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// Atsushi Shiozaki 1, * , Shoichiro Hikami 1, * , Daisuke Ichikawa 1, 2 , Toshiyuki Kosuga 1 , Hiroki Shimizu 1 , Michihiro Kudou 1 , Yuzo Yamazato 1 , Toshiyuki Kobayashi 1 , Katsutoshi Shoda 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Shuhei Komatsu 1 , Takeshi Kubota 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Mitsuo Kishimoto 3 , Eiichi Konishi 3 , Yoshinori Marunaka 4, 5 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan 2 Department of Gastrointestinal, Breast and Endocrine Surgery, Faculty of Medicine, University of Yamanashi, Chuo 409-3898, Japan 3 Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan 4 Departments of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan 5 Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto 602-8013, Japan * These authors contributed equally to this work Correspondence to: Atsushi Shiozaki, email: shiozaki@koto.kpu-m.ac.jp Keywords: AE2; esophageal squamous cell carcinoma; MMPs; migration; cellular physiology Received: June 30, 2017 Accepted: April 28, 2018 Published: May 25, 2018 ABSTRACT Background: Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC). Results: AE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the invasive front was associated with shorter postoperative survival. Conclusions: The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by activating MMP signaling pathways and are related to a poor prognosis in patients with ESCC. Methods: In human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.

Background: Recent studies have reported important roles for chloride intracellular channel 1 (CLIC1) in various cancers; however, its involvement in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of the present study was to investigate the role of CLIC1 in human ESCC. Methods: CLIC1 expression in human ESCC cell lines was analyzed by Western blotting. Knockdown experiments were conducted with CLIC1 siRNA, and their effects on cell proliferation, the cell cycle, apoptosis, migration, and invasion were analyzed. The gene expression profiles of cells were analyzed using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. Results: ESCC cells strongly expressed CLIC1. The depletion of CLIC1 using siRNA inhibited cell proliferation, induced apoptosis, and promoted cell migration and invasion. The results of the microarray analysis revealed that the depletion of CLIC1 regulated apoptosis via the TLR2/JNK pathway. Immunohistochemistry showed that CLIC1 was present in the cytoplasm of carcinoma cells, and that the very strong or very weak expression of CLIC1 was an independent poor prognostic factor. Conclusions: The present results suggest that the very strong expression of CLIC1 enhances tumor survival, while its very weak expression promotes cellular movement. The present study provides an insight into the role of CLIC1 as a switch among tumor behaviors in ESCC.

Magnetic variations calculated by the Ground-to-topside model of Atmosphere and Ionosphere for Aeronomy (GAIA) are compared with those observed at global magnetic observatory network in geomagnetic calm days in order to evaluate accuracy of the ionospheric current system calculated by GAIA. The calculated Y-component magnetic variations can reproduce more than 50% of the observed variations at more than half observatories treated. In particular, GAIA can reproduce more than 75% of the observed Y-component variations in the equinox. Whereas, there is tendency of low correlation of the waveform between the calculated and observed variations in the winter season. Next, GAIA reproduces so well of the X-component variations at the low-latitude observatories. Low correlation between the calculated and observed X-component variations at middle-latitude observatories seems to be caused by inaccurate determination of the position of the ionospheric Sq current vortex. Last, although the calculated Z-component variations does not so well reproduce the observed ones compared with other component, GAIA can reproduce more than 50% of the observed Z-component variation at about half observatories in general. Calculated amplitude of the horizontal magnetic variations (X- and Y-components) exhibit smaller than the observed one, whereas that of the vertical variation (Z-component) is larger than the observed one. This tendency is roughly explained by the induction effect of the Earth that is not considered in GAIA. Thus, GAIA considerably well reproduces the pure ionospheric current system that is not affected by the solid Earth.

BACKGROUND AND AIM No study has compared the incidence of postoperative bone metabolic disorders between Billroth-I (B-I) and Roux-en-Y (R-Y) reconstructions after distal gastrectomy (DG) for gastric cancer (GC). In this study, we wished to examine the impact of reconstruction method on postoperative bone mineral density (BMD) loss. METHODS We investigated a total of 148 consecutive patients who underwent DG with B-I or R-Y reconstruction for stage I GC between 2008 and 2012. We retrospectively assessed the BMD data using computed tomography attenuation values of the first lumbar vertebra after surgery. RESULTS In multivariate analysis for the whole study series, R-Y reconstruction was identified as an independent risk factor for BMD loss after DG (P

5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.

The effects of decreasing the intrinsic magnetic field on the upper atmospheric dynamics at low-to middle- latitudes are investigated using the Ground-to-topside model of Atmosphere and Ionosphere for Aeronomy (GAIA). GAIA incorporates a meteorological reanalysis data set at low altitudes (

A lymphocele is one of the complications of systematic pelvic or para-aortic lymphadenectomy. Although most patients are entirely asymptomatic, our patient exhibited an obstructive ileus at the jejunum compressed by a lymphocele. We report here a case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection. A 68-year-old woman with sigmoid colon cancer (T3N2bM1a) underwent laparoscopic sigmoidectomy. After 4 courses of chemotherapy (CapeOX + Bmab), para-aortic lymphadenectomy was additionally performed. One month later, an obstructive ileus occurred suddenly due to a lymphocele. A drainage catheter was placed into the lymphocele and a total of 35 mL of autologous peripheral blood was injected in 4 divided doses through the catheter. The volume of the lymphocele gradually reduced and the ileus improved after blood injection. This is the first report of a successful case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection without any complications.

