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Biomedical subjects

M Henke

Publications and source records attributed to M Henke.

At least 19 recordsLinked to original sources

[Multimodal treatment of non small cell lung cancer].

The primary treatment of lung cancer depends on tumor stage. Chest CT scan and bronchoscopy are used to define the TNM stage and resectability. In case of lung cancer without mediastinal lymph node enlargement or direct mediastinal involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended. The use of adjuvant chemotherapy has to be defined, but will be indicated in stage II and IIIa. Expected 5-year survival achieves 40 to 80 % depending on tumor stage. Exceeds the shorter diameter of mediastinal lymph nodes in chest CT scan more than 1 cm (or in case of positive PET scan) mediastinoscopy is indicated. In case of N2-disease and after tumor response to preoperative chemotherapy (about 60 %) secondary resection of the tumor leads to higher 5-year survival rates (20-40 %) compared to patients without induction therapy (5-20 %). In these patients and after unexpected detection of solitary lymph node metastasis by primary resection adjuvant mediastinal radiotherapy should be added. If the tumor has infiltrated the mediastinum or the upper sulcus (T3/4) and/or mediastinal lymph nodes are obviously tumor burden (e. g. > 3 cm, N2 bulky, N3) radical primary resection may not be possible. In these patients combined radio- and chemotherapy induces a high percentage of tumor regression and can be used before secondary resection (5-year survival 5-20 %). Locally advanced tumors infiltrating the main bronchus close to the carina or the carina itself and tumors with metastases in the same lobe, both without mediastinal lymph node metastases (T3/4N0-1), can be resected by sleeve pneumonectomy and lobectomy with satisfactory results respectively. In patients with resectable lung cancer and no clinical sign of tumor disease (f. e. anemia, weight loss, pain) limited staging procedure with chest CT scan including upper abdomen and bronchoscopy is reasonable. In the remaining patients complete staging is necessary. We recommend an interdisciplinary approach to patients with lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer.

PURPOSE: The purpose of this study was to evaluate the impact of [18F]fluorodeoxy-D-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC). METHODS: FDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients. Results of FDG-PET were compared with those of conventional staging procedures. FDG-PET detected markedly increased FDG uptake in the primary tumours of all 120 patients (sensitivity 100%). RESULTS: Complete agreement between FDG-PET results and other staging procedures was observed in 75 patients. Differences occurred in 45 patients at 65 sites. In 47 sites the FDG-PET results were proven to be correct, and in ten, incorrect. In the remaining eight sites, the discrepancies could not be clarified. In 14/120 patients, FDG-PET caused a stage migration, correctly upstaging ten patients to extensive disease and downstaging three patients by not confirming metastases of the adrenal glands suspected on the basis of CT. Only 1/120 patients was incorrectly staged by FDG-PET, owing to failure to detect brain metastases. In all cases the stage migration led to a significant change in the treatment protocol. Sensitivity of FDG-PET was significantly superior to that of CT in the detection of extrathoracic lymph node involvement (100% vs 70%, specificity 98% vs 94%) and distant metastases except to the brain (98% vs 83%, specificity 92% vs 79%). However, FDG-PET was significantly less sensitive than cranial MRI/CT in the detection of brain metastases (46% vs 100%, specificity 97% vs 100%). CONCLUSION: The introduction of FDG-PET in the diagnostic evaluation of SCLC will improve the staging results and affect patient management, and may reduce the number of tests and invasive procedures.

Brain Neoplasms↗

[Erythropoietin in patients with head and neck carcinomas?].

