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p57 immunostaining is performed on hydropic products of conception to diagnose hydatidiform moles (HMs), which can progress to gestational trophoblastic neoplasia. Partial hydatidiform mole (PHM) and hydropic abortion (HA) display positive staining in stromal and cytotrophoblastic cells, whereas complete hydatidiform mole (CHM) is characterized by loss of p57 expression in both cell types. In some cases, an aberrant pattern is observed, called discordant p57 expression, with positive cytotrophoblast staining and negative stromal staining, or vice versa. The aim of this study was to describe the clinical, biological, and pathological characteristics of p57-discordant villi (p57DV) and other associated populations in cases of divergent p57 expression and to compare the evolutions of p57DV-associated and classic CHMs. Seventy cases of p57DV diagnosed by referent pathologists were divided into two groups, G1: p57DV ± non-CHM component (n = 22) and G2: p57DV + CHM component (n = 48). p57DV morphology was similar in the two groups. Observation of more than two populations and hybrid villi on p57 immunostaining were significantly more frequent in G2. The clinical, ultrasound, and biological presentations of p57DV-associated and classic CHMs were similar. The initial pathological diagnosis was more frequently incorrect, missing the CHM component, for the p57DV-associated CHMs. Molecular genotyping was informative in seven cases and identified as androgenetic/biparental mosaicism in four cases. These results show that p57DV are a diagnostic challenge for pathologists and that most are associated with a CHM component. However, the clinical management of p57DV-associated CHMs should be the same as that of classic CHMs.

Bardet-Biedl syndrome (BBS) is an emblematic ciliopathy associated with retinal dystrophy, obesity, postaxial polydactyly, learning disabilities, hypogonadism and renal dysfunction. Before birth, enlarged/cystic kidneys as well as polydactyly are the hallmark signs of BBS to consider in absence of familial history. However, these findings are not specific to BBS, raising the problem of differential diagnoses and prognosis. Molecular diagnosis during pregnancies remains a timely challenge for this heterogeneous disease (22 known genes). We report here the largest cohort of BBS fetuses to better characterize the antenatal presentation. Prenatal ultrasound (US) and/or autopsy data from 74 fetuses with putative BBS diagnosis were collected out of which molecular diagnosis was established in 51 cases, mainly in BBS genes (45 cases) following the classical gene distribution, but also in other ciliopathy genes (6 cases). Based on this, an updated diagnostic decision tree is proposed. No genotype/phenotype correlation could be established but postaxial polydactyly (82%) and renal cysts (78%) were the most prevalent symptoms. However, autopsy revealed polydactyly that was missed by prenatal US in 55% of the cases. Polydactyly must be carefully looked for in pregnancies with apparently isolated renal anomalies in fetuses.

Valvular heart disease is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the serotonin system has been associated with valvular heart disease.

Valvular heart disease (VHD) is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the 5-HT system is associated with VHD. Here, we investigated the contribution of 5-HT receptors in a model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens, dexfenfluramine and benfluorex.Nordexfenfluramine was infused chronically (28 days) in mice ((WT and transgenic HtrChronic treatment of mice with nordexfenfluramine activated 5-HTBM-derived endothelial progenitor cells make a crucial contribution to the remodelling of mitral valve tissue. Our data describe a new and important mechanism underlying human VHD.

Context and Objective: Considering the lack of accurate and up-to-date information available about neural tube defects (NTDs) in France, the purpose of this study was to review clinical and epidemiological data of NTDs and to evaluate the current efficiency of prenatal diagnosis in Alsace (northeastern France). Methods: A population-based retrospective study was performed from data of the Registry of Congenital Malformations of Alsace between 1995 and 2009. Data were analyzed as a whole and according to the anatomical type of the malformation (anencephaly, cephalocele and spina bifida). Statistical analyses were carried out using the Statistical Package for the Social Sciences. Results: 272 NTDs were recorded divided in 113 cases of anencephaly (42%), 35 cases of cephalocele (13%) and 124 cases of spina bifida (45%). The total prevalence at birth of 14/10,000 (95% CI 13-16) was stable throughout the reporting period. A chromosome abnormality was identified in 27 cases (12% of all karyotyped cases). NTDs were prenatally diagnosed by ultrasound in 88% of the cases. The mean age upon prenatal diagnosis slightly declined during the 15-year period, significantly for spina bifida only. The global rate of terminations of pregnancy following prenatal diagnosis was 97% (230/238). Conclusion: This work constitutes a unique population-based study providing accurate and specific up-to-date data from a unique center over a longer period (1995-2009). The most important information concerns the high and stable prevalence, which calls into question the efficiency of the primary prevention by folic acid supplementation and the efficiency of prenatal diagnosis.

We report the prenatal diagnosis of a 12q22q23.2 de novo interstitial deletion performed by array based comparative genomic hybridization (array CGH) in a fetus with cystic hygroma colli, intrauterine growth retardation, microcephaly and micrognathism. Haploinsufficiency for insuline-like growth factor 1 gene ( IGF 1), which is mapped in the deleted region, is suggested because of its implication in prenatal and postnatal growth and in neuronal maturation. This case demonstrates the contribution of array CGH in prenatal diagnosis for detecting small unbalanced chromosomal abnormalities in malformed fetuses and, subsequently, for genetic counselling.