// Kenichi Aratani 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Takuma Ohashi 1 , Mahito Miyamae 1 , Wataru Okajima 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Keiji Nishibeppu 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Hitoshi Tsuda 2, 3 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Japan 2 Department of Pathology, National Cancer Center Hospital, Tokyo, Japan 3 Department of Basic Pathology, National Defense Medical College, Saitama, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: adenocarcinoma of the esophagogastric junction, gastric cancer, CTEN, prognosis, oncogene Received: April 19, 2017 Accepted: September 04, 2017 Published: September 20, 2017 ABSTRACT Background: To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether C-terminal tensin-like (CTEN), a member of the tensin gene family and frequently overexpressed in various cancers, acts as a cancer-promoting gene through overexpression in AEG. Materials and Methods: We analyzed 5 gastric adenocarcinoma (GC) cell lines and 104 primary AEG tumors curatively resected in our hospital between 2000 and 2010. Results: CTEN overexpression was detected in GC cell lines (2/5 cell lines; 40%) and primary AEG tumor samples (35/104 cases; 34%). CTEN knockdown using several specific siRNAs inhibited the proliferation, migration, and invasion of CTEN-overexpressing cells. CTEN overexpression was significantly correlated with more aggressive venous and lymphatic invasion, deeper tumor depth, and higher rates of lymph node metastasis and recurrence. Patients with CTEN-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors ( P < 0.0001, log-rank test) in an expression-dependent manner. CTEN positivity was independently associated with a worse outcome in the multivariate analysis ( P = 0.0423, hazard ratio 3.54 [1.04–16.4]). Conclusions: CTEN plays a crucial role in tumor cell proliferation, migration, and invasion through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG.

// Toshiyuki Kosuga 1 , Atsushi Shiozaki 1 , Michihiro Kudou 1 , Yuzo Yamazato 1 , Daisuke Ichikawa 1 , Shuhei Komatsu 1 , Hirotaka Konishi 1 , Kazuma Okamoto 1 , Katsutoshi Shoda 1 , Tomohiro Arita 1 , Ryo Morimura 1 , Yasutoshi Murayama 1 , Yoshiaki Kuriu 1 , Hisashi Ikoma 1 , Masayoshi Nakanishi 1 , Hitoshi Fujiwara 1 , Yoshinori Marunaka 2, 3 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan 2 Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan 3 Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, Japan Correspondence to: Atsushi Shiozaki, email: shiozaki@koto.kpu-m.ac.jp Keywords: gastric cancer; peritoneal lavage; peritoneal dissemination; potassium channel; regulatory volume decrease Received: January 17, 2017 Accepted: August 07, 2017 Published: September 08, 2017 ABSTRACT Background: Peritoneal lavage with distilled water has been used for surgeries of various cancers to reduce peritoneal recurrence. This study examined whether blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects in gastric cancer (GC). Results: A potassium channel blocker inhibited the occurrence of regulatory volume decrease (RVD) induced by mild hypotonic stimulation, and significantly enhanced cytocidal effects on GC cells. Incubating MKN45 cells with hypotonic solutions containing a potassium channel blocker significantly reduced the formation of peritoneal metastases in nude mice. Methods: The three human GC cell lines (HGC-27, Kato III, and MKN45) were exposed to mild hypotonic solutions, and the effects of blockade of potassium ion transports during hypotonic stimulation on cell volume changes and cell viabilities were examined. In the in vivo study, MKN45 cells stimulated with mild hypotonic solutions were intraperitoneally injected into nude mice, and the effects of blockade of potassium ion transports during hypotonic stimulation on the formation of peritoneal metastases were evaluated. Conclusions: Blockade of potassium ion transports enhances hypotonicity-induced cytocidal effects on GC cells, which may contribute to development of a novel lavage method for further reduction of peritoneal recurrence in GC.

// Taisuke Imamura 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Mahito Miyamae 1 , Wataru Okajima 1 , Takuma Ohashi 1 , Jun Kiuchi 1 , Keiji Nishibeppu 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Kazuma Okamoto 1 , Hitoshi Fujiwara 1 and Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: gastric cancer, tumor suppressor microRNA, plasma, biomarker Received: April 16, 2017 Accepted: August 15, 2017 Published: September 13, 2017 ABSTRACT Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC). Results: The miR-101 expression level was significantly lower in GC tissues ( P = 0.0038) and GC cell lines ( P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers ( P = 0.0281 and P < 0.0001, respectively). Low miR-101 plasma level was significantly associated with advanced T factor, advanced disease stage, and peritoneal metastasis and predicted poor prognosis in GC patients ( P = 0.0368; hazard ratio, 3.079; 95% confidence interval: 1.06–11.08). Overexpression of miR-101 in GC cells induced apoptosis by inhibiting MCL1 and suppressed cell migration and invasion by regulating ZEB1. Conclusions: Depletion of the tumor suppressor miRNA-101 in plasma is related to tumor progression and poor outcomes. Low plasma miR-101 may be a biomarker for GC, and its restoration might be a novel anticancer treatment strategy.

Intravascular ultrasound (IVUS)-guided guidewire manipulation technique is often useful to cross the lesion of chronic total occlusion (CTO) antegradely and solve retrograde CTO failure cases. However, this technique is usually complex because we need many devices and it requires many steps. Some steps usually take time and/or sometimes create a large dissection space which cause the procedure to fail. To overcome a weakness in this technique, we introduce the new IVUS-guided wiring technique with double lumen catheter named “Slipstream technique” here. This technique is simple, easy, and associated with less injury. It will be helpful for penetrating into the true lumen from the subintimal space with a guidewire correctly and safely.

