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Biomedical subjects

T Lehnert

Publications and source records attributed to T Lehnert.

At least 73 records · Page 4Linked to original sources
PubMed1998

Intraoperative radiotherapy as adjuvant treatment for stage II/III rectal carcinoma.

In recent years, many efforts have focused on combined radiotherapy and chemotherapy as adjuvants to curative surgery in patients with stage II and III (UICC) rectal carcinomas. Intraoperative radiotherapy (IORT) makes it possible to increase the total irradiation dose in a locally restricted area while sparing normal mobile organs, but it is limited by increased late toxicity. A prospective phase I/II study was designed to evaluate the efficacy of moderate-dose intraoperative and external beam radiotherapy (IO-EBRT), in some cases with concomitant chemotherapy. Sixty-three patients with a stage II or III rectal carcinoma were eligible for analysis (median follow-up 30.6 months). Fifty-four patients had undergone a complete resection (RO). Mean IORT dose was 11.3 Gy and mean EBRT dose 41.4 Gy. In 45 patients (71.4%) concomitant chemotherapy was delivered (5-FU, leucovorin). Two patients suffered local failure. However, overall local tumor control was markedly improved compared to historical controls (96.8% vs 66.2%). Patients treated with IO-EBRT showed a reduced incidence of distant metastases after concomitant chemotherapy (17.6% vs 38.8%). A 4-year actuarial relapse-free survival of 82% was obtained after IO-EBRT plus chemotherapy, and 59% after IO-EBRT alone. The postoperative course was unremarkable in 47.6% of patients. No radiation colitis or neuropathy occurred. Moderate-dose IORT and EBRT is safe, taking into account related late toxicities. It is an effective local treatment approach, resulting in an encouraging local control rate.

Combined Modality Therapy↗
PubMed1998

[Multimodal therapy of colon carcinoma].

A large variety of immunological and cytotoxic adjuvant treatment concepts and application routes have been observed to be effective in colon cancer by randomized trials during the past three decades. Presently adjuvant 5-fluorouracil based chemotherapy is favoured for patients with lymph node metastases (UICC stage III), since this treatment was associated with a 5-10% increase in 5-year survival. Uncertainty persists regarding the optimal use of adjuvant treatment, since marked differences in prognosis have been recognized within stage III and because the impact of surgical treatment on long-term survival has not been thoroughly controlled for in past trials. Current and future studies will have to determine precisely which patients will benefit most from adjuvant treatment and which combination of surgical and adjuvant treatment will be most effective.

Chemotherapy, Adjuvant↗
PubMed1998

[Multimodal therapy of rectal carcinoma].

Multimodal therapy for rectal carcinoma is--in contrast to colon cancer--largely based on adjuvant or neoadjuvant radiotherapy. Although radiotherapy reduces local recurrence rates, overall survival is hardly improved, while on the other hand specific complications of radiotherapy are recognized. Extended neoadjuvant treatment concepts including chemotherapy may improve long-term outcome, but to date this has not been demonstrated conclusively by randomized trials. New developments include intraoperative radiotherapy and the combination of hyperthermia with radiochemotherapy. Initial results from randomized studies are promising, but require confirmation by larger trials. At the same time the importance of optimal surgical treatment has been recognized as a prerequisite for favourable long-term results. Since this aspect has not received due attention in past protocols the optimal combination of surgery with other modalities and their time sequence cannot be determined presently.

Chemotherapy, Adjuvant↗
PubMed1998

Moderate dose intraoperative and external beam radiotherapy for locally recurrent rectal carcinoma.

