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Thomas Lehnert

Publications and source records attributed to Thomas Lehnert.

At least 19 recordsLinked to original sources

Adrenal metastases: CT-guided and MR-thermometry-controlled laser-induced interstitial thermotherapy.

The aim of the study was to evaluate the feasibility, safety and effectiveness of CT-guided and MR-thermometry-controlled laser-induced interstitial thermotherapy (LITT) in adrenal metastases. Nine patients (seven male, two female; average age 65.0 years; range 58.7-75.0 years) with nine unilateral adrenal metastases (mean diameter 4.3 cm) from primaries comprising colorectal carcinoma (n = 5), renal cell carcinoma (n = 1), oesophageal carcinoma (n = 1), carcinoid (n = 1), and hepatocellular carcinoma (n = 1) underwent CT-guided, MR-thermometry-controlled LITT using a 0.5 T MR unit. LITT was performed with an internally irrigated power laser application system with an Nd:YAG laser. A thermosensitive, fast low-angle shot 2D sequence was used for real-time monitoring. Follow-up studies were performed at 24 h and 3 months and, thereafter, at 6-month intervals (median 14 months). All patients tolerated the procedure well under local anaesthesia. No complications occurred. Average number of laser applicators per tumour: 1.9 (range 1-4); mean applied laser energy 33 kJ (range 15.3-94.6 kJ), mean diameter of the laser-induced coagulation necrosis 4.5 cm (range 2.5-7.5 cm). Complete ablation was achieved in seven lesions, verified by MR imaging; progression was detected in two lesions in the follow-up. The preliminary results suggest that CT-guided, MR-thermometry-controlled LITT is a safe, minimally invasive and promising procedure for treating adrenal metastases.

Adrenal Gland Neoplasms↗

Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with repetitive transarterial chemoembolization (TACE) before percutaneous MR-guided laser-induced thermotherapy (LITT).

This study aims to evaluate the efficacy and safety of a neoadjuvant treatment protocol with repeated transarterial chemoembolization (TACE) before MR-guided laser-induced thermotherapy (LITT) for large-sized hepatocellular carcinomas (HCC). Repeated TACE (mean, 3.5 treatments per patient) was performed in 48 patients with neoadjuvant intention (the largest lesion was between 50 and 80 mm in diameter, and there were no more than five lesions). For the TACE treatment, we used 10 mg/m(2) mitomycin, 10 ml/m(2) Lipiodol and microspheres. The tumor volume was measured by MRI. Lipiodol retention of the tumors was evaluated with CT. After the diameter of the tumors had decreased to less than 50 mm, the patients were treated with MR-guided LITT 4 to 6 weeks after embolization. Repeated TACE reduced the tumor size in 32 patients (66.7%), forming the basis for performing MR-guided LITT procedures. These patients received one to four laser treatments (mean, 1.9 per patient) for tumor ablation, resulting in a median survival of 36.0 months after the first treatment. For the remaining patients, no reduction in tumor size was achieved in 12 patients and disease progression in 4 patients. Neoadjuvant TACE appears to be an effective treatment of large-sized HCC, which extends the indication for MR-guided LITT.

Aged↗

Treatment of gastrointestinal stromal tumor with imatinib mesylate: a retrospective single-center experience in Heidelberg.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. METHODS: We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings. RESULTS: Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash. CONCLUSION: Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST.

Adult↗

Effect of laser-induced thermotherapy on liver metastases.

Laser-induced thermotherapy, or laser ablation, is an established minimally invasive percutaneous technique of tumor ablation. It is performed routinely in hepatic tumors and in other indications. Most patients treated with laser-induced thermotherapy suffer from liver metastases from primary tumors, particularly colorectal cancer. In this review, the local control rate, including morphological response and local recurrence, is evaluated. Survival data, including median survival time and 1-, 2- and 3-year survival, are discussed; treatment complications are also explored. The method of treatment performance and evaluation, results, and the authors' views on the current status of treatment are outlined.

Contraindications↗

Combined MRI and MR spectroscopy of the prostate before radical prostatectomy.

