Biomedical subjects

G Friedel

Publications and source records attributed to G Friedel.

At least 37 records · Page 2Linked to original sources

PubMed1998

Intraoperative thoracic sonography.

In contrast to its use in other surgical disciplines, intraoperative sonography has so far been of minor importance in thoracic surgery. The technique of intrathoracic, intraoperative, ultrasonic examination was applied in 85 patients with different indications: in 61 patients during thoracoscopy, in 24 patients during open thoracic surgery. 6 patients eventually underwent a combination of both procedures. In order to improve the intrathoracic maneuverability of the sonographic probe we developed an electrically controllable handle for the probe. The examinations showed a high sensitivity of thoracoscopic ultrasonography for localization of intrapulmonary tumors. In addition, ultrasound was applied to assess the operability of central tumors. The sound frequency available so far for intraoperative application allows a safe distinction of non-infiltrating tumors from vascular structures; the reliable identification of an infiltration mostly requires a higher resolution. If our experiences are confirmed by further application of the method, explorative thoracotomies will surely be partly replaced by explorative thoracoscopic interventions. Ultrasonography has also proved to be useful in visualisation of mediastinal lymph-nodes and tumors, with the possibility of assessing their size.

Abscess↗

PubMed1997

Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site.

Lack of tumor selectivity is a severe limitation of cancer chemotherapy. Consequently, reducing dose-limiting organ toxicities such as the cardiac toxicity of doxorubicin (Dox) is of major clinical relevance. Approaches that would facilitate a more tumor-selective anticancer therapy by using nontoxic prodrugs that are converted to active anticancer agents at the tumor site have been the subject of intensive research. One potential method to overcome the cardiac toxicity of Dox is to apply a nontoxic, glucuronide prodrug (HMR 1826) from which Dox is released by the action of beta-glucuronidase, an enzyme present at high levels in many tumors. Using a recently developed, isolated, perfused human lung model, we compared the uptake of Dox into normal lung and lung tumors after a 2.5-h lung perfusion with doxorubicin (n = 8) and with the novel doxorubicin glucuronide prodrug (n = 8). Dox showed a poor uptake into lung tumors as compared with normal lung [mean Dox concentration at the end of perfusion, 1.78 +/- 3.11 (median, 0.66) microg/g versus 22.03 +/- 10.4 (median, 18.5) microg/g; P < 0.001]. However, after perfusion with HMR 1826, the level of Dox in tumor tissue was about 7-fold higher than after perfusion with Dox itself [14.04 +/- 12.9 (median, 12.9) microg/g versus 1.78 +/- 3.11 (median, 0.66) microg/g, P < 0.05, n = 8]. In vitro experiments showed a significantly higher beta-glucuronidase expression and activity in the tumors. The extent of in vitro cleavage of HMR 1826 by homogenized lung tissue was closely related to the content of beta-glucuronidase (r = 0.9834, P < 0.0001). When D-saccharolactone, a specific inhibitor of beta-glucuronidase, was added to the perfusate containing HMR 1826, no accumulation of Dox in lung tissue was seen. These data indicate that the high Dox levels achieved in the tumors with HMR 1826 resulted from cleavage of the prodrug by beta-glucuronidase at the tumor site. Thus, the problem of poor Dox uptake into lung tumors could be circumvented by applying the doxorubicin glucuronide prodrug. Several lines of evidence based on both ex vivo and in vitro results indicate that the approach described using a glucuronide prodrug may be useful in facilitating more selective delivery of chemotherapy to tumors in humans.

Aged↗

PubMed1997

Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases.

OBJECTIVES: The International Registry of Lung Metastases was established in 1991 to assess the long-term results of pulmonary metastasectomy. METHODS: The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), the United States (n = 4) and Canada (n = 1). Of these patients, 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 cases, sarcoma in 2173, germ cell in 363, and melanoma in 328. The disease-free interval was 0 to 11 months in 2199 cases, 12 to 35 months in 1857, and more than 36 months in 1620. Single metastases accounted for 2383 cases and multiple lesions for 2726. Mean follow-up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risks of death, and multivariate Cox model. RESULTS: The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years, and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease-free interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27% for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free intervals of 36 months or more, and single metastases. CONCLUSIONS: These results confirm that lung metastasectomy is a safe and potentially curative procedure. Resectability, disease-free interval, and number of metastases enabled us to design a simple system of classification valid for different tumor types.