Rossi G, Gasser B, Sartori G, Migaldi M, Costantini M, Mengoli M C, Piccioli S, Cavazza A & Rivasi F (2012) Histopathology 60, 1133–1143 MUC5AC, cytokeratin 20 and HER2 expression and K-RAS mutations within mucinogenic growth in congenital pulmonary airway malformations Aims: To analyse the expression of several mucins (MUC1, MUC2, MUC3, MUC5AC and MUC6), epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2 (HER2), thyroid transcription factor-1 (TTF-1), caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20), and the presence of mutations of EGFR, KRAS and HER2 in congenital pulmonary airway malformations (CPAM). Methods and results: Forty-one cases of CPAM and six pulmonary sequestrations were included. TTF-1 expression was observed in all cases but was not seen in mucinogenic growths in CPAM. CDX2 expression was completely negative. MUC1 expression was noted in 12 (29%) CPAM and in 33% sequestrations. MUC5AC was noted in only five cases (26%) by immunohistochemistry and was found in the mucinogenic proliferations of type 1 CPAM. No immunolabelling was noted for the other mucins. EGFR was expressed variably in almost all cases, while HER2 and CK20 was seen exclusively in the mucinogenic proliferations. All mucinous growths were characterized by KRAS mutations. No EGFR and HER2 gene alterations were identified. Conclusions: KRAS mutations and MUC5AC, CK20 and HER2 expression was seen in all mucinogenic proliferations, supporting the neoplastic nature of these cytologically bland growths. These findings emphasize the importance of complete surgical resection of such lesions.

The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year-old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease.

Cobblestone lissencephaly represents a peculiar brain malformation with characteristic radiological anomalies, defined as cortical dysplasia combined with dysmyelination, dysplastic cerebellum with cysts and brainstem hypoplasia. Cortical dysplasia results from neuroglial overmigration into the arachnoid space, forming an extracortical layer, responsible for agyria and/or ‘cobblestone’ brain surface and ventricular enlargement. The underlying mechanism is a disruption of the glia limitans, the outermost layer of the brain. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal recessive diseases with cerebral, ocular and muscular deficits, Walker–Warburg syndrome, muscle–eye–brain and Fukuyama muscular dystrophy. Mutations in POMT1 , POMT2 , POMGNT1 , LARGE , FKTN and FKRP genes attributed these diseases to α-dystroglycanopathies. However, studies have not been able to identify causal mutations in the majority of patients and to establish a clear phenotype/genotype correlation. Therefore, we decided to perform a detailed neuropathological survey and molecular screenings in 65 foetal cases selected on the basis of histopathological criteria . After sequencing the six genes of α-dystroglycanopathies, a causal mutation was observed in 66% of cases. On the basis of a ratio of severity, three subtypes clearly emerged. The most severe, which we called cobblestone lissencephaly A, was linked to mutations in POMT1 (34%), POMT2 ( 8%) and FKRP (1.5%). The least severe, cobblestone lissencephaly C, was linked to POMGNT1 mutations (18%). An intermediary type, cobblestone lissencephaly B, was linked to LARGE mutations (4.5%) identified for the first time in foetuses. We conclude that cobblestone lissencephaly encompasses three distinct subtypes of cortical malformations with different degrees of neuroglial ectopia into the arachnoid space and cortical plate disorganization regardless of gestational age. In the cerebellum, histopathological changes support the novel hypothesis that abnormal lamination arises from a deficiency in granule cells. Our studies demonstrate the positive impact of histoneuropathology on the identification of α-dystroglycanopathies found in 66% of cases, while with neuroimaging criteria and biological values, mutations are found in 32–50% of patients. Interestingly, our morphological classification was central in the orientation of genetic screening of POMT1 , POMT2 , POMGNT1 , LARGE and FKRP . Despite intensive research, one-third of our cases remained unexplained; suggesting that other genes and/or pathways may be involved. This material offers a rich resource for studies on the affected neurodevelopmental processes of cobblestone lissencephaly and on the identification of other responsible gene(s)/pathway(s). * Abbreviations : MDDGA : muscular congenital α-dystroglycanopathy with brain and eye anomalies OMIM : Online Mendelian Inheritance in Man

Humoral immunodeficiencies, which are characterized by defective production of antibodies, are the most common types of primary immunodeficiency. Pulmonary changes are present in as many as 60% of patients with humoral immunodeficiency. Chronic changes and recurrent infections in the respiratory airways are the main causes of morbidity and mortality in those affected by a humoral immunodeficiency. Medical imaging, especially computed tomography (CT), plays a crucial role in the initial detection and characterization of changes and in monitoring the response to therapy. The spectrum of abnormalities seen at thoracic imaging includes noninfectious airway disorders, infections, chronic lung diseases, chronic inflammatory conditions (granulomatosis, interstitial pneumonias), and benign and malignant neoplasms. Recognition of characteristic CT and radiographic features, and correlation of those features with clinical and laboratory findings, are necessary to differentiate between the many possible causes of parenchymal and mediastinal disease seen in patients with primary humoral immunodeficiencies.

Many compounds (pergolide, fenfluramine, ectasy) were described as inducers of fibrotic valvular lesions. All these compounds share in common to activate the 5HT2B serotonergic receptor. This observation leads to the hypothesis that cardiac valves express a « serotonergic system » that could be activated by serotonin (5-HT) or 5-HT receptor (5-HTR) agonists. In this work, we characterized the expression pattern of 5-HT2A, 2B, 4 R and the 5- HT transporter (SERT) in whole and cell subpopulations of 30 human mitral and aortic valves collected at the time of surgical valve replacement (Aortic: 11 calcified, 5 sclerotic, 4 bicuspid; Mitral: 12 dystrophic). All samples express 5HT2A, 2B, 4 R and SERT, the amount of 5HT2B R mRNA being higher than the 5HT2A R whatever the valve and etiology. 5HT2BR expression is found in endothelial cells (CD31+) at the valve surface, but also inside valve lesions, expressed by interstitial cells (smooth muscle α-actin and vimentin positive cells) located in an abundant glycosaminoglycan matrix. In fact, fibromyxoid lesions and calcified aortic valves express a high amount of CD34+ cells. These cells are endothelial progenitors because they express VEGFR2 and eNOS together with 5-HT2R. After collagenase treatment, valve samples were labeled with CD31 and CD34 antibodies: 60.1 (± 11) % of all mitral valvular cells are CD34+ compared to 36.1 (±8) % of aortic valvular cells (FACS analysis and sorting). To summarize, 5HT2A, 2B, 4 receptors and SERT are expressed in aortic and mitral diseased valves. The amounts of 5HT2A, 2B R mRNA are equivalent between mitral and aortic valves. High amount of CD34+ endothelial progenitors, expressing 5HT2AR and 5HT2BR, are found in degenerated valves. The contribution of the two 5-HT2 receptors and endothelial progenitors in valve degeneration is now under investigation.

