Gene‐expression‐based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients

Metastasis is the primary cause of mortality in Neuroblastoma (NB) patients, but the metastatic process in NB is poorly understood. Metastsis is a multistep process that requires the coordinated action of many genes. The identification of genes that promote or suppress tumor metastasis can advance our understanding of this process. In the present study, we utilized a human NB xenograft model comprising local and metastatic NB variants, which was recently developed in our laboratory. We set out to identify molecular correlates of NB metastasis and to determine the clinical relevance of these molecules. We first performed genome‐wide expression profiles of metastatic and nonmetastatic NB variants that have an identical genetic background. We found that some of the proteins highly expressed in the metastatic NB variants are localized in the cytoplasm and endoplasmic reticulum. Other proteins are linked to metabolic processes and signaling pathways, thereby supporting the invasive and metastatic state of the cells. Subsequently, we intersected the differentially expressed genes in the human xenografted variants with genes differentially expressed in Stage 1 and Stage 4 primary tumors of NB patients. By using the same gene‐expression platform, molecular correlates associated with metastatic progression in primary NB tumors were identified. The resulting smaller gene set was clinically relevant as it discriminated between high‐ and low‐risk NB patients.     

High Meat Consumption Is Prospectively Associated with the Risk of Non-Alcoholic Fatty Liver Disease and Presumed Significant Fibrosis

Non-alcoholic fatty liver disease (NAFLD) has been associated with meat consumption in cross-sectional studies. However, only a few prospective studies have been conducted, and they did not test for liver fibrosis. We aimed to assess the association between meat consumption changes and the incidence and remission of NAFLD and significant liver fibrosis. We used a prospective cohort study design, including 316 subjects aged 40–70 years, participating in baseline and follow-up evaluations at Tel-Aviv Medical Center. NAFLD was determined by liver ultrasound or controlled attenuation parameter (CAP), and liver fibrosis was determined by FibroScan. Meat consumption (g/day) was assessed by a food frequency questionnaire (FFQ). In multivariable-adjusted analyses, high consumption of red and/or processed meat (≥gender-specific median) was associated with a higher risk of NAFLD with elevated alanine aminotransferase (ALT) (OR = 3.75, 1.21–11.62, p = 0.022). Consistently high (in both baseline and follow-up evaluations) total meat consumption was associated with 2.55-fold (95% CI 1.27–5.12, p = 0.009) greater odds for new onset and/or persistence of NAFLD compared to consistently low meat consumption. A similar association was shown for consistently high consumption of red and/or processed meat (OR = 2.12, 95% CI 1.11–4.05, p = 0.022). Consistently high red and/or processed meat consumption was associated with 4.77-fold (95% CI 1.36–16.69, p = 0.014) greater odds for significant fibrosis compared to consistently low consumption. Minimizing the consumption of red and/or processed meat may help prevent NAFLD and significant fibrosis.     

Do individuals with a family history of colorectal cancer adhere to medical recommendations for the prevention of colorectal cancer?

Individuals with a family history of colorectal cancer (CRC), have a two-to-five-fold increased lifetime risk to develop CRC. Thus, they are particularly likely to benefit from adherence to medical recommendations for CRC prevention. Despite this increased risk, previous studies have shown an underutilization of colonoscopy for screening and a paucity of data on lifestyle habits that could enhance colonoscopy rates in this population. The primary aims were (a) to assess CRC screening patterns and lifestyle choices among siblings and children of CRC patients, (b) to ascertain discrepancies between actual behavior and medical recommendations, and (c) to identify family members with multiple unhealthy lifestyle habits. The secondary aim was to test for possible associations between utilization rates for CRC screening and other preventive health services. A cross-sectional study was conducted among 318 first-degree relatives (FDRs) of 164 CRC patients treated at the Tel Aviv Sourasky Medical Center. Interviews were conducted with a structured questionnaire. There was significant underutilization of colonoscopy for screening with only 73 FDRs (23.0 %) adhering to the recommended screening schedule. This rate was slightly improved (N = 58, 31.9 %) among subjects aged 40 years and above, although it was still far below the optimum. A similar result (N = 70, 21.7 %) was observed for other cancer screening tests and routine medical check-ups. A significant association (P < 0.0001) was found for healthful lifestyles, overall use of preventive health services, and adherence to CRC screening recommendations. CRC screening is significantly underutilized among FDRs of CRC patients. FDRs who do not comply with CRC screening guidelines, lead unhealthy lifestyles, and avoid other cancer screening tests are at increased risk and should be addressed specifically in future interventions.     

