A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study.

BACKGROUND: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. RESULTS: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. CONCLUSIONS: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.

Ampollas Hemorrágicas en Purpura de Henoch - Schönlein en paciente pediátrico a propósito de un caso y revisión de la literatura / Hemorrhagic Bullous in Henoch - Schönlein Purpura in childrenabout a case and review of the literature

RESUMEN La Púrpura de Henoch - Schönlein (PHS) es una vasculitis leucocitoclástica, autolimitada que en la mayoría de los casos presenta manifestaciones cutáneas de purpura palpable acompañada de dolor articular, abdominal y alteración de la función renal. Reportamos un caso pediátrico de púrpura con ampollas de contenido hemorrágico variedad rara de presentación y difícil diagnóstico.

SUMARY Henoch-Schönlein purpura (HSP) is a self-limited a leukocytoclastic vasculitis, the most case have palpable purpura skin manifestations with arthralgia strong abdominal pain, and renal function compromise. We report a pediatric case of purpura with hemorrhagic blisters rare variety of presentation and difficult diagnosis.

Treatment patterns for metastatic colorectal cancer in Spain.

PURPOSE: The primary aim of this retrospective study was to describe the treatment patterns according to the type of treatment received by patients with metastatic colorectal cancer (mCRC) in Spain. METHODS: This was a retrospective, observational, multicenter study performed by 33 sites throughout Spain that included consecutive patients aged 18 years or older who had received or were receiving treatment for mCRC. RESULTS: At the time of inclusion, of the 873 evaluable patients, 507 (58%) had received two lines, 235 (27%) had received three lines, 106 (12%) had received four lines, and the remaining patients had received up to ten lines. The most frequent chemotherapy schemes were the FOLFOX or CAPOX regimens (66%) for first-line treatment, FOLFOX, CAPOX or FOLFIRI (70%) for second-line treatment, and FOLFOX, FOLFIRI or other fluoropyrimidine-based regimens for third- and fourth-line (over 60%) treatment. Sixty percent of patients received targeted therapy as part of their first-line treatment, and this proportion increased up to approximately 70% of patients as part of the second-line of treatment. A relevant proportion of patients were treated with unknown KRAS, and especially the BRAF, mutation statuses. CONCLUSIONS: This study reveals inconsistencies regarding adherence to the recommendations of the ESMO guidelines for the management of mCRC in Spain. Improved adherence to the standard practice described in such guidelines for the determination of RAS and BRAF mutation statuses and the use of targeted therapies in first-line treatment should be considered to guarantee that patients can benefit from the best therapeutic approaches available.

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

SEOM Clinical Guideline of localized rectal cancer (2016).

Localized rectal adenocarcinoma is a heterogeneous disease and current treatment recommendations are based on a preoperative multidisciplinary evaluation. High-resolution magnetic resonance imaging and endoscopic ultrasound are complementary to do a locoregional accurate staging. Surgery remains the mainstay of treatment and preoperative therapies with chemoradiation (CRT) or short-course radiation (SCRT) must be considered in more locally advanced cases. Novel strategies with induction chemotherapy alone or preceding or after CRT (SCRT) and surgery are in development.

[Satisfaction of professionals taking part in a project of telemonitoring in-home patients with chronic diseases (TELBIL-A project)]. / Satisfacción de los profesionales con la telemonitorización de pacientes crónicos domiciliarios en atención primaria (proyecto TELBIL-A).

OBJECTIVE: To analyze, through an on-line survey, the satisfaction of professionals (nurses/general practitioners) taking part in a project of telemonitoring in-home patients with chronic diseases (heart failure and/or pulmonary disease) with ≥2 hospital admissions in the last year (TELBIL-A project). MATERIAL AND METHODS: An on-line questionnaire designed by the researchers (using «easy survey¼ application) was sent to professionals' email. It consisted of several items to assess satisfaction (Likert scale from 1-strongly disagree, negative appreciation- to 5- strongly agree, positive appreciation-), age, number of years working in Primary Care, and an open question for comments. Data were analyzed using SPSS 18.0. RESULTS: We received responses from 50 out of 55 professionals (90.9%), of whom 94% were female, and 68% aged ≥40 years, with 90% working >5 years in Primary Care. They chose in 86% answer 4 or 5 for the item on overall satisfaction with the project, with the average score being 4.4. The means for the rest of questions were: 3.8 for interference with other professional daily tasks, 4.5 appreciating advantages in the management of patients, 4.2 for the feeling that patients are more involved in their own care, 3.9 for technological aspects, and 4.3 for recommending to a friend/relative. CONCLUSIONS: The study explores one aspect, satisfaction with the project, which is critical because of the association with the correct compliance and developing of the intervention. We found a high satisfaction of professionals involved with the TELBIL-A project.

Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation.

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.

A sporadic case of early-onset sarcoidosis resembling Blau syndrome due to the recurrent R334W missense mutation on the NOD2 gene.

Sarcoidosis is a multisystem granulomatous disorder characterized by the infiltration of noncaseating granulomata in the affected tissues. We report here the clinical case of a Caucasian Spanish patient suffering from sporadic early-onset sarcoidosis (EOS) with simultaneous cutaneous and articular symptoms. NOD2 (nucleotide-binding oligomerization domain; previously known as CARD15, caspase recruitment domain) gene mutational analysis revealed the presence of the recurrent R334W missense mutation. As in previously reported EOS cases, our patient was initially misdiagnosed with dermatitis.

[Treatment of bone metastatic pain with Sm153-EDTMP. Evaluation of the analgesic response and the existence of differences according to the primary tumor and the metastatic pattern]. / Tratamiento del dolor óseo metastásico con Sm153-EDTMP. Valoración de la respuesta analgésica y de la existencia de diferencias según el tipo de tumor y el patrón metastásico.

AIMS: To evaluate the response to Sm153-EDTMP treatment in patients with metastatic bone pain and the existence of differences in the response according to the scintigraphic pattern (99mTc-MDP) and the primary tumor. MATERIAL AND METHODS: We have evaluated the response to Sm153-EDTMP treatment in 32 patients (17 male and 15 female) who received 38 doses (1 mCi/kg). The primary tumor was prostate cancer in 15 patients, breast in 13, lung in 2, intestinal carcinoid in one and unknown in one. Two types of response were considered: a) effective and b) non-effective. Patients were classified into 3 groups according to the metastatic pattern: 1) Superscan (SS), 2) Generalized metastases (GM) and 3) Regional metastases (RM). RESULTS: There was effective response in 24 doses (63.15%) and non-effective in 14 (36.84%). The mean duration of the response was 12.08 weeks. Patients with GM pattern showed 16 effective responses (76.19%) and 5 non-effective (23.8%). In SS pattern there were 6 effective responses (60%) and 4 non-effective (40%) and 2 effective (28.57%) and 5 non-effective (71.53%) in RM pattern. These differences did not reach statistical significance (p > 0.05). We did not find differences in the response between prostate cancer (12 effective and 6 non-effective) and breast cancer (10 effective and 6 non-effective) (p = 0.79968). CONCLUSIONS: Sm153-EDTMP treatment is efficacious in patients with metastatic bone pain with effective response in 63.15% of the treatments. The response percentage was lower in patients with RM pattern but the differences did not reach statistical significance. There were no differences in the response between prostate and breast cancer patients.

[Complex renal cyst. A new case]. / Quiste renal complejo. A propósito de un caso.

Approximately 15% of cases of renal cell carcinoma present cystic configuration on radiologic and pathologic examination. These lesions are often difficult to differentiate from the multiloculated renal cyst or other benign cystic lesions such as hemorrhagic cyst and so on. We report a case of multilocular cyst of the right kidney complicated with clear cell type renal cell carcinoma in which MRI suggested benign cyst. The diagnosis of complicated benign cyst must be proposed very cautiously and the persistence of doubtful images justifies surgical exploration.

[Penile hematoma caused by deep dorsal vein rupture during intercourse]. / Hematoma peneano por rotura de vena dorsal profunda durante el coito.

OBJECTIVE: To describe a case of rupture of the deep dorsal vein of the penis during sexual intercourse. METHODS: A 21-year-old patient consulted at the emergency services for acute penis after vigorous sexual intercourse, with clinical features suggestive of rupture of the corpora cavernosa. RESULTS: Surgery demonstrated complete rupture of the deep dorsal vein of the penis, which was repaired. Examination showed no injury to the corpora cavernosa. CONCLUSIONS: Early surgical management is advocated in acute penis, since it will permit us to make the correct diagnosis and treat the underlying cause to avoid future sequelae. Rupture of the deep dorsal vein of the penis is another condition that should be considered in the differential diagnosis of acute penis. Its clinical features are similar to those of cavernosal rupture. Ultrasound and cavernosography are not diagnostic.

[Inguinal bladder hernias. A report of 2 cases]. / Hernias vesicales inguinales. Aportación de dos casos.