BACKGROUND: Various studies have demonstrated the prognostic significance of the pretherapeutic blood hemoglobin concentration for patients with head and neck cancer following surgery or primary definitive or adjuvant radio- or radiochemotherapy. It was the aim of this study to evaluate whether the prognosis of these patients might be improved when correcting decreased pretherapeutic hemoglobin values by administering erythropoietin. METHOD: In a prospective placebo-controlled double-blind study (Cochrane "evidence-based medicine" level Ib) the effect of erythropoietin was analyzed in patients with locally advanced head or neck tumours with low blood hemoglobin values (women: < 12 g/dL; men: < 13 dL) and a Karnofski value of > 60 following primary definite or adjuvant radiotherapy (up to 70 Gy). The time to local tumour progression and survival was evaluated. Kaplan-Maier estimates were applied and, the relative risk of well-known prognostic factors tested for with a Cox Proportional Hazards model. RESULTS: 157 patients of the Freiburg University ENT-clinic were recruited from 1997 to 2001. Study conduct was performed according to the GCP guidelines. A rapid increase of the blood hemoglobin value happened during the first five weeks of treatment under epoetin beta. Placebo patients experienced only minor changes of the hemoglobin value. Following adjuvant radiotherapy local tumour control probability at two years was 68 % +/- 7 % and 72 +/- 7 % for placebo and epoetin beta patients, respectively (p = 0.64). Patients who had undergone primary definite radiation experienced a local control probability of 36 % +/- 11 % in the placebo arm after two years, compared to epoetin beta with 23 % +/- 11 % (p = 0.05). CONCLUSION: Epoetin beta resulted in prompt and stable correction of blood hemoglobin values in anemic patients with advanced head or neck tumours, but tumour control and survival was impaired particularly in patients with a high tumour burden.

Anemia↗

Alteration of radiation-induced hematotoxicity by amifostine.

PURPOSE: To investigate whether amifostine can reduce radiation hematotoxicity. PATIENTS AND METHODS: Seventy-three patients undergoing radiotherapy for squamous cell carcinoma of the head and neck at the university clinics of Freiburg, Heidelberg, and Erlangen were evaluated. All received 60 Gy (50-70 Gy) at 5 x 2 Gy fractions per week employing standard techniques. Thirty-five were randomized to receive 200 mg/m(2) amifostine i.v. 30 min before radiation; 38 served as control patients. Blood counts (total n = 501) were determined before, during, and while completing radiotherapy. Changes of leukocyte, platelet, and hemoglobin levels were determined and compared using the t test. RESULTS: The blood hemoglobin level and the platelet count were not affected by irradiation, for either the amifostine-treated or control patients. Similarly, the leukocyte counts of amifostine-treated patients did not change during irradiation. However, control patients experienced a decrease in leukocyte count from 8.1 x 10(3)/mm(3) to 5.8 x 10(3)/mm(3) (difference: 2.3 x 10(3)/mm(3)). This seems to be line specific: Whereas amifostine does not affect lymphocyte count, a radiation-induced decrease of neutrophil granulocytes seems to be prevented. CONCLUSION: Amifostine protects from radiation hematotoxicity, particularly affecting the granulocytopoiesis. These data confirm results from our former study.

Amifostine↗

Analysis of single-chain antibody production in Pichia pastoris using on-line methanol control in fed-batch and mixed-feed fermentations.

In the last few years the Pichia pastoris expression system has been gaining more and more interest for the expression of recombinant proteins. Many groups have employed fermentation technology in their investigations because the system is fairly easy to scale up and suitable for the production in the milligram to gram range. A large number of heterologous proteins from different sources has been expressed, but the fermentation process technology has been investigated to a lesser extent. A large number of fermentations are carried out in standard bioreactors that may be insufficiently equipped to meet the demands of high-cell-density fermentations of methylotrophic yeasts. In particular, the lack of on-line methanol analysis leads to fermentation protocols that may impair the optimal expression of the desired products. We have used a commercially available methanol sensor to investigate in detail the effects of supplementary glycerol feeding while maintaining a constant methanol concentration during the induction of a Mut(+) strain of Pichia pastoris. Specific glycerol feed rates in the range of 38-4.2 mg. g(-1). h(-1) (mg glycerol per gram fresh weight per hour) were investigated. Expression of the recombinant scFv antibody fragment was only observed at specific feed rates below 6 mg. g(-1). h(-1). At low specific feed rates, growth was even lower than with methanol as the sole carbon source and the harvest expression level of the scFv was only half of that found in the control fermentation. These results show that glycerol inhibits expression driven by the AOX1 promoter even at extremely limited availability and demonstrate the benefits of on-line methanol control in Pichia fermentation research.

Bioreactors↗

FDG-PET imaging for the staging and follow-up of small cell lung cancer.

The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6x limited disease, 12x extensive disease, 5x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic mediastinal and hilar lymph nodes and bone metastases. Finally, all findings considered suspicious for tumour involvement on the other staging procedures were also detected by FDG-PET. It is concluded that FDG-PET has potential for use as a simplified staging tool for small cell lung cancer.

