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Using a self-expanding metal stent as a bridge to surgery (BTS) is considered a reasonable strategy for patients with acute malignant large bowel obstruction. Since postoperative complications have a negative impact on patient survival, we aim to clarify the predictors of complications in patients undergoing BTS using a self-expanding metal stent.We conducted a retrospective review of 61 patients with colorectal cancer (CRC) who underwent stenting as a BTS at our institution. We analyzed the association of postoperative complications with clinicopathologic, surgical, and patient factors, and with the prestenting or preoperative laboratory data.Both postoperative complications in general and severe complications were significantly associated with a longer stenotic-section length (p = 0.007 and p = 0.003), lower preoperative hemoglobin levels (p 0.001 and p = 0.081), and lower prestenting hemoglobin levels (p = 0.006 and p = 0.042). Multivariate logistic regression analysis showed that lower prestenting (13.0 g/dl) and preoperative (11.5 g/dl) hemoglobin levels were independent predictive factors for postoperative complications (odds ratio [OR]: 4.15; 95% confidence interval [CI]: 1.07-18.90; p = 0.040; and OR: 4.93; 95% CI: 1.35-20.28; p = 0.016). A stenotic-section length of 5.0 cm or greater was predictive of severe complications (OR: 25.67; 95% CI: 1.95-1185.00; p = 0.011).Our data suggest that lower hemoglobin levels before stenting and a longer length of the stenotic section of bowel might predict postoperative complications in patients with CRC undergoing BTS for obstruction.

Aim Severe postoperative pleural effusion (sPOPE) after hepatectomy can lead to respiratory distress and may require thoracic drainage, leading to prolonged hospitalization. Preventive chest tube insertion may be useful for patients at high risk for sPOPE. We aimed to develop a predictive model for sPOPE after hepatectomy and evaluate indications for preventive chest tube insertion using our model. Methods We evaluated all patients who underwent hepatectomy from 2013 to 2020. Risk factors for sPOPE were used to develop a predictive model for sPOPE, which was validated in a cohort that received preventative chest tube placement postoperatively. Results A total of 325 patients were analyzed. Thirty‐one (9.5%) patients had a preventive chest tube placed at the end of their operation. Twenty‐one patients out of the remaining 294 patients developed sPOPE. Multivariate analysis identified resection containing segment 8 [relative risk (RR) 3.24, P = .022], intraoperative bleeding ≥ 500 g (RR 4.02, P = .008), intraoperative diaphragmatic incision (RR 6.96, P = .042) and open hepatectomy (RR 7.51, P = .016) as independently associated with sPOPE. The estimated probability of sPOPE ranged from 0.4% in patients with none of these factors to 73.4% in the presence of all factors. Among the 31 patients who received a preventive chest tube, more patients in the high‐risk group defined by the model had postoperative pleural effusions compared to the low‐risk group (P = .012). Conclusion Our predictive model for sPOPE using four risk factors allows for reliable prediction and may be useful for selection of preventive chest tube in patients undergoing hepatectomy., We established a predictive model for severe posthepatectomy pleural effusion (sPOPE). Our predictive model of sPOPE using four risk factors allows for reliable prediction and may be useful for selection of preventive chest tube in patients undergoing hepatectomy.

BACKGROUND AND AIM Clinical significance of endoscopic response (ER) after neoadjuvant chemotherapy (NAC) for esophageal cancer has not been fully understood. Thus, the present study aimed to investigate the association between ER to NAC and its clinicopathological outcomes in patients with esophageal squamous cell carcinoma (ESCC). METHODS In total, 141 patients who underwent NAC and subsequent esophagectomy for ESCC were included. ER to NAC was retrospectively evaluated based on macroscopic findings of the primary tumor, which was classified into three categories: endoscopic no response (eNR), endoscopic partial response (ePR), and endoscopic good response (eGR). An endoscopic responder was defined as patients with eGR/ePR. RESULTS Approximately 89.4% of patients had cStage II-III disease, and 7.1% had pathological complete response. Upon ER evaluation, eNR, ePR, and eGR were observed in 46 (32.6%), 54 (38.3%), and 41 (29.1%) patients, respectively. Pathological responders significantly increased as the ER grade became better. Among preoperative clinical factors, only ER significantly correlated with pathological response in univariate and multivariate analysis. Endoscopic responders showed a significantly better prognosis than did eNR patients (P

Background Subtotal cholecystectomy in patients with severe acute cholecystitis is considered a “bailout” option when the safety of the bile duct cannot be guaranteed. However, subtotal cholecystectomy has a long-term risk of remnant cholecystitis. The appropriate management of remnant cholecystitis has not been fully elucidated. Case presentation Case 1 was a 66-year-old man who had undergone subtotal cholecystectomy 14 years prior to the development of remnant cholecystitis. We first performed endoscopic gallbladder drainage to minimize inflammation, and then proceeded with elective surgery. We performed a reconstituting procedure for the residual gallbladder due to significant adhesions between the cystic and common bile ducts. Case 2 was a 56-year-old man who had undergone subtotal cholecystectomy for abscess-forming perforated cholecystitis 2 years prior to the development of remnant cholecystitis. He underwent endoscopic drainage followed by complete remnant cholecystectomy 4 months later. Conclusion Endoscopic gallbladder drainage is a useful strategy to improve inflammation and reduce the risk of bile duct injury during remnant cholecystectomy.