BACKGROUND AND PURPOSE: Late adverse effects (i.e. neuropathy, chronic bowel obstruction) limit the effective dose given in intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT). Initial results of a multi-modality treatment approach using moderate dose IORT and moderate dose EBRT are presented. PATIENTS AND METHODS: Thirty-one consecutive patients with recurrent rectal carcinomas had IORT and EBRT after complete (R0, n = 14) or incomplete resection (R1, n = 9; R2, n = 8). The mean [ORT dose was 13.7 Gy (range 12-20 Gy) supplemented with an EBRT dose of 41.4 Gy. Twenty-two patients had preoperative EBRT and 22 patients had concomitant chemotherapy (5-FU, Leucovorine). RESULTS: After a median follow-up of 28 months, 16 patients had re-recurrent disease and 11 patients had died. Nine patients failed locally (four in-field, four marginal and one anastomotic re-recurrence), three combined with distant metastasis, resulting in overall and IORT infield local control rates of 71% and 87%, respectively. Distant metastases alone were found in seven patients. The 4-year overall and relapse-free survival rates were 58% and 48%, respectively. After incomplete resection the local failure rate increased (R0 21%, R1/2 35%) and the 4-year relapse-free survival rate decreased significantly (29% versus 71%) due to a markedly increased distant metastasis rate (53% versus 7%). Acute and late toxicities were not increased. CONCLUSION: The combination of moderate dose IORT and EBRT is a safe and efficacious component in a multi-modality treatment approach.

Antineoplastic Agents↗
PubMed1998

Surgery for local recurrence or distant metastases in patients aged 75 years or older.

Between 1982 and 1997, a total of 105 patients aged 75 years or older (median age 78 years) underwent surgical treatment for recurrent solid tumours. The most frequent primary tumours were melanoma, colorectal carcinoma and breast cancer. Sixty-one patients had complete removal of recurrent tumour. Post-operative mortality was 3.8% (four of 105 patients). The median hospital stay was 16 days and the post-operative hospital stay was 10 days. At a median follow-up of 57 months, 77 patients had died. Twenty one patients died of causes unrelated to the tumour. The overall survival of 105 patients was 35% at 3 years and 27% at 5 years. Following R0 resection, 5-year survival was 43%, (n = 61) and in the absence of post-operative complications even reached 50% (n = 47). Survival correlated with completeness of tumour resection (P<0.0001) and post-operative complications (P=0.021). No significant correlation could be established between survival and age, ASA score, blood replacement, primary tumour location or sex. Elderly patients presenting with recurrent tumour should be evaluated for surgical resection. If tumour removal is complete and post-operative complications are avoided, a 5-year survival rate of over 40% may be expected.

Aged↗
PubMed1998

No evidence for cancer-related CD44 splice variants in primary and metastatic colorectal cancer.

The expression of alternatively spliced CD44 adhesion molecules has been implicated in the pathogenesis and metastasis of colorectal cancer. Using a new set of primers for exon-specific reverse transcription-polymerase chain reaction (RT-PCR) we delineated the exact exon composition of CD44 mRNAs in normal colorectal mucosa, including isolated colonic crypts, in colorectal carcinomas and in their hepatic metastases. In addition, the surface expression of CD44 isoforms was analysed by immunohistochemistry. We identified by RT-PCR eight variant transcripts expressed in colorectal carcinomas and their metastases, but also constitutively in normal colorectal epithelia. In the normal colorectal epithelium, the surface expression of CD44 standard and variant molecules was restricted to proliferating cells at the bottom of the crypts. Despite expression of these transcripts in colorectal cancers and their metastases, monoclonal antibodies specific for standard or variant epitopes encoded by exons v5 and v6 stained only a few neoplastic lesions. These data point to a differentiation-specific CD44 expression and splicing pattern in proliferating colorectal epithelia. However, they do not support a cancer- or metastasis-specific CD44 splicing pattern. Instead, cell surface availability of CD44 epitopes was reduced rather than increased in primary tumours and particularly in liver metastases.

Alternative Splicing↗
PubMed1998

Detection of SYT-SSX1/2 fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) is a valuable diagnostic tool in synovial sarcoma.

