Jean-Marie Wihlm

MET Gene Copy Number in Non-small Cell Lung Cancer: Molecular Analysis in a Targeted Tyrosine Kinase Inhibitor Naïve Cohort

Introduction: Recent clinical success of epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) have raised hopes that targeting other deregulated growth factor signaling, such as the hepatocyte growth factor/MET pathway, will lead to new therapeutic options for NSCLC. Furthermore, NSCLC present secondary EGFR-TKIs resistance related to exons 20 and 19 EGFR mutations or more recently to MET amplification. The aim of this study was to determine MET copy number related to EGFR copy number and K-Ras mutations in a targeted TKI naive NSCLC cohort. Methods: We investigated 106 frozen tumors from surgically resected NSCLC patients. Genes copy number of MET and EGFR were assessed by quantitative relative real-time polymerase chain reaction and K-Ras mutations by sequencing. Results: MET is amplified in 22 cases (21%) and deleted in nine cases (8.5%). EGFR is amplified in 31 cases (29%). K-Ras is mutated in 11 cases (10.5%). As observed for EGFR amplification, MET amplification is never associated with K-Ras mutation. MET amplification could be associated with EGFR amplification. MET amplification is not related to clinical and pathologic features. MET amplification and EGFR amplification showed a trend toward poor prognosis in adenocarcinomas. Conclusion: In EGFR-TKIs naive NSCLC patients, MET amplification is a frequent event, which could be associated with EGFR amplification, but not with K-Ras mutation. MET amplification may identify a subset of NSCLC for new targeted therapy. It will also be important to evaluate MET copy number to properly interpret future clinical trials.

Tracheobronchial lacerations after intubation and tracheostomy

BACKGROUND Although long-term complications of intubation and tracheostomy are well documented, little has been reported on acute complications of airway access techniques. METHODS Fourteen patients (1 male and 13 female patients) aged 15 to 80 years presented with tracheobronchial lacerations after single-lumen intubation (n = 9), double-lumen intubation (n = 1), or tracheostomy (n = 4). RESULTS A left bronchial laceration after double-lumen intubation was discovered and repaired intraoperatively. A tracheal laceration after single-lumen intubation was recognized during induction of anesthesia. The remaining 12 were diagnosed within 6 to 126 hours (median, 24 hours) after injury. All patients had mediastinal and subcutaneous emphysema. At endoscopy, 12 injuries were located in the thoracic trachea and 1 in the cervical trachea. Twelve underwent primary repair through a right thoracotomy (n = 11) or left cervicotomy (n = 1), and 1 was treated conservatively. Two patients with tracheostomy injury died postoperatively. All repairs healed well but one. The latter was performed 5 days after the injury; a dehiscence occurred, but healed spontaneously. CONCLUSIONS We conclude that prognosis of tracheal lacerations depends both on the general health of the patient and on the rapidity of diagnosis and treatment.

Pleuropulmonary aspergilloma: Clinical spectrum and results of surgical treatment

From 1974 to 1991, 77 patients were admitted for pulmonary (55), pleural (16), or bronchial (6) aspergilloma. About 50% were asymptomatic. Sixty-three underwent operation. Pulmonary aspergillomas were operated on for therapeutic need in 26 and on principle in 18; the procedures were 28 lobar or segmental resections, 10 thoracoplasties, and 5 pleuropneumonectomies (1 patient had exploration only). Pleural aspergillosis was treated by operation on principle in 5 and for therapeutic need in 8 patients; 10 thoracoplasties, 1 attempt at pleuropneumonectomy, and 2 decortications were performed. All six bronchial lesions were operated on as a rule. Overall postoperative mortality was 9.5%. Major complications were bleeding (n = 37), pleural space problems (n = 24), respiratory failure (n = 6), and postpneumonectomy empyema (n = 4). All patients with pleural disease experienced complications. The outcome was better after lobar or segmental resection than after thoracoplasty (mortality, 6% versus 15%). Asymptomatic and nonsequellary pulmonary or bronchial aspergilloma also had an improved outcome. We conclude that operation is at low risk in pulmonary or bronchial locations in asymptomatic patients and in the absence of sequellae; the risk is high in symptomatic patients for whom operation is the only definite treatment. Pleuropneumonectomy should be avoided. Only symptomatic pleural aspergilloma should be operated on.

Minimally invasive management for first and recurrent pneumothorax

Minimally invasive techniques for treatment of pneumothorax should yield the standard of results set with open procedures: the operative morbidity should remain less than 15%, and the recurrence rate less than 1%. In the era before video-assisted thoracic surgery, two minimally invasive variants were used. Chemical pleurodesis resulted in an unsatisfactory recurrence rate of at least 15%. In contrast, pleurectomy and apical stapling performed through a transaxillary minithoracotomy compared favorably with larger thoracotomy approaches, and allowed a reduced hospital stay. Evaluation of video-assisted thoracic surgical operations for spontaneous pneumothorax is hampered by a lack of controlled studies. The general impression is that morbidity did not decline significantly; the main determinant of complications is the patients underlying health status. However, published recurrence rates range from 5% to 10%, in spite of a shorter follow-up time span. Optimized results are achieved when classic principles combining apical wedge resection and pleurodesis are applied. Reduction of hospital stay is not only a result of the new technology, but also changing drainage and discharge policies. Reduction of cost is debatable, because many studies do not consider the cost of video equipment. The main advantage when compared with open thoracotomy is reduction of postoperative pain. The only two available controlled studies conclude that there is no obvious advantage of video-assisted thoracic surgery when compared with conventional limited-access surgery. The future role of video-assisted thoracic surgery in this disease remains to be determined by a large-scale prospective evaluation.