To investigate the factors predictive of anastomotic leakage in patients undergoing elective right-sided colectomy. The subjects of this retrospective study were 247 patients who underwent elective right hemicolectomy or ileocecal resection with ileocolic anastomosis between April 2012 and March 2019, at our institution. Anastomotic leakage occurred in 9 of the 247 patients (3.6%) and was diagnosed on median postoperative day (POD) 7 (range POD 3–12). There were no significant differences in the background factors or preoperative laboratory data between the patients with anastomotic leakage (anastomotic leakage group) and those without anastomotic leakage (no anastomotic leakage group). Open surgery was significantly more common than laparoscopic surgery (P = 0.027), and end-to-side anastomosis was less common (P = 0.025) in the anastomotic leakage group. The C-reactive protein (CRP) level in the anastomotic leakage group was higher than that in the no anastomotic leakage group on PODs 3 (P

A 72-year-old woman was referred to our hospital with the diagnosis of peritonitis due to the rupture of a huge abdominal cystic tumor, 27 cm in diameter. Abdominal computed tomography 14 years before revealed the tumor, which was 18 cm in diameter. She had undergone no examinations or treatment in the interim. She was in shock upon presentation to our hospital. She was intubated immediately and underwent an emergent laparotomy. The huge ruptured tumor with adherent small intestine was resected. The tumor weighed 6 kg and consisted of solid and cystic components filled with 4 kg of brown feces-like fluid. Bacteroides fragilis was detected in a fluid specimen. The cystic component of the tumor was filled with old blood clots, and a portion of the tumor wall was highly calcified. Old blood and fibrin with blood vessels of various sizes inside the tumor were observed during the pathologic evaluation; there were no malignant features. The final pathologic diagnosis was a chronic expanding hematoma (CEH). The patient had an uneventful recovery and was discharged 16 days post-operatively. She was involved in a traffic accident approximately 30 years before the current hospital admission; however, she did not recall if she had abdominal pain at that time. A CEH is a benign lesion, but rupture of a CEH can be life-threatening.

Perforated marginal ulcer after pancreaticoduodenectomy(PD)is a delayed complication. We evaluated the characteristics of the patients presenting perforated marginal ulcer after PD.Five cases of perforated marginal ulcer after PD were reported at our hospital between 2008 and 2018, and the characteristics of these patients were evaluated.All 5 patients(4 females)with median age 73 years underwent subtotal stomach-preserving PD(SSPPD). In spite of the administration of gastric antisecretory medication, perforated marginal ulcer occurred in 3 patients(60%). All patients were treated with direct suture and omentum patch, and no mortality was reported.The perforating marginal ulcer after SSPPD occurred despite the administration of the gastric antisecretory medication. Treatment with direct suture and omentum patch was effective in perforated marginal ulcer after SSPPD.

Approximately 10–20 % of esophageal cancer patients in whom recurrence is diagnosed experience late recurrence beyond 2 years after esophagectomy. However, the risk of late recurrence is still unclear. The aim of this study was to identify the risk factors of late recurrence for appropriate postoperative surveillance. A total of 447 patients underwent radical esophagectomy and reconstruction for esophageal cancer from 2005 to 2014. Patients who had recurrence beyond 2 years after esophagectomy were defined as the late recurrence group and the remaining patients with recurrence as the early recurrence group. A comparison of the clinicopathological factors and prognosis was performed between patients with early recurrence, late recurrence, and no recurrence. Recurrences were recognized in 117(26.2 %) of the 447 patients. Recurrence was diagnosed within 2 years after surgery in 103 patients (88.0 %) and after 2 years in 14 patients (12.0 %). Patients with late recurrence showed a favorable prognosis compared with those with early recurrence (P = 0.0131), and late recurrence was an independent factor associated with a favorable prognosis after recurrence (HR 0.199, P = 0.025). In the comparison between patients with late recurrence and those with no recurrence who had a minimal recurrence-free survival of 2 years, pathological lymph node metastasis at esophagectomy was found to be an independent predictor of late recurrence (HR 7.296, P = 0.043). Pathological lymph node metastasis at esophagectomy is a risk factor of late recurrence for esophageal cancer, and a close, lifelong follow-up is recommended for such patients.

Metastasis of breast cancer to the gastrointestinal tract is relatively rare. We hereby report a case of breast cancer recurrence in the esophagus, stomach, and liver, 15 years following primary surgery. A 67-year-old woman presented with a 2-month history of dysphagia. Fifteen years previously, she had undergone right mastectomy for breast carcinoma. Upper gastrointestinal endoscopy revealed circumferential stenosis without mucosal abnormality in the lower esophagus and enlarged gastric folds and defective extension in the upper stomach. Biopsy specimens from the esophagus and gastric folds were consistent with invasive lobular carcinoma. Abdominal computed tomography and magnetic resonance imaging showed two hepatic tumors, and liver biopsy revealed breast cancer recurrence. Immunohistochemistry supported the diagnosis of breast cancer recurrence in the esophagus, stomach, and liver. Gastrointestinal metastases should be considered for patients with breast cancer who present with gastrointestinal symptoms, even if the primary tumor was treated many years previously.

Primary mucosal malignant melanoma (PMMM) is a rare and highly lethal neoplasm associated with a poor prognosis. CXC chemokine receptor 4 (CXCR4) is expressed on various tumor cells, including malignant melanoma. Recent data indicate that CXCL12 and CXCR4 play a critical role in the behavior of cancer cells and in the survival of cancer patients. However, there has been no study that has addressed the expression and function of CXCR4/CXCL12 signaling in PMMM. Immunohistochemical staining for CXCL12 and Ki67 in biopsy tissues from 10 cases of PMMM was performed. We analyzed the correlations between the clinicopathological features and expression levels of CXCL12 and Ki67. Six cases showed a high level of CXCL12 expression, while four cases had a low level of expression. High expression of CXCL12 correlated with a poor prognosis, although statistical significance was not reached (p = 0.054). Ki67 was highly expressed in five cases, while the expression in the other five cases was low. There was no correlation between the Ki67 expression and prognosis. The findings of this study suggest that CXCL12 expression may play an important role in the biological behavior of PMMM and may be associated with a poor prognosis of PMMM patients.

