Search

Background and Objectives Elevated serum CRP levels are associated with tumor progression and poor prognosis of esophageal cancer. The aim of this study was to clarify the clinical significance of CRP in relation to response to chemoradiotherapy in patients with esophageal cancer. Methods The relationship between serum CRP levels and response to chemoradiotherapy and prognosis was analyzed in 34 patients with advanced esophageal squamous cell carcinoma who underwent induction chemoradiotherapy followed by surgery. The relationship between response to chemoradiotherapy and interleukin-6 (IL-6) expression in sera and tumor tissues was also analyzed. Results Although elevated serum CRP levels were associated with poor response to chemoradiotherapy, significant difference in CRP levels between pathological responders (n = 18) and non-responders (n = 16) was observed after chemoradiotherapy, but not before. Patients with elevated CRP levels had shorter cause-specific survival, but significant difference was observed only after chemoradiotherapy. In addition, serum levels of IL-6 were also associated with poor treatment response following chemoradiotherapy and were correlated with residual tumor volume. IL-6 expression was detected in residual tumor tissues by immunohistochemistry. Conclusions Elevated serum CRP levels after chemoradiotherapy may predict poor response to chemoradiotherapy more accurately than before chemoradiotherapy, and IL-6 may be a possible target associated with chemoradiotherapy resistance. J. Surg. Oncol. 2011;103:62–68. © 2010 Wiley-Liss, Inc.

Background The procedure for mediastinal lymph node dissection using a laparoscopic transhiatal approach (LTHA) had not been established for esophageal and esophagogastric junction (EGJ) cancers because of the difficulties associated with surgery. We developed a novel and simple technique for their en-bloc dissection using LTHA. To date, 296 patients had undergone our method during various esophageal surgical procedures, including 39 cases with EGJ cancer. We describe our technique and evaluate the optimal range of mediastinal lymph node dissection for EGJ cancer. Methods The esophageal hiatus was opened and CO2 was introduced into the mediastinum. The posterior plane of the pericardium was extended, and the anterior side of the subcarinal, main bronchial, thoracic paraaortic and pulmonary ligament lymph nodes were separated. The posterior side of these lymph nodes was then separated. Finally, while lifting lymph nodes like a membrane, they were resected from bilateral mediastinal pleura, main bronchi and tracheal bifurcation. Results 1) Patients with EGJ cancers performed middle and lower mediastinal lymph node dissection by LTHA (n = 39) were compared with those performed by the right thoracotomy (n = 41). The total operative time and bleeding were significantly decreased by LTHA. The number of resected middle and lower mediastinal lymph nodes, pR0 rate, and mediastinal recurrence in the two groups were not different. In 87.2% of patients treated by LTHA, extubation was performed at 0 POD. Postoperative respiratory complications was decreased by LTHA (LTHA: 7.7%, thoracotomy: 17.0%). 2) Patients with EGJ cancers performed total mediastinal lymph node dissection by thoracotomy for the time before introducing LTHA were analyzed (n = 37). Upper and/or middle mediastinal lymph nodes metastasis was observed in 10 cases, and all of them had advanced tumors. All of 6 cases with upper mediastinal lymph nodes metastasis were squamous cell carcinoma. Even in adenocarcinoma, middle mediastinal lymph node metastasis was observed in 2 cases, suggesting the importance of mediastinal lymph node dissection for advanced EGJ cancers. Conclusion Our surgical procedure resulted in a good surgical view, safe en-bloc mediastinal lymph node dissection, and the decrease of postoperative respiratory complications. Disclosure All authors have declared no conflicts of interest.

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. Conclusion 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. Disclosure All authors have declared no conflicts of interest.

Background Purpose: 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). 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. 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 (IF) of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the IF was associated with shorter postoperative survival. Conclusion s: The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by affecting MMP signaling pathways and are related to a poor prognosis in patients with ESCC. Disclosure All authors have declared no conflicts of interest.

Background Aquaporin 1 (AQP1) is a membrane protein whose main function is to transfer water via cellular membranes. Recent studies have described important roles for AQP1 in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AQP1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Methods Immunohistochemistry for the AQP1 protein was performed to investigate the expression of AQP1 in primary tumor tissues of 50 human ESCC samples underwent curative esophagectomy. Samples were categorized into two groups according to the expression of AQP1 in each of cytoplasm and nuclear membrane, and relationships with the clinicopathological features and prognosis of ESCC patients were investigated. Next, the location of AQP1 protein in TE5, TE15, and KYSE70 cells was investigated using immunofluorescence analysis. In addition, apoptosis assay was performed in these ESCC cells and the gene expression profiles of AQP1-depleted TE5 cells was analyzed using microarray and bioinformatic studies. Results In an immunohistochemical analysis, AQP1 was primarily located in the cytoplasm and/or the nuclear membrane of carcinoma cells. The 5-year survival rate of patients with the ‘cytoplasm dominant’ expression of AQP1 (46.8%) was significantly lower than other patients (77.6%). A multivariate analysis of the 5-year overall survival rate showed that the pT categories and cytoplasm dominance groups of AQP1 were independent prognostic factors (P = 0.042 and 0.036, respectively). Immunofluorescence analysis revealed that AQP1 protein mainly existed in the cytoplasm in TE5 and TE15 cells. On the other hand, the expression of AQP1 in KYSE170 cells was confirmed on the nuclear membrane. The depletion of AQP1 using siRNA induced apoptosis in TE5 and TE15 cells. The results of microarray analysis revealed that Death receptor signaling pathway-related genes were changed in AQP1-depleted TE5 cells. Conclusion The results of the present study suggested that the cytoplasm dominant expression of AQP1 is related to a poor prognosis in patients with ESCC, and that it regulates tumor progression by affecting Death receptor signaling pathway. These results provide insights into the role of AQP1 as a biomarker for ESCC. Disclosure All authors have declared no conflicts of interest.

Background (Bachground) The radical esophagectomy for esophageal cancer is an invasive therapy for a long one-lung ventilation. We have been stylized trans-mediastinal radical esophagectomy in order to relieve the pulmonary complications. Methods (Candidates) The radical esophagectomy (R0/1, gastric tube reconstruction) by thoracotomy/thoracoscopy (groupT) or mediastinoscopy (groupM) were performed for 120/58 or 131 esophageal cancer patients. The long-term therapeutic results of trans-mediastinal radical esophagectomy and complications (Clavien-Dindo classification≧ 2) are investigated. Results (Results) In clinicopathological features, neoadjuvant therapy, cStage III/IV advanced cases, or R1 resection was significant in groupT (P Conclusion (Discussion) The trans-mediastinal radical esophagectomy was effective for the relief of pulmonary complication, and was not inferior to the esophagectomy by thoracotomy or thoracoscopy in the prognosis. Disclosure All authors have declared no conflicts of interest.

