Abstract Background Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host ...inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. Patients and methods Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. Results Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽2. A NLR ⩾3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06–1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02–1.56, P = 0.035) and hilar cancer: overall group ( N = 149) (HR-1.70, 95% CI; 1.10–2.50, P = 0.01) and advanced group ( N = 111) (HR-1.57, 95% CI; 1.04–2.44, P = 0.048). Conclusion Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.
Grades II and III gliomas have unpredictable rates of progression, making management decisions difficult. Currently, several clinical and radiological characteristics are utilized to predict ...progression and survival but collectively are suboptimal.
In this study, we analyzed a set of 108 nonenhancing hemispheric grade II-III gliomas. Demographic variables, including patient age, tumor diameter, extent of resection, and performance status, were combined with molecular data (IDH mutation status mIDH, 1p/19q codeletion, PTEN deletion, and EGFR amplification). A complete dataset for all variables was compiled for 70 of the 108 patients. Both univariable and multivariable analyses were performed to determine whether the molecular data singly or in combination offer advantages over tumor type and grade for prediction of overall survival (OS) and/or progression-free rate (PFR).
Patient age, clinical variables (tumor diameter, extent of resection, performance status), and pathology (tumor type and grade) were not predictive of OS or PFR. IDH mutation status alone was predictive of longer OS and PFR for the entire group of tumors; 1p/19q deletion alone was predictive of OS but not PFR. In the multivariable analysis, none of the clinical or demographic factors were predictive of OS or PFR. IDH mutation status, 1p/19q codeletion, and PTEN deletion were predictive of OS (P = .003, P = .005, P = .02, respectively). Both mIDH (P < .001) and the interaction term of 1p/19q and PTEN (P < .001) were found to be predictive of PFR.
We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified.
Abstract Objective In the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to ...determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. Methods All women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. Results Of 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p = 0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p = 0.032) while the time to genetic counseling decreased (p = 0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. Conclusions Despite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.
Abstract Objective As treatment based genetic testing becomes a reality, it is important to assess the attitudes and preferences of women newly diagnosed with ovarian cancer regarding genetic ...testing. The objective of this study was to determine when women with a diagnosis of high grade serous ovarian cancer would prefer to undergo genetic testing and factors that influence this preference. Methods Women over 18 years of age with a known diagnosis of high grade serous ovarian cancer diagnosed between October 2010–2013 were identified via the Princess Margaret Cancer Center Registry. Participants completed a questionnaire, which obtained preferences and attitudes towards genetic testing, cancer history, and demographic information. Results 120 of the 355 women identified (33.8%) completed the questionnaires. The median age at time of ovarian cancer diagnosis was 57 years (range 35–84). The majority of participants in this study were offered (94.6%) and pursued (84.8%) genetic testing. In this cohort, testing was most frequently offered at diagnosis (41.8%) or during treatment (19.1%). In this study, women with high grade serous ovarian cancer felt that genetic testing should be offered before or at the time of diagnosis (67.8%). Having a family history of breast or ovarian cancer was significantly (p = 0.012) associated with preferring genetic testing at an earlier time point in the disease course. Conclusions Our results demonstrate that women with high grade serous ovarian cancer acknowledge the personal and clinical utility of genetic testing and support test implementation at the time of cancer diagnosis.
Hyperglycemia is commonly present in the perioperative period in patients undergoing cardiac surgery, even during administration of insulin. A direct relationship between postoperative hyperglycemia ...and mortality has been established in diabetic patients undergoing cardiac surgery. However, this relationship might be confounded because patients with poor outcome receive more glucogenic drugs postoperatively. We assessed the influence of hyperglycemia (highest glucose level) during cardiopulmonary bypass on perioperative morbidity and mortality in diabetic and nondiabetic patients.
We performed a multivariate logistic regression analysis on all diabetic (n = 1579) and nondiabetic (n = 4701) patients undergoing cardiac surgery at the Toronto General Hospital between 1999 and 2001. Boluses of insulin were given during cardiopulmonary bypass when the glucose level exceeded 15 mmol/L, when the serum potassium level exceeded 6.0 mmol/L, or both.
Overall mortality was 1.8% (n = 115). A high glucose level during cardiopulmonary bypass was an independent predictor of mortality in both diabetic (odds ratio, 1.20; confidence interval, 1.08-1.32) and nondiabetic (odds ratio, 1.12; confidence interval, 1.06-1.19; per millimole per liter increase in glucose) patients. A high glucose level during cardiopulmonary bypass was also an independent predictor of all major adverse events in both patient groups (odds ratio, 1.06; confidence interval, 1.03-1.09). A high glucose level was not closely related to cardiopulmonary bypass (
r = 0.3) or aortic crossclamp times (
r = 0.4).
A high peak serum glucose level during cardiopulmonary bypass is an independent risk factor for death and morbidity in diabetic patients and unexpectedly also in nondiabetic patients.
HLA-B27 represents a family of 38 closely related cell surface proteins (encoded by the alleles HLA-B*2701-39) called subtypes of HLA-B27, most of which have evolved from the ubiquitous HLA-B*2705 ...(specifically the B*27052 allele). HLA-B27 subtypes are largely characterized by nucleotide substitutions (mostly nonsynonymous) in exons 2 and 3 which encode alpha1 and alpha2 domains ofthe peptide binding groove respectively. Table 1 shows the description of sequences of HLA-B27 allele sequences. The subtypes could have arisen from B*2705 by point mutation (B*2703, B*2709, B*2704), gene conversion (B*2701, B*2702, B*2708) and reciprocal recombination (B*2707) B*2706 could have arisen by interlocus gene conversion. Studies from different parts of the world reveal differences in the population distribution.
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