N-myristoyltransferase 2-based Blood Test for the Detection of Colorectal Adenomatous Polyps and Cancer.

Background: Colorectal cancer is the second leading cause of cancer-related deaths. This study demonstrates the utility of a simple blood test with high sensitivity and specificity for colorectal adenomatous polyps and cancer. A simple blood test with high sensitivity and specificity for adenomas would help identify individuals for a follow-up colonoscopy during which any adenomatous polyps found could be removed, thus preventing colorectal cancer (CRC). Methods: We determined the H-score by using immunohistochemical analyses of N-myristoyltransferase 2 (NMT2) in peripheral blood mononuclear cells (PBMC) isolated from the blood. We determined the sensitivity and specificity of the NMT2-based blood test in identifying colorectal adenomatous polyps and cancer. Design: All experimental procedures were performed by research personnel blinded to the colonoscopy status of the participants. Setting: In this cohort study, participants were recruited from those coming for an outpatient colonoscopy at a referral center. Participants: PBMC were collected from 74 subjects at the Health Sciences Centre, Winnipeg, Canada. Samples were collected from colonoscopy patients prior to colonoscopy. All 74 subjects were included in CRC vs. non-CRC analysis, whereas only 70 subjects were analyzed for colorectal adenomatous polyps and cancer versus individuals with no evidence of disease and non-adenomatous polyps. NMT2 expression was tested in samples by immunohistochemistry. Results: The expression of NMT2 was significantly higher in PBMC of subjects with colorectal adenomatous polyps and cancer (n = 34) compared with individuals with non-adenomatous polyps or no evidence of disease (n = 36) (P < 0.0001). The test had an overall sensitivity of 91% (95% confidence intervals: 84.49-97.80) and specificity of 81% (95% confidence intervals: 71.28-89.83) in detecting colorectal adenomatous polyps and cancer (all stages). Conclusions: Our results suggest that the sensitivity of NMT2 in detecting adenomatous polyps is high (91%). A simple blood-based CRC screening test using NMT2 expression detects colorectal adenomatous polyps and cancer with high sensitivity and specificity has the potential of increasing the compliance for CRC screening as has been reported for other blood-based CRC screening tests.

A Narrative Review of Methodological Considerations in Magnetic Resonance Imaging of Offspring Brain Development and the Influence of Parenting.

Parenting has been robustly associated with offspring psychosocial development, and these effects are likely reflected in brain development. This hypothesis is being tested with increasingly rigorous methods and the use of magnetic resonance imaging, a powerful tool for characterizing human brain structure and function. The objective of this narrative review was to examine methodological issues in this field that impact the conclusions that can be drawn and to identify future directions in this field. Studies included were those that examined associations between parenting and offspring brain structure or function. Results show four thematic features in this literature that impact the hypotheses that can be tested, and the conclusions drawn. The first theme is a limited body of studies including repeated sampling of offspring brain structure and function, and therefore an over-reliance on cross-sectional or retrospective associations. The second involves a focus on extremes in early life caregiving, limiting generalizability. The third involves the nature of parenting assessment, predominantly parent- or child-report instead of observational measures which may be more ecologically valid measures of parenting. A closely related fourth consideration is the examination of detrimental versus positive parenting behaviors. While studies with one or more of these thematic limitations provide valuable information, future study design should consider addressing these limitations to determine how parenting shapes offspring brain development.

Personality Trait Predictive Utility and Stability in Transcranial Magnetic Stimulation (rTMS) for Major Depression: Dissociation of Neuroticism and Self-Criticism.

