9 research outputs found

    Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

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    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team

    Estudi al·lòmetric del comportament cinètic del tiamfenicol en diferents espècies animals

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    L'objectiu principal de la tesi doctoral fou la recerca d'una eina que permetés la predicció dels paràmetres farmacocinètics del tiamfenicol (TAP) -un antibiòtic d'ampli espectre- en qualsevol espècie, a partir de les relacions al·lomètriques establertes entre set espècies animals -ratolí, rata, conill, gos, porc, ovella i vedell-. En primer lloc, s'estudià el comportament cinètic del fàrmac en cadascuna de les espècies mitjançant els paràmetres farmacocinètics principals (volum de distribució aparent, aclariment plasmàtic i semivida plasmàtica), calculats a partir de les corbes temps-concentració plasmàtica de cada animal. Aquestes corbes s'elaboraren a partir de l'administració d'una dosi terapèutica de TAP per via iv i la presa de mostres de sang a diferents temps, mostres que s'analitzaren mitjançant una tècnica d'HPLC (High Performance Liquid Chromatography) per tal de quantificar la presència de TAP en cadascuna. El pas següent consistí a calcular les equacions al·lomètriques per a cada paràmetre farmacocinètic, representant en una escala logarítmica el pes de l'espècie enfront del valor del paràmetre en cadascuna, i realitzant una anàlisi de regressió lineal de la recta obtinguda. Paral·lel·lament, s'estudiaren diferents unitats de temps farmacocinètic per tal de trobar aquella unitat que millor definia la disposició del TAP en totes les espècies estudiades. Per acabar, s'efectuà una predicció dels paràmetres farmacocinètics del TAP en cada espècie segons el seu pes, a partir dels equacions al·lomètriques i de la unitat de temps farmacocinètic que millor definia el comportament del TAP en totes les espècies (apolysichrons, en aquest cas). Es calculà l'exactitud de la predicció dels dos mètodes mitjançant l'error mitjà percentual (E.M.) i s'avaluà quin dels dos era més adequat per a la predicció de la disposició del TAP en qualsevol espècie. Els resultats obtinguts suggerien que la disposició del TAP és similar en totes les espècies. En tots tres paràmetres, el valor de r2 de la recta de regressió fou superior a 0.85, valor que indica una elevada correlació entre el paràmetre i el pes de l'espècie. L'exactitud de la predicció fou similar per als dos mètodes d'escalatge interespecífic, tot i que la predicció mitjançant apolysichrons presentava valors d'E.M. lleugerament superiors per a la majoria d'espècies i paràmetres.The main objective was the research of a method that allows to predict the pharmacokinetic parameters of thiamphenicol (TAP) -a broad spectrum antibiotic- in any animal species, from the allometric relations established among seven animal species -mouse, rat, rabbit, dog, pig, sheep and cattle-. The first step consisted on the study of the kinetics disposition of the TAP in every species from the analysis of the main pharmacokinetic parameters (apparent volume of distribution, plasma clearance and plasma half-life). These parameters were calculated from the mathematical analysis of the time-concentration curves constructed from the administration of a therapeutic dose of TAP intravenously. The quantitation of the plasma samples was made by a HPLC (High Performance Liquid Chromatography) technique. The relationship between the main pharmacokinetic parameters of thiamphenicol and body weight was studied across these the seven mammalian species, using double-logarithmic plots and by analizing the regression lines. At the same time, different pharmacokinetic time units were studied to analize which of them was the best to define the pharmacokinetic disposition in all the studied species. Finally, a prediction of the pharmacokinetic parameters in every species was made from the allometric equations and from the selected pharmacokinetic time unit. (apolysichrons, in our case). The accuracy of the two methods was calculated by using the mean percent error (M.E.) formula, and their suitability for the prediction of the TAP disposition was evaluated. The obtained results suggested that the TAP disposition is similar in all the studied species. The regression analysis of the three parameters indicated a good correlation between the parameter value and the body weight (correlation coefficient, r2>0.85). The accuracy of the prediction was similar for the two methods assayed, but the values of E.M. for the prediction from apolysichrons were slightly higher than from the allometric equation

    Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

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    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team

    Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

    No full text
    AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team
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