Molecular Predictors of Response to Neoadjuvant Chemoradiation for Rectal Cancer.

OBJECTIVES: To determine whether the expression of specific molecular markers in the rectal cancer biopsies prior to treatment, can correlate with complete tumor response to chemoradiotherapy (CRT) as determined by the pathology of the surgical specimen. METHODS: We retrospectively examined pretreatment rectal biopsies of patients aged 18 years or older with locally advanced rectal cancer who had been treated with neoadjuvant CRT and surgical resection in our tertiary-care, university-affiliated medical center, between January 2001 and December 2011. Samples were analyzed for expression of B-cell lymphoma 2, P53, Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor, and the tumor regression grade after CRT and radical surgery. RESULTS: Forty-seven patients were included in the final analysis. Main outcome measures were the correlation between the expression of the molecular markers tested in the pretreatment biopsy, and complete tumor response. Complete pathologic response after CRT was attained in 27% of the patients. Percentage of cells expressing EGFR in the pretreated biopsies of patients having complete pathologic response after CRT and surgery was 33.08±7.87% compared to 19±15.36% (P=0.38), 6.66±2.83% (P<0.003), and 12.5±4.93% (P=0.033) in patients with partial response and tumor regression grades of 2, 3, and 4, respectively. The other molecular markers tested in the pretreatment biopsy did not corresponded with complete pathologic response. CONCLUSIONS: EGFR expression pattern in the pretreatment biopsies of rectal tumors can assist in identifying patients who will benefit from neoadjuvant CRT.

C reactive protein and long-term risk for chronic kidney disease: a historical prospective study.

INTRODUCTION: C reactive protein (CRP) is an acute phase reactant that primarily produced by hepatocytes yet may be locally expressed in renal tubular cells. We assessed the association of CRP and the risk for chronic kidney disease (CKD) development. METHODS: Historical prospective cohort study was conducted on subjects attending a screening center in Israel since the year 2000. Subjects with an estimated GFR (eGFR) above 60 ml/min/1.73 m(2) at baseline were included, and high sensitive (hs) CRP levels as well as eGFR were recorded for each visit. Follow up continued for at least 5 years for each subject until 2013. Risk for CKD at end of follow up was assessed in relation to mean hs-CRP levels of each subject. The confounding effects of other predictors of CKD were examined. A logistic regression model treating CRP as a continuous variable was further applied. RESULTS: Out of 4,345 patients, 42 (1%) developed CKD in a mean follow up of 7.6 ± 2 years. Elevated levels of CRP were associated with greater risk for CKD (crude OR 4.17, 95% CI 1.46-11.89). The OR for the association of CRP with CKD when controlling for age and gender was 5.2 (95% CI 1.7-16.2). When controlling for established renal risk factors, elevated CRP levels remained significantly associated with greater risk for CKD (OR 5.42, 95% CI 1.76-16.68). When applying logistic regression models treating CRP as a continuous variable, for patients with diabetes mellitus (DM), hypertension (HTN) or eGFR between 60-90 ml\min\1.73 m(2), the predictive role of CRP for CKD was highly significant. CONCLUSION: Elevated CRP level is an independent risk factor for CKD development. In patients with DM, HTN or baseline eGFR between 60-90 ml\min\1.73 m(2) its predictive role is enhanced.

Vomiting and dysphagia predict delayed gastric emptying in diabetic and nondiabetic subjects.

