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OBJECTIVE: To compare the effect of tibolone to conjugated estrogens with medroxyprogesterone-acetate (CEE + MPA) on breast density, as a predictor for breast cancer risk, in women with a high risk of breast and ovarian cancer. METHODS: Women aged 30-50 (N = 114) who had undergone risk-reducing salpingo-oophorectomy (RRSO) were randomized to tibolone or CEE + MPA. RESULTS: Breast density decreased 46% after RRSO in untreated women, 39% after treatment with tibolone, and 17% after treatment with CEE + MPA; the decrease in breast density after CEE + MPA was significantly different compared with that of untreated women (P = 0.017). CONCLUSIONS: A decline in breast density is seen after premenopausal RRSO despite the use of both CEE + MPA or tibolone, although lower breast density is seen after tibolone use.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR)= 1.02 (0.66-1.58), two-sided P= 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR= 0.95 (0.59-1.52), P= 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade =3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Sammendrag: Som lærer møter man på mange ulike elever som viser flere ulike typer atferd. Det skilles ofte mellom to ulike former for atferdsvansker; innagerende og utagerende. Sistnevnte er den typen atferd som ofte får mest fokus. Utagerende atferd kan gi negative konsekvenser både for eleven som viser atferden og for de rundt, i tillegg til at atferden tar mye oppmerksomhet. Fokuset på den utagerende atferden gjenspeiles i forskning og litteratur om atferdsvansker. Men, den begrensede tilgangen til litteratur om innagerende atferd betyr ikke nødvendigvis at denne atferden er mindre problematisk eller mindre utbredt (Lund, 2004). Innagerende atferdsproblematikk er nesten like vanlig som utagerende (Nordahl, Sørlie, Manger, & Tveit, 2005).1 Innagerende atferd er et atferdsproblem, på lik linje med andre atferdsvansker. Denne studien handler om lærerens møte med elever som viser innagerende atferd i skolen. Studien viser til betydningen læreren kan ha for elever som viser innagerende atferd, og viser til viktigheten av et godt og trygt miljø rundt disse elevene. Formålet med studien er å øke egen, og forhåpentligvis andres, kunnskap og forståelse for hvordan man som lærer kan legge til rette for trivsel i skolen hos elever som viser innagerende atferd på småskoletrinnet. I tillegg fokuseres det på hvilke utfordringer man kan møte på i dette arbeidet, og hvilke tanker lærere har om tilrettelegging for elever med disse vanskene. Tematikken i studien blir belyst via følgende problemstilling: «Hvilke erfaringer har tre kontaktlærere med styrking av trivsel i skolen hos elever som viser innagerende atferd på småskoletrinnet?». Dette forskningsprosjektet har en kvalitativ tilnærming, ved bruk av dybdeintervju som datainnsamlingsmetode. Forskningsprosjektet har et fenomenologisk perspektiv, hvor forskerens ønske er å forstå forskningsdeltakernes opplevelser, erfaringer og refleksjoner knyttet til elever som viser innagerende atferd. Funn er gjort gjennom dybdeintervju, hvor disse intervjuene har blitt tolket og drøftet i lys av teori. Via studien kom det frem at lærerne har mye erfaring med arbeid knyttet til elever som viser innagerende atferd. Til tross for et stort sprik innenfor antall års erfaring i læreryrket, var lærerne enig i at denne elevgruppen er en av de mest utfordrende gruppene å jobbe med. Årsaken til dette var forskjellig, men en av grunnene som ofte ble nevnt var generelt lite kunnskap om atferdsvansken, teoretisk, og ikke erfaringsmessig, og det å kunne knytte en god relasjon til disse elevene. En utilstrekkelig eller mangelfull relasjon til en elev som viser innagerende atferd gjør det igjen vanskeligere å legge til rette for læring og utvikling. En fellesnevner hos samtlige av lærerne var utfordringen med å ha nok tid til disse elevene. De trenger tid. Og kjærlighet. Som alle andre elever. Og for å skape trygghet og gode relasjoner til disse elevene, så trenger de kanskje også enda litt mer tid enn det vi faktisk har. Derfor gjelder det å være bevisst på hvordan man kan bruke de få mulighetene som oppstår i løpet av skolehverdagen til å anerkjenne og styrke relasjonen til disse elevene. Den største utfordringen, og bekymringen, lærerne rapporterte, var at elevene som viser innagerende atferd lett kunne bli usynlige og glemt i den travle skolehverdagen. Lærerne har ofte dårlig samvittighet knyttet til disse elevene. Lærerne i studien opplever at de via ulike tiltak og tilpasninger tilrettelegger for trivsel i skolen for også disse elevene. Lærerne er klar over at disse elevene lett kan bli usynlige, og det jobbes derfor systematisk for å ikke la elevene faktisk bli det. I tillegg har flere av lærerne holdninger til atferden hvor de opplever at barn gjør det bra hvis de kan. Det handler altså ikke om at de ikke vil. Noen av lærernes viktigste oppgaver knyttet til dette vil være tiltak og tilpasninger som for disse elevene ofte vil handle om styrking av sosiale ferdigheter og forventning om mestring. Målet er å styrke elevenes