[A case of Sweet syndrome in a patient receiving erlotinib for lung adenocarcinoma]. / Syndrome de Sweet chez une patiente traitée par erlotinib pour un adénocarcinome bronchique.

INTRODUCTION: Sweet syndrome is a neutrophilic dermatosis and is often idiopathic, although its onset may be drug-induced or paraneoplastic. The purpose of this case report is to describe the very first occurrence of Sweet syndrome following erlotinib intake in a patient diagnosed with lung adenocarcinoma. PATIENTS AND METHODS: We observed Sweet syndrome, as assessed by clinical, laboratory and histological examination, in a middle-aged female patient presenting lung adenocarcinoma diagnosed three years prior to her cutaneous symptoms. DISCUSSION: Given the extremely long time between the diagnosis of lung cancer and the onset of Sweet syndrome, as well as the occurrence of skin lesions during administration of the medication and their subsidence after drug withdrawal, we suggest a possible link between this particular EGFR tyrosine kinase inhibitor and the patient's neutrophilic dermatological signs. To our knowledge this association has not previously been described in the medical literature.

Preoperative frailty assessment: a review.

Elderly surgical population is growing faster than the rate of population ageing. The risk of postoperative complication is higher in this population, the type of complication and the risk indicators are different from younger patients. There is also a huge heterogeneity in the elderly population. The concept of frailty-emerges to explain these specific aspects and to risk stratify older patients. The present work intends to help the anaesthesiologist to take into account the concept of frailty at the preoperative visit. We reviewed, in the light of surgical context, the physiopathology of ageing, the definitions of frailty concept,the current existing strategies for peri-operational optimisation and the different frailty assessment tools. Our conclusions are that preoperative frailty assessment is essential in modern perioperative medicine practice and that the Edmonton Frail Scale stands out from other tools even though it cannot yet be considered as a gold standard.

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

BACKGROUND: In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. PATIENTS AND METHODS: Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). RESULTS: Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). CONCLUSION: Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to elucidate DNA repair mechanisms will help define novel therapeutic approaches. TRIAL REGISTRATION: NCT00617656/GECP-BREC and ChiCTR-TRC-12001860/BREC-CHINA.

[Pulmonary nodules and arachnophobia]. / Nodules pulmonaires et arachnophobie.

Pulmonary nodules are a common reason for consultation and their investigation must always exclude a possible neoplastic cause. This means that, in addition to a thorough history, investigations may be necessary which are sometimes invasive and therefore potentially a cause of iatrogenic harm. The toxic aetiologies for pulmonary nodules are rare. We report a case of a patient with pulmonary nodules occurring predominantly in the right lung, about 1cm in diameter, non-cavitating without calcification, and sometimes surrounded by a peripheral halo. The nodules were a chance finding during preoperative evaluation. After a comprehensive review, a reaction to an inhaled irritant was the preferred hypothesis, specifically overuse of a compound insecticide containing, in addition to the propellant gas and solvent type hydrocarbon - a mixture of piperonyl butoxide, of esbiothrine and permethrin. Removal of this led to the complete disappearance of nodules. Pathological examination identified bronchiolitis obliterans with organising pneumonia accompanied by non-necrotizing granulomas and lipid vacuoles.

Valproate-doxorubicin: promising therapy for progressing mesothelioma. A phase II study.

No treatment is recommended for patients with malignant mesothelioma (MM) failing after first-line cisplatin-based chemotherapy. In vitro data suggested that valproic acid, a histone deacetylase inhibitor (HDACi), had a proapoptotic effect and synergised with doxorubicin to induce apoptosis in MM cells. Our primary end-point was to determine response rate of combined valproic acid and doxorubicin in patients with unresectable MM failing after platinum-based chemotherapy. Treatment consisted of doxorubicin (60 mg·m⁻²) plus valproic acid. An interim analysis for response rate was planned after the first 16 registered patients. All the cases were centrally reviewed. From July 2006 to March 2009, 45 eligible patients with pleural MM were registered. The majority of the patients were male (73%), had a performance status (PS) ≥ 80 (76%) and an epithelioid subtype (80%). There were seven partial responses (response rate 16%; 95% CI 3-25%), all in patients with PS 80-100. The best disease control rate was 36% (95% CI 22-51%). Two toxic deaths were observed (febrile neutropenia and cerebral thrombotic event), both in patients with poor PS (60-70). Valproic acid, an HDACi, plus doxorubicin appeared an effective chemotherapy regimen in good PS (80-100) patients with refractory or recurrent MM, for which no standard therapy was available.

[Obliterative bronchiolitis with organising pneumonia following FOLFOX 4 chemotherapy]. / Bronchiolite oblitérante avec pneumonie organisée après chimiothérapie de type FOLFOX 4.

INTRODUCTION: FOLFOX 4 chemotherapy (5-fluorouracil, leucovorin and oxaliplatin) is the standard adjuvant treatment for stage III colon cancer. The principal secondary effects described are haematological, gastro-intestinal or neurological. A single case of obliterative bronchiolitis with organising pneumonia has been described recently. CASE REPORT: We report the case of a female patient aged 74 years who, after 12 courses of FOLFOX 4 chemotherapy, developed acute onset of severe shortness of breath and a dry cough but remained afebrile. A thoracic CT-scan showed symmetrical bilateral interstitial infiltration that was reticular in appearance, and predominantly basal and peripheral in distribution. Broncho-alveolar lavage revealed an alveolitis with 9% eosinophils and 4% neutrophils. Transbronchial biopsies showed the appearances of obliterative bronchiolitis with organising pneumonia. Systemic corticosteroid treatment led to a remarkable clinical and functional improvement. CONCLUSION: To our knowledge, this is the second case of obliterative bronchiolitis with organising pneumonia that has been described following adjuvant treatment based on FOLFOX 4.