Adolescent↗

PubMed1997

Analysis of CYP2D6 expression in human lung: implications for the association between CYP2D6 activity and susceptibility to lung cancer.

We have studied whether CYP2D6 is expressed in human lung tissue, using a specific and sensitive reverse transcriptase-polymerase chain reaction method and immunohistochemistry. Seven out of the eight patients were extensive metabolizers as shown by genotyping for the CYP2D6 (debrisoquine-sparteine) polymorphism. To investigate whether expression of CYP2D6 in lung tumours is different from that in normal lung tissue, tumour tissue samples were also obtained from the same eight patients. Correctly spliced CYP2D6 mRNA was detected by RT-PCR analysis in human liver and duodenum but not in any of the lung samples. In accordance with these negative results, immunoreactivity for CYP2D6 protein, using specific monoclonal and polyclonal antibodies, was very low or absent. No specific cell type of lung tissue showed strong immunoreactivity for CYP2D6, although expression of CYP3A could be clearly demonstrated in the same tissue samples. Moreover, a Western blot analysis revealed no signal in lung microsomes from two additional extensive metabolizers. Taken together, these results indicate that expression of CYP2D6 in human lung is absent or very low. These findings thus argue against a significant local metabolic activation of procarcinogenic agents by CYP2D6 in the lung.

Aged↗

PubMed1997

[Assessment of current pleurodesis procedures exemplified by pneumothorax].

This survey addressed common methods of video-assisted thoracoscopic pleurodesis for spontaneous pneumothorax. A questionnaire asking for frequency, recurrence rate and complications of the different methods of pleurodesis was sent to all hospitals that belong to the German Society for Thoracic Surgery. 19 hospitals reported on a total of 1365 operations. 88 recurrences (6.5%), 26 severe bleeding complications (1.9%), 39 persisting air leaks (2.9%) and two hospital deaths (0.1%) had been observed. Pleurectomy and pleural abrasion were the most common procedures but induced significant (p = 0.01) more bleeding complications (3.1% and 2.6%) than all other methods of pleurodesis (0.4%). Overall recurrence rates depended significantly on the chosen procedure (p = 0.0013). Pleurectomy (4.4%) and coagulation of the pleura (2.7%) showed better results than the average. Due to smaller numbers of operations and the widely differing results this significance cannot be shown for the individual recurrence rates of the different clinics. This survey demonstrated a trend towards lower rates of recurrence and complications after coagulation of the pleura parietalis. The retrospective character of the investigation and extremely different recurrence rates for different hospitals demand cautious interpretation of these results.

Blood Loss, Surgical↗

PubMed1997

[Guidelines for quality assurance in bronchial carcinoma].

Quality management in lung cancer needs interdisciplinary cooperation among thoracic surgeons, pneumologists, oncologists and radiologists. This requires defined standards in the structure, process and outcome quality of the involved departments. The German Society for Thoracic Surgery has established a concept for internal and external quality assurance of operative treatment of lung cancer, according to the requirements for quality management developed by Selbmann. The future calls for the integration of nonoperative treatments in conjuction with relevant specializations.

Carcinoma, Bronchogenic↗

PubMed1996

The ex-vivo isolated, perfused human lung model: description and potential applications.

