Biomedical subjects

F Willeke

Publications and source records attributed to F Willeke.

At least 19 recordsLinked to original sources

PubMed2006

Overexpression of a member of the pentraxin family (PTX3) in human soft tissue liposarcoma.

A unique feature of human soft tissue liposarcoma is a stable (12;16)(q13;p11) translocation observed mainly in myxoid and roundcell liposarcomas. This translocation results in FUS/CHOP fusion transcripts with a corresponding oncogenic protein. We hypothesised that genes downstream of FUS/CHOP might serve as attractive candidates for novel tumour associated antigens. Among a panel of analysed genes, only pentraxin related gene (PTX3) demonstrated high expression in liposarcomas as compared to normal tissues. The analysis of RNA and protein expression demonstrated concordant results. However, the level of RNA and protein overexpression did not correlate in all cases. Finally, PTX3 expression was not related to presence of a FUS/CHOP fusion transcript within the liposarcoma tissues. PTX3 has been associated with adipocyte differentiation and now, additionally, is characterised by a markedly increased expression in human soft tissue liposarcoma. This finding mandates further research efforts to clarify the exact role of PTX3 in liposarcoma oncogenesis.

Adult↗

PubMed2006

Fluorescence-guided minimally invasive parathyroidectomy: a novel detection technique for parathyroid glands.

BACKGROUND: Detection of normal and pathologic parathyroid glands often is difficult because of their variability in number and location. The feasibility and efficacy of a fluorescence technique for identifying parathyroids have already been proved in an experimental setting. This is the first report of human fluorescence-guided parathyroidectomy. METHODS: A 72-year-old man with primary hyperparathyroidism underwent minimally invasive videoscopically assisted parathyroidectomy after photosensitization with aminolevulinic acid. Under special fluorescence illumination by the D-light, a unilateral directed neck exploration was performed. RESULTS: The enlarged adenoma and an atrophic parathyroid gland could be identified rapidly and removed because of their intense red fluorescence. Surrounding structures such as thyroid, muscles, and soft tissue remained nonfluorescent and could easily be distinguished from the parathyroid glands. CONCLUSIONS: The aminolevulinic acid-induced fluorescence technique represents a convincing visual detection method for intraoperative identification of parathyroid glands. The technique serves as an additional tool requiring only moderate technical and clinical expenditure for help in guiding dissection down to a preoperatively localized adenoma. When used together with preoperative ultrasonography and sestamibi scan, the fluorescence technique may justify a unilateral, minimally invasive approach for selected patients.

Adenoma↗

PubMed2006

Morphological features of enlarged parathyroid glands in B-mode-ultrasound.

Successful preoperative localisation of parathyroid glands is essential for minimal-invasive surgery of hyperparathyroidism. The knowledge of the sonomorphology of the parathyroid glands, therefore, is an important prerequisite. This article shows that the sonomorphology of normal and pathologically transformed parathyroid glands is subject to a wide variety. The often simplified standard description of parathyroid glands as hypoechogenic and oval may lead to false negative cervical ultrasound examinations.

Diagnosis, Differential↗

PubMed2006

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

Adenocarcinoma↗

PubMed2006

[Neoadjuvant treatment of rectal cancer: towards an individualised therapy].

Neoadjuvant radiation or chemoradiation followed by oncological resection is the current treatment of choice for locally advanced rectal cancer. Profound diagnostics are mandatory to stratify patients for neoadjuvant treatment or primary surgery. Here, magnetic resonance tomography most probably will become the standard modality due to its ability to predict involvement of the circumferential resection margin during surgery. While the initiation of chemoradiation in T4 rectal cancer and patients with distal tumours potentially undergoing sphincter-preserving surgery is unequivocal, the treatment of choice for the remaining patients is undecided. Here, short-term radiotherapy (5 x 5 Gy) competes with chemoradiation of different intensity. In surgical oncology, minimally invasive surgery of the rectum needs further evidence before it can be accepted as an equivalent. Finally, the increase in multimodality treatment will ultimately increase the incidence of late functional sequelae which, up to now, are underrepresented in most reports due to the priority of oncological results. Since responders to neoadjuvant treatment are the ones who benefit most from these therapies, research related to prediction of treatment response has a fundamental role.

Chemotherapy, Adjuvant↗

PubMed2005

[Sonographic localisation procedures in hyperparathyroidism -- persistent hyperparathyroidism after removal of four parathyroid glands].

This case report will give an example for the necessity of performing an ultrasound examination of the neck before resection of the parathyroid glands. In end-stage renal failure a 38-year-old man developed secondary hyperparathyroidism (HPT). Four glands were removed. Two years later the patient revealed persisting HPT. At this point an ultrasound examination was performed and demonstrated a fifth parathyroid gland located inside the thyroid gland. The case illustrates the benefit of cervical ultrasound, even in cases of secondary hyperparathyroidism, prior to any cervical exploration.

