[Tracheal lipoma: An exceptional cause of tracheal tumors]. / Lipome trachéal : une cause exceptionnelle de tumeur trachéale.

INTRODUCTION: Tracheal tumors are rare, they are most often malignant and can manifest themselves by a non-specific respiratory symptomatology with progressively increasing dyspnea orienting in the first place towards a COPD or even an asthma. Among them, tracheal lipoma is exceptional. Its management is based on removal by rigid bronchoscopy. OBSERVATION: We report the case of a 73-year-old male patient who presented with non-specific dyspnea that progressively worsened over several months. The EFR showed a flattening of the flow-volume curves, the CT scan showed an anterolateral oval tracheal tumor with fatty density, the bronchial endoscopy showed a tumor lesion with stenosis of about 90% of the airway. Management consisted of a rigid bronchoscopy to delete obtruction with biopsies. Anatomopathology concluded to a tracheal lipoma. CONCLUSION: Progressively worsening dyspnea, especially if there are signs of inspiratory dyspnea, required a systematic bronchial endoscopy to avoid the possibility of a tracheal tumor.

[Rapid outpatient diagnostic pathways for lung cancer: Evaluation after one year]. / Parcours de diagnostic rapide du cancer du poumon : évaluation à un an.

INTRODUCTION: The introduction of coordinated care pathways for lung cancer diagnosis and treatment is a complex process. The purpose of the French Cancer Plan 2014-2019 was to improve referral to treatment waiting times in people with suspected malignancy. The aim of this study was to assess a rapid outpatient diagnostic program for lung cancer established in 2016. METHOD: This retrospective study was carried out in the Pulmonology Department at Tenon Hospital, Paris, France between May 2016 and May 2017. RESULTS: During this period, 118 patients (60%) of patients in the pathway were diagnosed with lung cancer. The median waiting time to first consultation (D1) was 4 (2-7) days. The median waiting time between diagnosis and treatment decision (D4) was 4 (0-8) days. The median waiting time to the first treatment (D5) was 10 (4-15) days for chemotherapy and 27 (16-34) days for surgery. The median waiting time between the first abnormal chest X-ray and the first treatment (D6) was 49 days (34-70). CONCLUSION: Referral to treatment waiting times was consistent with international recommendations. Coordinating nurses improved care pathways in lung cancer patients.

Correlation between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in Obstructive Sleep Apnea Patients Treated with Positive Airway Pressure.

BACKGROUND: The Epworth sleepiness scale (ESS) is often used to evaluate the impact of treatment in patients with obstructive sleep apnea hypopnea syndrome (OSA). We aimed to evaluate the correlation between ESS and the Maintenance of Wakefulness Test (MWT) in a population of OSA patients treated with positive airway pressure (PAP). METHODS: We retrospectively included all patients during a 2-year period who were diagnosed with OSA in our sleep clinic and required PAP therapy. ESS was evaluated at baseline and after PAP therapy for all patients, and all had a concomitant MWT. Correlation between final ESS, change in ESS, and MWT were evaluated using Spearman's correlation. Given that MWT is considered as the gold standard, the diagnostic performance of ESS was evaluated against MWT. RESULTS: Hundred thirty-four OSA patients were included. At the time of MWT, 89.6% of the patients were compliant (PAP use ≥4hours/night), and only 9 (6.7%) had persistent sleepiness despite PAP treatment (mean sleep latency at MWT<19.4min). Moderate correlation was observed between final ESS and MWT (Spearman's correlation coefficient=-0.42), but no correlation was found between change in ESS and MWT. Diagnostic performance was as follows for final ESS: sensitivity=55.6%, specificity=84.8%, PPV=20.8%, and NPV=96.4%. CONCLUSIONS: ESS was moderately correlated with MWT in a population of OSA patients compliant with PAP therapy. In this population, ESS showed poor diagnostic performance in identifying patients with persistent excessive daytime sleepiness. CLINICALTRIALS. GOV IDENTIFIER: NCT03629834.

Susceptibility of pike Esox lucius to VHSV and IHNV and potential transmission to rainbow trout Oncorhynchus mykiss.