Adult↗

Epithelial cells in the peripheral blood of patients with cancer of the head and neck: incidence, detection and possible clinical significance.

In this study amplification of cytokeratin-19 mRNA by Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect circulating tumor cells in the peripheral blood of patients with cancer of the head and neck before, during and after radiation therapy. Detection of cytokeratin-19-positive cells coincided with local failure, distant metastasis and anemia.

Adult↗

Correction of cancer anemia--impact on disease course, prognosis and treatment efficacy, particularly for patients undergoing radiotherapy.

Almost one cancer patient in two is anemic, with a correspondingly poorer prognosis and quality of life. A low blood hemoglobin level seems to directly impair treatment efficacy, particularly of radiotherapy, possibly because low tissue oxygenation causes a decrease in radiosensitivity. Tissue hypoxia may also facilitate tumor progression and impair the efficacy of cytostatic drugs. This constitutes a powerful rationale for correcting cancer anemia. Red cell transfusion is immediately effective, but carries risks of infection and immunosuppression. A safer alternative is recombinant human erythropoietin (rhEPO), which has already proved feasible and effective in correcting anemia and improving quality of life of cancer patients. Several ongoing radiotherapy studies are presently investigating whether rhEPO conclusively increases cancer cure rates. First results should be available in 2001. Given the efficacy of rhEPO to stimulate erythropoiesis and improve quality of life of cancer patients and its potential to enhance radiation's efficacy seem to earn it a firm place at least in the radiooncologist's arsenal.

Anemia↗

Protective effect of amifostine on dental health after radiotherapy of the head and neck.

PURPOSE: The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients. The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia. METHODS AND MATERIALS: The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospective randomized and multicenter open-label Phase III study (WR-38) at the University Hospitals of Heidelberg, Freiburg, and Erlangen. The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine. RESULTS: Patient and treatment characteristics (particularly the radiation dose and percentage of parotids included in the treatment volume) were equally distributed between the patients who received (n = 17) or did not receive (n = 18) amifostine. Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector (p = 0. 015, two-tailed Fisher exact test). CONCLUSION: Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck. The dental status should be used as a primary endpoint in future studies on amifostine.

Adult↗

Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients. PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade > or =2 acute xerostomia, grade > or =3 acute mucositis, and grade > or =2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point. RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade > or =2 acute xerostomia from 78% to 51% (P<.0001) and chronic xerostomia grade > or = 2 from 57% to 34% (P=.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P=.04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively. CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.

Adult↗

Blood hemoglobin level may affect radiosensitivity-preliminary results on acutely reacting normal tissues.

PURPOSE: To evaluate the influence of blood hemoglobin concentration on the radiosensitivity of acutely reacting normal tissues. METHODS AND MATERIALS: Weekly scores (EORTC/RTOG criteria) for acute reactions of skin and mucosa are available for 60 patients with cancer of the head and neck undergoing a standard conventional radiotherapy. The prognostic significance of blood hemoglobin levels on the development of acute reactions is studied by multivariate analysis (Cox Proportional Hazards Model). Further, the incidence and the time to development of these reactions is looked at in cohorts of patients with different mean blood hemoglobin concentrations during radiotherapy. Patients are therefore classified into a "severely anemic group" (hemoglobin < 11.0 g/100 mL), and into a cohort with a blood hemoglobin value equal or above 11.0 g/100 mL. RESULTS: Normal tissue scoring and monitoring of blood hemoglobin levels allows for a detailed analysis of possible correlations. A decrease in the mean blood hemoglobin value of 1 g/100 mL predicts a reduced risk to develop a skin reaction of Grade 2 or 3 (RR = 0.9; p = 0.08; RR = 0.8; p = 0.26, respectively) or a mucosa reaction of Grade 3 (RR = 0.8; p = 0.16), independent from the radiation dose, the treatment time and from previous surgery within the radiation volume (multivariate analysis). Likewise, patients with severe anemia develop grade 3 mucositis or dermatitis less often (0%; 13%) as compared to those with blood hemoglobin concentrations equal or above 11.0 g/100 mL (21%; 19%). Skin and mucosa reactions further tend to occur later in the course of radiation. The observations are not statistically significant and possible reasons will be discussed. CONCLUSIONS: A decreased blood hemoglobin concentration may-perhaps by an impaired tissue oxygenation-reduce the radiosensitivity of normal tissue such as skin and mucosa. However, the data is preliminary and needs further confirmation.

