Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension.

Mutations in the gene encoding bone morphogenetic protein (BMP) receptor type 2 (BMPR-2) have been reported in pulmonary arterial hypertension (PAH), but their functional relevance remains incompletely understood. BMP receptor expression was evaluated in human lungs and in cultured pulmonary artery smooth muscle cells (PASMCs) isolated from 19 idiopathic PAH patients and nine heritable PAH patients with demonstrated BMPR-2 mutations. BMP4-treated PASMCs were assessed for Smad and p38 mitogen-activated protein kinase (MAPK) signalling associated with mitosis and apoptosis. Lung tissue and PASMCs from heritable PAH patients presented with decreased BMPR-2 expression and variable increases in BMPR-1A and BMPR-1B expression, while a less important decreased BMPR-2 expression was observed in PASMCs from idiopathic PAH patients. Heritable PAH PASMCs showed no increased phosphorylation of Smad1/5/8 in the presence of BMP4, which actually activated the p38MAPK pathway. Individual responses varied from one mutation to another. PASMCs from PAH patients presented with an in vitro proliferative pattern, which could be inhibited by BMP4 in idiopathic PAH but not in heritable PAH. PASMCs from idiopathic PAH and more so from heritable PAH presented an inhibition of BMP4-induced apoptosis. Most heterogeneous BMPR-2 mutations are associated with defective Smad signalling compensated for by an activation of p38MAPK signalling, accounting for PASMC proliferation and deficient apoptosis.

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.

Pulmonary hypertension associated with myeloproliferative disorders: a retrospective study of ten cases.

BACKGROUND: Pulmonary hypertension (PH) is a severe hemodynamic disorder in which the pulmonary artery pressure is persistently elevated, leading to right-sided heart failure. Some studies have suggested an association between PH and myeloproliferative diseases (MPD). OBJECTIVES: This study describes clinical, hematological and hemodynamic characteristics of PH associated with MPD. METHODS: We retrospectively reviewed 10 cases of PH associated with MPD: polycythemia vera (8 patients) and essential thrombocythemia (2 patients), followed between 1993 and 2002. The baseline evaluation was established by right-sided heart catheterization, ventilation/perfusion lung scan and pulmonary angiography if required. RESULTS: Six patients had confirmed chronic thromboembolic pulmonary hypertension (CTEPH) and 4 had pulmonary arterial hypertension (PAH) associated with MPD without other risk factors for PAH. The hemodynamic characteristics of CTEPH and PAH associated with MPD were similar. The diagnosis of CTEPH was concomitant to that of MPD in all cases (5 polycythemia vera and 1 essential thrombocythemia). The PAH associated with MPD occurred later in the evolution of the MPD (3 polycythemia vera and 1 essential thrombocythemia) with a median of 162 months after the diagnosis of MPD, and it was associated with myeloid metaplasia (p < 0.01). CONCLUSION: We describe 2 distinct forms of PH in the context of MPD: CTEPH, which is diagnosed at an early stage of the MPD, and PAH, which occurs later in the course of the MPD and is associated with myeloid metaplasia. Progressively increasing dyspnea in a patient with an MPD warrants further investigation to rule out PAH and CTEPH, while a diagnosis of CTEPH warrants ruling out MPD.

[Invasion of the pulmonary artery by an undifferentiated carcinoma]. / Obstruction tumorale de l'artère pulmonaire par un carcinome indifférencié

INTRODUCTION: The diagnosis of chronic obstruction of the pulmonary artery is difficult. We present the case of a woman with an invasive, undifferentiated carcinoma of the pulmonary artery. CASE REPORT: A 61 year old woman complained of increasing dyspnoea. This was evaluated by computed tomography which showed a defect in the main pulmonary artery. There was no clinical or radiological improvement following anticoagulant treatment for two months. A repeat CT scan showed a persisting intravascular defect and the diagnoses considered included post-embolic pulmonary arterial hypertension and angiosarcoma. A surgical biopsy was performed and pericardial and aortic tumour nodules were found during the operation. The pathological examination revealed undifferentiated carcinoma. Further investigations failed to reveal the primary site. CONCLUSION: Invasion of the pulmonary artery by angiosarcoma or other tumour is part of the differential diagnosis of chronic thromboembolic disease. The diagnosis rests on histology obtained by an intravascular or surgical procedure. Complete surgical excision may be possible in angiosarcoma but it was impossible in our patient. The patient died despite two courses of chemotherapy and targeted therapy with erlotinib.

