[Bronchopleural fistula: a serious complication after thoracic surgery]. / La fistule bronchopteurale: une complication grave de la chirurgie thoracique.

Postsurgical bronchopleural fistula (BPF) is a serious complication accompanied with a high mortality, requiring early and correct diagnosis. The acute form of BPF is usually a technical failure of the surgical stump requiring an immediate surgical reoperation. The subacute or chronic BPF is more difficult to diagnose because of non specific symptoms. It requires well targeted antibiotics depending on microbiology, an adequate drainage of the thoracic cavity and very often repeated surgical or endoscopic procedures.

Implication of dipeptidylpeptidase IV activity in human bronchial inflammation and in bronchoconstriction evaluated in anesthetized rabbits.

BACKGROUND: Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. OBJECTIVE: To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. METHODS: DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. RESULTS AND CONCLUSIONS: DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor.

Muscle capillary basement membrane in identical twins discordant for insulin-dependent diabetes.

Although hereditary factors clearly modulate susceptibility to develop diabetes, their role as determinants of vascular complications associated with diabetes remains unclear. These studies were undertaken to further assess the extent to which capillary basement membrane thickening (CBMT) is governed by metabolic derangements associated with relative or absolute insulin deficiency versus genetic determinants of vascular disease closely linked to but independent of those modulating susceptibility to develop relative or absolute insulin deficiency. Quadriceps muscle capillary basement membranes obtained by needle biopsy were examined in eight pairs of identical twins discordant for insulin-dependent diabetes (IDD) for 11-29 yr. Biopsy material from one of the diabetic twins was technically unsuitable for study. The average CBM width of the IDD twins was found to be significantly thicker than that of their nondiabetic (ND) twin mates (t = 2.50, P less than 0.025). Three IDD, but none of the ND twins, had basement membrane width values in excess of 95% upper tolerance intervals for age- and sex-matched controls with no family history of diabetes. The absence of CBMT in all of the ND twins and in four of the IDD twins with diabetes of 15-24 yr duration argues against the existence, in this group of subjects, of hereditary determinants of diabetic vascular disease linked to those governing susceptibility to develop diabetes. In addition, the absence of CBMT in four subjects with IDD of 15-24 yr duration is consistent with evidence from other studies indicating that diabetic microangiopathy is not an inevitable consequence of the diabetic milieu.(ABSTRACT TRUNCATED AT 250 WORDS)

Massive cerebral edema after I.V. cyclosporin overdose.

We describe a patient who accidentally received an infusion of cyclosporin at a rate of 30 mg/hr during 13 hr instead of the prescribed dose of 3 mg/hr and who concomitantly developed massive intracerebral edema with brainstem compression and death. A cyclosporin level as high as 1700 ng/ml could have been reached before the drug was withdrawn. To the best of our knowledge, this is the first case of fatal cyclosporin overdose reported in an adult patient.

Successful single-lung transplantation after paraquat intoxication.

Severe acute lung injury frequently develops after poisoning by paraquat, and respiratory failure is the major cause of death in patients surviving more than 2 days after ingestion. We describe a 17-year-old man with confirmed paraquat intoxication by lung and muscle biopsy, in whom single-lung transplantation was performed 44 days after poisoning for end-stage lung disease. The patient was discharged from the hospital 122 days after ingestion of paraquat and 88 days after lung transplantation. Before 1996, repeated lung transplantation had been performed for patients with terminal respiratory insufficiency due to paraquat toxicity, but all died. This patient survived probably because transplantation was performed very late after paraquat ingestion.

Early chimerism of macrophages and lymphocytes in lung transplant recipients is predictive of graft tolerance.

