Biomedical subjects

S Pistorius

Publications and source records attributed to S Pistorius.

18 recordsLinked to original sources

PubMed2001

[The value of colour duplex sonography in the assessment of surgical resectability of pancreatic tumors].

UNLABELLED: The Value of Colour Duplex Sonography in the Assessment of Surgical Resectability of Pancreatic Tumors. AIM: The aim of this study was to evaluate the assessment by modern colour duplex imaging (CDI) concerning the relation between tumour and vessels including haemodynamic parameters in the main abdominal arteries and the portal system, and to evaluate the influence of these results on surgical decision making. METHOD: From January 1997 to October 1998, 146 patients with a tumour of the pancreas were included in a prospective study. Tumour contact to vessels and to the retroperitoneum, data on the flow in the main abdominal arteries and the portal circulation (regional topography) as well as the detection of liver metastases, enlarged lymph nodes and peritoneal carcinomatosis were defined as representing criteria of resectability. The results were compared with the intraoperative situation and with the definite histological findings. RESULTS: In 57 resectable tumours, the portal system was found to be infiltrated by the tumour up to a length of 1.5 cm. The flow velocity reached between 4 and 53 cm/s (mean flow) and 9 to 105 cm/s (maximum flow). Out of 146 pancreatic tumours, 89 were found as being non-resectable. In these cases, the measured parameters differed depending on the degree of tumour infiltration in to the portal circulation. We measured values from 0 to 96 cm/s (mean flow) and from 0 to 201 cm/s (maximum flow) with loss of breath-dependent modulation. The contact area between tumor and portal vessel was longer than 2 cm. Pathological flow in the main abdominal arteries was only found in 2 of 13 cases. The local situation was assessed correctly in 140 out of 146 cases by CDI (sensitivity of 93.0 %, specificity of 97.8 %, positive predictive value of 96.4 %, negative predictive value of 95.6 %). Regarding the complete oncological status (local situation, metastases, lymph node involvement and peritoneal carcinomatosis), a sensitivity of 82.5 % and a specificity of 92.1 % (positive predictive value of 87.0 %, negative predictive value of 89.1 %) was found. CONCLUSION: Modern CDI can reliably assess the resectability of pancreatic tumours by the evaluation of morphological and haemodynamic parameters. There are still difficulties in the assessment of lymph node involvement as well as in the detection of small liver metastases and of peritoneal carcinomatosis without ascites.

Adult↗

PubMed2001

Dosimetric investigation and portal dose image prediction using an amorphous silicon electronic portal imaging device.

A two step algorithm to predict portal dose images in arbitrary detector systems has been developed recently. The current work provides a validation of this algorithm on a clinically available, amorphous silicon flat panel imager. The high-atomic number, indirect amorphous silicon detector incorporates a gadolinium oxysulfide phosphor scintillating screen to convert deposited radiation energy to optical photons which form the portal image. A water equivalent solid slab phantom and an anthropomorphic phantom were examined at beam energies of 6 and 18 MV and over a range of air gaps (approximately 20-50 cm). In the many examples presented here, portal dose images in the phosphor were predicted to within 5% in low-dose gradient regions, and to within 5 mm (isodose line shift) in high-dose gradient regions. Other basic dosimetric characteristics of the amorphous silicon detector were investigated, such as linearity with dose rate (+/- 0.5%), repeatability (+/- 2%), and response with variations in gantry rotation and source to detector distance. The latter investigation revealed a significant contribution to the image from optical photon spread in the phosphor layer of the detector. This phenomenon is generally known as "glare," and has been characterized and modeled here as a radially symmetric blurring kernel. This kernel is applied to the calculated dose images as a convolution, and is successfully demonstrated to account for the optical photon spread. This work demonstrates the flexibility and accuracy of the two step algorithm for a high-atomic number detector. The algorithm may be applied to improve performance of dosimetric treatment verification applications, such as direct image comparison, backprojected patient dose calculation, and scatter correction in megavoltage computed tomography. The algorithm allows for dosimetric applications of the new, flat panel portal imager technology in the indirect configuration, taking advantage of a greater than tenfold increase in detector sensitivity over a direct configuration.

Algorithms↗

PubMed2001

[Hereditary colorectal carcinomas - reflection on preventive surgery].