[Diagnosis and care of postembolic pulmonary hypertension: the role of the pneumologist]. / Diagnostic et prise en charge de l'hypertension pulmonaire postembolique : le rôle du pneumologue.

The prognosis of postembolic pulmonary hypertension, a rare and serious disease, has been transformed with the curative intervention of pulmonary endarteriectomy. The screening is based on two key non invasive examinations, the cardiac ultrasound and ventilation-perfusion scintigraphy. The confirmation of the diagnosis and the determination of the best therapeutic options then relies on the expertise of the national reference centre, based on the haemodynamics and the morphological data provided by pulmonary angiography and spiral computerised tomography. Although the technique of endarteriectomy is fully validated, a drug approach is in the assessment process, both in the inoperable forms or when confronted with persistent postsurgical pulmonary hypertension.

Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension.

Hyperplasia of pulmonary artery smooth muscle cells (PA-SMCs) is a hallmark pathological feature of primary pulmonary hypertension (PPH). Here we found that PA-SMCs from patients with PPH grow faster than PA-SMCs from controls when stimulated by serotonin or serum and that these effects are due to increased expression of the serotonin transporter (5-HTT), which mediates internalization of indoleamine. In the presence of 5-HTT inhibitors, the growth stimulatory effects of serum and serotonin were markedly reduced and the difference between growth of PA-SMCs from patients and controls was no longer observed. As compared with controls, the expression of 5-HTT was increased in cultured PA-SMCs as well as in platelets and lungs from patients with PPH where it predominated in the media of thickened pulmonary arteries and in onion-bulb lesions. The L-allelic variant of the 5HTT gene promoter, which is associated with 5-HTT overexpression and increased PA-SMC growth, was present in homozygous form in 65% of patients but in only 27% of controls. We conclude that 5-HTT activity plays a key role in the pathogenesis of PA-SMC proliferation in PPH and that a 5HTT polymorphism confers susceptibility to PPH.

[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.

Extended surgery for T4 lung cancer: a 30 years' experience.

T4 non-small cell lung carcinomas (NSCLC) were deemed unresectable. Advances in surgery have challenged this dogma. We describe technical aspects and result on superior vena cava (SVC), carinal, thoracic inlet tumor surgeries, and resection under cardiopulmonary bypass (CPB). SVC reconstruction requires hemodynamic control to reverse SVC clamping cerebral effects and excellent cephalic venous bed patency. Among 50 SVC resections, including 25 carinal pneumonectomies, post-operative mortality rate was 8%. In the N0-N1 group, 5- and 10-year survival rates were 46.6 and 37.7%, respectively. Right carinal pneumonectomy was performed through right thoracotomy. Sternotomy was favored for left carinal pneumonectomy or carinal resection alone. Among 138 carinal resections, including eight right upper lobectomies, 123 right pneumonectomies, four left pneumonectomies, and three isolated carinal resections, the post-operative mortality rate was 9.4%. In the N0-N1 patients, 5-year survival rate was 47%. 191 patients underwent resections of thoracic inlet tumors through a transclavicular cervicothoracic anterior approach combined in 63 patients with a posterior midline incision for limited spine invasion. In N0-N1 group, 5- and 10-year survival rates were 41.5 and 29.7%, respectively. CPB allowed resection of tumors invading the heart or great vessels in 13 patients. R0 resection and post-operative mortality rate were 94.4 and 5.5%, respectively. In this series of 388 T4 NSCLC, the post-operative mortality rate was 4%. In the R0 and N0-N1 groups, the 5-year survival rates were 44 and 41%, respectively. Surgical resection of T4 locally advanced NSCLC is worth being performed in selected N0-N1 patients, provided that a radical resection is expected.

