A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Volatile anticancer drug determination by thermal desorption technique with polydimethylsiloxane-coated macroporous silica adsorbent in gas chromatography-mass spectrometry.

An analytical method for quantifying the volatile anticancer drugs ifosfamide (IF) and cyclophosphamide (CP) in air was developed on the basis of thermal desorption (TD)-gas chromatography-mass spectrometry. Polydimethylsiloxane-coated macroporous silica was used as the adsorbent. The extraction tube was prepared by packing 0.2 g of adsorbent particles into a glass tube. The extraction and desorption efficiencies of the proposed method were quantitatively investigated in this study. The limits of detection of the proposed method for IF and CP were 3.3 ng L-1 at an air sampling volume of 3.0 L (30 min). The sensitivity of the proposed method was compared with using a Tenax TA packed tube that is widely used as the extraction medium in TD analysis. Finally, detection of IF and CP that evaporated from aqueous standard solution was investigated.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3).

PURPOSE: We previously reported the primary results of JCOG0701, a randomized, multicenter, phase 3, noninferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer. In the primary results, although the similar efficacy of 3-year progression-free survival and toxicity of Ax compared with SF was observed, the noninferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. METHODS AND MATERIALS: In JCOG0701, 370 patients were randomly assigned to receive SF of 66 to 70 Gy (33-35 fractions; n = 184) or Ax of 60 to 64.8 Gy (25-27 fractions; n = 186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia were analyzed. RESULTS: With a median follow-up period of 7.1 years (range, 0.1-12.4), progression-free survival of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (P = .44). OS of the SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (P = .92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of the SF and Ax arms were 11.9% and 7.4% at 8 years (hazard ratio, 0.53; 95% CI, 0.28-1.01; P = .06). Central nervous system ischemia of grade 2 or higher was observed in 4.1% for the SF arm and 1.1% for the Ax arm (P = .098). CONCLUSIONS: After long-term follow-up, Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early glottic cancer because of its convenience in minimizing treatment time, cost, and labor.

Sampling bag-based emission chamber for measuring volatile organic compounds from household materials using solid-phase extraction-type collection device.

A simple screening analytical method for determining the emission of volatile organic compounds (VOCs) from household materials was developed using a solid-phase extraction (SPE)-type collection device and a gas sampling bag. The VOCs emitted from the sample material placed in the gas sampling bag with a volume of 20 L were extracted on the SPE-type collection device. In this study, complete sampling mode was developed in addition to a conventional flow sampling mode. The extracted VOCs were then eluted with 8 mL of acetone and measured using gas chromatography-mass spectrometry. The proposed method does not require a stainless-steel chamber and a thermal desorption system; therefore, VOC emission from household materials could be easily evaluated with an affordable cost, suggesting that the method is suitable for the screening technique for evaluating VOC emission from solid materials.

Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

Needle extraction device for rapid and quantitative gas chromatographic determination of volatile chlorinated hydrocarbons and benzene in soil.

A rapid and quantitative analytical method for volatile chlorinated hydrocarbons and benzene, such as chloroethylene, dichloromethane, and carbon tetrachloride, in soil samples was developed using a needle-type extraction device packed with activated carbon-based adsorbents. The soil sample of 10 g was placed in a glass cartridge and fixed with quartz wool to make sure not to move during the extraction process. After the internal standard solution was spiked into the soil sample, the cartridge was sealed with a polytetrafluoroethylene adapter, and the needle extraction device was used to collect the headspace gas. Analytes were purged from the soil sample and collected on the adsorbent, while pure nitrogen gas was introduced to the soil sample during the sample collection. The sampling time was approximately 10 min for 100 mL of gas sampling. After the sampling process, the extraction needle was directly inserted into a heated injection port of gas chromatography equipped with flame ionization detector (GC-FID) or that hyphenated to mass spectrometry (GC-MS). The extracted VOCs were thermally desorbed and simultaneously introduced to a GC capillary column for subsequent separation and determination. The limit of detection and limit of quantification of all the examined analytes was less than 20 and 60 ng/10 g soil in GC-FID and less than 2.5 and 7.5 ng/10 g soil in the case of GC-MS. Linear calibration curves were obtained up to 10 µg/10 g soil for all the analytes. The relative standard deviations of the ratio of analyte peak area and internal standard peak area were less than 10%. The recovery and sensitivity of analytes confirmed in the proposed method were compared with that obtained with a standard method conventionally employed.

Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by dilated abdominal aorta. Immune cells have been shown to contribute to the development of AAA, and that the gut microbiota is associated with numerous diseases, including cardiovascular diseases, by regulating immune systems or metabolic pathways of the host. However, the interaction between the gut microbiota and AAA remains unknown. METHODS: Apolipoprotein E-deficient male mice were fed a high-cholesterol diet and divided into three groups: the control group was maintained under normal water (control group), the oral AVNM group was maintained under drinking water supplemented with ampicillin, vancomycin, neomycin, and metronidazole, and the i.p. AVNM group was injected AVNM intraperitoneally. After 1 week of pretreatment with antibiotics, these mice were administrated Ang II via subcutaneous osmotic pumps for 4 weeks and euthanized to evaluate AAA formation. RESULTS: Depletion of gut microbiota by oral AVNM ameliorated the incidence of AAAs (control group: 58.9% versus oral AVNM group: 28.6% versus i.p. AVNM group: 75.0%, P = 0.0005) and prevented death due to ruptured aneurysms (control group: 11% versus oral AVNM group: 0% versus i.p. AVNM group: 15%). Oral AVNM suppressed monocyte storage in the spleen, but not in other organs. Despite possessing a higher level of cholesterol, recruitment of monocytes into the suprarenal aorta was suppressed in the oral AVNM group. In AVNM drinking mice, NOD1 ligand, a kind of PRR ligands, increased the development of AAAs and accumulation of macrophages in the aortae. CONCLUSIONS: The gut microbiota plays a critical role in AAA formation. Therefore, regulation of the microbiota or the immune system can be a therapeutic approach for AAA.

Screening of chronic radiation proctitis and colorectal cancer using periodic total colonoscopy after external beam radiation therapy for prostate cancer.

OBJECTIVE: To investigate the incidence of colorectal cancer and chronic radiation proctitis after prostate radiotherapy using periodic total colonoscopy screening. METHODS: From February 2013 to January 2018, 270 patients who underwent external beam radiation therapy for prostate cancer were advised to receive periodic total colonoscopy screening annually. We evaluated the incidence and characteristics of colorectal cancer and chronic radiation proctitis. RESULTS: First, second, third, fourth and fifth total colonoscopy were performed in 256 (95%), 151 (56%), 60 (22%), 23 (8.5%) and 7 (2.6%) patients at a median of 14, 31, 42, 54 and 72 months after radiotherapy, respectively. The prevalence proportion of colorectal cancer in the first colonoscopy since radiotherapy was 3.9%. Twelve (4.4%) patients were diagnosed with colorectal cancer, including four invasive cancers, during a follow-up period. Eight of these 12 patients had not experienced rectal bleeding. The median time to diagnosis of colorectal cancer was 21 months. Chronic radiation proctitis was observed in 136 (50%) patients, including 67 (25%) patients with symptomatic bleeding. CONCLUSIONS: The high detection rate of asymptomatic radiation proctitis suggests the utility of total colonoscopy to screen for early-stage colorectal cancer prior to or following radiotherapy for prostate cancer. Considering the longevity after localized prostate cancer treatment, the awareness of chronic radiation-induced proctitis and the risk of colorectal cancer masked by bleeding is needed in treatment decision -making.

Final analysis of a Multicenter Single-Arm Confirmatory Trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety and efficacy of hypofractionated whole breast irradiation for Asian women after breast-conserving surgery. This is an updated report with 5-year follow-up. METHODS AND MATERIALS: Asian women who had invasive breast cancer with clinical tumor size ≤3 cm, pN0-1c and negative inked margins were enrolled. Hypofractionated whole breast irradiation of 42.56 Gy/16 fractions was delivered, and boost irradiation of 10.64 Gy/4 fractions was added when the surgical margin was ≤5 mm. The primary endpoint was the proportion of grade ≥ 2 late adverse reactions within 3 years. Secondary endpoints included early adverse events, overall survival, disease-free survival, ipsilateral breast relapse-free survival, late adverse reactions and cosmetic outcome. Toxicities were evaluated using CTCAE ver3.0. Cosmetic outcomes were assessed using a 4-point scale and CTCAE ver3.0 for hyper/hypopigmentation, breast nipple/areolar deformity and breast volume/deformity. RESULTS: Between February 2010 and August 2012, 312 patients were enrolled, and 306 received hypofractionated whole breast irradiation. Median follow-up was 70.5 (range 7.6-88.9) months. The proportion of grade ≥ 2 late adverse reactions within 3 years was 4.3% (90% confidence interval 2.5-6.7%). Grade 2 early adverse events occurred in 38 (12.4%); none had grade 3/4. Five-year overall survival, disease-free survival and ipsilateral breast relapse-free survival were 98.7, 95.4 and 98.0%, respectively. Of the 304 evaluable patients, 29 (9.5%; 95% confidence interval 6.5-13.4%) had grade 2/3 late adverse reactions; none had grade 4/5. At 5 years, 70/289 (24.2%) showed any worsening of breast cosmetic changes. CONCLUSIONS: Hypofractionated whole breast irradiation is considered a standard treatment for Asian women with margin-negative invasive breast cancer after breast-conserving surgery.