Nonpolyposis Colorectal Cancer (HNPCC) accounts for about 5% of all colorectal cancers and is the most frequent familial form; familial adenomatous polyposis coli accounts for about 1%. Prerequisitive for individually tailored surveillance is the identification of the pathogenic germline mutation. In classical FAP, surgical standard is a restorative proctocolectomy while in HNPCC there is no surgical standard other than standard oncological resection due to missing evidence. In HNPCC, prophylactic colectomy before the onset of the first colorectal cancer is not recommended. Main arguments for the extension of the resection in the case of the first colorectal carcinoma in HNPCC are the rate of metachronous colorectal carcinomas of 40-45% in a 10-year interval and rapid tumor progression. In HNPCC, in the case of first colon cancer a subtotal colectomy seems to be indicated. A proctocolectomy or, if indicated, a restorative proctocolectomy may be considered in the case of carcinomas in the lower rectum. These considerations should be evaluated in a prospective clinical trial. Counselling, molecular diagnosis and surgery in patients with hereditary colorectal cancers should only be performed in interdisciplinary centers.

Adenomatous Polyposis Coli↗

PubMed2001

[Can molecular genetic knowledge from studies of hereditary carcinoma be applied to sporadic colorectal carcinoma?].

Colorectal carcinomas without a family history are considered to be "sporadic" carcinomas, however, also have a genetic basis. Within the hereditary forms there are 15-50% of patients without a family history being carriers of de novo germline mutations. In addition, non-pathogenic polymorphisms in these tumorsyndrome-genes as well as in genes involved in the carcinogen metabolism (GST, NAT, CYP, MTHFR) are associated with an increased or decreased colorectal cancer risk. Identification of these genetic risk factors will enable individually tailored surveillance and recommendations for prophylaxis as well as individually tailored treatment.

Adenomatous Polyposis Coli↗

PubMed2000

Sequence analysis of the mismatch repair gene hMSH6 in the germline of patients with familial and sporadic colorectal cancer.

To evaluate the involvement of hMSH6 in colorectal cancer, the complete coding sequence and flanking intron regions of the gene were analyzed by DNA sequencing in 10 patients fulfilling Bethesda Guidelines for colorectal tumors and 10 patients with sporadic colorectal carcinoma. In addition, 10 mono- and 10 dinucleotide repeat markers were analyzed for microsatellite instability. A protein-truncating T insertion at codon 218 was identified in the index person of a hereditary non-polyposis colorectal cancer (HNPCC)-like kindred and was accompanied by a somatic T deletion in the tumor. The tumor of this patient was positive for mono- but negative for dinucleotide repeat instability and lacked allelic losses at loci frequently affected in colorectal carcinomas. A novel amino acid change, F340S, was found in a patient with sporadic colon and breast cancer and leukemia but was not detected in 246 chromosomes from healthy anonymous blood donors. In addition, we describe 2 silent and 15 intronic sequence variants not previously reported. Although the frequency is low, we present further evidence for hMSH6 germline mutations that predispose patients to HNPCC-like phenotypes and suggest that mono- and dinucleotide repeat instability testing may be useful for distinguishing between individuals harboring an hMSH2 or hMLH1 mutation and a mutation of the hMSH6 gene.

Adaptor Proteins, Signal Transducing↗

PubMed2000

A two-step algorithm for predicting portal dose images in arbitrary detectors.

Recently, portal imaging systems have been successfully demonstrated in dosimetric treatment verification applications, where measured and predicted images are quantitatively compared. To advance this approach to dosimetric verification, a two-step model which predicts dose deposition in arbitrary portal image detectors is presented. The algorithm requires patient CT data, source-detector distance, and knowledge of the incident beam fluence. The first step predicts the fluence entering a portal imaging detector located behind the patient. Primary fluence is obtained through ray-tracing techniques, while scatter fluence prediction requires a library of Monte Carlo-generated scatter fluence kernels. These kernels allow prediction of basic radiation transport parameters characterizing the scattered photons, including fluence and mean energy. The second step of the algorithm involves a superposition of Monte Carlo-generated pencil beam kernels, describing dose deposition in a specific detector, with the predicted incident fluence. This process is performed separately for primary and scatter fluence, and yields a predicted dose image. A small but noticeable improvement in prediction is obtained by explicitly modeling the off-axis energy spectrum softening due to the flattening filter. The algorithm is tested on a slab phantom and a simple lung phantom (6 MV). Furthermore, an anthropomorphic phantom is utilized for a simulated lung treatment (6 MV), and simulated pelvis treatment (23 MV). Data were collected over a range of air gaps (10-80 cm). Detectors incorporating both low and high atomic number buildup are used to measure portal image profiles. Agreement between predicted and measured portal dose is better than 3% in areas of low dose gradient (<30%/cm) for all phantoms, air gaps, beam energies, and detector configurations tested here. It is concluded that this portal dose prediction algorithm is fast, accurate, allows separation of primary and scatter dose, and can model arbitrary detectors.