Postoperative morbidity remains common after esophagectomy. There are currently few tools that can be used to estimate the incidence of complications. This study aimed to create a novel scoring system for predicting postoperative morbidity. A total of 365 patients who underwent elective esophagectomy with two- or three-field lymphadenectomy for esophageal cancer were retrospectively analyzed. Patients were divided into development (n = 250) and validation datasets (n = 115). A scoring system was established by specifying the expected morbidity incidence values for all independent predictors in the development dataset, after which, the reproducibility was confirmed in the validation dataset. The incidence of any morbidity was 44.7 %. Male sex, severe emaciation (body mass index

Although a survival benefit of neoadjuvant treatment for patients with esophageal cancer has been highlighted, the influence of neoadjuvant treatment on the nutritional status of patients with esophageal cancer is not well understood.Changes in body composition parameters were assessed in 30 patients who underwent neoadjuvant chemotherapy (NAC) comprising docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy from August 2009 to April 2013. Body composition was evaluated before and after NAC using multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan). Postoperative complications were graded according to the Clavien-Dindo classification.Twenty-three postoperative events occurred in 16 patients. A decrease in body protein was observed in 13 patients (43.3 %), while skeletal muscle (SM), body cell mass (BCM), and fat-free mass (FFM) declined in 11 patients (36.7 %) during NAC. Changes in these four parameters during chemotherapy significantly differed between patients with postoperative complications and those without: protein, -1.6 ± 0.9 versus +4.4 ± 2.1 kg (P = 0.01); SM, -1.3 ± 1.1 versus +4.7 ± 2.4 kg (P = 0.02); BCM, -2.4 ± 1.6 versus +3.8 ± 2.2 kg (P = 0.03); and FFM, -1.4 ± 1.4 versus +4.3 ± 2.3 kg (P = 0.04).Changes in body composition parameters are possible predictive markers of postoperative complications after esophagectomy after NAC. Further analysis is needed to clarify whether nutritional intervention improves such parameters and thus contributes to reduced postoperative morbidity.

A limited number of patients with resectable advanced esophageal cancer can be cured by surgery alone. Although a regimen that consists of docetaxel, cisplatin, and 5-fluorouracil (DCF) is a potential preoperative chemotherapy (PCT) option for squamous cell carcinoma of the esophagus, the influence of DCF on subsequent esophagectomies remains unclear. A total of 80 patients who received preoperative DCF chemotherapy, and 174 patients who did not receive any preoperative treatment were retrospectively analyzed. There were no treatment-related deaths. No delays in surgery due to adverse events related to DCF were reported. Although patients who received PCT had significantly more advanced cancers and worse preoperative conditions, the incidence rates of complications did not increase. Although the frequency of severe complications was significantly higher in patients who received PCT, this treatment was not an independent factor for the occurrence of severe complications. PCT with DCF did not negatively affect subsequent esophagectomies with regard to the frequency of complications.

Sivelestat, a selective inhibitor of neutrophil elastase, has been reported to reduce acute lung injury associated with systemic inflammatory response syndrome. This study retrospectively investigated the effect of sivelestat on respiratory function in patients who underwent esophagectomy.Patients who underwent esophagectomy for thoracic esophageal cancer between 2005 and 2010 were included in this study. Forty-two were treated perioperatively with sivelestat (4.8 mg/kg/day; sivelestat group) and the remaining 35 were not (control group). Sivelestat was administered continuously from the beginning of surgery until postoperative day 3. All patients were administered methylprednisolone for 3 days. The perioperative clinical and laboratory data, total sequential organ failure assessment score, PaO2/FiO2 ratio (P/F ratio) and postoperative complications were compared between the two groups.There were no significant differences between the groups in the patients' background data. The P/F ratio immediately after surgery was significantly higher in the sivelestat group than in the control group (p0.05). The respiratory rate immediately after surgery and the temperature on postoperative day 2 were significantly lower in the sivelestat group than in the control group (p0.05). There were no differences in any of the other clinical data or complications.Perioperative administration of sivelestat improves postoperative respiratory function in patients after esophagectomy.

Background: The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown. Methods: Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated. Results: Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth. Conclusion: The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cisplatin. Everolimus could be a useful anti-cancer drug for patients with OSCC.

Background and Objectives D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin–eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated. Results An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P

The CellSearch system (Veridex, LLC) is useful for detecting circulating tumor cells (CTCs) in various carcinomas, including colorectal cancer (CRC); however, there are some problems associated with its clinical use. A transcription–reverse transcription concerted reaction (TRC) method, which is a PCR-based technique producing more stable and reliable results, because it is a more simplified process compared with the conventional techniques, has been introduced for detecting micrometastasis in some carcinomas. We aimed to demonstrate the effectiveness of TRC method in the CTC detection. We compared the two methods for the sensitivity for CTC detection using the colon cancer cell line and 42 whole-blood samples from patients with advanced or metastatic CRC. Furthermore, 25 patients with metastatic CRC were enrolled to investigate the correlation between CTC detection and prognosis in both methods. The sensitivity of the TRC method was similar to that of the CellSearch system. The overall survival rate was significantly worse in the patients diagnosed as CTC-positive by the TRC method than in those diagnosed as CTC-negative; this finding was similar to the prognosis indicated by the CellSearch system. However, clinically, the TRC method could detect CTCs more rapidly and at a reduced cost compared with the CellSearch system. The TRC method seems to be a useful alternative to the CellSearch system for clinically detecting CTCs in patients with metastatic CRC.

