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Biomedical subjects

H Toomes

Publications and source records attributed to H Toomes.

At least 19 recordsLinked to original sources
PubMed2001

Reduced blood loss by aprotinin in thoracic surgical operations associated with high risk of bleeding. A placebo-controlled, randomized phase IV study.

OBJECTIVE: Although the blood-saving effect of aprotinin has been well documented in cardiac surgery and lung transplantation, its use in lung surgery has received less attention. We present our experience with the intraoperative application of aprotinin in lung resections with a predicted high risk of bleeding. METHODS: Thirty-eight patients undergoing major thoracic surgical procedures were randomized into treatment and placebo groups. The treatment group (n=18) received a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin followed by 5 x 10(5) KIU/h during surgery. The placebo group (n=20) received an isotonic saline infusion instead. RESULTS: There was no significant difference between the groups concerning diagnosis, co-morbidity, age, sex, height, and weight. The mean intraoperative blood loss in the treatment group was significantly reduced (342 vs. 808 ml, P<0024), postoperative blood loss was also reduced (623 vs. 1282 ml, P<0.0007) and the need for blood transfusion was less (14 vs. 60, n.s.). No severe side effects of aprotinin were registered. Re-thoracotomy was necessary in two patients of the placebo group because of postoperative bleeding. CONCLUSION: Aprotinin reduces the perioperative blood loss and the need for blood transfusion in thoracic surgical procedures in patients with an increased risk of bleeding.

Aprotinin↗
PubMed2000

Variability of cyclophosphamide uptake into human bronchial carcinoma: consequences for local bioactivation.

PURPOSE: The alkylating cytostatic prodrug cyclophosphamide is bioactivated by the human cytochrome P450 enzyme system. Since these enzymes are not only expressed in human liver, but also in extrahepatic tissue, local bioactivation of this drug may play an important role in its antineoplastic effects, e.g., chemotherapy of lung tumors. This would require uptake of significant amounts of cyclophosphamide into tumor tissue, which has not yet been demonstrated. METHODS: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. RESULTS: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P < 0.05) than in healthy lung tissue and showed pronounced interindividual variability. Median concentrations were 36.8 microg/g (26.9 44.2 microg/g) in healthy tissue and 5.1 microg/g (0.0-26.8 microg/g) in tumor samples. Tumor cyclophosphamide concentrations varied between 0 and 75% of those reached in healthy tissue. CONCLUSIONS: Our results indicate that CP tumor concentrations are modulated by factors different from dose and that expression of bioactivating enzymes in human lung or transfection of genes encoding these enzymes into tumor cells does not necessarily lead to local bioactivation of cyclophosphamide.

Aged↗
PubMed2000

The validity of telepathological frozen section diagnosis with ISDN-mediated remote microscopy.

We investigated 109 randomly selected frozen section specimens from lung surgery patients in a retrospective blind mode using telepathology equipment. The telepathology system applied (HISTKOM) used one ISDN B-channel and telemicroscopy with a remotely operated robotic microscope. The performance of telepathological frozen section diagnosis was compared with that of conventional frozen section diagnosis. The false-positive rate achieved was identical for both methods. The sensitivity (P=0.03), but not the specificity, was significantly lower for the telepathological method. The time needed to establish a diagnosis with the remote microscope was too high; therefore, upgrading to multichannel technology is recommended. The quality of the images transmitted was judged to be sufficient by the pathologists involved in the study. In conclusion, with further technical improvements in telemicroscopy and additional experience in telepathology, remote diagnosis seems to be feasible.

Adult↗
PubMed2000

Neoadjuvant chemoradiotherapy of stage III non-small-cell lung cancer.

Twenty to 30% of patients with non-small-cell lung cancer (NSCLC) in stage III are not resectable primarily with 5-year survival less than 10%. Since the majority of patients die from metastases, efforts have been made in the past to improve prognosis by application of neoadjuvant chemoradiotherapy regimens followed by subsequent resection. In a phase II study performed between 1993 and 1998, 93 patients in stage III (IIIA, 16%; IIIB, 84%) received an induction chemotherapy consisting of two cycles cisplatin (100 mg/m2) and vindesine (3 mg/m2) with subsequent sequential radiotherapy of 36 Gy. Sixty-five patients demonstrated partial or complete remission. Sixty underwent surgery; in 49 of them complete resection was possible. Five-year survival in the whole group was 24%, and that in the surgical cohort 39%. Six patients had no residual tumor. Postoperative N0 status was associated with a 5-year survival of 75%, and stage N1-3 with 13%. Thirty-day mortality was 7% postoperatively. Neoadjuvant chemoradiotherapy can significantly improve long-term survival in stage III NSCLC with an acceptable therapy-induced mortality.

Adult↗
PubMed2000

[Pharmacokinetics of cyclophosphamide, adriamycin and adriamycin prodrug (HMR 1928) using an ex vivo isolated perfused human lung model (IHLP)].