BACKGROUND: Cost-efficient and non-invasive predictors of antidepressant response to repetitive transcranial magnetic stimulation (rTMS) are required. The personality vulnerabilities­neuroticism and self-criticism­are associated with antidepressant outcomes in other modalities; however, self-criticism has not been examined in response to rTMS, and the literature on neuroticism and rTMS is inconsistent. METHODS: This naturalistic, 4-week study involved daily dorsolateral prefrontal cortex (DLFPC) rTMS for major depression (15 unipolar, 2 bipolar). Participants completed the Big Five Inventory (neuroticism) and the Depressive Experiences Questionnaire (self-criticism) at baseline and at the end of treatment. Changes in depressive symptoms, as rated by the clinician, were quantified using the 21-item Hamilton Depression Rating Scale. Given the inconsistencies in data regarding the stability of neuroticism in patients receiving rTMS, we performed a systematic review and quantitative meta-analysis of trials examining rTMS and neuroticism. RESULTS: rTMS significantly improved depressive symptoms, and this was predicted by higher levels of self-criticism but not neuroticism. Self-criticism was stable over the 4 weeks of rTMS; however, neuroticism decreased, and this was not related to decreases in depressive symptoms. Our quantitative meta-analysis of 4 rTMS trials in major depression (n = 52 patients) revealed decreases in neuroticism, with a moderate effect size. LIMITATIONS: Our results are limited by a small sample size, and the absence of a sham-rTMS group. Our meta-analysis included only 4 trials. CONCLUSION: Highly self-critical patients appear to benefit more from rTMS than less self-critical patients. Neuroticism, a conceptually similar but distinct personality domain, does not appear to predict antidepressant response, yet this vulnerability factor for depression decreases after rTMS.

Modular surgical training for endoscopic extraperitoneal radical prostatectomy.

OBJECTIVE: To develop a modular training scheme which enabled the use of individual steps of laparoscopic radical prostatectomy (RP) for teaching and training surgeons with varied experience, including residents with no experience in open RP, as in extending laparoscopic surgery to more complex operations like RP, the proper training of urologists is crucial. SUBJECTS AND METHODS: The technique of endoscopic extraperitoneal RP (EERP) was divided into 12 individual steps of differing complexity. The levels of difficulty were called "modules" and graded according to their requisite skills from module 1 (lowest level of difficulty) to module 5 (highest level). Based on this modular system we established a training programme whereby the trainee learns the procedure in a mentor-initiated schedule. During each training operation the trainee only performs the modules (steps) of the operation, which correspond with his or her actual skill level. The mentor performs all the other steps, with the trainee assisting. Four trainees with different surgical experience participated in the study. RESULTS: After a phase of assisting and camera holding during EERP, the trainees entered the modular training programme and required 32-43 procedures until they were considered to be competent. An analysis of the first 25-50 procedures done independently by the trainee showed mean operative times of 176-193 min and a transfusion rate of 1.3%. Complications during and after EERP requiring re-intervention were one each of recto-urethral fistula, haemorrhage, symptomatic lymphocele and anastomotic leak. The positive margin rate for pT2 disease was 12.2% and for pT3 tumours 37%. CONCLUSION: The modular concept for teaching EERP is an attractive concept, which overcomes many of the problems involved in complex laparoscopic procedures. Based on a highly standardized technique, this concept offers a short learning curve; it enables training on different sites in cooperation with a high-volume centre, and it makes it possible to start with this complex procedure as a beginner or with no experience in open RP.

Post-biopsy rise in serum PSA. A potential tool for the dynamic evaluation of prostate cancer/prostatic intraepithelial neoplasia (PIN).

OBJECTIVES: The biochemical response of prostatic cells to needle core biopsies is known to manifest as a rise in serum PSA. The aim of this study is to evaluate the PSA response to mechanical trauma in prostate cancer patients, when compared to benign controls. MATERIALS AND METHODS: 50 consecutive patients undergoing transrectal ultrasound guided prostatic needle biopsies had their total serum PSA measured thirty minutes after the procedure. Change from the baseline PSA was estimated and correlated to histology. RESULTS: Data was analysed in 48 patients (mean age 68 years; range 55-87 years). Histology showed benign, cancer and PIN results in 24, 19 and 5 patients respectively. The highest rise in post biopsy PSA was observed in the PIN group. A significant difference in the rise in serum PSA was noted between controls and the cancer group. CONCLUSION: Post biopsy PSA response differs significantly between benign and malignant prostatic tissue. PIN causes an excessive in PSA values on mechanical stimulation. This small study indicates that the biopsy model may help us to assess the dynamics of prostate cancer.

Smiley incision: a direct surgical approach for retropubic radical prostatectomy.

Two standard incisions are used for retropubic radical prostatectomy, a midline vertical and a transverse Pfannenstiel incision. Both of these incisions have their advantages and disadvantages. A geometric union of these two standard incisions has been devised and tried on 45 patients with very desirable results.