Air↗

PubMed2000

Photon scatter in portal images: physical characteristics of pencil beam kernels generated using the EGS Monte Carlo code.

Pencil beam kernels describing scattered photon fluence behind homogeneous water slabs at various air gap distances were generated using the EGS Monte Carlo code. Photon scatter fluence was scored in separate bins based on the particle's history: singly scattered, multiply scattered, and bremsstrahlung and positron annihilation photons. Simultaneously, the mean energy and mean angle with respect to the incident photon pencil beam were tallied. Kernels were generated for incident photon pencil beams exhibiting monoenergetic spectra of 2.0 and 10.0 MeV, and polyenergetic spectra representative of 6 and 24 MV beams. Reciprocity was used to generate scatter fractions on the central axis for various field sizes, phantom thicknesses, and air gaps. The scatter kernels were further characterized by full width at half-maximum estimates. Modulation transfer functions were calculated, providing theoretical estimates of the limit of performance of portal imaging systems due to the intrinsic scattering of photon radiation through the patient.

Humans↗

PubMed2000

Monte Carlo studies of the exit photon spectra and dose to a metal/phosphor portal imaging screen.

The energy spectra and the dose to a Cu plate/Gd2O2S phosphor portal imaging detector were investigated for monoenergetic incident beams of photons (1.25, 2, and 5 MeV). The Monte Carlo method was used to characterize the influence of the patient/detector geometry, detector material and design, and incident beam energy on the spectral distribution and the dose, at the imaging detector plane, of a photon beam scattered from a water phantom. The results show that radiation equilibrium is lost in the air gap and that, for the geometries studied, this effect led to a reduction in the exit dose of up to 40%. The finding that the effects of the air gap and field size are roughly complementary has led to the hypothesis that an equivalent field size concept may be used to account for intensity and spectral changes arising from air gap variations. The copper plate preferentially attenuates the low-energy scattered photons incident on it, while producing additional annihilation, bremsstrahlung, and scattered photons. As a result, the scatter spectra at the copper surface entrance of the detector differs significantly from that at the Cu/phosphor interface. In addition, the mean scattered photon energy at the interface was observed to be roughly 0.4 MeV higher than the corresponding effective energy for 2 MeV incident beams. A comparison of the dose to various detector materials showed that exit dosimetry errors of up to 24% will occur if it is assumed that the Cu plate/Gd2O2S phosphor detector is water equivalent.

Computer Simulation↗

PubMed2000

Photon scatter in portal images: accuracy of a fluence based pencil beam superposition algorithm.

The accuracy of a pencil beam algorithm to predict scattered photon fluence into portal imaging systems was studied. A data base of pencil beam kernels describing scattered photon fluence behind homogeneous water slabs (1-50 cm thick) at various air gap distances (0-100 cm) was generated using the EGS Monte Carlo code. Scatter kernels were partitioned according to particle history: singly-scattered, multiply-scattered, and bremsstrahlung and positron annihilation photons. Mean energy and mean angle with respect to the incident photon pencil beam were also scored. This data allows fluence, mean energy, and mean angular data for each history type to be predicted using the pencil beam algorithm. Pencil beam algorithm predictions for 6 and 24 MV incident photon beams were compared against full Monte Carlo simulations for several inhomogeneous phantoms, including approximations to a lateral neck, and a mediastinum treatment. The accuracy of predicted scattered photon fluence, mean energy, and mean angle was investigated as a function of air gap, field size, photon history, incident beam resolution, and phantom geometry. Maximum errors in mean energies were 0.65 and 0.25 MeV for the higher and lower energy spectra, respectively, and 15 degrees for mean angles. The ability of the pencil beam algorithm to predict scatter fluence decreases with decreasing air gap, with the largest error for each phantom occurring at the exit surface. The maximum predictive error was found to be 6.9% with respect to the total fluence on the central axis. By maintaining even a small air gap (approximately 10 cm), the error in predicted scatter fluence may be kept under 3% for the phantoms and beam energies studied here. It is concluded that this pencil beam algorithm is sufficiently accurate (using International Commission on Radiation Units and Measurements Report No. 24 guidelines for absorbed dose) over the majority of clinically relevant air gaps, for further investigation in a portal dose prediction algorithm.

Air↗

PubMed2000

[Surgery of hereditary colorectal carcinoma].

