RESUMEN

PURPOSE: To evaluate and compare the dynamic vault range (DVR) as well as the asymmetry of the vault during a 3-month follow-up after the implantation of two posterior chamber phakic intraocular lenses (pIOLs). SETTING: Aver Clinic, Madrid, Spain. DESIGN: Prospective comparative study. METHODS: One hundred and nineteen eyes (65 patients) that underwent refractive surgical correction with implantation of one of two distinct pIOLs were enrolled: Eyecryl Phakic from Biotech Vision Care (Eyecryl group, 72 eyes) and Evo Visian Implantable Contact Lens from Staar Surgical (ICL group, 47 eyes). Besides evaluation of visual acuity, refraction, and ocular integrity, the pIOL vault was measured centrally and at 2 mm nasally and temporally as well as the DVR from photopic (50 lux) to mesopic (10 lux) illuminations conditions. RESULTS: No significant differences were found between pIOL groups in visual and refractive outcomes (p≥0.454). No significant differences between groups were found in central (523.72±168.4 vs. 494.16±156.7 µm, p=0.248) and temporal vault (499.43±155.8 vs. 431.28±150.5 µm, p=0.067). However, nasal vault was significantly lower in ICL group (465.6±149.1 vs. 375.4±144.0 µm, p=0.045). A trend to a larger DVR was observed in the ICL group, although differences between groups did not reach statistical significance (54.00±36.39 vs. 86.5±57.9 µm p=0.070). The pIOL diameter only correlated significantly with vault measurements in ICL group (r≥0.650, p<0.001). CONCLUSIONS: The Eyecryl pIOL shows more symmetric vaults and a trend to fewer light-induced changes in the central vault compared to the ICL pIOL. The clinical relevance of this finding should be investigated further.

RESUMEN

Aim: To describe the evolution of regorafenib use, since its approval, in patients with previously treated metastatic colorectal cancer (mCRC) in routine clinical practice in Spain.Methods: We extracted patient characteristics, dosing, safety and efficacy data for the Spanish cohorts of the CORRECT and CONSIGN trials, and the real-world CORRELATE study.Results: The Spanish cohorts represented 10.7-13.8% of the global cohorts. Efficacy and safety in the Spanish cohorts reflected findings from the global cohorts, with evidence of a flexible dosing approach being adopted in routine clinical practice.Conclusion: Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients.Clinical trial registration: The CORRECT trial is registered at ClinicalTrials.gov, number NCT01103323; the CONSIGN trial is registered at ClinicalTrials.gov, number NCT01538680; the CORRELATE study is registered at ClinicalTrials.gov, number NCT02042144.

---

Bowel cancer (also called colorectal cancer) affects the large bowel, including the colon and rectum. Approximately one in ten patients with advanced bowel cancer that has spread to other areas of the body (metastatic bowel cancer) survive 5 years after diagnosis or the start of treatment.Regorafenib is a treatment for patients with advanced bowel cancer that has continued to spread after receiving other treatments. It can slow down cancer growth, as shown in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, bowel cancer is the most common type of cancer and the cancer that causes the second most deaths. This study describes how the use of regorafenib in Spain has changed since it was approved in 2012, by looking at the patients from Spain who made up 11­14% of the participants in the three international studies.The CORRECT trial that compared regorafenib with a non-therapeutic placebo and the CONSIGN trial of regorafenib alone showed that treatment with regorafenib prolonged life and was well tolerated in patients with metastatic bowel cancer who had previously received or were not suitable to receive other treatments. The CORRELATE study showed that in the real world (i.e., outside of a controlled clinical trial), patients are sometimes prescribed regorafenib at lower starting doses than the recommended dose, without an apparent overall effect on how well regorafenib works or side effects. In the future, it will be important to continue researching how doctors prescribe regorafenib in daily clinical practice in Spain.

Asunto(s)

Neoplasias Colorrectales , Compuestos de Fenilurea , Piridinas , Humanos , Piridinas/uso terapéutico , Piridinas/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , España/epidemiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento , Adulto , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto

RESUMEN

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.

