Systematic identification of genotype-dependent enhancer variants in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10-8) and 27 additional loci of suggestive significance (5 × 10-8 < p < 1 × 10-5). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease.

Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.

BACKGROUND: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. RESULTS: In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. CONCLUSIONS: This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

[Cardiac compression of hydatid origin]. / Compression cardiaque d'origine hydatique.

INTRODUCTION: Cardiac hydatid disease is uncommon and occurs in 0.5 to 2% of patients with hydatidosis. Isolated intrapericardial hydatid cystic disease is extremely rare. OBSERVATION: We report the case of a young woman with cardiac compression due to multiple primary intrapericardial hydatid cysts. Since 1 year, she had gradual general health deterioration including dyspnoea, sweats and weight loss of 8kg. A widening of the mediastinum was observed on chest X-ray. The CT-scan, echocardiography and the dynamic IRM showed multiple mediastinal cysts with mass effect on the heart and main pulmonary artery. The size of the main pulmonary artery was reduced to 5 mm in diameter and the right upper pulmonary vein was nearly closed by posterior cysts. The right and left ventricular ejection fractions were estimated at about 34%. A complete resection of the cysts was performed by sternotomy. The surgical procedure was technically difficult because of major local inflammatory process. The postoperative outcome after an initial pulmonary embolism event was finally favourable. CONCLUSION: Hydatidosis can lead to severe cardiac involvement. These rare forms of hydatid cystic disease must be known even in non endemic regions by surgeons because of increasing mobility of the world's population.

[Evolution of species: Lung cancer evolution over one third of a century]. / De l'évolution des espèces : évolution du cancer du poumon en un tiers de siècle.

INTRODUCTION: Management of non-small cell lung cancer (NSCLC) is getting better and results on long-term survival have improved. We reviewed the modifications observed in surgery over a 32-year time period. PATIENTS AND METHOD: Data of 6105 patients who underwent surgery from 1979 to 2010 were analyzed over three equal time-periods: gender, age, type of surgery, histology, pTNM, tobacco addiction, comorbidity and time periods. RESULTS: Age, number of females and high-risk patients with comorbidity (including the history of a previous cancer) increased with time periods. Number of exploratory thoracotomy (7.7 % to 1.6 %) and pneumonectomy (48 % to 18 %) decreased. Number of wedge resection (0.5 % to 6 %) and lobectomy (42 % to 64 %) increased. Rates of the other types of resection were unchanged. Neoadjuvant treatments accounted for more than 20 % of patients in the last time period. Postoperative mortality (4 %) did not vary but non-lethal complication rates increased (16.9 % to 27.7 %). Global 5-year survival rates dramatically increased with time going from 37.4 % to 49.8 % (P<10(-6)). Survival improvement was observed in the different components of the pTNM and whatever the type of treatment. However, survival was affected by increasing age and multiplication of comorbidities but without impairing the general better outcome trend. CONCLUSION: NSCLC itself, its diagnostic and therapeutic management, and patient's characteristics evolved with time. Survival improved in most studied prognosis factors. Time period factor was of paramount importance and might be included in research dealing with NSCLC.

[Lung cancer measuring 1cm or less: A miniature subset requiring surgery]. / Cancers du poumon de 1 à 10millimètres : des cancers miniatures à opérer.

INTRODUCTION: Lung cancer measuring 1cm or less has an apparently very good outcome. However, the characteristics permitting their oncological management are unappreciated. PATIENT AND METHOD: We reviewed 187 patients with such a cancer (145 men and 42 women, mean age 60.2years) and studied the type of surgery performed, the pTNM, and the histological features. RESULTS: Surgery (19 wedge-resections, 12 segmentectomies, 136 lobectomies, 20 pneumonectomies) was complete (R0) in 97.3%. The tumors, each precisely defined among 98 adenocarcinomas (52.4%), 83 squamous cell carcinomas (44.4%), and 6 others, measured 1mm to 10mm:<5mm (n=41), 6 to 9mm (n=43), and 10mm (n=103). There were 161 pT1 (86.1%), 22 pT2 (11.8%) and 4 pT3; 148 pN0 (79.6%), 18 pN1 (9.7%) and 20 pN2 (10.7%). pN1 and pN2 were present in tumors<5mm (12/41, 29.3%) as well as in the others (26/146, 17.8% P=0.11). Histological examination frequently discovered visceral pleura involvement (tumors:<5mm 12.2% (5/41), 6 to 9mm 7% (3/43), 10mm 13.6% (14/103), P=0.53) and lympho-vascular invasion (12.9%). Five-year survival rate (66.4%) was adversely influenced by age, type of resection, pN and histological features. The survival rate was not better in tumor<5mm. CONCLUSION: Surgical resection allows the local control of lung cancers<1cm and their complete histological study, a key issue in the therapy of the future, which renders surgery an absolute must even in very small tumors.

