Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial.

BACKGROUND: The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. PATIENTS AND METHODS: Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. RESULTS: CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. CONCLUSION: We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00433563.

Analysis of the local and systemic inflammatory response in hospitalized infants with respiratory syncitial virus bronchiolitis.

BACKGROUND: Respiratory syncytial virus acute bronchiolitis (RSV-AB) is a major cause of hospital admission among our infants. The immune and inflammatory mechanisms involved in the RSV-AB and factors influencing severity have not been clearly established, although an imbalanced Th1 and Th2 response seems to be crucial. OBJECTIVES: To assess the local and systemic inflammatory response in RSV-AB. To find a possible marker of clinical severity and/or oxygen requirements. PATIENTS AND METHODS: Levels of nine cytokines were measured in nasopharyngeal aspirate (NPA) and peripheral blood (PB) of 45 infants with RSV-AB and 27 peer controls, including IFNγ, TNFα, VEGF, interleukins 4, 6 and 10, and chemokines (IL-8 and macrophage inflammatory proteins 1-α and 1-ß). RESULTS: The levels of the analyzed cytokines and chemokines were significantly higher in the NPA of RSV-AB group, with a decrease in IL-4/IFNγ ratio. IL-6 and MIP-1ß levels in NPA were directly correlated to oxygen therapy. PB showed an increase in IL-8 and a decrease in MIP-1α and MIP-1ß in the RSV-AB group (only MIP-1ß associated to the need for oxygen therapy). No correlation was found between cytokines and chemokines levels in NPA and PB. CONCLUSIONS: This study shows that RSV triggers an inflammatory response fundamentally at the respiratory level, with scant systemic repercussion. This local response is characterized by an increase in Th1 and Th2 cytokines, although with a relative predominance of Th1. The determination upon patient admission of IL-6 and MIP-1ß levels in NPA, and of MIP-1ß in PB could help predict severe forms and the need for oxygenotherapy.

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer.

INTRODUCTION: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. METHODS: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. RESULTS: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. CONCLUSIONS: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

[Retractile mesenteritis. Report of 3 cases]. / Mesenteritis retráctil. A propósito de tres casos.

Mesenteric panniculitis is an infrequent pathology; the diagnosis is made by the pathologist and it is characterized by inflammation, fibrosis and retraction of the mesenteric fat. We report three new cases of retractile mesenteritis or mesenteric panniculitis, two cases presented with intestinal obstruction and the other had an abdominal tumour. In all cases the pathological diagnosis was retractile mesenteritis.

Analysis of the quality of life in patients after pelvic pouch operation.

AIM: The aim of this study is to analyse the quality of life in patients with ileoanal pouch respect to a diverting loop ileostomy. MATERIALS AND METHODS: Fifteen patients (8 women and 7 men) with mean average age of 33 years who underwent mucosal proctectomy, colectomy, ileal-pouch-anal anastomosis and temporary loop ileostomy. Quality of life was studied when the patients had an ileostomy and follow-up evaluation, one year after restitution of anal defecation. The surgeons' evaluation was done using a health scale. RESULTS: Among the patients with temporary ileostomy, 40% reported bad tolerance, 53% leakage of stoma bag and 26% skin problems. The mean stool frequency among ileoanal anastomosis was four per day, 87% reported total continence, 13% had major complications and they needed pouch removal. 67% patients with ileostomy reported dietary restrictions against 13% patients functioning with pelvic pouch (p = 0.004). 13% patients with ileostomy had restricted sport activities. Social activities were restricted for 40% and 26% had limitations in their ability to work. Sex life was affected in 20% of patients with ileostomy and 13% of patients with ileal pouch anastomosis. 73% of patients presented an excellent level of satisfaction with pouch. CONCLUSION: Quality of life after ileoanal pouch anastomosis is higher than ileostomy.

Thoracic esophageal perforations: surgical management with mechanical bipolar exclusion.

We report 12 cases of thoracic esophageal perforation diagnosed during the last seven years. Management was nonsurgical in 2 patients and the rest were treated surgically. Primary repair and drainage were performed in 2 patients, and 7 patients underwent suture of the perforation and bipolar exclusion using nonresorbable staples. The remaining patient was treated with proximal unipolar exclusion. The approach was always through a posterolateral thoracotomy. The result was optimal in 8 patients; the most important postsurgical complications were 2 esophageal fistulas that required surgery, and only one of the patients died of fulminating sepsis. Bipolar exclusion is a procedure that needs only one operation and provides excellent morbidity-mortality rates compared with other exclusion techniques with later reconstruction. We consider suturing with nonresorbable staples to be a simple and safe procedure, with spontaneous recanalization of the esophageal lumen in 2 weeks.

[Cerebellar tuberculoma. Clinical and radiological course]. / Tuberculoma cerebeloso. Evolución clínica y radiológica.

A six-year-old child with intracranial hypertension is described. Cranial computed tomography showed an expansive mass surrounded by a contrast enhancement ring in the right cerebellar hemisphere. Chest roentgenograms showed signs of pulmonary tuberculosis. Intracranial lesion was diagnosed as a tuberculoma and treated with tuberculostatic agents. Serial computed tomography scans showed a reduction of size of tuberculoma and appearance of a residual calcified image.

[Prognostic value of the electroencephalogram and cerebral CT scan in neonatal hypoxic-ischemic encephalopathy]. / Valor pronóstico del electroencefalograma y la TAC cerebral en la encefalopatía hipóxico-isquémica neonatal.

This study has evaluated the usefulness of EEG and TC-scan to predict neurological and developmental outcome in 31 full-term newborns sustaining perinatal asphyxia. Both methods have appeared to be valuable early predictors of neurodevelopmental sequelae.

