Airway epithelium-derived transforming growth factor-beta is a regulator of fibroblast proliferation in both fibrotic and normal subjects.

BACKGROUND: In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately. OBJECTIVE: The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model. RESULTS: Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2+/-6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 microm indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-beta, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-beta antibodies. CONCLUSION: These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-beta, which induces the prostaglandin E(2) synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication.

Induction chemotherapy followed by parenchyma-sparing surgery in medically inoperable NSCLC-results of a feasibility study.

PURPOSE: Feasibility trial to test the toxicity and outcome of three cycles of induction chemotherapy followed by limited surgery in medically inoperable early stage NSCLC patients. PATIENTS AND METHODS: Thirteen patients with NSCLC (stages I-IIIB) with insufficient cardio-respiratory reserves for the oncologically required lung resection, received three cycles of induction chemotherapy with cisplatin (100mg/m(2)) and docetaxel (85mg/m(2)) followed by parenchyma-sparing lung surgery. Operability was evaluated with pulmonary function tests, perfusion scintigraphy and cardiopulmonary exercise testing. In selected patients coronary angiography or myocardial perfusion scintigraphy was performed. Rate of R0-resections was taken as primary outcome. RESULTS: Twelve of 13 patients received the three cycles of chemotherapy as planned. The main grade 3/4 hematological toxicity was neutropenia (62%), non-hematological toxicity was neutropenic fever (23%) and cough/dyspnea (31%). Complete, partial and stable responses to chemotherapy were seen in 1, 10 and 2 patients, respectively-the overall response rate was 85%. No patient had tumor progression. Eleven/13 (85% (CI 95% 54, 97) %) patients underwent surgery (4 lobectomies, 2 segmentectomies, and 5 wedge resections), all had a pathologically complete resection of the tumor. There was one postoperative death due to myocardial infarction. The median disease-free and overall survivals were 57(CI 95% 36-78) months and 66(CI 95% 40-92) months, with a median follow up time of 58 months. The 1-, 2- and 4-year OS was 85%, 85% and 67%, respectively. There were no significant changes in any lung function parameter compared to the preoperative assessment. The FEV(1) showed a trend for improved values after surgery. CONCLUSION: Induction chemotherapy in medically inoperable patients followed by parenchyma-sparing surgery is feasible and yields very promising results.

Large cystic tumour at the chest wall mimicking an echinococcosis: a case report.

The authors report an atypical late onset of a big axillary lymphatic malformation in a 41-year-old male. Considering the patient's history and clinical findings at first presentation, the swelling was highly suspicious for malignancy or cystic echinococcosis. A consequent CT showed non infiltrative growth with inhomogeneous density but remained non conclusive regarding diagnosis. Subsequently incision biopsy revealed lymphatic tissue and raised suspicion for lymphatic malformation. The tumour was excised completely and showed no recurrence in a 1-year follow up. Late onset lymphatic malformations can mimic malignant tumours or other rare conditions such as echinococcosis which has to be taken into consideration as differential diagnosis especially in known areas of hydatid diseases.

The relevance of surgical therapy for bilateral and/or multiple pulmonary metastases in children.

PURPOSE: Pulmonary surgery is frequently used for the treatment of metastases in children with various malignant diseases. The benefit of an aggressive surgical treatment in children with bilateral and/or multiple pulmonary metastases is still discussed controversially. METHODS: A retrospective analysis of 10 children (7 girls, 3 boys; age range from 2 to 16.5 years) who underwent thoracotomy for bilateral and/or multiple pulmonary metastases was performed. The primary malignancies were osteosarcoma (n = 4), hepatoblastoma (n = 3), malignant peripheral nerve sheath tumor (n = 1), adrenocortical carcinoma (n = 1) and alveolar rhabdomyosarcoma (n = 1). Unilateral but multiple pulmonary metastases were found in 3 children. 7 patients showed bilateral pulmonary metastases. Preoperative induction chemotherapy with tumor regression and a subsequent decrease in the size and number of pulmonary metastases was mandatory for the surgery of metastases. RESULTS: Standardized bilateral thoracotomy was performed in 4 patients in 1 operation (in 1 patient combined with a hemihepatectomy), and in 3 patients, in 2 operations on different days. 5 children underwent re-thoracotomy due to recurrent pulmonary metastases (2 patients: unilateral; 3 patients: bilateral; 1 patient: twice bilateral). All visible and palpable metastases (1 - 25) were excised, either by wedge resection, by segment resection or by lobectomy. Postoperative artificial ventilation was necessary for 0 to 24 hours. Postoperative complications included intrathoracic secondary hemorrhage in 3 cases and pneumonia in 1 patient. 2 patients (20%) died of recurrent metastatic disease (osteosarcoma: 1; adrenocortical carcinoma: 1). During a mean follow-up period of 49 months (14 to 66 months after the last thoracotomy), 8 patients (80%) remained in complete remission without clinically relevant respiratory restrictions. CONCLUSION: Complete surgical resection of pulmonary metastases after response to induction chemotherapy may increase survival in carefully selected children, even in cases with multiple and recurrent metastatic disease. In children, bilateral thoracotomy within a single operation is possible without an increased complication rate.

Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC.

There are no data available combining transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and positron emission tomography (PET) in the staging of nonsmall cell lung cancer (NSCLC). The aim of the current study was to determine if these two methods can enhance the negative predictive value of the individual modality alone, for a specific lymph node station, and if this integrated approach can reduce the number of mediastinoscopies. A total of 113 patients with enlarged mediastinal lymph nodes (> or = 1 cm), who underwent both TBNA and PET scanning, were included. In 51 patients, histopathology, confirmed by surgical lymph node dissection, was compared with PET results and TBNA. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect malignant lymphadenopathy was 68 (13/19), 89 (119/134), 46 (13/28), 95 (119/125) and 86% (132/152) for PET, respectively; 54% (6/11), 100 (53/53), 100 (6/6), 91 (53/58) and 92% (59/64), respectively for TBNA; and 100 (11/11), 94 (50/53), 79 (11/14), 100 (50/50) and 95 (61/64) for combined TBNA and PET, respectively. Combination of transbronchial needle aspiration and positron emission tomography has the potential to allow adequate mediastinal staging of nonsmall cell lung cancer with enlarged lymph nodes in most patients without the need for mediastinoscopy.

Short- and long-term outcome after lung resection for invasive pulmonary aspergillosis.

BACKGROUND: Lung resection for invasive pulmonary aspergillosis (IPA) is controversial. Neutropenia, thrombopenia and poor general condition may increase perioperative morbidity and mortality, and the redeeming benefit is questionable. Therefore we analyzed short- and long-term outcome after lung resection for IPA. METHODS: 41 patients with hematological disease underwent lung resection for suspected IPA: lobectomy (23 patients), wedge-resection (16) and enucleation (2). RESULTS: 4 (10%) patients developed major complications: pleural aspergillosis, bronchial stump insufficiency, severe bleeding, ARDS. 11 (27%) patients showed minor complications: pleural effusion (6), pneumothorax (2), seroma (2) and hematothorax (1). 30-day mortality was 10 % (4 of 41 patients): two died of bacterial septicemia, two of disseminated aspergillosis. One (2%) death was possibly surgery-related. IPA was cleared in 87% of patients, fungal relapse occurred in 4 (10%) patients. Overall survival was 65%, 58% and 40% at 6 months, 12 months and 5 years. CONCLUSION: Lung resection for IPA even in profound cytopenia is feasible with acceptable morbidity and mortality. Fungal infection can be cured in more than 80 % of patients. Long-term outcome can be achieved if the hematological disease is under control.

[Thoracic drainage. What is evidence based?]. / Thoraxdrainagen. Was ist "evidence based"?

Pleural drainage becomes a vital measure to restore physiological conditions in cases of loss of pleural negative pressure, regardless its etiology. Therefore, it is not surprising that hardly any evidence based publications on this topic are available. For the treatment of pleural empyema,the history of pleural drainage goes back to antiquity.Nowadays, quite a number of synonymously used terms are wrongly employed instead of the correct terms of thoracic or pleural drainage. Indications for placing a pleural drainage are: pneumothorax, pleural effusion, pleural empyema,hemothorax and chylothorax. As a standard method, it is recommended that the pleural drainage be placed in the fifth or sixth intercostal space in the anterior axillary line. It is not advisable to use a closed insertion with the help of a trocar due to the significantly increased risk of injury. The insertion of a pleural drainage when correctly placed is a safe procedure; rare typical complications involve the wrong placement of the drainage, hemorrhage or infection like pleural empyema. The complication rate, however, does not exceed 3%.

