Pharmacokinetic population study to describe cefepime lung concentrations.

Pharmacokinetic parameters of cefepime in 2 g plasma and lung tissue bid over 3 days to achieve the steady-state was studied in 16 patients (15 male, one female) subjected to lung surgery for bronchial epithelioma. The aims of this study were firstly to quantify cefepime lung diffusion with cefepime lung concentrations in comparison with cefepime serum concentrations, and secondly to estimate population pharmacokinetic parameters of cefepime in lung tissue using NONMEM. The mean characteristics of patients were: age, 60 years (range, 51-69 years), weight, 73 kg (range, 62-87 kg) and creatinine clearance, 77 ml/min (range, 62-92 ml/min). Both serum sample (two per patient) and lung sample (one per patient) cefepime concentrations were analysed by HPLC with UV detection. Five groups were made according to the time of sampling after the last cefepime intravenous infusion at the fifth infusion: 0.5 h (n=2), 2 h (n=5), 4 h (n=3), 8 h (n=3) and 12 h (n=3). The cefepime concentration ratio between lung and serum was calculated for each group and statistical analysis show no significant difference between groups. The mean concentration ratio between lung and serum was 101% (range, 70-130%). To explain this observation a two-compartment pharmacokinetic model with a population approach was used to describe pharmacokinetic parameters of cefepime both in lung and in serum. Serum was assimilated at the central compartment and lung was the peripheral compartment. NONMEM was used to estimate the mean and the variance of the pharmacokinetic parameters. Central volume of distribution (V(d)), steady-state volume of distribution (V(ss)), central clearance (CL) and transfer constants (K(cp)) from serum to lung and (K(pc)) from lung to serum were estimated. Central elimination half-life t(1/2Kbeta)was extrapolated from elimination constant beta. Results were: V(d)= 15.62 +/- 2.56 l, V(ss)= 17.58 +/- 2.58 l, CL = 3.65 +/- 1.25 l/h, beta = 0.234 h(-1), t(1/2beta)= 2.96 hours, K(cp)= 12.25 +/- 8.56 h(-1)and K(pc)= 0.242 +/- 0.085 h(-1). The results show that cefepime diffusion in lung occurs quickly without lagtime and in similar concentrations to that in serum.

Esophageal patching for an unsuturable tracheoesophageal fistula.

We herein report a case of unsuturable tracheoesophageal fistula developed after chemotherapy of a mediastinal lymphoma. Esophageal exclusion was primary performed to prevent continued contamination of the respiratory tract. In a second stage procedure the fistula was patched with the esophageal posterior wall and the digestive tract was restored by a substernal colic bypass. This case leads to discuss the management of extrinsic tumoral tracheal compression and reminds us of an old reported procedure for the cure of large tracheoesophageal fistula.

Esophagectomy for cancer in the patient aged 70 years and older.

BACKGROUND: Advanced age increases the risk of any major surgical intervention, particularly esophageal resection. High morbidity and increased mortality have been reported in operations for esophageal cancer in the elderly. METHODS: To determine outcome, risk factors, and the advisability of esophageal resection in the elderly, a single-institution retrospective review was performed of esophagectomy for cancer over a 14-year period. From January 1, 1980, to December 31, 1993, 540 patients underwent esophageal resection for esophageal cancer. These patients were divided into two groups: group 1, n = 89, patients 70 years of age or older; and group 2, n = 451, patients younger than 70 years of age. The two groups were compared according to preoperative risk factors, morbidity rate, mortality rate, mean stay in the hospital after operation, and long-term survival. RESULTS: Adenocarcinoma of the esophagogastric junction was the most common tumor in group 1 and was usually managed with a single incisional approach. There were no significant differences between the groups concerning morbidity (24.7% in group 1), mortality (7.8% in group 1), mean stay in the hospital (23.3 days in group 1), or long-term survival (59%, 23%, and 13% at 1, 3, and 5 years, respectively, in group 1). CONCLUSIONS: These results suggest that esophagectomy can be performed in selected elderly patients without increasing morbidity or mortality and with long-term survival.

Techniques of management of subglottic stenoses with glottic and supraglottic problems.

Glottic problems complicating a subjacent tracheal or subglottic stenosis may result from various causes, such as glottic closure due to fixation or paralysis of vocal cords, fibrous stenosing scars of the glottis, or instability of arytenoid cartilages. Resecting scar tissues, molding the closed glottis, and stenting a patent laryngeal lumen until consolidation are the basic means which, when associated in selected indications, allow recovery of respiration and speech through the normal routes.

Intermediate-term results after en bloc double-lung transplantation with bronchial arterial revascularization. Bordeaux Lung and Heart-Lung Transplant Group.