There have been a number of papers reporting that the statistical occurrence rate of the sporadic E (Es) layer depends not only on the local time and season but also on the geographical location, implying that geographical and seasonal dependence in vertical neutral wind shear is one of the factors responsible for the geographical and seasonal dependence in Es layer occurrences rate. To study the role of neutral wind shear in the global distribution of the Es layer occurrence rate, we employ a self-consistent atmosphere-ionosphere coupled model called GAIA (Ground-to-topside model of Atmosphere and Ionosphere for Aeronomy), which incorporates meteorological reanalysis data in the lower atmosphere. The average distribution of neutral wind shear in the lower thermosphere is derived for the June–August and December–February periods, and the global distribution of vertical ion convergence is obtained to estimate the Es layer occurrence rate. It is found that the local and seasonal dependence of neutral wind shear is an important factor in determining the dependence of the Es layer occurrence rate on geographical distribution and seasonal variation. However, there are uncertainties in the simulated vertical neutral wind shears, which have larger scales than the observed wind shear scales. Furthermore, other processes such as localization of magnetic field distribution, background metallic ion distribution, ionospheric electric fields, and chemical processes of metallic ions are also likely to make an important contribution to geographical distribution and seasonal variation of the Es occurrence rate.

Using an atmosphere-ionosphere coupled model, the excitation source and temporal (seasonal and interannual) variations in non-migrating tides are investigated in this study. We first focus our attention on temporal variations in eastward moving diurnal tide with zonal wavenumber 3 (DE3), which is the largest of all the non-migrating tides in the mesosphere and lower thermosphere (MLT). Our simulation results indicate that upward propagation of the DE3 excited in the troposphere is sensitive to the zonal mean zonal wind in the stratosphere and mesosphere. The DE3 amplitude is enhanced in the region where the vertical shear of the zonal mean zonal wind is positive (westerly shear). Quasi-2-year variation in the DE3 amplitude in the MLT region is generated by quasi-2-year variation in the zonal mean zonal wind between 40 and 70 km, which is modulated by the stratospheric QBO. The excitation mechanisms of SW3 (westward moving semidiurnal tide with zonal wavenumber 3) and SW1 (westward moving semidiurnal tide with zonal wavenumber 1) are also investigated. During equinoxes, the SW3 and SW1 are excited by tropospheric heating (latent heat release and solar radiative heating) associated with cumulus convection in the tropics, and propagate upward into the MLT region. On the other hand, during solstices, SW3 and SW1 are generated in the winter stratosphere and mesosphere through the nonlinear interaction between the stationary planetary wave and migrating semidiurnal tide, and propagate upward to the lower thermosphere. The excitation sources of other non-migrating tides are also discussed.

AIM To investigate the efficacy of thrombomodulin (TM)-α for treatment of disseminated intravascular coagulopathy (DIC) in the field of gastrointestinal surgery. METHODS Thirty-six peri-operative DIC patients in the field of gastrointestinal surgery who were treated with TM-α were retrospectively investigated. The relationships between patient demographics and the efficacy of TM-α were examined. Analysis of survival at 28 d was also performed on some parameters by means of the Kaplan-Meier method. Relationships between the initiation of TM-α and patient demographics were also evaluated. RESULTS Abscess formation or bacteremia was the most frequent cause of DIC (33%), followed by digestive tract perforation (31%). Twenty-six patients developed DIC after surgery, frequently within 1 wk (81%). TM-α was most often administered within 1 d of the DIC diagnosis (72%) and was continued for more than 3 d (64%). Although bleeding tendency was observed in 7 patients (19%), a hemostatic procedure was not needed. DIC scores, systemic inflammatory response syndrome (SIRS) scores, quick-sequential organ failure assessment (qSOFA) scores, platelet counts, and prothrombin time ratios significantly improved after 1 wk (P < 0.05, for all). The overall survival rate at 28 d was 71%. The duration of TM-α administration (≥ 4 , ≤ 6) and improvements in DIC-associated scores (DIC, SIRS and qSOFA) at 1 wk were significantly better prognostic factors for 28-d survival (P < 0.05, for all). TM-α was administered significantly earlier to patients with severe clinical symptoms, such as high qSOFA scores, sepsis, shock or high lactate values (P < 0.05, for all). CONCLUSION Early administration of TM-α and improvements in each parameter were essential for treatment of DIC. The diagnosis of patients with mild symptoms requires further study.

To detect the best cut-off value of the positive lymph node ratio (PLNR) for stratifying the prognosis and analyzing its value with regard to stage migration effect using PLNR in gastric cancer.We retrospectively analyzed 1069 consecutive gastric cancer patients, who underwent curative gastrectomy with radical lymphadenectomy from 1997 through 2009.1) The mean number of dissected lymph nodes was 42.6 in pStage I, 32.4 in pStage II and 37.1 in pStage III. The PLNR of 0.2 was proved to be the best cut-off value to stratify the prognosis of patients into two groups (P 0.0001; PLNR0.2 vs. PLNR ≥0.2), and patients were correctly classified into four groups: PLNR 0, PLNR 0-0.2, PLNR 0.2-0.4 and PLNR ≥0.4 by the Kaplan-Meier method. 2) Compared patients with the PLNR0.2, those with the PLNR ≥0.2 had a significantly higher incidence of pT3 or greater, pN2 or greater, lymphatic invasion, vascular invasion and undifferentiated cancer. Multivariate analysis showed that the PLNR ≥0.2 was an independent prognostic factor [P 0.0001, HR 2.77 (95% CI: 1.87-4.09)]. 2) The PLNR cut-off value of 0.2 could discriminate a stage migration effect in pN2-N3 and pStage II-III, which patients with PLNR ≥0.2 might be potentially diagnosed as a lower stage after gastrectomy.The PLNR contributes to evaluating prognosis and stage migration effect even in a single institute and enable to identify those who need meticulous treatments and follow-up in patients with gastric cancer.

