T Cells Promote Bronchial Epithelial Cell Secretion of Matrix Metalloproteinase-9 via a C-C Chemokine Receptor Type 2 Pathway: Implications for Chronic Lung Allograft Dysfunction.

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity in epithelial cell differentiation. Primary human bronchial epithelial cells (BECs) were treated with activated T cells in the presence or absence of transforming growth factor (TGF)-ß. The expression of epithelial and mesenchymal markers was investigated. The secretion of inflammatory cytokines and matrix metalloproteinase (MMP)-9 was measured in culture supernatants and in plasma from lung transplant recipients (LTRs): 49 stable, 29 with BOS, and 16 with RAS. We demonstrated that C-C motif chemokine 2 secreted by T cells supports TGF-ß-induced MMP-9 production by BECs after binding to C-C chemokine receptor type 2. Longitudinal investigation in LTRs revealed a rise in plasma MMP-9 before CLAD onset. Multivariate analysis showed that plasma MMP-9 was independently associated with BOS (odds ratio [OR] = 6.19, p = 0.002) or RAS (OR = 3.9, p = 0.024) and predicted the occurrence of CLAD 12 months before the functional diagnosis. Thus, immune cells support airway remodeling through the production of MMP-9. Plasma MMP-9 is a potential predictive biomarker of CLAD.

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

PURPOSE: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease. MATERIALS AND METHODS: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates. RESULTS: Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P<0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P>0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size>2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P<0.01). CONCLUSION: RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) carries a poor prognosis and lung transplantation is the only curative treatment. In PVOD, epoprostenol therapy is controversial, as this condition may be refractory to specific therapy with an increased risk of pulmonary oedema. We retrospectively reviewed clinical, functional and haemodynamic data of 12 patients with PVOD (10 with histological confirmation) treated with continuous intravenous epoprostenol and priority listed for lung transplantation after January 1, 2003. All PVOD patients had severe clinical, functional and haemodynamic impairment at presentation. Epoprostenol was used at low dose ranges with slow dose increases and high dose diuretics. Only one patient developed mild reversible pulmonary oedema. After 3-4 months, improvements were seen in the New York Heart Association functional class (class IV to III in seven patients), cardiac index (1.99+/-0.68 to 2.94+/-0.89 L x min(-1) x m(-2)) and indexed pulmonary vascular resistance (28.4+/-8.4 to 17+/-5.2 Wood units x m(-2); all p<0.01). A nonsignificant improvement in the 6-min walk distance was also observed (+41 m, p = 0.11). Two patients died, one patient was alive on the transplantation waiting list on December 1, 2008 and nine patients were transplanted. Cautious use of continuous intravenous epoprostenol improved clinical and haemodynamic parameters in PVOD patients at 3-4 months without commonly causing pulmonary oedema, and may be a useful bridge to urgent lung transplantation.

Surgical treatment of celiac artery aneurysm associated with median arcuate ligament.

Celiac artery aneurysms are rare but potentially fatal because of the risk of rupture. Atherosclerosis and fibrous dysplasia are the two most common etiologies. Median arcuate ligament compression of the celiac artery is common but usually asymptomatic. We report three cases of post-stenotic celiac artery aneurysm with median arcuate ligament compression admitted to our hospital over the past two years. Although the incidence is rare with only 8 cases reported in the literature, a median arcuate ligament may have a role in the development of celiac artery aneurysms and its presence can influence the surgical strategy.

[Postembolic pulmonary hypertension]. / Hypertension pulmonaire postembolique.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterized by the persistence of thromboemboli obstructing the pulmonary arteries as an organized tissue. The consequence is an increase in pulmonary vascular resistance resulting in pulmonary hypertension (PH) and progressive right heart failure. BACKGROUND: It is difficult to recognize the postembolic nature of PH because there is no known history of thromboembolic disease in more than 50% of cases. Diagnosis is based on the presence of mismatched segmental defects in the ventilation-perfusion scanning. When CTEPH is suspected, pulmonary angiography and high-resolution CT scan are required to establish the diagnosis and to assess the operability. Pulmonary angiography is always performed in conjunction with a diagnostic right heart catheterization, which is required to confirm the diagnosis of PH and to determine the degree of hemodynamic impairement. If there is a good correlation between the pulmonary vascular resistance and the anatomical obstruction, pulmonary endarterectomy (PEA) must be proposed. Otherwise, vasodilator and antiproliferative treatments and lung transplantation represent interesting alternatives. VIEWPOINT AND CONCLUSION: PEA remains the treatment of choice for eligible patients. Nevertheless, there is a need to conduct randomized trials to assess the efficacy of novel medical therapies in some situations: (1) in inoperable CTEPH due to distal lesions, (2) before PEA (therapeutic bridge) in patients who are considered "high risk" due to extremely poor hemodynamics, (3) in patients with persistent pulmonary hypertension after surgery.