Fibroblast growth factors (FGF), hepatocyte growth factor (HGF) and their receptors, FGFR and c-Met, are essential components of the regulatory networks between the epithelium and mesenchyme in embryonic lung, but their respective roles in tumour growth are not clear. We performed allelotyping at loci containing the candidate genes FGFR-1-2-3-4, FGF-1-2-7-10, c-Met and HGF in 36 non-small cell lung cancer (NSCLC) (20 squamous-cell carcinomas (SQC) and 16 adenocarcinomas (ADC)), by surrounding each locus with two microsatellites (MS), as close as possible to the genes of interest. Unexpectedly, SQC and ADC were frequently altered at all of these loci, and SQC showed more simultaneously altered loci. In ADC, alterations at the 15q13-22 locus (FGF7 candidate gene) were significantly more frequent. Thus, these loci showed different patterns of molecular alterations between SQC and ADC. Finally, alterations at loci containing FGFR and HGF candidate genes were inversely correlated to the lymph node status in SQC and ADC, respectively.

A distinct syndrome was ascertained in a 3-year-old girl and her brother. The proband was the first child of first cousin parents. She was born after an uneventful pregnancy. At birth, multiple congenital anomalies were noted: ptosis of the left eyelid, hypertelorism, anteverted nares, large fontanel, long philtrum, ungueal hypoplasia, polysyndactyly, single transverse crease, complex cardiopathy, and hepatic cysts. During another pregnancy of the mother, fetal ultrasonographic examination showed an hypertrophy of the right ventricle and atria, a dextroposition of the aorta, a bilateral renal pelvis dilatation, and a club foot. After termination of the pregnancy, necropsy showed facial anomalies, a small penis, a polysyndactyly, a ventricular septum defect, and a malformation of the ductal plate. Bonneau et al. [1983: J Genet Hum 2:93-105] described a family in which three sibs had a complex cardiac malformation, hexadactyly of the first toe, and syndactyly of the third and fourth fingers. Rajab [1997: Clin Dysmorphol 6:85-88] described two sibs with similar features in an Omani family. The sibs described in this report had anomalies of the ductal plate which were not reported in the two other families. These new findings are in favor of autosomal inheritance of this condition which is amenable to antenatal diagnosis.

The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cell lung cancer (SCLC) and 23 nonsmall cell lung cancer (NSCLC) (12 adenocarcinomas, 11 squamous cell carcinomas) and 20 controls. Allelotyping was performed with a selected panel of 12 microsatellites from 9 chromosomal regions 3p21, 3p24, 5q, 9p, 9q, 13q, 17p, 17q and 20q. Plasma DNA allelic imbalance (AI) was found in 88% (30 of 34 patients), with a similar sensitivity in SCLC and NSCLC. In the 24 paired available tumor tissues, 83% (20 of 24) presented at least 1 AI. Among these patients, 85% (17 of 20) presented also at least 1 AI in paired plasma DNA, but the location of the allelic alterations in paired plasma and tumor DNA could differ, suggesting the presence of heterogeneous tumor clones. None of the 20 controls displayed plasma or bronchial DNA alteration. A reduced panel of six markers (at 3p, 5q, 9p, 9q) showed a sensitivity of 85%. Moreover, a different panel of microsatellites at 3p and 17p13 in SCLC and at 5q, 9p, 9q and 20q in NSCLC patients could be specifically used. Analysis of plasma DNA using this targeted panel could be a valuable noninvasive test and a useful tool to monitor disease progression without assessing the tumor.

In congestive heart failure, the chronic sympathetic hyperactivity contributes to a poor prognosis. In this respect, clonidine, a centrally acting sympathoinhibitory drug, has previously been tested in clinical trials. The aim of the current study was to evaluate the effects of clonidine on morbidity and mortality in an experimental model of cardiac hypertrophy associated with hypertension, renal failure, and intense sympathetic activation. One-kidney, one-clip Goldblatt hypertensive rats were treated orally with clonidine (200 microg/kg/d) during 30 days and were compared with untreated rats and with sham-operated animals. Cardiac hemodynamics, left ventricular volume and elasticity, cardiac morphometry and histology, and renal function were evaluated. A survival study was also performed. Clonidine normalized cardiac function, ventricular stiffness, and prevented ventricular structural remodeling. Moreover, despite a marked renal function impairment, survival of the animals was increased in the clonidine group. The centrally acting sympathoinhibitory drug clonidine exhibited marked cardioprotective properties. This study emphasized the interest of evaluating drugs whose aim is to treat congestive heart failure, in an experimental model of cardiac and renal failure.

Cystic masses of the mediastinum are well-marginated round lesions that contain fluid and are lined with epithelium. Major cystic masses include congenital benign cysts (ie, bronchogenic, esophageal duplication, neurenteric, pericardial, and thymic cysts), meningocele, mature cystic teratoma, and lymphangioma. Many tumors (eg, thymomas, Hodgkin disease, germ cell tumors, mediastinal carcinomas, metastases to lymph nodes, nerve root tumors) can undergo cystic degeneration-especially after radiation therapy or chemotherapy-and demonstrate mixed solid and cystic elements at computed tomography (CT) or magnetic resonance (MR) imaging. If degeneration is extensive, such tumors may be virtually indistinguishable from congenital cysts. A mediastinal abscess or pancreatic pseudocyst also appears as a fluid-containing mediastinal cystic mass. However, clinical history and manifestations, anatomic position, and certain details seen at CT or MR imaging allow correct diagnosis in many cases. Familiarity with the radiologic features of mediastinal cystic masses facilitates accurate diagnosis, differentiation from other cystlike lesions, and, thus, optimal patient treatment.