Cytogenetically, most synovial sarcomas are characterised by a specific chromosomal translocation [(X;18) (p11.2;q11.2)], which results in the generation of fusion transcripts comprising SYT (18q11) and either SSX1 or SSX2 (Xp11) sequences. By using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) protocol, specific SYT-SSX1/2 fusion transcripts were detected in 10 histopathologically confirmed synovial sarcomas. Control tumours with morphological spindle cell patterns mimicking monophasic synovial sarcoma tested negative (18/19) in the RT-PCR protocol, with the exception of one spindle cell sarcoma originally classified as a fibrosarcoma. Furthermore, the established RT-PCR protocol was used to evaluate the feasibility of SYT-SSX1/2 fusion transcript detection for minimal residual disease analysis. Analyses of surgical margins revealed a fusion transcript in two of four operations for synovial sarcoma analysed, one of which was diagnosed with tumour free margins by conventional histopathology. These data suggest that the RT-PCR amplification of SYT-SSX1/2 fusion transcripts is a valuable tool in the differentiation of synovial sarcomas, especially in cases of equivocal morphology. Additionally, the RT-PCR approach may be used for the detection of residual tumour cells in synovial sarcoma patients.

Adolescent↗
PubMed1998

Improved outcome after emergency surgery for cancer of the large intestine.

BACKGROUND: Emergency surgery for colorectal cancer has become more aggressive and radical over the past decade. This retrospective review analyses the impact on outcome. METHODS: The results of emergency surgery within 24 h of admission were compared between 1982 and 1987 (77 patients) and 1988 and 1993 (75 patients). Patient and tumour characteristics were similar in both groups. RESULTS: Right colonic obstruction or perforation was treated by primary resection and anastomosis in 11 of 12 patients before 1988 and in all 19 patients thereafter. Primary resection was also the treatment of choice for perforated cancer of the left colon and rectum before 18 of 20) and after (20 of 21) 1988. The rate of primary resection for obstructing cancer of the left colon and rectum increased from 17 of 45 to 30 of 35. One-stage resections for obstructing cancer were performed in ten of 45 and 22 of 35 patients before and after 1988 respectively. The overall mortality rate declined from 14 of 77 to three of 75 after 1988 (P< 0.01). The rate of radical lymphadenectomy rose from six of 46 patients to 42 of 69 after 1988. The 3-year survival rate increased from 50 to 74 per cent (P < 0.05). CONCLUSION: The data support further efforts towards improving the immediate and late outcome of emergency surgery in complicated colorectal cancer.

Aged↗
PubMed1998

Effect of haemodialysis after contrast medium administration in patients with renal insufficiency.

BACKGROUND: The study was designed to investigate the influence of haemodialysis on the pharmacokinetics of the non-ionic contrast medium iopentol and the outcome of radiocontrast nephropathy in patients at risk undergoing angiography. METHODS: We prospectively studied 30 patients with reduced renal function (mean serum creatinine concentration (+/- SEM), 2.4 +/- 0.16 mg/dl (212 +/- 14 mumol/l)). Patients were randomly assigned to receive either a haemodialysis procedure for 3 h, started as soon as possible (63 +/- 6 min) after administration of contrast medium, or a conservative treatment. Serum concentrations of iopentol and creatinine were followed for up to 14 days. RESULTS: The extracorporal plasma clearance of contrast medium was 71 +/- 2.5 ml/min. The fraction of the dose eliminated was 32 +/- 3%. The rate of radiocontrast nephropathy (defined as serum creatinine increase of > or = 0.5 mg/dl (44 mumol/l) within 48 h) after administration of contrast medium was similar in both groups (53 and 40% in group 1 (haemodialysis) and group 2 (conservative treatment) respectively). The course of absolute changes in serum creatinine over the whole observation period was not different in both groups. CONCLUSIONS: The data indicate that haemodialysis eliminates contrast medium effectively, but it may not influence the incidence or outcome of contrast induced nephropathy.

Contrast Media↗
PubMed1998

Pseudolesions at T1-weighted gradient-echo imaging after administration of superparamagnetic iron oxide: comparison with portal perfusion abnormalities at CT during arterial portography.