[Angiosarcoma mimicking recurrent pulmonary embolism]. / Un angiosarcome mimant une embolie pulmonaire récidivante.

INTRODUCTION: Pulmonary artery sarcoma is a rare disease with non-specific symptoms. The clinical and radiological presentation can mimic pulmonary embolism with chronic thromboembolic pulmonary hypertension. Management is essentially surgical but the prognosis remains poor. CASE REPORT: A patient presented with symptoms of pulmonary embolism. Despite vitamin K antagonist therapy, he suffered from extension of the endovascular defects and his pulmonary hypertension increased. Suspicious results of positron emission tomography suggested the diagnosis of pulmonary artery sarcoma that was confirmed by surgery. However, the outcome was unfavourable, leading to death of the patient. CONCLUSION: This case reinforces the idea that the clinical and tomodensitometric presentations of pulmonary arterial sarcoma and chronic thromboembolic pulmonary hypertension are similar. The positron emission tomography seems to be a key to distinguishing these two diagnoses.

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

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

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

[Catamenial pneumothorax. Failure of videothorascopic treatment]. / Pneumothorax cataménial. Echec du traitement par vidéothoracoscopie.

INTRODUCTION: Catamenial pneumothorax occurs in women during the menses. It is frequently associated with diaphragmatic fenestrations or episodes of pleural endometriosis. OBSERVATION: We report the case of a patients who had presented 25 episodes of right pneumothorax despite treatment with videothorascopy initiated after the 10th episode. These episodes coincided with menstruation. Diagnosis of catamenial pneumothorax was evoked and thoracic surgery was indicated. Exploration of the pleural fossa did not reveal symphysis but 7 diaphragmatic orifices, which were sutured before conducting mechanical pleurodesis. No relapse of pneumothorax was reported following surgery. COMMENTS: Around one hundred cases of catamenial pneumothorax have been reported in the literature. They represent 2.8 to 5.6% of spontaneous pneumothroax in women. Diagnosis is evoked on the occurrence of recurrent pneumothorax appearing 24 to 72 hours after the onset of menstruation. The pathogeny is uncertain and several mechanisms are frequently evoked. In the prevention of relapses, treatment consists in closing the diaphragmatic orifices with thoracotomy, resection of eventual bubbles, and pleural symphysis. Videothorascopy does not appear adapted to treatment.

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

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

[Surgical treatment of pulmonary arterial hypertension]. / Traitement chirurgical de l'hypertension artérielle pulmonaire.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe disease that has undergone a dramatic improvement in therapeutic management over the past 20 years. Among the new therapeutic options, surgery has the potential to dramatically improve or, in some cases, cure PAH. BACKGROUND: Surgical treatment of PAH includes pulmonary endarterectomy which can cure PAH when the cause is obstruction of the pulmonary arteries by fibrous tissue resulting from pulmonary embolism, by tumours as angiosarcomas, and echinococcus cysts. Transplantation is required in end-stage PAH after failure of medical treatment. Atrial septostomy and Potts procedure are palliative surgical procedures that can delay transplantation. VIEWPOINT: Extracorporeal cardiopulmonary support is the latest surgical improvement, not only as a bridge to transplantation in end-stage PAH but also during recovery after transplantation or pulmonary endarterectomy. CONCLUSIONS: Surgery is part of the therapeutic management of PAH. Dialogue between physicians and surgeons is a prerequisite for any reasoned therapeutic decision.

Surgical management of mediastinal goiters: when is a sternotomy required?