Adult↗

Are guidelines followed in Helicobacter pylori diagnosis and therapy? An inquiry among gastroenterologists, referring physicians and patients in Munich.

BACKGROUND AND STUDY AIMS: Attempts to standardize Helicobacter pylori (Hp) diagnosis and therapy have led to the publication of guidelines by various national gastroenterological societies in Europe and the USA. However, little information is available either regarding the compliance of gastroenterologists and referring physicians with these guidelines, or regarding the patients' perspective. PATIENTS AND METHODS: A retrospective analysis was conducted of all outpatient upper gastrointestinal endoscopy reports for a one-month period in eleven different centers (two university hospitals and nine private practice gastroenterology offices) with a total of 24 gastroenterologists. Endoscopy reports from patients wit the indications of reflux, diarrhea, and tumors were excluded. Diagnoses and treatment recommendations given by gastroenterologists were recorded. Questionnaires concerning Hp diagnosis, treatment indications and performance, and follow-up were sent to referring physicians and patients. RESULTS: A total of 772 endoscopy reports were included in the study; analyzable questionnaires were returned by 287 referring physicians (47%) and by 265 patients (59%). Gastroenterologists recommended Hp eradication in all ulcers and in 29% of gastritis/nonulcer dyspepsia (NUD) cases. Referring physicians thought that 94% of ulcers should be treated by Hp eradication, which was also considered to be an absolute and relative indication in NUD by 15% and 53% of the referring physicians, respectively. Among the patients who replied, 52% had received Hp eradication regimens; ulcers were found in 22% of the total patient group. Check-up examinations after Hp therapy were considered necessary by 75% of the referring physicians, but only 22% of the responding patients actually underwent some form of check-up (upper gastrointestinal endoscopy in 91%). CONCLUSIONS: Gastroenterologists and (to a somewhat lesser extent) referring physician appear to be following the current guidelines for Hp treatment. As expected, two thirds of referring physicians consider NUD to be absolute or relative indication for Hp eradication. Check-up examinations are apparently being performed less frequently than recommended.

Adolescent↗

High frequency jet ventilation in interventional fiberoptic bronchoscopy.

UNLABELLED: High frequency jet ventilation (HFJV) is a well accepted method for securing ventilation in rigid and interventional bronchoscopy. We describe a technique of HFJV using a 14F nylon insufflation catheter placed in the trachea to support stent implantation or endobronchial balloon dilation in endobronchial stenoses with the flexible fiberscope. One hundred sixty-one cases were treated with either a metal wire stent (n = 105) or with balloon dilation (n = 56). In addition to HFJV, IV anesthesia was applied in 132 cases. Driving pressure was 1125-1275 mm Hg, frequency 80-100/min, and inspiratory:expiratory ratio of 1:2. Fraction of inspired oxygen ranged from 0.3-1.0. The effects on alveolar ventilation were assessed by using blood-gas analysis and continuous monitoring of transcutaneous oxygen and carbon dioxide tension (P(tc)CO(2)). Complications consisted of hypertension (n = 8), hypotension (n = 6), bronchospasm (n = 5), and hypoxia (n = 6). In 52% of the cases, mild hypercarbia (P(tc)CO2 50-60mm Hg) was observed. In two cases, a P(tc)CO(2) > 80 mm Hg resolved spontaneously when the patients returned to normal breathing after intermittent superimposed ventilation with a face mask. During placement of stents in the proximal trachea, the jet catheter had to be withdrawn, resulting in displacement of the catheter into the pharynx in one case, which was managed safely with the bronchoscope. In conclusion, HFJV achieves satisfactory operating conditions and provides adequate gas exchange for interventional bronchoscopic procedures with the fiberscope. IMPLICATIONS: Safe ventilation is desired when performing tracheobronchial stent implantation and balloon dilation with the fiberscope. High frequency jet ventilation, applied with a 14F insufflation catheter through the nasotracheal route, offers safe ventilatory support with minimal complications. This was evaluated in 161 procedures treating benign and malignant airway stenoses.