Background: We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients. Methods: We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients. Results: The plasma C/D ratio was significantly higher in the ESCC group than the controls (P=0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P=0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P=0.0266; hazard ratio 5.988). Conclusion: Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients.

Background: We examined plasma microRNA (miRNA) concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. Methods: We initially investigated the appropriateness of plasma miRNA assay, and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients, and also compared plasma miRNAs between pre- and post-operative paired samples from 10 GC patients. Then, plasma miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b and let-7a) were analysed in 69 GC patients and 30 healthy volunteers in total. Results: The initial analysis showed that miRNAs were stable and detectable in all plasma samples, and the plasma miRNA levels reflected the tumour miRNAs in most cases. The levels of these miRNAs were significantly reduced in post-operative samples. In large-scale analysis, the plasma concentrations of miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b) were significantly higher in GC patients than controls (P=0.05, 0.006, 0.008 and

The purpose of this nonrandomized retrospective study was to report our new procedures using polyethylene glycolic acid (PGA) felt with fibrin sealant to prevent severe pancreatic fistula in patients undergoing pancreatic surgery.From 2000 to 2008, 54 and 63 patients underwent pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), respectively. Of those patients, we applied PGA felt with fibrin sealant to 18 PD patients and 26 DP patients. In PD patients, the PGA felt was wrapped around the pancreatic suture site, while in DP patients, the PGA felt was wrapped around the predictive division site. The pancreaticojejunostomy site in PD patients and the cut stump in DP patients were coated with fibrin sealant. We compared the occurrence rates for severe postoperative pancreatic fistula (POPF) that occurred after PD or DP both with and without our new procedures.Before introduction of our procedures, severe POPF developed in 14 of 36 PD patients (39%) and 10 of 37 DP patients (27%). In contrast, after introduction of our procedures, the incidence of POPF was only one in both of 18 PD (6%; P = 0.016) and 26 DP (4%; P = 0.017) patients.In summary, our procedure using PGA felt with fibrin sealant may reduce the risk of severe POPF.

In order to illustrate morphological features and variations of temperature in the upper thermosphere, we performed numerical simulations with a whole atmosphere general circulation model (GCM) for the solar minimum and geomagnetically quiet conditions in March, June, September, and December. In previous GCMs, tidal effects were imposed at the lower boundaries assuming dominant diurnal and semi-diurnal tidal modes. Since the GCM used in the present study covers all the atmospheric regions, the atmospheric tides with various modes are generated within the GCM. The global temperature distributions obtained from the GCM are in agreement with ones obtained from NRLMSISE-00. In addition, the GCM also represents localised temperature structures which are superimposed on the global day-night distributions. These localised structures, which vary from hour to hour, would be observed as variations with periods of about 2–3 h at a single site. The amplitudes of the 2–3 h variations are significant at high-latitude, while the amplitudes are small at low-latitude. The diurnal temperature variation is more clearly identified at low-latitude than at high-latitude. When we assume the same high-latitude convection electric field in each month, the temperature calculated in the polar cap region shows diurnal variation more clearly in winter than in summer. The midnight temperature maximum (MTM), which is one of the typical low-latitude temperature structures, is also seen in the GCM results. The MTMs in the GCM results show significant day-to-day variation with amplitudes of several 10s to about 150 K. The wind convergence and stream of warm air are found around the MTM. The GCM also represent the meridional wind reversals and/or abatements which are caused due to local time variations of airflow pattern in the low-latitude region.

We developed a new numerical model of the Jovian magnetosphere–ionosphere coupling current system in order to investigate the effects of diurnal variation of ionospheric conductance. The conductance is determined by ion chemical processes that include the generation of hydrogen and hydrocarbon ions by solar EUV radiation and auroral electrons precipitation. The model solves the torque equations for magnetospheric plasma accelerated by the radial currents flowing along the magnetospheric equator. The conductance and magnetospheric plasma then change the field-aligned currents (FACs) and the intensity of the electric field projected onto the ionosphere. Because of the positive feedback of the ionospheric conductance on the FAC, the FAC is the maximum on the dayside and minimum just before sunrise. The power transferred from the planetary rotation is mainly consumed in the upper atmosphere on the dayside, while it is used for magnetospheric plasma acceleration in other local time (LT) sectors. Further, our simulations show that the magnetospheric plasma density and mass flux affect the temporal variation in the peak FAC density. The enhancement of the solar EUV flux by a factor of 2.4 increases the FAC density by 30%. The maximum density of the FAC is determined not only by the relationship between the precipitating electron flux and ionospheric conductance, but also by the system inertia, i.e., the inertia of the magnetospheric plasma. A theoretical analysis and numerical simulations reveal that the FAC density is in proportion to the planetary angular velocity on the dayside and to the square of the planetary angular velocity on the nightside. When the radial current at the outer boundary is fixed at values above 30 MA, as assumed in previous model studies, the peak FAC density determined at latitude 73°–74° is larger than the diurnal variable component. This result suggests large effects of this assumed radial current at the outer boundary on the system.

Background Laparoscopy-assisted distal gastrectomy (LADG) has recently been accepted as a preferred surgical procedure for patient with early gastric cancer. The Billroth-I method has been performed widely because of physiologic advantages and technical simplicity. Methods Since September 2007, we performed standardized LADG for 35 patients with early gastric cancer. Of these 35 patients, 27 patients were reconstructed by Billroth-I anastomosis. Gastroduodenostomy was performed under direct vision for 11 patients (extracorporeal) and remaining 16 patients were anastomosed under laparoscopic vision facilitated by abdominal wall lifting with a right angle retractor (intracorporeal). Results The mean duration of the anastomosis procedure was 17 and 20 minutes in extracorporeal and intracorporeal patients, respectively. The abdominal lifting method with a right angle retractor provided a good visual field without reestablishing pneumoperitoneum. The laparoscopic fine view could prevent surrounding fatty tissues and organs from intervening between the anastomosis planes and consequently guided an accurate and safe anastomosis. Neither anastomotic-related nor pancreatic-related complication was observed in this series. Conclusions This anastomotic technique should be useful as an easy and safe reconstruction method in LADG and is especially recommendable for less-experienced laparoscopic gastric surgeons.