[Life threatening haemoptysis associated with partial abnormal pulmonary venous return and pulmonary arterial hypertension]. / Hémoptysie grave, retour veineux pulmonaire anormal partiel et hypertension artérielle pulmonaire.

A 73-year-old man with chronic respiratory insufficiency was referred to the intensive care unit because of life threatening haemoptysis and hypoxemia. The patient was in respiratory failure with pulmonary arterial hypertension. The bleeding was issuing from the left inferior lobe. A small arterio-venous fistula was suspected on tomodensitometry. Arterial embolization was contraindicated because of diffuse vascular disease. A left inferior lobectomy was performed. The left superior pulmonary vein was draining into the brachiocephalic vein forming a partial anomalous pulmonary venous return. An anatomic restoration of the venous return to the left atrium was performed. The postoperative course was uneventful. No recurrence of haemoptysis was observed, after 9-month follow-up the vascular anastomosis was patent. Despite the pulmonary vascular bed reduction following lobectomy, echocardiography showed a globally mild improvement of cardiac status that might be attributed to right heart preload amelioration.

[Lung cancer surgery in a single-lung]. / Chirurgie du cancer bronchique sur poumon unique.

INTRODUCTION: The diagnosis of a second lung cancer in a patient with a previous medical history of lung cancer is no longer a rarity. Also, it is possible to observe a new location in a patient who underwent pneumonectomy in the past. Surgery remains the best treatment. Our objective was to overview this subject. PATIENTS AND METHODS: Among 5611 patients operated in our institution, 186 (3.3%) had metachronous cancer and 17 had previous pneumonectomy (0.7% of pneumonectomies and 0.2% of NSCLC treated in our department). The procedure was diagnostic and therapeutic in 88% of cases (n=15). RESULTS: There were 16 males and 1 female, mean age was 62.5-years. All were smokers (11 were former smokers) and 6 had other medical history. Mean FEV was 52% (range 35-95%). Types of resection were 2 lobectomies, 4 segmentectomies, and 11 wedge resections. There were no postoperative deaths, but two complications. Histological subtype of the first and second cancer was the same in 11 patients. All patients were pN0 after second surgery. The long-term survival (median 33 months) was 35.3% at 5-years and 14.1% at 10-years. Two patients treated with pneumonectomy for their first cancer were pN2. Patients who underwent upper right lobectomy for treatment of their second cancer survived longer than 5-years. CONCLUSION: Surgical resection for lung cancer on single-lung is associated with acceptable morbidity and mortality. Prolonged survival can be achieved in selected patients.

Prognostic factors after surgical resection of N1 non-small cell lung cancer.

OBJECTIVES: Non-small cell lung carcinoma (NSCLC) with N1 involvement is associated with 5-year survival rates ranging from 7% to 55%. Numerous factors have been independently reported to explain this heterogeneous prognosis, but their relative weight on long-term survival is unknown. METHODS: Patients who underwent surgical resection for NSCLC in two French centers from 1993 to 2010 were prospectively recorded and retrospectively reviewed. The overall survival (OS) of patients undergoing first-line surgery for pN1 disease was analyzed according to the type of extension, number of metastatic LN, number and anatomic location of metastatic stations. RESULTS: The study group included 450 patients (male 80.2%, mean age 63.3 ± 9.9 years, 5-year overall survival 46%). The number of metastatic station was 1 in 340 (75.6%, single-station disease) and ≥2 in 110 patients (24.4%, multi-station disease). The number of metastatic stations was correlated with the number of metastatic LN (p < .001), and associated with adverse OS (p = .0014). The presence of intralobar metastatic LN (station 12-13-14) was associated with a mechanism of direct extension (p < .001), but did not impact OS (p = .71). The location of metastatic stations was of prognostic significance only in case of multi-station disease, with hilar (station 10) involvement being associated with adverse OS (p = .005). The 110 patients with multi-station pN1 disease and the 134 patients operated on for single-station pN0N2 (skip-N2) disease during the study period yield comparable outcome (p = .52). CONCLUSIONS: In patients with resected pN1 NSCLC, the number of metastatic stations and their location in case of multi-station disease have a prognostic value.