Adult↗

PubMed2004

Hematogenous tumor cell dissemination during colonoscopy for colorectal cancer.

BACKGROUND: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy. METHODS: Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts. RESULTS: Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar's test: tumor cell detection before after colonoscopy). All control samples consistently tested negative. CONCLUSIONS: Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.

Adenocarcinoma↗

PubMed2004

Impact of chemoradiotherapy-induced anemia on survival in uniformly staged patients with locally advanced squamous cell carcinoma of the esophagus.

AIM: Objective of this study was to evaluate the hemoglobin level (Hb) as potential prognostic factor in uniformly staged patients (pts) undergoing primary chemoradiotherapy (ChRT) for locally advanced squamous cell carcinoma (SCC) of the esophagus. PATIENTS AND METHODS: Pts with histologically proven SCC of the esophagus (uT3/4 Nx or uTx N+) were included in the analysis. Staging procedures comprised endoscopic ultrasound, barium swallow and computed tomography. All pts received radiotherapy (> or =40 Gy) and > or =2 courses of fluorouracil/folinic acid, and cisplatin (5 days/month). In selected pts surgical resection after neoadjuvant ChRT was carried out. Clinical parameters, especially Hb were retrospectively evaluated for their impact on survival. RESULTS: 46 pts were treated between 1996 and 2001. Median survival was 16 months. Survival for pts treated with definitive ChRT (n = 28) was 14 months, whereas pts treated surgically after neoadjuvant ChRT (n = 18) survived 19 months (p = 0.79). Pts with low Hb levels at baseline did not show a worse outcome in comparison with pts with normal Hb levels (16 months), whereas a significant decrease in Hb level within the time period of ChRT was associated with a significantly inferior outcome (11 vs. 31 months; p = 0.046). Pts requiring blood transfusion tended to have inferior survival (11 vs. 24 months; p = 0.07). CONCLUSION: In this retrospective analysis a significant decrease of Hb level during ChRT was identified as prognostic factor for pts undergoing ChRT of SCC of the esophagus.

Aged↗

PubMed2002

Significance of surgery in the multimodality treatment of rectal cancer.

Since the NIH recommendations in 1990 the majority of patients with rectal cancer are treated by a multimodality approach. The last decade has seen considerable improvements in the overall management of rectal cancer, therefore a certain reorientation seems justified. Although many questions remain to be answered, some general recommendations for the treatment of rectal cancer focussed on the small pelvis can be given. Surgery with total mesorectal excision is the standard therapy for cancers of the middle and low rectum in stages T1/2 N0. Adjuvant radiochemotherapy and shortterm pre-operative radiotherapy are both feasible approaches for the treatment of stage II and stage III rectal carcinomas. The superiority of either concept awaits clarifying randomised trials. Patients with T4 rectal cancers should undergo long-term neoadjuvant radiochemotherapy with consecutive oncological resection. The exact mode of the neoadjuvant regimen combining high remission rates with low treatment-associated morbidity needs further refinements. Local excision should be restricted to patients with well-differentiated, less than semi-circumferential T1 carcinomas. Tumours with less favourable histologies should not be treated locally unless general patient conditions forbid oncological resections. In these instances, additional radiochemotherapy appears able to reduce the risk of local recurrence.

Chemotherapy, Adjuvant↗

PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗

PubMed2001

Minimal residual disease in soft-tissue sarcomas.

Soft-tissue sarcomas are characterized by the development of disease recurrence in a distinct subgroup of patients. Despite intense efforts in applying multimodal treatment, the risk of local recurrence or distant metastases remains a considerable threat to patients with soft-tissue sarcoma. This review focuses on the efforts aimed at defining local and systemic tumor extent at the level of minimal residual disease (MRD) tumor cell detection. Examination of MRD in soft-tissue sarcomas has experienced a significant boost from the definition of fusion transcripts resulting from stable chromosomal translocations. The sensitivity and exclusive specificity of the reverse-transcription polymerase chain reaction (RT-PCR) protocols have given insights into tumor cell residues in nearly all body compartments. The accumulated data demonstrates that even after oncologic resections most patients will still harbor a significant tumor burden. Clinical concepts arising out of these new data are under way. One of these concepts is the targeting of the fusion transcript for therapy. However, this approach is still restricted to the experimental setting. The development of clinical applications remains a challenging task, requiring the treatment of as many patients as possible in centers specializing in all of the affected disciplines.

