Examination of factors affecting the intraoral perception of object size: a preliminary study.

Oral sensory function is essential for the successful performance of a range of ingestion. Although the perception of object size is important in determining the degree of manipulation, evidence suggests that people does not always perceive the size of the object in oral cavity accurately. The purpose of this study was to investigate the factors affecting the intraoral perception of object size. Twenty-three healthy young volunteers detected the size of cylinders inserted into oral cavity blindly and identified it from the reference set. The diameter of cross section varied from 10 to 14 mm in a gap of 1 mm and had three different temperatures (5, 36, 50 °C) in each. The perceived size was recorded, and the difference with the actual size was assessed. The required time for identification was also measured and compared between gender and between temperatures. The results demonstrated that the direction of size illusion was significantly affected by the required time for identification. Long manipulation led to overestimation, and short manipulation led to underestimation of object size irrespective of temperature and size. Gender was the other factor affecting intraoral size perception. The rate of overestimation was low in female participants comparing with male participants in this experiment, although the number of participants was limited. We therefore concluded that in order to detect the other factors affecting intraoral size perception, regulating oral manipulation time is indispensable.

Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma.

BACKGROUND: The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. RESULTS: Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. CONCLUSION: In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. CLINICALTRIALSGOV: NCT01170663.

Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.

BACKGROUND: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease. RESULTS: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%). CONCLUSION: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS. CLINICAL TRIAL NUMBER: JapicCTI-101021.

Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer.

BACKGROUND: This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). METHODS: Ninety patients were randomised to a standard dose of wPTX (80 mg m(-2)) or an escalated dose of wPTX (80-120 mg m(-2)) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8. RESULTS: The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34). CONCLUSION: Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.

Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours.

BACKGROUND: TAS-102 consists of α, α, α-trifluorothymidine (TFT) and an inhibitor of thymidine phosphorylase (TPI). We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours. METHODS: TAS-102 was administered twice daily on days 1-5 and days 8-12 in a 28-day cycle to patients with solid tumours refractory to standard chemotherapy, to determine its maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics (PKs). MTD was evaluated in cycle 1. RESULTS: Safety and PKs were evaluated in 21 patients treated with TAS-102 at 30, 40, 50, 60, or 70 mg m(-2) per day. DLTs, such as grade 4 leucopenia, grade 4 neutropenia, and grade 4 thrombocytopenia, were observed in two patients at doses of 30 and 70 mg m(-2). α, α, α-trifluorothymidine and TPI exposures increased dose dependently, and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated. The disease control rate was 50.0% with a median progression-free survival of 2.4 months in 18 colorectal cancer patients. The dose of TAS-102 was not increased above 70 mg m(-2) per day because of the increased tendency for grade 3 and 4 neutropenia, and 70 mg m(-2) per day was the recommended dose for phase II studies. CONCLUSIONS: TAS-102 at 70 mg m(-2) per day was tolerated in Japanese patients with advanced solid tumours. Phase II studies are ongoing in patients with colorectal cancer.

A phase II study to explore biomarkers for the use of mFOLFOX6/XELOX plus bevacizumab as a first-line chemotherapy in patients with metastatic colorectal cancer (WJOG7612GTR).