[Small breast carcinomas--less axillary surgery?]. / Kleine Mammakarzinome--weniger axilläre Chirurgie?

In view of introducing less invasive or selective axillary procedures for small breast cancers we investigated our own pT1 tumor patients. The incidence of pT1 carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the overall survival were analyzed. From 1983 till 1997 185 consecutive patients have been treated for breast cancers with a diameter of < or = 20 mm. The survival data after Kaplan-Meier are based on a cohort of 117 patients with a median follow up of at least seven years. There were seven patients with a pT1a carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary lymph nodes were counted by the pathologists. The axillary involvement clearly depends on the size of the primary tumor: no nodal involvement in patients with pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c carcinoma. Not one single axillary relapse was detected after this follow up time. The overall ten years survival for patients with pT1a was 100%, 91% for pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to detect more small breast cancers in pN0 stage. Risks and benefits of axillary dissection have to be carefully evaluated. Axillary involvement of small breast cancers is rare. Only a minority of patients will benefit from routine axillary lymphadenectomy, while the majority runs the risk of complications. The sentinel lymph node (SLN) procedure offers a selective approach to this dilemma.

Histopathological criteria for intestinal neuronal dysplasia of the submucosal plexus (type B)

The aim of this study was to review critically the diagnostic features of intestinal neuronal dysplasia type B (IND B). Over a period of 5 years colonic mucosal biopsies of 773 children with symptoms of chronic constipation were examined. Four biopsies taken 2-10 cm above the pectinate line were cut in serial sections and histochemical lactate dehydrogenase, succinate dehydrogenase, (SDH) and acetylcholinesterase (AChE) reactions performed. Presence of giant ganglia of the submucosal plexus, being characterized by more than seven nerve cells, established the diagnosis of IND B. Giant ganglia were found to be age-independent changes, while hyperplasia of the submucosal plexus, increase of AChE activity in nerve fibres of the lamina propria and low SDH activity in nerve cells proved to be age-dependent findings which disappear during the maturation of the enteric nervous system. Using these criteria IND B was diagnosed in 209 children. In 64 of these patients a combination of IND B and aganglionosis (Hirschsprung's disease) was found. IND B seems to be related to premature expression of laminin A during embryogenesis, resulting in premature nerve cell differentiation in the myenteric and submucosal plexus, which in turn blocks neuroblast colonization of the rectum. IND B, hypoganglionosis and aganglionosis, which are often combined, may therefore be considered to be different manifestations of the same developmental abnormality.

The neuropathological diagnosis of neuronal intestinal dysplasia (NID B).

Between 1986 and 1991 773 infants were investigated by biopsy. 209 children suffered from a neuronal dysplasia of the submucous plexus (NID B). 64 of these 209 cases had concomitant Hirschsprung's disease with NID. The combination of Hirschsprung's disease with NID was established at biopsy not earlier than at 12 +/- 6 months of age. The classical form of an isolated aganglionosis had a median age at diagnosis of 4 +/- 2 months. The preconditions for a reliable diagnosis of NID are mucosal biopsies with submucosa taken 1, 3 and 9 cm above the pectinate line, the preparation of 15 microns thick serial sections, a acetylcholinesterase- and lactate-reaction and a systematic examination of all serial sections. Giant ganglia, which are 2-3 times as large as normal ganglia and having more than 7 LDH-positive nerve cells (10 +/- 3 nerve cells in the mean), are the most relevant parameters in the diagnosis of NID. They can be observed in infants as well as in adults. The NID proximal to aganglionosis is in principle not different from an isolated form of NID. Increase of acetylcholinesterase-activity in muscularis mucosae and lamina propria mucosae and a "hyperplasia" of the submucous plexus in early infancy disappears with advancing age and are very seldom observed at 2 years of age or in adulthood. NID B is the mildest form of a developmental abnormality of the autonomic nervous system, which shows in most cases a spontaneous normalization of gut motility.(ABSTRACT TRUNCATED AT 250 WORDS)