We quantitatively evaluated the Na density depletion due to charge transfer reactions between Na atoms and molecular ions produced by high-energy electron precipitation during a pulsating aurora (PsA). An extended period of PsA was captured by an all-sky camera at the European Incoherent Scatter (EISCAT) radar Tromso site (69.6°N, 19.2°E) during a 2 h interval from 00:00 to 02:00 UT on 25 January 2012. During this period, using the EISCAT very high frequency (VHF) radar, we detected three intervals of intense ionization below 100 km that were probably caused by precipitation of high-energy electrons during the PsA. In these intervals, the sodium lidar at Tromso observed characteristic depletion of Na density at altitudes between 97 and 100 km. These Na density depletions lasted for 8 min and represented 5–8% of the background Na layer. To examine the cause of this depletion, we modeled the depletion rate based on charge transfer reactions with NO+ and O2+ while changing the R value which is defined as the ratio of NO+ to O2+ densities, from 1 to 10. The correlation coefficients between observed and modeled Na density depletion calculated with typical value R = 3 for time intervals T1, T2, and T3 were 0.66, 0.80, and 0.67, respectively. The observed Na density depletion rates fall within the range of modeled depletion rate calculated with R from 1 to 10. This suggests that the charge transfer reactions triggered by the auroral impact ionization at low altitudes are the predominant process responsible for Na density depletion during PsA intervals.

// Atsushi Shiozaki 1, * , Michihiro Kudou 1, * , Daisuke Ichikawa 1 , Hiroki Shimizu 1 , Tomohiro Arita 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Shuhei Komatsu 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Mitsuo Kishimoto 2 , Yoshinori Marunaka 3, 4 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 2 Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 3 Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan 4 Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, 602-8013, Japan * These authors have contributed equally to this work Correspondence to: Atsushi Shiozaki, email: shiozaki@koto.kpu-m.ac.jp Keywords: AE1, esophageal squamous cell carcinoma, MAPK, Hedgehog signaling pathway, cellular physiology Received: April 20, 2016 Accepted: January 04, 2017 Published: January 30, 2017 ABSTRACT Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.

Background Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. Methods This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. Results The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448–7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221–4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). Conclusion The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Background: Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). Methods: Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. Results: TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. Conclusion: The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.

BACKGROUND/AIM This study examined whether the prognostic nutritional index (PNI) is a useful predictor of pathological lymph node metastasis (pN+) in gastric cancer (GC). PATIENTS AND METHODS This study retrospectively examined 167 patients with advanced GC (cT2-T4) undergoing curative gastrectomy. The predictive ability of PNI for pN+ was evaluated in comparison with that of clinical lymph node metastasis (cN+) determined by computed tomography (CT). RESULTS The optimal cut-off value of PNI for predicting pN+ was 46 according to the receiver operating characteristic curve analysis. Multivariate analysis revealed a PNI

This study investigated the prognostic value of preoperative serum C-reactive protein(CRP)level in patients with gastric cancer(GC).This retrospective study examined 446GC patients undergoing curative gastrectomy. The associations between preoperative CRP level and postoperative long-term outcomes were examined by univariate and multivariate analyses.The patients were divided into high(n=147)or low(n=299)CRP groups based on an optimal cut- off CRP value of 0.13mg/dL according to the ROC curve analysis. High CRP levels were significantly associated with other clinical factors such as older age(B65 years), high BMI(B25 kg/m2), poor performance status(PS), and advanced cT and cN+. In the survival analyses using only the clinical factors, high CRP levels were significantly associated with worse 5-year overall and cancer-specific survivals. The multivariate analysis for 5-year overall survival identified preoperative CRP to be an independent factor(HR: 1.95, 95%CI: 1.15-3.36, p=0.0129), as well as PS, tumor location, and cT.Preoperative CRP level could be a useful prognostic indicator in patients with GC undergoing curative gastrectomy.

This study examined the significance of preoperative neutrophil-lymphocyte ratio(NLR)as a predictor of postoperative outcomes of gastric cancer(GC).NLR was calculated in 447 patients with GC undergoing curative gastrectomy, and its associations with postoperative short- and long-term outcomes were retrospectively examined.Patients were divided into high-(n=313)or low-(n=134)NLR groups using an optimal cut-off NLR value of 1.6 according to the ROC curve analysis. A high-NLR was significantly associated with other clinical factors such as undifferentiated histology, advanced cT, and cN+. There was no difference in the incidence of postoperative complications between the 2 groups. Meanwhile, a high NLR was associated with a poor 5-year overall survival. Multivariate analysis identified preoperative NLR to be an independent prognostic factor(hazard ratio: 2.77, 95% confidence interval: 1.39-6.33, p=0.003)along with performance status, tumor location, and cT.Preoperative NLR could be one of the useful predictors of postoperative long-term outcomes of GC.

Background: The aim of this study was to compare the short- and long-term outcomes of laparoscopic total gastrectomy (LTG) with those of open total gastrectomy (OTG) for the upper part of clinical Stage I gastric cancer. Methods: Between 2000 and 2015, 122 and 96 consecutive gastric cancer patients who had undergone curative LTG and OTG with lymphadenectomy were enrolled in the study. We performed the simple intracorporeal techniqueof esophagojejunostomy using a circular stapler in LTG. This technique comprised of laparoscopic trans-abdominal anvil insertion into the esophagus, which was assisted by lifting up the nasogastric tube connected to the anvil head. Results: By the Clavien-Dindo classification defined as grade II or high, the rate of postoperative complications was 14.8% (14/112: Grade II (7), IIIa (4), and IIIb (3)) in LTG and 15.6% (15/96) in OTG. There was no anastomotic leakage (0% (0/122)) and only 3.3% (4/122) of anastomotic stenosis in LTG. There was no significant difference in the short-term outcomes between both groups in all enrolled and propensity score-matched patients (LTG vs. OTG: 15.4% (10/65) vs. 16.9% (11/65)). Regarding the long-term outcomes, there was no significant difference in overall survival between both groups in all enrolled (P = 0.190) and propensity score-matched patients (P = 0.643). Conclusions: LTG for the upper part of clinical Stage I gastric cancer is a safe and reliable procedure and could have similar short- and long-term outcomes as OTG.