OBJECTIVE: Between May 1990 and January 1994, 18 patients underwent en bloc double-lung transplantation with tracheal anastomosis and bronchial arterial revascularization. Because at that time it was already suggested that chronic ischemia could be a contributing factor in occurrence of obliterative bronchiolitis, the purpose of this study was to evaluate, with a follow-up ranging from 22 to 69 months, the midterm effects of bronchial arterial revascularization on development of obliterative bronchiolitis. RESULTS: Results were assessed according to tracheal healing, functional results, rejection, infection, and incidence of obliterative bronchiolitis. There were no intraoperative deaths or reexplorations for bleeding related to bronchial arterial revascularization, but there were three hospital deaths and five late deaths, two of them related to obliterative bronchiolitis. According to the criteria previously defined, tracheal healing was assessed as grade I, IIa, or IIb in 17 patients and grade IIIa in only one patient. Early angiography (postoperative days 20 to 40) demonstrated a patent graft in 11 of the 14 patients in whom follow-up information was obtained. Ten patients are currently alive with a 43-month mean follow-up. Among the 15 patients surviving more than 1 year, functional results have been excellent except in five in whom obliterative bronchiolitis has developed and who had an early or late graft thrombosis. Furthermore, those patients had a significantly higher incidence of late acute rejection (p < 0.02), cytomegalovirus disease (p < 0.006), and bronchitis episodes (p < 0.0008) than patients free from obliterative bronchiolitis. CONCLUSION: We conclude that besides its immediate beneficial effect on tracheal healing, long-lasting revascularization was, at least in this small series, associated with an absence of obliterative bronchiolitis, thus suggesting but not yet proving the possible role of chronic ischemia in this multifactorial disease.

Acquired tracheoesophageal fistula and its management.

Tracheoesophageal fistulae (TEF) are severe lesions leading to serious and eventually fatal pulmonary complications. Currently, TEF are mainly iatrogenic, occurring in the course of tracheal intubation for resuscitation or malignant after invasion of both esophageal and tracheal walls. Difficulty in treatment results from the need to manage both the consequences of esophagotracheal communication and those of the illness responsible for fistula. Various carefully selected means may be used to achieve this aim: division and closure of the TEF, esophageal exclusion followed by gastric or colic bypass or push-through intubation. Abstention from treatment may be appropriate in hopeless situations.

Surgical treatment of nontumoral stenoses of the upper airway.

BACKGROUND: After 1970, the widespread use of nasotracheal intubation, avoiding tracheostomy and its pitfalls, resulted in more frequent laryngeal or laryngotracheal stenoses, which required more complex and sometimes multistaged procedures. METHODS: A series of 217 nontumoral stenoses of the upper airway were treated following the same therapeutic principles in the period 1978 to 1992. Two hundred one of them were iatrogenic postintubation strictures (92%); the others were posttraumatic (7), idiopathic (5), and various (4). RESULTS: One hundred twenty (55%) were tracheal stenoses and treated by resection and primary end-to-end anastomosis with 117 excellent or good results and three deaths. Length of the stenosis, old age, neuropsychological sequelae, and overall poor respiratory status of the patients made up the remaining difficulties in the treatment. Ninety-seven (45%) were laryngotracheal stenoses with much more complex surgical indications: 57 patients underwent tracheal and subglottic resection and anastomosis with 56 successes and one death, 7 had laryngotracheal resection and anastomosis with total cricoidectomy and consequently laryngeal stenting for 3 to 6 months (six successes, one death), 3 had supraglottic resection and anastomosis (three successes), 12 patients with glottic opening difficulties and short laryngeal stenosis underwent a laryngeal enlargement over a T tube without resection (11 successes, one death), and 18 were subjected to a complex combination of resection and modeling with 16 successes, 2 failures, and 1 death. Final results were successful in 208 cases (96%) with seven deaths and two failures. Mild phonetic sequelae were observed after laryngeal modeling. A minimal follow-up of 1 year has shown long-term stability of most repairs. CONCLUSIONS: Despite acceptable results, the therapeutic approach remains difficult for laryngotracheal stenoses involving the glottic and the supraglottic level as well as for those that have not responded to previous attempts at repair. In a few cases, despite a meticulous preoperative assessment, the surgical strategy can only be adopted intraoperatively. The key to surgical success is undoubtedly a careful preoperative treatment of infection and inflammation as well as a meticulous muco-mucosal approximation of healthy margins at the anastomosis.

The bronchial arteries: anatomic study and application to lung transplantation.