OBJECTIVE: The purpose of this study was to evaluate a routine protocol for combined MR and spectroscopic imaging of the prostate for staging accuracy. SUBJECTS AND METHODS: Fifty patients with biopsy-proven prostate carcinoma were examined with our sequence protocol, which consisted of T2-weighted fast spin-echo sequences and a pelvic T1-weighted spin-echo sequence. For spectroscopy, we used a 3D chemical shift imaging (CSI) spin-echo sequence. Image interpretation was performed by two radiologists. The total number of tumor voxels and tumor voxels per slice were counted to estimate the tumor volume in every patient. The potential of MR spectroscopy to differentiate between T2 and T3 tumors, based on the estimated tumor volumes, was compared with the staging performance of MRI. RESULTS: The MR measurement time was 19.01 minutes, and the total procedure time averaged 35 minutes. Seventy-six percent of the spectroscopic examinations were successful. Statistically significant differences in the number of tumor voxels per slice and tumor volumes were found between T2 and T3 tumors. The descriptive parameters of MRI and MR spectroscopy did not differ significantly; sensitivity and specificity were 75% and 87%, respectively, for MRI and 88% and 70%, respectively, for MR spectroscopy. The combination of both methods resulted in only a slight improvement in staging performance and was not statistically significant. CONCLUSION: Combined MRI and MR spectroscopy of the prostate has no diagnostic advantage in staging performance over MRI alone. The mean tumor volumes, estimated by MR spectroscopy, differ statistically significantly between T2 and T3 tumors.

Aged↗

Testing for anti-p53 antibodies increases the diagnostic sensitivity of conventional tumor markers.

The aim of this study was to determine whether anti-p53 antibodies are of clinical significance as a serological marker in the diagnosis and monitoring of malignancies. A total of 1874 serum samples from 591 patients with various types of cancer, esophageal, gastric, colorectal, pancreatic, hepatocellular, breast, and urogenital cancer, and 436 control individuals were analyzed by immunoblot for antibodies against p53. The anti-p53 antibody test was correlated with expression of conventional tumor markers, survival and the clinicopathological features of malignant disease. Anti-p53 antibodies were found in 23.4% (138/591) of the sera of patients with malignant disease (range 11.5-34%). The detection of anti-p53 serum antibodies had a specificity of 100% for malignancy (p<0.0001). The overall sensitivity of measuring established tumor markers was 62.9% (372/591). The elevation of conventional tumor markers and the presence of anti-p53 antibodies in the sera of patients with malignant disease turned out to be an independent variable (p<0.05). Combination of established tumor markers with the anti-p53 antibody test led to an increase in diagnostic sensitivity of 8% (49/591) (p<0.01). Thus, the independence of anti-p53 antibodies from established tumor markers allows the serological detection of additional tumor patients. Kaplan-Meier analysis revealed a trend toward a poorer prognosis in hepatocellular carcinoma and breast cancer patients who were anti-p53 serum positive. In conclusion, testing for anti-p53 antibodies can increase the diagnostic sensitivity when used in combination with measurement of conventional tumor markers. This increase is achieved without a parallel decrease in specificity.

Adult↗

MR-guided laser ablation.

MR-guided LITT is a safe and effective treatment modality that improves survival in well-selected patients who have liver metastases. A major advantage of MR-guided LITT is that it can be easily performed under local anesthesia in an outpatient setting with a low complication rate.

Adolescent↗

Prognostic significance of preoperative [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in patients with resectable soft tissue sarcomas.

