The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.
Orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in phosphoribosylation of 5-fluorouracil (5-FU), an essential step that leads to tumor growth inhibition. In our study, the prognostic relevance of OPRT, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in resectable colorectal cancer (CRC) patients treated by oral 5-FU were compared to further clarify the prognostic value of OPRT. Tumor tissue was collected from 90 CRC patients and the patients were followed for 5.2 years (Median). TS, DPD and OPRT activities in the extract of tumor tissue were determined enzymatically. The cut-off value of OPRT (0.147 nmol/(min mg), TS (0.044 pmol/mg) and DPD (72.10 pmol/ (min mg) were determined by maximal v 2 method. Among these 5-FU metabolic enzymes, only high OPRT group demonstrated significantly better disease-free survival (DFS) (p 5 0.0152) and better overall survival (p 5 0.0078). In Cox regression analysis, node status (p < 0.0005) and OPRT (p 5 0.044) were significant factors for DFS. OPRT activity in tumor tissue was a predictor of prognosis in resectable CRC patients treated by oral 5-FU-based adjuvant chemotherapy, and was useful to pick-up high risk patients independent from known prognosis factors. ' 2006 Wiley-Liss, Inc.Key words: orotate phosphoribosyl transferase; thymidylate synthasel; dihydropyrimidine dehydrogenase; oral 5-fluorouracil; adjuvant chemotherapy; colorectal cancer 5-fluorouracil (5-FU) is widely used all over the world for the treatment of a variety of tumors, and it is especially a key drug in the treatment of colorectal cancer (CRC). In western countries, 5-FU injection has been evolved as a constituent of multidrug chemotherapy, as represented by biochemical modulation of leucovorin. In Japan, in contrast, oral form of the drug was developed for the convenient administration, and has been used widely in adjuvant chemotherapy. In this connection, the usefulness of chemotherapy with oral fluoropyrimidine has been recently reported in adjuvant chemotherapy of CRC. 1,2 The analysis of correlation between 5-FU metabolic enzymes and antitumor effect has been widely investigated to predict the effect of 5-FU. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are such enzymes and the association to 5-FU efficacy has been frequently reported in the literature. TS plays a part in DNA synthesis from thymidine and known be inhibited by forming ternary complex together with 5-fluorodeoxyuridine monophosphate (FdUMP) and active folic acid when 5-FU is administered. 3,4 High TS activity in tumor cells often associate with low 5-FU sensitivity and low TS activity associate with high sensitivity. 5 It has been reported that patients with high DPD activity in the tumor showed low 5-FU sensitivity, whereas those with low DPD activity showed high 5-FU sensitivity. 6 Also, Salonga et al. have studied the impact of the enzymes on the 5-FU efficacy and then clarified that a combination of two enzyme activities, TS and DPD, is useful to predict the res...
Purpose There are few reports about postoperative outcome of penoplasty (PP). We present the results of mid-to long-term follow-up of PP performed for congenital megaprepuce (CMP). Methods Data from 65 CMP cases treated by PP performed by a single surgeon from 2000 to 2014 were collected prospectively. All cases were treated using the technique reported by Cuckow (Pediatric surgery. Springer, Berlin, pp [543][544][545][546][547][548][549][550][551][552][553][554] 2006). Results Mean age at PP was 5.9 years (range 0.4-13.9). All cases presented as infants and some 12 cases (18.5 %) had PP when 10 or more years old. There were no intraand postoperative complications. Mean duration of followup was 3.6 years (range 0.1-17.5). Duration of follow-up was 4 years or less in 48 (73.8 %), 5-9 years in 13 (20.0 %), and 10 or more years in 4 (6.2 %). While postoperative penile cosmesis was good in 63/65 (96.9 %) cases without scrotal deformity, 2/65 (3.1 %) had redundant penile skin excised upon the recommendation of the treating surgeon even though the patients and parents were unconcerned. Conclusion Mid-to long-term follow-up of our PP cases shows that outcome is cosmetically acceptable and stable.
The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated in a total of 12 cases - nine in which partial gastrectomy was performed and three in which total gastrectomy was performed. A single oral dose of S-1, 50 mg as tegafur, was administered, serial peripheral blood samples were collected, and the concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured. The pre-operative S-1 dose was administered about 7 days before surgery and the post-operative dose was administered around post-operative hospital day 14. In the partial gastrectomy cases the maximum post-operative blood concentration (Cmax) of 5-FU and CDHP tended to be lower than before surgery, and the difference in 5-FU concentrations was significant. The area under the blood concentration-time curve (AUC0-8 h) for CDHP was significantly smaller post- than pre-operatively, but no significant difference was observed with regard to 5-FU. In the total gastrectomy cases the post-operative tmax of both 5-FU and CDHP was shorter than the pre-operative tmax, and no significant differences were observed between the pre- and post-operative AUC0-8 h values. Thus, the results of the present study showed that around post-operative hospital day 14, when total oral feeding had become possible after surgery for gastric cancer, the AUC0-8 h values of 5-FU and CDHP after S-1 administration were almost the same as before surgery and that gastrectomy had hardly any effect on the pharmacokinetics of S-1.
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