Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.

BACKGROUND: Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours. PATIENTS AND METHODS: We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies. RESULTS: Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4. CONCLUSIONS: Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.

[Surgical treatment of chronic thromboembolic pulmonary hypertension]. / Traitement chirurgical de la maladie thromboembolique pulmonaire chronique.

Chronic thromboembolic pulmonary hypertension is a condition that has long remained in the shadows, a kind of orphan disease, because of the lack of any curative treatment. The renewal of interest by pulmonary specialists, cardiologists and thoracic surgeon is due to the development over the past 20 years of major new treatments: lung transplantation, continuous prostacyclin infusion, and pulmonary endarterectomy, in chronological order. Most patients with postembolic pulmonary arterial hypertension (PEPAH) in a sufficiently proximal location can benefit from curative surgical treatment by bilateral endarterectomy of the pulmonary arteries. This complex surgery, performed under deep hypothermic circulatory arrest, clears out the pulmonary vascular bed down through its subsegmental branches and results in a frank reduction in pulmonary vascular resistance and normalization of cardiopulmonary function. It is a curative procedure with a perioperative mortality rate less than 7% and a definitive result, unlike pulmonary and cardiopulmonary transplantation, which have a postoperative mortality rate of 20% and a 5-year survival rate of 50%. It is difficult to recognize the postembolic nature of pulmonary hypertension because there is no known history of venous thrombosis or embolic phenomena in more than 50% of cases. Diagnosis is based on the presence of mismatched segmental defects in the radioisotopic ventilation-perfusion scanning. To be accessible to endarterectomy, lesions must involve the main, lobar, or segmental arteries. When conducted by experienced operators according to specific protocols, pulmonary (frontal and lateral views of each lung) and multislice CT angiography optimize assessment of the lesion site. When the pulmonary vascular resistance evaluated by catheterization is correlated with the anatomical obstruction visible on the images, pulmonary endarterectomy has a mortality rate below 4% and offers the patient a substantial chance to regain normal cardiorespiratory function. In cases of pulmonary arterial hypertension due to older embolisms, major arteriolitis occurs in the nonobstructed areas and aggravates the pulmonary hypertension, which may become suprasystemic. The endarterectomy mortality rate is then higher, and in specific cases justifies preoperative medical treatment. Pulmonary or cardiopulmonary transplantation is indicated in this disease only when the lesions are too distal and thus inaccessible to endarterectomy.

[Surgical treatment of post-embolism pulmonary hypertension]. / Traitement chirurgical de l'hypertension artérielle pulmonaire post-embolique.

Pulmonary hypertension is a serous condition which, after a long history as an orphan disease, has raised renewed interest due to the development of efficacious therapeutic options including lung transplantation and continuous infusion of prostacycline. Bilateral endarteriectomy of the pulmonary arteries is another possibility for post-embolism pulmonary hypertension. The procedure is complex and must be performed in conditions of cardiac arrest and deep hypothermia but, unlike transplantation, provides definitive cure. Recognizing the post-embolic nature of pulmonary hypertension is not simple because old episodes of venous thrombosis or embolus migration are not found in 50% of patients. Segmentary defects on the perfusion scintigraphy contrasting with the homogeneous respiratory scintigraphy is the primary diagnostic feature. Lesions must be located in a main trunk or at the origin of lobular or segmentary branches to be accessible to endarteriectomy. An antero-posterior and lateral angiogram of each lung and a multiple-array helicoidal angioscan performed with a precise protocol by an experienced team are needed to identify the localization of the lesions. If the pulmonary resistance determined at right catheterism is correlated with anatomic obstruction, the risk of mortality of pulmonary endarteriectomy is low, offering patients a significant chance for normal or nearly normal cardiorespiratory function.

[Endobronchial lipomas. Apropos of 16 cases]. / Les lipomes endobronchiques. A propos de 16 observations.

Intrabronchial lipomas are rare and benign tumours. Sixteen cases treated between 1956 and 1988 at the Marie Lannelongue Surgical Centre, Paris, are reviewed. The patients presented with various symptoms such as cough, haemoptysis, infection or dyspnoea. Radiography was abnormal in 15 cases, and the lesion was regularly located at bronchoscopy. Treatment was chiefly surgical. Owing to the slow and silent growth of intrabronchial lipomas, there is a risk of progressive bronchial obstruction resulting in bronchopulmonary lesions. With an early detection, treatment should be as conservative as possible.

Distribution of cells binding anti-IgE in the trachea and in the thoracic lymph nodes of ovalbumin-sensitized rats.

