[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.

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.

BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

Influence of thoracic epidural analgesia on cardiovascular autonomic control after thoracic surgery.

BACKGROUND: Thoracic epidural analgesia (TEA) is effective in alleviating pain after major thoracoabdominal surgery and may also reduce postoperative mortality and morbidity. This study investigated cardiovascular autonomic control in patients undergoing elective thoracic surgery and its modulation by continuous TEA. METHODS: Thirty-eight patients were randomly assigned to receive patient-controlled analgesia (PCA group) or thoracic epidural analgesia (TEA group) with doses of bupivacaine (0.25% during operation, 0.125% after operation) and fentanyl (2 microg ml(-1)). Heart rate variability (HRV), baroreflex function and pressure response to nitroglycerine and phenylephrine were assessed before operation, 4 h after the end of surgery (POD 0) and on the first and second postoperative days (POD 1 and POD 2). RESULTS: Early after surgery, all HRV variables and baroreflex sensitivities were markedly decreased in both groups. In the TEA group, total HRV and its high-frequency components (HF) increased towards preoperative values at POD 1 and POD 2, whereas the ratio of low to high frequencies (LF/HF) was significantly reduced (mean (SD), -44 (15)% at POD 0, -38 (17)% at POD 1, -37 (18%) at POD 2) and associated with blunting of the postoperative increase in heart rate and blood pressure. In the PCA group, the ratio of LF/HF remained unchanged and the decrements in HRV variables persisted until POD 2. In the two groups, baroreflex sensitivities and pressure responses recovered preoperative values at POD 2. CONCLUSIONS: In contrast with PCA management, TEA using low concentrations of bupivacaine and fentanyl blunted cardiac sympathetic neural drive, resulting in vagal predominance, while HRV variables were better restored after surgery.

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.

Management of postpneumonectomy Aspergillus empyema extending into the thoracic wall: a plea for radical surgery and caution when using liposomal amphotericin B.

Semi-invasive aspergillosis is a rare disease leading to severe complications even in fully immunocompetent patients. The therapeutic role of systemic and intrapleural antifungal agents remains not well known. We report herein the case of a 54-year-old woman who developed Aspergillus empyema invading the thoracic wall and subcutaneous tissues after completion pneumonectomy for aspergilloma. She initially was treated conservatively with systemic and intrapleural amphotericin B without any success and developed a severe anaphylactic reaction to intravenous liposomal amphotericin B (Ambisome). She then underwent an open-window thoracotomy with intrathoracic transposition of a latissimus dorsi muscle flap and was started on itraconazole therapy. The thoracostomy was closed after 6 months and the patient is doing well without any signs of recurrent infection after 3 years.

Management of women with ductal carcinoma in situ of the breast: a population-based study.

BACKGROUND: Increasing incidence of ductal carcinoma in situ (DCIS) confronts patients and clinicians with optimal treatment decisions. This multidisciplinary study investigates therapeutic modalities of DCIS in daily practice and provides recommendations on how to increase quality of care. PATIENTS AND METHODS: All women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from 1995 to 1999 were considered. Information concerned patient and tumor characteristics, treatment and outcome. Factors linked to therapy were determined using a case-control approach. Cases were women with treatment of interest and controls other women on the study. RESULTS: Most DCIS cases (62%) were discovered by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS), 18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%) chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction after mastectomy. Method of discovery, multifocality, tumor localization, size and differentiation were linked to the use of BCS or lymph node dissection. CONCLUSIONS: Because of important disparities in DCIS management, recommendations are made to increase quality of care, in particular to prevent axillary dissection or bilateral mastectomy and to increase the use of radiotherapy after BCS.

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.

Myocardial revascularization and bilateral lung transplantation without cardiopulmonary bypass.

Coronary artery disease is occasionally encountered in lung transplant recipients and is a risk factor for perioperative complications and poor survival. Besides combined heart-lung transplantation, various techniques of myocardial revascularization can be performed before, or at the time of lung transplantation. We report herein a patient with end-stage bronchoemphysema and two-vessel coronary disease who underwent 'off-pump' coronary artery bypass graft immediately followed by bilateral lung transplantation.

Carcinoma arising in congenital lung cysts.