Hereditary colorectal cancer syndromes account for about 7% of all colorectal carcinomas. The most frequent form is Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Identification, cloning and sequence analysis of the predisposing genes enables identification of mutation carriers and non-mutation carriers, respectively. These genetic informations can be used in an individually tailored clinical surveillance program and may ultimately result in standard preventive surgical treatment. In classical FAP the surgical standard is performing a restorative proctocolectomy. It is still unclear now, if this procedure should be modified in attenuated forms (colectomy with ileorectostomy). Due to a high rate of synchronous and metachronous carcinomas a subtotal colectomy in the case of first colon cancer seems to be indicated in HNPCC patients. A proctocolectomy or a restorative proctocolectomy should be weighed in case of carcinomas in the lower rectum. These procedures should be performed under the precondition of identification of the pathogenic germline mutation in the patient, only. In addition, a synchronous prophylactic hysterectomy with oophorectomy should be recommended postmenopausal gene carriers. Intensive counseling of the patient should proceed these preventive procedures involving surgeons, gastroenterologists, geneticists, molecular biologists, gynecologists, physicians and psychologists. It is recommended to have patients treated exclusively in specialized centers. Currently, six interdisciplinary centers for cancer surveillance and early diagnosis in hereditary colorectal cancer are being sponsored in Germany by the Deutsche Krebshilfe since 1999. In the future clinical studies have to be conducted to evaluate the efficacy of extended colorectal resections versus efficacy of surveillance and conventional resections according to general oncological principles.

Adenomatous Polyposis Coli↗

PubMed1999

[Preventive surgery of inherited colorectal cancer identified through molecular diagnosis].

Numerous inherited genetic changes predisposing to cancer have already been identified and the number is increasing. Accurate prediction of individual risk by means of molecular diagnosis implies clinical consequences in the treatment of cancer-predisposing syndromes. Using familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) as an example, we present here the underlying genetic changes that contribute to tumor development. These genetic alterations can be efficiently identified through molecular diagnostic techniques. Identification of the familial germline mutation permits one to distinguish mutation carriers from non-mutation carriers within affected families and results in individually tailored surveillance and prevention. Therefore, molecular diagnosis is making a contribution to the advances in preventive surgical therapy. The indications are discussed.

Colorectal Neoplasms↗

PubMed1999

Determination of equivalent photon fields through integrated 1D convolution kernels.

The equivalent fields concept has been studied using a variation of the convolution dose calculation method. This allows a better understanding of this classic, widely-used concept and its relation to modern dose calculation techniques. Total scatter energy contribution as a function of field size was computed by radially integrating three-dimensional point interaction scatter kernels representing cobalt-60, 6 MV and 24 MV photon beam spectra and utilizing reciprocity. For arbitrarily shaped treatment fields, equivalent square or circular fields are chosen based on a conservation of energy approach. Associated depth dose curves are generated via convolution of primary fluence with pre-integrated scatter kernels. For the energy spectra used, the resulting equivalent circle to square relationships agree with the empirical equation recommended in the British Journal of Radiology Supplement 25 (BJR 25) (to within 2%). Tables converting rectangular fields to equivalent squares and circles have been generated and most (approximately 63%) of the equivalent square (and circular) field sizes are within 0.5 cm of the BJR 25 tables. This agreement provides an explanation for the successful use of a single relationship for all therapeutic energies. Fields of different shape will be approximately equivalent only when the scatter kernels are similar in shape and total energy content. The equivalent field concept inevitably results in an optimal match of depth dose curves at a single depth only. These ideas are demonstrated for a highly elongated (2 x 30 cm2) field and its equivalent square field. The invalidity of the equivalent fields concept off-axis is demonstrated by examining predicted dose deposition for several points in and around a 15 x 15 cm2 cobalt-60 beam. Modern convolution techniques are shown to offer a unique approach to the classic equivalent fields method. The appropriate use of the BJR 25 equivalent fields tables is recommended for all photon energies.

Monte Carlo Method↗

PubMed1999

[Predictive molecular diagnosis and preventive surgical treatment of hereditary colorectal carcinoma: a new field of interest for surgical research].

Colorectal cancer is one of the most frequent cancers in the Western hemisphere. It seems to be well established that colorectal tumors develop as a result of an accumulation of inherited and/or acquired somatic mutational events in tumor suppressor genes and oncogenes. An increasing understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Therefore, strategies have been developed for predictive molecular diagnosis and preventive surgical treatment of colorectal cancer syndromes. In the future surgical research will participate in research and development in the field of molecular diagnosis of colorectal cancer and will then evaluate the clinical management concepts as a result.

Adenomatous Polyposis Coli↗

PubMed1998

[Molecular diagnosis and clinical consequences in families with HNPCC syndrome].