PURPOSE: To compare specific findings at T1-weighted gradient-echo (GRE) magnetic resonance (MR) imaging performed after administration of superparamagnetic iron oxide (SPIO) with nontumorous regional portal perfusion abnormalities seen at computed tomography (CT) during arterial portography (CTAP). MATERIALS AND METHODS: The results of CTAP, MR imaging, and surgery were compared in 19 patients with liver metastases and five with benign liver tumors. MR imaging was performed by using turbo spin-echo (SE) sequences and a GRE sequence before and after infusion of SPIO. RESULTS: At CTAP, 34 nontumorous portal perfusion defects ("straight line sign," pseudolesions) were seen. After intravenous administration of SPIO, 18 nontumorous signal intensity differences were seen on T1-weighted GRE images in corresponding locations. No corresponding nontumorous signal intensity differences were seen on unenhanced MR images. The mean signal-to-noise ratio on the SPIO-enhanced GRE images was reduced from 26.3 to 16.6 in the areas of nontumorous signal intensity differences, whereas that in areas of normal portal perfusion (normal CTAP findings) was reduced to 10.2. CONCLUSION: Impaired portal perfusion decreased the uptake of SPIO in histopathologically normal regions of liver parenchyma. Resultant differences in signal intensity were better visualized on GRE than on turbo SE images.

Adolescent↗
PubMed1998

[Analysis of chromosome copy number changes in leiomyosarcoma through molecular cytogenetic methods].

Leiomyosarcoma (LMS) is a rare type of malignant soft tissue tumor occurring predominantly in adults. Up to now only few zytogenetic data resulting from chromosomal banding analyses were obtained from this tumor type. In general, highly complex karyotypes were observed, but no recurrent chromosomal aberrations could be identified. The aim of the present study was to analyze chromosomal imbalances in 14 cases of LMS using comparative genomic hybridization (CGH). Imbalances were detected in all cases analyzed, with chromosomal gains occurring more frequently than losses (9.9 gains/case vs. 6.9 losses/case, respectively). Chromosome arms predominantly overrepresented included Xp (9/14 cases), 5p and 8q (8/14 each), as well as 17p and 17q (6/14 each). Nineteen distinct high level amplifications, indicative for the location of relevant proto-oncogenes in LMS, were identified in nine different tumors. Interestingly, in three cases chromosomal arm 17p was involved. Interphase analysis with probes derived from the commonly amplified region 17p11-p12 revealed, that the tre oncogene is co-amplified and therefore could play a relevant role in LMS development. With regard to losses chromosome 13q was affected in 12/14, 10q in 8/14, and 2p as well as 2q in 7/14 tumors, respectively. The frequent deletions of chromosome 13 with a minimal affected region 13q14-q15 strongly support preliminary molecular evidence, that loss of the RB1 tumor suppressor gene is a critical step in LMS tumorigenesis.

Adult↗
PubMed1998

[Demonstration of SYT-SSX11/2 fusion transcripts in synovial sarcomas using RT-PCR].

Various mesenchymal malignancies with a spindle cell morphology may mimic monophasic synovial sarcomas. We analysed, whether detection of SYT-SSX1/2 fusion transcripts, present as a consequence of a specific translocation [t(X;18)(p11.2;q11.2)] found in synovial sarcomas, are useful to confirm the diagnosis of synovial sarcoma. A nested RT-PCR protocol was established for the detection of SYT-SSX1/2 fusion transcripts. After RNA extraction of snap frozen tissue reverse transcription was carried out. In a nested PCR, the resulting cDNA samples were amplified and visualized on agarose gels. DNA sequencing of PCR products enabled the assignment of fusion transcripts to either the SYT-SSX1 or the SYT-SSX2 variant. We detected SYT-SSX1/2 fusion transcripts in seven monophasic and three biphasic synovial sarcomas. 20 out of 21 control tumour including leiomyosarcomas, malignant peripheral nerve sheath tumours, gastrointestinal stromal sarcomas and fibrosarcomas were negative in RT-PCR analysis. One case of recurrent spindle cell sarcoma originally classified as a fibrosarcoma revealed a SYT-SSX2 fusion transcript. These data provide further evidence that the RT-PCR amplification of SYT-SSX1/2 fusion transcripts permits the specific identification of synovial sarcomas. This diagnostic approach may be especially useful in cases with equivocal histomorphology.

Chromosome Mapping↗
PubMed1998

Technical aspects of virtual liver resection planning.