OBJECTIVE: The objective of this study was to evaluate the prognostic significance of preoperative positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) by calculating the mean standardized uptake values (SUV) in patients with resectable soft tissue sarcomas (STS). SUMMARY AND BACKGROUND DATA: FDG-PET might be used as an adjunctive tool (in addition to biopsy and radiologic tomography) in the preoperative prognostic assessment of resectable STS. METHODS: A total of 74 adult patients with STS underwent preoperative FDG-PET imaging with calculation of the SUV. Clinicopathologic data and the SUV were analyzed for an association with the clinical outcome. The first and the third quartiles of the SUV distribution function were used as cutoff values (1.59 and 3.6). Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. RESULTS: In 55 cases, STS were completely resected (follow up 40 months): 5-year recurrence-free survival rates in patients with SUV <1.59, 1.59 to <3.6, and > or =3.6 were 66%, 24%, and 11%, respectively (P = 0.0034). SUV was a predictor for overall survival (5-year rates: 84% [SUV <1.59], 45% [SUV 1.59 to <3.6], and 38% [SUV > or =3.6]; P = 0.057) and local tumor control (5-year rates: 93% [SUV <1.59], 43% [SUV 1.59 to <3.6], and 15% [SUV > or =3.6]; P = 0.0017). By multivariate analysis, SUV was found to be predictive for recurrence-free survival. The prognostic differences with respect to the SUV were associated with tumor grade (P = 0.002). CONCLUSION: The semiquantitative FDG uptake, as measured by the mean SUV on preoperative PET images in patients with resectable STS, is a useful prognostic parameter. SUV with cutoff values at the first and the third quartiles of the SUV distribution predicted overall survival, recurrence-free survival, and local tumor control. Therefore, FDG-PET can be used to improve the preoperative prognostic assessment in patients with resectable STS.

Adult↗

Three-dimensional 1H-magnetic resonance spectroscopy of the prostate in clinical practice: technique and results in patients with elevated prostate-specific antigen and negative or no previous prostate biopsies.

To assess the benefit of routinely used three-dimensional 1H-spectroscopy of the prostate combined with magnetic resonance imaging in patients with elevated prostate-specific antigen (PSA) levels and negative or no previous prostate biopsies. Fifty-four patients were examined with our combined imaging protocol, which consisted of transversal, coronal and sagittal T2-weighted fast spin echo sequences. For spectroscopy, we used a three-dimensional chemical shift imaging spin echo (3D-CSI-SE) sequence. The study population consisted of patients with elevated PSA levels and histologically proven prostate carcinoma and patients with elevated PSA levels and negative or no previous prostate biopsies. Examination time was 31 min, a time feasible for routine use. Eighty-eight tumour voxels and 67 control voxels of 27 patients with histologically proven prostate carcinoma were analysed. Ratios of (choline + creatine)/citrate [(Cho + Crea)/Cit] below 0.6 were classified as normal and above 0.6 as pathological. Applying this classification to 20 patients with tumour-suspicious lesions of the prostate and negative or no previous prostate biopsies, we could obtain a sensitivity and specificity for tumour detection of 100% and 69%, respectively. Our combined imaging protocol is feasible for routine use and can add valuable information for the diagnostic management of patients with negative or no previous prostate biopsies.

Aged↗

Breast cancer metastases in liver: laser-induced interstitial thermotherapy--local tumor control rate and survival data.

PURPOSE: To evaluate the local tumor control rate and survival data for magnetic resonance (MR) imaging-guided laser ablation of breast cancer liver metastases by using laser-induced interstitial thermotherapy (LITT). MATERIALS AND METHODS: MR-guided LITT was performed in 232 female patients with 578 liver metastases from breast cancer. Survival rates were calculated with the Kaplan-Meier method. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter, as follows: recurrent liver metastases after partial liver resection (8.2%), metastases in both liver lobes (45.2%), locally nonresectable tumors (19%), general contraindications for surgery (2.6%), or refusal to undergo surgical resection (25%). RESULTS: Local recurrence rate at 6-month follow-up after LITT was 2.3% (five of 213) for metastases up to 2 cm in diameter, 4.3% (seven of 162) for metastases 2-3 cm in diameter, 3.2% (two of 63) for metastases 3-4 cm in diameter, and 1.9% (one of 52) for metastases larger than 4 cm in diameter. No additional local tumor progression was observed beyond 6 months. The mean survival rate for all treated patients, with calculation started on the date of diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence interval: 4.3, 5.4). The median survival was 4.3 years; 1-year survival, 96%; 2-year survival, 80%; 3-year survival, 63%; and 5-year survival, 41%. The mean survival after the first LITT treatment was 4.2 years (95% confidence interval: 3.6, 4.8). CONCLUSION: MR-guided LITT yields high local tumor control and survival rates in patients with liver metastases from breast cancer.

