Clinical significance of definite muscle layer in TUR specimen for evaluating progression rate in T1G3 bladder cancer: multicenter retrospective study by the Sapporo Medical University Urologic Oncology Consortium (SUOC)

Purpose

To evaluate the clinical impact on progression and recurrence according to presence and absence of a muscle layer, we conducted a retrospective, multicenter study.

Methods

We retrospectively reviewed 247 patients who received transurethral resection (TUR) of bladder tumors and were pathologically diagnosed as having T1G3 bladder cancer from 1990 to 2009. We ruled out 8 patients who received immediate cystectomy and analyzed the remaining 239 T1G3 patients. Patients who had invasion to the prostatic urethra and patients who underwent a second TUR were not included.

Results

TUR specimens from 194 patients were confirmed to have a definite muscle layer and those from 45 did not. The median follow-up period was 53 months, ranging from 3 to 181 months. The progression-free survival rates at 5 years after TUR were 91.1 % for patients who had a muscle layer in their specimen and 77.3 % for those who did not (p = 0.005, log-rank test). Multivariate analysis indicated that the absence of a muscle layer was a risk factor for progression (p = 0.006, Cox proportional hazards analysis).

Conclusions

Patients without a muscle layer in the specimen had high risk for progression. The initial TUR must have a muscle layer in the specimen. Variations of progression rates in previous studies might be due to different proportions of patients who had a muscle layer in TUR specimens.     

NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia

The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against NGF or GDNF on TRPV1 expression within the groups were then analysed by immunohistochemical means. The data were compared with the time course of trophic factor expression and the effects of their antibodies on thermal hyperalgesia against radiant heat after inflammation. Although the levels of both NGF and GDNF were increased by inflammation, NGF rapidly and transiently increased whereas GDNF increased gradually over a period of approximately one week. TRPV1 expression was increased within both trk-A positive and IB4 positive neurons after inflammation. Increased TRPV1 expression within trk-A positive neurons was prevented by anti-NGF but not by anti-GDNF, whereas TRPV1 induction within the IB4 positive group was blocked by anti-GDNF but not by anti-NGF. Both antibodies prevented the short latency of withdrawing an inflamed paw from radiant heat. These results suggest that inflammation differentially increases both NGF and GDNF, which facilitate TRPV1 expression within distinctive neurons to induce thermal hyperalgesia.     

Ultrasound evidence of the optimal wrist position for radial artery cannulation

Purpose

Radial artery cannulation is a common medical procedure for anesthesia and critical care. To establish the ideal wrist position for radial artery cannulation, we performed ultrasound examinations of the radial artery to investigate the effect of the angle of wrist extension on radial artery dimensions.

Clinical features

Measurements were performed in 17 healthy subjects and 17 surgical patients scheduled for coronary artery bypass graft (CABG) surgery. The radial artery was echographically visualized near the styloid process of the radius at the wrist. Radial artery dimensions were measured at wrist joint angles of 0, 15, 30, 45, 60 and 75°.

Observations

In both groups, radial artery height was affected by the wrist joint angle. Vessel height was decreased at 60° (one way ANOVA P = 0.027 vs 0°) and 75° (P < 0.001 vs 0, 15, 45°) in healthy subject and at 75° in CABG patients (P < 0.001 vs 0°). The mean differences in radial artery height at 0 and 75° were 0.33 ± 0.09 mm and 0.20 ± 0.06 mm for healthy and CABG patients, respectively. Vessel width was not affected by wrist joint angulation up to 75° of extension.

Conclusion

Our results demonstrate that in healthy subjects, radial artery dimensions are unaltered when the wrist joint is extended up to an angle of 45°. Extension at 60° for healthy subjects and 75° for CABG patients, however, results in a decrease in the height of the radial artery, which could possibly render arterial catheterization more difficult.     

Microscopic observations reveal that fusogenic peptides induce liposome shrinkage prior to membrane fusion

To study the mechanisms involved in membrane fusion, we visualized the fusion process of giant liposomes in real time by optical dark-field microscopy. To induce membrane fusion, we used (i) influenza hemagglutinin peptide (HA), a 20-aa peptide derived from the N-terminal fusion peptide region of the HA2 subunit, and (ii) two synthetic analogue peptides of HA, a negatively (E5) and positively (K5) charged analogue. We were able to visualize membrane fusion caused by E5 or by K5 alone, as well as by the mixture of these two peptides. The HA peptide however, did not induce membrane fusion, even at an acidic pH, which has been described as the optimal condition for the fusion of large unilamellar vesicles. Surprisingly, before membrane fusion, the shrinkage of liposomes was always observed. Our results suggest that a perturbation of lipid bilayers, which probably resulted from alterations in the bending folds of membranes, is a critical factor in fusion efficiency.     

Natural history of lower urinary tract symptoms in Japanese men from a 15-year longitudinal community-based study

Study Type – Symptom prevalence (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? There have been few longitudinal community‐based studies on LUTS suggestive of BPH. It is important to determine the natural history of LUTS suggestive of BPH among men in various countries because it is known that there are differences according to race. Although we previously reported a cross‐sectional community‐based survey on LUTS suggestive of BPH in Japanese men, no longitudinal data were available. The present study provides 15‐year longitudinal data on LUTS suggestive of BPH and related variables in Japanese men.

