Kazuyuki Okada

Effects of Ghrelin Administration After Total Gastrectomy: A Prospective, Randomized, Placebo-Controlled Phase II Study

BACKGROUND & AIMS Body weight (BW) loss and reduction of blood ghrelin level are commonly observed after total gastrectomy (TG). A prospective study was designed to elucidate whether exogenous ghrelin administration prevents postoperative BW loss by improving appetite and oral food intake in patients with gastric cancer after undergoing TG. METHODS In this randomized phase II study, 21 patients undergoing TG were assigned to a ghrelin (11 patients) or placebo group (10 patients). They received intravenous infusion of synthetic human ghrelin (3 microg/kg) or saline twice daily for 10 days after starting oral food intake following surgery. Changes in BW, appetite visual analog scale score, food intake calories, body composition, basal metabolic rate, and various blood test results were evaluated. RESULTS Excluding one patient who developed profound diaphoresis during ghrelin infusion, 20 patients completed the study. Food intake and appetite were significantly higher with ghrelin compared with placebo (average, 13.8 vs 10.4 kcal/kg/day [P = .030] and 5.7 vs 3.9 cm [P = .032], respectively). BW loss was significantly lower in the ghrelin than in the placebo group (-1.4% vs -3.7%; P = .044). Fat mass, lean body mass, and basal metabolic rate decreased significantly in the placebo group; however, the reductions in lean body mass and basal metabolic rate were not significant in the ghrelin group, although that of fat mass was significant. CONCLUSIONS Short-term administration of synthetic ghrelin was safe and successfully lessened postoperative BW loss and improved appetite and food intake after TG.

Injection of LPS Causes Transient Suppression of Biological Clock Genes in Rats

BACKGROUND The biological clock regulates circadian rhythm and is important for sustaining homeostasis. Here we examined the response of biological clock genes to systemic inflammatory stimulation. MATERIALS AND METHODS At 08:00 h (= Zeitgeber time [ZT] 01), male Wistar rats (7-wk-old) maintained on a 12:12 h light:dark cycle (light on 07:00-19:00 h) received intravenous injection of 1 mg/kg lipopolysaccharide (LPS group) or 0.3 mL saline (control group). They were then sacrificed every 4 h (09:00 h = ZT 02, 13:00 h = ZT 06, 17:00 h = ZT 10, 21:00 h = ZT 14, 01:00 h = ZT 18, 05:00 h = ZT 22) over a 2-d period, and blood, brain, and liver samples were obtained for analysis (n = 4 at each time for each group). The expression levels of clock gene, rPer2, and those of clock controlled gene, rDBP, were quantified in the suprachiasmatic nucleus by in situ hybridization, while those of rPer1, rPer2, rDBP, rPPARA, and rFKBP51 in the liver were determined by quantitative RT-PCR. RESULTS In the suprachiasmatic nucleus of control rats, rPer2 and rDBP mRNA expression levels showed robust circadian patterns with peak levels at ZT 06 and ZT 10, respectively. LPS significantly suppressed both genes on day 1 but recovery was noted on day 2. Similarly, LPS significantly suppressed rPer1, rPer2, rDBP, rPPARA, and rFKBP51 mRNA expression levels in the liver on day 1 but recovery was noted on day 2, whereas a robust circadian pattern was noted in the control group. CONCLUSION Our results indicate that LPS causes transient suppression of the biological clock genes and suggest that the biological clock plays an important role in the response to systemic inflammatory stimulation.

Long‐term and short‐term evaluation of esophageal reconstruction using the colon or the jejunum in esophageal cancer patients after gastrectomy