We investigated in the present study the distribution of anti-IgE binding cells in the trachea and in the thoracic lymph nodes of ovalbumin (OA)-sensitized rats. Sensitization of the airways was induced through a single intratracheal injection of the antigen, and was controlled by recording in vitro the antigen-induced contraction of the tracheal muscle: 12 of 15 (80%) OA-injected rats had a demonstrable status of tracheal sensitization. An immunohistochemical method was used for the localization of the anti-IgE binding cells in cryostat and in Carnoy fixed tissue sections. Virtually no cell was found to bind anti-IgE in the tracheas or in the thoracic lymph nodes from control animals. Conversely, we found in OA-sensitized rats that: 1) numerous IgE plasma cells appeared in the medullary cords of the lymph nodes (not in the trachea); 2) in tracheal sections, IgE concentrated in the cytoplasm of subepithelial mast cells and of nonciliated rounded epithelial cells (possibly the so-called globule leukocytes), but few if any mast cells of the connective tissue bound the anti-IgE conjugates.

Subclavian artery resection and reconstruction for thoracic inlet cancers.

PURPOSE: We previously described an original transcervical approach to resect primary or secondary malignant diseases that invade the thoracic inlet (TI). The purpose of this study was to evaluate the technical aspects and long-term results of the resection and revascularization of the subclavian artery (SA). METHODS: Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc resection of TI cancer that had invaded the SA. The surgical approach was an L-shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this approach was associated with a posterolateral thoracotomy (n = 10) or a posterior midline approach (n = 4). In one patient, the procedure was achieved with a single posterolateral thoracotomy approach. An end-to-end anastomosis was performed in 16 patients. In one patient, a subclavian-left common carotid artery transposition was performed. In one other patient, an end-to-end anastomosis was performed between the proximal innominate artery and the SA. The right carotid artery was transposed into the SA in an end-to-side fashion. In 16 patients, prosthetic revascularization with a polytetrafluoroethylene graft was performed. Thirty-three patients underwent postoperative radiation therapy. RESULTS: There were no cases of perioperative death, neurologic sequelae, graft infections or occlusions, or limb ischemia. There were two delayed asymptomatic polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5 local and systemic and 13 systemic), one of respiratory failure, and one of an unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5-year disease-free survival rate was 18%. CONCLUSION: Tumor arterial invasion per se should not be a contraindication to TI cancer resection. This study shows that cancers that invade the SA can be resected through an L-shaped transclavicular cervicotomy, with good results with a concomitant revascularization of the SA.

[Pulmonary thromboendarterectomy with video-angioscopy and circulatory arrest: an alternative to cardiopulmonary transplantation and post-embolism pulmonary artery hypertension]. / Thrombo-endartériectomie pulmonaire sous vidéo-angioscopie et arrêt circulatoire: une alternative à la transplantation cardiopulmonaire dans l'hypertension artérielle pulmonaire postembolique.

The best predictor of poor or suboptimum outcome from pulmonary thromboendarterectomy (PTE) is insufficient relief of obstruction, especially in the lower lobes. The aim of this study is to emphasize that the use of video-assisted angioscopy may increase the quality of PTE and thus improve outcome. PTE included a median sternotomy, intrapericardial dissection limited to the superior vena cava, institution of cardiopulmonary bypass, deep hypothermia and sequential circulatory arrest periods. PTE was always bilateral and performed through two separate arteriotomies of both main intrapericardial pulmonary arteries. A rigid 5 mm angioscope connected to a video camera was introduced through the arteriotomy into the lumen to increase the visibility and perform the video-assisted endarterectomies of all obstructed segmental branches, including normally inaccessible anterior segmental branches. Between January 1996 and December 1997, 48 patients with severe postembolic pulmonary hypertension had PTE. Patients were in New York Heart Association (NYHA) class II (n = 2), III (n = 28) or IV (n = 18) with the following hemodynamics: mean pulmonary arterial pressure (PAP) 53 +/- 13 mmHg, cardiac index 2.16 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 1,152 +/- 414 dyne.s-1.cm-5. Six patients died from alveolar hemorrhage (n = 1), high residual pulmonary pressure and rethrombosis (n = 4) and hypoxic cardiac arrest (n = 1). The functional outcome in surviving patients was as follows: (NYHA) class I (n = 24), II (n = 16) or III (n = 2) with improved hemodynamics: mean pulmonary arterial pressure: 30 +/- 9 mmHg, cardiac index: 2.78 +/- 0.5 L/min/m2, pulmonary vascular resistances (PVR): 484 +/- 159 dynes.s-1.cm-5. Video-assisted angioscopy allows much improved quality and degree of pulmonary endarterectomy. This expands the indications to include patients with previously inaccessible distal disease and candidates for heart-lung transplantation.