BACKGROUND: Gastroparesis is a heterogeneous disorder most often idiopathic, diabetic, or postsurgical in nature. The demographic and clinical predictors of gastroparesis in Israeli patients are poorly defined. METHODS: During the study period we identified all adult patients who were referred to gastric emptying scintigraphy (GES) for the evaluation of dyspeptic symptoms. Of those, 193 patients who were referred to GES from our institution were retrospectively identified (76 (39%) males, mean age 60.2 ± 15.6 years). Subjects were grouped according to gastric half-emptying times (gastric T 1/2). Demographic and clinical data were extracted from electronic medical records or by a phone interview. KEY RESULTS: Gastric emptying half-times were normal (gastric T 1/2 0-99 min) in 101 patients, abnormal (gastric T 1/2 100-299 min) in 67 patients, and grossly abnormal (gastric T 1/2 ≥ 300 min) in 25 patients. Vomiting and dysphagia, but neither early satiety nor bloating, correlated with delayed gastric emptying. Diabetes was associated with grossly abnormal gastric T 1/2. Idiopathic gastroparesis was associated with a younger age at GES. No correlation was observed between gastric T 1/2 values and gender, smoking, H. pylori infection, HBA1C, or microvascular complication of diabetes. CONCLUSIONS INFERENCES: Vomiting and dysphagia are predictive of delayed gastric emptying in both diabetic and nondiabetic subjects. Diabetes is associated with more severe gastroparesis.

Genetic considerations in human sex-mate selection: partners share human leukocyte antigen but not short-tandem-repeat identity markers.

PROBLEM: Previous studies support a role for MHC on mating preference, yet it remains unsettled as to whether mating occurs preferentially between individuals sharing human leukocyte antigen (HLA) determinants or not. Investigating sex-mate preferences in the contemporary Israeli population is of further curiosity being a population with distinct genetic characteristics, where multifaceted cultural considerations influence mate selection. METHOD OF STUDY: Pairs of male-female sex partners were evaluated in three groups. Two groups represented unmarried (n = 1002) or married (n = 308) couples and a control group of fictitious male-female couples. HLA and short-tandem-repeat (STR) genetic identification markers were assessed for the frequency of shared antigens and alleles. RESULTS: Human leukocyte antigen results showed that Class I and/ or Class II single antigen as well as double antigen sharing was more common in sex partners than in control group couples (P < 0.001). Married versus unmarried pairs were not distinguishable. In contrast, STR-DNA markers failed to differentiate between sex-mates and controls (P = 0.78). CONCLUSION: Sex partnerships shared HLA determinants more frequently than randomly constituted male-female pairs. The observed phenomenon does not reflect a syngenetic background between sex-mates as STR markers were not selectively shared. Thus, sex-mate selection in man may contravene the evolutionary pressure for genetic diversity in regard to HLA.

A longitudinal assessment of the natural rate of decline in renal function with age.

BACKGROUND: Cross-sectional studies have long suggested that renal function declines with age. Longitudinal studies regarding this issue are limited. METHODS: We retrospectively analyzed a database of subjects attending a screening center in Israel between the years 2000-2012. Only subjects with normal estimated glomerular filtration rate (eGFR) were included. eGFR was assessed consequently at 5 or more yearly visits. The rate of decline in GFR with age was assessed in healthy subjects and in subjects with comorbidities. RESULTS: The cohort included 2693 healthy subjects and 230 subjects with different comorbidities. Mean (±standard error) annual rate of decline in eGFR in healthy subjects was 0.97 ± 0.02 ml/min/year/1.73 m(2). This decline increased significantly from 0.82 ± 0.22 in age-group 20-30 years to 0.84 ± 0.08, 1.07 ± 0.08 and 1.15 ± 0.12 ml/min/year/1.73 m(2) in age groups 31-40, 41-50 and 50 years and older respectively (p < 0.001). No correlation was found between the annual decline in eGFR and body mass index. In subjects with hypertension, diabetes mellitus, impaired fasting glucose or combined comorbidity the decline in eGFR was 1.12 ± 0.12, 0.77 ± 0.16, 0.85 ± 0.17, and 1.18 ± 0.26 ml/min/year/1.73 m(2) respectively. CONCLUSIONS: This large longitudinal study provides new data on the decrease in eGFR with age. Accurate prediction of the natural rate of GFR decline might be used to distinguish between normally aging kidneys and those with chronic disease. This approach could avoid unnecessary diagnostic procedures in the former and facilitate appropriate treatment in the latter.