Primary Malignant Melanoma of the Esophagus

Primary malignant melanoma of the esophagus is rare, and its symptoms are similar to those of squamous cell carcinoma. This tumor tends to be polypoid, pediculated, and irregular. Hematogenic and lymphogenic metastases are common. Surgical resection with reestablished continuity of the gastrointestinal tract is the treatment of choice, and postoperative irradiation may be useful. Despite these measures, however, the prognosis is poor, with a 5-year survival of 4.2%. The case of a 47-year-old man with esophageal melanoma is described, and a review of the world literature is presented.

Operative Risk and Prognostic Factors of Typical Bronchial Carcinoid Tumors

BACKGROUND This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.

Blood vessel invasion is a major prognostic factor in resected non-small cell lung cancer

BACKGROUND We examined the prognostic value of histologic indices in non-small cell lung cancer with particular interest in major blood vessel invasion. METHODS We studied 593 patients who had curative resection between November 1983 and December 1988. We determined the histology, T and N status, peritumoral lung tissue invasion, tumor stroma, necrosis, mitotic rate, and blood vessel invasion. RESULTS The median patient survival of the whole series was 3.2 years, with a 5-year survival of 38.9%. In univariate analysis, a high T stage, a high percentage of necrosis, blood vessel invasion, and N stage significantly worsened the survival. In multivariate analysis, only blood vessel invasion and, less significantly, T stage and lymph node metastasis remained independent prognostic factors. CONCLUSIONS These results highlight the negative prognostic value of blood vessel invasion in non-small cell lung cancer and suggest that blood vessel invasion, T stage, and node metastasis are three unrelated and distinctive characteristics of resected non-small cell lung cancer.

Pneumonectomy for chronic infection is a high-risk procedure.

BACKGROUND The purpose of this study was to estimate operative risk, and to identify indicators of adverse prognosis, in patients undergoing pneumonectomy for chronic infection. METHODS Twenty-five patients aged 41 +/- 15 years underwent pneumonectomy (three completions) for chronic infection: sequelae of tuberculosis, 15; cystic bronchiectasis, 9; and radiation pneumonitis, 1. Eight patients had aspergilloma (7 after tuberculosis, 1 with radiation pneumonitis). RESULTS Operative mortality was 4%. Operative blood loss was estimated at 1,983 +/- 1,424 mL, ranging from 150 to 5,600 mL. A single patient required reexploration. Eight patients (32%) had empyema, and a further 3 (12%) had bronchopleural fistula; thoracoplasty was required for 10 (40%). Sequelae of tuberculosis heralded increased operative bleeding (t = 2.884; p < 0.005). Incidence of empyema or bronchopleural fistula was increased in patients with sequelae of tuberculosis (chi 2 = 3.896; p < 0.05), patients with aspergilloma (chi 2 = 4.588; p < 0.05), patients in whom the parenchymal cavities were entered (chi 2 = 11.5; p < 0.001), and those in whom blood loss was in excess of 1,000 mL (chi 2 = 4.911; p < 0.05). CONCLUSIONS We conclude that pneumonectomy is a high-risk procedure, especially in patients with sequelae of tuberculosis.

Pectus excavatum: history, hypotheses and treatment options

Pectus excavatum and pectus carinatum represent the most frequent chest wall deformations. However, the pathogenesis is still poorly understood and research results remain inconsistent. To focus on the recent state of knowledge, we summarize and critically discuss the pathological concepts based on the history of these entities, beginning with the first description in the sixteenth century. Based on the early clinical descriptions, we review and discuss the different pathogenetic hypotheses. To open new perspectives for the potential pathomechanisms, the embryonic and foetal development of the ribs and the sternum is highlighted following the understanding that the origin of these deformities is given by the disruption in the maturation of the parasternal region. In the second, different therapeutical techniques are highlighted and based on the pathogenetic hypotheses and the embryological knowledge potential new biomaterial-based perspectives with interesting insights for tissue engineering-based treatment options are presented.

Respiratory complications after surgical treatment of esophageal cancer. A study of 309 patients according to the type of resection.

This study analyzes the respiratory complications in a retrospective study of 309 resections for esophageal cancer. We mainly performed two types of resections according to the height of the tumor: the Ivor-Lewis resection for middle thoracic lesions (182 cases), and the Akiyama resection for upper thoracic lesions (127 cases). We compared the respiratory complications occurring after these two procedures. Our overall mortality and morbidity rates were, respectively, 9% and 37%. In our series, the mortality rate was 4 times higher after the Akiyama procedure than after the Ivor-Lewis procedure, and the morbidity was twice as high. Respiratory complications accounted for 64% of the postoperative deaths. The Akiyama procedure yielded more respiratory complications, especially isolated bronchopneumonia and necrosis of the trachea or of the right or left main bronchus. Respiratory complications accounted for 53% of morbidity, mainly recurrent nerve paralysis with false passages and stasis in the transplant. Both are directly related to the surgical act and often result in bronchopneumonia. Rather than the surgical technique or the skill of the surgeon, it seems that local factors, such as the position of the tumor on the esophagus, increased the incidence of recurrent nerve paralysis following the Akiyama procedure. However, the rate of respiratory complications remained high after the Ivor-Lewis procedure. Patient history, which sometimes included a previous ENT cancer, must be taken into account, as well as the gravity of the operation and the duration of the intubation. Frequent false passages and reflux must be fought by intensive physiotherapy and, when necessary, by early tracheotomy before the patient develops postoperative acute respiratory distress syndrome.