RESUMEN

PURPOSE: To evaluate the short-term clinical outcomes of a specific toric diffractive trifocal intraocular lens (IOL) implanted following an optimized clinical protocol in a large population. METHODS: Retrospective analysis of 337 eyes of 231 patients (mean age, 62.2 years) undergoing cataract surgery with implantation of the trifocal diffractive IOL AT.LISA tri toric 939M/MP (Carl Zeiss Meditec). A strict and careful clinical protocol was followed, including an accurate measurement of corneal astigmatism, use of a latest generation IOL power calculator, photography-based method intraoperative control of IOL alignment and IOL reposition at 1 week postoperatively if needed. Clinical outcomes in terms of visual acuity, refraction, efficacy of astigmatic correction analysed by vector analysis and patient satisfaction were evaluated during a 3-month follow-up. RESULTS: A total of 82% and 98% of eyes achieved a postoperative uncorrected distance visual acuity of 0.00 and 0.10 logMAR or better, respectively. Furthermore, 99.7%, and 100.0% of eyes showed a postoperative spherical equivalent within ± 0.50 D and ± 1.00 D, with 97.9% of eyes having a postoperative cylinder ≤ 0.50 D. Uncorrected near and intermediate visual acuities were 0.2 logMAR or better in 89.0% and 99.1% of eyes, respectively. Mean difference vector, magnitude of error and angle of error were 0.02 ± 0.14 D, 0.02 ± 0.13 D and 0.11 ± 1.18°. Patient satisfaction was referred as high or very high by 97.6% of patients. CONCLUSIONS: The implantation of the trifocal toric IOL evaluated following a careful clinical protocol provides an efficacious visual rehabilitation and astigmatic correction, leading to high levels of patient satisfaction.

Asunto(s)

Astigmatismo , Lentes Intraoculares , Facoemulsificación , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Diseño de Prótesis , Refracción Ocular , Astigmatismo/cirugía

RESUMEN

PURPOSE: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. RESULTS: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. CONCLUSIONS: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. GOV IDENTIFIER: NCT02835924.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Compuestos de Fenilurea , Piridinas , Neoplasias Colorrectales/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico

RESUMEN

Nowadays, dairy products, especially fermented products such as yogurt, fromage frais, sour cream and custard, are among the most studied foods through tribological analysis due to their semi-solid appearance and close relationship with attributes like smoothness, creaminess and astringency. In tribology, dairy products are used to provide information about the friction coefficient (CoF) generated between tongue, palate, and teeth through the construction of a Stribeck curve. This provides important information about the relationship between friction, food composition, and sensory attributes and can be influenced by many factors, such as the type of surface, tribometer, and whether saliva interaction is contemplated. This work will review the most recent and relevant information on tribological studies, challenges, opportunity areas, saliva interactions with dairy proteins, and their relation to dairy product sensory.

RESUMEN

Plastic waste generation has become an important problem that critically affects marine and oceans environments. Fishing nets gear usually have a relatively short lifespan, and are abandoned, discarded and lost, what makes them one of the largest generators of ocean plastic waste. Recycled polyolefin resins from fishing nets (rFN), especially from polyethylene (PE), have poor properties due to the presence of contaminants and/or excessive degradation after its lifetime. These reasons limit the use of these recycled resins. This work aims to study the incorporation of recycled fishing nets PE-made to different grades of virgin PE, in order to evaluate the potential use of these rFN in the development of new products. The recovered fishing nets have been fully characterized to evaluate its properties after the collection and recycling process. Then, different PE virgin resins have been mechanically blended with the recovered fishing nets at different recycling contents to study its feasibility for fishing nets or packaging applications. Critical mechanical properties for these applications, as the elongation at break, impact strength or environmental stress cracking resistance have been deeply evaluated. Results show important limitations for the manufacture of fibers from recycled PE fishing nets due to the presence of inorganic particles from the marine environment, which restricts the use of rFN for its original application. However, it is proved that a proper selection of PE raw resins, to be used in the blending process, allows other possible applications, such as non-food contact bottles, which open up new ways for using the fishing nets recyclates, in line with the objectives pursued by the Circular Economy of Plastics.