Determining the origin of recurrent outbreaks of fish diseases occurring on fish farms is essential for disease prevention and control measures. In this study, we investigated the potential reservoir role of wild fish species living near salmonid farms which were regularly found to be positive for viral hemorrhagic septicemia virus (VHSV). In addition to VHSV, infectious hematopoietic necrosis virus (IHNV) was also isolated from several pike Esox lucius samples collected from a pond near the salmonid farms of interest. All isolates of VHSV and IHNV analyzed had 100% identical partial glycoprotein gene sequences. VHSV pike strain OO128-25 belonged to the Ia genotype and shared 99.1 to 99.5% nucleotide identity with strains recently isolated from the farms. IHNV pike strain OO121-8, European genotype, appeared to be different from strains from France characterized since the first isolation in 1987. Isolates representative of both viral species were highly virulent in rainbow trout Oncorhynchus mykiss. OO128-25 induced 65% mortality in pike fingerlings, whereas only weak mortality was observed with OO121-8, despite characteristic symptoms in infected fish. High levels of specific antibodies to VHSV and IHNV were detected in adult pike in the absence of clinical signs. Infection of rainbow trout in contact with experimentally VHSV- or IHNV-infected pike fingerlings indicates possible horizontal transmission. These results suggest that pike could act as a reservoir for VHSV and IHNV in the wild, providing additional evidence to explain viral persistence and resurgence in certain areas.

First detection of Cyprinid Herpesvirus 2 (CyHV-2) in goldfish (Carassius auratus) in France.

Massive mortalities of Carassius auratus (L.) occurred in a farm in France during summer 2014. Fish presented anorexia, loss of scales and large amounts of mucus on the gills. Necrosis of the distal tip of the filament and the lamellae, combined with fusion of the lamellae, was observed, as well as necrosis in the hematopoietic organs and in the digestive tract. The histological examination led to hypothesize the implication of a virus in the mortality. The presence of cyprinid herpesvirus 2 (CyHV-2) in dead fish was demonstrated by amplification and sequencing of portions of the DNA polymerase and helicase genes, both sequences exhibiting 100% identity with CyHV-2 from Japan. In an attempt to find genetic markers of variation, two regions containing tandem repeats in the Japanese genome were amplified from a virus-positive sample from the present outbreak. A first region (mB) was fully identical to the Japanese isolate. However, the second region (mA) exhibited a range of deletions and substitutions compared to CyHV-2 from Japan. This is the first report of CyHV-2 in France in association with mortality of goldfish and the first identification of a molecular marker for its tracing.

[Adjuvant chemotherapy of non-small cell lung cancer: Tolerance of combined cisplatin-pemetrexed therapy]. / Traitement adjuvant des cancers bronchiques non à petite cellules : tolérance de l'association platine-pemetrexed.

RATIONALE: Adjuvant chemotherapy is standard for non-small cell lung cancer (NSCLC) after surgical resection. In this context, the tolerance of the treatment is an essential criterion in the choice of chemotherapy. This exploratory study evaluated, in the situation of adjuvant chemotherapy, the tolerance of combined cisplatin-pemetrexed. The study analyzed a cohort of non-squamous NSCLC patients treated in an adjuvant setting by combined cisplatin (75 mg/m(2)) and pemetrexed (500 mg/m(2)), under vitamin B12 and folic acid cover, 4 cycles at 21-day intervals. RESULTS: The analysis included 23 patients (age: 58.7 ± 5 years, men: 56%, average creatinin clearance (Clea): 94 ± 22 mL/min, average haemoglobin: 13.8 ± 1.6g/dL). Over 92 planned courses, 7.6% are postponed (neutropenia), 4.3% were not given (asthenia). We noted 7 episodes of vomiting (4 grade 3), with two hospitalizations in the same patient; 5 episodes of anaemia grade 1-2 not requiring EPO prescription or transfusion and no febrile neutropenia. At the end of the treatment, three patients had a Clea<50 mL/mn and 5 a haemoglobin between 9 and 11 g/dL. CONCLUSION: Combined cisplatin-pemetrexed in an adjuvant situation has a satisfactory tolerance.

Epidural injection of hydroxyethyl starch in the management of postdural puncture headache.

Epidural blood patch is the standard treatment for postdural puncture headache when symptomatic therapy is ineffective. We report the cases of two patients who received an epidural injection of hydroxyethyl starch when an epidural blood patch was contraindicated; one due to Streptococcus agalactiae bacteraemia and one due to acute leukaemia. Relief of headache was achieved in both patients with no adverse effects. The use of an epidural hydroxyethyl starch injection may be a suitable alternative for treatment of postdural puncture headache if epidural blood patch is contraindicated.