Adult↗

PubMed2001

Evaluation of Bethesda guidelines in relation to microsatellite instability.

PURPOSE: The Bethesda guidelines were developed for selection of patients whose tumors should be tested for high microsatellite instability. This study examined the validity of the different Bethesda criteria in relation to microsatellite instability status to simplify their use in clinical practice. METHODS: A total of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer-associated cancers were registered on the basis of the Amsterdam criteria without age limitations (11 cases), multiple tumors (2 cases), the accumulation of colorectal cancer in the family (no first-degree relatives affected or the index patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13 cases), morphologic and histopathologic manifestations (right-sided colorectal cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria (92 cases). The microsatellite instability status of tumors was determined using the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high microsatellite instability tumors were identified in our hereditary nonpolyposis colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent (27/92) of the Bethesda-positive patients displayed high microsatellite instability compared with 6 percent of patients (4/72) not meeting these criteria (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different distribution of the microsatellite instability status when compared with those of the remaining patients registered (P < or = 0.001). These three criteria detected high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36), and 31 percent (21/67) of patients, respectively. When applying these criteria only, a cumulative detection rate of 77 percent of all (24/31) high microsatellite instability cases was found, thereby identifying 89 percent of high microsatellite instability tumors among the Bethesda-positive patients. Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline mutations and tumor-specific loss of protein expression. CONCLUSION: In our hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria showed the highest sensitivity to identify patients with high microsatellite instability tumors. However, for general medical practice outside academic centers, three criteria are reasonably accurate for adequate high microsatellite instability tumor selection.

Adult↗

PubMed2001

[The search for therapeutic gain in radiation oncology].

The Search for Therapeutic Gain in Radiation Oncology Novel strategies in radiation oncology aim at increasing the therapeutic gain, i.e., to decrease side effects while maintaining cure rates, or to increase cure rates at the same level of complications. Over the years, physical and biological strategies have been developed to achieve this goal. The physical development led to the possibility of precise, computer-controlled beam application by using modern imaging techniques and three-dimensional treatment planning. Improved patient immobilization methods allow minimal safety distances, resulting in steep dose gradients when used together with isocentric multi-field techniques. These predominantly stereotactic irradiation techniques yield therapeutic gain towards the tumor surrounding normal tissue. A critical issue that determines the tolerance of radiation therapy are structures at risk within the target volume. Fractionation is a reliable method to exploit the differential potential for recovery of radiation-induced DNA damage in normal tissues. Radiogenetic strategies aim at the sensibilization of tumor cells by targeting specific characteristics like mutations of p53. The reverse idea, gene-therapeutic radioprotection of normal tissue, is under investigation.

DNA Damage↗

PubMed2001

Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading.

UNLABELLED: The purpose of this study was to evaluate (18)F-FDG PET studies of primary and recurrent sarcomas for diagnosis and correlation with grading. METHODS: The evaluation included 56 patients, 43 with histologically proven malignancies and 13 with benign lesions. Seventeen patients were referred with suspicion on a primary tumor, and the remaining 39 were referred with suspicion on a recurrent tumor. The FDG studies were accomplished as a dynamic series for 60 min. The evaluation of the FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx, computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a two-tissue-compartment model, and fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: Visual evaluation revealed a sensitivity of 76.2%, a specificity of 42.9%, and an accuracy of 67.9%. The vascular fraction VB and the SUV were higher in malignant tumors compared with benign lesions (t test, P < 0.05). Although the FDG SUV helped to distinguish benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. The SUV and fractal dimension accounted for significant differences in six of the nine diagnostic pairs. Whereas grade (G) II and G III tumors were differentiated from lipomas on the basis of the fractal dimension and some other kinetic parameters, no differences were found between G I tumors and lipomas. On the basis of the discriminant analysis, the differentiation of soft-tissue tumors was best for the use of six parameters of the FDG kinetics (SUV, VB, K1, k3, influx, and fractal dimension). Eighty-four percent of G III tumors, 37.5% of G II tumors, 80% of G I tumors, 50% of lipomas, and 14.3% of scars could be classified correctly, whereas inflammatory lesions were misclassified. CONCLUSION: FDG PET should be used preferentially for monitoring patients with G III sarcomas. Visual analysis provides a low specificity. In contrast, the evaluation of the full FDG kinetics provides superior information, particularly for the discrimination of G I and G III tumors (positive predictive value, >80%).

Diagnosis, Differential↗

PubMed2000

[Results of oncological reoperation in primary soft tissue sarcomas].

