Proposing a common platform of shipping cost analysis of the Northern Sea Route and the Suez Canal Route

Maritime trade between East Asia and Northwest Europe using the Northern Sea Route (NSR) has been recently increasing, because ship operators may take advantage of the shorter sailing distance of NSR whose navigable season has become longer because of retreating Arctic sea ice. As Arctic sea ice continues to retreat because of global warming, the NSR is now approximately 40 per cent shorter than the Suez Canal Route (SCR) for such trade. In 2013, shipping on the NSR marked a record 10 year-high volume of 1.36 million tons with 71 voyages. Accordingly, comparative analyses of estimated shipping cost via the NSR and the alternative conventional routes, especially the SCR, have been carried out. Furthermore, NSR/SCR-combined shipping, that is, when a vessel transits the NSR during the warmer months and the SCR in the colder months, has already been proposed as a realistic scenario for Arctic shipping in the previous studies. Since assumptions used in the cost estimations vary among the studies, as discussed by Lasserre, there remain some difficulties when comparing estimated shipping costs. This study aims at establishing a common platform of a wide range of cost estimation assumptions, through clarifying and analysing the cost components contained in the current literature. In addition, interviews with NSR shipping professionals were conducted concerning the NSR fee on an unofficial basis, since typically such fees are determined based on negotiations between ice breaker escort service provider and shipping company. An empirical analysis revealed that NSR/SCR-combined shipping of container cargo between East Asia and Northwest Europe can be commercially feasible

Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors

The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained

Correlations between Extranodal Metastasis and Prognosis in Patients with Squamous Cell Carcinoma of the Esophagus

Background Extranodal metastasis (EM) has been reported in carcinomas of many organs. However, the clinicopathological significance of EM in squamous cell carcinoma of the esophagus remains unclear, and this study sought to clarify this issue. MethodsThis study included 220 patients who underwent an esophagectomy with lymphadenectomy for primary esophageal carcinoma from 1996 to 2008. EM was defined as the presence of cancer cells in the soft tissue that were discontinuous with the primary lesion, or in the perinodal soft tissue distinct from the lymph nodes. Results EM was detected in 25 (9.6%) of the 220 patients, and in 56 (0.7%) of the 8,186 nodules retrieved as ‘lymph nodes’. The incidence of EM was significantly higher in patients who had tumors of a larger size (diameter ≥ 4 cm), lymphatic vessel invasion, lymph node metastasis, a high pathological stage, infiltrative growth pattern, or a high pT-stage. The 5-year overall survival rates in N0-1 patients with EM were significantly lower than in the patients without EM (P = 0.005). Conclusion EM is closely associated with the development and aggressiveness of esophageal carcinoma, and the presence of EM can be useful for predicting prognosis after surgery in N0-1esophageal carcinoma patients

Prognostic Factors for Recurrence after Tegafur-uracil Plus Leucovorin Adjuvant Chemotherapy in Patients with Colorectal Cancer

To evaluate prognostic factors for recurrence after tegafur-uracil plus leucovorin (UFT/LV) adjuvant chemotherapy in patients with colorectal cancer (CRC). Consecutive patients with CRC who received UFT/LV as adjuvant chemotherapy at Showa University Hospital between June 2005 and December 2008 were included in the study, 5-year disease-free survival (DFS) and overall survival (OS) rates were estimated, and prognostic factors for recurrence were analyzed using the Cox proportional hazards model for multivariate analysis. Of 92 patients included in the study, 17 (18.5%) had disease recurrence. The 5-year DFS and OS rates were 82.2% and 91.9%, respectively. In the multivariate analysis, preoperative CA19-9 level＞37U/ml, emergency operation, and T4 lesions were independent significant prognostic factors after treatment with UFT/LV adjuvant chemotherapy. The three independent prognostic factors —T4 lesions, emergency operation, and high preoperative CA19-9 levels— may be useful for decision-making regarding whether patients should receive 5-fluouracil-based or L-oxaliplatin-based adjuvant chemotherapy. As this was a single-institution study with a small number of patients, our findings need to be confirmed in larger multicenter studies

Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

SummaryPrenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running

Efficiency of Incentive Spirometry for Video-Assisted Thoracoscopic Surgery for Esophagectomy

Transthoracic subtotal esophagectomy for esophageal cancer is a highly invasive procedure, associated with high mortality and morbidity rates. We examined the use of video-assisted thoracoscopic and laparoscopic surgery for esophagectomy (VATS-E). Further, incentive spirometry (IS) is commonly used in perioperative rehabilitation for esophagectomy. We investigated whether pulmonary complications after VATS-E are related to changes in the perioperative IS volumes and whether such changes could be predictive of these complications. This study included 63 patients who underwent VATS-E from June 2008 to December 2009. IS volumes before and after surgery were recorded for all patients. The perioperative IS volumes and clinicopathological factors were correlated with the incidence of postoperative pneumonia and atelectasis. Nine patients (14.5%) had postoperative pneumonia, and thirteen (22.2%) had atelectasis. Univariate analysis showed an increased risk of atelectasis in patients with diabetes and an increased risk of pneumonia in patients with a long operating time and for whom the lung was adhered to the thoracic wall. The vital capacity (VC) correlation coefficient was 0.674. Further, the risk of pneumonia was high in patients with 13% less than the minimum IS volume/preoperative VC ratio and 22% with less than the average IS volume/preoperative VC ratio. Multivariate regression models for pneumonia showed the same results regarding the IS volume/VC ratio. The results indicated that IS volumes could be used to predict the incidence of complications after VATS-E, and thereby facilitate early application of interventions to prevent pulmonary complications