BACKGROUND: The persistence of donor cells derived from the graft (chimerism) has been documented in various tissues after organ transplantation. It was suggested that stable chimerism might reflect a state of donor-specific tolerance. Chimerism of macrophages and lymphocytes were studied over time after lung transplantation as well as its impact on graft tolerance. MATERIAL AND METHODS: Macrophages and lymphocytes were purified from bronchoalveolar lavage sequentially obtained from 24 patients between 1 and 41 months posttransplantation (20, 22, 24, and 17 patients at, respectively, 1, 3, 6, and 12 months). DNA was extracted from these cells and their recipient-donor origin was evaluated by PCR amplification of highly polymorphic DNA regions (minisatellites). RESULTS: We show that the remaining donor cells over the first month vary from 10 up to 50% and 5 up to 55% for lymphocytes and macrophages respectively (+/-2 SD). All patients presented some chimerism up to the 6th postoperative month. Good correlation was observed between the residual amount of donor lymphocytes and macrophages during the first 3 months (P<0.001). Patients with at least 30% donor lymphocytes at 1 month after transplantation had less rejections (> or =stage II) in the follow up (P=0.0007). The same observation is true for donor macrophages although to lower extend (P=0.02). The chimerism lost its predictive value beyond 3 months. CONCLUSIONS: These data demonstrate that a level of chimerism above 30% of either donor lymphocytes or macrophages at 1 month is related to a better state of graft tolerance. However, chimerism decreases markedly beyond 3 months and has then no predictive value.

Improvement of drug-induced chronic renal failure in lung transplantation.

BACKGROUND: Nephrotoxicity is a frequently encountered adverse effect of calcineurin inhibitors (cyclosporine and tacrolimus)-combined immunosuppressive regimens. METHODS: We have compared the glomerular filtration rate in 14 patients who underwent lung transplantation, before and after replacement of azathioprine by mycophenolate mofetil and reduction of associated calcineurin inhibitors doses. RESULTS: After a mean follow-up of 16+/-4 months with the modified immunosuppressive regimen, the mean glomerular filtration rate increased by 20% with no change in lung function. CONCLUSION: By its strong immunosuppressive effect, mycophenolate mofetil allows the decrease of associated calcineurin inhibitor doses, with subsequent improvement of renal function without jeopardizing the transplanted lung.

Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion injury.

BACKGROUND: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability. METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung). RESULTS: Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group. CONCLUSION: MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.

Mitomycin C for control of recurrent bronchial stenosis: a case report.

A 27-year-old patient with cystic fibrosis underwent a bilateral lung transplantation despite the presence of multiresistant Burkholderia cepacia. Postoperatively, the patient presented with bilateral bronchial necrosis. During the 14th week, his FEV(1) dropped to 2.5 L from a baseline level of 3.4 L. A subtotal occlusion of the right mainstem bronchus below the suture was noted. Using argon electrocoagulation, the right upper lobe bronchus, the intermediate bronchus, and the right middle lobe bronchus were reopened. During the period between weeks 20 and 42 post-transplantation, a recurrent stenosis required eight endoscopic interventions combining dilatation and stenting. During the 42nd week, dilatation followed by mitomycin C application stabilized the right lung function. This case report is the first to describe the effectiveness of the local application of mitomycin C to stop recurring extensive bronchial stenosis following bronchial necrosis secondary to lung transplantation.

Sex differences in presentation, management, and prognosis of patients with non-small cell lung carcinoma.

OBJECTIVE AND METHODS: To characterize gender differences in lung cancer, we conducted a retrospective analysis including all patients undergoing surgery for non-small cell lung carcinoma in a single institution over a 20-year period. RESULTS: Compared with men (n = 839), women (n = 198) were more likely to be asymptomatic (32% vs 20%, P =.006), nonsmokers (27% vs 2%, P <.001), or light smokers (31 pack-years vs 52 pack-years; P <.001). Squamous cell carcinoma predominated in men (65%), and adenocarcinoma predominated in women (54%). Preoperative bronchoscopy contributed more frequently to a histologic diagnosis in men (69% vs 49% in women, P <.001), and fewer pneumonectomies were performed in women (22% vs 32% in men, P =.01). After multivariate Cox regression analysis, women survived longer than men (hazard ratio, 0.72; 95% confidence interval, 0.56-0. 92; P =.009) independently of age, presence of symptoms, smoking habits, type of operation, histologic characteristics, and stage of disease. The protective effect linked to female sex was present in early-stage carcinoma (stage I and II) and absent in more advanced-stage carcinoma (stage III and IV). CONCLUSIONS: This study emphasizes strong sex differences in presentation, management, and prognosis of patients with non-small cell lung cancer.

