Anaesthesia-dependent oscillatory EEG features in the super-elderly.

OBJECTIVE: Although the characteristics of electroencephalograms (EEGs) have been reported to change with age, anaesthesia-dependent oscillatory features and reactivity of the super-elderly EEG to anaesthesia have not been examined in detail. METHODS: Participants comprised 20 super-elderly patients (age; mean ±â€¯standard deviation, 87.1 ±â€¯3.8 years) and 20 young adult patients (35.5 ±â€¯8.5 years). At three levels of sevoflurane anaesthesia (minimum alveolar concentration [MAC] of 0.3, 0.7, and 1.4), oscillatory features of the frontal EEG were examined by analysing quadratic phase coupling (bicoherence) and power spectrum in α and δ-θ areas and compared in an anaesthesia-dependent manner, using the Friedman test. RESULTS: Among super-elderly individuals, bicoherences in the δ-θ area showed anaesthesia-dependent increases (median [interquartile range], 12.9% [5.2%], 19.2% [9.1%], 23.3% [8.7%]; 0.3, 0.7, 1.4 MAC sevoflurane, p = 0.000), whereas bicoherence in the α area did not change at these different anaesthesia levels (11.2% [3.9%], 12.5% [4.4%], 14.1% [5.7%], respectively; p = 0.142), counter to the results found in young adult patients, where both δ-θ and α bicoherences changed with anaesthesia. CONCLUSIONS: In the super-elderly, δ-θ bicoherence of EEG shows anaesthesia- dependent changes, whereas α activity remains small irrespective of anaesthesia level. SIGNIFICANCE: Quantification of δ-θ bicoherence is a candidate for anaesthesia monitoring in the super-elderly.

Radiofrequency identification tag system improves the efficiency of closed vitrification for cryopreservation and thawing of bovine ovarian tissues.

PURPOSE: A radiofrequency identification (RFID) tag system was designed to streamline cryopreservation and thawing procedures. This study evaluated the usefulness of the RFID tag system for improving the efficiency of cryopreserving/thawing bovine ovarian tissue by the closed vitrification protocol. METHODS: Six participants carried out closed vitrification and thawing of bovine ovarian tissues procedures using either the conventional or the new RFID tag method, and the time required to perform each step of the respective methods was measured. After normality of data was confirmed by the Shapiro-Wilk test, the significance of differences was assessed by the unpaired t test. RESULTS: When closed vitrification was performed, the time required for each step showed a significant difference between the two methods (t(4) = 2.938, p = 0.042, d = 2.40), and the total cryopreservation time was 11 min shorter using the RFID tag system. When thawing was performed, the time required for each step also showed a significant difference between the two methods (t(4) = 2.797, p = 0.049, d = 2.28), and the total thawing time was 2 min shorter using the RFID tag system. CONCLUSION: The RFID tag system tested in this study seems to be suitable for managing biological samples stored in liquid nitrogen. Adoption of an RFID tag system by fertility centers may not only improve the efficiency of cryopreserving/thawing reproductive tissues but could also reduce human error.

Hyperglycaemia augments lipopolysaccharide-induced reduction in rat and human macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein pathway.

BACKGROUND: Macrophage phagocytosis constitutes an essential part of the host defence against microbes and the resolution of inflammation. Hyperglycaemia during sepsis is reported to reduce macrophage function, and thus, potentiate inflammatory deterioration. We investigated whether high-glucose concentrations augment lipopolysaccharide-induced reduction in macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein (CHOP) pathway using animal and laboratory investigations. METHODS: Peritoneal macrophages of artificially ventilated male Wistar rats, divided into four groups based on target blood glucose concentrations achieved by glucose administration with or without lipopolysaccharide, were obtained after 24 h. Human macrophages were also cultured in normal or high glucose with or without lipopolysaccharide exposure for 72 h. Changes in the phagocytic activity, intranuclear CHOP expression, and intracellular Akt phosphorylation status of macrophages were evaluated. These changes were also evaluated in human macrophages after genetic knock-down of CHOP by specific siRNA transfection or resolvin D2 treatment. RESULTS: Lipopolysaccharide impaired phagocytosis, increased intranuclear expression of CHOP, and inhibited Akt phosphorylation in both rat peritoneal and human macrophages. Hyperglycaemic glucose concentrations augmented these changes. Genetic knock-down of CHOP restored phagocytic ability and Akt phosphorylation in human macrophages. Furthermore, resolvin D2 co-incubation restored the inhibited phagocytosis and Akt phosphorylation along with the inhibition of intranuclear CHOP expression in human macrophages. CONCLUSIONS: These findings imply that controlling endoplasmic reticulum stress might provide new strategies for restoring reduced macrophage phagocytosis in sepsis-induced hyperglycaemia.

mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury.

Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that controls protein synthesis in the nervous system. Here, we characterized the role of protein synthesis regulation due to mTOR signaling in rat dorsal root ganglion (DRG) following plantar incision. The number of phosphorylated mTOR (p-mTOR)-positive neurons was increased 2-4days after the incision. Rapamycin inhibited p-mTOR expression in the DRG and thermal hypersensitivity 3days but not 1day after the incision. Vesicular glutamate transporter 2 (VGLUT2) expression was increased after the plantar incision, which was inhibited by rapamycin. These results demonstrated that tissue injury induces phosphorylation of mTOR and increased protein level of VGLUT2 in the DRG neurons. mTOR phosphorylation involves in maintenance of injury-induced thermal hypersensitivity.

Comparative study of Poincaré plot analysis using short electroencephalogram signals during anaesthesia with spectral edge frequency 95 and bispectral index.

The return or Poincaré plot is a non-linear analytical approach in a two-dimensional plane, where a timed signal is plotted against itself after a time delay. Its scatter pattern reflects the randomness and variability in the signals. Quantification of a Poincaré plot of the electroencephalogram has potential to determine anaesthesia depth. We quantified the degree of dispersion (i.e. standard deviation, SD) along the diagonal line of the electroencephalogram-Poincaré plot (named as SD1/SD2), and compared SD1/SD2 values with spectral edge frequency 95 (SEF95) and bispectral index values. The regression analysis showed a tight linear regression equation with a coefficient of determination (R(2) ) value of 0.904 (p < 0.0001) between the Poincaré index (SD1/SD2) and SEF95, and a moderate linear regression equation between SD1/SD2 and bispectral index (R(2)  = 0.346, p < 0.0001). Quantification of the Poincaré plot tightly correlates with SEF95, reflecting anaesthesia-dependent changes in electroencephalogram oscillation.

Tumor necrosis factor-alpha induces expression of C/EBP-beta in primary afferent neurons following nerve injury.

CCAAT/enhancer binding protein-beta (C/EBP-beta) is a transcription factor that belongs to the C/EBP family. To understand the role of C/EBP-beta in the peripheral nervous system, we investigated the expression of C/EBP-beta in the dorsal root ganglion. C/EBP-beta was weakly detected in nuclei of naive dorsal root ganglion (DRG) neurons. Spinal nerve ligation increased the expression of C/EBP-beta in L4 and L5 DRG neurons. Treatment with anti-TNF-alpha prevented SNL-induced pain hypersensitivity and C/EBP-beta expression in the DRG. Injection of TNF-alpha into the sciatic nerve produced transient pain hypersensitivity and induction of C/EBP-beta expression in the DRG. These results demonstrate that C/EBP-beta is activated in the DRG neurons by a TNF-alpha-dependent manner and might be involved in the activation of primary afferent neurons after nerve injury.

Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan Oncology Group LETS study.

BACKGROUND: A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented. RESULTS: The updated analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713; 95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC. CONCLUSIONS: These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.

Nitric oxide/soluble guanylyl cyclase signaling mediates depolarization-induced protection of rat mesencephalic dopaminergic neurons from MPP⁺ cytotoxicity.

Neuronal electrical activity has been known to affect the viability of neurons in the central nervous system. Here we show that long-lasting membrane depolarization induced by elevated extracellular K(+) recruits nitric oxide (NO)/soluble guanylyl cyclase/protein kinase G signaling pathway, induces 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)-mediated protein S-guanylation, and confers dopaminergic neuroprotection. Treatment of primary mesencephalic cell cultures with 1-methyl-4-phenylpyridinium (MPP(+)) for 72 h decreased the number of dopaminergic neurons, whereas the cell loss was markedly inhibited by elevated extracellular concentration of K(+) (+40 mM). The neuroprotective effect of elevated extracellular K(+) was significantly attenuated by tetrodotoxin (a Na(+) channel blocker), amlodipine (a voltage-dependent Ca(2+) channel blocker), N(ω)-nitro-l-arginine methyl ester (l-NAME) (a nitric oxide synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (a soluble guanylyl cyclase inhibitor), and KT5823 or Rp-8-bromo-ß-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate (Rp-8-Br-PET-cGMPS) (protein kinase G inhibitors). Elevated extracellular K(+) increased 8-nitro-cGMP production resulting in the induction of protein S-guanylation in cells in mesencephalic cultures including dopaminergic neurons. In addition, exogenous application of 8-nitro-cGMP protected dopaminergic neurons from MPP(+) cytotoxicity, which was prevented by zinc protoporphyrin IX, an inhibitor of heme oxygenase-1 (HO-1). Zinc protoporphyrin IX also inhibited the neuroprotective effect of elevated extracellular K(+). On the other hand, KT5823 or Rp-8-Br-PET-cGMPS did not inhibit the induction of HO-1 protein expression by 8-nitro-cGMP, although these protein kinase G inhibitors abrogated the neuroprotective effect of 8-nitro-cGMP. These results suggest that protein S-guanylation (leading to HO-1 induction) as well as canonical protein kinase G signaling pathway plays an important role in NO-mediated, activity-dependent dopaminergic neuroprotection.

