Therapeutic Drug Monitoring in Oncohematological Patients: A Fast and Accurate HPLC-UV Method for the Quantification of Nilotinib in Human Plasma and Its Clinical Application.

Nilotinib, a second-generation tyrosine kinase inhibitor, has demonstrated clinical activity in chronic myeloid leukemia. As an exposure-response relationship has been observed for nilotinib, its therapeutic drug monitoring could be a valuable tool in clinical practice. Therefore, the aim of this study was to develop and validate a selective and precise high performance liquid chromatography-ultraviolet method for the measurement of nilotinib in plasma from patients with cancer. After protein precipitation extraction with acetonitrile, nilotinib and rilpivirine were separated using isocratic elution on a Tracer Excel 120 ODS C18 column using a mobile phase consisting of a mixture of potassium dihydrogen phosphate-buffered solution (pH 5.5; 0.037 M)-methanol-acetonitrile (45:45:10, v/v/v), pumped at a flow rate of 1.7 mL·min-1. A wavelength of 254 nm was selected for the quantification of the analyte and the internal standard (IS). The technique was validated following the guidelines for the validation of analytical methods of regulatory agencies (Food and Drug Administration (FDA) and the European Medicines Agency (EMA)). Linearity was established in a concentration range between 125 and 7000 ng/mL. The detection limit was 90 ng/mL, and the lower limit of quantification was 125 ng/mL. For all concentrations in the calibration curve, the intraday and interday coefficients of variation were less than 4.1%. Median recovery of nilotinib from plasma was ≥65.1% (±21.4%). The method described is sensitive, selective, reproducible, and rapid, and can be used for the accurate determination of nilotinib in human plasma for pharmacokinetics studies and for therapeutic drug monitoring (TDM) of nilotinib in routine clinical practice.

Assessment of Body Composition as an Indicator of Early Peripheral Parenteral Nutrition Therapy in Patients Undergoing Colorectal Cancer Surgery in an Enhanced Recovery Program.

BACKGROUND: A poor body composition (BC) has been identified as a risk factor for patients with colorectal cancer (CRC). This study was performed to assess the effect of early peripheral parenteral nutrition (PPN) on BC in patients undergoing CCR surgery within an enhanced recovery program. METHODS: Patients with normal nutritional status were prospectively included between October 2016 and September 2019, randomized into two groups (PPN with periOlimel N4-E versus conventional fluid therapy) and subsequently classified according to their preoperative CT scan into high- or low-risk BC groups. Postoperative complications and length of hospital stay (LOS) were assessed. RESULTS: Of the 156 patients analyzed, 88 patients (56.4%) were classified as having high-risk BC according to CT measurements. PPN led to a 15.4% reduction in postoperative complications in high-risk vs. 1.7% in low-risk BC patients. In the multivariate analysis, high-risk BC was related to an OR (95% CI) of 2 (p = 0.044) of presenting complications and of 1.9 (p = 0.066) for major complications, and was associated with an increase in LOS of 3.6 days (p = 0.039). CONCLUSIONS: The measurement of patients' BC can allow for the identification of target patients where PPN has been proven to be an effective tool to improve postoperative outcomes.

Effect of Early Peripheral Parenteral Nutrition Support in an Enhanced Recovery Program for Colorectal Cancer Surgery: A Randomized Open Trial.

BACKGROUND: Peripheral parenteral nutrition allows repletion of acute nutrient deficiencies and could prevent further nutrition deficits before and after colorectal surgery. A randomized open study was performed to evaluate the effect of perioperative peripheral parenteral nutrition (PPN) support on postoperative morbidity after colorectal cancer surgery within an enhanced recovery program. METHODS: Patients were randomized into two groups: peripheral parenteral nutrition (PPN) (with Peri-Olimel N4-E) versus conventional fluid therapy (FT). Ninety-day postoperative complications, laboratory parameters, length of hospital stay, and compliance with the ERAS protocol were assessed. RESULTS: A total of 158 patients were analysed. The overall 90-day complication rate was 38.6% (61 patients), and 24 patients had major complications (Clavien-Dindo III-V) (15.2%). In the multivariate analysis, the intervention (PPN vs. FC) showed a protective effect against postoperative complications (p = 0.0031, OR = 0.2 (CI: 0.08-0.87)). Following ordinal regression, PPN and early oral tolerance showed a protective effect, being less likely to develop complications or to move from minor to major complications. In patients with low compliance to ERAS during the first postoperative day, PPN showed a protective effect, preventing 28% of morbidity. CONCLUSIONS: Perioperative peripheral parenteral nutrition (PPN) support with Peri-Olimel N4-E in colorectal cancer surgery associated with early oral intake could reduce postoperative complications.

Perioperative Standard Oral Nutrition Supplements Versus Immunonutrition in Patients Undergoing Colorectal Resection in an Enhanced Recovery (ERAS) Protocol: A Multicenter Randomized Clinical Trial (SONVI Study).