[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.

In situ production of interleukin-6 within human lung allografts displaying rejection or cytomegalovirus pneumonia.

Interleukin-6 (IL-6) is a pleiotropic cytokine that is a regulator of inflammation and immunity. As production of IL-6 may be an important mechanism by which local and systemic inflammatory processes are regulated during lung transplantation, we measured this cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) collected in 27 lung recipients. IL-6 bioactivity was analyzed using a B cell hybridoma proliferation assay (B9 cell line). Three groups of clinical situations were analyzed: control lung recipients, rejections, and CMV pneumonia. Serum IL-6 concentrations (mean +/- SEM) were 24.2 +/- 3.3 U/ml in the 26 control samples. In 20 allograft rejection episodes, the serum IL-6 concentration was higher than in control samples but the difference was not significant (59.3 +/- 20.5 U/ml, P > 0.05). IL-6 serum levels were significantly increased during the 14 CMV pneumonias (61.2 +/- 11.5 U/ml, P < 0.01). In BALF, IL-6 levels were increased during CMV pneumonia (52.4 +/- 21.9 U/ml BALF), and to a lesser extent during rejection events (14.1 +/- 3.7 U/ml BALF), as compared with controls (5.6 +/- 1.6 U/ml BALF, P < 0.005, and P < 0.05, respectively). Similar results were observed when IL-6/albumin and IL-6/urea ratios were determined so as to compensate for possible dilution effects in BALF. IL-6 in BALF was produced in situ during CMV pneumonia as shown by in situ hybridization experiments that revealed a significant number of IL-6 gene-expressing alveolar cells in this condition. IL-6 concentrations in the serum and in the BALF were compared. There was no correlation between serum and BALF IL-6 concentrations, showing that serum IL-6 levels do not accurately reflect intrapulmonary IL-6 levels do not accurately reflect intrapulmonary IL-6 production. Thus IL-6 is produced within lung transplants during CMV pneumonia, and to a lesser extent during allograft rejection.

Emergence of inflammatory alveolar macrophages during rejection or infection after lung transplantation.

Local activation of macrophages may play an important role in immune complications following lung transplantation. To document such a phenomenon, we have investigated the possible changes of alveolar macrophage surface antigen expression after lung transplantation. Using immunocytofluorometry, we have analyzed the phenotype of alveolar macrophages from 41 bronchoalveolar lavage fluids obtained from 19 lung transplant recipients displaying various complications. The strong expression of HLA-DR observed on almost all alveolar macrophages was similar among groups I (no complication), II (minimal acute rejection), and III (mild to severe acute rejection), but was enhanced in group IV (bronchial infection) (P < 0.03). We observed no significant variation in the monocyte lineage CD14 antigen expression among the 4 groups, and about 83% of alveolar macrophages expressed this marker strongly. Membrane expression of the 27E10 antigen that characterizes infiltrating macrophages in acute inflammatory lesions was significantly higher during mild to severe rejection episodes than in controls (P < 0.02) and during bronchial infections (P < 0.05) but not during minimal rejection. Double staining experiments confirmed that 27E10-positive cells in groups III and IV belonged to the macrophage lineage. In addition, the expression of the 27E10 antigen on cultured alveolar macrophages was found to be increased after stimulation by bacterial lipopolysaccharide or IFN-gamma. These results indicate that a particular alveolar macrophage subpopulation is activated during immune events after lung transplantation. This population, recognized by the 27E10 mAb, might be involved in cytokine production during severe acute rejection and infection episodes.

Use of embryonic human trachea grown in nude mice to patch-repair congenital tracheal stenosis.

BACKGROUND: Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results. METHODS: Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes. RESULTS: The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium. CONCLUSIONS: Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.

Intrapulmonary production of RANTES during rejection and CMV pneumonitis after lung transplantation.