Acute occlusion of the superior mesenteric artery (SMA) causes extensive bowel necrosis, resulting in a poor prognosis with an extremely high mortality rate. An 82-year-old woman was admitted to our hospital with the complaint of abdominal pain. She was diagnosed as having acute SMA occlusion by enhanced CT. Five hours from onset, the first thrombolytic therapy with urokinase was performed, but failed to complete thrombolysis and recanalization of peripheral blood flow. An exploratory laparotomy following the first thrombolytic therapy showed a mild ischemic change in the affected intestine and mesentery, but no sign of necrosis. After the laparotomy, local thrombolytic therapy with angiographic evaluation of blood flow at 24, 36 and 48 h from the first thrombolysis was performed. As a result, the residual thrombus disappeared and all branches of the SMA became well visualized. The patient was discharged well without a second-look operation or major bowel resection. Sequential intermittent thrombolytic therapy with meticulous angiographic evaluation of blood flow is effective for early-stage acute SMA occlusion.

Background and Objectives This study investigated the prognostic impact of lymphatic invasion on the outcome of patients with node-negative gastric cancer. Methods A total of 828 patients with node-negative gastric cancer who underwent curative gastretomy were reviewed retrospectively. The clinicopathological features and prognoses of patients with lymphatic invasion were compared to those of patients without such invasion. Results The total rate of lymphatic invasion was 18.2% in node-negative gastric cancers, with a significant difference between early gastric cancers (9.8%) and advanced gastric cancers (49.2%). The presence of lymphatic invasion correlated significantly with tumor location, size and depth of tumor (P

Using a general circulation model that contains the region from the ground surface to the upper thermosphere, we have examined characteristics of gravity waves in the equatorial thermosphere. At an altitude of 150 km, the dominant periods of gravity waves for zonal wave number 20 (zonal wavelength λ x ≈ 2000 km), 40 (λ x ≈ 1000 km) and 80 (λ x ≈ 500 km) are 3, 1.5 and 1 h, respectively. For individual zonal wave numbers, the corresponding dominant period becomes shorter at higher altitudes due to dissipation processes in the thermosphere, such as molecular viscosity and ion drag force, indicating that gravity waves with a larger horizontal phase velocity (larger vertical wavelength) can penetrate into the thermosphere. The longitudinal variation of gravity wave activity in the equatorial thermosphere and upward propagation of gravity waves from the lower atmosphere were also studied. The longitudinal distribution of gravity wave activity in the thermosphere is quite similar to that of gravity wave activity in the lower atmosphere and the cumulus convective activity in the tropical troposphere. Our results indicate that the strong energy flux due to gravity waves from the enhanced cumulus convective activity propagates upward into the upper thermosphere. The relation between the wind fluctuation associated with gravity waves and the ionospheric variation is discussed. Fluctuations of the neutral zonal wind with periods of 1–2 h are significant in the 200- to 300-km height region, and its amplitude sometimes exceeds 50 m s−1. These results suggest that upward propagating gravity waves can affect the ionospheric variation in the F-region.

Hepatocyte growth factor (HGF) plays a definitive role in invasive, angiogenic, and metastatic activities of tumor cells by binding to the c-Met receptor. NK4, a competitive antagonist for HGF and the c-Met receptor, prevents tumor cell growth and metastasis via its bifunctional properties to act as an HGF antagonist and angiogenesis inhibitor. In the present study, we investigated the inhibitory effectiveness of NK4 on hematogenous pulmonary metastasis of the CT26 murine colon cancer cell line, focusing on tumor cell adhesion to endothelial cells. In an in vitro adhesion assay, HGF facilitated adhesion of CT26 cells to a murine endothelial cell line (F-2) in a dose-dependent manner. Furthermore, the enhancing effect of HGF on CT26-F-2 cell interaction was blocked by NK4 as well as by anti-HGF antibody. Similarly, HGF-induced phosphorylation of focal adhesion kinase (FAK), downstream of integrin signaling, was reduced by NK4 and by anti-HGF antibody. However, distinct integrin expression on the surface of CT26 cells was not altered by HGF. In an in vivo experimental pulmonary metastasis assay, stable NK4 expression potently decreased the number of pulmonary metastatic foci. The NK4-induced suppression of pulmonary metastasis was partially reversed when HGF was intraperitoneally administered in an adhesive phase. These results suggest that NK4 could act on tumor cells to inhibit CT26 adhesion to endothelial cells by reducing FAK phosphorylation, which is regulated by inside-out HGF/c-Met signaling, and thereby suppress hematogenous pulmonary metastasis.

A 51-year-old woman with an unresectable pancreatic tumor that was histologically diagnosed as an adenosquamous carcinoma underwent chemoradiotherapy with 5-fluourouracil (FU) and low-dose cisplatin (low-dose FP). Because we recognized a partial response to the chemoradiotherapy, we subsequently administered combined chemotherapy with S-1 and cisplatin. After one course of this combined chemotherapy, the tumor was further reduced in size and became difficult to discern on abdominal computed tomography (CT). We have continued to administer the S-1 and cisplatin combined chemotherapy, and the patient is still alive. After 20 months of treatment, the tumor has not recurred (as assessed by abdominal CT). Additionally, we have not seen elevation of tumor markers. This report presents the successful use of chemoradiotherapy with low-dose FP and additional combined chemotherapy with S-1 and cisplatin for unresectable pancreatic adenosquamous carcinoma.

13????????????????????????????????????69????????????. ??????????????????????????????????????????????????????, 2?????????????????????????????????????????????????????????????????????????????????. ????????????????????????????????????????????????, ???????????????, 3DCT?????????. ??????????????????????????????????????????2.5×2.5×1.5cm???????????????????????????, ??????????????????????????????. ????????????????????????????????????. ?????????????????????????????????, ???????????????????????????. ???????????????????????????????????????????????????, ????????????????????????????????????????????????. ???????????????????????????????????????????????????. ??????????????????????????????????????????????????????????????????????????????????????????, ????????????.