[Pneumonectomy for benign disease: indication and factors affecting the postoperative course]. / Pneumonectomie pour lésions bénignes: indications et facteurs affectant les suites opératoires.

Pneumonectomy for benign disease is rare but may generate more postoperative morbimortality than when performed for lung cancer. We questioned this assessment and retrospectively reviewed 1436 pneumonectomies and 54 completions of which 82 and 10 performed for benign disease (5.7% and 18.5%, respectively): left n=65 and right n=27. Indications were: post-tuberculosis destroyed lung (n=37), aspergilloma (n=18), bronchiectasis (n=19), infection (n=5), congenital malformations (n=5), inflammatory pseudotumor (n=3), trauma (n=2), post-radiation (n=2) and mucormycosis (n=1). Pneumonectomy consisted of 48 standard and 44 pleuro-pneumonectomies. Stump coverage by flaps was performed in 66.3% (61/92). Complications occurred in 21.7% (20/92) and postoperative deaths in 7.6% (7/92, of which 5 with fungal infections), which was not different than what was observed in lung cancer. There was no difference in fistula formation and mortality regarding the side, the type of resection and the protective role of stump coverage. Considering patients with fungal infections versus others, mortality was 26.3% (n=5/19) and 2.7% (n=2/74), respectively (P=0.0028). Pneumonectomy for benign disease achieves cure with acceptable mortality and morbidity. However, presence of fungal infection should raise the attention for possibility of increased postoperative risks.

[Clinical and paraclinical prognostic factors in non-small cell lung cancer surgery]. / Facteurs pronostiques cliniques et paracliniques dans la chirurgie du cancer du poumon non à petites cellules.

INTRODUCTION: Lung cancer prognosis is mainly based on the TNM, histology and molecular biology. Our aim was to analyze the prognostic value of certain clinical and paraclinical variables. PATIENTS AND METHODS: We studied among 6105 patients operated on, divided during 3 time-periods (1979 to 2010), the following prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history, clinical presentation, and paraclinical variables. RESULTS: Postoperative mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5-year overall survival was 43.2% and 10-year was 27%. Best survival was observed after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(-6)). All these factors were confirmed by multivariate analysis, except gender. Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became significant in the multivariate one (P=0.013). CONCLUSION: Medical and human factors, and the general physiological state, play an important role in prognosis after surgery. We do not know their exact meaning and, like studies on chemotherapy, they justify special research.

[Place of limited resections and prognostic factors in non-small lung cancer]. / Place des résections limitées et leurs facteurs pronostiques dans le cancer bronchique non à petites cellules.

INTRODUCTION: Results of surgery for non-small-cell lung cancer (NSCLC) are poorer after limited resection, wedge and segmentectomy, than after lobectomy. Guidelines recommend avoiding wedge-resection, which new techniques (radiofrequency ablation and cyberknife) tend to replace. This work aimed to study the wedge-resection carcinological value. PATIENTS AND METHODS: NSCLC without previous other cancer history and neoadjuvant therapy measuring less than 31 millimetres and operated from 1980 to 2009 were reviewed. Analyzed variables were: location, gender, age, FEVS, type of resection, histology, pT and pN. RESULTS: There were 66 wedge-resections (10.9%), 32 segmentectomies (5.3%), 507 lobectomies (83.8%), nine postoperative deaths (1.5%), 136 complications (22.5%), 557 complete resections (R0=92%); 72.2% of NSCLC upper lobe location (437/605). Age was more advanced in wedge-resection and segmentectomy, FEVS lower and NSCLC most often a squamous cell pN0 and pStage I carcinoma than in lobectomy. Lymphadenectomy was not performed in half the wedge-resections. Five-year survival rates were poorer after wedge-resection: 50% versus segmentectomy 59.8% (P=0.09), and lobectomy 66% (P=0.0035), but the number of recurrences was similar. Multivariate analysis demonstrated that age, FEVS, type of surgery and lymphadenectomy, pN in pTNM were the only prognosis factors. CONCLUSION: Wedge-resection is less carcinological than segmentectomy when the patient-status and NSCLC location allow performing the latter, but more than the new techniques, because of its pathological yield, when the patient-status and nodule peripheral location allow wedging.