The bronchial arterial system (BAS) and its territory was studied in dissections of 40 fresh adult cadavers. The arterial distribution was assessed by catheterisation of the ostia and injection of contrast medium. The number of bronchial aa. varied from 2 to 4. The origin of the arteries was between the upper border of T5 and the lower border of T6 in 90% of cases. The intercostobronchial trunk was the virtually exclusively component of the right bronchial arterial system, present in 97.5% of cases. It was associated with an accessory right bronchial a. in 7.5% of cases, which was merely supplementary. A common arterial trunk for both bronchial systems was present in 50% of cases. The left BAS was characterised by the presence of a direct left bronchial a. (LBA) in 76% of cases, and by the combination of two LBAs in 20%, one of which was usually dominant. However, major anatomic networks between the different vessels found allowed reimplantation of the LBA alone in the former situation, and in the latter it was possible to rely on the dominant LBA alone when reimplantation of the different ostia was impossible. The proximity of the different ostia and the interostial interval, which was less than 1.5 cm on average, permitted multiple revascularisations by the same vascular supply.

Trasplante pulmonar y cardiopulmonar. Experiencia en 60 casos / Lung and cardiopulmonary transplantation. 60 cases experience

Se revisan 60 trasplantes pulmonares y cardiopulmonares (39 cardiopulmonares, catorce bipulmonares y siete unipulmonares) realizados entre 1988 y 1991 en Burdeos. La incidencia primaria del trasplante fue enfermedad respiratoria en 46 y enfermedad cardiaca en catorce casos. Seis pacientes fallecieron durante el primer mes del postoperatorio; doce entre el primero y el sexto mes debido fundamentalmente a complicaciones infecciones y episodios de rechazo agudo y cuatro después del sexto mes. En 37 pacientes con un período de seguimiento superior a seis meses se observaron seis casos de bronquiolitis obliterativa; uno de ellos requirió trasplante y los otros conco presentaron parámetros espirométricos sugestivos de brocquiolitis. Los otros 31 presentaron volúmenes pulmonares y flujos respiratorios entre el 70 y el 110 por ciento de los valores teóricos. Los factores de riesgo que pueden desaconsejar el trasplante pulmonar incluyen la presencia de infección en el receptor, la corticodependencia, adherencias pleurales y el mal estado general con desnutricón. El desarrollo de una nueva técnica de revascularización traqueobronquial ha permitido ampliar las indicaciones del trasplante bipulmonar,el cual se realiza hoy día con la misma frecuencia que el trasplante cardiopulmonar. Las técnicas de elección, según la patología de base, son: trasplante unipulmonar en las fibrosis pulmonares no acompañadas de infección; trasplante bipulmonar en las enfermedades pulmonares con supuración crónica y enfisema con gran hiperinsuflación; y trasplante cardiopulmonar en pacientes con enfermedad cardica y pulmonar asociadas.

[Left thoracotomy in the excision of cancers of the cardia and the lower third of the esophagus. Apropos of a series of 210 cases]. / La thoracophrénotomie gauche dans l'exérèse des cancers du cardia et du tiers inférieur de l'oesophage. A propos d'une série de 210 cas.

From January 1 1980 to December 1993, 210 patients underwent exeresis of a cancer of the cardia or the lower third of the oesophagus. There were 193 males and 17 females (mean age 63.5 years, range 18-84). Cancers were in an advanced stage in 56.6% (stage 0, 0.95%; stage 1, 9.04%; stage 3, 43.3%; stage 4, 6.19%). Postoperative morbidity was 21% and hospital mortality was 3.81%. Actuarial survival rate at 1, 3, 5 and 10 years were 64.1%, 23.9%, 17.7% and 12.8% respectively. The advent of the CT scan, better patient selection and improved nutrition management and postoperative care have greatly improved hospital mortality (7 deaths for 118 operations before 1987, i.e. 5.93% and 1 death for 92 operations since 1987, i.e. 1.08%. Creating a circumferential instead of radial phrenotomy and the possibility of raising the anastomosis to upper thorax or in combination with left access and cervicotomy have led to excellent immediate results and confirm our choice in this method.

[Iatrogenic stenoses of the respiratory tract. Evolution of therapeutic indications. Based on 217 surgical cases]. / Sténoses iatrogènes de la voie respiratoire. Evolution des indications thérapeutiques. A partir de 217 cas chirurgicaux.