The 49,XXXXY syndrome is a rare sex chromosome anomaly with an approximate incidence of 1 in 85 000 male live births. The diagnosis is usually ascertained postnatally by the association of mental retardation, variable growth deficiency, Down syndrome-like facial dysmorphy, hypogenitalism and other malformations, especially involving the heart and skeleton. Prenatal diagnosis of the pentasomy 49,XXXXY is generally fortuitous and sonographic features have rarely been described in the literature. We report here on two cases of 49,XXXXY syndrome diagnosed prenatally because of sonographic abnormalities. In the first, amniocentesis was performed at 26 weeks' gestation for polyhydramnios, unilateral clubfoot and micropenis. In the second, a karyotype was carried out on chorionic villi at 13 weeks' gestation for cystic hygroma. These observations and the six previously reported cases demonstrate that cystic hygroma in first or second trimester of pregnancy may be associated with sex chromosome aneuploidy other than Turner syndrome. Moreover, they emphasize the importance of detailed sonographic examination in the second trimester, as small penis and abnormal posturing of the lower extremities are very suggestive of the 49,XXXXY syndrome. Copyright © 2002 John Wiley & Sons, Ltd.

Non-invasive aortic valve implantation has become an alternative technique to surgical valve replacement in patients at high risk for open-chest surgery. With over 100,000 procedures already performed clinically, the technology is expected to involve less-critical patients in future. Whereas, biological valve tissue is a fragile material when folded for low-diameter catheter insertion purposes, textile polyester is a less-fragile material and may offer an alternative material to replace valve leaflets. One issue related to textile is the porosity of the material, which may induce exaggerated tissue ingrowth. Today, data relating to interactions between living tissues and fabrics used as valve materials are available only in the mitral position. Hence, the study aim was to observe the interaction pattern when the valve is implanted in the aortic position, and to assess the influence of sinus whirls on this pattern.

Many compounds (pergolide, cabergoline, fenfluramine, ectasy) were described as inducers of fibrotic valvular lesions, a rare but severe drug reaction. All these drugs share in common the pharmacological property to activate a serotonergic receptor subtype, the 5HT2B. Together with the well known “carcinoid heart” that is a valvulopathy due to high amounts of circulating serotonin, these observations lead to the hypothesis that cardiac valves express a “serotonergic system” that could be activated by 5-HT or 5-HTR agonists. The aim of this work was to characterize the pattern of expression of 5-HT2A,2B,4 receptors, the serotonin transporter (SERT) and the biosynthesis peripheral enzyme (Tph1) in various valvulopathies. Thirty degenerated human valves were collected: 11 calcified aortic valves (CAV), 5 sclerotic aortic valves (SAV), 11 dystrophic mitral valves (DMV). They were analyzed by RT-qPCR and immunohistochemistery. All samples express 5HT2A,2B,4 receptors, SERT and Tph1. In these valve tissues, the amount of 5HT2B receptor (5HT2B R) mRNA is higher than the 5HT2A one (5HT2A R) : Δ Ct (5HT2B R -18S) = 12,53±1,12 vs Δ Ct (5HT2A R -18S) = 15,95±2,37 for CAV, Δ Ct (5HT2B R -18S) = 13,04±2,62 vs Δ Ct (5HT2A R - 18S)=16,00±1,46 for SAV, Δ Ct (5HT2B R -18S) = 12,34±0,77 vs Δ Ct (5HT2A R -18S) = 16,14±0,86 for DMV. The amounts of SERT, Tph1 and 5HT4 receptor mRNA are negligible whatever valve and etiology. At a topographical point of view, 5HT2BR expression is found in endothelial cells (at the valve surface) but also inside valve lesions, by interstitial cells (smooth muscle α-actin and vimentin positive cells) located in an abundant glycosaminoglycan matrix. Characterization of these cells is in progress. In particular, we characterize the high amount CD34+ hematopoietic progenitors that are highly present in fibromyxoid lesions. To summarize, 5HT2A,2B,4 receptors, SERT and Tph1 are expressed in aortic and mitral diseased valves. The amounts of 5HT2A,2B R mRNA are equal between mitral and aortic valves. The contribution of the two 5-HT2 receptors in valve degeneration is now under investigation whatever the pathological process considered.

Objective: This retrospective study evaluates probability of survival and mode of recurrence in patients with a microscopically positive bronchial resection margin following resection for primary bronchogenic carcinoma, as well as influence of radiotherapy on survival. Methods: From January 1986 to July 1997, 40 patients had a microscopically positive bronchial resection margin following a macroscopically complete resection (17 lobectomies, three bilobectomies, four sleeve-lobectomies, and 16 pneumonectomies). Tissue diagnosis was squamous cell carcinoma in 32 patients, adenocarcinoma in four, adenosquamous carcinoma in two and neuroendocrine carcinoma in two. Lymph node status was N0 in 14 patients, N1 in 10, and N2 in 16. The bronchial margin contained carcinoma in situ in 20 patients, invasive mucosal carcinoma in five, and peribronchial infiltration in 15. All patients except the three most recent underwent adjuvant radiation therapy. Results: At the conclusion of the study (January 31st, 1999), 30 patients had died: two with post-operative complications, 17 with progressive disease, ten without relation to cancer, and one under undefined circumstances. Six of 10 unrelated deaths were interpreted as respiratory complications of radiotherapy. Recurrent disease appeared in 24 patients (60%). Nineteen had progression of initial disease (47.5%): metastatic spread in 12 (30%), isolated local recurrence in four (10%), and combined local recurrence and metastases in three (7.5%). Five patients developed metachronous cancer, with bronchial location in four (10%) and laryngeal in one (2.5%). 5-year survival (Kaplan‐Meier) in 20 patients with carcinoma in situ was 38:7 ^ 13:7% (median 31 months), but rose to 55:0 ^ 16:6% when excluding seven deaths not related to cancer (five of whom were secondary to radiotherapy) (x 2 a 3:080; Pa 0:0792). Survival in 13 patients classified N0 was 51:3 ^ 16:3% (median 61 months), and 71:1 ^ 18:0% following exclusion of unrelated deaths (x 2 a 3:939; Pa 0:0472). Adverse prognosis of peribronchial infiltration was correlated to a positive N status (13 N2 and 2 N1), 5-year survival being 20:0 ^ 10:3% (median: 18 months). Conclusions: Prognosis of peribronchial infiltration is similar to N2 disease. In situ carcinoma does not influence survival per se. Local control of disease is probably in part due to radiotherapy. However, the high prevalence of unrelated late deaths suggests an adverse impact of radiotherapy on survival. q 2000 Elsevier Science B.V. All rights reserved.