Background: Despite improvements in the surgical management of esophageal cancer, the prognosis of patients with lymph node metastases is still unsatisfactory. Recently, survival benefit of neoadjuvant or induction chemotherapy for patients with esophageal cancer has been highlighted. Methods: Efficacy and toxicity of induction chemotherapy for esophageal cancer were reviewed. In addition, our experience on modified docetaxel/cisplatin/5-FU (DCF) as induction chemotherapy was also demonstrated. The modified DCF consisted of 60 mg/m2 of docetaxel on day 1, and 350 mg/m2 of 5-FU and 6 mg/m2 of cisplatin on days 1–5. Two courses have been administered as induction chemotherapy in 51 patients with node-positive esophageal cancer. Response was evaluated by RECIST v1.0 and changes in standardized uptake value by 18F-fluorodeoxyglucose positron emission tomography. Results: Induction chemotherapy may be beneficial for node-positive esophageal cancer, although the consensus has not yet been established. A regimen of induction chemotherapy should have a high response rate and cisplatin/5-FU may be underpowered as an induction setting. DCF can be a candidate for the regimen of induction chemotherapy for esophageal cancer, although severe adverse events have been reported. Several modified regimens to reduce the toxicity have been reported. The response rate of our series was 61% and a significant decrease in standardized uptake values was observed after the induction chemotherapy. Although high-grade neutropenia was still observed with this regimen, neither treatment-related death nor delay in the following treatment was observed. Conclusions: Modified DCF can be a regimen of induction chemotherapy for node-positive esophageal cancer because of its high efficacy, although an adequate care for severe neutropenia is needed.

Improvements in imaging technology have resulted in an increase in the incidental detection of intraabdominal tumors. Diagnostic computed tomography (CT)- and ultrasound (US)-guided biopsy, while minimally invasive, often provides specimens that are insufficient for histological evaluation. Moreover, it can be difficult to perform because the location and size of the tumor. In such cases, laparoscopic biopsy is useful because it is less invasive than laparotomy, but more reliable than imaging-guided biopsy, to obtain a sufficient specimen, regardless of the location and size of the tumor. We report a series of seven patients who underwent laparoscopic biopsy of intraabdominal tumors of unknown origin. There were no cases of conversion to laparotomy and all patients were able to resume oral intake on postoperative day 1. There were no intraoperative or postoperative complications. Thus, laparoscopic biopsy for a tumor of unknown origin is useful and minimally invasive.

Background and Objectives The aim of this study is to clarify the extent of lymphatic spread of cancer cells using a novel genetic test to examine patients with thoracic esophageal squamous cell carcinoma (ESCC). Methods A total of 35 patients who underwent an esophagectomy with three-field lymph node (LN) dissection were eligible. The regional LN stations were categorized into the cervical (C), recurrent nerve (RN), paraesophageal (PE), tracheo-bronchial (TB), and perigastric (PG) nodes. Lymphatic spread was pathologically diagnosed with Hematoxylin-Eosin (HE) and anti-cytokeratin immunohistochemistry (IHC) staining, and CEA-mRNA expression was examined using the transcription-reverse transcription concerted (TRC) reaction. Results The rates of lymphatic spread with HE, IHC, and TRC were 7.2%, 10.1%, and 55.5%, respectively. The number of CEA-mRNA(+) LN stations significantly correlated with tumor depth, LN metastasis diagnosed by HE, and vascular invasions. CEA-mRNA expression was observed in 42.9%, 94.3%, 77.1%, 80.0%, and 82.9% of C, RN, TB, PE, and PG nodes, respectively. Conclusions The high frequency of CEA-mRNA expression suggests that systemic therapy is necessary in addition to esophagectomy with adequate LN dissection. Conversely, a relatively low frequency of CEA-mRNA expression in the C node does not support the routine dissection of the LNs in this area. J. Surg. Oncol. 2010;102:509–515. © 2010 Wiley-Liss, Inc.

Peritoneal dissemination of gastric cancer is often refractory to systemic therapies. Although adenoviral gene therapy has been reported to be a potentially useful therapeutic modality, the adenovirus itself has a dose-limiting toxicity. A novel system was constructed using adenoviral oncolytic suicide gene therapy targeting carcinoembryonic antigen (CEA), and its therapeutic effect and the possibility to reduce the total viral dose while still preserving the antitumor effect were assessed.Three types of adenoviruses were prepared for this novel system: (A) Ad/CEA-Cre, (B) Ad/lox-CD::UPRT for a Cre/loxP system, and (C) Ad/CEA-E1 for conditionally replicating adenovirus. The antitumor effect of the oncolytic suicide gene therapy (A + B + C) was then evaluated in vitro. Mice bearing peritoneal dissemination of human gastric cancer were treated with either this system (A + B + C) or with a tenfold viral dose of suicide gene therapy (A + B). The adverse effects in terms of hepatotoxicity were then evaluated between the two groups.The current system (A + B + C) demonstrated significantly better cytotoxic effect for CEA-producing cell lines than did suicide gene therapy (A + B) at the same viral dose in vitro. The effect of oncolytic suicide gene therapy was almost equal to that of the tenfold viral dose of suicide gene therapy in vivo. The hepatotoxicity of the two treated groups was also found to be equivalent.It was possible to reduce the total adenoviral dose of oncolytic suicide gene therapy while still preserving the antitumor effect.

Introduction: Neutrophil gelatinase-associated lopocalin (NGAL) is well known as the biomarker of acute kidney injury. Currently, serum NGAL is reported as the biomarker which is associated with mortality and multiple organ dysfunction syndrome in septic patients. In this study, we measured serum NGAL in post cardiac arrest syndrome (PCAS) patients to investigate the predictive value of neurological outcome. Hypothesis: Serum NGAL is associated with favorable neurological outcome of PCAS patients. Methods: 43 cases of PCAS patients were measured serum NGAL on day 1 and 2, and serum neuron specific enolase (NSE) was also measured on day 2. Patients were divided into two group (group G: CPC 1-2 and group P: CPC 3-5, CPC: cerebral performance categories). Serum NGAL and NSE were compared between group G and P. Receiver operation characteristic (ROC) curve analysis were performed of both NGAL and NSE. Results: Group G (n = 20) and P (n = 23) were analyzed. Serum NGAL showed significant difference in day 2 (G: 282±116 ng/mL v.s. P: 299±87 ng/mL in day1: P = 0.609, G: 185±124 ng/mL v.s. P: 353±110 ng/mL in day 2: P Conclusions: Serum NGAL in PCAS patients had the predictive value for neurological outcome which is comparable to serum NSE. (This study was supported by grants from Japanese Ministry of Health, Labour and Welfare: No. 25462824)

