Differences of cerebral oxygen saturation in dialysis patients: a comparison of three principals of near infrared spectroscopy.

PURPOSE: It has been reported that cerebral oxygen saturation (rSO2) measured by near infrared spectroscopy is low in dialysis patients. We compared the rSO2 values of dialysis patients before living donor kidney transplantation and their donors as controls by using three spectroscopes that utilize different principals, the INVOS 5100C (spatially resolved spectroscopy), FORE-SIGHT ELITE (modified Beer-Lambert law) and tNIRS-1 (time-resolved spectroscopy). METHODS: Before induction of anesthesia, the sensors of one of the three spectroscopes were placed on the forehead and rSO2 values were recorded followed by the same measurement using the other two spectroscopes. The primary objective was to compare the rSO2 values of the dialysis patients and controls using the three spectroscopes by the unpaired t test. Then we compared the rSO2 values among the spectroscopes in both dialysis patients and controls by one-way ANOVA. Finally, we examined the relations between the rSO2 values and the physiological values by using the Pearson correlation coefficient. RESULTS: Fifteen pairs of dialysis patients and controls were studied. With the INVOS 5100 C, the values of the dialysis patients (59.7 ± 9.7% (mean ± standard deviation) were 13% lower than those of the controls (73.3 ± 6.9%) (P < 0.01). With the tNIRS-1, the values were 57.8 ± 4.8% in the dialysis patients and 63.3 ± 3.5% in the controls (P < 0.01). Almost no differences were observed with the FORE-SIGHT ELITE (71.6 ± 4.9% [dialysis patients] vs. 70.8 ± 4.3% [Controls]) (P = 0.62). Among the spectroscopes, the values were significantly different in both dialysis patients and controls. For the INVOS 5100C and tNIRS-1, correlation coefficients between rSO2 values and blood Hb and serum Alb were more than 0.5. CONCLUSIONS: The rSO2 values for comparisons between the dialysis patients and the controls were different according to differences of the principles of the near infrared spectroscopes. In the INVOS 5100C and tNIRS-1, rSO2 values may be related to blood Hb and serum Alb.

Changes in Cerebral Hemodynamics During Systemic Pulmonary Shunt and Pulmonary Artery Banding in Infants with Congenital Heart Disease.

Palliative surgery is often performed in the treatment of congenital heart disease. Two representative palliative procedures are the systemic pulmonary shunt and pulmonary artery banding. Dramatic changes in cerebral hemodynamics may occur in these operations due to changes in the pulmonary-to-systemic blood flow ratio and systemic oxygenation. However, there seem to be almost no studies evaluating them. Accordingly, we evaluated cerebral perfusion by transcranial Doppler ultrasonography and cerebral oxygenation by near infrared spectroscopy during these procedures. In the post hoc analysis of a previous prospective observational study, cerebral blood flow velocities of the middle cerebral artery measured by transcranial Doppler were compared between the start and end of surgery as were the pulsatility index and resistance index. The cerebral oxygenation values were also compared between the start and end of surgery. Twenty-two infants with systemic pulmonary shunt and 20 infants with pulmonary artery banding were evaluated. There were no significant differences of the flow velocities between the start and end of surgery in either procedure. The pulsatility index significantly increased after pulmonary artery banding, which may compete with the increase in cerebral perfusion due to the increase in systemic blood flow. The cerebral oxygenation decreased in both procedures, possibly due to an increase in body temperature. Arterial oxygen saturation was almost the same before and after both procedures. Contrary to our expectation, the changes in cerebral hemodynamics in the palliative operations were small if the management of physiological indices such as arterial oxygen saturation was properly performed during the procedures.

Change in cerebral circulation during the induction of anesthesia with remimazolam.

