Biomedical subjects
P Y Brichon
Publications and source records attributed to P Y Brichon.
Comorbidities and Charlson score in resected stage I nonsmall cell lung cancer.
Patients with nonsmall cell lung cancer (NSCLC) have been shown to have a higher prevalence of comorbidity associated with age and tobacco consumption. The objective of the present study was to determine the impact of comorbidity on survival after surgery of stage I NSCLC. In total, 588 consecutive patients operated on for a pathological stage I NSCLC between January 1, 1979 and December 31, 2003 were studied. Comorbidities were analysed individually. Overall comorbidity was assessed using the Charlson index of comorbidity (CCI). Survival data were collected for each patient from the date of operation, with a median duration of follow-up of 104 months. Survival analyses and Cox proportional hazards model analyses were used. The mean age of patients was 62.7 yrs, and 529 (89%) patients were male. The distribution of overall comorbidity severity was as follows. CCI grade 0: 47.1%; grade 1-2: 43.7%; grade 3-4: 8.3%; and grade > or =5: 0.8%. The 2, 3 and 5 yrs survival were 69, 62 and 50%, respectively. Multivariable analysis showed that T stage, age, a concomitant history of moderate-to-severe liver disease, a past history of cured cancer, cerebrovascular disease and CCI were independent predictors of survival (Hazard Ratio for CCI grade >2: 1.81; 95% confidence interval 1.25-2.63). In conclusion, comorbidity has a significant impact on survival after surgical resection of patients with stage I nonsmall cell lung cancer. The use of a validated index of comorbidity in prognostic analyses of resected nonsmall cell lung cancer is recommended.
Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours.
Human telomerase reverse transcriptase is a ribonucleoprotein that synthesises telomeric sequences, which decrease at each cell division. In cancer cells, its activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. To evaluate the prognostic value of the catalytic subunit telomerase reverse transcriptase (hTERT), we analysed its expression by immunohistochemistry in 122 formalin-fixed lung tumours including 42 squamous cell carcinoma (SCC), 43 adenocarcinoma (ADC), 19 basaloid carcinoma (BC) and 18 small-cell lung carcinoma (SCLC) in comparison with detection of hTERT mRNA by in situ hybridisation and relative telomerase activity by TRAP assay in a subset of tumours. We observed a high concordance between hTERT protein expression and detection of hTERT mRNA and telomerase activity. Telomerase expression varied according to histology (P=0.0002) being significantly lower in ADC than in SCC, BC and SCLC (P<0.0001). Adenocarcinoma and SCC exhibited either a nuclear or a nucleolar staining in contrast with a diffuse nuclear staining observed in most BC and all SCLC (P=0.01). In stage I NSCLC telomerase expression was lower than in other stages (P=0.04), and a nucleolar staining was correlated with a short survival (P=0.03). We concluded that telomerase expression and pattern are distinctive among histopathological classes of lung cancer and convey prognostic influence.
[Bronchopleural fistula after radiation therapy for a lung cancer].
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[Bronchial carcinoid tumors: role of imaging for diagnosis and local staging].
PURPOSE: To describe the imaging features of bronchial carcinoids and to define the role of CT as a diagnostic and pretherapeutic tool. MATERIALS AND METHODS: We performed a retrospective study including 54 carcinoids. We evaluated and compared the clinical, radiographic, CT, fiberoptic, and pathologic data. RESULTS: At presentation, the mean age was 48.5 years (14-81) and patients mainly complained of signs related to bronchial obstruction (55.7%). 72% of bronchial carcinoids were located in the proximal airway. CT showed calcifications in 26% of 54 cases and contrast enhancement in 60%. Typical carcinoids differed from atypical carcinoids in their size and lymph node extension. As compared to fiberoptic bronchoscopy, CT identified proximal carcinoids with exo-bronchial extension (7.4%), peripheral tumors (20.4%), and parenchymal complications. The sensitivity and predictive positive-value of CT for lymph node extension was 28% and 20%, respectively. CONCLUSION: CT is a useful technique for diagnosing and localizing bronchial carcinoids. The results of CT in determining lymph node extension is disappointing, and should raise caution in case of localized treatment using fiberoptic bronchoscopy.
Adenocarcinoma of the lung mimicking inflammatory lung disease with honeycombing.
Pulmonary adenocarcinoma of the lung and its variants are well-defined entities, since the recent WHO classification of lung tumours. However, scant descriptions have been allocated to associated stromal changes, such as prominent inflammation and fibrosis, which can overshadow a tumoral proliferation and masquerade as a benign reactive process and this has not been recognised as a histopathological variant. The case of a 72-yr-old farmer who presented a multifocal well-differentiated adenocarcinoma that mimicked honeycomb lung with bronchiolectasis radiologically, on computed tomography scan and histologically at open lung biopsy, is reported. Histological pitfalls in the biopsy were represented by mild atypical cuboidal or columnar epithelial cells lining bronchiolar structures resembling florid bronchiolar metaplasia in a background of extensive fibrosis and inflammation, features that mimicked inflammatory honeycombing. However, histological analysis of the surgical resection of the main lesion, performed because of a clinical alteration of the patient, confirmed the diagnosis of multifocal adenocarcinoma of mixed subtype. A monomorphic proliferation of clear cells, lack of associated ciliated or squamous cells and presence of significant cytologic atypia gave a diagnosis of malignancy. This case illustrates how inflammatory and fibrotic changes may conceal a correct diagnosis of carcinoma and emphasises the importance of adequate sampling in such cases.
