Performance Improvement (Pi) score: an algorithm to score Pi objectively during E-BLUS hands-on training sessions. A European Association of Urology, Section of Uro-Technology (ESUT) project.

OBJECTIVE: To evaluate the variability of subjective tutor performance improvement (Pi) assessment and to compare it with a novel measurement algorithm: the Pi score. MATERIALS AND METHODS: The Pi-score algorithm considers time measurement and number of errors from two different repetitions (first and fifth) of the same training task and compares them to the relative task goals, to produce an objective score. We collected data during eight courses on the four European Association of Urology training in Basic Laparoscopic Urological Skills (E-BLUS) tasks. The same tutor instructed on all courses. Collected data were independently analysed by 14 hands-on training experts for Pi assessment. Their subjective Pi assessments were compared for inter-rater reliability. The average per-participant subjective scores from all 14 proctors were then compared with the objective Pi-score algorithm results. Cohen's κ statistic was used for comparison analysis. RESULTS: A total of 50 participants were enrolled. Concordance found between the 14 proctors' scores was the following: Task 1, κ = 0.42 (moderate); Task 2, κ = 0.27 (fair); Task 3, κ = 0.32 (fair); and Task 4, κ = 0.55 (moderate). Concordance between Pi-score results and proctor average scores per participant was the following: Task 1, κ = 0.85 (almost perfect); Task 2, κ = 0.46 (moderate); Task 3, κ = 0.92 (almost perfect); Task 4 = 0.65 (substantial). CONCLUSION: The present study shows that evaluation of Pi is highly variable, even when formulated by a cohort of experts. Our algorithm successfully provided an objective score that was equal to the average Pi assessment of a cohort of experts, in relation to a small amount of training attempts.

Probiotics, dendritic cells and bladder cancer.

What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer.

The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer, and mediates proliferation, motility, and survival. Many prostate cancers harbor inactivating PTEN mutations, enhancing Akt phosphorylation. This activates the principal antiapoptotic pathway downstream of the IGF1R, calling into question the value of IGF1R targeting in this tumor. The aim of the current study was to assess the effect of IGF1R gene silencing in prostate cancer cells that lack functional PTEN protein. In human DU145, LNCaP and PC3 prostate cancer cells, transfection with IGF1R small interfering RNA induced significant enhancement of apoptosis and inhibition of survival, not only in PTEN wild-type DU145 but also in PTEN mutant LNCaP and PC3. This was attributed to attenuation of IGF signaling via Akt, ERKs and p38. In both DU145 and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone, etoposide, nitrogen mustard and ionizing radiation. There was no sensitization to paclitaxel or 5-fluorouracil, which do not damage DNA, suggesting that chemosensitization results from impairment of the DNA damage response, in addition to removal of apoptosis protection. These results support the concept of IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render tumor cells refractory to this strategy.

Does cooling Sengstaken-Blakemore tubes aid insertion? An evidence based approach.

OBJECTIVE: To survey current clinical practice concerning the use of Sengstaken-Blakemore (SB) tubes and to determine whether cooling the tubes alters their stiffness. METHODS: A telephone questionnaire was conducted of gastroenterology registrars and ITU departments in the North Thames region. The current clinical practice for insertion of SB tubes and the basis for this practice were determined in each case. The stiffness of the tubes was measured at -10 degrees C and 20 degrees C by measuring the extension (in mm) resulting from an applied load (in newtons). The time for tube warming from -30 degrees C when in stationary air and when in contact with skin was also recorded. RESULTS: Fifty registrars were contacted and 20 ITU departments were surveyed. All ITU departments involved the gastroenterologists in the management of acute variceal bleeds. Eight registrars had never placed an SB tube. The majority of the remainder (95%) used a cooled SB tube. All of the registrars based this practice upon their clinical teaching, and 75% of these registrars thought cooling aided the insertion of the tube. There was no significant difference in the stiffness of the tubes at -10 degrees C and 20 degrees C. Upon warming, an SB tube took 30 s to rise from 0 degrees C to room temperature (20 degrees C) when in skin contact and 120 s when placed in stationary air. CONCLUSION: The current clinical practice of trainees for the insertion of SB tubes is to cool the tubes in the belief that this 'standard' practice aids tube insertion. We found no significant change in SB tube stiffness even after cooling to temperatures that would not be achieved during routine insertion. Furthermore, the rapid rise in tube temperature means that tubes approach room temperature by the time they reach the bedside. In the present era of evidence based medicine the current dogma that SB tubes should be cooled prior to insertion must be discarded.

Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease.

The type 1 insulin-like growth factor receptor (IGF1R) mediates tumor cell growth, adhesion, and protection from apoptosis. High plasma IGF-I levels predispose to prostate cancer, but there is no consensus regarding IGF1R expression in primary and metastatic prostate cancer. Recent studies in a human cell line and a mouse model suggest that metastatic prostate cancer cell detachment may be favored by impairing cadherin function via loss of expression of insulin receptor substrate-1 (IRS-1), the principal IGF1R docking molecule. This may be accompanied by PTEN mutation, reactivating a key antiapoptotic pathway, and by IGF1R down-regulation to prevent Shc-mediated differentiation. We studied IGF1R expression in 54 samples of primary prostate tissue including 44 archival and 10 prospectively collected biopsies. We performed semiquantitative immunostaining for the IGF1R, IRS-1, and PTEN, and in situ hybridization for IGF1R. The IGF1R was significantly up-regulated at the protein and mRNA level in primary prostate cancer compared with benign prostatic epithelium. There was a trend toward increased expression of IRS-1 in the malignant biopsies. We also measured IGF1R, IRS-1, and PTEN expression in 12 paired biopsies of primary prostate cancer and subsequent bone metastases. In four cases, IGF1R and IRS-1 levels were lower in the metastases than in the primary tumors. Three of these metastases also lacked significant PTEN staining, compatible with findings in the model systems described above. However, this pattern was relatively uncommon, and 8 of 12 cases expressed detectable IGF1R and IRS-1 in both primary and metastatic biopsies. These findings challenge earlier reports of IGF1R down-regulation in metastatic disease and reinforce the importance of the IGF1R in prostate cancer biology.