Somatic profile in lung cancers is associated to reproductive factors in never-smokers women: Results from the IFCT-1002 BioCAST study.

BACKGROUND: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. METHODS: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. RESULTS: Two hundred and sixty women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age>14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; P=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (P=0.048), and by 9% for each year at age at first birth (P=0.035). ALK alteration frequency was greater in women with high parity (50% in≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; P=0.021). CONCLUSION: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.

Management of malignant pleural mesothelioma: a French multicenter retrospective study (GFPC 0802 study).

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease with poor prognosis in spite of significant improvement in survival, due to new chemotherapy regimens. We describe here patients' profiles and management in daily practice in France. METHODS: Observational retrospective study. Data were collected from medical files. All patients with histologically proven MPM diagnosed from January 2005 to December 2008 were included in the participating sites. RESULTS: Four hundred and six patients were included in 37 sites: mean age 68.9 ± 9.8 years, male predominance (sex ratio 3.27), latency of the disease 45.7 years, epithelioïd type 83 %. Diagnosis was made using thoracoscopy in 80.8 % of patients. Radical surgery was performed in 6.2 % of cases. Chemotherapy was administered to 74.6 % of patients. First line regimens consisted mainly of platinum + pemetrexed (91 %) or pemetrexed alone (7 %). Objective response rate was 17.2 % and another 41.6 % of patients experienced disease stabilization. Half of these patients underwent second line chemotherapy (platinium + pemetrexed 31.6 %, pemetrexed alone 24.6 %), resulting in a 6 % response rate. Third-line chemotherapy (56 patients) yielded disease control in 5.4 % of cases. CONCLUSIONS: The management of MPM in France is usually in accordance with guidelines. Response rates are somewhat lower than those described in clinical trials.

Fractionated stereotactic radiotherapy for acoustic neuromas: long-term outcomes.

AIMS: Acoustic neuromas are rare, benign intracranial tumours. There are a variety of treatment options, with no clear optimal management strategy and wide variation in treated outcomes. We report the outcomes from a 15 year cohort of patients treated at our centre using fractionated stereotactic radiotherapy (52.5 Gy in 25 fractions). MATERIALS AND METHODS: We analysed a retrospective case series. Patients were identified from patient records and a retrospective review of case notes and imaging reports was undertaken. We assessed tumour response using RECIST criteria and recorded toxicity. Progression-free survival was estimated using the Kaplan-Meier method. The study was conducted according to the STROBE guidelines. RESULTS: In total, 93 patients were identified; 83 patients had follow-up data, with a median follow-up period of 5.7 years. The overall control rate using RECIST criteria was 92%. Data on complications were available for 90 patients, with six (7%) experiencing a reduction in hearing, one (1%) developing trigeminal nerve dysfunction and one (1%) a deterioration in facial nerve function. Other toxicities included four (4%) patients who developed hydrocephalus, requiring the placement of a shunt and one (1%) patient who developed radiation brainstem necrosis. After further evaluation this patient was deemed to have been treated within acceptable dose constraints. CONCLUSION: These data suggest that a good control rate of acoustic neuromas is achievable using fractionated stereotactic radiotherapy to a dose of 52.5 Gy in 25 fractions. Toxicity is considered acceptable but the episode of radiation brainstem necrosis remains of concern and is the subject of further work.

[Pulmonary metastases from malignant meningioma]. / Métastases pulmonaires de méningiome malin.

INTRODUCTION: Pulmonary metastases from meningioma are rare and present with specific clinical and radiological features. The diagnostic and therapeutic management of metastatic meningioma illustrate the concept of orphan thoracic oncology. CASE REPORT: We report the case of a 58-year-old male, former smoker, with a previous history of atypical meningioma and resected lung adenocarcinoma. During oncologic surveillance, a computed-tomography scan disclosed multiple well-defined homogeneous nodules in the right lung. These nodules were hypermetabolic at positron-emission tomography with fluorodesoxyglucose. Pathological examination of metastasectomy specimens revealed metastatic malignant meningioma. CONCLUSIONS: Pulmonary metastases may occur in malignant meningioma. Twenty-one cases have been reported over the past 20 years. As for all rare tumours, multidisciplinary consensus is mandatory, in the absence of evidence-based recommendations based on prospective trials or observational studies.