Usefulness of a bidirectional e-learning material for explaining surgical anesthesia to cancer patients.

BACKGROUND: We developed an e-learning system, which is based on an interactive animation video that assists anesthesiologists in preanesthetic interviews. MATERIALS AND METHODS: First, the feasibility of the system was investigated in 18 anesthesiologists and 95 volunteers from the general public. Content/quantity, operability, and satisfaction were assessed with a five-point scale. Secondly, a randomized controlled trial was conducted on 211 cancer patients who were scheduled to undergo general anesthesia. They were divided into an e-learning group (n = 106) and a control group (n = 105). The patients in the e-learning group watched the interactive animation before a preanesthetic interview by an anesthesiologist. RESULTS: In 10 of the 11 items for content/quantity, operability, and satisfaction, the average score for both anesthesiologists and volunteers was ≥3.0 in feasibility study. Then, the level of patient comprehension of preoperative rounds and postoperative complications in the e-learning group was significantly higher than that in the control group (mean: 4.4 ± 0.5 versus 4.1 ± 0.7, P = 0.003, and 4.3 ± 0.5 versus 4.2 ± 0.5, P = 0.02); however, no significant difference in anxiety was seen between the two groups. Patient satisfaction in the e-learning group was significantly higher (mean: 4.3 ± 0.5 versus 4.0 ± 0.6, P = 0.002). CONCLUSION: The e-learning system is an effective supplementary tool for preanesthetic interviews in cancer patients.

Hyperventilation-induced hypocapnia changes the pattern of electroencephalographic bicoherence growth during sevoflurane anaesthesia.

BACKGROUND: Hyperventilation, with the resulting hypocapnia, reduces cerebral blood flow and causes slowing of the EEG activity. However, neuronal oscillating properties including the thalamocortical network during hyperventilation have not been elucidated. To assess these features provoked by hyperventilation, the present study examined quadratic phase coupling features by means of bicoherence analysis. METHODS: Twenty-two patients were anaesthetized using sevoflurane 1.5% combined with remifentanil or epidural anaesthesia. After a stable normocapnic period, hypocapnia was induced by hyperventilation, and the raw EEG signals were collected. Bispectral analysis (bicoherence) and power spectrum analysis were performed before and after hypocapnia. RESULTS: Mean (sd) peak bicoherence in the delta- area increased from 35.6 (10.9)% during normocapnia to 43.8 (10.9)% during hypocapnia (P<0.05), whereas mean (sd) peak bicoherence in the alpha area decreased from 42.8 (14.4)% during normocapnia to 37.5 (12.3)% during hypocapnia (P<0.05). Normalized power in the delta- frequencies on the power spectrum increased from 60.2 (13.1)% to 72.5 (12.7)% (P<0.05). Bispectral index and spectral edge frequency changed from 45.9 (7.0) to 40.1 (5.6) (P<0.05) and from 15.0 (2.3) to 14.0 (2.5) Hz (P<0.05), respectively. No significant differences in these values were observed between the two types of anaesthesia. CONCLUSIONS: Hypocapnia enlarged bicoherence growth in the delta- frequency range, suggesting the contribution of subcortical oscillating mechanisms in regulating EEG during hyperventilation.

Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403).