RESUMEN

Objetivo: determinar las características de los pacientes con diagnóstico de Pie Diabético en un servicio de Urgencias. Materiales y métodos: estudio retrospectivo, descriptivo, basado en la revisión de 525 historias clínicas de pacientes que acudieron al servicio de Urgencias-Adultos del Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción, Paraguay entre los años 2015 y 2016. Se recopilaron los siguientes datos: edad, sexo, comorbilidades, tratamiento, tipo de amputaciones, identificación del mecanismo y lugar de inicio de lesiones; destino de los pacientes luego de Urgencias y mortalidad. Resultados: La frecuencia de Pie Diabético fue del 40% de 2718 pacientes con Diabetes;60% era del sexo masculino, el promedio de edad 63 años (±10);34 (65,3%) tenían antecedentes de hipertensión arterial; amputación previa 99 (18,9%);cardiopatía isquémica 56 (10,7%);accidente cerebro vascular 21(4%);tabaquismo 18 (3,4%). Recibieron tratamiento quirúrgico 274 (52%), de ellos 199 fueron amputaciones (73%); el 56% fueron amputaciones mayores;256 de 356 pacientes (72%) no identificaron un traumatismo causal de la lesión; 270 (51%) refirieron a los dedos como el lugar de inicio de lesiones. Hubo336 altas (64%) y 14 (2,67%) fallecieron. Conclusión: Se observó una alta frecuencia de pacientes con pie diabético en Urgencias, lo cual urge establecer programas estructurados para prevención y tratamiento multidisciplinario.

---

Objective: to determine the characteristicsof patients diagnosed with Diabetic Foot in an emergency service. Materials and methods: a retrospective, descriptive study, based on the review of 525 medical records of patients who attended the Emergency-Adult service of the Hospital de Clínicas, Faculty ofMedicine, National University of Asunción, Paraguay between the years 2015 and 2016. The following data were collected: age, sex, comorbidities, treatment, type of amputations, identification of the mechanism and place of initiation of injuries; destination of patients after emergencies and mortality. Results:The frequency of Diabetic Foot was 40% of 2718 patients with Diabetes, 60% were male, average age was 63 years (± 10),34 (65.3%) had a history of high blood pressure, previous amputation 99 (18.9%),ischemic heart disease 56 (10.7%), stroke 21 (4%), smoking 18 (3.4%),274 (52%) received surgical treatment, of which 199 were amputations (73%); 56% major amputations,256 of 356 patients (72%) did not identify a traumatic cause of the injury; 270 (51%) referred to the fingers as the place of initiation of lesions. There were 336 discharges (64%) and 14 patients (2.67%) died. Conclusion:High frequency of patients with diabetic foot in the Emergency Department, which makes it urgent to establish structured programs for prevention and multidisciplinary treatment.

Asunto(s)

Humanos , Masculino , Femenino , Pie Diabético , Diabetes Mellitus , Urgencias Médicas , Amputación Quirúrgica

RESUMEN

Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.

Asunto(s)

Adenocarcinoma/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Paclitaxel/administración & dosificación , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Femenino , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/estadística & datos numéricos , Paclitaxel/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , España/epidemiología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Ramucirumab