We report on a patient presenting with a bronchioloalveolar carcinoma fortuitously detected in the wall of a bronchogenic cyst. Evidence suggests that unstable epithelial cells contained within the cyst wall may lead to premalignant proliferation and neoplasia. In the current case, we demonstrated an increased proliferative activity in some areas of the cyst consistent with atypical adenomatous hyperplasia. Hence, we stress the importance of close follow-up of all suspected congenital lung cysts because of their potential malignant degeneration.

Management and outcome of patients undergoing thoracic surgery in a regional chest medical centre.

BACKGROUND AND OBJECTIVE: The main objective of this study was to assess mortality and morbidity after thoracic surgery in a medical centre, without resident chest surgeons and anaesthesiologists, and to determine specific risk factors. METHODS: A prospective cohort study using a local database which includes patients' clinical characteristics, results of preoperative investigations, surgical and anaesthesia data and all postoperative complications was undertaken. Two hundred and seventy-three consecutive patients undergoing thoracic surgery from 1992 to 1999 were studied. The referral chest medical centre was without resident thoracic surgeons or anaesthesiologists; postoperative care was led by local chest physicians according to standardized protocols and in close collaboration with university-based surgeons and anaesthesiologists. RESULTS: The majority of patients had lung cancer (71%) and underwent resection of at least one lobe (62%). Thirty-day mortality rate was 2.2% and one or more complications occurred in 74 patients (27%). Three patients had to be transferred to a university hospital for further treatment. Univariate predictors of complications included age (> 70 years), history of smoking, body mass index, as well as the extent and duration of surgery. After multiple logistic regression analysis, smoking (current or past), prolonged surgery (>120 min) and major lung resection (pneumonectomy or bilobectomy) remained the only independent risk factors. CONCLUSIONS: Overall perioperative mortality and morbidity rates did not exceed those reported from large teaching hospitals. In selected patients, thoracic surgery can be safely performed in a specialized chest medical centre without on-site surgeons and anaesthesiologists.

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.

Perioperative medical management and outcome following thymectomy for myasthenia gravis.

PURPOSE: To describe the evolution of the perioperative management of myasthenia gravis (MG) patients undergoing thymectomy and to question the need for systematic postoperative ventilation. CLINICAL FEATURES: We collected data retrospectively from 36 consecutive MG patients who underwent thymectomy over a 21-yr period, via transthoracic, -cervical or -sternal incisions (n=5, n=7, n=24, respectively). From 1980 to 1993, a balanced anesthetic technique (n=24) included various inhalational agents with opiates and myorelaxants (in eight cases); 22 patients were admitted to the intensive care unit (ICU). Since 1994, i.v. propofol was combined with epidural bupivacaine and sufentanil (n=12); all patients were admitted to the postanesthesia care unit. Short-term postoperative ventilation (median time four hours, range from three to 48 hr) was required in eight patients who had longer hospital stay (median stay=12 days, range (8-28) vs five days (4-15) for patients with early extubation, P <0.05) but similar clinical improvement six months after thymectomy. Postoperative ventilatory support was required more frequently when a balanced anesthetic technique was used (odds ratio=4.2 (1.1-9.7), P=0.03) and particularly when myorelaxants were given (odds ratio=13.9 (2.1-89.8), P=0.009). Leventhal's scoring system had low sensitivity (22.2%) and positive predictive values (25%). CONCLUSIONS: Our data show that the severity of MG failed to predict the need for postoperative ventilation. A combined anesthetic technique was a safe and cost-effective alternative to balanced anesthesia as it provided optimal operating conditions and resulted in fewer admissions in ICU and shorter hospital stays.

Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease.

OBJECTIVE: Approximately one out of five patients with Graves' disease (GD) undergoes a thyroidectomy after a mean period of 18 months of medical treatment. This retrospective and non-randomized study from a teaching hospital compares short- and long-term results of total (TT) and subtotal thyroidectomies (ST) for this disease. METHODS: From 1987 to 1997, 94 patients were operated for GD. Thirty-three patients underwent a TT (mostly since 1993) and 61 a ST (keeping 4 to 8 grams of thyroid tissue--mean 6 g). All patients had received propylthiouracil and/or neo-mercazole and were in a euthyroid state at the time of surgery; they also took potassium iodide (lugol) for ten days before surgery. RESULTS: There were no deaths. Transient hypocalcemia (< 3 months) occurred in 32 patients (15 TT and 17 ST) and persistent hypocalcemia in 8 having had TT. Two patients developed transient recurrent laryngeal nerve palsy after ST (< 3 months). After a median follow-up period of seven years (1-15) with five patients lost to follow-up, 41 patients having had a ST are in a hypothyroid state (73%), thirteen are euthyroid (23%), and two suffered recurrent hyperthyroidism, requiring completion of thyroidectomy. All 33 patients having had TT--with follow-ups averaging two years (0.5-8)--are receiving thyroxin substitution. CONCLUSIONS: There were no instances of persistent recurrent laryngeal nerve palsy in either group, but persistent hypoparathyroidism occurred more frequently after TT. Long after ST, hypothyroidism developed in nearly three of four cases, whereas euthyroidy was maintained in only one-fourth; recurrent hyperthyroidy was rare.