OBJECTIVE: Mediastinal goiters are frequently diagnosed, particularly in the elderly population. However, factors associated with an increased risk of median sternotomy have not been analyzed systematically. METHODS: Between 1980 and 2004, a total of 185 patients underwent surgery for mediastinal goiters in our institution. There were 126 women and 59 men with a median age of 68 years (range 24 to 94 years). The goiters were left-sided in 77 patients, right-sided in 69 patients, and bilateral in 39 patients. RESULTS: Clinical presentation was mainly dyspnea (37 %), palpation of a cervical mass (35 %), superior vena cava syndrome (5 %), dysphagia (4 %) and dysphonia (4 %). Goiters measured between 5 and 23 cm (median 10 cm) and were prevascular (38 %), retrovascular and paratracheal (33 %), and retrotracheal (27 %). Aberrant intrathoracic goiters were observed in 4 patients (2 %). The large majority of goiters could be removed transcervically, regardless of the location and extension of the goiters. A sternotomy was required in 13 patients (6 %), mainly because of recurrent goiter ( P = 0.1), ectopic goiter ( P < 0.001), or invasive carcinoma ( P < 0.001). Superior vena cava syndrome, emergent airway compression, dysphagia, retrotracheal goiter, or crossover goiters were not found to be associated with an increased risk of sternotomy. One patient (0.5 %) died postoperatively from massive intraoperative carcinomatous pulmonary emboli. Histology demonstrated a thyroid carcinoma in 18 patients (10 %). CONCLUSIONS: Surgery for mediastinal goiters should always be considered, even in elderly patients because of the high risk of tracheal compression and the low morbidity of the surgery. Most mediastinal goiters are benign and can be removed through a cervical approach. Sternotomy should only be performed in cases of previous cervical thyroidectomy, invasive carcinoma, or ectopic goiter.

Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension.

In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean+/-SEM number of DC-SIGN-positive cells.artery(-1) of 100-300 microm diameter was 1.4+/-0.4 in controls versus 26.4+/-2.7 in IPAH. In rats, the number of OX-62-positive cells.artery(-1) of 50-150 microm diameter was 0.5+/-0.2 in controls, and 0.7+/-0.5, 3.1+/-0.5 and 8.4+/-0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.

[The perforating vein of the Hunter's canal: incidence in varicose pathology and treatment]. / La veine perforante du canal de Hunter, son incidence dans la pathologie variqueuse et son traitement.

Hunter's perforator is a vein which joins the great saphenous vein with the femoral vein by passing through the aponeurosis of the adductor (Hunter's) canal, more or less at the junction of the lower and middle thirds of the thigh. It is constant, very variable in terms of its origin and may be twin or more, though there is a degree of regularity concerning its ending. It is important to detect its incontinence in varicose pathology, notably when there is recurrence following stripping of the great saphenous. Clinical examination is the most important, often combined with Doppler investigation and much more rarely with phlebography. The treatment of this perforator is essentially medical, by sclerosing injections, and sometimes surgical, after indications have been carefully weighed. New methods of treatment, such as the CHIVA technique, are also being developed but there is an insufficient follow-up time to enable any objective conclusion to be drawn.

Long-term results of cryopreserved arterial allograft reconstruction in infected prosthetic grafts and mycotic aneurysms of the abdominal aorta.

PURPOSE: This prospective, observational study determined the long-term outcome in patients with abdominal aortic infection (primary or prosthetic graft) who were treated with simultaneous aortic/graft excision and cryopreserved arterial allograft reconstruction. METHODS: From April 1992 to March 2000, patients with abdominal aortic infection underwent complete or partial excision of the infected aorta/prosthetic graft and cryopreserved arterial allograft reconstruction. Arterial allografts were harvested from multiple organ donors and cryopreserved at -80 degrees C without rate-controlled freezing. The patients were observed for survival, limb salvage, persistence and/or recurrence of infection, and allograft patency. The results were calculated with life-table methods. RESULTS: During the 8-year study period, 28 consecutive patients (27 men, 1 woman; mean age, 64 years) underwent treatment for abdominal aortic infection (23 graft infections, including 7 graft-enteric fistulas and 5 primary aortic infections). Allograft reconstruction was performed as an emergency procedure in 13 patients (46%). The mean follow-up period was 35.4 months (range, 6-101 months). The overall treatment-related mortality rate was 17.8% (17% for graft infection, 20% for primary aortic infection). The overall 3-year survival was 67%. There was no early or late amputation. There was no persistent or recurrent infection, and none of the patients received long-term (> 3 months) antibiotic therapy. Reoperation for allograft revision, excision, or replacement was necessary in four patients (17%) who were available for examination, with no reoperative perioperative death. The 3-year primary and secondary allograft patency rates were 81% and 96%, respectively. CONCLUSION: Our experience with cryopreserved arterial allograft in the management of abdominal aortic infection suggests that this technique seems to be a useful option for treating one of the most dreaded vascular complications.

Chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.