Thymidylate synthase (TS) gene polymorphisms are important as prognostic factors in cancer chemotherapy, but recent results describe that the TS enhancer region (TSER) polymorphic genotypes may also modulate risk for malignancies. Two functionally important and ethnically diverse polymorphisms are present on the TS transcript, TSER, a repeat polymorphism (2 or 3 repeats; 2R, 3R) affecting TS expression, and a 6 bp ins/del polymorphism on the 3 UTR (position TS1494, del6 or ins6), which may influence mRNA stability. Hungarian population has one of the highest colorectal cancer (CRC) mortality rates in Europe, and several elevated dietary risk factors affect a large part of the population. In our study (99 primary CRC cases), population analysis of the patient group genotype frequencies revealed a departure from the Hardy-Weinberg equilibrium and significant heterozygote deficiency (p < 0.05) at the TSER locus. Despite the strong linkage between the 2 polymorphic loci, case TS1494del genotype frequencies were normally distributed, as well as the genotype frequencies of the healthy control population (n ؍ 102), at both loci. Case-control comparison demonstrated a lower relative risk of TSER heterozygotes (OR ؍ 0.47; CI ؍ 0.27-0.83; p ؍ 0.008) and a possible higher prevalence of the 3R3R&ins6/del6 in the CRC group. The observation that heterozygotes are those less susceptible for CRC in the Hungarian population may support the possibility of 2 different pathways in which TS may play a role in colorectal carcinogenesis, probably nutrient (or folate)-dependently. The lack of similar genotype effect seen with TS1494del polymorphism and the increased presence of one genotype combination (3R3R&ins6/del6) in the patient group suggest a possible TS haplotype effect influencing CRC risk.
The biofragmentable anastomosis ring (BAR) has been used successfully for anastomoses from the stomach to the upper rectum. The healing of intrathoracic esophageal anastomoses performed with the BAR or an end-to-end anastomosis (EEA) stapler on an experimental model was compared. Parameters of tissue repair were evaluated: macroscopic examination, bursting strength (BS), collagen (hydroxyproline, or HP), histology (H&E and Picrosirius red staining for collagen). A series of 48 mongrel dogs were randomly separated into two groups (30 BAR, 18 stapler) and subgroups according to the time of autopsy (days 4, 7, 14, 28). Mortality was 13.3% (4 BAR cases) with two deaths not related to surgery (excluded). There were four leaks in the BAR group (14.3%) and no leaks or deaths but two strictures in the stapler group. BS was significantly higher in the BAR group during the first week, and values were almost equal from the second week with both methods. The HP rate was significantly reduced on days 4 and 7 in both groups compared to the reference values; the values were close to reference values from the second week (lower in the BAR group). Stapled anastomoses caused less pronounced inflammation and were associated with an earlier start of regeneration, but the difference was not significant compared to that in the BAR group. Accumulation of new collagen (green polarization) started on day 7 in both groups, but maturation (orange-red polarization) was significantly more advanced in the BAR group after the second week. A strong linear correlation between the BS and HP rate was found with both methods. There was no significant difference in the complication rate or healing of intrathoracic BAR and stapled anastomoses. The BAR method is simple, quick, and safe; and it seems to be a feasible procedure for creating intrathoracic esophageal anastomoses in dogs.
The aim of the present study was to determine the relative intratumoral activity of two pyrimidine biosynthetic enzymes, i.e. thymidylate synthase (TS) and thymidine kinase (TK), in human colorectal cancers to compare their possible relationship with demographic and pathologic characteristics of the patients and their tumors, and moreover to evaluate their predictive significance regarding 5-fluorouracil (5-FU) sensitivity and the overall survival of patients, respectively. TS and TK levels were significantly increased in the tumor compared to peritumoral tissue. However, no significant relationship between TS/TK activity and demographic features of the patients or pathologic characteristics of their tumors could be demonstrated. Kaplan-Meier analysis showed that the overall survival of patients with low TS activity was significantly longer (p < 0.012) compared to those with high TS activity. Such a difference could not be demonstrated between patients with high or low TK activity; however, combined evaluation of the two parameters proved that TK may contribute to the more precise assessment of disease prognosis, and it may further influence treatment decisions, i.e. the selection of patients for adjuvant therapy with 5-FU and folinic acid. Multivariate analysis showed that among the variables tested, beside Dukes’ stage, TS and TK activities were significant prognostic factors for the overall survival of colorectal cancer patients.
Lymphoscintigraphy followed by dual-agent guided inguinal SLNB is technically feasible for staging patients with primary anal cancer. The detection of metastases in the removed sentinel lymph node(s) may alter the treatment and thus may improve the locoregional control and overall survival of these patients.
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