[Lung cancer surgery and cirrhosis]. / Chirurgie du cancer du poumon chez le cirrhotique.

INTRODUCTION: Lung cancer is the leading cause of death by cancer and cirrhosis is the fourteenth, all causes included. Surgery increases postoperative risks in cirrhotic patients. Our purpose was to analyze this point in lung cancer surgery. METHODS: We collected, among 7162 patients, the data concerning those operated for lung cancer (n=6105) and compared patients with hepatic disease (n=448) to those presenting other medical disorder (n=2587). We analyzed cirrhotic patients' characteristics (n=49). RESULTS: Five-year survival of patients with hepatic disease was lower (n=5657/6105): 35.3% versus 43.8% for patients with no hepatic disease, P=0.0021. Survival of cirrhotic patients was not statistically different from the one of patients with other hepatic disorder, but none survived beyond 10 years (0% versus 26.4%). Surgery in cirrhotic patients consisted in one explorative thoracotomy, three wedges resections, two segmentectomies, 33 lobectomies and 10 pneumonectomies. Postoperative mortality (8.2%; 4/49) was not different for patients without hepatic disease (4.2%; 239/5657) (P=0.32), as well as the rate of complications (40.8%; 20/49 and 24.8%; 1404/5657, P=0.11). Only one postoperative death was associated to a hepatic failure. Multivariate analysis pointed age, histological subtype of the tumour and stage of disease as independent prognosis factors. CONCLUSION: When cirrhosis is well compensated, surgical resection of lung cancer can be performed with acceptable postoperative morbidity and satisfactory rates of survival. Progressive potential of this disease is worse after five years.

[Mucoepidermoid tracheo-bronchial tumors in adulthood. A series of 22 cases]. / Tumeurs muco-épidermoïdes trachéo-bronchiques chez l'adulte. À propos d'une série de 22 cas.

INTRODUCTION: Mucoepidermoid tumours (TME) are rare tumours arising from the submucosal glands of the tracheobronchial tree. The majority of these tumours develop in a benign fashion but some of them are malignant. The latter can be easily mistaken for adenosquamous carcinomas. PATIENTS AND METHOD: We have reviewed 22 patients suffering from TME observed over a period of 25 years. Two arose from the trachea and 20 from the cartilaginous bronchi; 12 of these tumours had macroscopic and histological criteria of low-grade malignancy, 4 had macroscopic and 6 macroscopic and microscopic criteria of high grade malignancy. RESULTS: Prognosis of the latter was very poor and no survival observed after 6 years follow-up, a behavior similar to that observed in non-small cell lung carcinomas and adenosquamous carcinomas. CONCLUSION: The best treatment of these orphan tumours remains surgery.

[Diaphragmatic palsy and dysfunction: from physiology to surgery]. / Dysfonctions et paralysies diaphragmatiques : de la physiopathologie au traitement chirurgical.

The clinical presentations of diaphragm dysfunctions vary according to etiologies and unilateral or bilateral diseases. Elevation of the hemidiaphragm from peripheral origins, the most frequent situation, requires a surgical treatment only in case of major functional impact. Complete morphological and functional analyses of the neuromuscular chain and respiratory tests allow the best selection of patients to be operated. The surgical procedure may be proposed only when the diaphragm dysfunction is permanent and irreversible. Diaphragm plication for eventration through a short lateral thoracotomy, or sometimes by videothoracoscopy, is the only procedure for retensioning the hemidiaphragm. This leads to a decompression of intrathoracic organs and a repositioning of abdominal organs without effect on the hemidiaphragm active contraction. Morbidity and mortality rates after diaphragm plication are very low, more due to the patient's general condition than to surgery itself. Functional improvements after retensioning for most patients with excellent long-term results validate this procedure for symptomatic patients. In case of bilateral diseases, very few bilateral diaphragm plications have been reported. Some patients with diaphragm paralyses from central origins become permanently dependent on mechanical ventilation whereas their lungs, muscles and nerves are intact. In patients selected by rigorous neuromuscular tests, a phrenic pacing may be proposed to wean them from respirator. Two main indications have been validated: high-level tetraplegia above C3 and congenital alveolar hypoventilation from central origin. After progressive reconditioning of the diaphragm muscles following phrenic pacing at thoracic level, more than 90% of patients can be weaned from respirator within a few weeks. This weaning improves the quality of life with more physiological breathing, restored olfaction, better sleep and better speech. The positive impact of diaphragm stimulation has also been evaluated in other degenerative neurological diseases, particularly the amyotrophic lateral sclerosis. For either central or peripheral diaphragm dysfunctions, a successful surgical treatment lies on a strict preoperative selection of patients.