BACKGROUND: The purpose of this prospective study was to assess the ability of plasma vascular endothelial growth factor-A short isoforms (pVEGF-Asi) to predict bevacizumab (BV) efficacy and to explore other circulating biomarkers in metastatic colorectal cancer (mCRC) patients treated with modified FOLFOX6/XELOX plus BV (mFOLFOX6/XELOX + BV). PATIENTS AND METHODS: Pre-treatment plasma samples were collected from 100 mCRC patients receiving first-line chemotherapy with mFOLFOX6/XELOX + BV. The plasma levels of 11 angiogenesis-associated molecules, including pVEGF-Asi and 22 cancer-associated gene mutations in circulating tumor DNA, were analyzed. For the primary endpoint, we assumed that the hazard ratio (HR) for progression-free survival (PFS) calculated using a Cox proportional hazards model was <1.15, comparing patients with a high versus those with a low pVEGF-Asi level divided according to the median pVEGF-Asi value. RESULTS: The median value of pVEGF-Asi was 37 (range 6.5-262) pg/ml. The HR for PFS between the high and low pVEGF-Asi patient groups was 1.3 [95% confidence interval (CI) 0.8-2.1; log rank, P = 0.25], which was larger than the predefined threshold of 1.15. The multivariate analysis demonstrated that PFS was significantly associated with plasma intercellular adhesion molecule-1 (pICAM-1) (≥190.0 versus <190.0 ng/ml; HR 2.1; 95% CI 1.3-3.5), RAS (mutant versus wild; HR 2.5; 95% CI 1.5-4.3), and FBXW7 (mutant versus wild; HR 2.8; 95% CI 1.2-6.8), whereas overall survival was significantly associated with pICAM-1 (HR 2.0; 95% CI 1.1-3.7) and RAS (HR 2.6; 95% CI 1.5-4.6). CONCLUSIONS: The addition of BV was unable to compensate for the poor PFS associated with a high pVEGF-Asi level, suggesting that pVEGF-Asi is unlikely to be a good predictive biomarker of the efficacy of mFOLFOX6/XELOX + BV therapy. The clinical significance of circulating ICAM-1, mutant RAS, and mutant FBXW7 levels should be studied further.

Impact of hemoglobin level on survival in definitive chemoradiotherapy for T4/M1 lymph node esophageal cancer.

We retrospectively investigated the impact of the pre-chemoradiotherapy hemoglobin level (pre-CRT Hb level) for T4 and/or M1 lymph node (LYM) squamous cell carcinoma of the esophagus. Chemotherapy consisted of protracted infusion with 5-fluorouracil (5-FU) at 400 mg/m(2)/day on days 1-5 and 8-12, combined with cisplatin at 40 mg/m(2)/day on days 1 and 8, repeated twice at a 5-week interval. Concurrent radiation therapy was started on day 1 and delivered at 2 Gy/day for five days a week for a total radiation dose of 60 Gy, with a two-week break after a cumulative dose of 30 Gy. Several factors considered to be related with treatment outcome were evaluated by univariate and multivariate analysis. A total of 48 patients with T4/M1 LYM (lymphocyte) esophageal cancer treated with chemoradiotherapy (CRT) between September 2002 and April 2005 were enrolled. The complete response rate to this regimen was 44% and median survival time was 13.6 months, with a median follow-up period of 26.8 months. Median pre-CRT Hb level was 13.5 (10.4-15.3) g/dL. The CR rate in patients with a pre-CRT Hb level of 13 g/dL or less was only 24% but it was 60% in those with a level that was more than 13 g/dL (P=0.01). As for survival, anovarevealed that a pre-CRT Hb of 13 g/dL or less was a significant prognostic factor with a hazard ratio of 0.45 (95% confidence interval [CI]); 0.21-0.97, P=0.04), while on manova, including performance status, tumor size, TNM stage and pre-CRT Hb level, a pre-CRT Hb level of 13 g/dL or less was the only significant prognostic factor, with a hazard ratio of 0.35 (95% CI; 0.13-0.90, P=0.03). In conclusion, the pre-CRT Hb level may be an important determinant of outcome in patients with T4/M1 LYM squamous cell carcinoma of the esophagus.

Influence of Oral Anaerobic Bacteria on Hematopoietic Stem Cell Transplantation Patients: Oral Mucositis and General Condition.

OBJECTIVE: Oral mucositis (OM) caused by infection facilitated by myelosuppression and immunosuppression can be controlled through oral care. We investigated changes in oral anaerobic bacterial flora during the onset of OM with hematopoietic stem cell transplantation (HSCT). METHODS: This study included 19 patients who underwent HSCT. All received professional oral care before initiating the preparative regimen. We assessed OM, oral health and obtained microbial samples from the oral cavity during 5 assessment points: before initiating the preparative regimen; the day before HSCT (day 1); and at 7, 14, and 30 days after HSCT. Microbial species were identified by using a mass spectrometer. RESULTS: The number of patients with serious OM increased initially after HSCT and decreased thereafter. Many Streptococcus species were identified before HSCT, but these gradually decreased and were replaced by coagulase-negative staphylococci. An increase in Candida species after HSCT and the identification of Enterococcus species were significantly associated with OM. Nutritional status recovery and prognosis were significantly worse in patients who developed OM. CONCLUSIONS: To the best of our knowledge, this study is the first which shows that anaerobic bacteria were identified in patients' oral flora before and after HSCT by using a mass spectrometer. These results indicate that Enterococcus species and Candida species may have been associated with OM. OM affected the patients' improvement in nutritional status and their prognosis. We concluded that it is important to provide more complete oral care instructions and interventions to prevent these bacterial infections.