Depletion of skeletal muscle mass (sarcopenia) indicates a poor prognosis for patients with several kinds of cancer, but it remains unclear whether esophageal squamous cell carcinoma (ESCC) is among these cancers. The aim of this study was to clarify the relationship between sarcopenia and postoperative outcome in patients with ESCC treated by esophagectomy. Skeletal muscle mass was assessed in 138 patients who underwent esophagectomy from August 2009 to May 2014. A multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan) was used to assess skeletal muscle mass just before surgery. Postoperative complications were graded according to the Clavien–Dindo classification, and univariate and multivariate analyses were performed for postoperative respiratory complications. Sarcopenia was determined in 61 patients (44.2 %). Preoperative pulmonary function was significantly lower and the rate of respiratory complications significantly higher in the sarcopenia group than in the non-sarcopenia group (p

症例は54歳の男性で, 職場検診にて肝S6に腫瘤を指摘された. HCV抗体陽性でAFPが301ng/ml, AFP-L3分画が72.5%と上昇していた. 腹部超音波では混合エコーを呈した. 単純CTでは低吸収域, 造影早期で辺縁のみが淡く造影され, wash-outは明らかではなかった. 肝後区域切除術を施行した. 腫瘍径は3cmで成人肝芽腫報告例では最小であった. 組織学的には被膜と隔壁があり, 出血や壊死を認めた. 核異型が強く, N/C比の高い細胞が不規則に増殖し, 幼若な胎児性肝組織に類似していた. その他に類骨形成, 粘液腫状の間質, 低分化の肝細胞癌など, 多彩な組織像を呈した. 以上より混合型肝芽腫と診断した. 背景肝はF3～F4, A2であった. 取扱い規約による進行度はStage IIIであった. 術後にCDDPとFarmorubicinによる予防的肝動注化学療法を行った. 手術後約2年の現在も無再発生存中で腫瘍マーカーも正常化している.

症例は57歳の女性で, 主訴は右季肋部痛. CEA, AFPは正常範囲内で, HBs抗原, HCV抗体は陰性. 腹部エコーで肝S6に8.3×6.5cm, S8に1.7×1.5cmの極めて低エコーな腫瘍を認めた. DIC (drip infusion cholangiography)-CT では, S8腫瘍内を偏位なく貫通する肝内胆管像が高濃度領域として確認された. 針生検診断は未分化癌であった. 術前は胆管細胞癌を疑い, 肝拡大右葉切除術を施行した. リンパ節転移や脾腫は認められず, 肝臓原発の腫瘍であった. 病理検査では, リンパ球が腫瘍内をびまん性に占居していた. 免疫染色では, CD 20陽性であり, 肝原発非ホジキンリンパ腫B細胞型と診断された. 術後に再発 (胸腔) を認めたが, CHOP療法を行い完全寛解に至った. 肝原発悪性リンパ腫においては, 特徴的な画像を手がかりに本症を疑い, 生検標本の免疫染色を行うことが術前の正確な診断につながる.

The mesh plug technique is one of the most popular procedures for inguinal hernia repair in Japan. This procedure is quick, easy, and low cost with a low recurrence rate. However, some complications associated with the mesh plug have been reported recently. We hereby present a case of an 80-year-old female admitted to our hospital with swelling and pain in the right lower abdomen 5 years after hernia repair with the PerFix plug. Discharge of urine through the route of exploratory needle puncture demonstrated the fistula of skin and the bladder. Computed tomography (CT), magnetic resonance imaging (MRI), abdominal US, and cystoscope examination revealed that the mesh plug had penetrated into the bladder. As far as we know, this is the first report that a mesh plug has migrated into the bladder.

The aim of this study was to determine the benefits of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) compared to CT alone in the preoperative assessment of lymph node metastasis in patients with esophageal cancer.One-hundred and seven patients who underwent esophagectomy with lymph node dissection between March 2007 and December 2009 were eligible. Sixty-seven patients were treated with surgery alone (SA group), while 40 patients received preoperative treatment prior to surgery (PT group). The pathological results of 1,403 dissected lymph node stations were compared with the results obtained using each imaging modality.PET/CT showed a significantly higher specificity and positive predictive value (PPV) than CT alone (97.7 vs. 94.1 % and 64.6 vs. 44.0 %, respectively), when analyzed by the lymph node stations. The PPV of PET/CT for N1 cases was significantly better than that of CT alone (78.9 vs. 53.9 %), particularly in the PT group (91.3 vs. 65.4 %). Among the patients in the SA group, the number of metastatic nodes was significantly higher in PET-N1 cases than in PET-N0 cases (5.78 vs. 1.90).PET/CT is useful for selecting patients with multiple lymph node metastases and also for detecting residual metastatic nodes after PT, and thus is beneficial to decide on the appropriate treatment strategy for patients with esophageal cancer.

The expression of Wingless/int-1 (Wnt)-induced secreted protein-1 (WISP-1/CCN4), a member of the Cyr61-CTGF-Nov (CCN) family, has been examined in several types of cancer. However, the correlation between the WISP-1 expression and the clinical features of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. This study aimed to clarify the expression of WISP-1 protein in patients with ESCC and also to examine the function of WISP-1 in esophageal cancer cells in vitro.One-hundred and ninety patients with thoracic esophageal carcinoma underwent transthoracic subtotal esophagectomy-between 2005 and 2009. All patients that had received previous therapy were excluded and 105 out of the 190 ESCC samples were analyzed immunohistochemically using WISP-1 antibody. The expression of WISP-1 mRNA in esophageal cancer cell lines was analyzed by RT-PCR. Growth assay and invasion assays were performed using WISP-1 transfected cells.The immunohistochemical analysis showed that WISP-1-positive cases were closely associated with tumor size, tumor type, lymph node metastasis and poor prognosis. There were significantly more WISP-1-positive infiltrative type tumors than expanding type tumors. In the esophageal cancer cell lines examined, only TE8 expressed WISP-1 mRNA. The growth of WISP-1-transfected cells was significantly increased in comparison to the control cells, but no differences in the invasion activity were observed between the transfected cells and control cells.The expression of WISP-1 may play an important role in the progression of ESCC. WISP-1 could therefore be a clinical marker for a poor prognosis in patients with ESCC and may also be a therapeutic target to control the progression of ESCC.