Metabolic alterations in plasma after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG. We collected plasma samples from 15 morbidly obese Japanese patients before and 3 months after LSG. A total of 48 metabolites were quantified using capillary electrophoresis time-of-flight mass spectrometry-based metabolomic profiling. Branched chain amino acids, several essential amino acids, choline, 2-hydroxybutyric acid, 2-oxoisovaleric acid and hypoxanthine were significantly decreased after LSG. Tricarboxylic acid cycle metabolites, including citric acid, succinic acid and malic acid, were significantly elevated after LSG. This is the first report to show dynamic alterations in plasma metabolite concentrations, as assessed using capillary electrophoresis time-of-flight mass spectrometry, in morbidly obese patients after LSG. Our results might show how LSG helps improve obesity, in part through metabolic status changes, and propose novel therapeutic targets to ameliorate obesity.

Extraction of Volatile Anticancer Drugs in Air Using a Solid-Phase Extraction Type Device Followed by Gas Chromatography-Mass Spectrometric Analysis.

Ifosfamide (IF), cyclophosphamide (CP), and bendamustine (BD) are widely used anticancer drugs. These drugs have slight volatility; therefore, medical-staff exposure is of concern in the medical field. However, an accurate and quantitative detection method of these volatile drugs in air has not been reported. In this study, we developed the quantitative extraction and detection method of these volatile anticancer drugs in air. For the extraction of analytes, a solid-phase extraction-type collection device packed with styrene-divinylbenzene polymer particles was used. The extracted analytes were quantitatively eluted with 5 mL of ethanol, and the solution was concentrated to 100 µL with nitrogen purging. The analytes were analyzed using gas chromatography-mass spectrometry (GC-MS). The limit of detection of the proposed method for IF and CP was 0.017 and 0.033 ng L-1, respectively in air at an air sampling volume of 300 L. IF and CP showed slight volatility, whereas BD was not detected in GC-MS due to its lower volatility. The spiked recoveries of IF and CP in the proposed method were within the range of 95.5 to 101%. Finally, the proposed method was applied to determine the exposure of IF and CP during the dispensing of CP within a hospital dispensary room. The investigated volatile anticancer drugs were not detected in real air samples, indicating that the protection measures employed are sufficient.

Chemoradiotherapy with FOLFOX for esophageal squamous cell cancer with synchronous rectal cancer: Four case reports and a literature review.

Chemoradiotherapy (CRT) is a valuable treatment option for localized esophageal cancer. Conventional baseline chemotherapy for this type of cancer includes cisplatin and fluorouracil. Recently, CRT with leucovorin-fluorouracil-oxaliplatin (FOLFOX) has become popular due to its convenience and lower toxicity. In Japan, the use of oxaliplatin for esophageal cancer is not yet approved, so experience with this treatment is limited to cases with colorectal cancer. As such patients are not usually included in clinical trials, little is known on the efficacy and safety of this treatment for this patient subpopulation, and treatment generalization in Japan is not allowed. We herein share our experience with CRT and FOLFOX for cases with esophageal cancer and synchronous rectal cancer at our institution. The clinical data of 4 patients who were treated for esophageal cancer with CRT/FOLFOX at our hospital between 2007 and 2016, who also had synchronous rectal cancer, were retrieved and analyzed. All the patients were male and had esophageal squamous cell cancer and synchronous rectal cancer. The median patient age was 68 years (range, 65-77 years). One patient received neoadjuvant CRT followed by surgery, and the other 3 patients received definitive CRT for esophageal cancer. FOLFOX was administered biweekly during radiotherapy (41.4-60 Gy). All 4 patients completed the treatment schedule and responded to CRT. No patients experienced progression of rectal cancer during treatment. Notably, 1 patient also achieved a complete response (CR) of rectal cancer after CRT for esophageal cancer. Moreover, 2 patients without dysphagia were treated as outpatients and achieved a CR. Encephalopathy was the only reported grade 3 adverse event. Although the present study included a limited number of cases, the findings suggest that CRT with FOLFOX may be a valuable option for the treatment of patients with esophageal squamous cell cancer and synchronous rectal cancer.

Commissioning of the Mobius3D independent dose verification system for TomoTherapy.