RESUMEN

BACKGROUND: Pancreatic neuroendocrine tumors are rare neoplasms for which few predictive and/or prognostic biomarkers have been validated. Our previous work suggested the potential of the combined expression of N-myc downstream-regulated gen-1 (NDRG-1), O6-methylguanine DNA methyltransferase (MGMT) and Pleckstrin homology-like domain family A member 3 (PHLDA-3) as prognostic factors for relapse and survival. METHODS: In this new multicenter study we evaluated immunohistochemistry expression in 76 patients with advanced PanNET who were treated with capecitabine-temozolomide or everolimus. Based on the immunohistochemistry panel, an immunohistochemistry prognostic score (IPS) was developed. RESULTS: In patients treated with capecitabine and temozolomide, low IPS was an independent prognostic factor for progression-free-survival and overall-survival. Similar findings were observed with highest IPS for overall-survival in patients treated with everolimus. CONCLUSION: From our knowledge, it is the first time that a simple IPS could be useful to predict outcome for patients with metastatic pancreatic neuroendocrine tumors treated with everolimus or capecitabine and temozolomide.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Everolimus/uso terapéutico , Inmunohistoquímica/métodos , Inmunosupresores/uso terapéutico , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Proteínas de Ciclo Celular/análisis , Línea Celular Tumoral , Metilasas de Modificación del ADN/análisis , Enzimas Reparadoras del ADN/análisis , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/análisis , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tumores Neuroendocrinos/mortalidad , Proteínas Nucleares/análisis , Neoplasias Pancreáticas/mortalidad , Pronóstico , Supervivencia sin Progresión , Análisis de Supervivencia , Proteínas Supresoras de Tumor/análisis , Adulto Joven

RESUMEN

BACKGROUND: Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The "Tratamiento de Tumores Digestivos" group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. METHODS: Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). RESULTS: In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). CONCLUSIONS: the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. TRIAL REGISTRATION: EudraCT number: 2009-010192-24 . Clinicaltrials.gov number: NCT01043484 .

Asunto(s)

Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/patología , Bevacizumab/administración & dosificación , Capecitabina/administración & dosificación , Quimioradioterapia , Femenino , Humanos , Masculino , Supervivencia sin Progresión , Neoplasias del Recto/patología

RESUMEN

PURPOSE: 5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab. PATIENTS AND METHODS: VISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS). RESULTS: The intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively. CONCLUSIONS: First-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.

Asunto(s)

Neoplasias Colorrectales , Células Neoplásicas Circulantes , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/efectos adversos , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo , Humanos , Leucovorina/efectos adversos , Compuestos Organoplatinos

RESUMEN

BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.

Asunto(s)

Neoplasias Colorrectales/patología , Embolización Terapéutica , Hepatectomía , Neoplasias Hepáticas/cirugía , Vena Porta , Cuidados Preoperatorios/métodos , Trasplante de Células Madre/métodos , Antígeno AC133 , Ensayos Clínicos Fase II como Asunto , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Insuficiencia Hepática/prevención & control , Humanos , Hígado/patología , Hígado/fisiología , Neoplasias Hepáticas/secundario , Regeneración Hepática , Metastasectomía , Tamaño de los Órganos , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

Colorectal cancer (CRC) is a public health problem: it is the third most common cancer in men (746,000 new cases/year) and the second in women (614,000 new cases/year), representing the second leading cause of death by cancer worldwide. The survival of patients with metastatic CRC (mCRC) has increased prominently in recent years, reaching a median of 25 to 30 months. A growing number of patients with mCRC are candidates to receive a treatment in third line or beyond, although the optimal drug regimen and sequence are still unknown. In this situation of refractoriness, there are several alternatives: (1) To administer sequentially the 2 oral drugs approved in this indication: trifluridine/tipiracil and regorafenib, which have shown a statistically significant benefit in progression-free survival and overall survival with a different toxicity profile. (2) To administer cetuximab or panitumumab in treatment-naive patients with RAS wild type, which is increasingly rare because these drugs are usually indicated in first- or second-line. (3) To reuse drugs already administered that were discontinued owing to toxicity or progression (oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenics, anti-epidermal growth factor receptor [if RAS wild-type]). High-quality evidence is limited, but this strategy is often used in routine clinical practice in the absence of alternative therapies especially in patients with good performance status. (4) To use specific treatments for very selected populations, such as trastuzumab/lapatinib in mCRC human epidermal growth factor receptor 2-positive, immunotherapy in microsatellite instability, intrahepatic therapies in limited disease or primarily located in the liver, although the main recommendation is to include patients in clinical trials.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/normas , Neoplasias Colorrectales/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Toma de Decisiones Clínicas/métodos , Ensayos Clínicos como Asunto , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Testimonio de Experto , Humanos , Inestabilidad de Microsatélites , Selección de Paciente , Supervivencia sin Progresión , España/epidemiología

RESUMEN

BACKGROUND: Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. METHODS: The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). RESULTS: A total of 1037 patients were treated. The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand-foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0). CONCLUSIONS: In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. TRIAL REGISTRATION: NCT02042144.