Adult↗

Erythropoietin in radiation oncology - A review. 1st international conference, Freiburg, June 11-12, 1999.

The therapeutic potential of erythropoietin gains increasing attention among radiation oncologists because the prognosis is better for patients with high blood hemoglobin levels following radiotherapy. However, there is still a debate on how hemoglobin affects radiotherapy. Further, the means to manipulate the hemoglobin level, their indication and administration need to be clarified. Available experimental and clinical data on hypoxia, anemia and on their treatment with erythropoietin have been extensively discussed at an international conference in Freiburg, Germany, in June 1999. This report gives a summary reviewing the topic.

Anemia↗

Erythropoietin for patients undergoing radiotherapy: a pilot study.

BACKGROUND AND PURPOSE: To evaluate the feasibility and efficacy of using recombinant human erythropoietin (rhEPO) to correct decreased hemoglobin levels in patients undergoing radiotherapy and to get an estimate of its influence on the efficacy of radiotherapy. MATERIALS AND METHODS: Fifty patients with cancer of the head and neck and the pelvis were randomized before radiotherapy to different rhEPO treatments (none, 3 x 150 U/kg per week i.v., 3 x 300 U/kg per week i.v. and 3 x 150 U/kg per week s.c.). Hematological parameters were evaluated weekly and the locoregional tumor control rates were determined in 38 patients with head and neck cancer. RESULTS: rhEPO-treated patients showed a significant increase in their hemoglobin values (0.7 g/100 ml per week). The rhEPO response was comparable for patients with cancer of the head and neck and the pelvis. A delayed recovery was seen when iron deficiency or impaired iron mobilization was present. No serious toxicity was observed. Locoregional tumor control was improved, although not statistically significantly, in those head and neck cancer patients who experienced a rapid rise of hemoglobin. CONCLUSIONS: Low hemoglobin levels can be safely and quickly corrected with rhEPO. This may improve the effectiveness of radiotherapy.

Adolescent↗

Identification of a subpopulation of merozoites of Sarcocystis singaporensis that invades and partially develops inside muscle cells in vitro.

The affinity of merozoites of Sarcocystis singaporensis obtained from the lungs of acutely infected rats to muscle cells and other cell lines grown in vitro was examined. Two distinct types of mature schizonts developed in the lungs 11-13 days p.i. with sporocysts: those containing PAS- merozoites (type 1) which mainly reacted with antibodies prepared against sporozoites, and others containing PAS+ merozoites (type 2) which were antigenically close to bradyzoites. When inoculated onto cell cultures, type 1-merozoites induced schizogonic development in brain capillary endothelial cells of the rat. In contrast, type 2-merozoites invaded L6 myoblasts. In long-term cultures (50 days) of L6 cells, zoites transformed to a 8-15 microns long uninucleate stage which, tentatively, could be unizoite sarcocysts. Although the observed dichotomy in merozoite development is unprecedented in this form, evidence from previous work suggests that these observations are relevant to other Sarcocystis species. The presented cell culture system could be a first step towards successful growth of sarcocysts in vitro.

Animals↗

[Alteration of radiation-induced hematotoxicity by amifostine (ethyol)].

BACKGROUND: Radiotherapy--even of small volumes--can decrease leukocyte counts. We examined whether the radio-protector amifostine can reduce this hematotoxicity. PATIENTS AND METHODS: Twenty-six patients (Table 1) undergoing radiotherapy for squamous cell carcinoma of the head and neck were evaluated. All were given 60 (to 70) Gy 5 x 2 Gy per week in standard radiation techniques. Thirteen patients are randomized to receive 200 mg/m2 amifostine i.v., 30 minutes before radiation. Blood counts and differentials were determined before, during and following radiotherapy. Differences of these parameters are calculated and compared by t-test. RESULTS: The blood hemoglobin and the thrombocyte levels did not change during the radiotherapy course, neither for the amifostine treated, nor the control patients. Similarly the leukocyte counts of amifostine treated patients did not change during irradiation. The control patients, however, had a decrease of leukocytes from 8.4 to 6.0 x 10(3)/microliter, p = 0.03 (Table 2), and the reduction of the neutrophilic granulocyte count was more impressive for these patients. CONCLUSION: In this explorative study amifostine diminished radiation induced leukocyte toxicity.

Amifostine↗