Retrograde transvenous obliteration for the prevention of variceal rebleeding in patients with hepatocellular carcinoma: a multicentre retrospective study.

AIM: To evaluate the effectiveness and safety of retrograde transvenous obliteration (RTO) for the prevention of variceal rebleeding variceal rebleeding in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This multicentre retrospective study enrolled 79 patients with HCC who underwent RTO for the prevention of variceal rebleeding. Successful occlusion of the gastrorenal shunt and obliteration of the gastric varices were achieved in 74 patients, with a technical success rate of 93.7%. Of the remaining 74 patients (mean age, 64.9±10.3 years; 56 men), 66 (90.4%) had gastroesophageal varices and seven (9.6%) had isolated gastric varices. Thirty-two patients (43.8%) underwent balloon-occluded RTO, 40 patients (54.8%) underwent plug-assisted RTO, and one patient (1.4%) underwent coil-assisted RTO. No patients had major procedural complications. RESULTS: Rebleeding occurred in seven patients (9.6%) during the follow-up period. The 6-week and 1-year actuarial probabilities of patients remaining free of rebleeding were 90.8±3.6% and 88.6±4.1%, respectively. The median survival was 12.6 (95% confidence interval [CI] 8-17.3) months. The 6-week, 1-year, and 3-year actuarial probabilities of survival were 83.2±4.4%, 51.1±6.6%, and 32.7±7%, respectively. New or worsening ascites and oesophageal varices occurred in 12 (16.4%) and 13 patients (17.8%), respectively, during the follow-up period. Overt hepatic encephalopathy occurred in one patient (1.4%) during the follow-up period. The Child-Pugh score remained comparable to that at baseline at 1 and 3 months. CONCLUSION: RTO was effective and safe in preventing variceal rebleeding in patients with HCC.

Dynamic assembly of liquid crystalline graphene oxide gel fibers for ion transport.

Colloidal dispersions with liquid crystallinity hold great promise for fabricating their superstructures. As an example, when graphene oxide (GO) sheets are assembled in the liquid crystalline state, they can turn into ordered macroscopic forms of GO such as fibers via the wet spinning process. Here, we report that by reinforcing intersheet interactions, GO liquid crystals (LCs) turn into mechanically robust hydrogels that can be readily drawn into highly aligned fibrillar structures. GO hydrogel fibers with highly aligned sheets (orientation factor, f = 0.71) exhibit more than twice the ionic conductivity compared to those with partially aligned structures (f = 0.01). The hierarchically interconnected two-dimensional nanochannels within these neatly aligned GOLC hydrogel fibers may facilitate controlled transport of charge carriers and could be potentially explored as cables for interconnecting biosystems and/or human-made devices.

High fibrin/fibrinogen degradation product to fibrinogen ratio is associated with 28-day mortality and massive transfusion in severe trauma.

PURPOSE: There is a lack of association between coagulation biomarkers and long-term mortality in severe trauma. We aimed to investigate the association between coagulation biomarkers on admission and outcome of late stage of trauma. METHODS: This retrospective observational study included patients admitted with severe trauma between 2012 and 2015. We used the area under the receiver operating characteristic curve (AUROC) of coagulation biomarkers to determine 28-day mortality. Head Abbreviated Injury Scale scores greater than 3 were defined as traumatic brain injury (TBI). The primary outcome was 28-day mortality and the secondary outcome was massive transfusion. RESULTS: Of the 1266 patients included in the study, 28-day mortality rate was 19.7% (n = 249) and 7.9% (n = 100) of patients received massive transfusion. The AUROC of fibrin/fibrinogen degradation product (FDP) to fibrinogen ratio had a significantly higher prognostic performance than other markers. Multivariate analysis revealed that D-dimer level [odds ratio (OR) 1.033; 95% confidence interval (CI) 1.016-1.051] and FDP/fibrinogen ratio (OR 1.007; 95% CI 1.001-1.013) were independently associated with 28-day mortality. D-dimer (OR 1.028; 95% CI 1.003-1.055) and FDP/fibrinogen ratio (OR 1.035; 95% CI 1.012-1.058) were associated with 28-day mortality in the TBI group. In the non-TBI group, D-dimer was associated with 28-day mortality (OR 1.033; 95% CI 1.008-1.059), but the FDP/fibrinogen ratio was not. FDP/fibrinogen ratio, not D-dimer level, was an independent predictor for massive transfusion (OR 1.005; 95% CI 1.001-1.010). CONCLUSIONS: High FDP/fibrinogen ratio on arrival is a predictor of 28-day mortality and the requirement for massive transfusion in severe trauma.