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Thymic carcinoma: a clinicopathological and immunohistological study of 19 cases.

AIMS: To study 19 cases of primary thymic carcinoma in order to define the clinicopathological features and the precise histochemical profile of this rare and heterogeneous group of tumours of the anterior mediastinum. METHODS AND RESULTS: The study group consisted of 13 males and six females, with a mean age of 58.5 years (range 29-75 years). Superior vena cava syndrome and chest pain were the main presenting symptoms. Three patients were asymptomatic. No patient had myasthenia gravis. Six different histological types were identified: neuroendocrine tumours (six patients), epidermoid carcinoma (five patients), sarcomatoid carcinoma (three patients), lymphoepithelioma-like carcinoma (two patients), mucoepidermoid carcinoma, clear cell carcinoma, and undifferentiated carcinoma (one patient each). The clear cell carcinoma was associated with a thymic cyst. No association with thymoma was observed. Surgical resection, performed in 10 cases, was complete in two. Sixteen patients received thoracic radiation, and 11 received systemic chemotherapy. Follow-up information was available in 16 cases; 12 patients presented with local or metastatic relapse, and 10 patients died of their tumour. The overall 5-year survival was 14.5%. CONCLUSION: Primary thymic carcinoma is a very heterogeneous group of tumours of the anterior mediastinum with an aggressive clinical behaviour, and a poor overall prognosis.

[Chronic cough after laparoscopic adjustable gastric banding]. / Toux chronique après gastroplastie par anneau modulable.

INTRODUCTION: Patients are frequently referred for chronic cough. The causes are various. CASE REPORT: We report two cases of chronic cough that occurred after laparoscopic adjustable gastric banding for treatment of morbid obesity. In both cases, the computed tomography scan showed an important oesophageal dilatation. The cough disappeared after the band deflation. CONCLUSION: Oesophageal dilatation after laparoscopic adjustable gastric banding is a new cause to be included in the aetiology of chronic cough.

A randomized prospective trial of low-dose OKT3 induction therapy to prevent rejection and minimize side effects in recipients of kidney transplants.

BACKGROUND: We attempted to minimize the undesired side effects and maximize the benefit of OKT3 induction therapy in renal transplantation. METHODS: One hundred and one recipients of kidney-only transplants were randomized to three groups. Each received low-dose 2.5-mg OKT3 induction for 7-14 days, but different premedication on days 0, 1, and 2. Group I was given 250 mg i.v. methylprednisolone at 1 and 6 hr, and group II received another 500 mg at 1 hr before initial OKT3. Group III received Atgam 15 mg/kg on day 0 and began OKT3 on day 1. A CD3+ T-cell cut-off of 50/mm3 was used to guide therapy. Maintenance therapy included cyclosporine and steroids for each patient. However, groups I and II were also given mycophenolate mofetil, and group III received azathioprine as a third agent. All rejections were biopsy confirmed and Banff scored. RESULTS: No differences in demographic or transplant characteristics were noted between groups I, II, and III, and mean follow-up was 25.7 (1-38) months. There was no significant difference in actuarial patient (90%, 91%, 94%) or graft survival (83%, 88%, 84%) at 3 years between the respective groups. Mean creatinine values and infectious complications were similar for each group. No patient experienced acute rejection during induction, and eight patients required dose escalation to sustain suppression of CD3 counts. The incidence of acute rejection at 6 and 12 months was significantly (P=0.004) greater in group III (38.2, 44.1%) than in either group I (15.1, 18.1%) or group II (14.7, 17.6%); relative risk 1.988 (95% CI 1.012-3.906). Formation of anti-OKT3 antibody was significantly (P=0.006) greater in group III (26.5%) than in group I (6%) or group II (2.9%). Group I recipients enjoyed significantly (P=0.001) fewer (2.17) OKT3 side effects on days 0, 1, and 2 than group II (3.03) or group III (2.49), and contained the largest number (61%) of recipients who experienced no side effects. Group I also exhibited the most suppressed profile of OKT3-induced release of tumor necrosis factor-alpha (P=0.006), interferon-gamma (P=NS), and interleukin-6 (P=0.01) on days 0 and 1. CONCLUSIONS: Low-dose 2.5-mg OKT3 with pretreatment of split-dose steroids on days 0, 1, and 2 provides the most effective method for OKT3 induction, which minimizes side effects for most patients. Subsequent maintenance therapy with cyclosporine, mycophenolate mofetil, and steroids provides effective rejection prophylaxis without increased complications for up to 3 years. Predepletion of T cells before exposure to OKT3 does not prevent cytokine release.

