EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.

Changes in cortical, cardiac, and respiratory activities in relation to spontaneous rhythmic jaw movements in ketamine-anesthetized guinea pigs.

It has been reported that rhythmic jaw movements (RJMs) spontaneously occur in ketamine-anesthetized animals. The present study investigated the physiological processes that occur during the cortical, cardiac, and respiratory events which contribute to the genesis of RJMs in animals after supplemental ketamine injections. Fourteen guinea pigs were prepared to allow electroencephalographic, electrocardiographic, and electromyographic activities to be recorded from the digastric muscle, measurement of jaw movements, and nasal expiratory airflow under ketamine-xylazine anesthesia. Rhythmic jaw movements spontaneously occurred with rhythmic digastric muscle contractions, 23-29 minutes after injection of supplemental ketamine (12.5 and 25.0 mg kg-1 , intravenously). The cycle length of RJMs did not differ significantly between the two doses of ketamine (mean±SD: 12.5 mg kg-1 , 326.5 ± 60.0 ms; 25 mg kg-1 , 278.5 ± 45.1 ms). Following injection of ketamine, digastric muscle activity, heart and respiratory rates, and cortical beta power significantly decreased, while cortical delta and theta power significantly increased. These changes were significantly larger in animals given 25.0 mg kg-1 of ketamine than in those given 12.5 mg kg-1 . With the onset of RJMs, the levels of these variables returned to pre-injection levels, regardless of the dose of ketamine administered. These results suggest that, following supplemental ketamine injections, spontaneous RJMs occur during a specific period when the pharmacological effects of ketamine wear off, and that these RJMs are characterized by stereotypical changes in cardiac, respiratory, and cortical activities.

Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P < 0.05), and greater variabilities were observed (P < 0.05). Rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep [median (interquartile range): 5.2 (2.6-8.9) times per h] was preceded by a transient decrease in RR intervals, and was accompanied by a transient decrease in delta elelctroencephalogram power. In humans, masseter bursts of rhythmic masticatory muscle activity were characterized by a lower activity, longer duration and longer cycle length than those of chewing (P < 0.05). Rhythmic masticatory muscle activity during non-rapid eye movement sleep [1.4 (1.18-2.11) times per h] was preceded by a transient decrease in RR intervals and an increase in cortical activity. Rhythmic masticatory muscle activity in animals had common physiological components representing transient arousal-related rhythmic jaw motor activation in comparison to human subjects.

Effect of the state of distribution of supported Pt nanoparticles on effective Pt utilization in polymer electrolyte fuel cells.

In polymer electrolyte fuel cells, it is essential to minimize Pt loading, particularly at the cathode, without serious loss of performance. From this point of view, we will report an advanced concept for the design of high performance catalysts and membrane-electrode assemblies (MEAs): first, the evaluation of Pt particle distributions on both the interior and exterior walls of various types of carbon black (CB) particles used as supports with respect to the "effective surface (ES)"; second, control of both size and location of Pt particles by means of a new preparation method (nanocapsule method); and finally, a new evaluation method for the properties of MEAs based on the Pt utilization (UPt), mass activity (MA), and effectiveness of Pt (EfPt), based on the ES concept. The amounts of Pt catalyst particles located in the CB nanopores were directly evaluated using the transmission electron microscopy, scanning electron microscopy and corresponding three-dimensional images. By use of the nanocapsule method and optimization of the ionomer, increased MA and EfPt values for the MEA were achieved. The improvement in the cathode performance can be attributed to the sharp particle-size distribution for Pt and the highly uniform dispersion on the exterior surface of graphitized carbon black (GCB) supports.

Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study.

INTRODUCTION: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000030489).

Long-term results of chest wall reconstruction with DualMesh.

The aim of this study was to evaluate the clinical outcomes of chest wall reconstruction using a new, expanded polytetrafluoroethylene prosthesis, 'DualMesh'. Between December 2005 and March 2010, chest wall reconstruction using 2-mm DualMesh was performed in 11 patients. The indication for resection was primary lung cancer in six patients, malignant mesothelioma in one patient, recurrent lung cancer in one patient, recurrent invasive thymoma in one patient, postirradiated osteomyelitis in one patient, and chondro-hamartoma in one patient. The mean observation period was 23 months, and four cases were observed for more than three years. There were no operative deaths and no wound infections. There were two postoperative complications: prolonged air leakage occurred in a patient with pulmonary emphysema who underwent right lower lobectomy, and slight paradoxical respiration occurred in the patient who underwent resection of the entire sternal body for osteomyelitis. Follow-up chest computed tomography was performed routinely. No dehiscence occurred in any cases. Chest wall reconstruction using DualMesh demonstrated acceptable durability and biocompatibility, even after long-term follow-up. DualMesh has the potential to become an ideal prosthesis for the bony chest wall as an alternative to conventional polytetrafluoroethylene or polypropylene grafts.