Influence of a ring-shaped pump beam on temperature distribution and thermal lensing in end-pumped solid state lasers.

A simple method for reducing thermal lensing in an end-pumped solid state laser using a ring-shaped pump beam is reported. Analytical expressions for the temperature distribution and the thermal lensing focal length in a laser medium end-pumped by a beam with a ring-shaped intensity profile are derived. The results indicate that thermal effects including thermal lensing can be significantly reduced due to a more uniform temperature distribution. This approach has been applied to a Nd:YVO4 amplifier operating at 1064 nm confirming that the brightness of the output beam can be remarkably improved at high power levels due to the better beam quality for the ring-shaped pumping compared to the conventional quasi-top-hat pumping. The prospects for power scaling and further improvement in laser performance will be discussed.

Locoregional relapse after gastrectomy with D2 lymphadenectomy for gastric cancer.

BACKGROUND: Risk for and site of locoregional relapse have not been well studied in patients undergoing gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: Patients who had undergone gastrectomy with D2 lymphadenectomy for gastric cancer between 2004 and 2007 were identified from an institutional database. The locoregional relapse rate was estimated by competing risk analysis, and risk groups were derived according to locoregional relapse risk using recursive partitioning analysis (RPA). The locations of nodal relapses were evaluated according to Japanese Classification of Gastric Carcinoma criteria. RESULTS: Some 2618 patients were included. With a median follow-up of 78·0 (range 28·5-122·6) months, relapse was diagnosed in 471 of 2618 patients (18·0 per cent). The cumulative incidence of locoregional relapse at 5 years was 8·5 (95 per cent c.i. 7·4 to 9·6) per cent. The 5-year locoregional recurrence rates for high-risk (N3), intermediate-risk (N1-2) and low-risk (N0) groups were 32·4, 12·3 and 1·7 per cent respectively (P < 0·001). Among patients with regional relapse, 90·4 per cent had involvement outside the D2 dissected area, and the most commonly involved site was station 16b1. This pattern was maintained in the RPA risk groups (P = 0·329). CONCLUSION: Locoregional relapse at 5 years after gastrectomy with D2 lymphadenectomy was 8·5 per cent, and was most often seen outside the D2 dissected area.

Aminophylline Effect on Renal Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Aminophylline increases the intracellular concentration of cAMP and exerts an anti-inflammatory effect. The aim of this study was to investigate the effect of aminophylline on renal ischemia-reperfusion (I/R) injury in mice. METHODS: Thirty C57BL/6 mice were divided into 3 groups. In the sham group (group S, n = 10), only right nephrectomy was performed. In the control group (group C, n = 10), after right nephrectomy, the mice were subjected to 30 minutes of left renal ischemia. In the aminophylline group (group A, n = 10), an intraperitoneal injection of aminophylline (5 mg/kg) was performed before renal ischemia. Twenty-four hours after reperfusion, the mice were euthanized, and plasma and kidney samples were obtained to analyze the serum creatinine, renal histology, and expression levels of nuclear factor-kappa B (NF-kB) and pro-inflammatory cytokines. RESULTS: The serum creatinine concentration in group C was markedly elevated at 24 hours after reperfusion. Aminophylline treatment significantly reduced serum creatinine, compared with group C. Aminophylline also reduced the histological evidence of renal damage. The expression levels of NF-kB, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and intercellular adhesion molecule-1 (ICAM-1) mRNA were significantly increased in group C (P < .001). Group A showed lower expression of NF-kB, TNF-α, MCP-1, MIP-2, and ICAM-1 mRNA than group C (P < .01). CONCLUSIONS: Aminophylline treatment improved the renal function and indexes of renal inflammation, which suggests that it provided reno-protection against renal I/R injury.