D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC).A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated.An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P 0.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P = 0.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P = 0.048).LVI detected by D2-40 staining was an independent prognostic factor in patients with node-negative ESCC.

We present three cases of patients diagnosed with esophageal cancer with distant metastases. We conducted chemotherapy, radiotherapy, RFA, and operation for main tumor and lymph node, lung, brain metastasis. They were for a long-term survival with multidisciplinary therapy. The longest survival time was about three years. We discussed our cases in light of review of the literature.

p12 CDK2-associating protein 1 (p12CDK2-AP1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. In addition, p12CDK2-AP1 has also been shown to interfere in DNA replication. A reduction of p12CDK2-AP1 expression is known to be a negative prognostic indicator in patients with oral squamous cell carcinoma. To elucidate the role of p12CDK2-AP1 expression in esophageal squamous cell carcinoma (ESCC), we immunohistochemically examined the expression of p12CDK2-AP1 protein in 120 resected ESCC specimens and determined its association with the clinicopathological characteristics and prognosis. Of the 120 ESCCs, 79 (65.8%) showed positive staining (>or=25% of cancer cells showing p12CDK2-AP1 expression), while 41 (34.2%) lacked the staining (

Purpose: MicroRNAs are ∼22 nucleotide noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was (a) to determine a role of microRNA-21 in esophageal squamous cell carcinoma and (b) to elucidate the regulation of the programmed cell death 4 (PDCD4) gene by microRNA-21. Experimental Design: MicroRNA-21 expression was investigated in 20 matched normal esophageal epitheliums and esophageal squamous cell carcinomas and seven esophageal squamous cell carcinoma cell lines (TE6, TE8, TE10, TE11, TE12, TE14, KYSE30) by TaqMan quantitative real-time PCR and in situ hybridization. To evaluate the role of microRNA-21, cell proliferation and invasion were analyzed with anti–microRNA-21–transfected cells. In addition, the regulation of PDCD4 by microRNA-21 was elucidated to identify the mechanisms of this regulation. Results: Of 20 paired samples, 18 cancer tissues overexpressed microRNA-21 in comparison with matched normal epitheliums. Specifically, patients with lymph node metastasis or venous invasion showed significantly high expression of microRNA-21. In situ hybridization for microRNA-21 showed strong positive staining in paraffin-embedded esophageal squamous cell carcinoma tissues. All seven esophageal squamous cell carcinoma cell lines also overexpressed microRNA-21, and anti–microRNA-21–transfected cells showed significant reduction in cellular proliferation and invasion. The PDCD4 protein levels in esophageal squamous cell carcinoma cells have an inverse correlation with microRNA-21 expression. Anti–microRNA-21–transfected cells increased PDCD4 protein expression without changing the PDCD4 mRNA level and increased a luciferase-reporter activity containing the PDCD4-3′ untranslated region construct. Conclusions: MicroRNA-21 targets PDCD4 at the posttranscriptional level and regulates cell proliferation and invasion in esophageal squamous cell carcinoma. It may serve as a novel therapeutic target in esophageal squamous cell carcinoma.

In general, cancer does not progress very rapidly, however, it sometimes causes an oncologic emergency that requires immediate treatment, depending on the location and progression of the disease. Hemorrhage, obstruction, and perforation are typical abdominal oncologic emergencies. As for gastrointestinal bleeding, endoscopic hemostasis is a common treatment of choice. Transcatheter arterial embolization is the first treatment to select in case of intra-abdominal hemorrhage caused by rupture of a hepatocellular carcinoma. Patients with upper-gastrointestinal obstruction for unresectable cancer need to be treated considering their prognoses and treatment effects. Those with colorectal obstructions with cancers first need decompression. Patients with colorectal perforation should be operated immediately to prevent septic shock. Acute obstructive suppurative cholangitis needs endoscopic retrograde cholangiography for immediate diagnosis and treatment. Abdominal oncologic emergencies have decreased due to recent diagnostic and therapeutic improvements. However, it remains a crucial disease requiring appropriate diagnoses and prompt treatment based on the conditions of the patients and disease.

Tetanus is a rare infectious disease in western countries, however, it remains one of the most common and fatal disease in developing countries. Several diseases can mimic tetanus, and the diagnostic procedure is important to distinguish tetanus from other disease. Here we report the case of tetanus caused by ulcerated phyllodes tumor. This case suggests that the diagnosis and introduction of effective therapy should not be delayed, even if wound on the extremity surface is not clear.

Background: The incidence of esophageal adenocarcinoma (EAC) or esophagogastric junction adenocarcinoma (EGJA) has been dramatically increasing. KRAS oncogenic alterations activate multiple pathways in various types of cancer. A recent comprehensive genetic study has reported that around 20% of EAC harbor KRAS copy number gain (Dulak AM et al, 2012, Nat Genet). However, the prognostic role KRAS amplification has not been well examined in EAC/EGJA. Methods: DNA was extracted from formalin-fixed paraffin-embedded tissue of 145 EGJA (Siewert types I-III). KRAS copy number was detected by real-time quantitative PCR, and KRAS copy number gain was defined as KRAS/RNase P (as a reference) ratio ≥ 2.5. The impact of KRAS amplification was analyzed in relation to clinicopathological factors, and patient outcomes [disease free survival (DFS), and overall survival (OS)]. Multivariate cox proportional hazards model was performed adjusting clinicopathological factors. Results: KRAS amplification was observed in 40 (33.1%) cases. KRAS amplification was significantly associated with the lymph node metastasis (P = 0.0145), and was significantly associated with poorer patient outcome (P = 0.0355 in DFS, and P = 0.0067 in OS). In multivariate analysis, KRAS amplification was an independent prognostic factor for OS [multivatiate hazard ratio (HR) = 2.53; 95% confidence interval (CI), 1.22-5.25, P = 0.014] and DFS [multivatiate hazard ratio (HR) = 1.94; 95% confidence interval (CI), 1.04-3.56, P = 0.0382]. Conclusions: KRAS copy number gain may be a useful prognostic marker in EGJA. Citation Format: Kenichi Nakamura, Yu Imamura, Ryuma Tokunaga, Mayuko Ohuchi, Yuki Kiyozumi, Keisuke Kosumi, Daisuke Izumi, Kazuto Harada, Junji Kurashige, Ryuichi Karashima, Yukiharu Hiyoshi, Shiro Iwagami, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Hideo Baba. Prognostic impact of KRAS copy number amplification in esophagogastric junction adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3861. doi:10.1158/1538-7445.AM2015-3861