PURPOSE: Remimazolam is a new ultra-short-acting benzodiazepine with unknown effects on cerebral circulation. We measured total cerebral hemoglobin concentrations, which reflect cerebral blood volume (CBV), and cerebral oxygen saturation, using time-domain near-infrared spectroscopy, which can measure the absolute values of cerebral hemoglobin concentrations. We also measured cerebral blood flow velocity (CBFV) in the middle cerebral artery using transcranial Doppler as an indicator of cerebral blood flow (CBF). We did so to examine the effect of remimazolam on cerebral circulation in humans, as assessed CBV, CBF, and cerebral oxygen saturation. METHODS: This was a prospective, observational study. Fifteen patients without serious complications scheduled for general anesthesia were recruited. We measured total cerebral hemoglobin concentrations, CBFV, and cerebral oxygen saturation throughout the anesthetic induction course with remimazolam. RESULTS: Total cerebral hemoglobin concentrations did not change during the process (p = 0.51). In contrast, the mean CBFV was reduced by 11% (significant, p = 0.04). The drop in mean blood pressure following the induction of anesthesia was 17%; however, it was within the range of cerebrovascular autoregulation. Moreover, cerebral oxygen saturation increased by 4% (statistically significant, p < 0.01). CONCLUSIONS: We found that anesthetic induction with remimazolam did not alter CBV and reduced CBF in uncomplicated patients.

The relationship between years of anesthesia experience and first-time intubation success rate with direct laryngoscope and video laryngoscope in infants: a retrospective observational study.

PURPOSE: Studies in adults have reported that video laryngoscope is more useful than direct laryngoscope when training less experienced anesthesiologists. However, whether this is true for infants remains unclear. Therefore, this study aimed to evaluate whether the use of video laryngoscope would result in smaller differences in success rate according to anesthesiologists' expertise than those in direct laryngoscope. METHODS: Medical records and video recordings from the operating room of patients aged < 1 year who underwent non-cardiac surgery between March 2019 and September 2021 were reviewed. Tracheal intubations between April 8, 2020, and June 20, 2021, were excluded due to the shortage of video laryngoscope blades during the COVID-19 pandemic. Rates of first-time tracheal intubation success were compared by years of anesthesia experience and initial intubation device. RESULTS: In total, 125 of 175 tracheal intubations were analyzed (direct laryngoscope group, n = 72; video laryngoscope group, n = 53). The first-time tracheal intubation success rate increased with years of experience as an anesthesiologist in the direct laryngoscope group (odds ratio OR 1.70, 95% confidence interval CI 1.15, 2.49; P = 0.0070), but not the video laryngoscope group (OR 0.99, 95% CI 0.74, 1.35; P = 0.99). CONCLUSION: The differences in success rate according to the anesthesiologists' years of experience were non-significant when using video laryngoscope in infants, compared to those in direct laryngoscope.

Age Difference of the Relationship Between Cerebral Oxygen Saturation and Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.

Recently, monitoring of cerebral oxygen saturation (ScO2) has become widespread in pediatric cardiac surgery. Our previous study reported that mean blood pressure (mBP) was the major contributor to ScO2 throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg. We speculated that this result might be attributable to incomplete cerebral autoregulation in such young children. Accordingly, our hypothesis is that the relationship between ScO2 and the physiological parameters may change according to the growth of the children. ScO2 was measured with an INVOS 5100C (Somanetics, Troy, MI). Random-effects analysis was employed with ScO2 as a dependent variable, and seven physiological parameters (mBP, central venous pressure, nasopharyngeal temperature, SaO2, hematocrit, PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods by dividing the patients into two groups: infants (Infant Group) and children who were more than 1 year old (Child Group). The Infant and Child Groups consisted of 28 and 21 patients. In the random-effects analysis, mBP was the major contributor to ScO2 during CPB in both groups. During the pre-CPB period, the effect of mBP was strongest in the Infant group. However, its effect was second to that of SaO2 in the Child Group. During the post-CPB period, SaO2 and mBP still affected ScO2 in the Infant group. However, the dominant contributors were unclear in the Child Group. Cerebral autoregulation may be immature in infants. In addition, it may be impaired during CPB even after 1 year of age.

Perioperative junctional ectopic tachycardia associated with congenital heart disease: risk factors and appropriate interventions.