BACKGROUND: Soft tissue sarcomas (STS) are frequently resected incompletely or without an adequate margin. In such clinical situations an oncological re-resection (wide or compartmental resection or amputation) is recommended. Here, we evaluate the results of oncological re-resection for STS. METHODS: Prospectively gathered data on 67 patients who underwent oncological re-resection after inadequate (intracapsular or marginal) surgery for primary soft tissue sarcomas were analyzed. RESULTS: STS were located in the extremities (85%) and trunk (15%). Advanced UICC stages (1992, 4th edn., 2nd Rev.), IIB-IIIB predominated (66%). Twenty-five patients received intraoperative radiotherapy. Morbidity of re-resection was 28.4%. Residual tumor was detected in 64% of the specimens and clear margins were obtained in 60 patients (90%). With a median follow-up of 57 months the overall local control in patients with tumor-free resection margins was 88% (UICC IA-IIA 100%, IIB-IIIB 82%). Patients treated by adjuvant intraoperative radiotherapy for UICC stages IIB-IIIB with clear margins achieved 90% local control. The 5-year overall survival rate was 87% in patients with tumor-free resection margins. CONCLUSIONS: These findings support the strategy of oncological re-resection after previously non-oncological surgery of STS and imply that re-resection is the prerequisite for any effective adjuvant therapy modality.

Adult↗

PubMed2000

Clinical value of [18-F]] fluorodeoxyglucose positron emission tomography imaging in soft tissue sarcomas.

OBJECTIVE: To evaluate positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) for clinical application in soft tissue sarcomas. SUMMARY AND BACKGROUND DATA: FDG PET is a promising noninvasive method for the preoperative assessment of soft tissue sarcomas and may complement radiologic tomography. METHODS: Data from 50 consecutive patients with 59 masses, either suspicious for primary or locally recurrent soft tissue sarcoma, were prospectively gathered. The semiquantitative FDG uptake (standardized uptake values [SUVs]) was calculated in tumor and normal tissue (muscle). Histopathology of surgical specimens and follow-up data were used as control criteria. RESULTS: In primary soft tissue sarcomas, PET displayed a sensitivity of 91% and a specificity of 88%. Local recurrence was detected with a sensitivity of 88% and a specificity of 92%. All intermediate-grade and high-grade soft tissue sarcomas (primary and locally recurrent) were visualized with a precise differentiation from muscle. Fifty percent of the low-grade sarcomas showed an FDG uptake equivalent to muscle (false-negative results in one primary and three recurrent soft tissue sarcomas). Benign soft tissue tumors (e.g., lipoma, leiomyoma, ganglion) did not accumulate FDG. Inflammation resulted in an increased FDG uptake. The semiquantitative FDG uptake (SUVs) correlated with tumor grade but not with size and histologic type. CONCLUSION: High-grade and intermediate-grade soft tissue sarcomas are amenable to PET imaging, whereas low-grade lesions may not be depicted. SUVs for FDG correlate with tumor grade in soft tissue sarcomas. Benign soft tissue tumors are differentiated from higher-grade soft tissue sarcomas. These data show that FDG-PET can complement preoperative radiologic assessment for soft tissue sarcomas and that FDG-PET is a powerful diagnostic tool for detecting high-grade and intermediate-grade local recurrence.

Adolescent↗

PubMed2000

Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.

OBJECTIVE: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems. METHODS: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction. RESULTS: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination. CONCLUSIONS: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

Adult↗

PubMed2000

Detection of chromosomal imbalances in leiomyosarcoma by comparative genomic hybridization and interphase cytogenetics.

Leiomyosarcomas comprise a group of malignant soft-tissue tumors with smooth-muscle differentiation. In this study, 14 cases of leiomyosarcoma were screened for changes in relative chromosome copy number by comparative genomic hybridization. A high number of imbalances (mean, 16.3; range, 6-26) was detected, with chromosomal gains occurring about twice as much as losses. The most frequent gains were found in 5p15, 8q24, 15q25-->q26, 17p, and Xp (43% to 50%), whereas the most frequent losses were found in 10q and 13q (50% and 78%, respectively). Twenty high-level amplifications affecting 15 different chromosomal subregions were detected in nine different tumors. In three leiomyosarcomas, sequences on chromosome arm 17p were found to be highly amplified, with a minimal overlapping region on subbands 17p12-->p11. We further discovered that the Smith-Magenis syndrome critical region on 17p11.2 is included in the 17p amplicons of two leiomyosarcoma cases. Using probes flanking this genetically unstable region, a mean of 14 and 22 signals per nucleus, respectively, was detected in both leiomyosarcomas by fluorescence in situ hybridization. In conclusion, this analysis identifies a number of characteristic chromosomal imbalances in leiomyosarcomas and provides evidence for the localization of potential oncogenes and tumor suppressor genes active in leiomyosarcoma genomes.

Adult↗