Economic implications of using pegfilgrastim rather than conventional G-CSF to prevent neutropenia during small-cell lung cancer chemotherapy.

BACKGROUND: For the prevention of chemotherapy-induced febrile aplasia, a single injection of pegfilgrastim per cycle has the same efficacy as six to ten injections of conventional granulocyte colony-stimulating factor (G-CSF). However, there are few data on the economic impact of pegfilgrastim use, especially in the context of small-cell lung cancer. METHODS: This retrospective study involved 31 patients and 129 treatment cycles (32 with pegfilgrastim and 97 with granulocyte colony-stimulating factor (G-CSF)). We estimated the direct costs for preventing and managing febrile aplasia from the payer's perspective and also conducted a willingness-to-pay study with 100 healthy subjects, in order to estimate how highly a single-jab strategy was valued relative to multiple injections. RESULTS: The costs per cycle were respectively 1743 euros+/- 837 euros and 1466 euros +/- 836 euros for the pegfilgrastim and G-CSF strategies (p < 0.001). The excess cost of the pegfilgrastim strategy was partly compensated for by the perceived value of the single-jab strategy: 88% of interviewees would prefer the pegfilgrastim strategy; 16% would be willing to pay all the excess cost (277 euros) and 67% would be willing to pay half the excess cost. CONCLUSION: In this willingness-to-pay survey, the excess cost associated with pegfilgrastim relative to other G-CSF-based prophylactic strategies is partly offset by the perceived convenience of a single injection.

[A prospective study of quality of life and treatment of chemotherapy-induced anaemia in lung cancer]. / Qualité de vie et traitement de l'anémie chimio-induite dans le cancer bronchopulmonaire: étude prospective.

INTRODUCTION: The impact of chemotherapy-induced anemia on the quality of life (QOL) of patients with lung cancer has been little studied. OBJECTIVE: We evaluated the feasibility of measuring QOL among patients receiving chemotherapy for lung cancer, and the possible correlation of QOL with the haemoglobin level. METHODS: This was a prospective study of 53 patients starting chemotherapy (total 155 cycles); QOL was measured with the specific Fact-An scale. RESULTS: The mean haemoglobin level before treatment was 13.1+/-2.3 g/dl. During chemotherapy 45.3% of patients received erythrocytic growth factors and 15.1% were transfused; 26.4% of patients refused to answer or could not answer the QOL questionnaire. There was a strong correlation between the Hb level and overall QOL (r=0.343, p=0.0004), as well as the physical and functional subscales (but not the cognitive and social subscales). CONCLUSIONS: Although QOL could not be measured in one-quarter of cases, it was clearly affected by anaemia, which supports a strategy of early diagnosis and management of anaemia due to chemotherapy for lung cancer.

Ultrastructural apoptotic lesions induced in bone marrow after neptunium-237 contamination.

This study describes the ultrastructure of lesions induced by neptunium-237 (237Np), a by-product of uranium in nuclear reactors, in the bone marrow. A group of rats were given a single injection of 237Np-nitrate solution in order to observe the acute toxicity effects of this actinide. Electron microscopy was used to describe the different lesions. Observations included the swelling of the cell membrane, nuclear membrane lyses, abnormal chromatin condensation or nucleus convolution. These ultrastructural alterations of the nucleus and the cellular membrane appeared shortly after treatment. This study demonstrates the toxic effects of neptunium and its implication in the induction of apoptosis in bone marrow.

[Chemoradiotherapy-chemotherapy for grade III inoperable non-small-cell lung cancer]. / Chimioradio-chimiothérapie des cancers broncho-pulmonaires non à petites cellules inopérables stade III.

PURPOSE: The purpose of this work was to assess results obtained with the MIP (mitomycin 6 mg/m(2) day 1, ifosfamide 1500 mg/m(2) days 1,2, 3, cisplatin 30 mg/m(2) days 1,2, 3) chemotherapy protocol combined with cisplatin-sensitized chest radiotherapy as developed in the French multicentric trial on perioperative chemotherapy. PATIENTS AND METHODS: Thirty-five patients with grade III non-small-cell lung cancer (NSCLC) were given two or three starter MIP cycles every 4 weeks then underwent radiation therapy for six weeks for a total dose of 60 Gy with injection of 8 mg/m(2) cisplatin every day for the first two weeks and the last two weeks of treatment. In case of objective response (OR) to MIP before radiotherapy, the MIP protocol was repeated for one to four supplementary cycles according to tolerance. RESULTS: The rate of OR after MIP was 51% and after chemoradiotherapy it was 69%. Toxic effects were limited to one death due to aplasia and 18 cases of grade 3-4 toxicity, mainly due to hematology disorders. Moderate esophagitis was observed in ten cases. Median survival was 13.5 months. Survival rates were 57% and 29% at one and two years. DISCUSSION: This novel scheme, which can be improved, has demonstrated its efficacy. Tolerance is satisfactory and the cost is low compared with associations using "new" drugs.