For esophageal cancer patients, the gastric tube is the first choice as an esophageal substitute, with the colon or the jejunum being used when the stomach cannot be used. We retrospectively compared these two methods from the viewpoint of peri-operative complications and long-term bodyweight alteration. From 1998 to 2005 53 patients who had undergone subtotal esophagectomy due to thoracic esophageal cancers were given reconstruction with the colon (28 cases) or the jejunum (25 cases). Both intestines were reconstructed via the subcutaneous route and were anastomosed to the internal mammalian artery and vein for a supercharged blood supply. There was no difference in operating time and blood loss. Compared with the colon reconstruction group, the hospital stay of the jejunum reconstruction group was significantly shorter (65 days vs 45 days, P = 0.0120) and the incidence of anastomotic leakage tended to be less (13 cases, 46%vs 6 cases, 24%, P = 0.1507), while other operative morbidity did not differ between the two groups. Bodyweight loss, which is a serious postoperative sequela after esophagectomy, was less in the jejunum group than in the colon group, showing a significant difference at 12 months after surgery. Our retrospective study revealed the jejunum to be superior to the colon for the reconstruction after esophagectomy along with gastrectomy, with respect to anastomotic leakage and bodyweight loss. The next step will be to conduct a prospective large cohort study.

Per2 gene expressions in the suprachiasmatic nucleus and liver differentially respond to nutrition factors in rats.

BACKGROUND We previously reported that parenteral nutrition (PN) altered the circadian rhythm of clock gene expression in the suprachiasmatic nucleus (SCN) and liver of rats. The present study was designed to investigate what factor(s) in the PN solution causes the alteration. METHODS Male Wistar rats, kept under light and dark conditions, were divided into 4 groups after cannulation. The sham operation group received saline solution from 8 am to 8 pm at the rate of 36 mL/kg/12 hours. The glucose, amino acid, and saline groups received a glucose solution (20% wt/vol glucose, 261 kcal/kg/d, Na(+) 50 meq/L and Cl(-) 50 meq/L), an amino acid solution (4.3% wt/vol 1.78 gN/kg/d, Na +50 meq/L and Cl(-) 50 meq/L) and a saline solution from 8 am to 8 pm at a rate of 240 mL/kg/12 hours, respectively. Rats were killed every 4 hours (9 am = Zeitgeber Time (ZT) 02, 1 pm = ZT06, 5 pm = ZT10, 9 pm = ZT14, 1 am = ZT18, 5 am = ZT22, n = 3 at each point), and brain and liver samples were removed. rPer2 expression in the SCN and liver was analyzed by in situ hybridization and Northern blotting, respectively. RESULTS Compared with the sham-operation rats, the peak time of rPer2 expression in the SCN was significantly affected by glucose, amino acid, and saline solutions. Among them, glucose-group rats showed the rPer2 expression most similar to that of diurnal PN. On the other hand, the rPer2 expression in the liver was shifted in the glucose and amino-acid-solution groups. The pattern of rPer2 expressions in the amino acid group was most similar to that of the diurnal PN group. CONCLUSIONS These results indicate that the most potent entrainer for the SCN clock is glucose, whereas that for the liver is amino acid.

Effects of fibrin on the secretion of plasminogen activator inhibitor-1 from endothelial cells and on protein kinase C

We previously demonstrated that cultured human umbilical vein endothelial cells (HUVECs) overlaid with a fibrin clot induced a slight increase in tissue-type plasminogen activator (t-PA) secretion and marked reduction in plasminogen activator inhibitor-1 (PAI-1) secretion. In this study, the intracellular signal transduction after fibrin stimulation was further investigated by analyzing cyclic AMP (cAMP) and protein kinase C (PK-C). When HUVECs were stimulated by fibrin clots, t-PA mRNA increased to 130% but PAI-1 mRNA decreased to 42%. These changes concurred with the data on the protein levels of t-PA and PAI-1 as previously reported. The effect of fibrin on t-PA production in HUVECs was not significantly altered after the elevation of cAMP by either forskolin or dibutyryl cAMP. Furthermore, an effect of fibrin on t-PA production did not appear when the cells were treated by phorbol 12-myristate 13-acetate (PMA) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The suppressive effect of fibrin on PAI-1 secretion from HUVECs was not altered by elevation of cAMP. Regarding the activation of PK-C by PMA, PAI-1 secretion was enhanced, but was suppressed by fibrin stimulation. H-7 suppressed PAI-1 secretion and further stimulation by fibrin almost completely abolished PAI-1 secretion. These changes were well associated with mRNA levels of t-PA and PAI-1. These results suggested that fibrin on HUVECs preferably down-regulates PK-C resulting in a decrease of PAI-1 in both the protein and mRNA levels and that effect of fibrin on t-PA secretion is neither involved in PK-C nor cAMP pathway.