sosiale ferdigheter og gi de redskap som de kan bruke både i undervisningssituasjon og i sosialt samspill med andre barn og voksne. Av tiltak og tilpasninger nevner lærerne ofte viktigheten av fokus på: uteskole, lek, vennskap, relasjoner, klassemiljø, forutsigbarhet og forventinger. I tillegg uttrykker lærerne at det aller viktigste er å ikke gi opp, og å ta seg tid til å komme innpå, forstå og anerkjenne disse elevene og deres vansker. Abstract: As a teacher, you will encounter many unique students that express different kinds of behaviour. We often differentiate into two groups of behaviour problems: withdrawn and disruptive behaviour. Disruptive behaviour usually gets the most attention. This behaviour can cause negative consequences for both the student and their fellow students in addition to taking a lot of the attention. The point that we are focusing on disruptive behaviour is reflected in research and literature on behavioural problems. However, the limited access to literature on withdrawn behaviour does not mean that this behaviour is less of a problem (Lund, 2004). Withdrawn behaviour is almost as usual as disruptive behaviour (Nordahl, Sørlie, Manger, & Tveit, 2005). Withdrawn behaviour is a behavioural problem, equal to other learning disabilities. This study is about the teachers encounter with students who show withdrawn behaviour in the school. The study refer to the importance the teacher can impose on students who show withdrawn behaviour and the importance of a good and safe environment around the students showing this behaviour. This study’s purpose is to improve my own and hopefully others knowledge and understanding of how, as a teacher, you can facilitate for wellbeing in the school for students showing withdrawn behaviour in the early years of being a student. In addition, I will focus on what kind of challenges teachers can encounter in this work and what thoughts teachers have about facilitating for students with these difficulties. The theme of the study will be enlightened through the following research question: ”What experiences has three contact teachers with strengthening of wellbeing in school for students who show withdrawn behaviour in school?” This study has a qualitative approach, by using in-depth interviews as a method to collect data. The study has a phenomenological perspective, where the researcher’s desire is to understand the participant’s experiences, observations and reflections regarding students who show withdrawn behaviour. The findings of the studies were made through on indepth interviews of three contact teachers about their experiences when working with students who show withdrawn behaviour. Through this study, I have found that the teachers have a lot of experience working with students who show withdrawn behaviour. Despite the fact that some of the teachers have a longer career than the rest, all of the teachers agreed to that the withdrawn students are one of the most difficult groups to work with. The reasons given was different, but the teachers often said the lack of theoretical knowledge rather than experience. In addition, the struggle to establish a good relationship to the students were often mentioned in the interview. A lacking relationship to the students who shows withdrawn behaviour makes it even harder to facilitate for good learning and development. Another frequent point made by the teachers was the challenge to find enough time for each student, because withdrawn students need a lot of time, and love, as every student does. To create safe and good relationships to these students, they might even need more time than we have. Therefore, it is very important to be aware of how we can use the few opportunity’s that appear in a school day to acknowledge and strengthen the relationship to these students. The biggest challenge and worry that the teachers reported was that students who show withdrawn behaviour easily became invisible and forgotten in the busy school day. The teachers often feel guilty towards these students. The teachers experience that through different adjustments and measures, they can facilitate for wellbeing for the students showing withdrawn behaviour. The teachers are aware that these students often can become “invisible”, and they work systematically to not allow the students to be forgot. Additionally multiple of the teachers have attitudes toward students that say that the students can succeed if they are “able to” succeed, rather than “want to”. These teachers view the work of improving the student’s social skills and adjusting expectations. They seek to give the students social skills and tools that are applicable in the classroom and in social activities with both kids and grownups. Of measures and adjustments, the teachers often point to the importance of focusing on the following: Outdoors education, playing, friendship, relations, classroom environment, predictability and expectations. In addition, the teachers express that the most important thing is to do not give up, take your time to build a relation, understand and acknowledge these students and their difficulties.

