Determination of the safety of Halomonas sp. KM-1-derived d-ß-hydroxybutyric acid and its fermentation-derived impurities in mice and Japanese adults.

The use of halophilic bacteria in industrial chemical and food production has received great interest because of the unique properties of these bacteria; however, their safety remains under investigation. Halomonas sp. KM-1 intracellularly stores poly-D-ß-hydroxybutyric acid under aerobic conditions and successively secretes D-ß-hydroxybutyric acid (D-BHB) under microaerobic conditions. Therefore, we tested the safety of Halomonas sp. KM-1-derived D-BHB and the impurities generated during D-BHB manufacturing at a 100-fold increased concentration in acute tests using mice and daily intake of 16.0 g D-BHB in Japanese adults for 12 weeks. In the mice test, there were no abnormalities in the body weights or health of mice fed the purified D-BHB or its impurities. In the Japanese adult test, blood parameters and body condition showed no medically problematic fluctuations. These findings indicate that Halomonas sp. KM-1 is safe and can be used for commercial production of D-BHB and its derivatives.

[A Case of Advanced Esophageal Cancer with pCR after Preoperative DCF Chemotherapy].

The patient is a man in his 60s. The patient was diagnosed with advanced esophageal cancer(cT3N0M0, cStage Ⅱ)and was treated with 2 courses of docetaxel/cisplatin/5-FU(DCF)combination as preoperative chemotherapy. On imaging, the tumor was markedly reduced. Adverse events were febrile neutropenia in the first course, neutropenia Grade 3 and vasculitis Grade 1 in the second course. We performed thoracoscopic subtotal esophagectomy and gastric tube reconstruction with lymphadenectomy. The histopathological findings showed no residual viable tumor cells. The pathological effect of chemotherapy was defined as Grade 3(pCR). Eight months post-operatively with no recurrence. Our case suggested that DCF chemotherapy is potentially a very effective treatment for advanced esophageal cancer.

Vertical migration of cesium in weathered granite soil under flowing water condition depending on Cs concentration and states of dissolved organic matter.

After the accident at the Fukushima Daiichi nuclear power plant in Japan, the migration of radioactive cesium (Cs) in soils has become a crucial issue since this can negatively affect human health and the surrounding environment. Dissolved organic matter (DOM) may have different influences on Cs migration in soils depending on Cs adsorption sites with different selectivity. It is unclear how DOM affects the rapid migration of Cs in soils under flowing water conditions during rainfall events. This study evaluated the effects of DOM on Cs migration in weathered granite soil depending on Cs adsorption sites by conducting laboratory experiments under different DOM conditions and Cs concentrations in the liquid phase. Cs concentration can affect the fraction of Cs adsorbed onto differently selective sites, and DOM can have different influences on Cs migration in the soil accordingly. Under condition of high-Cs concentration, the DOM adsorbed on the soil reduced Cs migration due to increasing Cs electrostatic adsorption to less selective sites in the soil. Meanwhile, under low-Cs concentration, the DOM adsorbed on the soil enhanced Cs migration because the DOM on the soil decreased the Cs adsorption to highly selective sites. Furthermore, DOM in the liquid phase detached the Cs adsorbed on the less selective sites and enhanced Cs migration in the soil, regardless of the Cs concentration.

[A Case of Multiple Liver Metastases of Mixed Adenonuroendocrine Carcinoma of the Ascending Colon with Poor Prognosis].

An 84-year-old woman presented with anorexia. CT showed ascending colon and multiple liver tumors, and a colonoscopy showed severe stenosis due to a tumor in the ascending colon. We diagnosed obstructive colon cancer with multiple liver metastases. It was difficult to approach this case with a colonic stent, and we suggested a colostomy, but the patient strongly objected and requested to undergo resection; thus, a laparoscopic right hemicolectomy was performed. Intraoperatively, there was no normal liver tissue, and liver metastases were diffuse. Histopathologically, neuroendocrine carcinoma and differentiated tubular adenocarcinoma were found; MANEC was diagnosed. Oral intake was started on the third postoperative day, but liver failure progressed gradually. Despite the best supportive care and medication, the patient died of liver failure 16 days after surgery. We report our experience of a MANEC case with a poor prognosis along with a literature review.