Speciation is not necessarily easier in species with sexually monomorphic mating signals.

Should we have different expectations regarding the likelihood and pace of speciation by sexual selection when considering species with sexually monomorphic mating signals? Two conditions that can facilitate rapid species divergence are Felsenstein's one-allele mechanism and a genetic architecture that includes a genetic association between signal and preference loci. In sexually monomorphic species, the former can manifest in the form of mate choice based on phenotype matching. The latter can be promoted by selection acting upon genetic loci for divergent signals and preferences expressed simultaneously in each individual, rather than acting separately on signal loci in males and preference loci in females. Both sexes in the Chrysoperla carnea group of green lacewings (Insecta, Neuroptera, Chrysopidae) produce sexually monomorphic species-specific mating signals. We hybridized the two species C. agilis and C. carnea to test for evidence of these speciation-facilitating conditions. Hybrid signals were more complex than the parents and we observed a dominant influence of C. carnea. We found a dominant influence of C. agilis on preferences in the form of hybrid discrimination against C. carnea. Preferences in hybrids followed patterns predicting preference loci that determine mate choice rather than a one-allele mechanism. The genetic association between signal and preference we detected in the segregating hybrid crosses indicates that speciation in these species with sexually monomorphic mating signals can have occurred rapidly. However, we need additional evidence to determine whether such genetic associations form more readily in sexually monomorphic species compared to dimorphic species and consequently facilitate speciation.

A multiple-channel, multiple-assay platform for characterization of full-range shear stress effects on vascular endothelial cells.

Vascular endothelial cells (VECs), which line blood vessels and are key to understanding pathologies and treatments of various diseases, experience highly variable wall shear stress (WSS) in vivo (1-60 dyn cm(-2)), imposing numerous effects on physiological and morphological functions. Previous flow-based systems for studying these effects have been limited in range, and comprehensive information on VEC functions at the full spectrum of WSS has not been available yet. To allow rapid characterization of WSS effects, we developed the first multiple channel microfluidic platform that enables a wide range (~15×) of homogeneous WSS conditions while simultaneously allowing trans-monolayer assays, such as permeability and trans-endothelial electrical resistance (TEER) assays, as well as cell morphometry and protein expression assays. Flow velocity/WSS distributions between channels were predicted with COMSOL simulations and verified by measurement using an integrated microflow sensor array. Biomechanical responses of the brain microvascular endothelial cell line bEnd.3 to the full natural spectrum of WSS were investigated with the platform. Under increasing WSS conditions ranging from 0 to 86 dyn cm(-2), (1) permeabilities of FITC-conjugated dextran and propidium iodide decreased, respectively, at rates of 4.06 × 10(-8) and 6.04 × 10(-8) cm s(-1) per dyn cm(-2); (2) TEER increased at a rate of 0.8 Ω cm(2) per dyn cm(-2); (3) increased alignment of cells along the flow direction under increasing WSS conditions; and finally (4) increased protein expression of both the tight junction component ZO-1 (~5×) and the efflux transporter P-gp (~6×) was observed at 86 dyn cm(-2) compared to static controls via western blot. We conclude that the presented microfluidic platform is a valid approach for comprehensively assaying cell responses to fluidic WSS.

The heart-rate-reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain.