As of 2018, women comprise almost half of the U.S. workforce (Catalyst, 2018), earning 57% of bachelor’s degrees, 60% of master’s degrees, and 52% of doctoral degrees (National Center for Education...

Resume Les inhibiteurs de checkpoints de l’immunite (ICPI) font partie integrante du traitement des cancers bronchiques non a petites cellules avances ainsi que d’un nombre de plus en plus grand de tumeurs. Leur toxicite est specifique, qu’elle concerne les antiPD1/PDL1 ou les antiCTLA4. La selection et le suivi des patients doivent etre organises, les principales toxicites connues et le patient eduque a les reconnaitre. La prise en charge en cas de symptome grave justifie l’utilisation large des corticoides avant un avis specialise. Des algorithmes diagnostiques et therapeutiques sont proposes notamment par l’ESMO. Des RCP specialisees de gestion des immunotherapies permettant l’acces a toutes les competences s’organisent rapidement.

In cases of advanced EGFR mutation-positive non-small cell lung cancer, first or second generation EGFR-tyrosine kinase inhibitors (TKI-EGFR 1G or TKI-EGFR 2G) are recommended as first line treatment. Inexorably, progressive disease occurs and, in 50-60% of the cases, is secondary to a T790M resistant mutation. The prescription of osimertinib (TKI-EGFR3G) in second line is dependent on identification of the T790M mutation. We report 7 cases in which the identification of the T790M mutation required repeated analyses of cell free DNA and/or biopsies over a period of time. In some cases, a positive result was obtained a long time after progressive disease had been diagnosed during treatment with first or second generation EGFR-TKI. We discuss here the different modalities of screening for the T790M mutation and we encourage persevering in this search when no alternative mechanism of resistance has been identified.

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).

Background Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling. Objective We have compared the levels of MMPs, eotaxin and soluble interleukin 2 receptor (IL-2R) in the plasma of healthy subjects, atopic patients and asthmatic patients. Methods The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP-9, TIMP-1, IL-2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography. Results An increased basal level of MMP-9 and IL2-R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP-9 in the plasma of all groups of patients. However, the MMP-9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP-1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP-9 (92 kDa) but not MMP-2 (66 kDa) in the plasma of patients with acute asthma. Conclusion The increased in MMP-9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP-9 as a non-invasive systemic marker of inflammation and airway remodelling in asthma.