// Tomohiro Arita 1 , Daisuke Ichikawa 1 , Hirotaka Konishi 1 , Shuhei Komatsu 1 , Atsushi Shiozaki 1 , Shinpei Ogino 1 , Yuji Fujita 1 , Hidekazu Hiramoto 1 , Junichi Hamada 1 , Katsutoshi Shoda 1 , Toshiyuki Kosuga 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan Correspondence to: Daisuke Ichikawa, email: ichikawa@koto.kpu-m.ac.jp Keywords: gastric cancer, exosome, peritoneal metastasis, fibronectin 1, laminin gamma 1 Received: December 20, 2015 Accepted: July 18, 2016 Published: July 28, 2016 ABSTRACT Background: Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. In this study, the effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis. Results: TEX were internalized in both mesothelial and gastric cancer cells in a cellular origin non-specific manner. Internalization of TEX into mesothelial cells promoted significant adhesion between mesothelial and gastric cancer cells, and TEX internalization into gastric cancer cells significantly promoted migratory ability, while internalization of mesothelial cell-derived exosomes did not. Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX from gastric cancer cell line and malignant pleural effusion. Methods: TEX were extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX on the malignant potential of gastric cancer were investigated in adhesion, invasion, and proliferation assays. PCR array as well as western blotting were performed to determine the underlying molecular mechanisms. The molecular changes in mesothelial cell after internalization of TEX derived from malignant pleural effusion were also confirmed. Conclusions: TEX may play a critical role in the development of peritoneal metastasis of gastric cancer, which may be partially due to inducing increased expression of adhesion molecules in mesothelial cells.

Gallbladder cancer (GBC) has a poor prognosis [1]. One reaon for this is the difficulty in determining the extent of cancer rogression. Therefore, determining the extent of cancer spread s important. Recent advances in diagnostic imaging have led to mprovement in the preoperative diagnosis rate of GBC. However, t is still difficult to diagnose minute foci of metastasis and assess he extent of cancer spread to regional lymph nodes, extrahepatic ile duct, and so on.

Irinotecan has been used in the first-line treatment of metastatic colorectal cancer. However, no clear predictive marker of irinotecan efficacy has been identified. It is controversial whether the response to irinotecan could be predicted by the expression level of topoisomerase-I, a direct target of irinotecan. The present study aimed to identify a feasible predictive marker of irinotecan efficacy. We hypothesized that the efficacy of SN38 (an active metabolite of irinotecan) is related to the cell proliferation and the phosphorylation status of RB in colorectal cancer cells. Indeed, the IC50 of SN38 was positively correlated with the doubling time of each cell line (R2=0.9315). Moreover, the phosphorylation level of RB was related to SN38 sensitivity. Consistent with the in vitro data, colorectal cancer tissues of irinotecan responders showed a significantly higher rate of phosphorylated RB (serine 780) expression using immunohistochemistry (P=0.0006), although a generally used proliferative marker, Ki-67, showed no significance. Finally, we investigated whether the phosphorylation of RB plays a crucial role in the efficacy of irinotecan. To suppress the expression of phosphorylated RB, we performed the knockdown of CDKs, which are known to phosphorylate RB. Intriguingly, the knockdown of both CDK4 and CDK6, but not CDK2, allowed RB to become the most hypophosphorylated form and converted the SN38-sensitive cells to a resistant state. Taking together the above findings from in vitro and clinical research, the immunohistochemistry of phosphorylated RB protein might be feasible to predict the irinotecan efficacy of colorectal cancer in clinical practice.

We herein reported a case of a dangerous anomaly of a pulmonary vein in subcarinal dissection. A 74-year-old man underwent esophagectomy with systematic nodal dissection using a laparoscopic transhiatal approach. Under pneumomediastinum pressure, dissection of the posterior plane of the pericardium was extended, and a vessel that independently drained into the left atrium was identified. Although this anomalous vein penetrated the subcarinal lymph nodes and crossed behind the right main bronchi, subcarinal dissection was successfully performed without its injury. Our surgical procedure enabled the intraoperative identification of this rare abnormality, an aberrant segmental vein in the right upper lobe, and safe en bloc subcarinal dissection.

Introduction Osteoblasts play essential roles in bone formation and regeneration, while they have low proliferation potential. Recently we established a procedure to directly convert human fibroblasts into osteoblasts (dOBs). Transduction of Runx2 (R), Osterix (X), Oct3/4 (O) and L-myc (L) genes followed by culturing under osteogenic conditions induced normal human fibroblasts to express osteoblast-specific genes and produce calcified bone matrix both in vitro and in vivo Intriguingly, a combination of only two factors, Oct3/4 and L-myc, significantly induced osteoblast-like phenotype in fibroblasts, but the mechanisms underlying the direct conversion remains to be unveiled. Materials and Methods We examined which Oct family genes and Myc family genes are capable of inducing osteoblast-like phenotypic conversion. Results As result Oct3/4, Oct6 and Oct9, among other Oct family members, had the capability, while N-myc was the most effective Myc family gene. The Oct9 plus N-myc was the best combination to induce direct conversion of human fibroblasts into osteoblast-like cells. Discussion The present findings may greatly contribute to the elucidation of the roles of the Oct and Myc proteins in osteoblast direct reprogramming. The results may also lead to establishment of novel regenerative therapy for various bone resorption diseases.

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.A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively.(i) The patients were divided into two groups using a cut-off RLN number of 16 (RLN 16 or RLN ≥ 16). There were significant differences in the survival rates of patients in pStage II (P 0.0001) and III (P = 0.0009), but not those of patients in pStage I (P = 0.0627) and IV (P = 0.1553). (ii) In 498 consecutive patients in pStage II and III, compared with patients in the RLN ≥ 16 group, those in the RLN 16 group had a significantly higher incidence of older age (P = 0.0004) and positive lymph node ratio (PLNR) (P 0.0001). Univariate and multivariate analyses showed that an RLN number of less than 16 was an independent poor prognostic factor (P 0.0001, HR 2.48 [95% CI: 1.60-3.70]). (iii) A cut-off RLN number of 16 could cause the stage migration effect in pStage II or III patients. A cut-off RLN number of 25 or more could eliminate the prognostic effect.The RLN number may potentially affect the prognosis and the stage migration in pStage II or III gastric cancer patients. An RLN number of 25 or more could be sufficient for nodal staging.

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.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.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 0.001), a larger amount of blood loss (P = 0.031), a higher incidence of stasis (P = 0.044), and a greater decrease in Hb for the first 2 years after surgery. Univariate and multivariate analyses identified that R-Y reconstruction was the only risk factor (P = 0.0487; odds ratio = 2.755; 95% confidence interval = 1.01-7.91) for a decrease in Hb, independent of age, tumor location, postoperative complications, and other factors. In addition, an age ≥ 75 was identified as an independent risk factor for a decrease in Hb, particularly for patients underwent R-Y reconstruction (P = 0.033; odds ratio = 6.99; 95% confidence interval = 1.15-68.3) according to the multivariate analysis.Billroth-I reconstruction might be preferable for the purpose of preventing a decrease in Hb in stage I GC patients, particularly in older patients.