The purpose of this study was to evaluate the efficacy of gefitinib and the feasibility of screening for epidermal growth factor receptor (EGFR) mutations among select patients with advanced non-small cell lung cancer (NSCLC). Stage IIIB/IV NSCLC, chemotherapy-naive patients or patients with recurrences after up to two prior chemotherapy regimens were eligible. Direct sequencing using DNA from tumour specimens was performed by a central laboratory to detect EGFR mutations. Patients harbouring EGFR mutations received gefitinib. The primary study objective was response; the secondary objectives were toxicity, overall survival (OS), progression-free survival (PFS), 1-year survival (1Y-S) and the disease control rate (DCR). Between March 2005 and January 2006, 118 patients were recruited from 15 institutions and were screened for EGFR mutations, which were detected in 32 patients--28 of whom were enrolled in the present study. The overall response rate was 75%, the DCR was 96% and the median PFS was 11.5 months. The median OS has not yet been reached, and the 1Y-S was 79%. Thus, gefitinib chemotherapy in patients with advanced NSCLC harbouring EGFR mutations was highly effective. This trial documents the feasibility of performing a multicentre phase II study using a central typing laboratory, demonstrating the benefit to patients of selecting gefitinib treatment based on their EGFR mutation status.

Stearoyl-CoA desaturase mRNA expression during bovine adipocyte differentiation in primary culture derived from Japanese Black and Holstein cattle.

Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of monounsaturated fatty acids (MUFAs). In cattle, the MUFAs are related to softness and flavor of meat. In order to investigate gene expression profile during bovine preadipocyte differentiation, we isolated stromal-vascular cells from perirenal adipose tissues of Japanese Black and Holstein steers. Gene expression level of adipocyte type fatty acid binding protein (FABP4), SCD, sterol regulatory element binding protein 1 (SREBP1) and CCAAT/enhancer binding protein alpha (C/EBP-alpha) were elucidated by real-time PCR assay. The levels of SCD mRNA expression were significantly increased to 10.8 and 6.3-fold in Japanese Black and Holstein, respectively, on day 1 of the culture. The difference in SCD expression between the two breeds may reflect differences in the fat development characteristics of the cattle breeds. Although transcription factors SREBP1 and C/EBP-alpha are supposed to regulate SCD expression, expression levels of the two factors were not completely consistent with that of SCD.

Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol.

BACKGROUND: The reticular and thalamocortical system is known to play a prominent role in spindle wave activity, and the spindle wave is related to the sedative effects of anaesthetics. Recently, bispectral analysis of the EEG has been developed as a better method to indicate nonlinear regulation including the thalamocortical system linking to the cortical area. In the present study, in order to explore the interference of ketamine with the nonlinear regulation of the sub-cortical system, we examined the effect of ketamine on spindle alpha waves through the bispectral analysis. METHODS: The study included 21 patients. Anaesthesia was induced and maintained using a propofol-TCI system (target-controlled infusion, with target concentration 3.5 microg ml(-1)). An A-2000 BIS monitor was used and the raw EEG signals were collected via an RS232 interface on a personal computer. Bicoherence, the normalized bispectrum, and power spectrum were analysed before and after i.v. administration of 1 mg kg(-1) racemic ketamine. RESULTS: Propofol caused alpha peaks in both power and bicoherence spectra, with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0) Hz, respectively. The addition of ketamine significantly shifted each peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz, respectively [P < 0.05, mean (SD)]. CONCLUSIONS: Ketamine shifted the alpha peaks of bicoherence induced by propofol to higher frequencies. This suggests that ketamine changes the alpha spindle rhythms through the modulation of the nonlinear sub-cortical reverberating network.

Metastasis in para-aortic lymph nodes in patients with advanced gastric cancer, treated with extended lymphadenectomy.

BACKGROUND/AIMS: Lymph node dissection is an essential component of curative resection for advanced gastric cancer. To improve the survival of N2 patients, Asian surgeons have been performing D2+para-aortic lymph node dissection. The current study presents the results of lymph node status from multicenter trial of D2 and D2 + para-aortic nodal (No.16) dissection (D4 dissection). METHODOLOGY: Patients enrolled in the study had potentially curable gastric adenocarcinoma in an advanced stage, T2, T3 or T4/N1 or N2. Patients were randomized to undergo either D2 or D4 gastrectomy. RESULTS: Two hundred and seventy patients were registered and 136 and 134 patients were allocated into the D2 or D4 group, respectively. The average nodal yield of No.16 in D4 group was 18.4 +/- 14.1, ranging from 2 to 84. No.16 metastasis was detected in 12 (9.0%) of 134 D4 patients. One, 9 and 2 patients had simultaneous involvement in N1, N2, and N3 (No.8p, 12, 13 or 14). Namely, in 39 patients who were diagnosed as N2 from the lymph node status in N1 and N2 levels, nine (23.0%) patients had No.16 metastasis. The stage migration by D4 was found in 10 (7.5%). Logistic regression analysis revealed that the stations of No.7 and No.8 were the significant predictors of No.16 involvement. CONCLUSIONS: The present study may strongly suggest that prophylactic D4 dissection may be indicated for patients with N2 involvement, and that No.7 and No.8 are the junctional nodes for D4 dissection.