Background and Study Aims: Locoregional progression of esophageal cancer can result in respiratory distress aving to tracheoesophageal (T-E) fistula or central airways stenosis. We report our experience of airway stenting in 51 patients with esophageal carcinoma involving the central airways. Patients and Methods: All data were recorded retrospectively. Fifty-one patients (44 men and seven women), with a mean age of 58.6 years, were analyzed. All had an esophageal squamous cell carcinoma. Severe respiratory impairment due to tumor invasion or to a tracheobronchial fistula (n=14) was present in all patients. Nine of the 14 patients witb fistula had dysphagia. Among the 37 patients without fistula, 19 had dysphagia. Results: Sixty-six tracheobronchial stents were inserted in 51 patients: 65 Dumon stents and one Wallstent. Forty stents were implanted in the trachea, 16 in the left main bronchus and 10 in the right main bronchus. In 47 patients there was a significant improvement of respiratory symptoms. Esophageal intubation, carried out in nine patients, allowed eating and drinking in all cases. Mean survival was 107.7 days, with the longest follow-up 587 days. There was no difference between mean survival in the patients with fistulae (103.3± days) and the others (109.3 ± days). In two cases stent placement was responsible for death (massive hemoptysis and pneumonia). The main complications were migration (n=6), granuloma (n=2), pneumonia (n=2) and pneumothorax (n = 2). In 13 patients tumor progression in the airways was noted from one to 11 months after stenting, inducing a relapse of dyspnea. Conclusions: Complications are easily detected by the appearance of respiratory symptoms and do not necessitate systematic flexible bronchoscopy, but only preventive measures such as regular aerosol therapy, adapted respiratory physiotherapy and regular clinical follow-up.

Primitive tumors of the trachea are rare, accounting for 0.1% of the airway tumors. Cystic adenoid carcinoma (or cylindroma) represents the second most frequent type of tracheal cancers. Histologically speaking, this tumor type is divided in three patterns: cribriform, tubular and solid; it presents a slow growth, perineural invasion and potential local recurrence and metastasis. We presented herein the case of a 56-year-old female suffering from a cystic adenoid carcinoma of the low trachea. She has been treated by carinal resection with negative airway margin and complete reconstruction, with the help of an extra corporeal membrane oxygenation (ECMO).

TNF blockers are widely used to treat inflammatory rheumatic diseases and also in the treatment of extrapulmonary sarcoidosis. TNFα plays a major role in the development and persistence of sarcoid granulomata. However, recent studies have reported the involvement of anti-TNF therapies in the development of granulomatosis associated with the clinical and radiological features of sarcoidosis.A 54-years-old man with ankylosing spondylitis was treated with etanercept for two years. He was admitted with symptoms of bronchitis associated with radiological evidence of bilateral pulmonary nodules and a right upper lobe infiltrate. Anti-TNF therapy was stopped even though the patient had received 3 months of prophylactic treatment with rifampicin and isoniazid before starting etanercept. Bronchoalveolar lavage excluded infection, particularly tuberculosis. The chest CT-scan showed bilateral pulmonary nodules with peribronchovascular micronodules and enlarged mediastinal lymph nodes. Surgical lung biopsy was performed and revealed non-caseating granulomata. All the data were consistent with a diagnosis of pulmonary sarcoidosis. The patient remained symptomatic despite discontinuation of etanercept for ten months. Corticosteroids were then introduced, leading to a clinical, functional and radiological improvement.This case report underlines the importance of studying the pulmonary complications of TNF blockers. The first priority is to exclude tuberculosis but a diagnosis of sarcoid-like granulomatosis has to be considered. Twenty-three cases have been described in the literature to date.

Ras genes encode a family of membrane proteins involved in the regulation of cell growth. Mutations of Ras stimulate cell growth and thus can play a role in carcinogenesis. The search for mutations of Ras is possible by PCR on bronchial biopsies or surgical specimens. They are found in 15 to 20% of non-small cell lung cancers. In the disease's early stage, the presence of a Ras mutation can be a negative predictor of the effectiveness of adjuvant chemotherapy. In the advanced stage of the disease, it is a factor predicting a poor prognosis. Although prospective studies have found no statistically significant negative influence of the presence of a mutation of Ras on the effectiveness of tyrosine kinase inhibitors of EGFR, it is likely that these treatments will be of limited value in this population given the lack of response observed when Ras is mutated. Prospective and functional studies are needed to determine the value of the different mutations observed.

The occurrence of pain during the course of bronchial carcinoma is nearly inescapable and often constitutes the main symptom for patients and those close to them. While pain control is held to be a priority of care in cancerology in the future, this goal is not always reached due to insufficient implementation of recommendations, however widely accessible. Our aim is to present the different aspects of pain treatment through the details of both pharmacological and nonpharmacological means.