Factors influencing improvement and remission rates after thymectomy for myasthenia gravis.

BACKGROUND: Thymectomy has become an accepted option in the treatment of myasthenia gravis (MG). However, the optimal selection of patients for surgery remains controversial. OBJECTIVE: The objective of the study is to define factors influencing improvement and remission rates after thymectomy for MG. METHODS: We retrospectively reviewed our experience in the surgical management of patients with MG over the last 20 years, and analyzed if patient's age, sex, preoperative Osserman Stage, thymic histology, duration of symptoms, or radiological findings influenced outcome. RESULTS: There were 25 women and 10 men. Most of them presented with Osserman stage IIA (n = 12) and stage IIB (n = 17). Hyperplasia of the thymus was observed in 15 patients (43%), thymoma in 12 (34%), and atrophic or normal thymus in 8 (23%). Computed tomography (CT) had a positive predictive value of 91% in detecting thymoma and of 80% in detecting thymic hyperplasia. Over a mean follow-up of 96 months, MG improved markedly in 26 patients. Postoperative improvement was significantly greater in patients with advanced MG (stage IIB, III and IV), whereas a higher rate of remission occurred in patients with mild MG (stage I and IIA), and in those with thymic hyperplasia. No relation was observed between outcome and age, sex, duration of symptoms and abnormal CT findings. CONCLUSIONS: The beneficial effects of thymectomy are characterized by postoperative clinical improvement in most patients with moderate to severe preoperative myasthenic involvement and by a higher remission rate in patients with thymic hyperplasia and/or mild myasthenic symptoms.

[Thyroid cancers: the Geneva experience]. / Cancers de la thyroïde: expérience genevoise.

AIM OF THE STUDY: To study the survival of patients with thyroid cancer operated in the same centre from 1978 to 1999. PATIENTS AND METHOD: This retrospective study included 218 patients operated on for thyroid carcinoma from january 1978 to december 1999. Modified neck dissection was performed only in the presence of one or more suspected lymph nodes. The stage of the cancer was defined according to the last TNM classification (1997). Survival data were taken from the Geneva Tumour Registry (168 patients = 77% of the series, 109 papillary carcinomas, 37 follicular, 14 undifferentiated and 8 medullary carcinomas). RESULTS: The overall 5, 10 and 15-year survival rates were respectively 88%, 84% and 80%. Papillary carcinoma was associated with the best survival at 5, 10 and 15 years (99%, 97% and 93%), despite a recurrence rate of 20% treated mainly by surgery often associated with radioiodine therapy. Follicular carcinoma had a survival rate of 83% at 5 years and 75% at 10 years. Undifferentiated carcinoma had a median survival rate of 56 days. None of the 8 patients with medullary carcinoma had died from that cancer in this series. CONCLUSION: Thyroid carcinoma carries such a good prognosis (except for undifferentiated carcinoma) that invasive surgery at first operation, like radical neck dissection, is not justified, despite a high rate of recurrence.

[Indications for lung transplantation in advanced cystic fibrosis]. / Indikation zur Lungentransplantation bei fortgeschrittener zystischer Fibrose.

Lung transplantation has become a valid therapeutic option for cystic fibrosis patients with end-stage lung disease. The indication for transplantation does not rely on strict criteria only but must be evaluated case by case. In particular, the dynamics of the clinical course need to be considered with regard to impaired physical performance, recurrent infections, decline in pulmonary function and weight loss. Important risk factors are a poor nutritional status, osteoporosis, liver involvement, previous pleurodesis and the occurrence of multiresistant bacteria. Management and assessment of cystic fibrosis patients for lung transplantation is complex. Therefore patients should be referred to specialised centres at an early stage.