An ex-vivo isolated, perfused, and ventilated human lung (IPHL) model is well suited for many kinds of physiological, pharmacological, and surgical studies, when the physiological and biochemical conditions in the lung can be maintained near to those in vivo. The aim of this work was to develop such a model. The lung preparations used were available after resection because of bronchial carcinoma. Since the tumor remains intact in these anatomical preparations, this model is particularly suitable for investigation of the pharmacokinetics and effects of anticancer agents. Carrying out a series of 52 IPHL experiments (with 11 whole-lung preparations and 41 lobe preparations), we have established an IPHL model which allows extracorporeal perfusion and ventilation of the resected lungs in physiological conditions for 2-3 hours. The net weight gain during the experiment, wet-to-dry weight ratio for lung tissue, angiography of the pulmonary artery, pulmonary vascular resistance, color and fluorescence of the lung surface, and alveolar gas diffusion into the perfusate proved to be useful parameters to assess the stability of the preparations and the quality of the experiments. To confirm that an intraparenchymal tumor was perfused via the pulmonary artery, methods to detect avidin and dextran-biotin in tumor tissue after administration into the perfusion solution were employed. Histological examination of bronchial as well as tumor tissue, a computerized histoanalyzation, and a tumor grading program demonstrated that IPHL experiments did not interfere with the grading and staging of the tumors-an important ethical precondition for the use of human preparations in an extracorporeal perfusion model.

Carcinoma, Bronchogenic↗

PubMed1996

Video-assisted thoracoscopic pleurodesis. A survey conducted by the German Society for Thoracic Surgery.

As video-assisted thoracoscopic surgery has been performed for more than five years an inquiry was made to register and if possible to evaluate different pleurodesis procedures in the treatment of pneumothorax in Germany. 19 institutions provided information about 1365 operations. Overall there were 88 recurrences (6.5%). 26 (1.9%) severe bleeding complications or hemothorax and 39 (2.9%) persisting air leaks required further interventions. There were two (0.1%) hospital deaths. Recurrence rates showed a significant (p < 0.001) correlation to the type of pleurodesis used. Talcum pleurodesis had no recurrences and fibrin glue pleurodesis had the highest rate of recurrence (16.4%) both procedures being less frequent. After causal treatment, i.e. resection without any pleurodesis, recurrence rate is inconsistent and was 10.2% overall. Pleural abrasion was followed by a recurrence rate of 7.9% and pleurectomy of 4.4%. Both procedures induced significantly (p = 0.01) more bleeding complications (about 3%) than other procedures (0.4%). Promising was coagulation of the pleura parietalis with a recurrence rate of only 2.7% and a low rate of complications.

Data Collection↗

PubMed1996

[Radical lung surgery interventions with special reference to lymphadenectomy].

Intraoperative lymph node staging plays an essential part in the surgical treatment of lung cancer. The mean number of resected lymph nodes in 237 patients was 17, with a minimum of 1 and a maximum of 60. The largest number was found in N1 regions as expected. The number of resected nodes in the paratracheal, tracheobronchial and subcarinal region was 4, in the paraoesophageal and ligament region 1.2. Twenty-two percent of the whole group showed an N2 situation. In 45% of the patients with N2 invasion, we found a lymph node skipping and in 25% only one positive N2 node. Thus, it is obvious that without a systematic lymph node dissection an exact staging is not possible.

Carcinoma, Bronchogenic↗

PubMed1996

[Thoracic surgery in advanced age].

From 1990 through 1992, 70 patients 70 years of age or older (mean 72.8 years) underwent surgery for lung cancer at our hospital (47 males/23 females). 68 patients took part in a follow-up. Operative treatment consisted of standard lung resections in 42 cases. 17 patients underwent enlarged resections. In the postoperative period, complications occurred in 32 cases (47%). The overall operative mortality rate of 13% was mainly due to concomitant cardiovascular diseases and enlarged lung resections. Critical preoperative evaluation of the patients' functional status and selection of the proper operative procedure promise a successful treatment of lung cancer in the elderly.

Aged↗

PubMed1995

Immunohistochemical localization of cytochrome P450 2E1 in human pulmonary carcinoma and normal bronchial tissue.