Although peritoneal lavage with distilled water performed after surgery prevents peritoneal seeding, cancer cells may avoid rupture under mild hypotonicity through regulatory volume decrease (RVD), which is the homeostatic regulation of ion and water transport. The aim of the present study was to investigate the effect of low temperature on cell volume and cell death under hypoosmolal conditions and determine the underlying molecular mechanisms in gastric cancer (GC). Three human GC cell lines (NUGC4, KATO‑III and MKN45) were exposed to hypotonic solutions, and the effects of low temperature on cell volume and viability were examined. Low temperature‑induced changes in membrane transporters were evaluated, and knockdown and overexpression experiments were conducted to determine their effects on cell volume during hypotonic stimulation. Low temperature (24˚C) during hypotonic stimulation inhibited RVD and enhanced the cytocidal effects on GC cells. The expression of leucine‑rich repeat containing protein A (LRRC8A), a component of a Cl‑ channel, was decreased, and aquaporin 5 (AQP5) expression was increased at low temperatures. LRRC8A knockdown markedly slowed the decrease in cell volume following cell swelling by hypotonic shock. AQP5 overexpression enhanced initial cell swelling after hypotonic shock and increased the final cell volume. These results suggest that a hypotonic solution at low temperature increased initial water influx via activation of AQP5 and decreased Cl‑ efflux via inhibition of LRRC8A. Therefore, low temperature enhanced the hypotonicity‑induced cytocidal effects on GC cells, and these results may contribute to the development of a novel lavage method effective in reducing peritoneal recurrence in GC.

The patient was a 69-year-old woman.Upper gastrointestinal endoscopy showed a protruding tumor in the mid-thoracic esophagus, and biopsy revealed small cell carcinoma in November 2012. Four courses of neoadjuvant chemotherapy comprising CDDP and CPT-11 were administered, and radical resection was performed in March 2013.I n March 2014, chest computed tomography revealed the recurrence of mediastinal lymph nodes; thus, we administered chemoradiotherapy comprising 5- FU and CDDP, and the size of the recurrent tumors decreased.However, in February 2015, positron emission tomographycomputed tomography revealed liver metastases.Therefore, we switched to a new chemotherapy regimen containing CDDP and VP-16.Although the treatment was very effective and the liver metastases significantly decreased in size, it was discontinued after 9 courses owing to neurotoxicity.Next, 7 courses of chemotherapy comprising amrubicin, which is administered for treating small cell lung carcinoma, were administered, which suppressed tumor growth for approximately 8 months.However, the tumor then re-grew.Chemotherapy comprising S-1 was administered; however, the tumor gradually progressed.The patient died 51 months after the initial treatment.

Background. The aim of this study was to assess the prognostic significance of residual cancer volume (RCV) in patients with esophageal squamous cell carcinoma (ESCC) who received esophagectomy after neoadjuvant chemotherapy. Methods. We measured RCV by using complete stepwise sections at 6- to 8-mm intervals obtained from 81 ESCC patients with clinical stages IB to III. RCV was defined as the summation of all products of residual cancer area and thickness, and its cutoff value was set by receiver operator characteristic curve analysis on 3-year disease-specific survival (DSS). The multivariate analyses were performed in comparison with histopathological factors including tumor regression grades according to the Japanese Classification of Esophageal Cancer (TRG-JPN) or reported by Becker et al (TRG-Becker). Results. The range of RCV was 0 to 49.3 cm3 (median = 1.4 cm3), and the cutoff value was set at 1.0 cm3 (sensitivity = 78%; specificity = 68%). In the Kaplan-Meier curve analysis with the log-rank test, RCV > 1.0 cm3 predicted poorer prognosis for relapse-free survival (RFS; 5-year RFS rate, 12% vs 47%; P < .001) and DSS (5-year DSS rate, 27% vs 61%; P < .001). The multivariate analyses by the Cox hazards model revealed that RCV > 1.0 cm3 was a factor predicting poor prognosis for RFS ( P = .013; hazard ratios [HR] = 2.62) and DSS ( P = .028; HR = 2.56) compared with histopathological factors including TRG-JPN; RFS ( P = .014; HR = 3.03) and DSS ( P = .045; HR = 2.71) compared with histopathological factors including TRG-Becker. Conclusions. The study suggested that determining RCV is a new method of predicting prognosis in ESCC patients after neoadjuvant chemotherapy.

This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. This retrospective study evaluated 477 patients with stage I–III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1–2). Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p

BACKGROUND/AIM Surgical therapy for stage IV gastric cancer patients is still debatable. The clinical outcomes were compared between gastrojejunal bypass and gastrectomy for metastatic gastric cancer patients. PATIENTS AND METHODS A total of 110 patients with metastatic gastric cancer who underwent surgery were retrospectively analyzed. Twenty-nine patients underwent gastrojejunal bypass (group B) and 81 underwent gastrectomy (group G). RESULTS There was no significant difference in the 3-year overall survival between Group G patients with partial gastrectomy and total gastrectomy. However, patients in group G had a significantly better prognosis compared to patients in group B (p=0.01 and 0.03, respectively). The prognosis of patients with postoperative chemotherapy was significantly better in group G compared to group B (p=0.03), whereas it was not significantly different for the patients without postoperative chemotherapy (p=0.24). CONCLUSION Gastrectomy in patients with metastatic gastric cancer may improve survival when combined with postoperative chemotherapy.