The authors report a series of 217 non-neoplastic stenoses of the upper airways operated in the period 1978-1991. One hundred and twenty patients with tracheal stenoses underwent tracheal resection and end-to-end anastomosis, with 117 excellent results and 3 deaths. The treatment of 97 patients with laryngotracheal stenoses was much more complex and difficult to manage: Fifty-nine underwent tracheal and subglottic resection-anastomosis with 58 successes and 1 death--Seven had resection-anastomosis with total cricoidectomy and stenting. They were 6 successes and 1 death--Three had supraglottic resection-anastomosis with 3 successes--Twelve underwent laryngeal enlargement over a T-tube with successes in 11 cases and failure in 1 case. Sixteen had complex combinations of resection and modeling with 13 successes, 2 failures, and 1 death. In this series under the same therapeutic options, the results were successful in 96% of cases, with 4% of failures (7% of them resulting in death). The anatomical type, tracheal or laryngotracheal, length of the stenosis, neuropsychological sequelae, and overall poor respiratory status of the patients must be taken into account before deciding the therapeutic strategy. Old age is not a contraindication to tracheal resection, but is certainly a risk factor for morbidity and mortality. The key to success is undoubtedly careful preoperative preparation, treatment of local infection and inflammation, as well as meticulous mucomucosal approximation of healthy margins at the anastomosis.

Tuberculosis in transplanted lungs.

Over a 4-year period in four of 61 patients (6.5%) who survived lung transplantation, pulmonary tuberculosis developed at a mean of 7.5 months (range 3 to 13 months) after operation. Clinical and radiologic features were atypical. Definitive bacteriologic diagnosis, which was established on bronchial, sputum, and pleural fluid samples, may be delayed by the concomitant presence of other infective organisms and the necessity for repeated sampling. All patients were treated successfully with antituberculous chemotherapy, but one patient also required lobectomy. At a mean follow-up of 2.25 years (range, 1 to 3 years), three patients are free of active disease, and one patient had a recurrence at 2 years. Tuberculosis in transplanted lungs is an uncommon but serious infection that may elude diagnosis but respond well to treatment.

Long-term functional results after bilateral lung transplantation. Bordeaux Lung and Heart-Lung Transplant Group.

Between February 1988 and January 1992, 61 patients have undergone bilateral lung transplantations (42 heart-lung and 19 double-lung) in Bordeaux. The underlying diseases were primary or secondary hypertension (20), emphysema (22), or other diseases including cystic fibrosis, pulmonary fibrosis, silicosis, and sarcoidosis (19). Actuarial survival for double-lung and heart-lung transplant recipients was 66% and 72% at 1 year and 57% and 53% at 3 years, respectively. Forty-two patients were still alive 6 months after operation, and we studied their pulmonary function at the short and long term. All parameters except arterial carbon dioxide tension had improved dramatically at 6 months (p < 0.0001). Vital capacity, forced expiratory volume in 1 second, and forced expiratory flow rate between 25% and 75% of vital capacity were at 79% +/- 3%, 92% +/- 5%, and 105% +/- 8% of the predicted values, respectively. Arterial oxygen tension was 88 +/- 3 mm Hg. Nine months after operation, a slight decrease in forced expiratory volume in 1 second and forced expiratory flow rate between 25% and 75% of vital capacity appeared but values remained more than 75% predicted. This was related to the occurrence of obliterative bronchiolitis in 6 patients (14%). At 9 months, flow rates and oxygen tension of these 6 patients were highly different from those of patients free of obliterative bronchiolitis (p < 0.0002 for flow rates and p < 0.01 for oxygen tension). Only 1 patient required retransplantation. The others are living an almost normal life. Our results are discussed in view of the published reports on single-lung transplantation. Short-term results of bilateral lung transplantation are thus excellent and maintained on a long-term basis. Therefore, in our opinion, bilateral lung transplantation is the therapy of choice for pulmonary hypertension and emphysema.

Expanding wire stents in benign tracheobronchial disease: indications and complications.

Prosthetic tracheobronchial stents provide palliative treatment for narrowed airways where surgical resection is inadvisable. Over a 1-year period, 28 Gianturco expanding wire stents were used in 15 patients for nonneoplastic indications: pure fibrous airway stenosis (6), fibroinflammatory stenosis (4), and tracheobronchial malacia (5). Insertion was technically straightforward. A satisfactory airway lumen with immediate improvement in ventilatory function was obtained in all patients. After insertion all patients had an irritation-type cough that either subsided spontaneously (10 patients) or was successfully suppressed with inhaled corticosteroid therapy (5 patients). The most common complication (12 patients) was granuloma formation leading to stent removal in 3 patients with fibroinflammatory stenosis. Other complications were dysphagia (1), suction catheter entrapment (1), and fatal massive hemoptysis (1). At a mean follow-up of 13 months (range, 3 to 19 months) all remaining stents are functioning well with no displacement or infection. Overall results were satisfactory in pure fibrous stenoses and tracheobronchial malacia but poor in the presence of inflammation. Tracheobronchial wire stents can be successfully used in selected patients.