Crohn’s disease can be associated with several respiratory manifestations. We report here a case of pulmonary migratory infiltrates associated with bilateral pleural thickening and peripheral eosinophilia. The histopathological findings show an association of necrotizing nodules, eosinophilic infiltration in the non-abscessed lung tissue, areas of non-caseating epithelioid granulomas, and an extensive pleural fibrosis. The different histopathological findings are detailed and the responsibility of either Crohn’s disease or treatment by mesalazine is discussed.

Pathologic processes that may involve the chest wall include congenital and developmental anomalies, inflammatory and infectious diseases, and soft-tissue and bone tumors. Many of these processes have characteristic radiologic appearances that allow definitive diagnosis. Sternal deformities can be visualized at radiography and their severity quantified with computed tomography (CT). In cervical rib, CT with multiplanar reconstruction may demonstrate relevant anatomic detail and the relationship between bone deformity and arterial compression. In Poland syndrome, radiography reveals an area of hyperlucency on the affected side, whereas CT demonstrates the absence of the greater pectoral muscle and clearly depicts associated musculoskeletal anomalies. Tuberculosis typically manifests at radiography and CT as osseous and cartilaginous destruction and soft-tissue masses with calcification and rim enhancement. Aspergillosis involving the chest wall manifests as pulmonary consolidations and permeative osteolytic changes of the rib and spine at CT and as an area of increased signal intensity at T2-weighted magnetic resonance (MR) imaging. Neurogenic tumors and hemangiomas also typically have high signal intensity at T2-weighted MR imaging. Apparent mass extension or unequivocal bone destruction seen at CT or MR imaging may indicate chest wall involvement by lymphoma. Radiologically, soft-tissue sarcomas typically appear as areas of soft-tissue density or attenuation, often associated with necrotic areas of low density or attenuation. At radiography, plasmacytoma typically manifests as well-defined, "punched-out" lytic lesions with associated extrapleural soft-tissue masses. Chondrosarcoma frequently appears as a large, lobulated excrescent mass arising from a rib with scattered flocculent calcifications characteristic of its cartilaginous mix. Familiarity with these radiologic features facilitates accurate diagnosis and optimal patient treatment.

Four cases of placental candidiasis, an uncommon complication of rupture of the membranes, are presented. In addition to chorioamnionitis, in one of these cases villitis was also observed. Villitis is a rare occurrence in Candida infection and this represents only the second case in the literature. The involvement of villi may be suggestive of blood-borne infection. However, since neither the mother nor the foetus presented any signs of systemic dissemination, the authors suggest a hypothesis of contamination of the villi from foci of chorioamnionitis.

Laser energy is able to ablate, coagulate, and vaporize tissues. Its transmissibility in thin optical fibers makes it an ideal tool for use in percutaneous procedures. This article describes two applications in interventional musculoskeletal radiology. In percutaneous laser disc decompression the laser source is used to vaporize a small portion of the nucleus pulposus. In interstitial laser photocoagulation of osteoid osteoma the laser energy is used to coagulate and destroy the tumor by direct heating.

Study objective The clinical characteristics, histopathologic condition, and outcome of bronchoalveolar carcinoma (BAC) were studied to detect possible prognostic indicators. Design A retrospective review was conducted of 97 patients who had a curative resection for BAC between 1975 and 1993. Patients There were 83 men and 14 women with a mean age of 59 years (30 to 75 years). Interventions Resection comprised lobectomy in 84 cases (87%), bilobectomy, pneumonectomy, and a wedge excision. Results Sixty-two percent of patients were asymptomatic. The radiographic pattern was a solitary nodule in 85% of patients and lobar pneumonitis or diffuse infiltrate in 15%. In 12% of patients, the solitary lesion had been stable for period of 2 to 7 years before diagnosis. The TNM staging of the disease included 71 patients with stage I, 14 with stage II, and 12 with stage IIIA. Review of the gross pathologic features revealed well-circumseribed tumors in 88% of patients and diffuse or multifocal tumors in 12%. Mucinous differentiation was present in 43% of patients, vascular invasion in 22%, and aerogenous spread in 49%. Overall survival was 89% at 1 year, 76% at 2 years, 48% at 5 years, and 39% at 10 years. The survival curves according to histologic features showed a statistically significant difference between diffuse lesions and nodular lesions, between lesions with and without aerogenous spread (diffuse lesions excluded), and between lesions with and without vascular invasion. Conclusions The natural history of BAC is especially influenced by its nodular or diffuse nature, vascular invasion, and aerogenous spread.