The risk factors and the appropriate interventions for perioperative junctional ectopic tachycardia (JET) in congenital heart disease (CHD) surgery have not been sufficiently investigated despite the severity of this complication. This study aimed to examine the risk factors and interventions for perioperative JET. From 2013 to 2020, 1062 surgeries for CHD (median patient age: 4.3 years, range 0.0-53.0) with or without a cardiopulmonary bypass (CPB) were performed at Hokkaido University, Japan. We investigated the correlation between perioperative JET morbidity factors, such as age, genetic background, CPB/aortic cross-clamp (ACC) time, use of inotropes and dexmedetomidine, STAT score, and laboratory indices. The efficacy of JET therapies was also evaluated. Of the 1062 patients, 86 (8.1%) developed JET. The 30-day mortality was significantly high in JET groups (7% vs. 0.8%). The independent risk factors for JET included heterotaxy syndrome [odds ratio (OR) 4.83; 95% confidence interval (CI) 2.18-10.07], ACC time exceeding 90 min (OR 1.90; CI 1.27-2.39), and the use of 3 or more inotropes (OR 4.11; CI 3.02-5.60). The combination of anti-arrhythmic drugs and a temporary pacemaker was the most effective therapy for intractable JET. Perioperative JET after CHD surgery remains a common cause of mortality. Inotrope use was a risk factor for developing JET overall surgery risk. In short ACC surgeries, heterotaxy syndrome could increase the risk of JET, which could develop even without inotrope use in long ACC surgeries. It is crucial not to delay the treatment in cases with unstable hemodynamics caused by this arrhythmia. It is recommended to reduce numbers not dose of inotropes.

Interleukin-1ß Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus.

BACKGROUND: Aging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. This study aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation, synaptic plasticity, and basal synaptic transmission during the acute phase of sepsis using Senescence-Accelerated Mice Prone 8 (SAMP8) and Senescence-Accelerated Resistant Mice 1 (SAMR1). METHODS: We used 6-month-old SAMP8 and SAMR1. Sepsis was induced using cecal ligation and puncture (CLP). The animal's hippocampi and blood were collected for subsequent investigations 24 h after surgery. RESULTS: Long-term potentiation (LTP) was impaired in the Shaffer-collateral (SC)-CA1 pathway of the hippocampus in SAMP8 without surgery compared to the age-matched SAMR1, which was reflective of cognitive dysfunction in SAMP8. CLP impaired the SC-CA1 LTP in SAMR1 compared to the sham-operated controls, but not in SAMP8. Moreover, CLP decreased the input-output curve and increased the paired-pulse ratio in SAMP8, suggesting the reduced probability of basal synaptic transmission due to sepsis. Immunohistochemical analysis revealed that CLP elevated IL-1ß levels, especially in the hippocampi of SAMP8 with microglial activation. In vivo peripheral IL-1 receptor antagonist (IL-1ra) administration in the septic SAMP8 revealed that the neuroinflammation was not correlated with the peripheral elevation of IL-1ß. Ex vivo IL-1ra administration to the hippocampus ameliorated LTP impairment in SAMR1 and the reduction in basal transmission in SAMP8 after sepsis. CONCLUSIONS: The mechanism of the modulation of synaptic transmission and synaptic plasticity by the acute stage of sepsis differed between SAMR1 and SAMP8. These changes were related to centrally derived IL-1 receptor-mediated signaling and were accompanied by microglial activation, especially in SAMP8.

Acute compartment syndrome of the lower leg causing cardiac arrest after resection of the right external iliac vein for autologous graft: a case report.

BACKGROUND: The right external iliac vein (REIV) is often used for portal vein reconstruction in patients undergoing pancreatoduodenectomy with portal-superior mesenteric vein resection. We report a case of cardiac arrest caused by acute lower leg compartment syndrome as a result of REIV resection. CASE PRESENTATION: A 53-year-old man underwent pancreatoduodenectomy with portal vein resection. Hyperkalemia progressed during surgery due to intestinal reperfusion injury, which caused recurrent ventricular arrhythmia required for cardio-pulmonary resuscitation. The surgery was discontinued after resuscitation, and portal vein reconstruction using the REIV was performed 2 days post-operatively. Acute compartment syndrome was diagnosed immediately following the surgery. Hyperkalemia progressed, causing pulseless ventricular tachycardia. Emergent fasciotomy was performed, but right leg dysfunction persisted after discharge. CONCLUSION: REIV resection can cause lower-extremity acute compartment syndrome. The status, including intracompartmental pressure, of the lower extremity should be carefully observed after REIV resection during and after surgery.