Objective and design: Chronic obstructive pulmonary disease (COPD) is characterized by an inflammatory process and airway remodeling involving matrix metalloproteinases (MMPs). Thus, we analyzed the expression and release of MMP-12 (macrophage metalloelastase) in bronchoalveolar lavage (BAL) and lung tissue from COPD patients and control subjects. Methods: Immunocytochemistry and immunochemistry were performed to analyze the expression of MMP-12 in BAL cells and bronchial biopsies. Western blotting was used for the evaluation of MMP-12 in BAL fluids. Results: The number of MMP-12 expressing macrophages together with the staining intensity was higher in BAL samples from COPD patients than in controls subjects. Similar results were noted in bronchial biopsies with higher MMP-12 expression in COPD subjects than in controls. Enhanced MMP-12 level was also observed in BAL fluids from patient with COPD in comparison to control subjects. Conclusion: This study demonstrated that COPD patients produce greater quantities of MMP-12 than controls, which may be a critical step in the pathogenesis of COPD and emphysema.

We report the case of a nonimmunocompromised female patient, who developed exogenous lipoid pneumonia with Mycobacterium fortuitum infection at diagnosis, later followed by Aspergillus fumigatus infection. The association of exogenous lipoid pneumonia with atypical mycobacterial infection is uncommon but well-recognized, but, to our knowledge, association with A. fumigatus infection has not previously been reported.

The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.

Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy.Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts.6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes.Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

To assess the toxicity and efficacy of high dose ifosfamide in stage IV NSCLC.In a previous trial, we have determined maximum tolerated dose for 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m2 according to hematologic tolerance. We therefore set up a phase II to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m2) was administered by a two hour infusion (3 g/m2) for three days every three weeks. Patients received three mesna bolus infusions (1 g/m2) at 4, 8 and 12 hours after the end of ifosfamide infusion. Antitumoral efficacy was performed after 2 cycles and treatment could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this study. Median age was 60.7 years +/- 1.33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, liver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudden death, 5 treatment interruptions before evaluation time and 3 toxic deaths (9.6%).neutropenia grade 4 (10 pts and 1 death), cardiotoxicity grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3.6-29.8), 10 progressive diseases (32.3%, 95CI: 16.7-51.4) and 10 stabilizations (32.3%, 95CI: 16.7-51.4). Median response duration was 91 days +/- 55 d. Median survival was 9.3 months, e.g. 280 days (8-863). Overall survival at one year is 48%.This modality of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones could be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment on a 5-day schedule basis.

Mature teratoma is the most frequent primary germ-cell tumor occurring in the mediastinum. These tumors present characteristic mature cells derived from all three types of embryogenesis tissues. We report two cases. The typical presentation is a cyst-like noninvasive, heterogeneous and calcified formation in the anterior mediastinum, usually in young subjects. Tumor markers, alpha-fetoprotein and beta-gonadotropin, are contributive as they rule out mature tumors if positive. Surgery is the treatment of choice, although adherence to neighboring structures usually makes complete excision difficult. Pathology provides the precise diagnosis, ruling out an immature component.

Lung damage due to inhalation of inflammable products, especially Kerdane, is mainly observed in young subjects. Lung damage is rarely severe and the diagnosis is facilitated by the notion of inhalation. These conditions regress favorably in a few days. We report six cases.

The main respiratory manifestations of amylosis are tracheobronchial involvement and modular or diffuse parenchymal disease. Amyloid deposits in the pleura are exceptional. We observed transsudative pleural effusion and heart failure in a patient with multiple myeloma, leading to the discovery of pleural amylosis. Amyloid deposits in the pleura may be fortuitous discoveries since pleural effusion is not necessarily observed. It is however important to be aware of this possibility since the localization is easily accessible for diagnosis. Specific stains are effective diagnostic tools even for transsudative effusions, particularly in suggestive clinical conditions such as multiple myeloma.

Serious acute asthma is a reality. The authors detail the factors that cover the areas usually met, the signs that are portents of a worrying development, regrouped to the threshold of the entirety of the "menacing syndrome", finally the signs of severity or distress, as well as the recommended treatments.