[Lung cancer with heart failure--a cardiac and thoracic surgeon's collaboration]. / Prise en charge chirurgicale cardiothoracique d'un cancer bronchique responsable d'une insuffisance cardiaque.

Surgical resection is a validated therapeutic option for selected cases of pulmonary tumors invading the important mediastinal structures (caval vein, atrium, aorta or supra-aortic trunks). Here, we present a patient with a necrosed pulmonary tumor invading the left atrium, causing cardiac insufficiency. A complete surgical resection under extracorporeal circulation was performed by the thoracic and cardiac teams. Admitted in a bed-ridden state, the patient was discharged completely rehabilitated on postoperative day 13. He survived 1 year at home with a good quality of life.

[Impact of induction therapies on pathology and outcome after surgical resection of non-small lung cancer: a 30-year experience of 859 patients]. / Traitements néoadjuvants : évaluation d'une pratique couramment indiquée en RCP.

UNLABELLED: The management of localized non-small cell lung cancer (NSCLC) has been modified over the last decades, with induction therapies being increasingly recommended as a prerequisite to surgical resection. However, the relative impact of chemo- and chemoradiotherapy on tumours' pathology and patients' survival is still discussed. METHODS: We set a retrospective study including every patient who underwent surgical resection for NSCLC in 2 French centres from 1980 to 2009. We then compared the tumours' pathology and patients' survival according to the use of induction chemotherapy (group 1) or induction chemoradiotherapy (group 2). RESULTS: There were 733 patients in group 1 and 126 patients in group 2. In group 1, 669 patients (91%) had platinum-based chemotherapy, for 2 to 3 cycles in 564 cases (77%). In group 2, chemoradiotheray was concomitant in 68 patients (54%), and sequential in 58 patients (46%). As compared with group 1, group 2 was characterized by younger age (mean 59.8±9.5 vs 56.4±9.6, respectively, P<.001), a higher rate of tumours deemed unresectable before induction treatment (25% vs 44%, P<.001), and a higher proportion of T4 (25% vs 44%, P<.001) or N2 diseases (56% vs 69%, P=.005). The type of resection, postoperative complications, and postoperative mortality were not significantly different between groups. On final pathologic report, as compared with group 1, there were more N0 and N1 disease in group 2 (N0: 43% vs 58%, P=.002; N1: 22% vs 10%, P=.002) while the rate of N2 disease was comparable (34% vs 32%, P=ns). The median, 5-, and 10-year survivals were 28 months, 35%, and 21% for group 1, and 29 months, 36%, and 23% for group 2, respectively (P=ns). CONCLUSION: As compared with induction chemotherapy, induction chemoradiotherapy was performed in more advanced NSCLC, and resulted in better downstaging, similar postoperative course, and comparable long-term outcome after surgical resection.

[Lymphatic spread of lung cancer: anatomical lymph node chains unchained in zones]. / Extension lymphatique du cancer du poumon : une anatomie enchaînée dans des zones.

Lung cancer is characterized by its lymphophilia. Its metastatic spread mainly occurs by tumor cells lymphatic drainage into the blood circulation. Initially, the lymph node TNM classification was based on clinical and therapeutic considerations, particularly concerning N2 involvement. The goals were to avoid futile exploratory thoracotomies without lung resection, to provide more accurate data from mediastinoscopy, and to take into account the radiation therapy fields. Since 1997, the international lymph node classification was more used to analyse the disparities within N1 and N2 groups. However, this attempt did not succeed in clarifying the lymphatic metastazing process, and was not progressing any more. Anatomy not being considered, it did not permit to grasp the anatomical and physiological significances of N2 and N3 involvement. In effect, this classification is now confined in zones and is lacking the anatomical and physiological descriptions that characterise the lymphatic pathways draining the lungs and their tumoral pathology. The stations proposed in numbers in cartographies should have gained in accuracy and in prognostic value if they had been expressed in their anatomical counterparts.