BACKGROUND: Peripheral nerve injury increases the excitability of primary sensory neurons. This triggers the onset of neuropathic pain and maintains its persistence. Because changes in hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are implicated in this process, we examined the action of the heart-rate-reducing agent, ivabradine, a clinically approved HCN blocker, in the rat chronic constriction injury (CCI) model of neuropathic pain. METHODS: The effects of ivabradine on mechanical allodynia were assessed using von Frey filaments, and the effects on cardiovascular parameters were monitored by telemetry. Ivabradine block of HCN channels in dorsal root ganglion neurons was confirmed by whole-cell recording. RESULTS: In rats subject to CCI, ivabradine (6 mg/kg by gavage twice a day) significantly reduced mechanical allodynia. Cumulative effects were seen with twice daily oral administration over a 4-day period. Allodynia returned 4 days after the final drug dose. Mean arterial pressure was maintained and only a 15% pharmacological reduction in heart rate was observed. There was no cumulative effect of ivabradine on cardiovascular parameters. CONCLUSION: Because ivabradine is effective at an oral dose that produces only moderate pharmacological heart rate reduction, and this is known to be well tolerated in a clinical context, these results underline its possible use in neuropathic pain management.

Risk factors for double primary malignancies and their clinical implications in patients with sporadic gastric cancer.

AIMS: We carried out a large scale study to identify the risk factors for double primary malignancy (DPM) development in gastric cancer patients and to evaluate the clinical implications for these patients. METHODS: A total of 2593 patients who underwent gastrectomy for primary gastric cancer from January 2005 to November 2010 were reviewed with regard to DPM. We compared the clinicopathological characteristics, risk factors for developing DPM, and prognosis between the DPM+ group and the DPM- group. RESULTS: Of the 2593 patients, 152 (5.9%) were diagnosed with DPM. The most common accompanying malignancies were colorectal, lung and thyroid. Multivariate analysis indicated that age (p = 0.016) and MSI status (p = 0.002) were associated with a higher frequency of DPM. 30.3% of patients were diagnosed with DPM within 1 year around perioperative period and 53.3% of patients had DPM detected during 5 years of post-operative follow up periods. Although there was no significant difference in overall survival between the DPM+ and DPM- group, DPM+ patients had a worse prognosis than DPM- patients in stage I gastric cancer. CONCLUSIONS: Gastric cancer patients over the age of 60 or with a MSI-high status had an increased risk for developing DPM. Further, in stage I gastric cancer, the presence of DPM was associated with a worse prognosis. Therefore, careful pre- and postoperative surveillance is especially important in these patients.

Minimally invasive surgery for serosa-positive gastric cancer (pT4a) in patients with preoperative diagnosis of cancer without serosal invasion.

BACKGROUND: Although surgeons normally use minimally invasive surgery (MIS) for patients with early gastric cancer, in Korea and Japan the procedure is also indicated for serosa-negative tumors. Serosal invasion is regarded to be a potential risk factor for peritoneal dissemination as a result of the effect of pneumoperitoneum and tumor manipulation during the operation. We compared operative outcomes between MIS and conventional open surgery for serosa-involved advanced gastric cancer patients who had a preoperative diagnosis of cancer without serosal invasion. METHODS: A total of 61 patients (39 patients treated by MIS and 22 by open surgery) treated between 2003 and 2009 who were first diagnosed preoperatively as serosa negative on the basis of computed tomography, endoscopy, and endoscopic ultrasound but then diagnosed as serosa positive upon final pathology were studied. We retrospectively compared recurrence and survival between the two treatment groups. RESULTS: Clinicopathologic characteristics, clinical stage, extent of surgery, and short-term operative outcome did not differ between the groups. 5-year overall survival (73.5 vs. 67.5 %, p = 0.518, respectively) and disease-free survival (67.8 vs. 54.2 %, p = 0.296, respectively) were comparable between the MIS and open surgery groups. There were recurrences in 12 patients in the MIS group and 11 patients in the open surgery group, with a median follow-up period of 64 months. Recurrence patterns did not differ between the groups; moreover, MIS did not increase peritoneal recurrences compared to open surgery (42.0 vs. 54.5 %, p = 0.537, respectively). In multivariate analyses, the type of surgery was not an independent prognostic factor. CONCLUSIONS: Similar survival and recurrence patterns were observed in advanced gastric cancer patients preoperatively diagnosed as serosa negative who were treated either by MIS or open surgery. MIS may be safely applied in patients with serosa-positive tumors.