Esophageal incisions repair by CO2 laser soldering

PURPOSE: This study evaluated the feasibility of fiberoptic CO2 laser soldering for the repair of esophageal injuries under tight temperature feedback control in an animal model. Healing was compared to conventional suture closure. MATERIALS AND METHODS: A CO2 soldering system equipped with infrared transmitting silver halide fibers was used. The soldered tissue temperature was monitored continuously, and laser power was adjusted to provide constant temperature. The procedure was done with 50% bovine serum albumin solder. Longitudinal incisions measuring 8 to 10 mm were made under general anesthesia in the cervical esophagus of 25 rats. Twenty rats (group I) underwent laser tissue bonding; 8 of which were tested in a preliminary study to determine optimal laser parameters. In the remaining 5 rats (group II, controls), closure was performed with 1 layer of 6/0 Vicryl sutures. The rats were sacrificed 2, 3, 4, and 6 weeks postoperatively, and the esophagus was examined histologically. RESULTS: Optimal temperature was found to be 65 to 70 degrees C and optimal exposure time, 150 to 200 seconds. Laser soldering was successful in 9 of the 12 rats (75%) treated under optimal settings; suturing was successful in 4 of the 5 control rats (80%). There were no significant differences between the groups in healing or complication rates. CONCLUSIONS: These results indicate that the CO2 laser soldering technique is a valid option for the correction of esophageal tears or incisions in rats. The confirmation and extension of these findings in further studies with larger animals may ultimately lead to the routine in vivo use of temperature-controlled laser repair for the esophagus and other organs. This method lends itself to endoscopic bonding of tissues.     

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus

Background and Aims: Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. Methods: We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Results: Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ～55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Conclusion: Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either ‘normal’ or ‘healthy’, with the later reflecting much lower values, above which an individual is at increased risk for DM.     

Colorectal carcinoma in inflammatory bowel disease: a comparison between Crohn’s and ulcerative colitis

Aim The study assessed the clinicopathological features and survival rates of inflammatory bowel disease (IBD) patients with colorectal carcinoma (CRC), which accounts for ～15% of all IBD associated death. Method The medical records of patients operated on for CRC in three institutions between 1992 and 2009 were reviewed, and those with Crohn’s colitis (CC) and ulcerative colitis (UC) were identified. Data on age, gender, disease duration, colitis severity, surgical procedure, tumour stage and survival were retrieved. Results Fifty‐three patients (40 UC and 13 CC, 27 men, mean age at operation 54 years) were found. All parameters were comparable between the groups. Mean disease duration before CRC was 22.7 years for UC and 16.6 years for CC patients (P = 0.04). CRC was diagnosed preoperatively in 43 (81%) patients. Twenty‐eight patients had colon cancer, 23 had rectal cancer and two patients had more than one cancer. All malignancies were located in segments with colitis. Over one‐half were diagnosed at an advanced stage (36% stage III; 17% stage IV). At a mean follow up of 56 ± 65 months, 60% were alive (54% disease free) and 40% were dead from cancer‐related causes. The 5‐year survival rate was 61% for the UC and 37% for the CC patients (P = NS). Conclusion CRC in IBD patients is frequently diagnosed at an advanced stage, a factor that contributes to poor prognosis. The risk of CRC in CC patients is comparable to those with UC. Long‐term surveillance is recommended for patients with long‐standing CC and UC.