Synapse-specific effects of IL-1ß on long-term potentiation in the mouse hippocampus.

Interleukin-1ß (IL-1ß) is a key molecule in the inflammatory responses elicited during infection and injury. It exerts local effects on synaptic plasticity by binding to IL-1 receptors that are expressed at high levels in the hippocampus. We examined the effects of IL-1ß on synaptic plasticity in different hippocampal regions in acute mouse brain slices by measuring long-term potentiation (LTP). IL-1ß (1 ng/mL) was applied for 30 min before LTP was induced with high-frequency stimulation (HFS). LTP was significantly impaired by either IL-1ß application to the Schaffer collateral-CA1 synapses or the associational/commissural (A/C) fiber-CA3 synapses, which are both dependent on N-methyl-D-aspartate (NMDA) receptor activation. However, mossy fiber-CA3 LTP, which is expressed presynaptically in an NMDA-independent manner, was not impaired by IL-1ß. Our results demonstrate that IL-1ß exerts variable effects on LTP at different kinds of synapses, indicating that IL-1ß has synapse-specific effects on hippocampal synaptic plasticity.

Comparison of the analgesic efficacy of ultrasound-guided rectus sheath block and local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children.

BACKGROUND: Ultrasound-guided rectus sheath block and local anesthetic infiltration are the standard options to improve postoperative pain for children undergoing surgery with a midline incision. However, there is no study comparing the effect of ultrasound-guided rectus sheath block with local anesthetic infiltration for children undergoing laparoscopic surgery. AIMS: The aim of this trial was to compare the onset of ultrasound-guided rectus sheath block with that of local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children. METHODS: We performed an observer-blinded, randomized, prospective trial. Enrolled patients were assigned to either an ultrasound-guided rectus sheath block group or a local anesthetic infiltration group. The ultrasound-guided rectus sheath block group (n = 17) received ultrasound-guided rectus sheath block with 0.2 ml·kg-1 of 0.375% ropivacaine per side in the posterior rectus sheath compartment. The local anesthetic infiltration group (n = 17) received local anesthetic infiltration with 0.2 ml·kg-1 of 0.75% ropivacaine. The Face, Legs, Activity, Cry, and Consolability (FLACC) pain scores were recorded at 0, 30, 60 min after arrival at the postanesthesia care unit. RESULTS: Of the 37 patients enrolled in this study, 34 completed the study protocol. A significant difference in the pain scale between the ultrasound-guided rectus sheath block group and local anesthetic infiltration group was found at 0 min (median: 0, interquartile range [IQR]: 0-1.5, vs median: 1, IQR 0-5, confidence interval of median [95% CI]: 0-3, P = 0.048), but no significant difference was found at 30 min (median: 1, IQR: 0-4 vs median: 6, IQR: 0-7, 95% CI: 0-5, P = 0.061), or 60 min (median: 0, IQR: 0-2 vs median: 1, IQR: 0-3, 95% CI: -1 to 1, P = 0.310). No significant difference was found in anesthesia time between the ultrasound-guided rectus sheath block and local anesthetic infiltration groups. No procedure-related complications were observed in either group. CONCLUSION: Ultrasound-guided rectus sheath block is a quicker way to control postoperative pain for pediatric patients undergoing laparoscopic extraperitoneal closure than local anesthetic infiltration, and thus may provide a clinical benefit.

Minocycline Prevents the Impairment of Hippocampal Long-Term Potentiation in the Septic Mouse.

Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. We divided mice into four groups; sham + vehicle, sham + MINO (60 mg/kg, i.p. for 3 consecutive days before slice preparation), CLP + vehicle, and CLP + MINO. We tested LTP in the CA1 region of the hippocampus, using slices taken 24 h after surgery. Because MINO is also anti-inflammatory, LTP was analyzed following 30 min of IL-1 receptor antagonist (IL-1ra) perfusion. The endotoxin level in the blood was increased at 24 h after CLP operations regardless of MINO administrations, and LTP in the CLP + vehicle group mice was severely impaired (P < 0.05). High doses of MINO prevented the LTP impairment during sepsis in the CLP + MINO group. Interleukin (IL)-1ra administration ameliorated LTP impairment only in the CLP + vehicle group (P < 0.05); it had no additional effects on LTP in the CLP + MINO group. In conclusion, we have provided the first evidence that MINO prevents impaired LTP related to sepsis-induced encephalopathy in the mouse hippocampus, and that mechanisms associated with IL-1 receptor activity may be involved.

[A Case of Repetitive Cardiac Arrest due to Coronary Vasospasm after Sugammadex Administration].

A 58-year-old man with no history of cardiac disease was scheduled for a cerebral aneurysm clipping surgery. Anesthesia was administered with propofol, rocuronium, fentanyl, and remifentanil. At the end of the surgery, extubation was performed 3 min after the administration of 200 mg sugammadex, along with a simultaneous blood-pressure decrease with ST elevation on lead II. Cardiopulmonary resuscitation was per- formed owing to the occurrence of lethal arrhythmia, and the patient was successfully resuscitated. Subsequent emergent coronary angiography revealed normal coronary arteries. Twelve days after the first surgery, a tracheostomy was performed owing to persistent disturbance of consciousness. Anesthesia was administered with sevoflurane, fentanyl, and rocuronium. Sugammadex 200 mg was administered after the insertion of a tracheal cannula, and 5 min later, the blood pressure were gradually decreased with ST depression on lead V5. Finally, cardiopulmonary resuscitation was required, and the patient recovered again. An acetylcholine provocation test performed later showed positive results. We suspect sugammadex to be the cause of coronary vasospasm, because the time courses of the two cardiac arrest episodes after sugammadex administration were very similar. Therefore, clinicians should consider sugammadex as one of the causative agents of cardiac arrest in the operating room.

[Examination of the Influence of Age and Cardiopulmonary Bypass on Cerebral Autoregulation in Pediatric Patients for the Cardiac Surgery by Using Near-infrared Spectroscopy].

BACKGROUND: We evaluated the impact of age and cardiopulmonary bypass (CPB) on cerebral autoregulation in pediatric patients for the cardiac surgery with near-infrared spectroscopy. METHODS: This retrospective study was conducted with 67 children undergoing closure of atrial or ventricular septal defects with CPB. The regression coefficient ((see symbol)regional cerebral oxygenation index ((see symbol)SO2)/ mean arterial blood pressure (mABP)) for each patient was calculated by simple regression analysis, assuming that higher regression coefficients indicate less functional cerebral autoregulation. In addition, to determine the vital parameters affecting rSO2 values during CPB, we analyzed the data from on-line continuous blood gas monitor with random effects-mixed model. RESULTS: The regression coefficients were frequently high among younger children (0-4 years), suggesting that the cerebral autoregulation was immature. Although regression coefficient values in younger children remained high through the operation, those in older children (5-14 years) increased significantly only during CPB, suggesting that cerebral autoregulation was dysfunctional during CPB. With random effects-mixed model, we revealed that mABP had the most significant effect on rSO2 values during CPB. CONCLUSIONS: Cerebral autoregulation in younger children is immature. Moreover, it does not work during CPB even in older children, and clinicians must ensure perfusion pressure carefully during CPB in pediatric patients.

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study.

INTRODUCTION: Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. METHODS: We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. RESULTS: We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00940654.

Regulation of androgen receptor expression through angiotensin II type 1 receptor in prostate cancer cells.