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes

Effect of Preoperative Carbohydrate and Amino Acid Infusion on Postoperative Counter-Regulatory Hormone in Patients Undergoing Elective Thoracoscopic Esophagectomy

Compared with the conventional open surgery, thoracoscopic esophagectomy results in decreased thorax destruction, fewer postoperative complications, and shorter hospitalisation. However, preoperative fasting causes hyperglycemia, prompting attempts to improve postoperative hyperglycemia by preoperatively administering carbohydrate orally or intravenously. Herein, we examined the effect of preoperative carbohydrate and amino acid infusion on counter-regulatory hormone levels in patients undergoing elective thoracoscopic esophagectomy. The glucose and amino acid (GA) group (n=12) were infused with a low concentration of sugar accelerant and amino acid, and the control (GAF) group (n=12) was infused with a sugar-free extracellular fluid, until entering the operating room. We evaluated plasma catecholamine 3 fractions, cortisol, and glucose, as well as 3-methylhistidine in the urine. Adrenaline levels were significantly higher in the GAF group (263.0±201.8µIU/ml) than in the GA group (114.7±127.0µIU/ml) at the end of the surgery (P=0.042), and at postoperative day (POD) 1 (200.8±137.4 vs. 80.5±64.3µIU/ml; P=0.013). The noradrenalin level was also significantly higher in the GAF group (517.9±523.6µIU/ml) than in the GA group (254.3±205.4µIU/ml) at POD1 (P=0.028), as was the cortisol level (20.0±10.6µIU/ml vs. 10.2±8.0µIU/ml; P=0.015). No significant differences were observed between the two groups in levels of blood glucose or 3-methylhistidine in the urine. Preoperative glucose-amino acid administration improved catabolism suppression in this study

Advantage of Long Ileus-tube Placement by Gastrostomy for Treating Patients with Refractory Intestinal Obstruction

Maintaining a long transnasal ileus tube for a long period can be quite painful for patients such as in those with refractory intestinal obstruction and peritonitis carcinomatosa and it can markedly decrease quality of life (QOL) due to unexpected respiratory complications associated with the tube placement. To mitigate such complications, we undertook a trial insertion of a long ileus tube by gastrostomy in five patients with refractory intestinal obstruction (four cases of peritonitis carcinomatosa and one case of chronic intestinal pseudo-obstruction). We inserted the transgastric ileus tube using a percutaneous gastrostomy catheter kit after puncture with a plastic skin (PS) needle covered with a protective sheath, and then endoscopically placed the tube beyond the ligament of Treitz. Subsequently, we removed the long transnasal ileus tube, and comparable decompression was achieved. In all cases, the entire procedure was easily performed with no complications. Moreover, patients experienced reduced pain and stress and they were able to regain some freedom during activity

Clinicopathological Significance of FOXP3 Expression in Esophageal Squamous Cell Carcinoma

The expression of transcription factor forkhead box protein 3 (FOXP3), a master control gene for regulatory T cells, has been reported to influence patient survival. However, there have been few reports of the relationship between FOXP3 positive cells and esophageal squamous cell carcinoma (ESCC). The aim of this study was to clarify the prognostic value of FOXP3 expression in ESCC. Ninety-five patients who were diagnosed with primary ESCC and underwent subtotal esophagectomy during 2009 and 2010 were retrospectively analyzed. Deepest sections from each tumor were selected for immunohistochemistry and the number of FOXP3 positive cells was counted. The median number was used as a cutoff to divide into FOXP3 positive and FOXP3 negative subgroups. Relationships between FOXP3 expression and clinicopathological features, disease-free survival (DFS) and overall survival (OS) were determined. Statistical values of p < 0.05 were considered significant. FOXP3 positive cells were found in all 95 cases and the number of FOXP3 positive cells was significantly higher in the peri-tumor compartment than in the intra-tumor compartment (p = 0.0006). For this reason, the peri-tumor compartment numbers were used for all of the association studies. Results showed that the FOXP3 positive group had a significantly larger mean tumor size (43.8 ± 4.1mm vs 29.1 ± 4.0mm, p = 0.0055), and the FOXP3 negative group had a significantly higher percentage of deep invasion (T2, T3, T4)(p = 0.0399). There was no significant association for DFS, however, for OS the FOXP3 positive group demonstrated a significantly better prognosis (p = 0.0024). Multivariate analysis showed that peri-tumor FOXP3 expression is an independent prognostic factor for OS (p = 0.0035). Peri-tumoral FOXP3 expression is an independent and favorable prognostic factor for ESCC