Beneficial effects of judo training on bone mineral density of high-school boys in Korea.

Bone mineralization is strongly stimulated by weight-bearing exercise during growth and development. Judo, an Olympic combat sport, is a well-known form of strenuous and weight-bearing physical activity. Therefore, the primary goal of this study was to determine the effects of Judo practice on the bone health of male high school students in Korea. The secondary goal of this study was to measure and compare the bone mineral density (BMD) of the hands of Judo players and sedentary control subjects. Thirty Judo players (JDP) and 30 sedentary high school boys (CON) voluntarily participated in the present study, and all of the sedentary control subjects were individually matched to the Judo players by body weight. BMD was determined by using dual-energy X-ray absorptiometry (Hologic, Bedford, MA, USA). The lumbar spine, femur and forearm BMD in the JDP group were significantly greater by 22.7%, 24.5%, and 18.3%, respectively, than those in the CON group. In addition, a significant difference in the CON group was observed between the dominant hand (DH) radius (0.710 ± 0.074 g/cm(2)) and the non-dominant hand (NDH) radius (0.683 ± 0.072 g/cm(2)), but this was not observed in the JDP group (DH = 0.819 ± 0.055 g/cm(2); NDH = 810 ± 0.066 g/cm(2)) (P < 0.05). Therefore, the results of this study suggest that Judo practice during the growth period significantly improves bone health in high school male students. In addition, it seems that Judo practice could eliminate the effect of increased BMD in the dominant hand.

Spontaneous resolution of acute T cell-mediated rejection in a renal transplant patient.

This case report presents spontaneous resolution of acute rejection in a 66-year-old man who underwent a kidney transplant and developed acute rejection and pneumonia. Our main concern in this case was how to treat the concurrent infection while maintaining the immunosuppressive therapy with a narrow available therapeutic range, in order to save the renal allograft without increasing antirejection therapy.

Major early complications following open, laparoscopic and robotic gastrectomy.

BACKGROUND: Laparoscopic and robotic gastrectomy have been adopted rapidly despite lack of evidence concerning technical safety and controversy regarding additional benefits. This study aimed to compare clinically relevant complications after open, laparoscopic and robotic gastrectomy. METHODS: This was a retrospective analysis of prospectively collected data on surgical complications in patients undergoing gastrectomy with curative intent for histologically proven adenocarcinoma between 2005 and 2010 at the Department of Surgery, Yonsei University College of Medicine in Seoul, Korea. Complications were categorized into wound infection, bleeding, anastomotic leak, obstruction, fluid collection and other. RESULTS: In a total of 5839 patients (4542 open, 861 laparoscopic and 436 robotic gastrectomies), overall complication, reoperation and mortality rates were 10·5, 1·0 and 0·4 per cent respectively. There were no significant differences between the three groups. Ileus (P = 0·001) and intra-abdominal fluid collections (P = 0·013) were commoner after conventional open surgery. However, tumour stage was higher and more complex resections were performed in the open group. Anastomotic leak, the leading cause of death, occurred more often after a minimally invasive approach (P = 0·017). CONCLUSION: Laparoscopic and robotic gastrectomy had overall complication and mortality rates similar to those of open surgery, but anastomotic leaks were more common with the minimally invasive techniques.

Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer.