[A Case Report of Recurrence on Umbilical Port Site and Ileum Close to Anastomotic Portion after Laparoscopic Ileocecal Resection for Cecal Cancer].

We report a case of recurrence on umbilical port site and ileum close to anastomotic portion after laparoscopic ileocecal resection for cecal cancer. A 62-year-old woman was diagnosed as cecal cancer and performed ileocecal resection with D3 lymphadenectomy. One year and half after surgery, recurrence on umbilical port site and ileum close to anastomotic portion was detected with computed tomography and positron emission tomography. Chemotherapy(CAPOX plus Bmab)was performed. As a result of partial response, we performed resection of umbilical portion and anastomotic portion. Adjuvant chemotherapy was not performed. Neither recurrence or metastasis have been detected until 10 months after surgery.

[A Case of Gastric Perforation Due to an Unresectable Advanced Gastric Cancer That Achieved pCR after Conversion Surgery following SOX plus T-mab Therapy].

This case pertains to a 72-year-old man who visited the emergency department with a complaint of upper abdominal pain. On examination, we suspected gastric perforation due to gastric cancer and decided to perform emergency surgery. We performed laparoscopic omentoplasty and collected #4d lymph nodes that were enlarged on CT. The pathological diagnosis was lymph node metastasis. Based on CT findings, we determined it was Bulky N. For initial management, we performed 3 preoperative chemotherapy(SOX therapy)courses and staging laparoscopy. On surgery, extensive disseminated nodules on the abdominal wall, stomach wall, and liver surface were found, and ascites cytology revealed positive findings. Therefore, we did not perform primary lesion resection. Although the disseminated nodule did not pathologically show tumor cells, CY1 was found, resulting to a diagnosis of unresectable gastric cancer. Since the tumor was HER2 3+, we initiated SOX/trastuzumab therapy. After 16 courses, staging laparoscopy was performed as the lymph nodes had shrunk significantly. The results showed no tumor cells in ascites and the disseminated nodules, and laparoscopic total gastrectomy was subsequently performed. Pathological findings showed no tumor cells in the primary lesion or lymph nodes; therefore, a diagnosis of pathological complete response was made. Currently, the patient is alive without recurrence for 6 months after surgery.

Rhizosphere modelling reveals spatiotemporal distribution of daidzein shaping soybean rhizosphere bacterial community.

Plant roots nurture a wide variety of microbes via exudation of metabolites, shaping the rhizosphere's microbial community. Despite the importance of plant specialized metabolites in the assemblage and function of microbial communities in the rhizosphere, little is known of how far the effects of these metabolites extend through the soil. We employed a fluid model to simulate the spatiotemporal distribution of daidzein, an isoflavone secreted from soybean roots, and validated using soybeans grown in a rhizobox. We then analysed how daidzein affects bacterial communities using soils artificially treated with daidzein. Simulation of daidzein distribution showed that it was only present within a few millimetres of root surfaces. After 14 days in a rhizobox, daidzein was only present within 2 mm of root surfaces. Soils with different concentrations of daidzein showed different community composition, with reduced α-diversity in daidzein-treated soils. Bacterial communities of daidzein-treated soils were closer to those of the soybean rhizosphere than those of bulk soils. This study highlighted the limited distribution of daidzein within a few millimetres of root surfaces and demonstrated a novel role of daidzein in assembling bacterial communities in the rhizosphere by acting as more of a repellant than an attractant.

Effects of the dissolved organic matter on Cs transport in the weathered granite soil.

It is important to understand the migration of Cesium (Cs) in soils, particularly after the nuclear power plant accident at Fukushima Dai-ichi, Japan. Dissolved organic matter (DOM) is one of factors affecting the migration of Cs in soils under flowing water conditions. We investigated the effect of DOM on the migration of Cs adsorbed to the clay planar site via laboratory column experiments. The sequence of DOM application had a significant influence on Cs transport in the soil. When DOM was applied concurrently with or prior to Cs application, the DOM adsorbed on to the clay planar site adsorbed onto the soil solid surface and enhanced Cs adsorption; consequently, it slowed Cs migration in the soil. In particular, in the case of DOM loaded prior to the application of Cs solution, a noticeable delay in Cs migration was observed. On the other hand, when DOM was applied to the soil where the Cs solution had been previously applied, the DOM desorbed Cs from the soil. DOM in liquid phase enhanced the migration of Cs through the formation of binding to organic matter. Majority of Cs affected by DOM was the exchangeable fraction that adsorbed to the clay planar site. In other words, DOM attached to the soil would adsorb Cs as a easily exchangeable form and depress migration of Cs. On the other hand, DOM in the soil solution may up take adsorbed Cs from the soil and enhanced the transport in the form of Cs bound to DOM.