Quantitative assessment of the first acute rejection as a predictor of renal transplant outcome.

BACKGROUND: Acute rejection (AR) of the transplanted kidney has been identified as the major risk factor for the development of chronic rejection and immunological graft loss. However, the clinical presentation and response to AR therapy can vary considerably between recipients. METHODS: We studied the first AR episode in 201 kidney-only recipients transplanted between January 1987 and June 1998 who were biopsied between April 1993 and June 1998 and were graded using the Banff schema. All patients received cyclosporine-based immunosuppression. There were 134 cadaver donor (66.7%) and 67 live donor (33.3%) recipients followed for a mean of 46.2 (range 4-128) months. All Banff grade 1-3 and 40/78 borderline (BL) cases were treated for rejection after biopsy. These patients were compared with a contemporaneous control population who did not experience AR. Demographic risk factors associated with graft loss were identified in both univariate and multivariate analysis. Daily (0-18) serum creatinine (SCr) values during and after the AR were plotted for each patient to generate curves and calculate area under the serum creatinine versus time curve (mg/dl/day). Four response patterns to treatment were identified according to the velocity of % increase (V1) and decrease (V2) of serum creatinine. These were identified as rapid rise and fall (n=62); rapid rise and slow fall (n=43); slow rise and fall (n=55); and slow rise and rapid fall (n=41). Kaplan-Meier graft survivals were compared between the groups. RESULTS: Any Banff grade was associated with increased risk for graft loss (P=0.0001). However, no significant differences were observed between the Banff BL and B1-3 groups, or among those BL patients who were treated or remained untreated for AR. Multivariate analysis identified a black recipient (P=0.03, risk ratio 2.0) and area under the serum creatinine versus time curve (P=0.0001, risk ratio 3.2) as significant risk factors for graft loss. The AR response pattern RS resulted in a significantly (P=0.0072) diminished 5-year graft survival (45%) compared with the other groups. Serum creatinine pattern, but not Banff grade, was also a significant (P=0.025) predictor of re-rejection. CONCLUSIONS: These data suggest that all Banff grades, including BL, carry a significant risk for graft loss, and the initial response to antirejection therapy can predict long-term graft outcome. They support the practice of treating AR promptly and definitively and suggest that the RS subgroup of rejecting grafts could be targeted for additional antirejection therapy. This subgroup can be identified by 10 days of AR therapy, and should be the subject of further study.

Outcome of renal transplantation in patients with a functioning graft for 20 years or more.

In the present study long-term morbidity, quality of life and over-all rehabilitation were assessed in 14 patients with a functioning renal allograft for 20 years or longer. Followup ranged from 20 to 27 years (mean 22.5 years). All patients enjoyed excellent and stable renal function, and the mean serum creatinine level at 20 years was 1.3 mg. per dl. Complications related to long-term immunosuppressive therapy comprised infection in 8 patients (57%), malignancy in 7 (50%), cardiovascular disease in 6 (43%), cataracts in 3 (21%) and avascular necrosis of the hip in 2 (14%). Over-all quality of life was excellent in 13 patients who were able to return to work, participate in pre-illness levels of activity and enjoy sexual activity. While successful renal transplantation allows patients with end stage renal failure to resume relatively normal lives, these patients remain prone to complications resulting from long-term immunosuppressive therapy.