Neo-adjuvant chemotherapy (NAC) followed by radical esophagectomy has been shown to prolong survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, neutropenia, one of the major adverse events due to NAC, influences the therapeutic course. The aim of this study is to clarify the relationship between neutropenia and therapeutic response in ESCC with NAC.A total of 117 patients with clinical stage II/III ESCC who had undergone NAC followed by radical esophagectomy were retrospectively analyzed in terms of the relationship between neutropenia and clinicopathological features or outcomes.Neutropenia was the major adverse event observed in 56 % (66/117) and grade 3/4 neutropenia occurred in 29 % of patients. Grade 3/4 neutropenia correlated with a high histological response (Grade 1b-3) (p0.01). Correlative analysis identified grade 3/4 neutropenia and poor differentiation as independent predictors of a high histological response (odds ratio 5.13 and 3.25, p0.01 and p = 0.01, respectively). Survival analysis showed that patients with a high histological response had significantly longer survival than those with a low histological response (Grade 0-1a) (p = 0.03), whereas no significant differences were found for survival according to the grade of neutropenia (p = 0.45). In a subgroup analysis according to histological response, grade 3/4 neutropenia correlated with worse survival in patients with a low histological response (p = 0.05).Severe neutropenia due to NAC correlates with a high histological response in ESCC. However, severe neutropenia may also result in a worse prognosis for patients with a low histological response.

This study was designed to evaluate the clinical significance and prognostic impact of the total diameter of enlarged lymph nodes (TDL) on preoperative multidetector computed tomography (MDCT) in gastric cancer (GC).Of a total of 480 GC patients between 2005 and 2009, 70 patients with a preoperative diagnosis of nodal metastasis on MDCT were included in this study. All regional lymph nodes showing metastatic involvement were preoperatively counted and measured.The TDL was calculated, and using a receiver operating characteristic curve, a cutoff value of 45 mm in the two groups of large TDL (LTDL) and small TDL was found to be appropriate for TDL. No significant differences were observed in clinicopathological features, except for tumor recurrence, between the two groups. Univariate survival analysis revealed that patients with LTDL had a worse prognosis as well as an upper tumor location, deeper tumor depth, and further advanced pathological stage. Multivariable prognostic analysis identified LTDL as an independent worse prognostic factor (P = 0.0128).GC patients with the total nodal diameter measuring 45 mm or more on MDCT have a worse prognosis. GC patients with the novel surrogate indicator of worse prognosis for a preoperative imaging diagnosis may have need of multimodal treatment to improve the survival.

AIM: To evaluate discrepancies between biopsy and resected specimens using the Japanese Classification of Gastric Carcinoma (JCGC) and tumor-node-metastasis (TNM) classification. METHODS: A total of 376 consecutive paired samples from biopsy and resected gastric specimens, which were derived from curative gastrectomy for gastric cancer between 2008 and 2011, were retrospectively analyzed. RESULTS: (1) Discrepancies in the histologic type were observed between biopsy and resected specimens; 11.7% (44/376) in the JCGC and 18.1% (68/376) in TNM. In specimens diagnosed as the differentiated type from biopsy specimens, 14.4% (28/195) in the JCGC and 41.1% (67/163) in TNM were finally diagnosed as the undifferentiated type from resected specimens; and (2) the incidence of mixed-type gastric cancer was significantly higher in specimens with discrepancies than in those without in both the JCGC and TNM (both P < 0.0001); 93.2% (41/44) of specimens with discrepancies in the JCGC and 97.1% (66/68) of specimens with discrepancies in TNM were mixed-type gastric cancers. CONCLUSION: Mixed-type gastric cancer was associated with a high incidence of histologic discrepancies between biopsy and resected specimens in both the JCGC and TNM definitions. Care should be taken in deciding treatments based on diagnosis of the histologic type for mixed-type gastric cancer from biopsy specimens.

AIM: To assess the clinical features of hepatoduodenal lymph node (HDLN) metastasis and to clarify the optimal indication of HDLN dissection. METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy, including HDLN dissection, for gastric cancer between 1999 and 2012. Of these, 26 patients (9.4%) had HDLN metastasis. First, we investigated the clinicopathological characteristics, their perioperative clinical outcomes, such as postoperative complications, and prognostic outcomes between patients with and without HDLN metastasis. Second, we detected the prognostic factors, particularly in patients with HDLN metastasis. Third, we assessed the therapeutic value of HDLN dissection to determine its optimal indication. RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location (the middle or lower stomach [P = 0.005, OR = 5.88 (95%CI: 1.61-38.1)] and pT category [T3 or T4, P = 0.017, OR = 4.45 (95%CI: 1.28-21.3)] were independent risk factors for HDLN metastasis. Cox proportional hazard analysis identified pN3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021, HR = 5.17 (95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection, HDLN metastasis was a prognostic indicator in pN3 gastric cancer (P < 0.0001), but not pN1-2 (P = 0.602). Furthermore, the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0, respectively. CONCLUSION: We suggest that HDLN dissection should be indicated for pN1 or pN2 gastric cancers located at the middle or lower stomach.

AIM: To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions. METHODS: A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach (U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography (CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach (ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth. RESULTS: Patients in the U group were older (P = 0.029), had a higher ratio of males to females (P = 0.015), and had more histologically differentiated tumors (P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients (8.3%), and was more frequent in the U group than in the ML group (16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group (P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors (P = 0.094) and in those larger than 4 cm (P = 0.024). The median follow-up period after surgery was 56 mo (range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group (P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study. CONCLUSION: Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors.