Changes in histological lesions and serum fibrogenesis markers in chronic hepatitis C patients non-responders to interferon alpha.

BACKGROUND/AIMS: The aim of this study was to evaluate the changes in histological lesions and serum N-terminal peptide of type III procollagen (PIIINP) and hyaluronate (HA) levels in virologic non-responder patients treated by Interferon alpha (IFNalpha). METHODS: We enrolled 183 patients treated by IFNalpha and 56 controls, all with paired biopsy specimens. Yearly liver fibrosis progression was estimated before and during a follow-up of 1 year. RESULTS: By contrast to sustained responders, non-responders (n = 105) did not achieve improvement of histological scores after therapy. Their yearly fibrosis progression rate was similar before and during follow-up (0.18, 95%CI: 0.16-0.20, vs 0.26 (95%CI: 0.12-0.40) fibrosis units/year, NS), and was not different in controls (0.17, 95%CI: 0.06-0.27). The levels of PIIINP and hyaluronate (HA) remained unchanged during follow-up. Histological improvement was observed for the second biopsy in 25% of non-responders, but also in 23% of controls. This improvement was not correlated with decrease of ALT level, viral load, PIIINP, or HA. CONCLUSIONS: Our results suggest that IFNalpha therapy is unable to decrease PIIINP or HA levels and cannot improve the histological outcome in virologic non-responder patients. The histological improvement observed in a subset of patients may be linked to sample fluctuation or lack of reproducibility of histological scores.

Characteristics of patients with dual infection by hepatitis B and C viruses.

BACKGROUND/AIMS: The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. METHODS: Twenty-three patients with chronic hepatitis C, who were anti-HCV positive and HBs antigen positive, were studied and subdivided into two groups according to the presence or absence of HBV DNA replication. They were compared to 69 age- and sex-matched patients with chronic hepatitis who were anti-HCV positive and HBs antigen negative. All patients were HCV RNA positive by PCR, anti-HIV negative and anti-HDV negative. HBV DNA and HCV RNA were detected in serum by means of a branched DNA assay and PCR. The HCV serotypes were determined by the Chiron Riba HCV serotyping SIA technique. The histological characteristics included the Knodell score. RESULTS: Epidemiological, biochemical and virological parameters were not different between the two groups. Only the prevalence of cirrhosis was greater in chronic hepatitis B and C patients than in patients with chronic hepatitis C alone (p = 0.01). Among chronic hepatitis B and C patients, HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA negative patients (p = 0.01). Indeed, histological lesions were more severe in HBV DNA positive than in HBV DNA negative patients, including prevalence of cirrhosis (p = 0.01), Knodell score (p = 0.05) and, among the latter, piecemeal necrosis (p = 0.01) and fibrosis (p = 0.05). The characteristics of patients with dual infection did not differ according to the mode of contamination and duration of HBV disease, except for a shorter duration in patients contaminated by drug abuse than in other patients. CONCLUSIONS: These results suggest that HBV DNA replication inhibits HCV RNA replication in patients with chronic active hepatitis B and C but increases the severity of histological lesions.

Tenoxicam, a non-steroid anti-inflammatory drug, is unable to increase the response rate in patients with chronic hepatitis C treated by alpha interferon.

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.

[Value of high-dose interferon-alpha in chronic viral hepatitis C patients non-responder to a 1st treatment. Pilot study prospective and randomized trial]. / Intérêt de l'interféron alpha à forte dose chez les malades atteints d'une hépatite virale chronique C non répondeurs à un premier traitement. Etude pilote prospective et randomisée.