Cytochrome P450 2E1 (CYP2E1) is a major xenobiotic-metabolizing enzyme but data concerning its extrahepatic expression are few. CYP2E1 can metabolically activate many procarcinogens and therefore its presence in the lung might play a role in bioactivation of procarcinogens, so we studied the expression and localization of CYP2E1 in primary pulmonary carcinomas and surrounding normal bronchial tissue from 28 patients. Seromucous glands showed expression of CYP2E1 in 19 and bronchial epithelium in 18 of the 28 samples of normal bronchial tissue. Thirteen of the corresponding cases of primary pulmonary carcinoma showed staining for CYP2E1. In 11 of these 13 cases, CYP2E1 was also present in normal bronchial tissue. There was no statistically significant difference in the expression of CYP2E1 between adenocarcinomas and squamous cell carcinomas. No association was observed between the expression of CYP2E1 in tumour tissue and normal bronchial tissue. However, there was a significant correlation between the expression of CYP2E1 in seromucous glands and bronchial epithelium (r = 0.61, P < 0.01) of normal tissue. We conclude that CYP2E1 can be present in both normal and neoplastic bronchial tissue.

Adenocarcinoma↗

PubMed1995

Immunohistochemical localization of cytochrome P450 3A in human pulmonary carcinomas and normal bronchial tissue.

The cytochrome P450 (CYP) enzymes metabolize drugs and other xenobiotics in liver and also in some extrahepatic tissues. We have studied the expression and localization of CYP3A in primary lung tumours and normal lung tissue from the same patients. Thirty-two patients undergoing partial or total lung resection for therapy of primary pulmonary carcinoma were included in this study. Immunohistochemical staining for CYP3A was performed with a modification of the ABC technique. Eight of the 32 cases of primary pulmonary carcinoma showed expression of CYP3A. In 12 of the 32 cases of normal tissue, the seromucous glands were positive for CYP3A. The bronchial epithelium was positive for CYP3A in 11 cases. We observed no correlation between CYP3A expression in tumour tissue and that in seromucous glands or bronchial epithelium. We conclude that CYP3A is present in both normal and cancerous lung tissue. Our findings suggest, however, no co-expression of CYP3A in lung cancer.

Adult↗

PubMed1995

[Minimally invasive surgery of large bullous pulmonary emphysema].

An enormous pulmonary cyst (phi approx. 20 cm) in a 72-year-old male patient with large bullous pulmonary emphysema caused compression of the right lung and the mediastinum with consecutive, O2-dependent dyspnoea at rest. The symptoms did not improve under conservative therapy of an accompanying COPD. Thus, in spite of two heart attacks in the previous history, an operation with bullectomy was indicated. A thoracotomy had to be avoided because of the very high cardiac risk. In the present case, a minimally invasive procedure enabled the complete cyst resection with a smooth postoperative course and an excellent functional therapeutic result.

Aged↗

PubMed1994

The significance of prognostic factors for the resection of pulmonary metastases of breast cancer.

Breast cancer is the most common malignant disease in women in Europe. In 15-25% of cases, the isolated formation of pulmonary metastases occurs. To date these metastases have been treated mainly by chemotherapy, radiotherapy, or hormone therapy. However, good results through pulmonary metastatic resection have been reported increasingly in recent times. From 1979 to 1992, 103 breast-cancer patients underwent surgery for suspected pulmonary metastases in our clinic. Intraoperatively in 88% of the whole group the metastases were confirmed, but in the other 12% they proved to be benign tumors or primary bronchial carcinomas. The operative therapy is standardized in our clinic. The approach is via a median or transverse sternotomy. Wedge resection is the normal procedure, undertaken in 55% of the cases. Complications, which were completely reversible in all cases, occurred in 3%. The 30-day mortality rate was 0%. In the whole patient population, the actuarial 5-year survival was 27%; it was 31% among the completely resected women, whereas no patient undergoing incomplete resection survived 5 years. Taking prognostic criteria into account, there are clear trends. When the disease-free interval exceeded 2 years, the actuarial 5-year survival was 33%, and if the receptor status of the primary tumor was positive, the 3-year survival was 61% compared to 38% for cases with negative receptor status. If a solitary metastasis was removed, the actuarial 5-year survival was 35% as opposed to 0% in cases with more than five metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[The status of surgical thoracoscopy in thoracic surgery].