// Hiroki Kobayashi 1, * , Shuhei Komatsu 1, * , Daisuke Ichikawa 1 , Tsutomu Kawaguchi 1 , Shoji Hirajima 1 , Mahito Miyamae 1 , Wataru Okajima 1 , Takuma Ohashi 1 , Toshiyuki Kosuga 1 , Hirotaka Konishi 1 , Atsushi Shiozaki 1 , Hitoshi Fujiwara 1 , Kazuma Okamoto 1 , Hitoshi Tsuda 2, 3 , Eigo Otsuji 1 1 Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 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 have contributed equally to this work Correspondence to: Shuhei Komatsu, e-mail: skomatsu@koto.kpu-m.ac.jp Keywords: gastric cancer, DTL, prognosis, oncogene, biomarker Received: March 13, 2015 Accepted: October 02, 2015 Published: October 13, 2015 ABSTRACT Background: Denticleless E3 ubiquitin protein ligase homolog (DTL) has been identified in amplified region (1q32) of several cancers and has an oncogenic function. In this study, we tested whether DTL acts as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). Methods: We analyzed 7 GC cell lines and 100 primary tumors that were curatively resected in our hospital between 2001 and 2003. Results: Overexpression of the DTL protein was detected in GC cell lines (4/7 cell lines; 57%) and primary GC tumor samples (42/100 cases; 42%). Knockdown of DTL using several specific siRNAs inhibited the proliferation, migration and invasion in a TP53 mutation-independent manner. Overexpression of the DTL was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with DTL-overexpressing tumors had a worse survival rate than those with non-expressing tumors in overall survival ( P = 0.0498, log-rank test) and disease-free survival ( P = 0.0324, log-rank test). In a multivariate analysis, DTL positivity was independently associated with a worse overall survival ( P = 0.0104, hazard ratio 3.7 [1.36–10.1]) and disease-free survival ( P = 0.0070 (hazard ratio, 3.9 (1.45–10.46)) following radical gastrectomy. Conclusions: These findings suggest that DTL overexpression plays a crucial role in tumor cell proliferation and highlights its usefulness as a prognosticator and potential therapeutic target in gastric cancer.

Prospective randomized controlled studies have indicated that endoscopic placement of self-expandable metal stents (SEMSs)is an effective treatment option for patients with malignant gastric outlet obstruction (GOO). We report a case of effective palliation of gastric cancer-related jejunum stricture with a SEMS. A7 7-year-old woman, who had previously undergone partial remnant gastrectomy and Roux-en-Y reconstruction, was diagnosed with abdominal recurrence of gastric cancer. After a 4 month observation period, which the patient opted for with informed consent, recurrent vomiting and loss of appetite ensued. Computed tomography (CT) and upper gastrointestinal series (UGI) examinations revealed a single intestinal stenosis caused by a recurrent tumor. Endoscopic placement of a SEMS palliated this intestinal obstruction, and her oral intake improved (GOOSS score improved from 0 to 3). Upper gastrointestinal series verified that the SEMS maintained its lumen 3 months after the procedure. Endoscopic treatment with a SEMS can be more effective for malignant intestinal stenosis caused by abdominal recurrence of gastric cancer, especially when it is difficult to laparotomy adhesion derived previous operation or peritonitis carcinomatosa. Further studies may be needed to clarify the clinical benefits of stent placement for patients with abdominal recurrence of gastric cancer.

5-aminolevulinic acid (5-ALA) is widely used in clinical practice because it shows tumor-selective accumulation of protoporphyrin IX, a fluorescent substance and a metabolite of 5-ALA. In addition, some studies have reported that 5-ALA increases the radiation sensitivity of glioma and melanoma. In this study, we investigated the radiosensitization effect of 5-ALA on colon cancer. Mice implanted with the human colon cancer cell line HT29 were administered 5-ALA and subsequently X-ray irradiated. These mice were compared with those not administered 5-ALA. Following multiple irradiations, the tumor volume of the 5-ALA group was significantly lower than that of the non-5-ALA group (day 5: p value=0.0489, day 8: p value= 0.0318, day 12: p value=0.0394). Tumor growth was inhibited by multiple irradiations in the 5-ALA group compared with the non-5-ALA group. These results suggest that 5-ALA also exhibits a radiosensitization effect on colon cancer.

Recent advances in anti-cancer drug treatments enable us to improve prognosis in Stage IV gastric cancer. In particular, in recent reports patients with only cytology positive (CY1) non-curative factors have comparatively better prognosis than others. This study was designed to evaluate our outcomes, to allow identification of CY1 gastric cancer patients and to investigate new treatment strategies.Between 2000 and 2008, 336 patients underwent peritoneal washing cytology for gastric cancer intra-operatively. Of these, 35 patients (10.4%) were diagnosed with CY1 gastric cancer.1 ) In all CY1 gastric cancers, 1-year, 3-year, and 5-year survival rates were 49%, 11%, and 5.7%, respectively. Clinical factors such as number of non-curative factors (p=0.008) and gastrectomy (p=0.001)were significantly related to poor prognosis. 2 ) The number of CY1 patients with only CY1 non-curative factors (Group C) and multiple non-curative factors (Group CM)were 14 and 21, respectively. The number of CY1 patients with gastrectomy and without gastrectomy were 30 (MST 366 days, Group C: 14 Group CM: 16) and 5 (MST: 88 days, Group CM: 5), respectively. 3 ) In CY1 patients with gastrectomy, patients treated with S-1 based chemotherapy had better prognosis in both Group C and Group CM. 4 ) 8 CY1 patients with neoadjuvant chemotherapy (NAC) followed by gastrectomy (MST 501 days, 1-year survival rate 62.5%) tended to have better prognosis than those without NAC (MST 132 days, 1-year survival rate 25.0% (p= 0.055).Gastrectomy, number of non-curative factor, S-1 based chemotherapy and NAC were keys to improving prognosis by subgroup analyses in CY1 gastric cancer.

A 78-year-old man presented with fever and jaundice. Computed tomography (CT) revealed a hepatocellular carcinoma in the hepatic left lobe as well as right-sided ligamentum teres (RSLT). Extended left hepatic lobetectomy was performed without division at the left Glissonian root in order to preserve the Glissonian branch at segment 8. No complications occurred during the post-operative course of 13 days. Pathologically, the tumor was diagnosed as a combined hepatocellular and cholangiocarcinoma. Additional congenital variations can exist in RSLT frequently; therefore, we must take care when performing hepatobiliary surgeries. Recently, advanced imaging modalities, such as multi-detector rowcomputed tomography (CT) and magnetic resonance imaging(MRI), help us obtain virtual images of vascular architecture and to plan the operative procedure.

We began performing laparoscopic transhiatal esophagectomies in patients with esophageal cancer in 2009. By June 2014, 172 patients had undergone this procedure. The main advantage of this method was that the dissection of the posterior mediastinal and abdominal lymph nodes(LNs)could be performed continuously under a magnified videoscopic view. An abdominal wall sealing device was placed in the upper abdomen, and 4 ports were inserted. The esophageal hiatus was opened, and carbon dioxide was introduced into the mediastinum. The posterior plane of the pericardium was separated and extended, and the anterior side of each posterior mediastinal LN was separated. The thoracic aorta's adventitia was exposed, and the posterior sides of the LNs were then separated. While lifting the LNs like a membrane, they were resected along the border of the left mediastinal pleura. Subsequently, dissection of the posterior mediastinal LNs was extended towards the caudal side from the crural diaphragm to the celiac artery. Thus, the LNs along the celiac and left gastric artery were dissected en bloc from the left side. Our surgical procedure allowed good views during surgery, and the continuous dissection of the posterior mediastinal and abdominal LNs was performed safely.

