Population pharmacokinetic models for cefuroxime and metronidazole used in combination as prophylactic agents in colorectal surgery: Model-based evaluation of standard dosing regimens.

The antibiotics used for prophylaxis in colorectal surgery must maintain appropriate plasma concentrations during the entire surgery to avoid surgical site infections caused by aerobes and anaerobes; cefuroxime plus metronidazole is one of the combinations used. The aim of this study was to evaluate the adequacy of cefuroxime plus metronidazole administration as prophylaxis in colorectal surgery. In total, 63 patients electively undergoing rectal or colon surgery were administered 1500mg of cefuroxime and 1500mg of metronidazole in 15-min and 1-h infusions, respectively, prior to surgery. Blood samples were withdrawn during and after surgery for determination of plasma concentrations by high-performance liquid chromatography. Population pharmacokinetic models were developed using NONMEM 7.2.0. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. Pharmacokinetics for both antibiotics were best described by a two-compartment model. Elimination of cefuroxime was conditioned by creatinine clearance (CLCr). The half-life of cefuroxime was 1.5h for patients with normal renal function and 4.9h in patients with renal impairment. Elimination and distribution of metronidazole were affected by patient body weight (BW). PK/PD analysis revealed that a single-dose protocol of 1500mg of cefuroxime and metronidazole is adequate in short surgeries (≤2h). However, for longer surgeries, recommendations are suggested depending on the patient's CLCr and BW. Additional doses of cefuroxime are needed for patients with moderate renal impairment or those presenting normal renal function. For metronidazole, an additional dose is needed for patients with a BW of 90kg.

Técnica del ganglio centinela en el cáncer de colon. Experiencia en 125 casos / Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases

Introducción El estudio de los ganglios linfáticos supone el factor pronóstico más importante en el cáncer colorrectal sin metástasis. La técnica del ganglio centinela identifica el ganglio que mejor predice el estado ganglionar de un paciente y permite realizar en él técnicas de estudio intensivo que mejoran la estadificación. El objetivo del trabajo es estudiar la eficacia de la técnica del ganglio centinela en la estadificación del cáncer de colon.Material y métodos Estudio prospectivo con 125 pacientes diagnosticados preoperatoriamente de cáncer de colon sin metástasis a distancia desde septiembre de 2009 hasta diciembre de 2011 en el Hospital Universitario de Álava-Txagorritxu en Álava. Realizamos la técnica del ganglio centinela ex vivo y con azul de metileno. El ganglio centinela se estudió realizando secciones múltiples y técnicas de inmunohistoquímica, además de hematoxilina-eosina. Realizamos un estudio comparativo con un grupo control con 170 pacientes estudiado de forma convencional mediante sección única y tinción de hematoxilina-eosina. Resultados Identificamos el ganglio centinela en el 98% de los casos, con una tasa de falsos negativos del 5,6%. La supraestadificación lograda en el grupo con estudio del ganglio centinela se encuentra en el 14,2% con respecto al grupo estudiado convencionalmente (p = 0,006).Conclusiones El estudio del ganglio centinela realizado ex vivo y con azul de metileno predice el estado ganglionar de los pacientes con cáncer de colon. Esta técnica supraestadifica, pasando al estadio iii a pacientes que el estudio convencional determinaba como estadios i y ii , permitiendo que accedan a un tratamiento quimioterápico que podría mejorar su pronóstico (AU)

Introduction The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. Materials and methods A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. Results The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006).Conclusions Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii , indicating chemotherapy that may improve their prognosis (AU)

[Sentinel lymph node biopsy technique in colon cancer. Experience in 125 cases]. / Técnica del ganglio centinela en el cáncer de colon. Experiencia en 125 casos.

INTRODUCTION: The level of lymph node involvement is the most important factor in staging colorectal cancer without metastasis. Sentinel lymph node mapping identifies the node(s) that most accurately reflect the lymph node status of patients, and intensive techniques that improve staging can be focused on these nodes. The aim of this study was to assess the efficacy of ex vivo sentinel lymph node mapping in the staging of colon cancer. MATERIALS AND METHODS: A prospective study was conducted on 125 patients from the Alava-Txagorritxu University Hospital Health Region (Alava), who were diagnosed prior to surgery with colon cancer without distant metastasis from September 2009 to December 2011. Ex vivo sentinel lymph node mapping with methylene blue was use in these patients to study the sentinel nodes with multiple slices using immunohistochemical techniques and haematoxylin-eosin staining. A comparative study was also performed based on a control group of 170 patients staged with conventional techniques, and involving a single slice and haematoxylin-eosin staining. RESULTS: The sentinel lymph node identification rate was 98%, with 5.6% false negatives. Upstaging occurred in 14.2% of cases compared to the group studied using conventional techniques (P=.006). CONCLUSIONS: Ex vivo sentinel lymph node mapping with methylene blue accurately reflects the lymph node status of patients with colon cancer. This approach upstages patients classified as stages i and ii by conventional techniques to stage iii, indicating chemotherapy that may improve their prognosis.