Nanobubble Retention in Saturated Porous Media under Repulsive van der Waals and Electrostatic Conditions.

An understanding of nanobubble (NB) migration in porous media is needed for potential environmental applications. The solution chemistry is well known to be a critical factor in determining interactions of other colloids and nanoparticles with surfaces. However, little quantitative research has examined the influence of solution chemistry on NB transport. One-dimensional column experiments were therefore conducted to investigate the transport, retention, and release of NBs in glass beads under different solution chemistry conditions. NB concentrations in the effluent were reduced with an increase in ionic strength (IS) or a decrease in pH due to a reduction in the repulsive force between the glass surface and NBs, especially when the solution contained Ca2+ as compared to Na+ and for larger NBs. This result was somewhat surprising because electrostatic and van der Waals interactions for NBs were both repulsive on a homogeneous glass bead surface. NB retention on the surface was explained by ubiquitous nanoscale roughness on the glass beads that significantly lowered the energy barrier and localized attractive charge heterogeneity and/or hydrophobic interactions. In contrast to Na+, adsorbed Ca2+ ions produced charge heterogeneity that enhanced NB retention and inhibited release with IS reduction.

Multicenter phase II study of biweekly CAPIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study).

BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. METHODS: Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). RESULTS: Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23-7.40 months], and median OS was 13.5 months (95% CI 11.57-20.23 months). The RR was 14.6% (95% CI 6.5-28.4%), and the DCR was 66.7% (95% CI 51.5-79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand-foot syndrome. CONCLUSIONS: In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.

Surfactant-enhanced flushing enhances colloid transport and alters macroporosity in diesel-contaminated soil.

Soil contamination by diesel has been often reported as a result of accidental spillage, leakage and inappropriate use. Surfactant-enhanced soil flushing is a common remediation technique for soils contaminated by hydrophobic organic chemicals. In this study, soil flushing with linear alkylbenzene sulfonates (LAS, an anionic surfactant) was conducted for intact columns (15cm in diameter and 12cm in length) of diesel-contaminated farmland purple soil aged for one year in the field. Dynamics of colloid concentration in column outflow during flushing, diesel removal rate and resulting soil macroporosity change by flushing were analyzed. Removal rate of n-alkanes (representing the diesel) varied with the depth of the topsoil in the range of 14%-96% while the n-alkanes present at low concentrations in the subsoil were completely removed by LAS-enhanced flushing. Much higher colloid concentrations and larger colloid sizes were observed during LAS flushing in column outflow compared to water flushing. The X-ray micro-computed tomography analysis of flushed and unflushed soil cores showed that the proportion of fine macropores (30-250µm in diameter) was reduced significantly by LAS flushing treatment. This phenomenon can be attributed to enhanced clogging of fine macropores by colloids which exhibited higher concentration due to better dispersion by LAS. It can be inferred from this study that the application of LAS-enhanced flushing technique in the purple soil region should be cautious regarding the possibility of rapid colloid-associated contaminant transport via preferential pathways in the subsurface and the clogging of water-conducting soil pores.

A review of source tracking techniques for fine sediment within a catchment.

Excessive transport of fine sediment, and its associated pollutants, can cause detrimental impacts in aquatic environments. It is therefore important to perform accurate sediment source apportionment to identify hot spots of soil erosion. Various tracers have been adopted, often in combination, to identify sediment source type and its spatial origin; these include fallout radionuclides, geochemical tracers, mineral magnetic properties and bulk and compound-specific stable isotopes. In this review, the applicability of these techniques to particular settings and their advantages and limitations are reviewed. By synthesizing existing approaches, that make use of multiple tracers in combination with measured changes of channel geomorphological attributes, an integrated analysis of tracer profiles in deposited sediments in lakes and reservoirs can be made. Through a multi-scale approach for fine sediment tracking, temporal changes in soil erosion and sediment load can be reconstructed and the consequences of changing catchment practices evaluated. We recommend that long-term, as well as short-term, monitoring of riverine fine sediment and corresponding surface and subsurface sources at nested sites within a catchment are essential. Such monitoring will inform the development and validation of models for predicting dynamics of fine sediment transport as a function of hydro-climatic and geomorphological controls. We highlight that the need for monitoring is particularly important for hilly catchments with complex and changing land use. We recommend that research should be prioritized for sloping farmland-dominated catchments.

[A Case of Extragastric-Developing Gastric Cancer with Hepatic and Pancreatic Invasion Suggesting Squamous Differentiation].

A 69-year-old man presented with left upper abdominal pain and weight loss. Contrast-enhanced CT showed a 9 cmsized extragastric tumor located between the left lateral liver section and the gastric lesser curvature. Gastroendoscopy showed a type 3 tumor located at the lesser curvature of the antrum. Biopsy confirmed that the tumor was an adenocarcinoma. With a diagnosis of extragastric-developing gastric cancer with hepatic and pancreatic invasion, the patient underwent a totalgastrectomy, D2 lymph node dissection, partiall iver resection, and pancreatic body tailexcision. The pathologicaldiagnosis was poorly differentiated adenocarcinoma suggesting squamous differentiation. Despite receiving postoperative adjuvant chemotherapy, the patient died of recurrence 7 months later.

[A Case of Rectal Villous Tumor Detected with Heart Failure and Electrolyte Imbalance].

A 74-year-old woman presented to our emergency department with a chief complaint of appetite loss, and already diagnosed dehydration and heart failure. After hospitalization, the signs of heart failure were improved with liquid supplementation and electrolyte revision. At admission, computed tomography incidentally detected a rectal tumor. She underwent colonography, which revealed a huge villous tumor in the rectum. Based on the result of the initial biopsy, it was classified as a group 4 tumor, but additional biopsy of specimens obtained from 6 places led to a diagnosis of group 5 tumor. Then, we performed laparoscopic super-low anterior resection and made an ileal stoma. The electrolyte imbalance was improved and did not recur after the operation. In this case, the electrolyte imbalance caused by the huge villous tumor was electrolyte depletion syndrome (EDS).

Corynebacterium glutamicum ArnR controls expression of nitrate reductase operon narKGHJI and nitric oxide (NO)-detoxifying enzyme gene hmp in an NO-responsive manner.

Corynebacterium glutamicum ArnR is a novel transcriptional regulator that represses expression of the nitrate reductase operon narKGHJI and the nitric oxide (NO)-detoxifying flavohemoglobin gene hmp under aerobic conditions. In a previous study, we showed that ArnR-mediated repression is relieved during anaerobic nitrate respiration, but we could not pinpoint the specific signal that ArnR senses. In this study, we show that in the absence of nitrate, ArnR-mediated repression is maintained under anaerobic conditions. The derepression in response to nitrate is eliminated by disruption of narG, suggesting that ArnR senses nitrate derivatives generated during nitrate respiration. Specifically, the hmp gene is upregulated in the presence of nitrite or nitric oxide (NO) in an ArnR-dependent manner, although the response of narK appears to be greatly affected by ArnR-independent regulation. In vitro binding of ArnR to the narK and hmp promoter regions is more strongly inhibited by NO than by nitrite. We previously showed that the UV-visible spectrum of ArnR is typical of a Fe-S cluster-containing protein. Site-directed mutagenesis of each of three cysteine residues, which are possibly involved in coordination of the cofactor in the ArnR protein, results in loss of the binding of this protein to its target promoters in vitro and eliminates the repression of the target genes in vivo under aerobic conditions. These observations suggest that the cofactor coordinated by these three cysteine residues in the ArnR protein plays a critical role in the NO-responsive expression of the narKGHJI operon and the hmp gene.

A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study).

BACKGROUND: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy. METHODS: The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups. RESULTS: Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p=0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p=0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p=0.289) but showed a delayed response. CONCLUSIONS: Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination. TRIAL REGISTRATION: Trial registration: UMIN000001791.