Case 1 was that of a 65-year-old woman. Radical esophagectomy was performed after neoadjuvant chemotherapy(NAC) for lower thoracic esophageal cancer. Nineteen months after surgery, local recurrence was indicated on the dorsal side of the descending aorta. After chemoradiotherapy(CRT)and chemotherapy, residual cancer with aortic invasion was diagnosed. Case 2 was that of a 64-year-old man. Radical esophagectomy was performed after NAC for middle thoracic esophageal cancer. Five months after surgery, local recurrence was indicated between the descending aorta and left inferior pulmonary vein. After CRT and chemotherapy, residual cancer with invasion of the aorta and left lung was diagnosed. In both cases, we inserted an aortic stent and safely performed residual cancer resection including the aortic adventitia. In summary, aortic stent insertion enables safe resection of local recurrent tumors in the aorta after radical esophagectomy.

A 68-year-old man was diagnosed with esophagogastric junction adenocarcinoma, cT4a(SE)N3aM0, cStage Ⅲ. Because "bulky N" was present, he was administered 2 courses of preoperative chemotherapy containing S-1 plus oxaliplatin(SOX). Both the primary tumor and enlarged lymph nodes had greatly decreased in size following chemotherapy, and total gastrectomy and lower esophagectomy with D2 lymphadenectomy were then performed. Histopathological examinations showed no residual cancer cell both in the primary lesion and dissected lymph nodes; thus, the efficacy of the chemotherapy was Grade 3. Preoperative chemotherapy containing SOX could be one of the useful treatment options for gastric cancer patients with extensive lymph node metastases including "bulky N".

The case is a 73-year-old man who underwent esophagectomy and retrosternal gastric conduit reconstruction for esophageal cancer. Reoperation was performed because the oral side of the gastric tube developed necrosis on the 31st postoperative day. The necrotic parts of the gastric tube were resected, and a cervical esophageal stoma was created. The remaining gastric tube was pulled up at the anterosternal subcutaneous location in preparation for the two-stage reconstructive operation. The reconstructive operation with a free jejunum graft through the anterosternal subcutaneous route was performed 35 days after the reoperation. Vascular anastomosis was performed with the right internal thoracic artery and vein by microsurgery. The postoperative course was satisfactory. Necrosis of the gastric tube is a rare and severe complication of esophagectomy. Reconstructive surgery for gastric tube necrosis is generally necessary but difficult to perform because of the severe surgical stress it confers on the patient. In this paper, we showed a new approach for two-stage reconstruction with a free jejunum graft through the anterosternal subcutaneous route. This operative procedure causes relatively less surgical stress than other procedures; hence, it is considered to be a beneficial reconstructive approach for patients with gastric tube necrosis.

A 58-year-old man was followed up for esophageal submucosal tumor at our hospital. Esophagogastroduodenoscopy showed the tumor was located on the left side of the thoracic esophagus and had gradually increased in size. Endoscopic ultrasonography revealed an 18×11.5mm hypoechoic tumor connected to the fourth layer of the esophagus and fine needle biopsy revealed c-kit(+), desmin(-)and a-SMA(-). Double-contrast barium study detected a tumor of diameter 20 mm in the middle-lower thoracic esophagus. We diagnosed an esophageal gastrointestinal stromal tumor(GIST)and performed mediastinoscope-assisted transhiatal esophagectomy with gastric tube reconstruction. The maximum tumor diameter was 25mm and pathological evaluation showed c-kit(+), Ki-67 index of less than 5%, and low-risk GIST by the Fletcher classification. Mediastinoscope-assisted transhiatal esophagectomy might be a useful approach for esophageal GIST, because dissection along the esophagus can be performed without thoracotomy.

The patient was a 67-year-old man. A Type 0-Ⅱa+Ⅱc tumor, 20mm in size was observed in the 1st portion of the duodenum under magnifying endoscopy. Mucosal cancer was suspected and endoscopic resection was performed, with pathological findings as follows: Type 0-Ⅱa+Ⅱc, 19×12 mm, tub1, pT1b(SM2: 700 mm), pUL0, Ly0, V0, pHM0, pVM0. He refused subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)because of the high morbidity and mortality rates. Instead, he underwent only laparoscopic sampling of No. 5, 6, 12b, and 13a lymph nodes, and metastasis in a No. 6 node was pathologically confirmed. He eventually underwent SSPPD with D2, but no metastases were found in other lymph nodes. Pancreaticoduodenectomy is currently considered the best treatment option for complete removal of regional lymph nodes in duodenal cancer despite high morbidity and mortality rates. Further studies are needed to determine the pattern and incidence of lymph node metastasis by location and depth of the primary tumor, to establish optimal treatment guidelines for duodenal cancer.

A 42-year-old woman with complaints of fever and abdominal pain, was diagnosed to have perforative appendicitis, for which emergency surgery was performed. Marked thickening and edema around the cecum, ileum, and the mesentery was observed. Ileocecal resection was performed, as malignant disease could not be excluded. Histopathological examination revealed abscess formation in the lining membrane of the intestine, inflammatory granulation and proliferation of the spindleshaped cells in the serosal membrane extensively, and an inflammatory pseudotumor(IPT)was diagnosed. It is generally difficult to clearly distinguish IPT from a malignant tumor before surgery. We thus report this case, along with a review of literature.

Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0929-3) contains supplementary material, which is available to authorized users.

