Background: The optimal treatment for locally recurrent rectal cancer (LRRC) is still a matter of debate. This study assessed the outcome of LRRC patients treated with multimodality treatment, consisting of neoadjuvant radio (chemo-) therapy, extended resection, and intraoperative radiotherapy.Methods: One hundred and forty-seven consecutive patients with LRRC who underwent treatment between 1994 and 2006 were studied. The prognostic values of patient-, tumor-and treatment-related characteristics were tested with uni-and multivariate analysis.Results: Median overall survival was 28 months (range 0-146 months). Five-year overall, disease-free, and metastasis-free survival and local control (OS, DFS, MFS, and LC respectively) were 31.5%, 34.1%, 49.5% and 54.1% respectively. Radical resection (R0) was obtained in 84 patients (57.2%), microscopically irradical resection (R1) in 34 patients (23.1%), and macroscopically irradical resection (R2) in 29 patients (19.7%). For patients with a radical resection median OS was 59 months and the 5-year OS, DFS, MFS, and LC were 48.4%, 52.3%, 65.5% and 68.9%, respectively. Radical resection was significantly correlated with improved OS, DFS, and LC (P \ 0.001). Patients who received re-irradiation or full-course radiotherapy survived significantly longer (P = 0.043) and longer without local recurrence (P = 0.038) or metastasis (P \ 0.001) compared to patients who were not re-irradiated.Conclusions: Radical resection is the most significant predictor of improved survival in patients with LRRC. Neoadjuvant radio (chemo-) therapy is the best option in order to realize a radical resection. Re-irradiation is feasible in patients who already received irradiation as part of the primary rectal cancer treatment.
Objectives: To study the association of serovars of Chlamydia trachomatis with clinical manifestations of genital tract infection and socio-demographic characteristics. Methods: In 1986-88 the C trachomatis isolates from 159 heterosexual men and 116 women attending a sexually transmitted disease (STD) clinic were collected and typed accordingly. A medical history was recorded, a physical examination took place and samples were taken for laboratory diagnostics.Results: Serovars E, F and D were the most common for both men (75%) and women (67%). Men infected with serovars of the C-complex had more often a history of STD (p = 0 06). The opposite was demonstrated in women (p = 0.07). In addition, women younger than 18 years at first intercourse were more often infected with C-complex serovars (p = 0.05). For men, the serovars F/G less often produced symptoms of urethral discharge (p = 0-01) than the serovars of the B-complex and C-complex and were less often associated with the presence of 10 or more leukocytes in a Gram-stained smear (p = 0.04). Conclusions: In this study, infections with serovars F and G caused less obvious symptoms and signs of inflammation in men; in women no differences were found in the clinical manifestation of infections with different serovars. (Genitourin Med 1996;72:261-265)
Thymidylate synthase (TS) is a potentially valuable marker for therapy response since it is the molecular target of 5-fluorouracil (5-FU). TS can be analyzed at the DNA (gene polymorphisms and amplification) and protein level (immunohistochemistry). This study investigated the predictive role of TS at the DNA and protein levels in patients with N 1 colon cancer (n 5 38). Tumor and normal tissues were genotyped using PCR for variable number of tandem repeats (VNTR), a single nucleotide polymorphism (SNP) in the 3R allele and a 6 bp deletion (1494del6) in the TS gene. Tumor tissues were additionally analyzed for loss of heterozygosity (VNTR polymorphism). A newly developed real time PCR assay was used to detect the presence of TS gene amplifications in tumor tissues. VNTR analysis in normal tissue was significantly associated with distant tumor recurrence (8% for 2R/2R vs. 52% for patients carrying a 3R allele, p 5 0.038) and cancer-specific survival (p 5 0.021). IHC was not found to be significantly associated with patients' outcome. No correlations between TS gene polymorphisms and IHC were found. However, TS gene amplification was correlated with a strong IHC staining intensity. In conclusion, this study indicates that DNA based analysis is more predictive for patientsÕ outcome than TS IHC. ' 2008 Wiley-Liss, Inc.Key words: thymidylate synthase; polymorphism; 5-fluorouracil; colon cancer; gene amplification A substantial number of patients with colon cancer who received adjuvant 5-fluorouracil (5-FU)-based therapy will not benefit from it. Therefore, predictive markers are needed in order to discriminate between responsive and nonresponsive patients. Thymidylate synthase (TS) is a central enzyme in DNA synthesis and is a potentially valuable marker since it is the molecular target of 5-FU. TS protein expression is affected by 3 different functional polymorphisms in the untranslated regions (UTRs) of the gene. Sensitivity to 5-FU based therapy might be largely influenced by the intracellular levels of the TS protein.TS protein levels can be studied directly by western blotting, enzyme activity assays, 1,2 ELISA 3,4 and immunohistochemistry (IHC). 5,6 The mainstream method is IHC because it is a relatively cheap, widely implemented technique that enables studying protein expression in situ. At the DNA level, TS protein expression is affected by different underlying functional polymorphisms as shown by several functional studies. [7][8][9][10][11][12] These polymorphisms are the following: a variable number of tandem repeats (VNTR) containing 2 (2R) or 3 (3R) repeats of 28 bp, 7 a single nucleotide polymorphism (SNP) of a G to C substitution in the 3R allele 9 in the 5 0 UTR and a 6 bp deletion at nucleotide 1494 in the 3 0 UTR (1494del6). 12 Recently, a SNP of a G to C substitution in the first repeat of the 2R allele has also been found (hereafter referred to as the 2RC allele). 13,14 TS mRNA with 3 repeats has greater translation efficiency than mRNA with 2 repeats. 7,11 Individuals with a 3R/3R genotype will,...
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