Beta-blockers may induce several types of adverse respiratory reaction such as asthma, interstitial lung disease with or without pleural effusion, systemic lupus erythematosus or hypersensitivity pneumonitis. More recently, bronchiolitis obliterans with organizing pneumonia (BOOP) has been described. We report here on pulmonary migratory infiltrates with combined histopathological features of both BOOP and eosinophilic pneumonia in a woman treated with sotalol long-term. The patient improved only partially with steroids. Tapering off corticosteroid dosage resulted in relapse, and complete recovery was only obtained after sotalol was stopped.

To evaluate interstitial laser photocoagulation (a minimally invasive percutaneous technique of thermal destruction of deep-seated tumors, with low-power laser energy) in local destruction of osteoid osteoma, with computed tomographic (CT) guidance.Fifteen patients (age range, 8-48 years) with presumed osteoid osteoma were treated with CT-guided interstitial laser photocoagulation of the nidus. A high-power semiconductor diode laser (805 nm) with a 400-microm optical fiber was used. The fiber was introduced into the nidus through an 18-gauge needle. Around the fiber tip, well-defined coagulative necroses from 5 to 9 mm (energy delivery, 400-1,000 J) were obtained.Fourteen patients had complete pain relief, which was apparent within 24 hours in eight patients. One patient had recurrence of pain after 6 weeks. The remaining nidus was treated a second time, with complete relief. Treatment was unsuccessful in one patient, and surgical excision was performed. Daily activities were not restricted after the intervention. All patients were followed up for more than 1 year, with no sign of recurrence. The only notable complication was a mild reflex sympathetic dystrophy of the wrist in one patient. Sclerosis of the nidus was observed 4-6 months after the procedure.Percutaneous interstitial laser photocoagulation of osteoid osteoma seems to be a promising, simple, precise, and minimally invasive alternative to traditional surgical and percutaneous ablations.

At 28 weeks of amenorrhea, 1 fetus of a monoamniotic twin pregnancy died. Ultrasound and Doppler investigations of the surviving twin were normal. Three weeks later, endovaginal ultrasound and magnetic resonance imaging revealed massive bilateral cerebral ischemic necrosis in the surviving twin. In utero fetal blood sampling carried out before the termination did not reveal either anemia or thrombopenia. Current data suggest that cerebral or renal ischemic complications could set in immediately after the death of the first twin as a result of a period of acute hypotension. At least 2 weeks are necessary for them to be identifiable by ultrasound. It seems that they cannot be prevented by prompt delivery of the second twin.

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.

The association of a normal and a molar egg within a twin pregnancy is extremely rare. The key to diagnosis is the fetal karyotype, thus allowing elimination of its principal differential diagnosis: partial triploid mole. We report a case where the evolution of the pregnancy was complicated by severe toxemia. Interruption of pregnancy was then necessary, even though a conservative attitude had first been considered. Throughout this case, we discuss the means of diagnosis and the clinical handling of this rare entity.

The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year-old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease.

To analyse the expression of several mucins (MUC1, MUC2, MUC3, MUC5AC and MUC6), epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2 (HER2), thyroid transcription factor-1 (TTF-1), caudal type homeobox 2 (CDX2) and cytokeratin 20 (CK20), and the presence of mutations of EGFR, KRAS and HER2 in congenital pulmonary airway malformations (CPAM). Forty-one cases of CPAM and six pulmonary sequestrations were included. TTF-1 expression was observed in all cases but was not seen in mucinogenic growths in CPAM. CDX2 expression was completely negative. MUC1 expression was noted in 12 (29%) CPAM and in 33% sequestrations. MUC5AC was noted in only five cases (26%) by immunohistochemistry and was found in the mucinogenic proliferations of type 1 CPAM. No immunolabelling was noted for the other mucins. EGFR was expressed variably in almost all cases, while HER2 and CK20 was seen exclusively in the mucinogenic proliferations. All mucinous growths were characterized by KRAS mutations. No EGFR and HER2 gene alterations were identified. KRAS mutations and MUC5AC, CK20 and HER2 expression was seen in all mucinogenic proliferations, supporting the neoplastic nature of these cytologically bland growths. These findings emphasize the importance of complete surgical resection of such lesions.

In 12–19 weeks old human fetuses, LHRH-immunoreactive (LHRH-Ir) cells were detected in the nerve fascicles arising from the vomeronasal organ (VNO), from their origin to their end point at the medial aspect of the olfactory bulb (vomeronasal and/or terminal nerves). In one 22-weeks-old fetus, LHRH-Ir cells were present only in the upper part of the nasal septum, in the nerve fascicles crossing the cribriform plate. No LHRH cells could be detected in two fetuses, 23 and 36 weeks old. Our results are discussed with regard to the migratory hypothesis of LHRH cells from the medial olfactory placode to the brain.

The authors describe the first case of an isolated bilateral radial ray reduction occurring in a fetus exposed in utero to valproic acid; the diagnosis was made by ultrasound during the second trimester. This case of an isolated radial ray reduction associated with valproic acid use in pregnancy is a reminder for sonographers to carefully examine not only the cardiac and neurologic system, but also the extremities, when a fetus is exposed in utero to valproic acid.

OBJECTIVE To evaluate the contribution of referent pathologists (RPs) to the quality of diagnosis of trophoblastic diseases and to study the level of diagnostic agreement between the initial pathologists and the RPs. METHODS This observational retrospective study was carried between 1 November 1999 and 11 January 2011 using the database of the French Trophoblastic Disease Reference Centre in Lyon. All files for hydatiform moles (HMs), trophoblastic tumours and non-molar pregnancies for which there was an initial suspicion of trophoblastic disease were included, whenever there was rereading of the slides by an RP. A total of 1851 HMs and 150 gestational trophoblastic tumours were analysed. RESULTS When the initial pathologist diagnosed a complete mole, the RP confirmed the diagnosis in 96% of cases. When the initial pathologist diagnosed a partial mole, the RP confirmed the diagnosis in only 64% of cases. For trophoblastic tumours, when the initial pathologist diagnosed a choriocarcinoma, the RP confirmed the diagnosis in 86% of cases. When the initial anatomopathology suggested an invasive mole, the diagnosis was confirmed in 96% of cases. Finally, when the initial diagnosis was a placental site trophoblastic tumour or an epithelioid trophoblastic tumour, the RP confirmed the diagnosis in 60 and 100% of cases, respectively. CONCLUSION A systematic policy of rereading of slides for all suspicious moles improves the quality of management of trophoblastic diseases at a national level.