Placental transmogrification of the lung: CT-pathologic correlation of a rare pulmonary nodule.
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Early detection of lung cancer: role of biomarkers.
Early detection of lung cancer requires none or few invasive techniques. Distal lung cancer (40% of the cases in most European countries) can be sensitively detected by spiral computed tomography. Theoretically, in 60% of cases, the proximal lesions (main to segmental bronchi, accessible by bronchoscopy) should be able to be detected by sputum cytology. Unfortunately, this very specific technique has a low sensitivity and is time consuming. Fluorescent bronchoscopy increases the detection rate of early or micro-invasive lesions and may be proposed in highly selected populations, but not as a screening test. Biomarkers in blood and sputum have not yet been clinically validated. However, the amount of data generated from studies first on resected tumours, then on early bronchial lesions and more recently on blood and sputum offer a wide field for investigation. Lung carcinogenesis is a multistep process characterised by the accumulation of successive molecular genetic and epigenetic abnormalities, resulting in selection of clonal cells with uncontrolled growth capacities throughout the whole respiratory tract (field cancerisation). Molecular lesions far precede morphological transformation of preneoplastic bronchial lesions (dysplasia) or alveolar lesions (atypical alveolar hyperplasia). Genetic and epigenetic abnormalities in the genes involved in cell cycle, senescence, apoptosis, repair, differentiation and cell migration control may be detected on bronchial biopsies, on respiratory cells from the sputum and even in the circulating deoxyribonucleic acid (DNA). The key genes involved include those in the P53-retinoblastoma (Rb) pathways. The balance between cyclin-dependent kinases and their inhibitors regulates the level of Rb phosphorylation and its function at G1-S transition; P53 plays at least two functions (cell cycle and apoptosis control). The balance of bax-bcl2 is important in the control of apoptosis as well as loss of fragile histidine triad expression. O(6)-methylguanine-DNA methyltransferase seems to be important in DNA repair control, the RARbeta receptor in differentiation, and cadherin H and E and different metalloproteases genes in cell migration. The demonstration of hyperexpression or silencing of these genes needs different validated techniques: immunohistochemistry on biopsies or cytological preparations, molecular biology techniques for mutations, loss of heterozygosity and aberrant methylation abnormalities. Automation and miniaturisation of these techniques will allow early detection and may be widely applied once clinically validated.
[Intrathoracic myeloid metaplasia revealing a primitive myelofibrosis].
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Patterns of relapse of N2 nonsmall-cell lung carcinoma patients treated with preoperative chemotherapy: should prophylactic cranial irradiation be reconsidered?
BACKGROUND: Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall-cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients. METHODS: In this study, the authors compared the patterns of relapse in 81 patients with clinically detectable N2 NSCLC who had been treated with preoperative chemotherapy with the relapse patterns of 186 comparable patients who had been treated with primary surgery. Clinically detectable N2 (cN2) denotes mediastinal lymph node enlargement on computed tomography scan, which then is confirmed by mediastinoscopy. RESULTS: Overall 20% of patients developed a locoregional recurrence. Chemotherapy decreased the risk of visceral metastasis as 28% of the patients preoperatively treated and 38%of those not treated with preoperative chemotherapy presented a visceral metastasis (P < 0.05). Preoperative chemotherapy and adenocarcinoma subtypes were associated with a higher rate of brain metastasis (P < 0.05). Thirty-two percent of the patients treated preoperatively and 18% of those not treated with preoperative chemotherapy presented a brain metastasis (P < 0.05), which was isolated in 22% and 11% of the patients, respectively (P < 0.05). CONCLUSION: The current study found that preoperative chemotherapy for cN2 decreases the risk of visceral metastasis but is associated with a high rate of isolated brain metastases. Prophylactic cranial irradiation may need to be reinvestigated in clinical trials, especially in patients who present with an adenocarcinoma.
[Parathyroid cyst].
The aim of this study was to report two cases of symptomatic and non-functional parathyroid cyst, diagnosed with ultrasonography and percutaneous punction and treated by surgical resection of the cystic gland.
Chylothorax complicating Gorham's disease.
Gorham's disease is a rare disorder characterized by a proliferation of thin-walled lymphatic vessels (lymphangiectasia) resulting in an osteolysis. A chylothorax is present in about one-fifth of the patients and carries a poor prognosis. In this circumstance, surgery including thoracic duct ligation, pleurodesis, and excision of involved tissue is probably the treatment of choice. It is facilitated by a precise radiological assessment using a computed tomographic scanning coupled with a lymphography. We report such a case.
Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung.
Basaloid carcinoma (BC) and large-cell neuroendocrine carcinoma (LCNEC) are 2 recently recognized variants of large-cell lung carcinomas that may overlap in their morphology, and are discriminated by expression of neuroendocrine markers in LCNEC. Because thyroid transcription factor 1 (TTF-1) is expressed in lung adenocarcinomas but not in squamous cell carcinomas (SCC), and 34betaE12 recognizes a set of high-molecular-weight cytokeratins characteristic of basal stem cells, we hypothesized that these 2 markers could help in distinguishing BC from LCNEC. Immunostaining for TTF-1 was detected in 40.9% of pure LCNEC but in no BC or basaloid variant of SCC. In contrast, immunoreactivity for 34betaE12 was shown in all BC and basaloid variant of SCC but in only 1 LCNEC. Bouin fixation was less efficient than formalin in the immunodetection of both markers for its well-known deleterious effect on antigen preservation. Specificity of TTF-1 for LCNEC (100%) and that of 34betaE12 for BC (98.3%) exceeded that of NE markers for distinction of these 2 entities. These data show that TTF-1 and 34betaE12, in association with specific neuroendocrine markers, represent a useful panel of antibodies in differentiating carcinomas presenting with a solid pattern, palisading, or pseudorosettes, the expression of TTF-1 excluding the diagnosis of BC, and staining with 34betaE12 excluding pure LCNEC.
Surgical management of non-small cell lung cancer with synchronous brain metastases.
OBJECTIVES: Published series on the synchronous combined resection of brain metastases and primary non-small cell lung cancer are small and scarce. We therefore undertook a multicenter retrospective study to determine long-term survival and identify potential prognostic factors. DESIGN: Our series includes 103 patients who were operated on between 1985 and 1998 for the following tumors: adenocarcinomas (74); squamous cell carcinomas (20); and large cell carcinomas (9). Three patients had two brain metastases, and one patient had three metastases; the remaining patients had a single metastasis. Ninety-three patients presented with neurologic signs that regressed completely after resection in 60 patients and partially, in 26 patients. Neurosurgical resection was incomplete in six patients. Seventy-five patients received postoperative brain radiotherapy. The time interval between the brain operation and the lung resection was < 4 months. Pulmonary resection was incomplete in eight patients. RESULTS: The survival calculated from the date of the first operation was 56% at 1 year, 28% at 2 years, and 11% at 5 years. Univariate analysis showed a better prognosis for adenocarcinomas (p = 0.019) and a trend toward a better prognosis for patients with small pulmonary tumors (T1 vs T3, p = 0.068), N0 stage disease (N0 vs N+, p = 0.069), and complete pulmonary resection (p = 0.057). In a multivariate analysis, adenocarcinoma histology also affected the survival rate (p = 0.03). CONCLUSIONS: It seems legitimate to proceed with lung resection after complete resection of a single brain metastasis, at least in patients with an adenocarcinoma and a small lung tumor and without abnormal mediastinal lymph nodes seen on the CT scan or during mediastinoscopy.
Chest wall implantation of a mediastinal liposarcoma after thoracoscopy.
We report a case of mediastinal liposarcoma resected by thoracoscopy. Despite the precautionary measures, chest wall implantations occurred rapidly at the port's sites in the chest wall and led to death within 24 months. We conclude that thoracoscopy is not a good approach for resection of anterior mediastinal masses in view of their possible malignant character.
Prevalence and consequences of nutritional depletion in lung transplant candidates.
Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT. Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW). Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall, 72% were depleted corresponding to groups 1, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group II. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III. To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant.
Resection of lung cancer invading the diaphragm.
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Bilateral oblique approach to parathyroid glands.
OBJECTIVE: To propose a simple and minimally invasive approach for parathyroid surgery. SUMMARY BACKGROUND DATA: Minimally invasive approaches to the parathyroid glands may involve preoperative morphologic explorations, perioperative biologic controls, or videocervicoscopy, a new method. METHODS: The authors describe 597 patients who underwent parathyroidectomy through an original bilateral oblique approach between 1976 and 1997. None underwent morphologic exploration or biologic perioperative monitoring. In primary hyperparathyroidism, the four glands are controlled and it is possible to check their abnormalities of location or number. In secondary hyperparathyroidism and multiple endocrine neoplasia (MEN), a total or subtotal parathyroidectomy is performed. RESULTS: The results and vocal morbidity are the same as that from authors using transverse cervicotomy, but this approach is more comfortable for the patient and allows total exploration of the location through short incisions without bleeding, visceral contusions, or muscle lesion. CONCLUSIONS: This cervicotomy is easy and secure even if the surgeon is not trained in this approach because it uses and respects the anatomy of the cervical fasciae. It can be used without preoperative localization, intraoperative monitoring, or specialized material. But this approach could be also proposed for unilateral exploration guided by these methods and for surgical treatment of recurrent hyperparathyroidism after a transverse cervicotomy.