Video-assisted thoracoscopic surgery is viewed as a sparing and safe alternative to thoracotomy for a wide spectrum of benign thoracic diseases. However the loss of palpation as well as the insufficiency of complete mediastinal lymphadenectomy are responsible for the uncertainty of the new method concerning curative oncological therapy. During the last two years we could replace thoracotomy by operative thoracoscopy in nearly all cases of recurrent pneumothorax and recurring pleural effusion. In a series of 447 endoscopic operations in 350 patients following distinct indications and strong prerequisites in terms of operating team and infrastructure of our department we could establish a high standard for this new operating method. The good postoperative results of this large series of thoracoscopic operations indicate the high rank of this new technique in thoracic surgery. Recurrence rates of 1.5% for pneumothorax surgery and 0 for pleurectomy for malignant pleural effusion can be compared to those in open thoracic surgery. Six weeks after the operation the postoperative lung function was normal in 80% of an initial group of patients.

Humans↗

PubMed1993

Prerequisites, indications, and techniques of video-assisted thoracoscopic surgery.

During the last two years video-assisted operative thoracoscopy has introduced new impetus into thoracic surgery. Today it is viewed as a sparing and safe alternative to thoracotomy for a wide spectrum of indications. The prerequisites, instruments, and operative techniques are discussed. In oncological thoracic surgery it still remains to be verified whether the criteria of radicality are fulfilled by this new technique. Using video-assisted operative thoracoscopy, we have successfully operated on 209 patients with the following indications: recurrent pneumothorax (n = 94), interstitial lung disease (n = 25), coin lesion (n = 20), pleural effusion (n = 17), hyperhidrosis (n = 14), mediastinal tumor or lymphoma (n = 10), thoracic empyema (n = 9), bullous emphysema (n = 8), pleural tumor (n = 5), hematothorax (n = 3), malignant pericardial effusion (n = 3), and chylothorax (n = 1). The advantages of this minimally traumatizing operating technique lie in a better view of the operative site, the objectively measurable reduction in postoperative restriction, less pain, earlier postoperative mobilization, and shorter hospital stay. This operating technique, in addition to being sparing, requires markedly less time than a thoracotomy. The disadvantages are the two-dimensional monitor picture and, especially, the loss of palpation.

Anesthesia, General↗

PubMed1993

Palmar thermometry for intraoperative success control of thoracic sympathectomy.

In a pilot study involving six patients, palmar thermometry was used as a non-invasive method for intraoperative success control during thoracic sympathectomy. Using commercially available thermo-elements and amplifier modules, a marked increase in temperature could be registered in five patients after the severance of their rami communicants grisei for the hand. This effect was associated with the long-term success of therapy for hyperhidrosis in all five patients. This initial experience demonstrates that palmar thermometry is sensitive enough to measure surgical success intraoperatively. The limit of the thoracic sympathectomy in the cranial direction is indicated intraoperatively and Horner's syndrome is avoided with certainty.

Body Temperature↗

PubMed1993

Selective video-assisted thoracoscopic sympathectomy.

Video-assisted and thermometrically controlled thoracoscopic sympathectomy demonstrates new ways in the treatment of upper-limb hyperhidrosis. An anatomical portrayal of the sympathetic chain is possible as a result of the improved visualization and magnification of the operative area provided by the video-optic technique. The difference in temperature, registered by means of a thermometric sensor in the palm of the hand, indicates that the sympathetic nerves responsible for the hyperhidrotic segments have been severed. The number of postoperative Horner's syndromes will be reduced significantly with this method. Until now, we have successfully treated six thermometrically controlled patients. No recurrences have arisen during an 18 months observation period. Neither intraoperative nor postoperative complications were recorded. One patient complained of increased compensatory sweating of the trunk. Thermometrically controlled thoracoscopic sympathectomy is expected to improve the various forms of treatment available for sympathetic reflex dystrophies in the future.

Body Temperature↗