Backgrounds: APOBEC3B is one of the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family, and APOBEC3B can induce transitions into target DNA through cytidine deamination. To date, APOBEC attracts attention due to its functioning as part of the innate immune system by protecting against retrovirus and retrotransposon propagation. And, recent studies revealed that APOBEC3B might contribute to several mutations in various types of cancers, including cervical, breast, head and neck, lung, bladder cancers, and APOBEC3B may have a crucial role in carcinogenesis and cancer development. Esophageal squamous cell carcinoma (ESCC) reportedly has several molecular features, and we recently reported that long interspersed nucleotide element 1 (LINE-1) hypomethylation might contribute to poor prognosis and PIK3CA mutation to good prognosis in ESCC. However, there is no report which investigates the relationship between APOBEC3B expression, clinical and pathological features in ESCC. Methods: We compared the expression of APOBEC3B mRNA between cancer tissues and noncancerous esophageal mucosae by using GEO profiles and ESCC frozen tissues. In addition, we investigated the relationships between the APOBEC3B immunohistochemical expression levels, clinical and pathological features, and molecular features including p53 expression, global DNA methylation level and PIK3CA mutation. We quantified LINE-1 retrotransposons, of which a substantial portion of the human genome consists, to assess global DNA methylation. Results: APOBEC3B expression at mRNA level was significantly higher in cancer tissues than in noncancerous esophageal mucosae (P = 0.050). In the immunohistochemical study, the APOBEC3B expression of ESCC was stronger than that of noncancerous esophageal mucosa. We found no significant correlation of APOBEC3B expression with tumor size, T stage, N stage and pStage (P = 0.74, P = 0.32, P = 0.19, P = 0.23, respectively). There were no correlation between APOBEC3B expression and prognosis. There was no correlation between APOBEC3B expression and p53 expression (P = 0.23), but, interestingly, a high expression of APOBEC3B was significantly associated with LINE-1 hypomethyaltion and PIK3CA mutation (P = 0.029, P = 0.020). Conclusions: APOBEC3B high expression had significant relationships with LINE-1 hypomethylation and PIK3CA mutation, supporting that APOBEC3B might contribute to malignant behavior through the molecular features in ESCC. Citation Format: Keisuke Kosumi, Yoshifumi Baba, Takatsugu Ishimoto, Kenichi Nakamura, Kazuto Harada, Mayuko Ohuchi, Yuki Kiyozumi, Daisuke Izumi, Ryuma Tokunaga, Junji Kurashige, Ryuichi Karashima, Yukiharu Hiyoshi, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba. The clinical significance of APOBEC3B in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4829. doi:10.1158/1538-7445.AM2015-4829

Two inaccurate technical descriptions appeared in above titled article. In the “Imaging studies” subsection, the dose of intravenously injected F-FDG was misdescribed as 370 MBq (10 mCi). Actual dose of F-FDG was 185–296 MBq (5–8 mCi). In addition, injection rate of nonionic contrast medium during CT imaging was misdescribed as 2.5 ml/s, and accurate injection rate was 2.0 ml/s. The authors sincerely apologize for these errors.

Background: Lysine-specific demethylase 1 (LSD1) is the first discovered histone demethylase which specially removes H3K4me1/2 through a flavin-adenine-dinucleotide (FAD). Previous studies have indicated that LSD1 is associated with cell proliferation, cell invasion and epithelial-mesenchymal transition in human malignant tumors. Recently, it is accepted that LSD1 epigenetically regulates energy-expenditure genes in adipocytes depending on the cellular FAD availability. As a PET scan with a FDG tracer can detect cancers, the method is exceedingly useful for tumor staging or therapeutic effect determination of esophageal cancers. The aim of this study is to investigate the expression and function of LSD1 in esophageal cancer cell-lines and, to analyze the relationships between the LSD1 expression and clinicopathological data including SUVmax (standardized uptake value). Methods: The influence of LSD1 on cell proliferation and invasion was evaluated by knockdown experiments. Using 113 resected esophageal cancer specimens, we evaluated the LSD1 expression by immunohistochemistry and devided them into two groups; a low expression group (LEG) and a high expression group (HEG). We compared these two groups and analyzed the relationships between LSD1 expression and clinicopathological data. Results: In vitro analysis, knockdown of LSD1 did not impact cell proliferation, but suppressed cell invasion. In the immunohistochemical study, the HEG's age was significantly higher (P=0.021), and this group had esophageal cancers at lower locations (P=0.058). HEG was significantly correlated with the T-stage (P=0.020), lymph and blood vessels invasion (P=0.020, P=0.001), and a higher SUVmax (P=0.0088) and lower overall survival (P=0.0017). Conclusions: Our study demonstrated the relationships between the expression of LSD1 and T-stage, lymph and blood vessels invasion, and the SUVmax in esophageal cancers. It is suggested that LSD1 has a potential to impact the malignancy of the esophageal cancer, and may be a therapeutic target in patients with esophageal cancers. Citation Format: Keisuke Kosumi, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Akihisa Sakamoto, Shinjiro Hino, Mitsuyoshi Nakao, Hideo Baba. The clinicopathological significance of LSD1 in esophageal cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1361. doi:10.1158/1538-7445.AM2014-1361