[Lymphatics and lung transplantation. A review]. / Lymphatiques et transplantation pulmonaire : revue.

The role of lymph circulation in lung transplantation (LTx) has not really been studied since the first animal models, which allowed the development of solid organ transplantations. However, the oedema observed in the grafts immediately after LTx often remains unpredictable and unexplained. Although it is an integral part of the entity called "primary graft failure". Despite its multifactor aspects making the interpretation difficult, the possibility of a change in the lymph circulation is proposed to explain an oedema occurrence. The animal models focusing on this point were mainly developed in small bowel transplantation because of interesting similarities with LTx. The analysed criteria were the consequences of lymphatic vessels interruption as well as their regeneration modalities after LTx. These studies also analysed the role of lymphatic vessels in the rejection induction, the local immune response and the occurrence of obliterative bronchiolitis. This review allowed analysing the studies, which approached the lymphatic vessel issue in transplantation.

[Place and role of the pleura in non-small cell lung cancer dissemination]. / Place et rôle de la plèvre dans la dissémination des cancers du poumon non à petites cellules.

INTRODUCTION: The pleural involvement (PLI) in non-small cell lung cancer (NSCLC) has a poor prognosis, even though it might be very heterogeneous. PATIENTS AND METHODS: A multicentric retrospective descriptive study was performed over 2329 patients who were operated for NSCLC between 1979 and 2010. The patients with PLI were classified in P(Parietal)PLI and V(visceral)PLI and then each subdivided : VPLI to peripheric (VPLI-P) and fissural (VPLI-F) and PPLI to mediastinal (PPLI-M) and costal (PPLI-C). Characteristics and survival were compared between the subgroups as well as with patients without PLI (WPLI, n=1439). RESULTS: The sex-ratio was 2.8 (males: n=1713). The PLI patients were significantly younger, with a less sex-ratio, less R0 resections (96% versus 98.7%, P=0.000076), and less N0 (60% vs 70%, P<10(-6)) as their 5-year survival (45.7% vs 55.5%, P<10(-6)). The PLI was related to the size of NSCLC (P<10(-6)) and N2 involvement (P=0.0020). It was less frequent after neoadjuvant treatment (36.2% vs 39.1% P=0.03). In the VPLI-F or PPLI-M, pneumonectomies were more frequent (P<10(-6)). In VPLI-P (n=196/561), there were more pN1 and pN2 (P=0.0065) with a 5-year survival of 42.9% vs 54.4%, P=0.013. In multivariate analysis, the PLI was not an independent prognostic factor contrary to age, sex, type of resection, pT and pN. CONCLUSION: The pleura play a major role in NSCLC dissemination. Its involvement affects pN, the type of surgical resection and justifies the use of neoadjuvant treatment.

[Lung cancer surgery in solid organ transplanted patients]. / Chirurgie du cancer du poumon chez les greffés d'organe solide.

BACKGROUND: The incidence of lung cancer is reputed to be higher and prognosis worse in solid organ transplant recipients than in the general population. Our purpose was to review the results of surgery in this group of patients. METHODS: We retrospectively reviewed 49 male and 6 female patients; mean aged 60.6 years (38-85). Transplanted organ was heart (n = 37), kidney (n=12), liver (n = 5) and both-lungs (n = 1); 48 patients had smoking habits and 42 heavy comorbidities (76.4%). Lung cancer was diagnosed during surveillance (78.2%, n = 43) or because of symptoms (21.8%, n = 12). We reviewed TNM and other main characteristics, among them histology (squamous-cell-carcinoma n = 23, adenocarcinomas n = 24, others n = 8). RESULTS: Surgery consisted of: exploratory thoracotomy (n = 2), wedge resections (n = 6), segmentectomy (n = 1), lobectomy (n = 42), pneumonectomy (n = 4). Postoperative mortality was 7.4% (n = 4) and complication rate 34.5% (n = 19). Five-year survival rate was 46.4% (65.4% for stage I patients, n = 25). Among the 35 dead patients during follow-up, 14 died of their lung cancer (40%). Two had been re-operated from another lung cancer: one after 3 and 8 years who survived 16 years, and the other after 2 years who survived 70 months. CONCLUSIONS: Surgery results are good and postoperative events acceptable despite theoretically increased risks. This also supports performing a close follow-up of transplanted patients and particularly those with smoking history in view of detecting lung cancer appearing at an early stage.