Asunto(s)

Neoplasias Óseas/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Carcinoma/secundario , Neoplasias Colorrectales/genética , Fatiga/inducido químicamente , Femenino , GTP Fosfohidrolasas/genética , Síndrome Mano-Pie/etiología , Humanos , Hipertensión/inducido químicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/patología , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Supervivencia sin Progresión , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto Joven

RESUMEN

Introducción: Los enfermos de fibrosis quística tienen mayor supervivencia y calidad de vida en las últimas décadas, debido fundamentalmente a un diagnóstico precoz. Objetivo: Describir las características de los pacientes con fibrosis quística y el seguimiento de los vivos durante 40 años. Métodos: Estudio descriptivo longitudinal retrospectivo en 96 pacientes diagnosticados con fibrosis quística en el Hospital Pediátrico Universitario William Soler (1977-2017). Los datos se obtuvieron de las historias clínicas. Se analizaron variables demográficas, temporales, clínicas, genéticas y microbiológicas. Resultados: De la muestra, actualmente se mantienen con seguimiento 27, mayores de 19 años enviados a consulta de neumología 9, fallecieron 30, no se siguen en el centro 30. El 60,4 por ciento se diagnosticó antes del primer año de vida, predominó el sexo masculino 62,5 por ciento y el color de la piel blanco 88,5 por ciento. Sugirió el diagnóstico la forma clínica respiratoria 39,6 por ciento, mixta 38,5 por ciento, digestiva 19,8 por ciento y perdedora de sal 2,1 por ciento. De los 27 casos seguidos actualmente 74,1 por ciento son eutróficos y no hay desnutridos. En el primer aislamiento microbiológico predominó la Pseudomona aeruginosa en el menor de 1 año y el Staphilococcus aureus entre 1 y 4 años. Más del 37.0 por ciento tuvo complicaciones respiratorias, el 14,8 por ciento hepática y el 40,7 por ciento sin complicaciones. La caracterización genética fue mayormente ∆F508 (70,3 por ciento). Conclusiones: Es frecuente el aislamiento de Pseudomona aeruginosa en el menor de 1 año. Casi la mitad de los pacientes no tienen complicaciones, se consiguió mejorar el estado nutricional y disminuir la mortalidad(AU)

---

Introduction: Patients with cystic fibrosis have had a greater survival and life quality in the last decades; this is due to a precocious diagnostic, a better nutrition state, and diminution of respiratory infections. Objective: To describe the characteristics of cystic fibrosis patients and follow up process to survivors for the last 40 years. Methods: Descriptive, longitudinal and retrospective study in 96 patients diagnosed with cystic fibrosis in William Soler Pediatric University Hospital (1977-2017). Data was obtained from clinical records. Demographic, temporary, clinical, genetic and microbiological variables were analized. Results: From the sample, 27 patients keep under medical follow up; 9 patients older than 19 years old were remitted to the Neumology consultation; 30 died; and 30 patients are not followed up at the hospital. 60.4 percent of the patients was diagnosed before the first year of life, t was predominant the male sex (62.5 percent) and most of them were white skin (88.5 percent). Diagnosis suggested; the respiratory clinical symptoms, 39.6 percent; mixed, 38.5 percent; digestive symptoms, 19.8 percent; salt lost, 2.1 percent. Out of the 27 cases followed at present, 74.1 percent are eutrophics, and there are not patients with malnutrition. In the first microbiological isolation, Pseudomonas aeruginosa prevailed in patients under 1-year-old and Staphilococcus aureus in patients between 1 and 4 years old. More than 37.0 percent of patients had respiratory complications, 14.8 percent had hepatic complications, and 40.7 percent had no complications. The genetic characterization was mostly of ∆F508 (59.2 percent). Conclusions: Pseudomonas aeruginosa is frequently in patients under 1-year-old. Almost half of the patients has no complications; and it is improved their nutritional state and mortality decreased(AU)