Background: JMJD3 has been known to play important roles in transcriptional regulation and cell proliferation by demethylating histone3 lysin27 (H3K27) in various cancers. However, the mechanism underlying JMJD3-mediated transcriptional regulation and the relation with prognosis were unclear in colorectal carcinoma. Here, we investigated the expression of JMJD3 in clinical samples and the function of JMJD3 in colorectal carcinoma cell lines. Methods: Quantitative real-time PCR were performed to check the expression of JMJD3 mRNA using the carcinoma and normal colorectal tissue in 14 colorectal carcinoma patients who underwent a curative surgery. In vitro analysis, we investigated the expression of JMJD3 in colorectal carcinoma cell lines by Western Blotting, and we knocked down the expression of JMJD3 by using small interfering RNA in Colo201 and colo320. The influence of JMJD3 on cell growth, apoptosis and cell cycle was assessed by growth assay, apoptosis assay and cell cycle analysis. We checked the changes of cell cycle related genes by real time PCR. Results: In clinical samples, the expression of JMJD3 in carcinoma tissue was significantly lower than in normal tissue (P=0.02). In vitro analysis, we knocked down the expression of JMJD3 by siRNA targeting JMJD3 and checked the reduction on mRNA and protein level. Knockdown of JMJD3 significantly increased cell proliferation (P=0.02), reduced apoptosis (P=0.003), and increased G2/M phase population (P = 0.05) which was detected by FACS. Moreover, knockdown of JMJD3 significantly decreased the expression of p15INK4B in quantitative real-time PCR. Conclusion: We showed the expression of JMJD3 in carcinoma tissue was lower than in normal tissue and demonstrated that the down-regulation of JMJD3 resulted in the increase of cell proliferation, acceleration of cell cycle and anti-apoptosis in vitro analysis. These results suggest that JMJD3 is a tumor suppressor gene for colorectal carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Ryuma Tokunaga, Shigeki Nakagawa, Yasuo Sakamoto, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. JMJD3 suppresses progression of colorectal carcinoma by regulating cell cycle and anti-apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5150. doi:10.1158/1538-7445.AM2014-5150

Objectives: Gastric cancer is one of the most threatening malignancies with a high incidence and metastasis rate. Many patients are diagnosed in an advanced stage sometimes with multi-organ metastasis, which leads a poor prognosis of gastric tumors. Chemokine and their receptors have been originally demonstrated as essential mediators of leukocyte directional migration, particularly during infection and inflammation, and have further emerged as crucial players in all stages of tumor development. It has been reported that an important CXCL12-CXCR4 signaling is involved in tumor development and metastasis in several types of cancer including gastric cancer. Cancer associated fibroblasts (CAF) are reported to communicate microenvironment-derived signals through chemokine/chemokine receptor interaction such as CXCL12-CXCR4 signaling. The aim of our study was to evaluate the role of CXCL12-CXCR4 signaling in crosstalk between gastric cancer and CAF. Methods and Results: We evaluated CXCL12 and CXCR4 expression status by immunohistochemistry using a nonbiased database of 89 curatively resected gastric cancers. As a result, CXCL12/ CXCR4 expression are significant correlation with metastasis. Furthermore, we performed Western blotting analysis for CXCL12 and CXCR4 in human gastric cancer cell lines. CXCR4 expression was detectable in all gastric cancer cell lines. We isolated CAF from human gastric cancer tissue resected in our institute. We performed Western blotting analysis for alpha-SMA and CXCL12 in CAF, and confirmed higher expression in CAF than normal fibroblast (NF) isolated from normal gastric mucosa of same patients. Then we established stable AGS gastric cancer cell line expressing GFP. Invasion assay revealed that AGS (gastric cancer cell line) cells with CAF showed more invasive phenotype than that without CAF. We also found the motility of GFP-expressing AGS was elevated during direct co-culture of GFP-expressing AGS cells and CAF compared with NF. Conclusions: These findings revealed that cancer associated fibroblasts were implicated in cancer cell invasion and metastasis through CXCL12-CXCR4 signaling in gastric cancer. The therapeutic blockade of this pathway with CXCR4 antagonist might abrogate gastric cancer cell invasion and metastasis. Citation Format: Daisuke Izumi, Takatsugu Ishimoto, Hietaka Sugihara, Hiroshi Sawayama, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Shiro Iwagami, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Cancer associated fibroblasts stimulates cancer cell invasion through CXCL12-CXCR4 signaling in gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2014-185

Objective: DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Although the base 5-methylcytosine (5mc) and the DNA methyltransferase (DNMT) family of enzymes that catalyze DNA methylation are well-studied, the mechanisms of DNA demethylation are poorly understood. The Ten-eleven translocation (Tet) family of enzymes (Tet1, Tet2, and Tet3) has been implicated in DNA demethylation. These enzymes possess the dioxygenase activity and convert 5-mC to 5-hydroxymethylcytosine (5-hmC). Frequent Tet mutational inactivation or reduction has been reported to associate with decreased 5-hmC levels in various types of myeloid leukemia and melanoma. However, the status of 5hmC and Tet expression in esophageal squamous cell carcinoma (ESCC) remains still unknown. Method: We analyzed the 5-hmC status in DNA from ESCC frozen tissues utilizing the ELISA test, and 5-hmC expression was evaluated by immunohistochemistry. We next examined the expression levels of Tet family mRNA in both normal and tumor tissues by RT-qPCR. Results: 5-hmC level was significantly lower in ESCC than in paired normal tissue in ELISA test (n=33, P Conclusion: The 5hmC expression was decreased in ESCC tissues, and was associated with Tet2 expression level, suggesting that 5hmC and Tet2 might play a crucial role in the development of ESCCs. Citation Format: Asuka Murata, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Tet family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 420. doi:10.1158/1538-7445.AM2014-420