Adult↗

MR-guided transgluteal biopsies with an open low-field system in patients with clinically suspected prostate cancer: technique and preliminary results.

The purpose of this study was to examine the feasibility and safety of MR-guided biopsies with a transgluteal approach in patients with uncertain or suspicious prostate lesions. Twenty-five patients with uncertain or suspicious focal prostate lesions detected by high-field MR imaging of the prostate gland using endorectal coil imaging were biopsied with a transgluteal approach in a low-field MRI system (0.2 T, Concerto, Siemens). The procedures were guided using T1-weighted FLASH sequences. The prostate gland was biopsied repeatedly with a coaxial technique through a 15-gauge pencil tip with a 16-gauge biopsy handy (median 3.8 samples per patient). Complications and biopsy findings were documented retrospectively. Using T1-weighted sequences biopsy procedures were performed successfully with MR guidance in all cases without any side effects or complications. The median intervention time was 11.3 min. Pathological findings revealed ten cases of hyperplasia or atrophy, three cases of prostatitis, ten cases of carcinoma and two cases of normal tissue. The clinical follow-up showed that in two patients prostate cancer was missed at MR-guided biopsy. Transgluteal MR-guided biopsy of the prostate gland is a safe and promising approach for histological clarification of uncertain or suspicious lesions.

Aged↗

Interventional radiology in Carney triad.

Interventional therapeutic methods are presented in Carney triad, which is a syndrome defined as the simultaneous presence of gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma. The paragangliomas in the carotid bifurcation and the mediastinum were successfully treated via transarterial embolization with particles. Three intrapulmonary chondromas were ablated using MRI-guided laser-induced thermotherapy (LITT) after previous devascularization via transvenous pulmonary particle embolization. In summary, interventional techniques could be a therapeutic option in patients suffering from Carney triad.

Adult↗

Gastrointestinal stromal tumours and their response to treatment with the tyrosine kinase inhibitor imatinib.

Gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the digestive tract, are largely resistant to chemo- and radiotherapy. They are currently defined by their overexpression of the KIT receptor tyrosine kinase (CD117), a member of the family of receptor tyrosine kinases (RTKs), and exhibit KIT mutations in more than 85% of cases. Additionally, in more than one-third of KIT wild-type GISTs, mutations of platelet-derived growth factor receptor alpha (PDGF-R alpha), which also belongs to the family of RTKs, were recently found. Since these data indicate that uncontrolled RTK signalling may be implicated in the pathogenesis of GISTs, RTKs and the activated downstream signalling cascades are attractive targets in the therapy of these tumours. Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. We herein review the molecular pathological, preclinical and clinical data that identify imatinib as a valuable new agent in the treatment of GISTs.

Animals↗

Guanylin regulates chloride secretion in the human gallbladder via the bile fluid.

BACKGROUND & AIMS: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder. METHODS: Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments. RESULTS: Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration. CONCLUSIONS: Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.

Bile↗

Development and evaluation of an improved cochlear implant electrode design for electric acoustic stimulation.

OBJECTIVE: The objective of this study was to assess the intracochlear position and the extent of trauma to cochlear structures using a new prototype electrode carrier (Flex EAS). Special emphasis was placed on the practicality for combined electric and acoustic stimulation of the auditory system. STUDY DESIGN: Human temporal bones were evaluated histologically after insertion of the electrodes, and insertion forces were measured in an acrylic model of the scala tympani. METHODS: 1) Insertion forces with the regular C40+ array and the new electrode prototype were measured in an acrylic model of the scala tympani. 2) Ten human temporal bones were implanted using the same surgical procedure as in vivo. All bones underwent fixation methylmethacrylate embedding to allow cutting of the undecalcified bone with the electrode in situ. In addition, radiography of the implanted devices was performed and correlated to histologic results. Electrode positions and trauma to cochlear structures were then evaluated histologically. RESULTS: All insertions of the new electrode array were performed in the scala tympani of the cochlea. All insertions were atraumatic and covered one cochlear turn. The only effect on cochlear structures that could be observed was a slight lifting of the basilar membrane in the middle turn limited to the tip of the electrode. In three bones, basal trauma, which resulted from the cochleostomy itself, could be observed as well. All neural structures remained intact. CONCLUSIONS: The new electrode prototype provides very good mechanical properties for safe and atraumatic implantation. All criteria for the use in hearing-preservation cochlear implantation for electric and acoustic stimulation were fulfilled. Surgical measures to prevent basal trauma appear to be very important.