Fibrin glue injection method with diluted thrombin for refractory postoperative digestive fistula.

BACKGROUND: The injection of the biological adhesive fibrin glue is often performed to treat postoperative digestive fistulas. However, it is not always effective especially in case of complex fistulas with large cavities, because the fibrin glue will coagulate before the mixed solutions fill the cavity, creating dead space. We report the results of fibrin glue injection with diluted thrombin solution. METHODS: We studied the tensile strength and coagulation time of the resulting fibrin glue at each dilution of the thrombin solution. Based on in vitro study, 18 patients who had developed postoperative digestive fistula were treated by fibrin glue injection with diluted thrombin solution. RESULTS: In vitro study proved that the dilution of thrombin prolonged the coagulation time of the fibrin glue to more than 1 minute with almost no change to the tensile strength of the glue until a certain dilution was reached. The fistulas of 16 patients were successfully closed. CONCLUSIONS: Our simple method of fibrin glue injection is useful for refractory postoperative digestive fistula, even in cases of complex fistula with large cavities.

Efficacy of absorbable clips compared with metal clips for cystic duct ligation in laparoscopic cholecystectomy.

PURPOSE: This study was conducted to examine the usefulness and safety of absorbable clips in laparoscopic cholecystectomy (LC). METHODS: We retrospectively compared the clinical data of 328 patients who underwent LC using absorbable clips for cystic duct ligation and 444 patients who underwent LC using metal clips for cystic duct ligation. RESULTS: The mean operative time in the absorbable clip group was significantly shorter than that in the metal clip group. The mean intraoperative blood loss and hospital stay were not significantly different between the two groups. The rate of conversion to open laparotomy in the absorbable clip group was significantly higher than that in the metal clip group, at 6.7% vs 2.3%, respectively. The most common reason for conversion was difficult adhesions and inflammation around the gallbladder. The morbidity of the metal clip group was significantly higher than that of the absorbable clip group, at 8.4% vs 4.0%, respectively. The incidence of major postoperative complications requiring laparotomy did not differ between the two groups. There were no deaths in the absorbable clip group, but 1 of the 444 patients (0.23%) in the metal clip group died from disseminated intravascular coagulation on postoperative day 3. CONCLUSION: The results of this study suggest that absorbable clips are as safe and effective as standard metal clips for vessel and duct ligation in LC.

Adjuvant hepatic arterial infusion after curative resection of colorectal liver metastases using removable intra-arterial catheters with shape-memory alloy.

BACKGROUND AND OBJECTIVES: Although there are some reports that adjuvant hepatic arterial infusion (HAI) chemotherapy reduces the hepatic recurrence following curative resection of colorectal liver metastases, problems of indwelling catheters after chemotherapy cessation remains unsolved. The usefulness of adjuvant HAI was investigated using a removable port-catheter system. METHODS: Spiral catheterstrade mark were attempted to be placed in 17 patients who underwent curative hepatectomy. The catheter contains a special shape-memory alloy at its tip, which allows stable fixation to the vascular wall without coiling so the catheter can be removed if necessary. 5-fluorouracil (5-FU) in total dose of 12 g was intra-arterially administered. RESULTS: W spiral catheterstrade mark were successfully placed in the hepatic artery by percutaneous approach in 82% of the patients. All patients underwent scheduled chemotherapy without serious adverse events. Reservoir-catheter system was removed easily and uneventfully after discontinuation of the chemotherapy. 3D-CT angiography revealed that the hepatic artery was well preserved with short-term chemotherapy. Postoperative hepatic recurrence was observed only in 18% of the patients with the median follow-up time of 19.9 months. CONCLUSIONS: Prophylactic 5-FU HAI using W spiral cathetertrade mark and subsequent catheter extirpation is a promising strategy following curative resection of colorectal liver metastases.