Operability of a liver tumor is depending on its three dimensional relation to the intrahepatic vascular trees which define autonomously functioning liver (sub-)segments. Precise operation planning is complicated by anatomic variability, distortion of the vascular trees by the tumor or preceding liver resections. Because of the missing possibility to track the deformation of the liver during the operation an integration of the resection planning system into an intra-operative navigation system is not feasible. So the main task of an operation planning system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function and a quantifiable resection proposal. The system quantifies the organ structures and resection volumes by means of absolute and relative values. It defines resection planes depending on security margins and the vascular trees and presents the data in visualized form as a 3D movie. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are visualized in digital movies as well as in quantitative reports.

Humans↗
PubMed1998

[Detection of isolated disseminated tumor cells of colorectal carcinomas in lymph nodes].

Despite R0-resection up to 30% of patients with colorectal cancer stage UICC I and II die of recurrent disease. This tumor progression could be caused by isolated disseminated tumor cells in lymph nodes which are not detected by current staging methods. The purpose of this study was to develop a system for detecting lymphogenic tumor cell dissemination in colorectal cancer. With the established CK 20-RT-PCR we detected tumor cells in 32 of 107 histopathologically negative lymph nodes from patients with colorectal cancer. We conclude that the CK 20-RT-PCR is more sensitive than immunohistochemical methods in detecting isolated disseminated tumor cells of colorectal cancer in lymph nodes. To evaluate the prognostic significance of lymphogenic disseminated tumor cells the examination and follow-up of more patients is necessary.

Biopsy↗
PubMed1998

[Biologic characterization of soft tissue sarcomes by positron emission tomography (initial results)].

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG), carbon-11-labeled aminoisobutyric acid (AIB) and oxygen-15-labeled water (15O-labeled water) was evaluated for imaging soft tissue sarcomas (STS). Eleven pathologically confirmed STS were evaluated by PET using FDG, AIB and 15O-labeled water. All radiotracers showed an increased activity in viable tumor with a significant differentiation from normal tissue (muscle). An increased glucose metabolism in STS allowed a differentiation from normal tissue (muscle) with FDG. Furthermore, STS showed an increased AIB activity suggesting an increased "A-type" aminoacid transport. AIB therefore can be used for evaluation of STS. 15O-labeled water demonstrated an increased uptake with an overlap with blood vessel activity. These radiotracers supply information about biological properties of STS. Five patients with suspicious lesions in conventional radiodiagnostic but negative PET scans were free of local recurrence, diagnosed either by surgery or by follow-up. Two patients with PET findings suggesting local failure, ultimately demonstrated local recurrence. The differentiation of local recurrence from benign postoperative tissue alterations is encouraging and requires further evaluation.

Amino Acid Transport System A↗
PubMed1998

Dissemination of tumor cells in patients undergoing surgery for colorectal cancer.

The majority of patients with colorectal cancer present at a stage when the primary cancer can be resected with curative intent. However, despite the high resectability rate, about 30-50% of these patients subsequently develop metastatic disease. In these patients, neoplastic cells were disseminated either before or during surgery of the primary cancer. Due to the lack of appropriate detection systems, the extent of pre- and intraoperative hematogenic tumor cell dissemination has not yet been determined. Using a reverse transcription-PCR assay to amplify cytokeratin 20 transcripts, we were able to detect 10 colorectal cancer cells in 10 ml of blood. Blood samples were taken from 65 patients undergoing resection of primary colorectal cancer or liver metastasis of colorectal cancer pre-, intra-, and postoperatively. Circulating tumor cells were detected in 24 of 58 patients with colorectal resections in correlation to the tumor stage and in 6 of 7 patients who underwent hemihepatectomy for liver metastasis. In 8 of 58 patients with colorectal resection and in 5 of 7 patients with hemihepatectomy, tumor cells could only be detected during or during and after surgery. These results demonstrate that hematogenic tumor cell dissemination is a frequent and early event in colorectal cancer. Surgery enhances the release of tumor cells into the circulation. The long-term follow-up of our patient cohort will provide data on the prognostic relevance of circulating tumor cells and might lead to new therapeutic concepts for perioperative prophylaxis of tumor cell implantation or postoperative adjuvant therapy regimens.

Adult↗