Factores de riesgo de mortalidad postoperatoria en el cáncer colorrectal: seguimiento de una cohorte en una unidad especializada / Postoperative mortality risk factors in colorectal cancer: Follow up of a cohort in a specialised unit

Introducción El tratamiento del cáncer colorrectal (CCR) es habitualmente quirúrgico y conlleva una morbimortalidad. El objetivo de este estudio es cuantificar la mortalidad postoperatoria en nuestro hospital y determinar sus factores de riesgo. Material y método Estudio prospectivo observacional de los 1.017 pacientes operados en nuestro hospital por CCR desde 1996 hasta 2007. Identificación de factores de riesgo independientes de mortalidad postoperatoria mediante estudio multivariante. Resultados La edad media era de 67,8 años. La cirugía se programó en 879 pacientes (86,5%) y se consideró curativa en 878 (86,1%). La mortalidad postoperatoria fue del 3,6% (37 pacientes) (el 2,5% en la cirugía programada y el 10,9% en la cirugía urgente). Los factores de riesgo independientes identificados fueron el tipo de cirugía (odds ratio [OR] para urgente versus programada=2,8), el grado de la American Society of Anesthesiologists (ASA) (OR para ASA III–IV versus ASA I–II=2,4) y la edad (OR para edad ≥85 versus ≤74=7,6 y edad 75–84 versus ≤74=2,4).Conclusiones Tenemos una baja mortalidad postoperatoria que se asocia principalmente a una edad mayor de 75 años, a los grados ASA III–IV y a la cirugía urgente (AU)

Introduction The treatment of colorectal cancer (CRC) is usually surgical and involves morbidity-mortality. The aim of this study is to quantify the postoperative mortality in our hospital and to determine their risk factors. Materials and methods Prospective observational study from 1996 to 2007 included 1017 patients who underwent surgery for CRC in our hospital. Identification of independent risk factors for postoperative mortality by multivariate analysis. Results The mean age was 67.8 years. The surgery was elective in 879 (86.5%) and was considered curative in 878 (86.1%). The postoperative mortality was 3.6% (37 patients), 2.5% in the elective surgery and 10.9% in the urgent. Results The independent risk factors identified were: type of surgery (odds ratio for urgent vs. elective=2.8), American Society of Anesthesiologists (ASA) grade (odds ratio for ASA III–IV vs. I–II=2.4), age (odds ratio for age ≥ 85 vs. ≤ 74=7.6 and age 75–84 vs. ≤ 74=2.4).Conclusions We found a low postoperative mortality, which was mainly associated with age over 75 years, ASA III or IV stages and urgent surgery (AU)

[Postoperative mortality risk factors in colorectal cancer: follow up of a cohort in a specialised unit]. / Factores de riesgo de mortalidad postoperatoria en el cáncer colorrectal: seguimiento de una cohorte en una unidad especializada.

INTRODUCTION: The treatment of colorectal cancer (CRC) is usually surgical and involves morbidity-mortality. The aim of this study is to quantify the postoperative mortality in our hospital and to determine their risk factors. MATERIALS AND METHODS: Prospective observational study from 1996 to 2007 included 1017 patients who underwent surgery for CRC in our hospital. Identification of independent risk factors for postoperative mortality by multivariate analysis. RESULTS: The mean age was 67.8 years. The surgery was elective in 879 (86.5%) and was considered curative in 878 (86.1%). The postoperative mortality was 3.6% (37 patients), 2.5% in the elective surgery and 10.9% in the urgent. The independent risk factors identified were: type of surgery (odds ratio for urgent vs. elective=2.8), American Society of Anesthesiologists (ASA) grade (odds ratio for ASA III-IV vs. I-II=2.4), age (odds ratio for age > or = 85 vs. < or = 74=7.6 and age 75-84 vs. < or = 74=2.4). CONCLUSIONS: We found a low postoperative mortality, which was mainly associated with age over 75 years, ASA III or IV stages and urgent surgery.