Costs and outcomes of prolonged cytomegalovirus prophylaxis to cover the enhanced immunosuppression phase following lung transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease is one of the major challenges of lung transplantation that may determine outcome. The benefits of ganciclovir prophylaxis seem indisputable, but no consensus has been reached on the optimal duration of therapy. Results with different protocols suggest that efficacy is related to the duration of treatment. MATERIALS AND METHODS: To evaluate the additional effect of a prolonged regimen throughout the maximal immunosuppression phase, we conceived a protocol administering ganciclovir, 5 mg/kg/d for 20 weeks from the first postoperative day, to all CMV-seropositive patients undergoing lung transplantation or receiving the lung from a seropositive donor. Virus shedding was routinely measured in body fluids including through BAL. Costs and outcomes are compared with those in shorter prophylaxis protocols from previous reported studies. RESULTS: Of 30 lung transplant recipients, 22 patients at risk for CMV reactivations were observed for (mean SD) 22.9 +/- 13.2 months. CMV infections were detected in eight patients 8.6 +/- 5.1 months after transplantation. CMV pneumonitis developed in one patient 9 months following the transplant event. Prolonged IV ganciclovir prophylaxis was, in general, well tolerated. However, five patients had bacteremia and one had a local thrombosis, with no long-term consequences. A prescription for 8 additional weeks of prophylaxis to cover the whole period of enhanced immunosuppression decreased the cumulative incidence of first CMV infections by 29% 1 year after transplantation compared to 12-week regimens reported in other studies that indicated a 50% reduction in the incidence of first CMV infection. The total cost of 20 weeks of IV ganciclovir prophylaxis was $6,010 (US dollars) per patient more expensive than 12 weeks of IV ganciclovir therapy. This was not offset by the reduced requirement for treatment of infections. Indeed, extrapolating to our cohort of patients, the additional cost per patient was seven times greater than the treatment for the infections that were reported after the 12-week prophylaxis protocol. CONCLUSION: Prolonging ganciclovir prophylaxis to 20 weeks decreased by half the rates of CMV infection when compared to reports from centers using a shorter protocol of 12 weeks for ganciclovir prophylaxis. Additionally, a delay in the onset of the first infection was observed. Nevertheless, the increase in costs and the discomfort of long-term use of venous catheters are important factors that may favor a shorter regimen of 12 weeks followed by preemptive therapies each time CMV infections occur.

End-stage cystic fibrosis: improved diabetes control 2 years after successful isolated pancreatic cell and double-lung transplantation.

Over a period of years, insulin-dependent diabetes and respiratory insufficiency developed in a 35-year-old patient with end-stage cystic fibrosis. After waiting more than 4 years while receiving maintenance treatment with continuous liquid O2 and nasal ventilation, the patient underwent double-lung and pancreatic islet cell transplantation. Subsequently, the patient has enjoyed a normal life with full employment and much better control of his diabetes. Pancreatic islet cell transplantation is a simple and innocuous technique easily added to the end of lung transplantation. These new pancreatic cells, although locally injected, are still secreting more than 2 years later as assessed by repeated C-peptide measurements.

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements. RESULTS: Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.

Management of lung transplant recipients with bronchogenic carcinoma in the native lung.

Experience with lung transplantation for bronchogenic carcinoma is limited. In our experience, 3 of 6 patients died of recurrent carcinoma within 5 to 35 months after transplantation. Hence, we currently do not support lung transplantation for patients with pre-transplant diagnosis of bronchogenic carcinoma, with the exception of bronchioloalveolar carcinoma (BAC) confined to the lung. Patients with BAC should be staged thoroughly with chest and abdominal computerized tomography, brain magnetic resonance imaging, and bone scan repeated every 3 months while on the waiting list, and should undergo mediastinoscopy at the time of transplantation, with a plan for a backup recipient if metastatic lymph nodes are detected. Proposal for lung transplantation for patients with bronchogenic carcinoma, with the exception of BAC, probably should be performed in the setting of a clinical trial developed with input from the lung transplant community.

Transthoracic approach in the thoracic outlet syndrome: an alternate operative route for removal of the first rib.