BACKGROUND: Although the local renin-angiotensin system (RAS) of the prostate gland is related to cell proliferation and angiogenesis, the detailed mechanism remains unclear. We examined the effects of the angiotensin II type 1 receptor (AT1R) on androgen receptor (AR) expression in prostate cancer cells. METHODS: AR modulation by AT1R was examined by Western blot analysis, luciferase assay, and Immunocytochemical staining. The influence of AR expression by angiotensin II (Ang-II) and AT1R inhibition using siRNA was determined. Furthermore, using angiotensinogen or AT1R knockout (KO) mice, we performed quantitative real-time PCR to investigate the expression of AR. RESULTS: Ang-II induced cell proliferation with enhancement of AR, prostate specific antigen (PSA), NF-κB, and c-myc, and the activity of AR and PSA promoter. Cell proliferation of LNCaP transfected with AT1R siRNA was decreased by 75% at 7 days by inhibition of AR, PSA, NF-κB, and c-myc. Immunocytochemical staining confirmed the suppression of AR translocation into the nucleus in AT1R siRNA cells. AT1R KO mice showed a decrease in AR expression in the prostate gland. We also found that the expression level of AT1R could modulate the transcriptional level of AR by affecting NF-κB and c-myc expression. CONCLUSIONS: Knocking down of the AT1R protein resulted in significant inhibition of cell growth, associated with a marked decrease of AR protein. These results indicate that inhibition of AT1R has the potential to influence AR expression in prostate cells, and is anticipated to contribute to the development of novel therapeutic agents for prostate cancer.

Engagement of renin-angiotensin system in prostate cancer.

Angiotensin II (Ang-II) plays a role not only as a vasoconstrictor in controlling blood pressure and electrolyte and fluid homeostasis, but also as a mitogenic factor through the Ang-II type-1 (AT1) receptor in cardiovascular cells. Since a low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors has been reported, the molecular mechanisms of the renin-angiotensin system (RAS) in cancer cells have been elucidated. Interestingly, there is increasing evidence that the RAS is implicated in the development of prostate cancer. As previously reported, AT1 receptor blockers (ARBs), a class of antihypertensive agent, have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review highlights that the RAS plays a potential role in various aspects of prostate cancer, and ARBs could be useful for treatment of prostate cancer or its chemoprevention.

Analysis of NSAID-activated gene 1 expression in prostate cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce expression of NSAID-activated gene 1 (NAG-1). NAG-1 expression in prostate cancer has previously been detected by microarray and immunohistochemical analyses. We examined the mRNA expression of NAG-1 by quantitative real-time polymerase chain reaction using 51 human prostate cancer tissue specimens. The level of NAG-1 expression was higher in prostate cancer than in normal prostate tissues (p = 0.025). The level of NAG-1 expression was also significantly higher in well-differentiated prostate cancer than in moderately (p = 0.04) and poorly differentiated adenocarcinomas (p = 0.03). These data suggest that NAG-1 may be a new biomarker for evaluating the grade of malignancy in prostate cancer.

Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens.

OBJECTIVE: To determine whether the 2005 International Society of Urologic Pathology (ISUP) Gleason Grading Consensus is clinically more useful than the conventional Gleason score (CGS), we compared the CGS and ISUP GS (IGS) of prostate needle biopsy (NB) and radical prostatectomy (RP) specimens, and evaluated the prognostic value of the ISUP GS. PATIENTS AND METHODS: Of 250 patients undergoing RP, 103 with clinical stage T1-2 N0M0 were enrolled. Pathological tumour grades of NB and RP specimens were classified according to CGS by experienced pathologists in the central pathology department of our hospital, and retrospectively according to IGS by one uropathologist at the central pathology department of another hospital. All patients had RP with no neoadjuvant or adjuvant therapy. We analysed associations of CGS and IGS with biochemical recurrence-free survival (BRFS) after RP. RESULTS: The concordance rates between NB and RP specimens by CGS and IGS were 64.1% and 69.9%. Under-grading and over-grading rates by CGS and IGS were 28.2% and 7.8% for NB, and 27.2% and 2.9% for RP, respectively. There was a significant difference in the over-grading rate between CGS and IGS (P = 0.026). When CGS and IGS of NB and RP specimens were compared, the concordance rates were similar, at 67% and 69.9%. The IGS was higher, by 15.6% in NB and by 20.4% in RP specimens, than CGS. Patients were divided into three groups based on IGS of NB specimens (< or =6, 7 and > or =8). These groups differed significantly in BRFS after RP (P = 0.022); CGS showed no such association. CONCLUSIONS: The IGS of NB specimens were significantly associated with BRFS after RP. The ISUP system is thus clinically useful for determining the most appropriate treatments for patients with early-stage prostate cancer.