OBJECTIVE

• ? To report the natural history of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in Japanese men.

PATIENTS AND METHODS

• ? From 1992 to 1993, we conducted a cross‐sectional community‐based study on LUTS suggestive of BPH in Japanese men aged 40–79 years.
• ? After 15 fifteen years, a follow‐up study was conducted to determine their longitudinal changes of LUTS.
• ? Of the 319 participants taking part in the initial study, 135 participated again in the follow‐up study.
• ? We investigated International Prostate Symptom Score (IPSS), quality of life index and bother score using a questionnaire, and measured prostate volume (PV), prostate‐specific antigen (PSA) level and peak urinary flow rate (Q_max) using a method that we have employed previously.

RESULTS

• ? The change in the total IPSS during 15 years was significant (P= 0.001) and its mean (sd ) annual change was 0.11 (0.40).
• ? Although there was little change in the bother score, a significant correlation was observed between changes in the IPSS and bother score (r= 0.528, P < 0.001).
• ? For the individual IPSS and bother scores, only changes in urgency, weak stream and nocturia were significant.
• ? The changes in PV, PSA level and Q_max were significant.
• ? The change in the total IPSS did not correlate with the changes in these variables.

CONCLUSION

• ? In a 15‐year‐longitudinal community‐based study for Japanese men, we have shown that the IPSS and quality of life index deteriorated, PV and PSA level increased, and Q_max decreased.

     

Nitrergic neurons in the medial amygdala project to the hypothalamic paraventricular nucleus of the rat

We investigated nitric oxide (NO)-producing neurons in the amygdala which project to the hypothalamic paraventricular nucleus (PVN) of the rat using retrograde tracing and NADPH-diaphorase histochemistry. Numerous NADPH-diaphorase positive neurons with moderate staining were observed mainly in the medial amygdaloid nucleus. We confirmed that these NADPH-diaphorase positive neurons are identical to NO synthase (NOS)-immunoreactive neurons by double staining with NADPH-diaphorase histochemistry and NOS immunocytochemistry. Most neurons containing cholera toxin B subunit (CTb) – which was retrogradely transported from the PVN – were observed in the medial amygdaloid nucleus. In other amygdaloid nuclei, they were observed much less in the central nucleus, basomedial and anterior cortical nucleus. Double labeled neurons by NADPH-diaphorase and CTb were also identified mostly in the medial nucleus. Approximately 40% of the neurons projecting to the PVN were nitrergic neurons and 16% of NADPH-diaphorase positive neurons in the medial nucleus were revealed to project to the PVN. These results suggest that NO-producing neurons in the medial amygdala directly innervate PVN neurons and regulate neuroendocrine systems such as vasopressin and corticotropin releasing factor release.     

Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity

Prostaglandin E(2) (PGE(2)) is both an inflammatory mediator released at the site of tissue inflammation and a neuromodulator that alters neuronal excitability and synaptic processing. The effects of PGE(2) are mediated by four G-protein-coupled EP receptors (EP1-EP4). Here we show that the EP4 receptor subtype is expressed by a subset of primary sensory dorsal root ganglion (DRG) neurons, and that its levels, but not that of the other EP1-3 subtypes, increase in the DRG after complete Freund' adjuvant-induced peripheral inflammation. Administration of both an EP4 antagonist [AH23848, (4Z)-7-[(rel-1S,2S,5R)-5-((1,1'-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid] and EP4 knockdown with intrathecally delivered short hairpin RNA attenuates inflammation-induced thermal and mechanical behavioral hypersensitivity, without changing basal pain sensitivity. AH23848 also reduces the PGE(2)-mediated sensitization of capsaicin-evoked currents in DRG neurons in vitro. These data suggest that EP4 is a potential target for the pharmacological treatment of inflammatory pain.     

Influence of body mass index and total testosterone level on biochemical recurrence following radical prostatectomy

Objective: A high body mass index (BMI) and a low testosterone level wererecently reported to be prognostic factors for prostate-specificantigen (PSA) recurrence following radical prostatectomy (RP).The goal of this study was to clarify their relationship andinfluences on biochemical recurrence after RP. Methods: We analysed 126 patients whose data, including the pre-operativeBMI and pre-operative serum total testosterone level, were available.All patients underwent RP at our institution between March 1998and April 2006 without any adjuvant therapy or pelvic lymphnode metastasis. The Cox proportional hazards model was usedfor the multivariate analysis regarding PSA recurrence for thevariables of age, operation period, BMI, clinical stage, PSA,Gleason's sum, pre-operative serum total testosterone leveland margin status. Results: There were no internal correlations among the parameters weused, even between BMI and the total testosterone level. Thetotal testosterone level was not different between two BMI groups(BMI <26.4 and 26.4 kg/m²: the cut-off is the mean + 1 SD).BMI, PSA and Gleason's sum were found to be independent predictorsfor PSA recurrence through the multivariate analysis. PSA recurrence-freesurvival rates at 2 years were 77% for BMI <26.4 kg/m², and31% for BMI 26.4 kg/m² (P = 0.002, log-rank test, 95% CI: 1.489–7.726). Conclusions: The current study suggests that high BMI independently contributesto PSA recurrence but that the total testosterone level doesnot. Although the mechanism by which obesity promotes PSA recurrencein RP patients has not been established, careful observationis needed for patients with high BMI.