RANTES (regulated upon activation, normally T expressed and secreted) is a chemoattractant for macrophages, memory T lymphocytes, and eosinophils. We investigated whether intrapulmonary production of the chemokine RANTES contributes to the recruitment of immune cells during lung transplantation complications. RANTES concentration was measured in bronchoalveolar lavage (BAL) fluids using an ELISA assay. It was significantly higher during CMV pneumonitis (36.2 +/- l6 pg/ml, n=12, P=0.031) and allograft rejection (31.1 +/- 8.5 pg/ml, n=27, P=0.013) than in patients without complications (9.1 +/- 2.3 pg/ml, n=22). At least some of the RANTES was produced by lung macrophages: BAL macrophages cultured for 24 hr spontaneously released larger amount of RANTES during CMV pneumonitis (140 +/- 53 pg/ml, n=8, P=0.002) and allograft rejection (84 +/- 44 pg/ml, n=11, P=0.037) than in control patients (15.2 +/- 6.5 pg/ml, n=21). Moreover, macrophages in transbronchial biopsies were labeled by an anti-RANTES mAb. RANTES production by BAL macrophages was followed in 2 patients with CMV pneumonitis. It remained high as long as CMV-induced cytopathic effects or clinical symptoms were present, but it returned to baseline as the infection was controlled. These results suggest that the intrapulmonary production of the chemokine RANTES by activated macrophages contributes to the intrapulmonary accumulation of immune cells during complications of lung transplantation.

Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung transplantation. Paris-Sud University Lung Transplantation Group.

BACKGROUND: Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. METHODS: The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death. RESULTS: NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). CONCLUSIONS: Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.

Heart-lung transplantation. Technical modifications that may improve the early outcome.

After heart-lung transplantation, mortality and morbidity remain related, to a significant degree, to surgical problems such as uncontrollable bleeding, phrenic nerve palsy, and dehiscence of the tracheal anastomosis. The following modifications of the original Stanford technique were designed: (1) Back bleeding from the graft is avoided; (2) dissection of the posterior mediastinum is limited as much as possible, with only the tracheobronchial bifurcation being dissected free; (3) surgical stapling is extensively used to optimize hemostasis; (4) the surgical procedure is kept away from the phrenic and vagus nerves; (5) early corticosteroid therapy is avoided and the tracheal anastomosis may be wrapped with a pedicle of great omentum. These techniques were used in 21 patients. Postoperative bleeding remained minimal and never necessitated reoperation. There was no instance of phrenic nerve palsy. Dehiscence of the tracheal anastomosis occurred in two patients during the initial experience, but in subsequent patients this complication was prevented by adequate improvements (omentoplasty and avoidance of corticosteroids). Our technical modifications may reduce the risk of early surgical complications and thereby improve the early outcome and leave the patient in better condition to face the other hazards of heart-lung transplantation.

Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations.

BACKGROUND: Air leaks after pulmonary resections may contribute to increased patient morbidity, delayed removal of chest drainage tubes, and prolonged hospitalization. OBJECTIVE: The purpose of this study was to investigate the effects of a new synthetic, absorbable sealant on the healing of healthy bronchial and lung tissues (experimental study) and its safety and efficacy to stop air leaks after lung resection (clinical study). METHODS: Fifteen large white pigs underwent a left upper lobectomy. All parenchymal surgical sites were sealed; the bronchial stump was either stapled, sealed, or both (n = 5 each). In the clinical study, 26 consecutive patients were prospectively randomized, intraoperatively, to standard closure of parenchymal surgical sites with (n = 15) or without (n = 11) the sealant. RESULTS: In the experimental study, no postoperative air leaks occurred, with intact bronchial closures and normal tissues at death. In the clinical study, 100% of intraoperative leaks were sealed versus 18% of control patients (P =.001). Although 77% (n = 10) of treated patients remained leak-free from the end of the operation to chest tube removal versus 9% (n = 1) of control patients (P =.001), there was no statistical difference in the duration of postoperative chest tube time, hospital stay, or cost. There were no acute or late undesirable side-effects related to the sealant application. CONCLUSIONS: The surgical adhesive investigated here demonstrated a compelling safety profile and significant clinical efficacy to stop air leaks after lung resections.

Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group.

The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation.

Partial cricoidectomy with primary thyrotracheal anastomosis for postintubation subglottic stenosis.

OBJECTIVE: We describe a Pearson-type technique and evaluate its results for postintubation subglottic stenosis. METHODS: Forty-five patients underwent a partial cricoidectomy with primary thyrotracheal anastomosis, and 5 underwent simultaneous repair of a tracheoesophageal fistula as well. Twenty-four (53%) patients were referred to us after initial conservative (n = 21) or operative (n = 3) management. There were 27 cuff lesions, 7 stomal lesions, and 11 at both levels. The upper limit of the stenosis was 1.5 cm (range, 1-2.5 cm) below the cords, and the subglottic diameter was reduced by 60% in 38 (84%) of the patients. The length of airway resection ranged from 2 to 6 cm (median, 3 cm). Despite 23 thyrohyoid or suprahyoid releases, 8 anastomoses were under tension. RESULTS: Thirty-seven (82%) patients were extubated after the operation (n = 30) or within 24 hours (n = 7). Six patients required postoperative airway stenting (median, 5.5 days). Early (<30 days) complications occurred in 18 (41%) patients, mainly as transient airway and voice complaints, aspiration, and dysphagia. One (2%) patient died of myocardial infarction. Late morbidities were 2 failures occurring as bilateral recurrent nerve paralysis and restenosis requiring definitive tracheostomy. Patients had excellent or good anatomic (n = 42 [96%]), functional (n = 41 [93%]), or both types of long-lasting results, with no stenotic relapse. CONCLUSIONS: Partial cricoidectomy with primary thyrotracheal anastomosis can be applied in patients with postintubation stenosis extending up to 1 cm below the cords and measuring up to 6 cm in length with excellent-to-good definitive results. The association with a tracheoesophageal fistula does not contraindicate surgical repair.

Evaluation and outcome of different surgical techniques for postintubation tracheoesophageal fistulas.

OBJECTIVE: We evaluated the outcome of different surgical techniques for postintubation tracheoesophageal fistula. METHODS: Thirty-two consecutive patients aged 51 +/- 23 years had tracheoesophageal fistulas resulting from a median of 30 days of mechanical ventilation via endotracheal (n = 12) or tracheostomy (n = 20) tubes. Tracheoesophageal fistulas were 2.5 +/- 1.2 cm long and were associated with a tracheal (n = 10) or subglottic (n = 3) stenosis in 13 patients. RESULTS: All but 3 patients were weaned from respirators before repair. All operations were done through cervical incisions and included direct division and closure (n = 9), esophageal diversion (n = 3), muscle interposition (n = 6), or, more recently, tracheal or laryngotracheal resection and anastomosis with primary esophageal closure (n = 14). Nine thyrohyoid and two supralaryngeal releases reduced anastomotic tension. Twenty-three patients (74%) were extubated after the operation (n = 16) or within 24 hours (n = 7), and 7 required a temporary tracheotomy tube. One postoperative death (3%) was associated with recurrent tracheoesophageal fistula. Seven complications (22%) included recurrent tracheoesophageal fistula (n = 1), delayed tracheal stenosis (n = 2), dysphagia (n = 2), and recurrent nerve palsy (n = 2). Complications necessitated reoperation (n = 1), dilation (n = 2), definitive tracheostomy (n = 1), Montgomery T tubes (n = 1), and Teflon injection of the vocal cords (n = 1). Twenty-nine patients (93%) had excellent (n = 24) or good (n = 5) anatomic and functional long-term results. Complications have been less common (7% vs 38%) and long-term results better (93% vs 65%) recently with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure as compared with previous procedures. CONCLUSIONS: Postintubation tracheoesophageal fistula is usually best treated with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure even in the absence of tracheal damage.