BACKGROUND: Thrombocytosis has been associated with malignancies and poor prognostic implications in cancer patients. In the present study the prognostic significance of pretreatment platelet (PLT) level was assessed with regard to recurrence and survival in patients with primary gastric adenocarcinoma. METHODS: The authors reviewed the prospective data of 1593 gastric cancer patients who received curative gastrectomy with extended lymphadenectomy. The correlations of PLT level with recurrence and overall survival were evaluated by both univariate and multivariate analyses. RESULTS: Thrombocytosis (≥ 40 × 10(4)/ µL), present in 6.4% of the patients prior to curative surgery, was more frequently associated with advanced T and N classification, larger tumor size, anemia, and leukocytosis (p < 0.05). In patients with pretreatment thrombocytosis compared to those without it, five-year survival rate was worse (56.9% vs. 65.5%; p = 0.043), and recurrence rate was higher mainly due to the frequent hematogenous spread (51.0% vs. 34.5%; p < 0.001). Furthermore, risk of blood-borne metastasis was almost three-fold higher in patients with pretreatment thrombocytosis (Odds ratio 2.83 [95% CI 1.67-4.77], p < 0.001). CONCLUSIONS: Pretreatment thrombocytosis correlated significantly with poor prognosis and can be used as an independent predictor of recurrence by blood-borne metastasis in gastric cancer.

External validation of nomogram for the prediction of recurrence after curative resection in early gastric cancer.

BACKGROUND: Nomograms are statistics-based tools that provide the overall probability of a specific outcome. In our previous study, we developed a nomogram that predicts recurrence of early gastric cancer (EGC) after curative resection. We carried out this study to externally validate our EGC nomogram. PATIENTS AND METHODS: The EGC nomogram was established from a retrospective EGC database that included 2923 consecutive patients. This nomogram was independently externally validated for a cohort of 1058 consecutive patients. For the EGC nomogram validation, we assessed both discrimination and calibration. RESULTS: Within the follow-up period (median 37 months), a total of 11 patients (1.1%) experienced recurrence. The concordance index (c-index) was 0.7 (P = 0.02) and the result of the overall C index was 0.82 [P = 0.006, 95% confidence interval (CI) 0.59-1.00]. The goodness of fit test showed that the EGC nomogram had significantly good fit for 1- and 2-year survival intervals (P = 0.998 and 0.879, respectively). The actual and predicted survival outcomes showed good agreement, suggesting that the survival predictions from the nomogram are well calibrated externally. CONCLUSIONS: A preexisting nomogram for predicting disease-free survival (DFS) of EGC after surgery was externally validated. The nomogram is useful for accurate and individual prediction of DFS, patient prognostication, counseling, and follow-up planning.

The effect of green tea polyphenols on macrophage migration inhibitory factor-associated steroid resistance.

BACKGROUND: Recently, evidence has been obtained to suggest that inflammation is provoked through upregulation of macrophage migration inhibitory factor (MIF) expression by steroids. However, little is known regarding the effect of steroids on MIF expression in human keratinocytes and the counter-effect of epigallocatechin-3-gallate (EGCG), a member of the class of green tea polyphenols. OBJECTIVES: We determined whether or not steroids cause the upregulation of MIF in human keratinocytes, and if so, whether or not EGCG suppresses MIF upregulation in keratinocytes by steroids. We then assessed the effects of EGCG on MIF-induced Th-related chemokine and cytokine expression in keratinocytes. METHODS: HaCaT keratinocytes were first treated with dexamethasone in the presence or absence of EGCG in the culture medium. The keratinocytes were then treated with recombinant human (rh)-MIF in the presence or absence of EGCG in the culture medium. The expression of mRNA and protein in Th-related cytokines and chemokines, including MIF in the keratinocytes, was measured by real-time reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. RESULTS: Dexamethasone significantly enhanced MIF expression in human keratinocytes, and EGCG significantly downregulated the expression of dexamethasone-induced MIF. EGCG also significantly downregulated rh-MIF-induced expression of Th-related cytokines and chemokines, such as interleukin (IL)-6, IL-18, transforming growth factor-ß, CCL17, CCL22 and CXCL10, in human keratinocytes. CONCLUSIONS: These results demonstrated that EGCG may have a novel pharmacological effect to prevent steroid-induced tachyphylaxis and inflammation by suppressing the expression of MIF in human keratinocytes.