To compare immunonutrition versus standard high calorie nutrition in patients undergoing elective colorectal resection within an Enhanced Recovery After Surgery (ERAS) program.Despite progress in recent years in the surgical management of patients with colorectal cancer (ERAS programs), postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the extent to which the combination of ERAS protocols and immunonutrition benefits patients undergoing colorectal cancer surgery is unknown.The SONVI study is a prospective, multicenter, randomized trial with 2 parallel treatment groups receiving either the study product (an immune-enhancing feed) or the control supplement (a hypercaloric hypernitrogenous supplement) for 7 days before colorectal resection and 5 days postoperatively.A total of 264 patients were randomized. At baseline, both groups were comparable in regards to age, sex, surgical risk, comorbidity, and analytical and nutritional parameters. The median length of the postoperative hospital stay was 5 days with no differences between the groups. A decrease in the total number of complications was observed in the immunonutrition group compared with the control group, primarily due to a significant decrease in infectious complications (23.8% vs. 10.7%, P = 0.0007). Of the infectious complications, wound infection differed significantly between the groups (16.4% vs. 5.7%, P = 0.0008). Other infectious complications were lower in the immunonutrition group but were not statistically significantly different.The implementation of ERAS protocols including immunonutrient-enriched supplements reduces the complications of patients undergoing colorectal resection.This study is registered with ClinicalTrial.gov: NCT02393976.

Perioperative immunonutrition in normo-nourished patients undergoing laparoscopic colorectal resection.

OBJECTIVE: To determine whether the joint implementation of immunonutrition and a laparoscopic approach improves morbidity, mortality, and length of stay (LOS) compared with dietary advice. BACKGROUND: Despite progress in recent years in the surgical management of patients with colorectal cancer, postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the immunonutrition benefits in patients undergoing colorectal laparoscopic surgery are unknown. METHODS: This study was a prospective, randomized trial with two parallel treatment groups receiving an immune-enhancing dietary supplement for 7 days before colorectal resection and 5 days postoperatively or dietary advice. RESULTS: A total of 128 patients were randomized. At baseline, both groups were comparable with respect to age, sex, surgical risk, comorbidities, and analytical and nutritional parameters. The median postoperative LOS was 5 days and was not significantly different between the groups. Wound infection differed significantly between the groups (11.50 vs. 0.00 %, p = 0.006). No other differences between the groups were identified. CONCLUSIONS: The joint use of laparoscopy and supplementation with immunonutrients reduces surgical wound infection in patients undergoing colorectal surgery. TRIAL REGISTRATION: This study is registered with ClinicalTrial.gov : NCT0239396.

Filgrastim use in the emergency department of a Spanish general hospital.

BACKGROUND: Febrile neutropenia is a cause of dose reduction in hematological cancer treatments, with patient risk of infection proportional to duration and severity. In addition, colony-stimulating factors have been shown to be beneficial in a patient subgroup, although they are probably overused in the clinical setting. OBJECTIVE: Evaluation of compliance with American Society of Clinical Oncology 2006 criteria when it comes to filgrastim use in the Emergency Department of a Spanish general hospital. METHODS AND MATERIALS: A prospective observational study from August 2011 to February 2012 in a tertiary Spanish General Hospital. We included all patients prescribed with filgrastim in the Emergency Department. Data was collected on demographics, the pharmacotherapy history, the administered chemoprophylaxis, and the destination after discharge from a clinical department, the complete blood count, and the presence of fever >= 38 °C. RESULTS: 51 patients were recorded over the period of the study. 27.45% of prescriptions complied with the clinical practice guideline criteria given the risk of febrile neutropenia, whereas 72.34% of prescriptions did not comply with the criteria, 17.65% of which did not fulfil any requirements. CONCLUSIONS: A high percentage of colony-stimulating factors use in the Emergency Department does not comply with the medical practice guideline.

Ileitis tras ileostomía / Bleeding ileitis following ileostomy

Background: The incidence of ileitis following ileostomy is 5 percent. Material and Method: We report a 79 years old male with a sigmoid cancer presenting with an intestinal obstruction. Results: Patient required a subtotal colectomy, leaving a terminal ileostomy in the right lower flank. Three days after the intervention, the patient had a profuse bleeding through the ileostomy. An emergency endoscopy showed multiple bleeding ulcers in the ileostomy. The patient did not respond to medical treatment and required a new intervention, excising 20 cm of distal ileum and performing a new ileostomy. The pathological study of the excised segment showed multiple superficial ulcers with abundant inflammatory cells.

Introducción: La ileitis tras ileostomía es una entidad poco frecuente, pero que conlleva una importante morbilidad. Objetivo: Describir un caso de ileitis postileostomía sin respuesta al tratamiento médico y revisar la literatura sobre el tema. Material y Método: Presentamos el caso de un varón de 79 años con sangrado agudo por ileostoma tras colectomía subtotal. Resultados: Tras fracaso de la terapia médica fue necesario realizar resección de segmento de íleon terminal afecto. Conclusiones: Se debe pensar en ileitis postileostomía en caso de ileostomías muy productivas o ileorragias y comenzar tratamiento esteroideo temprano y realizar ileoscopia precoz. La cirugía se reserva para aquellos casos en los que no es eficaz el tratamiento médico.