Feeding-induced c-fos expression in the nucleus of the solitary tract and dorsal medullary reticular formation in neonatal rats.

We investigated feeding-associated activation of neurons in the medulla oblongata during the suckling period in rats, using the c-fos gene-encoded protein (Fos) immunohistochemistry. After an isolation from mothers for 12 h, neonates were either breast-fed intensively or further isolated for another 3 h, and sacrificed on postnatal day 1, 3, 5, 7 and 14 (P1-14). In the former pups, Fos-immunoreactive (FI) neurons were predominantly localized in the nucleus of the solitary tract (NST) and in the dorsal medullary reticular formation (RF). The number of FI cells peaked on P5-7 and decreased on P14 in the NST, and increased remarkably on P3 and was consistently high until P14 in the dorsal RF. In contrast, much fewer FI cells were found in the NST and RF in the latter pups. The results indicated that not only the NST but also the dorsal RF were implicated in feeding behavior in the suckled pups.

[Surgical treatment of mycobacterium avium complex infection in a patient with chronic empyema].

Atypical mycobacterial infection mostly develops in the lung and its occurrence outside of the lung is very rare. We report a case of mycobacterium avium complex (MAC) infection found with chronic empyema piercing out of the thoracic wall, to which surgical treatment was very successful. A 72-year old male had been treated for an abscess of right thoracic wall. MAC was isolated from thoracic effusion. Thoracic window and pan-pleuro-pneumonectomy was performed. No recurrence of MAC infection was found up to 1 year and 4 months when he died of accident.

Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study.

BACKGROUND: Most gastric cancer patients with peritoneal dissemination have been excluded from clinical studies because they usually have no measurable lesions. They also have a high risk of toxicity because of complications such as intestinal obstruction and ascites. We conducted a retrospective analysis to evaluate the efficacy and feasibility of sequential methotrexate (MTX) and 5-flurorouracil (5FU) therapy for this population. METHODS: This analysis was based on 56 consecutive chemotherapy-naive patients with confirmed peritoneal dissemination of gastric cancer who were being treated with sequential MTX/5FU. The therapy comprised a weekly schedule of MTX 100 mg/m2, given as a bolus infusion 3 h prior to a bolus infusion of 5FU 600 mg/m2. Leucovorin 10mg/m2 was administered six times, every 6h, starting 24h after MTX administration. RESULTS: Evidence of peritoneal dissemination was confirmed by laparotomy in 16 patients, by cytologic examination of ascites in 11 patients, and by clinical imaging in 29 patients (15 with ascites, 13 with intestinal obstruction; in 10 of the 29 patients, detection was by barium enema or computed tomography [CT] scan). Neutropenia of grade 3 or worse and anemia were observed in 8 (14%) and 10 (18%) of the 56 patients, respectively. There was one treatment-related death due to neutropenic sepsis. Of the 26 patients with measurable lesions, 9 showed a response (36%). The median survival time and median time to treatment failure were 259 days and 167 days, respectively. Objective improvement of ascites was seen in 13 of 26 patients (50%), including 5 with showed complete disappearance of ascites. Seven of the 15 patients (47%) with intestinal obstruction showed resolution, and 8 of the 21 patients (38%) who needed nutritional support before the treatment were free of that support for a median duration of 220 days after the completion of the treatment. Forty-seven of the 56 patients (84%) could be treated at outpatient clinics. CONCLUSIONS: This regimen may be of clinical benefit for patients with peritoneal dissemination of gastric cancer.