OBJECTIVES: The aim of this study was to evaluate the efficacy of two different doses of alpha interferon (IFN) for retreatment in chronic hepatitis C patients who were non responders to initial treatment by IFN at a dose of 3 MIU TIW for 6 months. METHODS: This open, pilot, prospective, randomized and bicentric study included patients with biopsy-proven chronic hepatitis C. Non response was defined as serum ALT levels > 2 upper limit of normal for the entire first treatment period, HCV RNA positivity by PCR at the end of the first treatment period, and the persistence of histologically-proven chronic active hepatitis after the first treatment period. Patients were randomized into two groups: group I received IFN alpha 2b 10 MIU TIW for 2 months, then 6 MIU TIW for 4 months, group 2 received IFN alpha 2b 6 MIU TIW for 6 months. RESULTS: Twenty three patients (17 male, 6 female, mean age: 38.7 +/- 9.1 years) were included: 14 were randomized in group 1 and 9 in group 2. Both groups were similar for the main clinical, biochemical, and histological variables. At the end of retreatment, 2 patients (14.2%) had biochemical and virological response in group 1 and 4 in group 2 (44.4%) (non significant). Only one biochemical and virological sustained response was observed in group 2 (11.1%) (non significant). There was no difference between the groups for complete and sustained response. An overall statistical significant improvement of Knodell score was observed (7.8 +/- 3.8 vs 9.6 +/- 3.2, P < 0.02) in the 18 patients who had a second biopsy 6 months after the end of therapy, while the Knodell score did not change at the end of the first treatment period. This improvement was statistically significant in group 2 (5.4 +/- 3.0 vs 9.2 +/- 9.5 before treatment, P < 0.02) and concerned intralobular necrosis (P < 0.05). The Metavir index did not change. The number of side-effects was similar in both groups. CONCLUSIONS: These results suggest that histological improvement may be obtained after IFN retreatment in some patients who are non-responders to the first treatment, despite an absence of biochemical and/or virological response.

Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer.

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.

Phase I-II and pharmacokinetic study of a new fotemustine schedule in advanced non-small cell lung cancer.

UNLABELLED: Fotemustine, a new nitrosourea derivative has already demonstrated activity in non-small cell lung cancer (NSCLC). In order to improve its therapeutic index, we designed a protocol in which Fotemustine was delivered with dose escalation on 3 consecutive days as induction therapy followed by a 5-week rest period. Maintenance therapy consisted of 100 mg/m2 once every 3 weeks. Pharmacokinetic data were assessed during this Phase I-II study and reported here. PATIENTS AND METHODS: Nineteen patients with metastatic (17) or locally advanced (2) NSCLC were included in the present study. Ten of those with metastatic disease had brain metastases and 15 had previously received chemotherapy. Fotemustine was given at 50 mg/m2 on day 1-2-3 (group 1: four patients), 75 mg/m2 on day 1-2-3 (group 2: 16 patients including two who had already received 50 mg/m2) and 100 mg/m2 on day 1-2-3 (group 3: one patient). RESULTS: The maximal tolerated dose was 75 mg/m2 on day 1-2-3 (total cumulated dose 225 mg/m2). At this dose level, we observed 25% of Grade 3-4 neutropenia and 31% of Grade 3-4 thrombocytopenia. One patient died of pulmonary infection during aplasia. No other significant toxicity occurred. Of the 17 evaluable patients, one obtained a PR lasting 6 months in group 2 and 1 PR lasting 3 months in group 3. No significant difference was noted in the AUC between days 1, 2 or 3 in any of the seven patients in whom a pharmacokinetic study of Fotemustine was performed. CONCLUSION: Administered on 3 consecutive days, Fotemustine seems to be less effective and more toxic than other schedules tested in NSCLC. Despite the quality of the two responses observed, this protocol has been discontinued and the standard administration on days 1 and 8 remains the schedule of choice in NSCLC.

[Are desquamated trophoblastic cells retrieved from the cervix suitable for a prenatal diagnosis?]. / La desquamation de cellules trophoblastiques recueillies au niveau du col utérin permet-elle un diagnostic prénatal?

Prenatal diagnosis based on sampling of fetal tissues, amniotic fluid or chorionic villi is associated with the risk of miscarriage and fetal damage. These risks would be avoided if diagnosis could be performed in desquamated trophoblast cells recovered non-invasively from the maternal cervix. We report on our experience of fetal karyotyping on endocervical lavage using in situ hybridization (FISH) and DNA amplification (PCR) fetal sex was correctly predicted in 8/10 cases by FISH and in 6/10 by PCR. FISH appeared to be a reliable technique for karyotyping when trophoblast can be recovered from the maternal endocervix (8/10).