Ketamine, an NMDA-antagonist, increases the oscillatory frequencies of alpha-peaks on the electroencephalographic power spectrum.

BACKGROUND: Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is known to activate the electroencephalogram (EEG), despite its sedative effects. Spindle oscillations are known to be related to the sedative actions of the reticular thalamic nucleus with links to thalamocortical neurons. This study was designed to examine the effect of ketamine on the spindle oscillations to understand the simultaneous sedative effect and EEG activation that occurs with ketamine, by comparing the EEG in emergence. METHODS: Anesthesia was induced with propofol using a target-controlled infusion (TCI) system (3.5 microg/ml). Seventeen patients, scheduled for non-cranial surgery under general anesthesia combined with epidural anesthesia, were randomly divided into two groups: (i) anesthesia was maintained with TCI-propofol alone (n= 8) and (ii) anesthesia was maintained with TCI-propofol and intravenously administered ketamine (n= 9). The EEG was continuously monitored and EEG indices and power spectra were determined. RESULTS: Propofol alone caused the alpha-peaks of the power spectra to occur at an average frequency of 10.4 +/- 0.9 Hz; the addition of ketamine shifted the peaks to higher frequencies of 15.1 +/- 1.4 Hz (P < 0.05). On the other hand, when the EEG was activated by discontinuation of propofol, the corresponding alpha-peaks disappeared. CONCLUSIONS: Ketamine increased the frequencies of alpha-spindle waves induced by propofol, but did not block their formations. The phenomena have the possibility to underlie the cooperative effect between propofol and ketamine concerning sedation and anesthesia.

Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model.

Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-alpha, and interleukin-beta concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.

Operative morbidity and mortality after D2 and D4 extended dissection for advanced gastric cancer: a prospective randomized trial conducted by Asian surgeons.

BACKGROUND/AIMS: A randomized study was performed to evaluate morbidity and mortality after D2 (level 1 and 2 lymphadenectomy) and D4 (D2 plus lymphadenectomy of para-aortic lymph nodes) dissection for advanced gastric cancer. METHODOLOGY: Two hundred and fifty-six patients with advanced gastric adenocarcinoma were enrolled (128 to each group). Patients were randomly allocated into D2 (N = 128) or D4 (N = 128) group. The first and second tiers of lymph nodes are removed in D2 dissection. In D4 gastrectomy, the paraaortic lymph nodes were additionally removed. RESULTS: There was no indication of significant distribution bias with regard to age, sex, T-grade, and N-grade between the two groups. Operation time of D4 gastrectomy (369 +/- 120 min) was significantly longer than that of D2 gastrectomy (273 +/- 1103 min), and blood loss of the D4 group (872 +/- 683 mL) was significantly greater than that of the D2 group 571 +/- 527 mL (P < 0.001). Five (4%) and two (2%) medical complications developed in the D2 and D4 groups, respectively. Surgical complications developed in 28 (22%) and 48 patients (38%) after D2 and D4 gastrectomy. The most common complications were anastomotic leakage, pancreatic fistula, and abdominal abscess. Pancreatic fistula developed in 6 (19%) of 32 patients after D4 plus pancreatosplenectomy, but the incidence of pancreatic fistula after D2 gastrectomy plus pancreatosplenectomy was low (6%, 1/16). Two patients died within 30 days of operation (0.8%, 2/256), and each patient belonged to the D2 and D4 group. CONCLUSIONS: Although there is a significantly higher surgical complication rate in D4 dissection, D4 dissection can be done safely as D2 dissection when performed by well-trained surgeons.

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

Targeting mechanisms of Pseudomonas aeruginosa pathogenesis.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for ventilator-acquired pneumonia, acute lower respiratory tract infections in immunocompromised patients and chronic respiratory infections in cystic fibrosis patients. High incidence, infection severity and increasing resistance characterize P. aeruginosa infections, highlighting the need for new therapeutic options. One such option is to target the many pathogenic mechanisms conferred to P. aeruginosa by its large genome encoding many different virulence factors. This article reviews the pathogenic mechanisms and potential therapies targeting these mechanisms in P. aeruginosa respiratory infections.