In radiation therapy, a secondary independent dose verification is an important component of a quality control system. Mobius3D calculates three-dimensional (3D) patient dose using reference beam data and a collapsed cone convolution algorithm and analyzes dose-volume histogram automatically. There are currently no published data on commissioning and determining tolerance levels of Mobius3D for TomoTherapy. To verify the calculation accuracy and adjust the parameters of this system, we compared the measured dose using an ion chamber and film in a phantom with the dose calculated using Mobius3D for nine helical intensity-modulated radiation therapy plans, each with three nominal field widths. We also compared 126 treatment plans used in our institution to treat prostate, head-and-neck, and esophagus tumors based on dose calculations by treatment planning system for given dose indices and 3D gamma passing rates with those produced by Mobius3D. On the basis of these results, we showed that the action and tolerance levels at the average dose for the planning target volume (PTV) at each treatment site are at µ ± 2σ and µ ± 3σ, respectively. After adjusting parameters, the dose difference ratio on average was -0.2 ± 0.6% using ion chamber and gamma passing rate with the criteria of 3% and 3 mm on average was 98.8 ± 1.4% using film. We also established action and tolerance levels for the PTV at the prostate, head-and-neck, esophagus, and for the organ at risk at all treatment sites. Mobius3D calculations thus provide an accurate secondary dose verification system that can be commissioned easily and immediately after installation. Before clinical use, the Mobius3D system needs to be commissioned using the treatment plans for patients treated in each institution to determine the calculational accuracy and establish tolerances for each treatment site and dose index.

Purge-and-trap Determination of Ammonia in Water Samples Using Needle-type Extraction Coupled with Gas Chromatography-Barrier Discharge Ionization Detection.

This manuscript describes the determination of ammonia (NH3) in aqueous samples by purge-and-trap extraction using a needle-type extraction device with gas chromatography-barrier discharge ionization detector (GC-BID). NH3 was purged from the aqueous samples in basic conditions and then salted out with sodium chloride. Purged ammonia was trapped onto non-volatile carboxylic acid-coated macroporous terephthalic acid particles, which were contained within the needle-type extraction device. The analyte (NH3) was thermally desorbed by heating the extraction needle in the GC injection port, and detected by BID. After the optimization of both purge and extraction conditions, the linearity and sensitivity of the proposed method were evaluated. The limit of detection was found to be 2.0 mg L-1 at a headspace sampling volume of 100 mL. The method applicability was confirmed by the determination of spiked NH3 in tap water and river water samples.

A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906.

OBJECTIVE: To evaluate the safety of hypofractionated whole breast irradiation in Japanese women after breast-conserving surgery. METHODS: Japanese women who had invasive breast cancer with a clinical tumor size ≤3 cm, pN0-1c and a negative inked margin were enrolled. Hypofractionated whole breast irradiation (42.56 Gy/16 fractions) was delivered, adding boost irradiation (10.64 Gy/4 fractions) when the surgical margin was ≤5 mm. The treatment course was meant to be completed within 29 days or 33 days (plus boost irradiation). The primary endpoint was the proportion of grade ≥2 of pre-specified late adverse reactions, including telangiectasia, ulceration, fibrosis, fracture, pneumonitis, cardiac ischemia/infarction, pericardial effusion and breast pain, within 3 years. A sample size of 310 patients was set, with one-sided alpha of 0.05, beta of 0.1, threshold value of 8% and expected value of 4%. Secondary endpoints included the proportion of treatment completion within the recommended period and early adverse events within 90 days. Adverse events/adverse reactions were evaluated using CTCAE-3.0. RESULTS: Between 2010 and 2012, 312 women were enrolled; 306 received hypofractionated whole breast irradiation, but 6 chose conventional fractionated WBI, with 301 patients (96.5%) treated within the recommended period. Grade 2 early adverse events were found in 38 patients (12.4%); none had grade 3/4. Among the 303 evaluable patients, 13 (4.3%; 90% CI 2.6-6.7) had grade 2/3 late adverse reactions, including one with grade 3 pneumonitis, which was under the threshold value. CONCLUSION: Hypofractionated whole breast irradiation is considered to be safe and one of the standard treatments for Japanese women with margin-negative invasive breast cancer after breast-conserving surgery.

Phase II feasibility study of preoperative concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil and elective lymph node irradiation for clinical stage II/III esophageal squamous cell carcinoma.