[The feasibility of reduced port surgery for sigmoid colon and rectal (Rs) cancer].

Laparoscopic surgery for colorectal cancer has the advantage of being less invasive and delivering better cosmetic appearance. Although single-incision laparoscopic surgery produces excellent cosmetic results, it is considered very difficult to perform. We performed reduced port surgery (single-incision plus one or 2 ports) on 42 patients in our institute. The operation time, number of dissected lymph nodes, morbidity rates, and length of hospital stay after the operation were not inferior to those in conventional laparoscopic surgery. The estimated blood loss in reduced port surgery was less than in conventional laparoscopic surgery. In conclusion, the procedure of reduced port surgery should be further standardized to make it safer and more feasible, and to provide a favorable cosmetic result for selected patients.

[Laparoscopic hemi-double stapling and reduced-port laparoscopic distal gastrectomy for gastric cancer].

INTRODUCTION: The hemi-double stapling method (HDS) is typically used for extracorporeal Billroth-I anastomosis. We used HDS for reduced-port surgery. Laparoscopic HDS is used for intracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy. We performed reduced-port laparoscopic distal gastrectomy for gastric cancer. METHODS: Reduced-port laparoscopic distal gastrectomy was performed using the multi-trocar method with 5mm and 3mm ports. Laparoscopic HDS was performed using an umbilical incision and a left upper abdominal incision. A total of 17 patients underwent reduced-port laparoscopic distal gastrectomy. A D1+or D1 lymph node dissection was performed, and laparoscopic HDS was used for reconstruction. RESULTS: The patients had no short-term complications. CONCLUSIONS: Laparoscopic HDS and reduced-port laparoscopic distal gastrectomy are safe and feasible procedures.

[Association between mesenteric phlebosclerosis and Chinese herbal medicine intake].

BACKGROUND: Mesenteric phlebosclerosis (MP) is a relatively rare disease of the colon. An association between MP and Chinese herbal medicine intake has recently been recognized. SUBJECTS AND METHODS: In the present study, we investigated the association between MP and Chinese herbal medicine intake in 42 patients, including those reported in the literature as well as those treated by us. RESULTS: Approximately 90% patients treated by us reported a history of Chinese herbal medicine intake, particularly kamishoyosan, orengedokuto, and sanshishi (gardeniae fructus), the lattermost being consumed by the majority of patients as a crude herbal medicine. DISCUSSION: Several MP patients report a history of Chinese herbal medicine intake. Furthermore, symptoms are exacerbated in MP patients who continue to consume the medicine after onset. Interestingly, MP was reported to develop in a married couple who had consumed the same Chinese herbal medicine for a prolonged period. These findings suggest that the intake of Chinese herbal medicine, particularly sanshishi, is strongly associated with MP development.

Dental Abnormalities in Pediatric Patients Receiving Chemotherapy.

Background: Chemotherapy is a common treatment for pediatric cancer. Although life prognosis is improving because of advances in medical science, it is important to deal with late effects such as dental abnormalities. We investigated the association between dental abnormalities and chemotherapy by age and tooth type. Methods: Among the 568 patients referred to the pediatric dentistry department of our hospital, we selected 32 patients (21 male and 11 female) who received chemotherapy between the ages of 0 and 6 and underwent panoramic examination after the age of 7. We recorded the age of chemotherapy commencement, diagnosis of systemic disease, and dental abnormalities such as congenital absence, microdonts, and short-rooted teeth. Results: Almost half of the patients had dental abnormalities such as congenital absence, microdonts, and short-rooted teeth, but there were no significant differences in the incidence of these abnormalities by age. When we analyzed the incidence of abnormal teeth by tooth type, the incidence of congenital absence was significantly higher in premolars (5.5%) and second molars (3.9%) than in incisor or canine or 1st molar (0.4%) (p < 0.01). The incidence of microdonts was significantly higher in premolars (3.9%) than in incisor or canine or 1st molar (0.2%) and second molars (0.0%) (p < 0.05). Conclusions: Patients who received chemotherapy had a high prevalence of dental abnormalities, and the incidence of abnormalities varied by tooth type. It is important to maintain long-term oral care for patients who have undergone chemotherapy even after the treatment is completed.