Asunto(s)

Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Fibrosis Quística/prevención & control , Diagnóstico Precoz , Estado Nutricional/fisiología , Epidemiología Descriptiva , Estudios Retrospectivos , Estudios de Seguimiento , Estudios Longitudinales

RESUMEN

INTRODUCTION: The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second-line therapy for metastatic colorectal cancer (mCRC). However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown. METHOD: The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan-based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web-based calculator. Harrell's c-index was used to assess discrimination. RESULTS: The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism-corrected c-index, 0.723; 95% confidence interval [CI], 0.666-0.778). Median OS was 6.1 months (95% CI, 5.1-8.8), 12.4 months (95% CI, 9.36-14.8), and 22.9 months (95% CI, 16.6-not reached) for high-, intermediate-, and low-risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3-4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029). CONCLUSION: We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI-aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials. IMPLICATIONS FOR PRACTICE: In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second-line FOLFIRI-aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice-based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second-line setting.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Nomogramas , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Análisis de Datos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

The involvement of GALNT12 in colorectal carcinogenesis has been demonstrated but it is not clear to what extent it is implicated in familial CRC susceptibility. Partially inactivating variant, NM_024642.4:c.907G>A, p.(D303N), has been previously detected in familial CRC and proposed as the causative risk allele. Since phenotypes of the described carrier families showed not only CRC but also a polyp history, we hypothesized that GALNT12 could be involved in adenoma predisposition and consequently, in hereditary polyposis CRC syndromes. For that purpose, we have screened the GALNT12 gene in germline DNA from 183 unrelated attenuated polyposis patients. c.907G>A, p.(D303N) was detected in 4 cases (MAF = 1.1%) and no other candidate variants were found. After segregation studies, LOH analyses, glycosylation pattern tests and case-control studies, our results did not support the role of c.907G>A, p.(D303N) as a high-penetrance risk allele for polyposis CRC.

Asunto(s)

Síndrome de Gardner/genética , Predisposición Genética a la Enfermedad , N-Acetilgalactosaminiltransferasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Linaje

RESUMEN

BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. RESULTS: Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6-1.5]; WT-RAS:13/15; HR: 0.7 [0.4-1.3]). Median OS was 37/41 months (HR:1.0 [0.6-1.8]; WT-RAS: 39/49; HR:0.9 [0.4-1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. CONCLUSIONS: In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov:NCT00885885).

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Panitumumab , España , Análisis de Supervivencia

RESUMEN

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) is an important management strategy in rectal carcinoma. Different systems grading response have shown varying prognostic influence. METHODS: To analyze the prognostic influence of pathological response in a series of 183 patients with rectal carcinoma receiving neoadjuvant therapy. To determine the prognostic significance of the histopathological patterns of response. RESULTS: A total of 183 patients from two hospitals. The concordance rate between pathologists was good. In total, 18% of the patients showed grade 0 (complete response), 31.7% grade 1, 19.2% grade 2 and 31.1% grade 3 regression. T down-staging was found in 51.9% of the cases. 46 patients recurred and 18 died of disease (median follow-up time: 39 months). We found a statistically significant association between pathological response and pT stage and down-staging. Inflammatory reaction in the tumor bed was significantly associated to regression and prognosis. Cox's multivariate analysis of survival revealed that down-staging and presence of mucin pools in the tumor bed behaved as significant predictors of recurrence and regression grade and mucin pools as significant predictors of survival. CONCLUSIONS: Pathological response is an important surrogate marker of prognosis in some large series, but results are varying. There are many systems to grade regression and this makes it difficult to compare the results by different groups. It is important to report the specific pattern of response, for some of them may have prognostic relevance. We feel there is an urgent need to develop standarized protocols and employ a universal regression scheme if we intend to use this factor to guide therapy.