BACKGROUND: Preoperative chemoradiotherapy (CRT) is a standard treatment for stage II/III esophageal cancer. Preoperative chemotherapy is also considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in patients who undergo radical lymph node dissection. We conducted a feasibility study of preoperative CRT with cisplatin plus 5-fluorouracil (CF) and elective lymph node irradiation followed by esophagectomy with radical lymph node dissection in patients with stage II/III ESCC. METHODS: Patients with clinical stage II/III, excluding T4, ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy comprised two courses of CF infusion repeated after 4-weeks. Radiation therapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes at a dose of 41.4 Gy. After the completion of CRT, transthoracic esophagectomy with 2-3 fields lymphadenectomy was performed. The primary endpoint was the completion rate of protocol treatment with R0 resection. RESULTS: Thirty-one eligible patients were enrolled. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%) and hyponatremia (16%). Thirty patients (96.8%) underwent surgery. One patient received palliative chemotherapy because of appearance of lung metastasis during CRT. The completion rate of protocol treatment was 93.5% (29/31). There was one treatment-related death after surgery. Pathological complete response was achieved in 42% (13/30). CONCLUSION: Preoperative CRT with CF and elective lymph node irradiation showed an acceptable toxicity and promising activity especially in ESCC.

SLCO1B1 Polymorphism Is a Drug Response Predictive Marker for Advanced Pancreatic Cancer Patients Treated With Gemcitabine, S-1, or Gemcitabine Plus S-1.

OBJECTIVES: The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. METHODS: Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study). The associations between OS and SNPs were investigated using log-rank test and Cox proportional hazards model. RESULTS: From the GEST study, the SNP rs4149086 in the 3' UTR of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene showed significant interaction with treatment (P = 0.02). In the gemcitabine group, the SNP was associated with short OS (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.30-10.8; P = 0.008) even after multiple-comparisons adjustment. In contrast, the SNP was not associated with OS in S-1 (HR, 0.77; 95% CI, 0.33-1.81; P = 0.55) or gemcitabine plus S-1 groups (HR, 1.18; 95% CI, 0.46-3.00; P = 0.72). CONCLUSIONS: Patients with advanced pancreatic cancer with the rs4149086 AG or GG genotype may obtain good clinical results when treated with S-1-containing regimens.

Determination of Aqueous Formic and Acetic Acids by Purge-and-Trap Analysis with a Needle-Type Extraction Device and Gas Chromatography Barrier Discharge Ionization Detector.

A purge-and-trap method using a needle-type extraction device and a gas chromatography-barrier discharge ionization detector for the analysis of formic (FA) and acetic acids (AA) in aqueous samples is presented. An activated carbon-based adsorbent, Carboxen 1000, was employed as the extraction medium for the needle-type extraction device. The sampling time was 5 min for collecting headspace gas in a glass vial, including 10 mL of an aqueous sample. The detection limits for FA and AA with a headspace sampling volume of 100 mL were 3.3 and 2.0 mg L-1, respectively. Since the proposed method was based on purge-and-trap collection, it was suitable for the determination of aqueous FA and AA in complex matrices with simple and rapid sample preparation steps. The proposed method was applied to the determination of FA and AA in fruit juice samples and FA generated by the electrochemical reduction of carbon dioxide.

Highly Viscoelastic Reverse Wormlike Micellar Systems from a Mixture of Lecithin, Polyglycerol Fatty Acid Monoesters, and an Oil.

We report new lecithin reverse wormlike micelles with high viscoelasticity formed using lecithin/polyglycerol fatty acid monoester (PGLFA)/oil systems. In this study, the influence of the amphiphilicity (i.e., hydrophile-lipophile balance, HLB) of PGLFA on the phase behavior and rheological properties of reverse wormlike micelles was investigated in detail. PGLFAs with degrees of polymerization of polyglycerol varying between 6-40 and constituent fatty acids with chains between 6-18 carbon atoms long were used. Partial phase diagrams of the lecithin/PGLFA/n-decane systems indicated that the appropriate PGLFA could change the lecithin/oil solution into a highly viscoelastic solution comprising reverse wormlike micelles. Rheological measurements showed that all systems that formed reverse wormlike micelles exhibited an unusual phenomenon called "shear-thickening". Furthermore, reverse wormlike micelles grew as the PGLFA concentration increased and the zero-shear viscosity (η0) of the solution rapidly increased. Our results indicate that the magnitude of the maximum η0 depends on the degree of polymerization of the constituent polyglycerol in the PGLFA, while the size of the reverse micellar region and the highly viscous region in the phase diagram depends on the HLB value of the PGLFA.

Radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma: long-term outcomes over 10 years.

This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31-84). Fifteen patients were Helicobacter pylori-negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30-39.5 Gy). The median follow-up period was 121 months (range: 8-176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases.