Selection of Resistance to Clarithromycin in Mycobacterium abscessus Subspecies.

Mycobacterium abscessus is an emerging pathogen against which clarithromycin is the main drug used. Clinical failures are commonly observed and were first attributed to acquired mutations in rrl encoding 23S rRNA but were then attributed to the intrinsic production of the erm(41) 23S RNA methylase. Since strains of M. abscessus were recently distributed into subspecies and erm(41) sequevars, we investigated acquired clarithromycin resistance mechanisms in mutants selected in vitro from four representative strains. Mutants were sequenced for rrl, erm(41), whiB, rpIV, and rplD and studied for seven antibiotic MICs. For mutants obtained from strain M. abscessus subsp. abscessus erm(41) T28 sequevar and strain M. abscessus subsp. bolletii, which are both known to produce effective methylase, rrl was mutated in only 19% (4/21) and 32.5% (13/40) of mutants, respectively, at position 2058 (A2058C, A2058G) or position 2059 (A2059C, A2059G). No mutations were observed in any of the other genes studied, and resistance to other antibiotics (amikacin, cefoxitin, imipenem, tigecycline, linezolid, and ciprofloxacin) was mainly unchanged. For M. abscessus subsp. abscessus erm(41) C28 sequevar and M. abscessus subsp. massiliense, not producing effective methylase, 100% (26/26) and 97.5% (39/40) of mutants had rrl mutations at position 2058 (A2058C, A2058G, A2058T) or position 2059 (A2059C, A2059G). The remaining M. abscessus subsp. massiliense mutant showed an 18-bp repeat insertion in rpIV, encoding the L22 protein. Our results showed that acquisition of clarithromycin resistance is 100% mediated by structural 50S ribosomal subunit mutations for M. abscessus subsp. abscessus erm(41) C28 and M. abscessus subsp. massiliense, whereas it is less common for M. abscessus subsp. abscessus erm(41) T28 sequevar and M. abscessus subsp. bolletii, where other mechanisms may be responsible for failure.

Cystic Pulmonary Myxoid Liposarcoma Mimicking Endobronchial Blood Clot.

A 71-year-old-man was transferred to our hospital in November 2012 for a bronchial artery embolization in the context of recurrent blood clots obstructing the left lower bronchus. Since June 2012, he had been explored for a cystic hypermetabolic lesion of the entire left lobe, and underwent 3 bronchoscopies and 2 computed tomography scan-guided biopsies, with no success. A fourth bronchoscopy enabled the extraction of a large blood clot (8×1.5 cm) that obstructed the left main bronchus. The pathologic examination of the mucosal biopsy samples was inconclusive, whereas the cytologic examination of the blood clot revealed myxoid liposarcoma. Liposarcomas are the most common histologic types of soft-tissue sarcomas. They preferentially metastasize to the lungs and can appear as cystic mass. Bronchial obstruction by blood clots is not a rare finding on bronchoscopy, their main problem is their removal which could require rigid bronchoscope and large forceps. However, bronchial blood clot containing tumoral process had never been reported before. In conclusion, this case conveys 2 messages. First, pulmonary metastasis of myxoid liposarcoma can appear as cyst secondary to endobronchial tumoral growth. Second, endobronchial blood clots should always be sent for pathologic analysis.

Interstitial Lung Disease in Werner Syndrome: A Case Report of a 55-Year-Old Male Patient.

Werner syndrome (WS) is a progeroid or premature aging syndrome characterized by early onset of age-related pathologies and cancer. The average life expectancy of affected people is 52.8 years and tends to increase. The major causes of death are malignancy and myocardial infarction. Increased telomere attrition and decay are thought to play a causative role in the clinical and pathological manifestations of the disease. Although telomere length, with or without germline mutation, is known to be associated with interstitial lung disease, the latter is not associated with WS. To the best of our knowledge, we report the first case describing a WS patient with fatal ILD. This case suggests that older patients with WS could develop ILD. Clinical outcome of WS patients may thus be improved by counselling them regarding smoking cessation or other exposure and by proposing antifibrotic therapy.

Out-of-hospital follow-up after low risk breast cancer within a care network: 14-year results.

The delegation of low-risk breast cancer patients' follow-up to non-hospital practitionners (NHP), including gynaecologists and general practitioners, has been assessed prospectively within a care network in the Paris region. Patients with early stage breast cancer were eligible. The follow-up protocol was built according to international guidelines. By 2012, 289 NHPs were following 2266 patients treated in 11 centres. Median follow-up time was 7.4 years. The mean intervals between two consecutive consultations were 9.5 [9.2-9.8] months for women supposed to be monitored every 6 months and 12.5 [12.2-12.8] for those requiring annual monitoring. The relapse rate was 3.2% [2.1-4.3] at 5 years and 7.8% [5.9-9.7] at 10 years. Seventy one percent of relapses were diagnosed on a scheduled assessment. Only 6% were lost-to-follow-up. Delegating follow-up after low risk breast cancer to NHPs in a care network is feasible, well accepted and provides an alternative to follow-up in specialized centres.

Induction chemotherapy before sleeve lobectomy for lung cancer: immediate and long-term results.

BACKGROUND: Induction chemotherapy does not increase the morbidity and mortality rates of bronchoplastic procedures, but the long-term efficiency remains unclear. The purpose of this retrospective study was to analyze the impact of chemotherapy on resectability and long-term survival. METHODS: From 1984 to 2005, 159 consecutive patients with non-small cell lung cancer underwent sleeve lobectomy without (n = 117) or with induction chemotherapy (n = 42). Indications for chemotherapy were N2 lymph node involvement (n = 15), T3 or T4 tumor invasion with doubtful resectability (n = 13), need for tumor size reduction (n = 8), lung function precluding pneumonectomy (n = 4), and brain metastasis (n = 2). None of the patients received induction radiation therapy. We studied tumor characteristics and immediate and long-term results in both groups. RESULTS: Clinical stage III was predominant in the induction chemotherapy group whereas stage II was predominant in the surgery-only group. Complication rates in the induction chemotherapy group and in the surgery-only group were 23.8% and 24.7%, respectively. We observed a greater rate of 1-month-delay smoking cessation before surgery in the induction chemotherapy group (40% versus 22%). The 5-year survival rates were 65.4% in the surgery-only group and 73.4% in the induction chemotherapy group (p = 0.5). The tumor size in the induction chemotherapy group was lower (17.5 versus 30.6 mm; p = 0.01), which reflected the positive impact of chemotherapy on sleeve resection feasibility. CONCLUSIONS: Induction chemotherapy before sleeve lobectomy achieves good long-term results. Tumor reduction and limited resection feasibility seemed to be increased, which justify further prospective trials.

Bronchial sleeve resections: lung function resurrecting procedure.

OBJECTIVE: Mainstem bronchus obstruction results in lung function exclusion. The aim of this study was to revisit lung function restoration obtained by different types of bronchial sleeve resections in selected patients with endobronchial tumors. METHODS: Eleven patients (9 women and 2 men, mean age 47 years) presented with endobronchial tumors and ipsilateral lung function exclusion. Mainstem bronchial sleeve resection was performed in 7 patients, right bilobar and mainstem bronchial sleeve resection in 2, and left upper sleeve lobectomy in 2. Tumors consisted in 8 bronchial carcinoids, 2 adenoid cystic carcinomas, and one inflammatory myofibroblastic tumor. Fiberoptic bronchoscopy and quantitative ventilation-perfusion lung scan were performed in all patients at work-up to assess lung function exclusion and during the first year following bronchoplastic procedure to study recovery. Long-term follow-up consisted of physical examination, thoracic computed tomographic scan and bronchoscopy every year. RESULTS: There was no postoperative death. The long-term follow-up was complete and ranged from 12 to 192 months (median: 102.7 months). The lung function was completely restored in all patients. The ventilation function was immediate, but the perfusion was restored in a mean interval of 8.2 months (ranging from 3 to 12 months). All patients are currently alive, and no local tumor recurrence was observed. CONCLUSIONS: Some obstructing tumors may be removed by various types of bronchial sleeve resections that permit lung function restoration and long-term local control of the disease. However, at least one year is required for lung perfusion to completely recover, despite immediate ventilation restoration.