Undernutrition and sarcopenia are associated with a higher incidence of chemotherapy-related toxicity and a poor prognosis in several kinds of cancer, but the impact of sarcopenia on the outcomes of chemotherapy for esophageal cancer remains unclear. Thus, the purpose of this retrospective study was to investigate whether sarcopenia affects the efficacy and toxicities of chemotherapy for advanced esophageal cancer patients. Data were collected from 31 esophageal cancer patients who underwent neo-adjuvant chemotherapy followed by surgery. Body composition was assessed at the start of chemotherapy by bioelectrical impedance analysis, and outcomes of chemotherapy were compared between sarcopenic and non-sarcopenic groups. Of the 31 patients, sarcopenia was observed in 16 (51.6%). The incidence of toxicities was not different between the two groups. However, as for pathologic response, a good therapeutic effect (Grade 2 or higher) was more common in the non-sarcopenic group than in the sarcopenic group (53.3% vs. 25.0%). Multivariate analysis showed that sarcopenia was an independent predictor of poor pathological response (odds ratio 8.02; P = 0.037). The results of this study suggest the potential utility of sarcopenia assessment in neoadjuvant patient selection strategies.

Purpose: The medial medullary lamina (MML) separates the medial globus pallidus (GPm) from the lateral. The aim of this study was to assess the changes in appearance of MML related to age using the phase difference-enhanced (PADRE) imaging and to determine whether PADRE can depict the MML in the patients with Parkinson’s disease (PD). Materials and Methods: We enrolled 20 patients with PD and 50 normal control subjects (NC). First, for the visualization of the MML in the NC, we compared the PADRE, susceptibility-weighted imaging (SWI)-like images and T2weighted imaging (WI) by using multiple comparison. The grading methods are as follows: grade 1; MML was not delineated, grade 2; less than half of MML was delineated, grade 3; more than half of MML was delineated and grade 4; whole MML was clearly delineated. We determined grade 3 and 4 as good depiction, delineating the GPm. Then, we evaluated patients with PD using the same method. Results: In NC, the delineation of MML was good in 84% of cases on PADRE, but only 34% of cases showed a good depiction on SWI-like images (average grading score 3.31 vs 2.11, P < 0.05). No MML was delineated in all cases on T2WI. Although younger subjects tended to show whole MML clearly, a part of MML tends to be obscured with age on PADRE. In patients with PD the depiction of MML on PADRE was also good in 90% of cases. Conclusion: The PADRE technique facilitates the depiction of the MML within globus pallidus (GP) on a broad range of age NC and patients with PD and it is superior to SWI-like images and T2WI.

Background: PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is a serine–threonine kinase and overexpressed in various types of cancer by inhibiting the transactivation activities of p53 and PTEN. We tested whether PBK/TOPK acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods: We analysed five GC cell lines and 144 primary tumours, which were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the PBK/TOPK protein was frequently detected in GC cell lines (4 out of 5 lines, 80.0%) was detected in primary tumour samples of GC (24 out of 144 cases, 16.6%) and was significantly correlated with venous invasion, tumour depth and recurrence rate. PDZ-binding kinase/T-LAK cell-originated protein kinase-overexpressing tumours had a worse survival rate than those with non-expressing tumours (P=0.0009, log-rank test). PDZ-binding kinase/T-LAK cell-originated protein kinase positivity was independently associated with a worse outcome in multivariate analysis (P

Aim The present study aimed to retrospectively investigate the utility of positron-emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (PET-CT) in regular follow-ups after esophageal cancer surgery.Clinical outcomes were retrospectively analyzed for 61 patients who were diagnosed with postoperative recurrence using PET-CT.A univariate analysis revealed that single recurrence, a low cytokeratin 19 fragment (CYFRA) value, chemoradiotherapy against recurrence, and recurrence over 6 months after surgery were significant prognostic factors. A low CYFRA level and single recurrence tended to be good prognostic factors in the multivariate analysis. The prognosis of cases with single recurrent tumor of size less than 10 mm was significantly better than those with tumors of 10 mm or more. PET-CT revealed small recurrent tumors, and contributed to the early detection of recurrence outside the body trunk.PET-CT contributes to the detection of single small recurrent tumors and those outside the body trunk. This follow-up method using PET-CT should be considered for patients after esophageal cancer surgery.

Hand-assisted laparoscopic surgery (HALS) is safe and useful in the management of gastric conduit reconstruction. By applying the HALS technique to mediastinal surgeries, we developed a novel technique for the en-bloc dissection of the middle and lower (M&L) mediastinal lymph nodes (LNs) using a laparoscopic transhiatal approach (LTHA). We describe our technique, with a focus on the roles of the operator’s left hand. In our procedure, the operator’s hand has several important roles, such as retraction, maintenance of the route for the laparoscope, and grasping the shaft of the energy device to stabilize operability. After the esophageal hiatus was opened, the pericardium was exposed. The posterior plane of the pericardium was extended, and the anterior side of the subcarinal, main bronchial, thoracic paraaortic, and pulmonary ligament LNs was separated. The posterior side of these LNs was then separated. While lifting these LNs like a membrane, they were resected from the bilateral mediastinal pleura, main bronchi, and tracheal bifurcation. The treatment outcomes of 84 patients with esophageal cancer who underwent M&L mediastinal LN dissection by LTHA were compared with those of 75 patients who underwent their dissection by right thoracotomy. The total operative time and bleeding were significantly decreased by LTHA. The number of resected M&L mediastinal LNs in the two groups was not significantly different. Postoperative respiratory complications occurred in 14.3 % of patients treated with LTHA and 25.3 % of those treated without it. In our surgical procedure, a specific technique of the operator’s left hand was essential and resulted in a good surgical view of the mediastinum, and en-bloc dissection of M&L mediastinal LNs was performed safely.