We describe fetal septopreoptic holoprosencephaly (HPE) associated with a thick corpus callosum (CC) diagnosed with MRI in a fetus at 31 weeks' gestation. Our report supports a recently published study connecting a thick fetal CC to other brain abnormalities. On diffusion tensor imaging (DTI), the body of the CC contained an abnormal longitudinal bundle, presumed to be a congenital heterotopic cingulum. Prenatal and postmortem brain MRI with DTI, CT, and pathological analyses are described and illustrated.

The vomeronasal organ (VNO) was studied in ten human foetuses, 12 to 36 weeks old. At 12 to 23 weeks, it was lined by a smooth pseudostratified epithelium, with neurone-specific enolase (NSE) positive cells looking like olfactory receptors. Clusters of NSE-positive cells were seen in relation with the posterosuperior end of the organ and along nerve fascicles in the nasal septum. At 36 weeks, the organ was lined by a respiratory epithelium and did not show any receptor-like cells; some pear-shaped NSE-positive cells of unknown significance were seen at the upper part of the respiratory epithelium. Our results suggest that during the early foetal period, the VNO could have some, as yet unknown, sensory function.

An evaluation of nephrogenesis according to fetal age was performed by quantifying the state of the nephrogenic blastema (NB) and the number of glomeruli (GN) on frontal renal sections in 99 control fetuses (gestational age ranging from 9 to 40 weeks) and in 17 aborted fetuses with low urinary tract obstruction (gestational age ranging from 14 to 36 weeks). In the control group, GN increases slowly from the 10th to the 18th week, then abruptly from the 18th to the 32nd week, reaching an upper limit with NB disappearance by the 32nd week. In the uropathy group, the renal changes show a wide range of severity clearly accounted for by the impairment of both NB and GN. The dysplastic effect of urinary backpressure is the more consistent pathogeny with the spectrum of observed renal changes. It is likely, from GN used as a time-dependent marker of renal development, that the most severe dysplasia is the result of early obstruction with abnormal disappearance of NB and subsequent arrest of nephrogenesis.

Parvovirus B19 infection during pregnancy can be transmitted to the fetus through the placenta. The consequences for the health of the fetus are very variable and can be very serious. They include intrauterine fetal death (IUFD) and miscarriage, which can lead to medico-forensic questions. For the most part, cases of IUFD take place during the second trimester of gestation and present an anatomopathologic picture characteristic of fetal infection with hydrops, placental edema, serous effusion, and erythroblastosis with nuclear inclusions. Endocardial fibroelastosis, medullar and thymic hypoplasia, and hepatic hemosiderosis are frequently present. In the third trimester, the cases are less frequent, not accompanied by hydrops, and can depend more on placental compromise than on direct infection of the fetus. We present 5 cases of IUFD resulting from parvovirus B19 and we discuss the pathogenetic and anatomopathologic aspects and obstetric liability. In 4 cases, the IUFD took place suddenly, in the absence of symptoms, in women who had not previously shown any symptom of the viral infection. In one case, the patient was hospitalized following an ultrasound diagnosis of fetal hydrops and IUFD took place 5 days after admission. Of these cases 3 were verified in the second trimester and 2 in the third trimester. Only the cases of the second trimester and one of the 2 cases of the third trimester presented the characteristic aspects of fetal infection. The other case of third trimester was characterized by placental involvement.

BACKGROUND Determination of tumor clonality has implications for molecular characterization and the optimal treatment of cancer. Allelotyping allows detection of the two alleles, maternal and paternal, and provides additional information regarding clonal genetic defects. The presence of allelic imbalances (AI) in tumors is a general event, but is not necessary at the same allele (alternative AI). The authors' goal was to determine whether the presence of alternative AI (AA) was a marker of heterogeneity and prognosis. METHODS To further analyze the heterogeneity of lung tumors, tumor DNA released in the plasma was compared with primary tumor DNA from 24 lung carcinoma patients. The comparison was performed by allelotyping using 12 microsatellites targeting 9 chromosomal regions, taking in each case leukocyte DNA as reference. To extend and confirm these observations, 26 primary colorectal carcinomas with paired synchronous liver metastasis were analyzed using an enlarged panel of 33 microsatellites. RESULTS AA were observed in 40% (20 of 50) of all patients, in 25% (6 of 24) of lung carcinoma patients but at a higher level, and in 54% (14 of 26) of colorectal carcinoma patients. They affected different chromosome localizations and each tumor stage. In both types of cancer, patients with AA had a higher AI mean frequency in their primary tumor. CONCLUSIONS Detection of AA is an original marker of heterogeneous tumors, demonstrating that independent events occurred on specific genetic sites required for cancer progression. Cancer 2003;97:2308–17. © 2003 American Cancer Society. DOI 10.1002/cncr.11324

We report a case of severe Churg-Strauss syndrome (CSS) with mediastinal eosinophilic lymphadenopathy, with relapse after standard therapy with steroids and cyclophosphamide, subsequently treated with interferon (IFN) alpha 2b. Our report shows that mediastinal lymph nodes mimicking lymphoma may be one of the clinical manifestations of CSS. We also show that patients with CSS who are resistant to first-line therapy and for whom hypereosinophilia is thought to play an important role may benefit from treatment with IFN.

The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.