Acoustic Stimulation↗

Primary human hepatocytes--a valuable tool for investigation of apoptosis and hepatitis B virus infection.

BACKGROUND/AIMS: Apoptosis is a key event in the pathophysiology of many liver diseases. Primary human hepatocytes (PHH) provide a useful model to study physiological and pathophysiological processes in the liver. Our aim was to optimize PHH cultures to allow studies on induction of apoptosis and of hepatitis B virus (HBV) infection. METHODS: PHH were isolated from human liver tissue by two-step collagenase perfusion. PHH and hepatoma cells were treated with different apoptosis-inducing agents in parallel. PHH cultures were infected with wild type HBV and transduced with HBV genomes using adenoviral vectors. RESULTS: PHH were successfully isolated from 40 different tissue samples with high viability and purity. Perfusion time and seeding density turned out to be critical parameters for optimal cell yield and culture conditions, respectively. Serum addition to the medium reduced viability of PHH. PHH allowed reproducible studies of CD95-dependent and -independent apoptosis. Sensitivity towards CD95-mediated apoptosis was markedly higher than in hepatoma cells. PHH could efficiently be infected with HBV, but infection did neither induce apoptosis nor prevent CD95-induced cell death. CONCLUSIONS: Our data show that PHH provide an excellent tool for the investigation of apoptosis induced by agents like death receptor-ligands and hepatotropic viruses.

Apoptosis↗

PTH pulsatility but not calcium sensitivity is restored after total parathyroidectomy with heterotopic autotransplantation.

In healthy humans, parathyroid hormone (PTH) is secreted via basal mode with superimposed oscillatory bursts every 8 to 12 min. Amplitude and frequency changes mediate the instantaneous response of the parathyroids to changes in ambient Ca(2+) concentrations. The parathyroid gland tetrad may be synchronized by autonomic innervation. This study investigated the effect of total parathyroidectomy and heterotopic autotransplantation of parathyroid tissue (PTX) on PTH secretion patterns in nine patients with end-stage renal disease. Intact-PTH versus time concentration profiles were obtained early (1 to 8 wk, n = 4) or late (15 to 33 mo, n = 5) after PTX. In four patients late after PTX, Ca(2+) responsiveness of PTH secretion was additionally investigated by citrate and calcium clamp studies. The nonrandomness of plasma PTH fluctuations was assessed by the approximate entropy (ApEn) statistic, and secretion characteristics by multiparametric deconvolution analysis. Results were compared with those of matched normal subjects and chronic renal failure (CRF) patients without PTX. PTH burst frequency was 2.9 +/- 0.1 h(-1) early and 7 +/- 0.4 h(-1) late after PTX as compared with 8.1 +/- 0.4 h(-1) in CRF and 7 +/- 0.3 h(-1) in healthy controls. Fractional pulsatile PTH secretion was diminished after PTX (18 +/- 2%) compared with healthy controls (32 +/- 5%, P < 0.05) and CRF patients (25 +/- 4%, P = 0.05). The orderliness of PTH release was significantly reduced after PTX (ApEn: 1.59 +/- 0.03 versus 1.41 +/- 0.09 in healthy and 1.46 +/- 0.03 in CRF controls, P < 0.01). Acute hypocalcemia elicited a lesser increase in pulsatile PTH secretion in PTX patients (147 +/- 134%) than in the CRF (500 +/- 92%, P = 0.05) and healthy controls (1410 +/- 290%, P < 0.05), mainly due to a diminished mass of PTH secreted per burst. Pulsatile PTH secretion was also resistant to hypercalcemia, wherein the suppression of burst mass was significantly reduced compared with that in healthy controls. In conclusion, pulsatile PTH secretion is partially restored within 2 yr of PTX. However, the capacity of the autotransplanted tissue to adapt to changes in ionized calcium remains profoundly disturbed.

Adult↗