Detection of antigenic proteins expressed by lymphocystis virus as vaccine candidates in olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

Although the major capsid proteins (MCPs) of lymphocystis disease virus (LCDV) have been characterized, little is known about the host-derived immune response to MCPs and other LCDV antigenic proteins. To identify antigenic proteins of LCDV that could be used as vaccine candidates in olive flounder, Paralichthys olivaceus, we analysed the viral proteins responsible for its virulence by applying immuno-proteomics. LCDV proteins were separated by one-dimensional gel electrophoresis, transferred to polyvinylidene difluoride membrane, and probed with homogeneous P. olivaceus antisera elicited by LCDV natural infection and vaccination with formalin-killed LCDV. Four immune-reactive proteins were obtained at 68-, 51-, 41- and 21 kDa using antisera collected from natural infection while two proteins at 51- and 21 kDa exhibited response to antisera from vaccinated fish, indicating that the latter two proteins have vaccine potential. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray MS/MS, the 51 and 21 kDa proteins were identified as MCP and an unknown protein, respectively.

Relevance of lymph node metastasis along the superior mesenteric vein in gastric cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of lymph node metastasis along the superior mesenteric vein (station 14v) to determine the need for 14v dissection in gastric cancer surgery. METHODS: A total of 1104 patients with gastric cancer who underwent gastrectomy including 14v dissection were enrolled. Patients were categorized into two groups: those with and those without 14v lymph node involvement by metastasis. RESULTS: Of the total study population, 73 patients (6·6 per cent) had 14v-positive gastric cancer. These patients were more likely to have advanced tumour (T), node (N) and distant metastatic (M) status, and histologically undifferentiated gastric cancers. The 3- and 5-year survival rates of patients with 14v-positive disease were 24 and 9 per cent respectively. Survival in this group was similar to that of patients who had gastric cancer with distant metastasis (M1). Multivariable analysis demonstrated that 14v status was a significant prognostic factor for gastric cancer (hazard ratio 2·13; P < 0·001). After histologically complete (R0) resection, the overall survival of 14v-positive patients with any stage of cancer was significantly worse than that for 14v-negative patients with stage IV cancer (P = 0·006). CONCLUSION: 14v status is an independent prognostic factor for gastric cancer, with 14v-positive gastric cancer having a poor prognosis, similar to that of M1 disease. The exclusion of 14v in regional lymph node dissection should be considered.

Mesolimbic dopaminergic activity responding to acute stress is blunted in adolescent rats that experienced neonatal maternal separation.

Neonatal maternal separation (MS), stressful experience early in life, leads to the development of depression-like behaviors in the offspring later in life. This study was conducted to define the neural basis of depression-like behaviors observed in our MS model. Sprague-Dawley pups were separated from dam for 3 h daily during the first 2 weeks of birth (MS) or left undisturbed (NH). All pups were sacrificed on postnatal day 41 with/without 1 h of restraint stress. Restraint stress significantly increased c-Fos expression in the nucleus accumbens (NAcb) of NH pups, but not in MS. In NH pups, restraint stress increased dopamine levels not only in the NAcb but also in the midbrain dopamine neurons; however, these increases were not observed in MS. Gene expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) was increased by acute restraint in NH pups, but not in MS pups. The raphe serotonin level was lower in MS than in NH, and not significantly changed by acute restraint neither in NH nor in MS. Results reveal that experience of neonatal MS may lead to a long-term suppression in the mesolimbic dopamine system of the offspring later in life, in which an epigenetic control may be implicated, such as suppressed gene expression of TH in the midbrain. We conclude that a decreased activity of the mesolimbic dopamine system may play a role in the pathophysiology of depression-like behaviors by neonatal MS, in addition to a decreased serotonin level in the raphe nucleus.