The effects of obstruction [urinary tract obstruction (UTO)] and relief on renal development were examined in an experimental model in the fetal lamb. Bladder outlet obstruction was performed at 60 days of gestation; relief was performed by vesicoamniotic shunting at 90 days of gestation. Studies were carried out in obstructed (OF60; n = 11), shunted (SF; n = 5), and control fetuses (CF; n= 11) at 120 days of gestation. Fetal UTO produced either hydronephrosis (64%) or dysplasia (36%); dysplasia was always associated with a reduction in the number of glomeruli [950 ± 99 (dysplasia) vs. 1,852 ± 249 (CF) glomeruli/section]. Obstructed fetuses had lower creatinine clearance [0.76 ± 0.41 (OF60) vs. 0.96 ± 0.21 (CF) ml · min−1· kg−1], higher sodium fractional excretion [17.2 ± 20.3 (OF60) vs. 2.4 ± 3.7% (CF)], and higher urinary concentration [80 ± 30 (OF60) vs. 43 ± 22 (CF) μmol/l] than controls. In SF, the number of glomeruli was increased at 120 days of gestation (1,643 ± 106 glomeruli/section) compared with nondiverted fetuses (1,379 ± 502 glomeruli/section), and the temporal pattern of PAX2, disrupted after obstruction, was restored. In conclusion, early fetal UTO leads to either renal hydronephrosis with normal glomerular development or dysplasia with a decreased number of glomeruli; in utero urine diversion performed before the end of nephrogenesis may allow a reversal of the glomerulogenesis arrest observed.

The aim of this study was to investigate whether repeated exposure to subclinical doses of cat allergens, not inducing asthma symptoms, could affect eosinophil cationic protein (ECP) levels in bronchoalveolar lavage (BAL) or in peripheral blood, without the appearance of clinical symptoms. Twelve patients with mild asthma, all sensitized to cats and not exposed to cat allergen at home, underwent a series of inhalations of cat allergen or placebo for 8 days over 2 weeks. A methacholine challenge was performed before and after the allergen and saline exposures, and BAL and blood were sampled for ECP measurements and eosinophil counts. No patients experienced asthma symptoms. However, PD20 methacholine (geometric mean) decreased significantly from 263 μg before to 126 μg after inhalation of allergen. Inhalation of saline did not induce any significant change in PD20. The change in log PD20 before and after cat allergen exposure was statistically different from the change in log PD20 before and after saline. Median ECP levels in BAL and serum increased significantly after allergen exposure, from 0.8 to 3.1 μg/l (p

A mast cell infiltration of the bronchial smooth muscle layer has been reported in patients sensitized to common allergens. Stem cell factor (SCF) is a chemotactic and survival factor for mast cells. SCF is expressed as a soluble (sSCF) and a membrane-bound (mSCF) form, after alternative splicing of the exon encoding the proteolytic cleavage site. SCF expression by human bronchial smooth muscle cells in culture was evaluated, comparing it to that of human lung fibroblasts in culture. sSCF released in the culture supernatant was assessed by an enzyme-linked immunosorbent assay. Total SCF messenger ribonucleic acid (mRNA) was measured by competitive polymerase chain reaction (PCR) after reverse transcription. Expression of the two forms of SCF mRNA was assessed by PCR, with primers spanning the alternatively spliced exon. Smooth muscle cells produced sSCF (21.9+/-2.6 pg x mL(-1)), although at lower levels than fibroblasts (35.9+/-3.5 pg x mL(-1)); the expression of total SCF mRNA was also at lower levels than in fibroblasts (8.6+/-0.2 and 19.0+/-2.0 amol x fmol glyceraldehyde 3-phosphate dehydrogenase complementary deoxyribonucleic acid(-1), respectively). However, smooth muscle cells expressed proportionally more (1.7-fold) mSCF mRNA than did fibroblasts. In conclusion, this study shows that bronchial smooth muscle cells express stem cell factor, with a relatively high expression of membrane-bound stem cell factor. This might be related to the presence of mast cells within the bronchial smooth muscle layer, i.e. at the site of bronchoconstriction, with possible implications in the pathophysiology of asthma.

Background: This study was designed to determine whether bronchoplastic resection could be an alternative to pneumonectomy in patients with operable primary lung cancer. Methods: From 1980 to 1996, 63 patients (59 males and four females; mean age 62 ^ 7 years) underwent a bronchoplastic lobectomy for non-small cell lung cancer, indicated because of a disabled respiratory function in 34 patients, and performed electively in 29 patients. There were 38 right upper lobectomies, four bilobectomies, one middle lobectomy combined with lower lobe apical segmentectomy, ten left upper and ten left lower lobectomies. The bronchoplasty was a full sleeve in 24 patients, and a bronchial wedge resection in 39. Results: A single patient died post-operatively (1.6%). Specific procedure-related complications are summarized as follows: six anastomotic complications managed conservatively (9.5%), 15 space problems (23.8%), nine sputum retentions (14.2%). Pathologic staging classified 30 patients in stage I, 21 patients in stage II, and 12 in stage IIIA. Estimated 5-year survival was 69:7 ^ 9:8% in stage I, 37:1 ^ 12:1% in stage II, and 8:3 ^ 8:0% in stage IIIA. Fourteen patients (22.2%) developed locoregional recurrence. Three of them died with local recurrence alone, whereas 10 developed metastatic progression; a single patient is alive following completion pneumonectomy. According to stage, three recurrences occurred in stage I (10%), six in stage II (28%), and five in stage IIIA (38%). Actuarial freedom from local recurrence was significantly higher after elective procedures (Pa 0:019); there was a trend towards improved outcome following right-sided procedures (Pa 0:079) and following wedge bronchoplasty (Pa 0:055). Five patients experienced a second primary cancer (7.9%), which was resected in four. Conclusion: Bronchoplastic resections achieve local control and long-term survival comparable to standard resections in patients with stage I or II disease, and may be considered as a valuable alternative to pneumonectomy. q 1999 Elsevier Science B.V. All rights reserved.