We report our experience with 2 male patients (71 and 74 years old, respectively) with advanced esophageal cancer who exhibited pulmonary embolism during treatment with neoadjuvant chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5- FU). The patients had no symptoms associated with pulmonary embolism. The pulmonary emboli were incidentally detected on computed tomography performed to assess the effect of chemotherapy. It was found that the pulmonary emboli were associated with the central venous catheter-associated thrombi. The pulmonary emboli were effectively treated with heparin in both patients. A recent meta-analysis showed that the risk of chemotherapy-associated venous thromboembolism was increased by 1.67-fold when CDDP was included in the chemotherapy regimen. The increased risk was proposed to be associated with CDDP-mediated endothelial cell injury, platelet activation, increased levels of coagulation factors, or renal damage. The pulmonary embolism in our cases may be ascribed to the central venous catheterization and the treatment with CDDP. A possible occurrence of venous thromboembolism should be kept in mind when CDDP is used, particularly with central venous catheterization, for the treatment of esophageal cancer.

The patient was a 53-year-old man whose chief complaint was dysphagia. Pretreatment examination revealed 2 types of locally advanced esophageal squamous cell carcinoma at the middle to lower thoracic esophagus. A computed tomography (CT) scan showed a bulky primary tumor suspicious of aortic invasion and cardiac lymph node metastasis. The pretreatment diagnosis was cT4N2M0, cStageIVa. After induction chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP) (the FP regimen) according to the JCOG9907 regimen, subtotal esophagectomy and 2-field lymphadenectomy with retrosternal stomach roll reconstruction were performed. Intraoperatively, the primary tumor showed extensive and firm adhesion to the aortic wall. The postoperative diagnosis was pT4N0M0, pStageIII, RM1. Postoperative chemoradiotherapy (65 Gy+FP) was performed for the residual tumor at the aortic wall. The patient is alive without recurrences 4 years and 6 months after the esophagectomy. Downstaging of the tumor with induction chemotherapy and effective local control with surgery and postoperative chemoradiotherapy may have contributed to the patient's long-term survival. For multimodal treatment of cT4 esophageal cancer, an effective combination of chemotherapy, surgery, and chemoradiotherapy is essential to improve the treatment outcome.

The present study investigated generational changes in the clinicopathological characteristics of younger patients with gastric carcinoma (GC). The medical records of 1,420 patients who had undergone gastrectomy for GC between 1997 and 2012 were reviewed retrospectively. The patients were divided into 2 groups based on age, with 49 patients below the age of 40 and 1,371 patients above the age of 40. Moreover, the clincopathological features of the 49 patients below the age of 40 were compared with age-matched GC patients who had undergone gastrectomy from 1985 to 1996. Younger GC patients group had a higher number of women and a higher incidence of undifferentiated GC, although there was no prognostic significance between the 2 groups. Comparison of three-generational younger GC patient groups (1985-1996, 1997-2002, and 2003-2012) demonstrated no difference in survival curve between the 3 groups, although a higher incidence of undifferentiated GC was observed with time. Furthermore, in younger patients with undifferentiated GC, the last generational group (2003-2012) had a tendency towards an improved prognosis in the early postoperative period. This study demonstrated that there was no prognostic significance between GC patients below the age of 40 and over the age of 40. Chemotherapy might contribute to improved prognosis in younger GC patients.

Herein, we report 9 patients who underwent esophagectomy after endoscopic submucosal dissection (ESD) between April 2003 and December 2013. All patients were men, with a mean age of 65 years. En bloc ESD was performed, and no complications arose in any patient. The mean surgical time of esophagectomy was 323 minutes, and mean blood loss was 295 mL. Postoperative complications were present in 5 patients(anastomotic leakage in 3, pulmonary complications in 2, and recurrent laryngeal nerve palsy in 1). In a patient diagnosed with pT1b-SM1 disease after ESD, a residual tumor(pT1a-MM, N0) was detected after esophagectomy. In another patient diagnosed with pT1b-SM2 disease, lymph node metastasis was detected after esophagectomy. In all patients, curative resection was performed, and no recurrences have been observed to date. This highlights the importance of additional esophagectomy after ESD for patients with pT1b disease. Esophagectomy after ESD can be considered a valid treatment because it provides high curative rates with acceptable safety.

We studied cases with single lymph node metastasis from thoracic esophageal squamous cell carcinoma.We reviewed the site of nodal metastasis in 73 cases with a single metastatic site.The lymph node metastases of the upper thoracic cases were located in the cervical, superior mediastinal, middle mediastinal, lower mediastinal, and abdominal lymph nodes in 5, 10, 3, 0, and 0 cases, respectively. The lymph node metastases of the middle thoracic cases were located in the cervical, superior mediastinal, middle mediastinal, lower mediastinal, and abdominal lymph nodes in 1, 18, 6, 0, and 11 cases, respectively. The depth of tumor in the middle thoracic case that had metastasis in a cervical lymph node was T1b, and the location of the metastatic lymph node was number 104 L. The lymph node metastases of the lower thoracic cases were located in the cervical, superior mediastinal, middle mediastinal, lower mediastinal, and abdominal lymph nodes in 0, 2, 2, 4, and 11 cases, respectively. The depth of tumor in the lower thoracic cases with metastasis in a superior mediastinal lymph node was T1b and T4.Even in superficial thoracic esophageal squamous cell carcinoma cases, distant metastasis was observed at an early stage. Therefore, the range of lymph node dissection should be decided carefully in these cases.

No ideal or generally accepted treatment strategy has been established for severe duodenum-related complications of gastrectomy for gastric cancer. Between 1997 and 2012, we successfully treated 5 patients with such complications using the retrograde intraduodenal drainage tube. Of the patients, 3 had anastomotic leakage of the duodenal stump, 1 had an intestinal injury, and 1 had the afferent loop syndrome. None of the patients experienced any further adverse events related to the procedure. This retrograde intraduodenal drainage technique was safe and effective, and may be considered as an optimal treatment strategy for severe duodenum-related complications of gastrectomy for gastric cancer.

