during pregnancy.

Ghrelin level and body weight loss after esophagectomy for esophageal cancer.

BACKGROUND Ghrelin is a peptide hormone predominantly produced by endocrine cells in the oxyntic mucosa of the stomach and is an endogenous ligand for the growth hormone secretagogue receptor. Ghrelin plays an important role in regulating appetite, food intake, and energy metabolism. We investigated the correlation between clinicopathologic factors and plasma ghrelin concentration before and after esophagectomy with gastric tube reconstruction for esophageal cancer treatment. METHODS The study group comprised 25 patients (22 men, three women, age range 46-78 y) with esophageal cancer who underwent esophagectomy with gastric tube reconstruction between 1999 and 2007. Blood samples were collected before and three times after the operation. Plasma concentrations of ghrelin were determined using a sandwich-type enzyme immunoassay kit. RESULTS Plasma ghrelin concentrations were significantly decreased to 38.7% of the preoperative concentration at postoperative d 7. Plasma ghrelin concentrations recovered slightly over 6-24 mo postoperatively. After 36 mo or longer, ghrelin concentrations had returned to preoperative levels. There was no relationship between ghrelin concentrations and gender, location of tumor, tumor stage, operative procedure, and reconstruction route at each time point. There was a significant relationship between the decrease in body mass index and decrease in plasma ghrelin in patients at 6-24 mo after esophagectomy (P < 0.01). CONCLUSIONS Plasma ghrelin concentrations decrease on a temporary basis after esophagectomy with gastric tube reconstruction and are associated with body weight loss after surgery.

Significance of Lymph Node Capsular Invasion in Esophageal Squamous Cell Carcinoma

BackgroundExtranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC.MethodsWe investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC.ResultsLNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases.ConclusionsLNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

Clinical study of inguinal and femoral incarcerated hernias.

PurposeInguinal and femoral hernias are common disorders associated with aging. Incarcerated external hernias, however, are often fatal. This study investigated the prognostic factors in patients with incarcerated hernias.MethodsThe study reviewed 38 patients (aged 35–97 years) diagnosed with incarcerated hernias who underwent emergency surgery. The patients were divided into those with or without a small intestinal resection, and they were then analyzed according to time from onset of symptoms to surgery.ResultsThe time from symptom onset to surgery was significantly longer in the resection group than in the group without resection. The patients were divided into those treated within or after 12 h using a receiver-operating characteristic curve. A sensitivity of 71.4% and a specificity of 83.4% were obtained using the time from symptom onset to operation of 12 h as a cutoff value. More patients who underwent surgery after 12 h from the onset of symptoms required an intestinal resection. Patients who underwent surgery later than 12 h after the onset of symptoms also stayed in the hospital longer than those operated on within 12 h.ConclusionsThe amount of time that elapses from the onset of symptom to surgery is considered to be an important prognostic factor in patients with incarcerated hernias. Early diagnosis and early treatment are therefore necessary in such patients.

Prognostic Significance of Inflammatory and Nutritional Parameters in Patients with Esophageal Cancer

BACKGROUND We evaluated the following preoperative prognostic factors in patients who underwent esophagectomy for esophageal cancer: C-Reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), serum albumin, prognostic nutritional index (PNI), and body mass index (BMI). PATIENTS AND METHODS This retrospective study included 173 men and 19 women with a mean age of 65.8 years (range=42-86 years) who were scheduled to undergo esophagectomy for esophageal cancer. The association of CRP, NLR, albumin, PNI, and BMI with various clinicopathological factors and prognosis were evaluated. RESULTS Univariate analysis revealed that male sex, depth of invasion, nodal metastasis, pStage, high CRP, low PNI, high NLR, and low BMI were significant risk factors for a poor prognosis. Multivariate analysis identified depth of invasion, pStage, and BMI as significant prognostic factors in the Cox proportional hazard model. CONCLUSION The preoperative nutritional status affected the postoperative survival time in patients with esophageal cancer. In particular, a low BMI was an independent prognostic factor for poorer survival in the multivariate analysis.