BACKGROUND: Today knowledge about pharmacokinetics of anticancer drugs in human malignant tumors is poor. Data from in vivo studies are limited and difficult to obtain due to ethical aspects. An ex vivo isolated perfused and ventilated human lung model however allows pharmacological studies of human bronchial carcinoma inside their host organ, the lung, under physiological conditions without compromising the patient. METHODS: Following surgery for bronchial carcinoma human lung preparations were reperfused and ventilated extracorporally for 2-3 hours. During the reperfusion anticancer drugs are added to the perfusion solution and their uptake into tumor, normal lung tissue, and lymph nodes is studied. RESULTS: An initial study showed that lung reperfusion under physiological circumstances over a period of 2-3 hours did not interfere with histo-pathological diagnostics and staging; an important precondition for potential adjuvant treatment. Pharmacokinetics of cyclophosphamid, adriamycin, and a water soluble adriamycin prodrug (HMR 1826) were measured. Final tissue concentrations of adriamycin and cyclophosphamid in peripheral lung parenchyma turned out to be 10 times higher compared to tumor tissue. However, following perfusion with adriamycin prodrug final tissue concentrations of adriamycin were in the same range in lung and tumor. CONCLUSIONS: The ex-vivo isolated human lung perfusion model (IHLP) has proven to be an ideal scientific model for pharmacological investigations of human tumors as an intermediate step between cell culture and in-vivo situation without any disadvantage for the patient. The tumor-to-host interaction is completely saved in this model. However, first pass reactions of drugs in other organs must not play a role for the substances studied with the IHLP. The role and future applications of the isolated perfused human lung model for other indications is discussed.

Antineoplastic Agents↗
PubMed1999

[Video-assisted thoracoscopic access in pleural empyema compared with mere chest tube drainage].

Video-assisted thoracoscopic (VAT) debridement is gaining importance in the fibrino-purulent phase of empyema thoracis. However, evaluation of this access compared with mere chest tube drainage or thoracotomy remains unsatisfactory. A total of 356 parapneumonic empyemas from 1986 to 1997 were retrospectively analyzed concerning the results after primary treatment (chest tube 225, thoracotomy 80, VAT 51). The three groups did not differ significantly for gender and associated diseases. Median age of the chest tube drainage group (54 years) was higher than for thoracotomy (43.5 years) or VAT (39 years). Median duration of chest tube treatment after thoracotomy (7 days) was shorter than after VAT (13 days) or chest tube drainage (20 days) (P < 0.0001). The more invasive procedures were also superior to the lesser invasive treatment concerning duration of postoperative hospitalization, recurrence rate and treatment failures. In spite of its better results thoracotomy will be pushed back by VAT in the treatment of empyema thoracis. Acceptance of VAT is reflected in rising numbers of admissions. Based on these retrospective results we are planning a prospective multicenter trial to evaluate the indication for VAT in empyema thoracis.

Adult↗
PubMed1999

Ligands for Viscum album agglutinin and galectin-1 in human lung cancer: is there any prognostic relevance?

Viscum album agglutinin (VAA) is an extract component of mistletoe. It belongs to the plant lectin family and exerts various biological effects such as cytotoxic properties for tumor cells in culture. VAA as well as galectin-1, an endogenous lectin, possess galactose-specific surface-binding sites. We therefore investigated 159 cases of lung cancer for their capacity to bind VAA and galectin-1 and for Lewis antigen reactivity. Three different methods were used for detection of VAA: a two-step method with biotinylated VAA; an immune complex three-step method, and a four-step method. The most sensitive results were obtained with the four-step method utilising VAA, a goat-anti-VAA antibody and a biotinylated rabbit-anti-goat antibody. Intensity and distribution of staining were assessed using an immunoreactive score index (0-12). Approximately 70% of all tumors exhibited moderate to strong binding capacity for VAA. Adenocarcinomas and bronchiolo-alveolar carcinomas were more frequently labeled than squamous carcinomas. No relationship between expression of binding sites for VAA and galectin-1 as well as of Lewis antigens was found. Moreover, there was no correlation between VAA-binding capacity and survival, whereas expression of galectin-1-binding sites was of prognostic significance. Patients showing expression of galectin-1-binding sites revealed a better prognosis than those lacking binding sites or showing a weak reactivity (P = 0.0257 log rank test of Kaplan-Meier statistics).

Binding Sites↗
PubMed1999

[Resection of lung metastases: long-term results and prognostic analysis based on 5206 cases--the International Registry of Lung Metastases].

The International Registry of Lung Metastases was established in 1991 to asses the long-term results of pulmonary metastasectomy. The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), USA (n = 4) and Canada (n = 1). Of these patients 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 (43%), sarcoma in 2173 (42%), germ cell in 363 (7%), and melanoma in 328 (6%) patients. The disease-free interval was 0 to 11 months in 1729 (33%) cases, 12 to 35 months in 1857 (36%) and more than 36 months in 1620 (31%). Single metastases accounted for 2383 (46%) cases and multiple lesions for 2726 (52%). Mean follow up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risk of death and multivariate Cox model. 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 interval of 36 months and more and single metastases. These results confirm that lung metastasectomy is a safe and potentially curative procedure.

Adolescent↗
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

[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↗