Bladder hernia is a very uncommon but not exceptional condition. It tends to occur in adult patients over 50, and is favoured by a cervical-urethral obstruction. It is often diagnosed during inguinal hernia surgery, although in other cases pre-operative diagnosis can be achieved through radiological studies (filling cystography), in patients with urinary signs and symptoms associated to inguinal hernia. Treatment involves the association of herniography and deobstructive surgery at the cervical-urethroprostatic level. The use of a polypropylene mesh [correction of stent] to reinforce a damaged abdominal wall is evaluated and it presents an improved result over the traditional techniques. The excellence acceptance by the body should also be taken into account, as no rejection or infection problems were reported the present cases.

[Giant calcifications of a double-J ureteral catheter]. / Calcificaciones gigantes de cateter ureteral doble J.

We present a case of recurring gigantic calcifications of both extreme of a double-J ureteral catheter, with long permanency of the same. We expose the technical maneuvers that were specified for the managing of so important complication. We emphasize the renal functional conservation found in spite of the magnitude of the calcifications. We check the national literature in this regard of this complication and we expose the etiological mechanisms, prophylactic recommendations and therapeutic managing of this complication to the extended use of ureteral catheters.

[Nutritional status assessment in a group of cystic fibrosis patients]. / Valoración del estado nutricional en un grupo de pacientes con fibrosis quística.

The objectives of this study were to evaluate the nutritional status and the efficiency of high density oral supplements in patients with cystic fibrosis. Twenty patients with cystic fibrosis (10 boys and 10 girls) with a mean age of 11.63 years (SD:6.3) were studied. Sixty percent of these patients were receiving high density oral supplements. A clinical and nutritional evaluation, including a three day evaluation of food intake, were performed. Patients were separated into two groups according to oral supplement intake and the presence or not of pulmonary colonization. We found the patients to have a mild to moderate clinical status. Anthropometric values were lower than ideal. Intake of calories, macronutrients and micronutrients were similar (except for folic acid) in both groups of patients and were close or above the established dietetic recommendations for cystic fibrosis. Patients with pulmonary colonization scored lower in the Shwachman and Brasfield tests, had lower weights, subscapular skinfolds and nutritional indices, and higher plasma immunoglobulin A concentrations. We conclude that a free hypercaloric diet allows cystic fibrosis patients to maintain an adequate nutritional status. Oral supplements should be prescribed on an individual basis according to the results of periodic food records and clinical and anthropometric status evaluation.

[Hepatic actinomycosis: radiologic findings and percutaneous drainage]. / Actinomycosis hepática: hallazgos radiológicos y drenaje percutáneo.

We report a case of hepatic actinomycosis in a woman with previous duodenal ulcer. The findings of ultrasound, computed tomography and abscess imaging are presented. The diagnosis was made by thin needle aspiration biopsy under computed tomography guidance. The treatment consisted in percutaneous drainage and intravenous antibiotic therapy.

[Ulcerative colitis and Crohn disease: echographic diagnosis with water enema]. / Colitis ulcerosa y enfermedad de Crohn: diagnóstico mediante ecografía con enema de agua.

Water enema procures a suitable acoustic window for ultrasonographic study of the colon, allowing a detail vision of the lumen and colon wall, as well as large bowel intestine surround connective tissue. In this work we present echographic findings in two patients with active and severe intestinal inflammatory disease. Ultrasound scanning results were confirmed by colonoscoy and histological test. Distinction between ulcerative colitis and colonic Crohn's disease is possible because of different echographic pattern. This findings show than colonic echography may be a very useful diagnostic technique in detection and differentation of inflammatory large bowel diseases.

Variación mensual de las concentraciones de ácido ascórbico en leucocitos durante el embarazo / Monthly variation in the concentration of ascorbic and in leucocytes during pregnancy

El presente trabajo se reallizó para determinar las variaciones de la concentración del ácido ascórbico en leucocitos durante el embarazo. Se realizó un estudio prospectivo en que se evaluó mensualmente a 30 mujeres embarazadas sanas asistentes a al consulta externa del INPer, que no consumieron suplementos vitamínicos durante el periodo comprendido entre las 20 y 36 semanas de la gestación, con la finalidad de conocer las variaciones de la consentración de ácido ascórbico en leucocitos. Se determinó la ingestión de alimentos ricos en este nutrimiento mediante evaluaciones dietéticas. La menor concentración correspondió a la semana 28 y la diferencia con las concentraciones observadas en las semanas 32 y 36 fueron significativas con valores de p = 0.04 y 0.01 respectivamente. Las concentraciones tendieron a aumentar hacia el final de la gestación. Se observó un consumo irregular de frutas y verduras. Los resultados indican la necesidad de brindar orientación alimentaria oportuna a las gestantes a fin de que su estado de nutrición en vitamina C no se vea alterado.