Quality of life and comorbidity score as prognostic determinants in non-small-cell lung cancer patients.

BACKGROUND: Both quality of life (QoL) and comorbidity influence therapy and prognosis of non-small-cell lung cancer (NSCLC). We previously developed a lung cancer disease-specific simplified comorbidity score (SCS) and demonstrated the prognostic impact of this disease-specific instrument. This study aimed at validating the SCS in a prospective bicentric NSCLC population by measuring its relative prognostic determinant impact taking into account well-established variables such as QoL, performance status (PS), Charlson comorbidity index (CCI) and disease stage. PATIENTS AND METHODS: Prognostic values of different pretherapeutic features were tested in univariate and multivariate analyses in a population of 301 NSCLC. RESULTS: Median survival was 17 months. One-third of patients reporting difficulties in their normal daily activities and an overall poor QoL. The following pretreament variables were independent determinants of a shorter overall survival: advanced disease, SCS, Lung Cancer Symptoms Scale global symptoms score, anaemia, hyponatremia, serum alkaline phosphatases level, serum CYFRA 21-1 and serum neuron-specific enolase. CONCLUSION: In this extended validation population, the SCS is more informative than the CCI in predicting NSCLC patient outcome as the former is also more disease specific. Combination of both SCS comorbidity score and LSCC QoL yields a more accurate information that conventional analysis of PS.

Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD.

Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown. In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function. Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression. The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.

Echocardiography for management of low cardiac output state after axillary block in a dehydrated patient with aortic stenosis: case report.

We report an episode of transient low cardiac output in a dehydrated elderly woman having an undetected clinically significant aortic stenosis, after an axillary blockade. Cardiac echography was determinant for management of this patient. Events were considered to be from hemodynamic origin.

A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson's index.

Treatment of non-small-cell lung cancer (NSCLC) might take into account comorbidities as an important variable. The aim of this study was to generate a new simplified comorbidity score (SCS) and to determine whether or not it improves the possibility of predicting prognosis of NSCLC patients. A two-step methodology was used. Step 1: An SCS was developed and its prognostic value was compared with classical prognostic determinants in the outcome of 735 previously untreated NSCLC patients. Step 2: the SCS reliability as a prognostic determinant was tested in a different population of 136 prospectively accrued NSCLC patients with a formal comparison between SCS and the classical Charlson comorbidity index (CCI). Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The SCS summarised the following variables: tobacco consumption, diabetes mellitus and renal insufficiency (respective weightings 7, 5 and 4), respiratory, neoplastic and cardiovascular comorbidities and alcoholism (weighting=1 for each item). In step 1, aside from classical variables such as age, stage of the disease and performance status, SCS was a statistically significant prognostic variable in univariate analyses. In the Cox model weight loss, stage grouping, performance status and SCS were independent determinants of a poor outcome. There was a trend towards statistical significance for age (P=0.08) and leucocytes count (P=0.06). In Step 2, both SCS and well-known prognostic variables were found as significant determinants in univariate analyses. There was a trend towards a negative prognostic effect for CCI. In multivariate analysis, stage grouping, performance status, histology, leucocytes, lymphocytes, lactate dehydrogenase, CYFRA 21-1 and SCS were independent determinants of a poor prognosis. CCI was removed from the Cox model. In conclusion, the SCS, constructed as an independent prognostic factor in a large NSCLC patient population, is validated in another prospective population and appears more informative than the CCI in predicting NSCLC patient outcome.

Epidemiology of the adverse hemodynamic events occurring during "clonidine anesthesia": a prospective open trial of intraoperative intravenous clonidine.

STUDY OBJECTIVE: Determine the hemodynamic consequences of intraoperative clonidine during major abdominal surgery. DESIGN: Prospective open trial. SETTING: Teaching hospital. PATIENTS: 402 consecutive patients scheduled for major abdominal surgery. INTERVENTIONS: 350 consecutive patients received intravenous (IV) clonidine (loading dose of 4 micrograms/kg in 20 minutes at anesthesia induction, followed by a continuous infusion of 2 micrograms/kg/h until the end of surgery). Fifty-two additional patients served as controls. Anesthetic technique consisted of balanced anesthesia (isoflurane, fentanyl, atracurium). ECG, invasive arterial blood pressure (BP), expiratory PCO2 and pulse oximetry were continuously recorded. Hemodynamic events (HEs) were defined as moderate for a 20% reduction of the baseline systolic blood pressure (SBP) or a heart rate (HR) decreasing between 50 beats per minute (bpm) and 40 bpm. A 30% reduction of the baseline SBP or a HR below 40 bpm was considered an important HE. The rate and duration of these events were recorded from induction to recovery. HEs requiring a specific treatment were noted. Central venous pressure, volume of fluid infused, and urinary output were also recorded. MEASUREMENTS AND MAIN RESULTS: 21% of control patients and 31% of clonidine patients had no adverse HEs. A moderate reduction of the baseline BP was the most common episode in both groups. The incidence of the HEs (moderate and important) was similar in both groups but the duration HEs was significantly longer in the clonidine patients (p < 0.05). 40% of the control patients and 13% of the clonidine patients required specific management for their HEs (p < 0.05), the most common of which was hypotension without bradycardia. Neither coexisting pathology nor preoperative medications influenced the incidence of HEs. CONCLUSION: IV clonidine can be used routinely during anesthesia for major abdominal surgery.