UNLABELLED Backgtound/Aim: Since hepatocellular carcinoma (HCC) has a high recurrence rate, accurate diagnosis of its location and curative resection is important to improve survival. This study evaluated the utility of photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) for HCC. MATERIALS AND METHODS We used two human hepatoma cell lines (HuH-7 and Hep G2). Cells were treated with 5-ALA for 4 h. 5-ALA-induced fluorescence was then examined under a fluorescence microscope. We designed hepatoma mouse models, with mice receiving an intraperitoneal injection of 5-ALA. After 4 h, their liver tumors were removed and examined under a fluorescence microscope. We also analyzed 12 HCC patients who underwent curative liver resection. The patients were administered 5-ALA orally before surgery. The excised livers were sectioned and examined by fluorescence microscopy. RESULTS In vitro and in vivo, red fluorescence of protoporphyrin IX (PpIX) was observed in tumors. In 11 of 12 patients, red fluorescence was observed in their HCC. The tumor of only one patient did not exhibit red fluorescence because it had been necrosed by transcatheter arterial chemoembolization (TACE). CONCLUSION Red fluorescence of PpIX was observed in hepatoma cells, tumors of HCC mouse models and HCC of patients. PDD of HCC using 5-ALA is simple and may be useful for real-time diagnosis during liver resection.

BACKGROUND In gastric cancer, although at least 16 lymph nodes of retrieved lymph nodes (RLNs) are recommended for nodal staging in Japanese Classification of Gastric Carcinoma and TNM classifications, we wished to clarify their appropriateness. STUDY DESIGN A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively. RESULTS (i) The patients were divided into two groups using a cut-off RLN number of 16 (RLN

Background The aim of this study was to evaluate the clinical characteristics of early signet ring cell carcinoma of the stomach (SRC) and to investigate the optimal treatment strategy for early SRC. Methods A total of 746 patients with pT1 gastric cancer (GC), who had undergone surgical resection between 1997 and 2012 were analyzed. Of these, 190 patients with SRC were enrolled in this study. Results (i) The patients with SRC showed a significantly longer overall survival (P = 0.012) and disease free survival (P = 0.004) than patients with the other histological types. Multivariate analysis identified SRC as an independent factor predicting favorable prognosis in pT1 GC (HR = 0.38; 95% CI: 0.11-0.96; P = 0.041). Specifically, in undifferentiated pT1 GC, SRC was significantly less associated with lymph node metastasis (LNM) (OR = 0.39; 95% CI: 0.15-0.96; P = 0.042). (ii) From the viewpoint of a histological mixed-type, pure-SRC with pT1a was not associated with LNM regardless of tumor size (0.0%, 0/110), whereas mixed-SRC was an independent risk factor for LNM (OR = 7.19; 95% CI: 1.51-43.9; P = 0.012). Conclusions Patients with early SRC have a favorable prognosis with a low incidence of LNM. However, care should be taken with mixed-SRC, which consists of SRC and other histological types. J. Surg. Oncol. 2016;114:607-612. © 2016 Wiley Periodicals, Inc.

// Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Tsutomu Kawaguchi 1, * , Hiroki Takeshita 1 , Mahito Miyamae 1 , Takuma Ohashi 1 , Wataru Okajima 1 , Taisuke Imamura 1 , Jun Kiuchi 1 , Tomohiro Arita 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachihirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan * These authors contributed equally to this work Correspondence to: Shuhei Komatsu, email: skomatsu@koto.kpu-m.ac.jp Keywords: plasma, microRNA, biomarker, prognosis, chemoresistance Received: March 27, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT BACKGROUND: This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach. RESULTS: (1) Four candidate microRNAs ( miR-223, 103a, 23b and 23a ), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT–PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response ( p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro . (5) A high level of plasma miR-23a , which tended to correlate with lymphatic invasion ( p = 0.0808) and deep depth of invasion ( p = 0.0658), was an independent risk factor for chemoresistance in ESCC ( p = 0.0222; odds ratio: 12.4; range 1.46–105). MATERIALS AND METHODS: We used the Toray ® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil. CONCLUSIONS: Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.

A one-dimensional full-particle model of the Martian upper thermosphere-exosphere has been developed, where the Direct Simulation Monte Carlo (DSMC) method is applied to both thermal and non-thermal components. Our full-particle model can self-consistently solve the transition from collisional to collisionless domains in the upper thermosphere, so that the energy deposition from non-thermal energetic components to thermal components in the transition region is properly described. For the solar EUV condition during the Viking-1 measurement (1 EUV case), computed density profiles are in good agreement with those observed by Viking 1 and with the conventional model. For a solar EUV flux six times the Viking-1 condition (6 EUV case), the computed heating efficiency is essentially the same as 1 EUV case but slightly increases by about 10 % below the exobase, and temperature deviates from the conventional model in and above the transition region. This result suggests that the conventional heating efficiency of 0.18 is a good approximation for low (1 EUV case) to moderately strong (6 EUV case) solar EUV conditions but would be inappropriate for an extremely strong solar EUV (up to ~100 times stronger flux) environment. We also find that applying different models of the CO2-O collisional energy transfer rate results in a difference in the calculated exobase temperature by 150 K for 6 EUV case.

Background and Aim: No study has compared the incidence of postoperative anemia between two reconstruction methods, Billroth-I (B-I) and Roux-en-Y (R-Y) reconstructions, after distal gastrectomy for gastric cancer (GC). In this study, we wished to examine the postoperative decrease in hemoglobin (Hb) as an indicator of iron-deficiency anemia. Methods: We investigated a total of 119 consecutive patients who underwent distal gastrectomy with B-I or R-Y reconstruction for Stage I GC between 2006 and 2012. We retrospectively assessed the clinical data, including Hb results, of the first 2 years after surgery. Results: Compared with B-I reconstruction, R-Y reconstruction was performed more frequently in older patients (P = 0.017), and it was associated with a longer surgical duration (P

T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.