Ablative Acceleration of Pellet Shells Irradiated by External Soft X-ray Sources

The first direct experimental measurement of soft X-ray driven ablation pressure has been done using a spherical pellet target and external soft X-ray sources. It has been found that the pressure is about 10 Mbar at an incident X-ray intensity Ix of 1013 W/cm2 for glass and CH targets, and its intensity scaling is Ix0.8. X-ray backlighted pellet images indicate that X-ray geometrical smoothing at indirect irradiation is very effective for symmetrizing the implosion.

The clinical importance of a transcription reverse-transcription concerted (TRC) diagnosis using peritoneal lavage fluids in gastric cancer with clinical serosal invasion: a prospective, multicenter study.

PURPOSE We have developed a novel molecular method of diagnosis using the technique of transcriptase-reverse transcriptase concerted reaction (TRC) for the detection of cancer micrometastasis. This study prospectively examined the clinical importance of the TRC diagnosis with peritoneal lavage fluids collected from gastric cancer operations at multiple institutes. METHODS TRC amplification targeting carcinoembryonic antigen mRNA was applied to detect gastric cancer cells in peritoneal lavage fluids obtained during gastric cancer resections from nine different hospitals. A total of 137 patients with a clinical diagnosis of serosa-invading neoplasms were enrolled to investigate the correlation between the TRC diagnosis and patient prognosis. RESULTS Of the 137 patients, 27 (20%) were positive by cytologic examination. In contrast, TRC targeting carcinoembryonic antigen mRNA was positive in 59 of 137 (54%) patients. TRC positivity was associated with a poorer overall survival in all patients and in the 104 patients who underwent a curative operation. TRC positivity also was associated with the peritoneal recurrence-free survival rate in the 104 curative cases. Multivariate analysis showed that TRC positivity and the pathologic N factor were prognostic factors for the overall survival time. CONCLUSION Our prospective multicenter study showed that the TRC test using peritoneal lavage fluids could be a potential prognostic factor to predict patient survival and peritoneal recurrence with clinically diagnosed, serosa-invading gastric cancer.

Evaluating the surgeon's stress when using surgical assistant robots

We propose a method for using surgeons biological information to evaluate the surgeons stress in his/her using a surgical assistant system. The surgeons biological information were saliva and heart rate. The stress was measured by analyzing Cortisol, alpha-amylase, and total protein in saliva, and we analyzed the acceleration plethysmogram variability as the indexes of autonomic nervous activity, those were coefficient of variance of the a-a interval and low-frequency band power spectrum(LF), high-frequency band power spectrum (HF), the ratio of LF to HF (LF/HF). To validate the effectiveness of the proposed method, we conducted a laparoscopic cholecystectomy simulation. In conclusion, we confirmed our method had an ability to objectively evaluate the surgeons stress during surgery.

Laser implosion of thick low‐Z foam coated glass microballoon

Driving pressure uniformity on the pusher surface has been significantly improved using a thick low density foam coated pellet with 120‐ps laser pulse irradiation. The pusher surface is geometrically kept at 100 μm from the laser absorption region. The hydrodynamic converging mechanism in the foam medium may be responsible for the observed smoothing.

Optical Beam Guides For Medical CO 2 And Excimer Lasers

The metal and polymer compound hollow tube is effective guide for cw CO2laser beam transmission. We have tride to high peak pulse CO2laser beam delivery with the hollow tube guide. Using the CO2 pulse laser have high peak (46MW max. ,short pulse width(80ns) and repeat pulses(under lOpps). In this experiments, the laser beam transmittance was obtained ca.90%/m. So the hollow tube are confirmed as useful beam guide technique for also pulse CO2 laser. We are having also investigates of UV laser beam transmission with the hollow tube as CO2 laser beam. We have used KrF excimer laser(248nm wavelength). We found that the random polarized beam transmittance was ca.26%/m, if polarized beam was ca.37%/m, delivery average power and energy were ca.1 watt(220kW peak power) and 5m.J. per pulse respectively. On the other hand, we have been developing UV optical fiber for Kr F laser, Results so far were obtained above 80%/m transmittance by OH ion added quartz glass fiber.