The patient in this case study was a 71-year-old male who underwent distal esophagectomy with gastric tube reconstruction via a posterior mediastinal route for esophageal cancer 12 years previously. An endoscopy revealed a hypopharyngeal tumor in the right piriform fossa, and the histopathological diagnosis, based on a biopsy sample, was squamous cell carcinoma. Preoperative angiography of the right gastroepiploic artery revealed poor blood flow in the remnant esophagus. First, the adhesion of the gastric tube to the surrounding tissue was dissected via a right thoracotomy. Then, the gastric tube was raised using a cervical approach, and total pharyngolaryngoesophagectomy with free jejunal transfer was performed. The patient was discharged 28 days after the operation without complications. We report a patient with hypopharyngeal cancer who had previously undergone distal esophagectomy with gastric tube reconstruction via a posterior mediastinal route upon whom we successfully performed a total pharyngolaryngoesophagectomy with free jejunal transfer. In such a case, it is important to carefully decide the surgical approach in order to prevent anastomotic leakage.

The aim of this study was to clarify the influence of a high body mass index (BMI) on short- and long-term outcomes of patients after esophagectomy for cancer.A total of 164 patients with a BM ≥ 18.5 who underwent esophagectomy for cancer from July 2008 through March 2013 were enrolled. Patients were divided into 2 groups according to BMI: BMI5 (normal BMI group) and BM ≥ 25 (high BMI group). Further, the short- and long-term outcomes after esophagectomy were retrospectively analyzed.The median BMI was 21.6. The high BMI group (n=26) had significantly more histological adenocarcinomas than the normal BMI group (p=0.003). Other clinicopathological factors such as the type of surgery performed, R0 resections, and perioperative complications, were not influenced by the BMI. There were no significant differences between the 2 groups in the 3-year disease-free rates and 3-year overall survival rates.Esophagectomy for patients with a high BMI is acceptable based on the similar short- and long-term outcomes when compared with normal BMI patients.

A 63-year-old man was admitted to our hospital for treatment of cervical esophageal cancer and hepatocellular carcinoma. He had undergone subtotal esophagectomy for esophageal cancer and partial hepatectomy for hepatocellular carcinoma after preoperative chemotherapy and transcatheter arterial embolization (TAE). Histologically, esophageal cancer was diagnosed as pT3, pN2, M0, pStage III. Five months after surgery, a 2.2 cm tumor with abnormal uptake of fluorodeoxyglucose (FDG) was found in the upper mediastinum by positron emission tomography-computed tomography (PET-CT). To obtain a definitive diagnosis, we performed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on the mediastinal tumor. A tumefactive mucosal lesion was present in the main bronchus and the presence of a tumor was confirmed by ultrasonography. We diagnosed the lesion as a mediastinal recurrence of the primary esophageal cancer because squamous cell carcinoma was observed upon cytological examination. Chemoradiotherapy was performed for the mediastinal recurrence. EBUS-TBNA was useful for the diagnosis of metastases and recurrence of esophageal cancer in the mediastinum.

In advanced gastric cancer patients, preoperative multi detector row computed tomography (MDCT) often reveals abnormal ascites, which can indicate the possibility of peritoneal metastasis. The aim of this study was to clarify the clinical significance of preoperative ascites revealed by MDCT in gastric cancer patients. The study included a total of 183 advanced gastric cancer patients who underwent consecutive surgical procedures from February 2008 to November 2011. The results indicate that the presence of ascites on MDCT is significantly correlated with peritoneal metastasis (p.005), pathological T4 (p0.005), R1-R2 (p.01), and a positive diagnosis of peritoneal washing cytology(p.05). Multivariate analysis indicated that the presence of ascites on MDCT was an independent prognostic factor (hazard ratio[HR]2.6). In conclusion, the presence of ascites on preoperative MDCT is strongly associated with peritoneal metastasis, and might indicate the need for diagnostic laparoscopy to evaluate Stage IV factors and select the best treatment strategy.

The patient was a 48-year-old woman who was diagnosed with early gastric cancer during a long-term follow-up period for Gardner syndrome. Subtotal colectomy for colon leiomyoma was performed when the patient was 22 years old. Partial resection of the ileum was performed for ileum leiomyoma at the age of 27. Total resection of the remaining colon with ileostomy was performed for a pelvic desmoid tumor at the age of 40. In addition, resection of a desmoid tumor of the abdominal wall was performed 8 times in the 25 years since the first operation. During the follow-up for gastric polyps associated with Gardner syndrome, gastric cancer was detected from biopsy specimens of a wide range of the fundus polyps. Endoscopic resection was considered not to be applicable because of the extensive nature of the lesion. Total gastrectomy was also considered not to be applicable because of concerns about short bowel syndrome due to intestinal reconstruction. Therefore, proximal gastrectomy with esophagogastric anastomosis was performed. The pathological diagnosis was 0-IIa, 70 × 44 mm, tub1, m, ly0, v0, n0, PM (-), DM (-), stageIA. The postoperative course was uneventful, and the patient was discharged on postoperative day (POD) 16. We speculate that long-term survival of patients with Gardner syndrome without severe short bowel syndrome might result in carcinogenesis of gastric polyps.

The advent of new satellite missions, ground-based instrumentation networks, and the development of whole atmosphere models over the past decade resulted in a paradigm shift in understanding the variability of geospace, that is, the region of the atmosphere between the stratosphere and several thousand kilometers above ground where atmosphere-ionosphere-magnetosphere interactions occur. It has now been realized that conditions in geospace are linked strongly to terrestrial weather and climate below, contradicting previous textbook knowledge that the space weather of Earth's near space environment is driven by energy injections at high latitudes connected with magnetosphere-ionosphere coupling and solar radiation variation at extreme ultraviolet wavelengths alone. The primary mechanism through which energy and momentum are transferred from the lower atmosphere is through the generation, propagation, and dissipation of atmospheric waves over a wide range of spatial and temporal scales including electrodynamic coupling through dynamo processes and plasma bubble seeding. The main task of Task Group 4 of SCOSTEP's CAWSES-II program, 2009 to 2013, was to study the geospace response to waves generated by meteorological events, their interaction with the mean flow, and their impact on the ionosphere and their relation to competing thermospheric disturbances generated by energy inputs from above, such as auroral processes at high latitudes. This paper reviews the progress made during the CAWSES-II time period, emphasizing the role of gravity waves, planetary waves and tides, and their ionospheric impacts. Specific campaign contributions from Task Group 4 are highlighted, and future research directions are discussed.