Periodontal disease as a risk factor for sporadic colorectal cancer: results from COLDENT study

Cancer Causes & Control - Colorectal cancer remains the top leading cancer worldwide. Accumulating evidence suggests periodontal pathogens are involved in colorectal carcinogenesis, indicating...     

Higher calcineurin inhibitor levels predict better kidney graft survival in patients with de novo donor‐specific anti‐HLA antibodies: a cohort study

The development of de novo anti‐HLA donor‐specific antibodies (dnDSA) is associated with poorer outcomes in kidney transplant recipients. Despite this, antibody screening post‐transplant is not widespread, largely because the optimal management of patients with dnDSA remains undetermined. We hypothesized that in this population, calcineurin inhibitor blood levels would be an independent predictor of graft loss. We analyzed a cohort of unsensitized patients for whom anti‐HLA antibody screening was performed prospectively post‐transplant. During the screening period between January 2005 and April 2016, 42 patients developed dnDSA. There was no difference in the clinical characteristics or the histological scores of patients biopsied for clinical indication versus those biopsied solely due to detection of dnDSA. Cox modeling revealed a strong relationship between mean tacrolimus levels following dnDSA detection and graft loss, with a hazard ratio of 0.49 (95% CI, 0.33–0.75), which persisted following adjustment for established independent predictors (HR, 0.52, 95% CI, 0.30–0.89). Kaplan–Meier analysis by tertiles of tacrolimus levels and receiver operating curve analysis concurred to show that a threshold of 5.3 ng/ml could be predictive of graft loss. These data suggest that anti‐HLA antibody monitoring post‐transplant could guide maintenance immunosuppression and improve graft outcomes.     

Cancer incidence in a cohort of Ontario and Quebec women having bilateral breast augmentation

The possibility that women, who receive breast implants for cosmetic purposes, have increased long-term risks of developing cancer continues to be debated. The objective of our study was to prospectively examine cancer incidence among women who received breast implants. A cohort was assembled of 24,558 women, 18 years of age and older, who underwent bilateral cosmetic breast augmentation, and 15,893 women who underwent other cosmetic procedures in Ontario or Quebec between 1974 and 1989. These plastic surgery patients were selected from the same clinics as the implant population. Incident cancers were identified by linking to Canadian registry data up to December 31, 1997. In total, 676 cancers were identified among women who received breast implants compared to 899 expected based on general population rates (standardized incidence ratio (SIR) = 0.75; 95% confidence interval (CI) = 0.70-0.81). Overall cancer incidence rates among women who received breast implants were similar to that of the other plastic surgery patients (relative risk (RR) = 0.91, 95% CI = 0.81-1.02). However, women who received breast implants had lower breast cancer rates than the plastic surgery patients (RR = 0.64, 95% CI = 0.53-0.79). No increased risks were observed among the implant population for any of the other cancer sites examined. Comparisons involving only women who received breast implants found no association between long-term breast cancer incidence and implant site (submuscular vs. subglandular), fill (saline vs. silicone) or envelope (polyurethane-coated or not). In conclusion, women undergoing cosmetic breast augmentation do not appear to be at an increased long-term risk of developing cancer.     

Refining the threshold of toxicological concern (TTC) for risk prioritization of trace chemicals in food

Due to ever-improving analytical capabilities, very low levels of unexpected chemicals can now be detected in foods. Although these may be toxicologically insignificant, such incidents often garner significant attention. The threshold of toxicological concern (TTC) methodology provides a scientifically defensible, transparent approach for putting low-level exposures in the context of potential risk, as a tool to facilitate prioritization of responses, including potential mitigation. The TTC method supports the establishment of tiered, health-protective exposure limits for chemicals lacking a full toxicity database, based on evaluation of the known toxicity of chemicals which share similar structural characteristics. The approach supports the view that prudent actions towards public health protection are based on evaluation of safety as opposed to detection chemistry. This paper builds on the existing TTC literature and recommends refinements that address two key areas. The first describes the inclusion of genotoxicity data as a way to refine the TTC limit for chemicals that have structural alerts for genotoxicity. The second area addresses duration of exposure. Whereas the existing TTC exposure limits assume a lifetime of exposure, human exposure to unintended chemicals in food is often only for a limited time. Recommendations are made to refine the approach for less-than-lifetime exposures.     

Folate deficiency does not alter the usefulness of the serum transferrin receptor concentration as an index for the detection of iron deficiency in mexican women during early lactation

The purpose of this study was to investigate the usefulness of soluble serum transferrin receptor (TfR) concentration, TfR index and log TfR:ferritin ratio (TfR outcomes) in detecting tissue Fe deficiency among breast-feeding Otomi women residing in Capulhuac, Mexico (2800 m above sea level) and to determine whether folate deficiency modifies the interpretation of these data. Lactating women (n = 68) provided blood samples at 22 +/- 13 d (mean +/- SD) postpartum. Using the 3-index Fe assessment model with and without Hb, 2 women (3%) had Fe-deficient erythropoiesis, 24 (36%) Fe deficiency anemia, and 19 (29%) indeterminate Fe status; 29 (43%) and 5 (7.5%) women had plasma and erythrocyte folate concentrations below normative cutoff values, respectively. Mean values for TfR outcomes were higher among women classified as Fe deficient than those who were Fe sufficient, but did not differ with low or normal blood folate concentrations. Similarly, TfR outcomes did not differ among women with normocytic or macrocytic erythrocytes. Receiver-operating characteristic (ROC) curves generated for TfR outcomes yielded areas under the curve from 0.62 to 0.68, indicating that each of these measures, on its own, is a poor predictor of tissue Fe deficiency in lactating women. In conclusion, low blood folate concentrations or the presence of macrocytosis in Otomi women from Capulhuac, Mexico (moderate altitude) did not influence the utility of TfR outcomes for the detection of Fe deficiency during early lactation. Further, on their own, TfR, TfR index, and TfR:ferritin ratio were poor predictors of tissue Fe deficiency for any given individual.     

Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy

BACKGROUND: To assess whether the expression of p21, p27, and p53 could predict biochemical failure in prostate cancer patients treated with neoadjuvant androgen deprivation prior to salvage radiotherapy for a rising post-radical prostatectomy (RP) prostate-specific antigen (PSA). METHODS: The expression of p21, p27, and p53 was determined by immunohistochemistry in a cohort of 74 formalin-fixed paraffin-embedded prostate cancer samples obtained from RP. Expression of these markers was then correlated with clinicopathological parameters and biochemical failure-free survival after salvage radiotherapy. RESULTS: Expression of p21, p27, and p53 was observed in 20%, 69%, and 74% of prostate cancer specimens, respectively. Overexpression of p21 correlated with a higher Gleason score (>7) (P = 0.024). Of the three markers, only p21 expression was correlated with PSA failure after radiotherapy (P = 0.034). In multivariate analysis, both positive p21 (P = 0.004) and pre-radiation serum PSA > 1 ng/ml (P < 0.0001) were independent predictors of biochemical failure after salvage radiotherapy. Patients with p21- tumors and a serum PSA level < or = 1 ng/ml before salvage radiotherapy had a biochemical failure-free survival at 5 years of 83%, compared to 16% at 5 years for those patients with either p21+ tumor or a PSA > 1 ng/ml. Patients with both p21+ and a PSA level > 1 ng/ml had a much lower biochemical failure-free survival rate of 25% at only 18 months (P < 0.0001). CONCLUSIONS: The expression of p21 in prostatectomy specimens could help predict the likelihood of response to salvage radiotherapy, particularly in patients treated before PSA reaches 1 ng/ml.     

Milk folate but not milk iron concentrations may be inadequate for some infants in a rural farming community in San Mateo, Capulhuac, Mexico

BACKGROUND: We were interested in identifying possible nutritional reasons for growth faltering among breastfed infants in the rural farming community of San Mateo, Capulhuac, Mexico (2800 m above sea level). OBJECTIVE: We examined the prevalence of inadequate iron and folate status among lactating Otomi women and determined to what extent their iron and folate nutriture influenced the milk concentrations of these nutrients. DESIGN: Lactating women (n = 71) provided blood and milk samples and dietary information at a mean (+/- SD) of 22 +/- 13 d postpartum. Blood indexes included hemoglobin, hematocrit, serum iron, total-iron-binding capacity, ferritin, transferrin receptor, mean cell volume, plasma folate, and erythrocyte folate. RESULTS: Approximately 62% and 58% of the women had nutritional anemia defined as a hemoglobin concentration 相似文献   

Phase I study on sentinel lymph node mapping in colon cancer: a preliminary report

BACKGROUND AND OBJECTIVES: Lymph node (LN) metastasis is one of the most significant prognostic factor in colorectal cancer. In fact, therapeutic decisions are based on LN status. However, multiple studies have reported on the limitations of the conventional pathological LN examination techniques, and therefore, the actual number of patients with LN positive colorectal cancer is probably underestimated. We assume that lymphatic tumor dissemination follows an orderly sequential route. We report here a simple and harmless coloration technique that was recently elaborated, and that allows us to identify the sentinel LN(s) (SLN) or first relay LNs in colorectal cancer patients. The main endpoint of this clinical trial is the feasibility of the technique. METHODS: Twenty patients treated by surgery for a colic cancer were admitted in this protocol. A subserosal peritumoral injection of lymphazurin 1% was performed 10 min before completing the colic resection. A pathologist immediately examined the specimens, harvested the colored SLN, and examined them by serial cuts (200 microm) with H&E staining, followed by immunohistochemical staining (AE1-AE3 cytokeratin markers), when serial sections were classified as cancer free. RESULTS: The preoperative identification of the SLN was impossible in at least 50 of the cases, however, SLNs were identified by the pathologist in 90% of cases. In two patients (10%) SLN was never identified. The average number of SLN was 3.9. Immunohistochemical analysis of the SLN has potentially changed the initial staging (from Dukes B to Dukes C) for 5 of the 20 patients (25%). On the other hand, there was one patient (5%) with hepatic metastasis from adenocarcinoma for whom SLN pathology was negative for metastasis (skip metastasis). CONCLUSIONS: SLN biopsy is readily feasible with identification of SLN in at least 90% of patients with colorectal cancers. Our results indicate that 45% of patients initially staged as Dukes B had tumor cells identified in their SLN when these were subjected to our protocol. This represented a 25% upgrading rate when our complete study population is considered. However, controversy persist about the clinical significance and metastatic potential of these often very small clusters of tumor cells.