Thirteen families were included in our HNPCC surveillance program, eight of which met strict and three incomplete Amsterdam criteria. Two index patients were younger than 35 years of age. Tumors of all index persons showed microsatellite instabilities in at least 50% of the ten markers studied. Immunohistochemical analysis of tumor sections was performed using antibodies against hMLH1 and hMSH2 proteins in order to identify the mutated gene, which is not expressed in the tumor. Coding regions of hMLH1 and hMSH2 genes were amplified by PCR from genomic DNA and sequenced. In nine families pathogenetic mutations all resulting in a truncated protein, could be identified. Furthermore, 21 intron and exon polymorphisms were found. Since July 1997 we have offered surgical and genetic counseling to families with hereditary cancer syndromes in a special outpatient clinic. In addition to 13 index patients three asymptomatic gene carriers were included and eight noncarriers were excluded from the HNPCC surveillance program, as recommended by the HNPCC study group of Germany. Molecular diagnosis has considerable clinical implication in hereditary nonpolyposis colorectal cancer (HNPCC) families with respect to family members who actually have the disease as well as gene carriers and noncarriers.

Adaptor Proteins, Signal Transducing↗

PubMed1997

The putative tumor suppressor gene FHIT at 3p14.2 is rarely affected by loss of heterozygosity in primary human brain tumors.

To elucidate the role of the recently identified FHIT gene, located at 3p14.2 in human brain tumor carcinogenesis, a total of 259 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D3S1313, D3S1234, D3S1300, and D3S1481. In primary brain tumors, LOH was detected at a frequency of 8.4% (n = 214). Low-grade gliomas exhibited insignificantly lower LOH rates in comparison to high-grade gliomas (5.3%, n = 19, versus 11.1%, n = 90). Notably, no allelic loss was observed in 12 recurrent glioblastomas analyzed in comparison to their corresponding primary tumor lesions and in two astrocytomas with progression to higher grades of malignancy. Our data indicate that allelic loss of the FHIT gene is neither a critical event in carcinogenesis of primary brain tumors nor tumor grade-associated in astrocytic tumors. In contrast, observed LOH rate for brain metastases was as high as 54.5% (n = 45), in accordance with data thus far accumulated from analyses of corresponding primary tumors.

Acid Anhydride Hydrolases↗

PubMed1997

An intronic germline transition in the HNPCC gene hMSH2 is associated with sporadic colorectal cancer.

The aim of this study was to determine whether an intronic germline substitution in the hereditary non-polyposis colorectal cancer (HNPCC) gene hMSH2 represents a genetic risk factor for sporadic CRC. Possible effects of this substitution were investigated by assessment of microsatellite instability and hMSH2 cDNA sequencing. Constitutional DNA from patients with sporadic CRC and healthy controls from the same region in Germany was analysed for the intronic germline T-->C transition six bases upstream of exon 13 of hMSH2. 29 of 106 patients (27%) were found to harbour the germline T-->C transition as opposed to only 13 of 125 controls (10%; P < 0.001; OR 3.2, CI 1.58-6.63). CRCs from patients with the substitution displayed neither clinical HNPCC-like features nor an increased rate of microsatellite instability. No abnormal cDNA sequence was found at the exon 12-13 border. These data suggest a 3.2-fold increased risk of sporadic CRC for individuals with the intronic hMSH2 transition. However, this substitution might not be pathogenic itself, but may be linked to a locus nearby that is.

Adult↗

PubMed1988

In vitro determination of bone mineral content of the femur neck. Use of computed tomography.

An accurate method for the in vitro measurement of mineral content of femoral bone by means of computed tomography (CT) is presented. The bone mineral content (BMC) of the femoral head in patients with a subcapital fracture was determined and compared with that in patients with osteo-arthritis. There was a satisfactory standard curve and a highly significant relationship between the CT number (Hounsfield number) and a standard bone equivalent reference (K2HPO4) was obtained at two different energies (96 and 125 kV). The calculated error in the calibration procedure was less than 1,5% and the overall error of the method was 8,8%. The femoral BMC of patients in the fracture group was found to be substantially lower (P less than 0.001) than that in osteoarthritis.

Aged↗

PubMed1987

The relative biological effectiveness of 100 kV X-rays determined by the V-79 cell colony assay.

The relative biological effectiveness (RBE) of 100 kV X-rays compared with cobalt-60-gamma-irradiation was determined using a cell colony assay based on the survival of Chinese hamster V-79 lung fibroblasts. The 37% dose (Do) was found to range from 1.12 to 1.47 and from 1.33 to 1.63 Gy for X-rays and 60Co-gamma-irradiation respectively. The mean RBE value calculated from the Do values was found to be 1.13 +/- 0.04. This figure compares favourably with RBE values calculated from Do values using other endpoints.

Animals↗