[Neonatal varicella: indications for the use of varicella-zoster specific immunoglobulin]. / Varicela neonatal: indicaciones para el uso de inmunoglobulina específica varicela-zoster.

Case reports from January-1986 through December-1988 of neonates born to women who develop varicella and neonates with household postnatal exposure are presented. Mother developed varicella in three cases (15 days before delivery, at delivery, 10 days after delivery), the last case was infected by direct exposure from his brothers. Only neonates with household contacts developed varicella. In every case varicella-zoster immunoglobulin a doses of 0.2 mg/kg/day from the three days was administered. Adding aciclovir intravenous a daily doses of 15 mg/kg/8h for seven days in neonates who developed varicella. Are propose considered a high risk group the neonates with postnatal exposure.

[Neonatal systemic candidiasis in the nineties]. / Candidiasis sistémica neonatal en los noventa.

OBJECTIVE: Retrospective study of newborns with systemic candidiasis during the period January 1990-March 1994 admitted to the Neonatology Unit at tertiary hospital. We analyzed the predisposing factors, clinical course, diagnosis, treatment and outcome. MATERIAL AND METHODS: Fourteen newborns were diagnosed of systemic candidiasis on the basis of positive blood culture associated with compatible clinical condition and/or involvement of any organ. All the patients had as predisposing factors the use of broad spectrum antibiotics, prolonged intravascular catheterization and parenteral nutrition, and 12 newborn infants had mechanical ventilation. RESULTS: Twelve newborns were preterm infants, 10 of them weighing less than 1.500 g and 2 were term infants who required abdominal surgery due to ileal atresia and omphalocele. The mean age at onset of systemic candidiasis was 40 days. Clinical presentation was indistinguishable from that of bacterial sepsis. C. albicans was isolated from the blood of 12 infants, from the urine of 6 infants and from the cerebrospinal fluid of two infants. Six infants were treated with intravenous amphotericin, one infant was treated with intravenous amphotericin B associated with oral flucytosine and two infants were treated with liposomal amphotericin. Six of the infants died one of them while still receiving antifungal therapy. CONCLUSION: Systemic candidiasis should be considered in any septic infant mainly preterm infant less than 1.500 g with predisposing risk factors. We truly believe that a high index of suspicion, rapid diagnosis, early initiation of systemic fungal therapy, and removal of indwelling catheters may markedly reduce the mortality and improve the prognosis associated with neonatal systemic candidiasis.

[Retinopathy of prematurity. The results after a 1-year follow-up]. / Retinopatía del prematuro. Resultados tras un año de seguimiento.

OBJECTIVE: To analyze prospectively the incidence and outcome of retinopathy of prematurity (ROP) in preterm infants admitted to a neonatal intensive care unit. PATIENTS AND METHODS: A high risk group of infants with birth weights less than 1,500 g, and/or a gestational age less than 30 weeks, was studied. Ophthalmoscopic examination was performed at six weeks of age. Frequent ophthalmoscopic examinations were then performed depending on the gravity of the ROP. RESULTS: ROP was found in 14 of the 20 preterm infants (70%). Two developed stage 3 and none of them stage 4 or 5. Cryotherapy for ROP was not used. None of the infants progressed to advanced stages of ROP and complete resolution was the rule. CONCLUSION: Despite the low incidence of advanced stages of ROP in our study, we suggest that all preterm infants less than 1,500 g and/or 30 weeks of gestational age, should be screened for ROP and repeated ophthalmoscopic examination performed in order to evaluate the progression and treatment of ROP.

[Eosinophilic fasciitis]. / Fascitis eosinofílica.

A three year old is described with clinical findings of oedema and induration of skin in the right leg, eosinophilia, hypergammaglobulinemia, and pathological lesions of eosinophilic fasciitis in the deep muscle's fascia. 94 cases published in the literature are reviewed and clinico-biochemical pathological findings and outcome of this syndrome discussed. In general this entity has a good prognosis with steroid therapy. Authors emphasise the rarity of the disease in children, and the early onset in their patient.

[Prospective study of Candida-related sepsis in the neonate]. / Estudio prospectivo de sepsis por Candida en el recién nacido.

OBJECTIVE: Our objective was to carry-out a prospective study of newborns with systemic candidiasis admitted to our Neonatology Unit in a teritiary hospital during the period of March 1994-September 1997. PATIENTS AND METHODS: To be included in the study the patient had to have Candida sp recovered from a normally sterile body fluid and clinical signs of sepsis. We analyzed perinatal and neonatal antecedents, risk factors, clinical course, diagnosis, treatment and outcome. RESULTS: The incidence of systemic candidiasis was 0.62% (14 newborns). Two were term infants and 12 preterm infants, 9 of which weighed less than 1500 g. All of the patients had as predisposing factors the use of broad spectrum antibiotics, prolonged intravascular catheterization and parenteral nutrition, while 64% had mechanical ventilation. The mean age at onset of sepsis was 22 days, with non-specific clinical presentation. Four infants were treated with intravenous amphotericin B and 9 with liposomal amphotericin B in association with fluconazole in one patient and with flucytosine and fluconazole in another. No adverse effects were observed. Mortality was 21%. C. parapsilosis was isolated in 7 cases and C. albicans in another 7 patients, with an important increase in C. parapsilosis in the last few years. CONCLUSIONS: Clinical suspicion of invasive candidiasis requires the removal of indwelling catheters and early initiation of systemic ungal therapy to reduce mortality. The increased incidence of species with more epidemic presentation like C. parapsilosis reinforce the importance of control measures such as handwashing for all personnel and aseptic management of intravascular catheters and solutions in order to prevent infections.