This retrospective study compares the results of two surgical procedures, a transaxillary and a transthoracic (that is, anterolateral thoracotomy) approach, in the treatment of the thoracic outlet syndrome by first rib resection. After transaxillary first rib removal (13 cases), initially our procedure of choice, 84% of conditions were improved, 8% were unchanged, and 8% were worse after 1 year. One permanent, disabling brachial plexus injury occurred after this operation. Transthoracic first rib resection (18 cases), presently our preferred technique, resulted in improvement in 87% of cases, with 13% of symptoms unchanged after 1 year. Although two female patients felt mild paresthesia of the mammary gland, no one has been made worse following this route. These two approaches have achieved similar results in the surgical management of this syndrome. Nevertheless, when first rib resection is indicated, our favored and recommended procedure is transthoracic, because this route appears less hazardous for brachial plexus damage.

Muscle-sparing anterior thoracotomy for one-stage bilateral lung volume reduction operation.

Bilateral lung volume reduction produces significant clinical and physiologic improvement in selected patients with end-stage emphysema. Current surgical approaches consist of median sternotomy and video-assisted thoracoscopy. This report describes an alternate technique of single-stage, bilateral lung volume reduction using muscle-sparing anterior thoracotomy in 18 patients with severe lung emphysema.

Long-term survival after surgical resections of bronchogenic carcinoma and adrenal metastasis.

There is some evidence that complete resection of both primary and metastatic sites of non-small cell lung carcinoma has more influence on survival than the locoregional stage of the lung cancer. We describe prolonged survival (>5 years) after complete surgical resection of a bronchogenic carcinoma (T3N0M1) and solitary adrenal metastasis.

Lung transplantation: how to perform the venous anastomosis when clamping is too distal.

During lung transplantation, the venous anastomosis is performed between the atrial cuffs of the donor and the receiver. In certain rare circumstances, however, the surgeon may find two veins and no possibility to reposition the clamp more proximally. A simple technique can be used in this case: both veins are reunited and the venous anastomosis carried out as usual between two large lumens.

Clinical behavior of solitary fibrous tumors of the pleura.

BACKGROUND: Solitary fibrous tumors of the pleura are rare and present unpredictable clinical behavior. METHODS: Between 1981 and 1998, 11 solitary fibrous tumors of the pleura were resected in 10 patients at the University Hospital of Geneva. Their clinical behavior and outcome were reviewed. RESULTS: Seven tumors arose from the visceral pleura, and three arose from the parietal pleura. Tumors arising from the parietal pleura were revealed to be more difficult to resect than those from the visceral pleura because of their size and adhesion to the chest wall requiring extrapleural resection. Eight tumors showed benign features, whereas two showed distinct features of malignity. One additional patient presented marked pleomorphism that could represent an intermediate form before frank malignity. Four tumors had been followed expectantly for 2 to 10 years before surgery. Although three enlarged rapidly, no signs of malignity were observed on histological examination. All patients are alive, from 2 months to 14 years after surgery (mean 55 months). In one case, however, a malignant tumor recurred 6 years after resection of a benign variant. CONCLUSIONS: Although histologically benign, solitary fibrous tumors of the pleura may enlarge rapidly and occasionally transform into malignant variants after several years. Therefore, complete surgical resection and long-term follow-up is recommended for all patients.

Predictability of FEV1 after pulmonary resection for bronchogenic carcinoma.

The aim of this study was to review the reliability of prediction of postoperative FEV1 in patients with bronchogenic carcinoma using a Tc-99m perfusion scan and simple spirometry. Over a 27-month period, 40 patients without known recurrent disease had their FEV1 measured. One quarter of the postoperative values for FEV1 differed from predicted values by less than 5% (2/11 pneumonectomies, 5/23 lobectomies, 3/6 segmental resections) and half differed by no more than 10% of predicted FEV1 (4/11 pneumonectomies, 12/23 lobectomies, 3/6 segmentectomies). One tenth of the predicted values differed by more than 30% and up to 760 mls (1/11 pneumonectomies, 2/23 lobectomies, 1/6 segmentectomy). Disease recurrence, phrenic nerve paralysis, exacerbation of obstructive pulmonary disease and poor collaboration during spirometry explained the most severe erroneous results. Age, preoperative smoking, tumour stage and histology, absence of symptoms at the time of diagnosis and adjuvant radiotherapy showed no statistically significant effect on predictability. Twenty-one patients had a postoperative Tc-99m pulmonary scan simultaneous to the spirometric control. Overestimation of postoperative FEV1 was associated with heterogeneous distribution of ventilation and perfusion.