[Complex pelvic and sarcoma surgery with vascular replacement]. / Komplexe Becken- und Sarkomchirurgie mit Gefäßersatz.

Due to optimization of surgical techniques in surgical oncology and vascular surgery, the most modern approaches of anesthesia and intensive care medicine and effective multimodal therapeutic strategies, locally advanced malignant tumors are resected more frequently with a potentially curative intent. In the case of extensive tumors with infiltration of vital vascular structures or of structures which are crucial for extremity preservation, the necessary surgical procedure for complete tumor removal poses a major challenge for the surgeon and incorporates a high risk of perioperative morbidity for the patient. The decision to attempt tumor resection should therefore always be based on a concept considering all aspects of the malignant disease. The treating team should be highly experienced in this complex field of surgery, not only with respect to the surgical approach but also regarding the management of postoperative complications. In this article relevant aspects of decision making, surgical technique and postoperative outcome for malignant tumors involving vascular structures of the retroperitoneum and pelvis are presented.

Poster - Thur Eve - 14: The effect of fluence and detector size on image quality in multi-projection compton scatter tomography.

PURPOSE: To assess how radiation dose and size of energy sensitive detectors affects image quality in multi-projection Compton scatter tomography. METHODS AND MATERIALS: A Compton scatter tomography system was simulated in Maltab. The system consists of a point source generated x-ray fan beam and energy sensitive photon counting detectors, placed along a line with the source outside the periphery of the primary beam. Single scattered photons from a low contrast phantom simulating breast tissues were simulated. Simulation parameters are dose-limited and closely matched to typical breast CT. Poisson distributed noise was added to simulate quantum noise. RESULTS: We have successfully reconstructed electron density images in a clinical fan-beam breast CT system, in the presence of noise. The reconstruction illustrates accurate spatial alignment of the structures of interest in the phantom. The increase in MSE due to noise was ∼11%. The optimal detector size of 2 × 2 mm2 is a trade off between the increased noise, that is present when smaller detector sizes are used, and the blurring of the image that occurs as larger detectors are employed. CONCLUSIONS: For breast CT dose of 4-12 mGy, the optimal detector size for a Compton scatter reconstruction using 360 projections and 1000 eV energy resolution was found to be 2 × 2 mm2 . The ability to visualize large low contrast (9%) and small (2 mm diameter) high contrast objects was demonstrated.

Poster - Thurs Eve-33: Initial implementation of a novel, measurement-based IMRT QA method.

Current measurement-based QA for IMRT typically involves a composite dose delivery to a phantom. However, this approach does not allow a direct dosimetric evaluation of the delivered treatment with respect to the patient anatomy. In this work we implement a novel, measurement-based IMRT QA method which provides an accurate reconstruction of the 3D-dose distribution in the patient model. The RPC Head&Neck phantom and two clinical prostate cases have been examined to date. Step & shoot plans were developed satisfying required dose metrics. A 2D-array of dose chambers (MatriXX, IBA Dosimetry) was mounted on a linear accelerator to capture delivered fluence. The measurement data were read directly by the control software (COMPASS, IBA Dosimetry), which also provides the ability to import patient plan data from the TPS. The COMPASS software also includes a dose calculation engine and head fluence model and requires beam commissioning procedures analogous to those of a TPS. Reconstructed doses and DVHs were compared to those calculated by the TPS. The beam model in the COMPASS software was able to predict percentage depth dose and X and Y profiles for MLC-defined apertures ranging from 1×1-20×20 cm∧2 to within 1.5% (depth-dose), 2.0% (in-field profiles), and 2.5% (out-of-field profiles). Reconstructed doses in the test plans were mostly within 2% of those in the TPS. DVHs compared to <1.2%. Reconstructed doses were overlaid on CT data and contoured structures, to enable a clinically useful understanding of discrepancies as compared to the TPS plan. Research partially sponsored by IBA Dosimetry.

Sci-Sat AM(1): Imaging-05: Analytical scatter estimation for cone-beam computed tomography.

A significant challenge to the implementation of cone-beam computed tomography (CBCT) for high-resolution imaging is the high scatter to primary ratio. Scatter causes cupping and shading artifacts, increased noise and decreased contrast in reconstructed images. Methods to reduce the impact of scatter in CBCT are thus very desirable. We are investigating methods for computational scatter estimation and compensation for CBCT, with the goal of incorporating a scatter estimator within a statistical reconstruction algorithm. We have developed an analytical method for estimating single scatter, based on Klein-Nishina cross-sections. We have compared scatter estimates generated with this method with the results of high-count EGSnrc Monte Carlo simulations. The analytical estimates compare favorably with the Monte Carlo estimates. The paper will discuss our method for analytical estimation of single scatter, including the assumptions and simplifications required to render it computationally tractable, along with the results of the comparison between the analytical method and Monte Carlo simulations. The paper will extend previous results obtained with small (40 × 40 × 40 voxel) homogeneous computational phantoms to include results for larger, more clinically relevant phantoms (128 × 128 × 128 voxels, simulated 50/50 breast tissue with inserts of varying contrast). The paper will also discuss computational acceleration obtained through the use of parallel processing via the WestGrid High-Performance Computing network.

[Inherited tumors of the gastrointestinal tract. Diagnosis and therapeutic aspects]. / Erbliche Tumoren im Gastrointestinaltrakt. Diagnostik und therapeutische Konsequenzen.

Familial tumors of the gastrointestinal tract, which often appear as autosomal-dominantly inherited tumor syndromes, account for only a small proportion of all gastrointestinal tumors. With the opportunities of modern molecular diagnostics, identifying the pathogenic mutation in families is often possible, with the option of predictive molecular testing and differentiation between mutation carriers and noncarriers. Thus a good chance exists for detection of early tumor stages by individually tailored surveillance programs and for improving prognosis by early intervention and prophylactic resection. Clinical manifestation, molecular basis at the root, individual surveillance programs, and their consequences for the treatment of familial gastric cancer, familial adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome, juvenile polyposis, hyperplastic polyposis, and familial pancreatic cancer are presented.

[The value of colour duplex sonography in the assessment of surgical resectability of pancreatic tumors]. / Farbduplexsonographie zur Beurteilung der Resektabilität von Pankreastumoren.

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.

[Hereditary colorectal carcinomas - reflection on preventive surgery]. / Hereditäre kolorektale Karzinome - Uberlegung zu präventiven chirurgischen Massnahmen.

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.

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.

Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families.

Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifetime risk in gene carriers for synchronous and for metachronous colorectal cancer and endometrial cancer in women, prophylactic and extended surgery are considered as options for gene carriers. A 54-year-old patient with a history of metachronous rectal cancer and a family history fulfilling the Amsterdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histological examination of the specimen showed three synchronous colon carcinomas. The 31-year-old son carrying the pathogenic mutation refused to be included in the HNPCC surveillance program. One year later he presented with symptoms of bowel obstruction, and a carcinoma of the descending colon was diagnosed. Intraoperatively, in addition to the colon cancer, a small bowel cancer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented with synchronous cancer of the ascending colon and the lower rectum at the age of 49 years. Proctocolectomy and prophylactic hysterectomy were performed, which revealed an additional colon cancer and endometrial cancer. We discuss approaches for individual decision making for surgery in HNPCC patients. Is a subtotal colectomy indicated in the case of first colon cancer in HNPCC patients, or if the first tumor occurs in the lower rectum, should a proctocolectomy or a restorative proctocolectomy be considered? The aim of prospective clinical studies should be to assess acceptability, survival rates, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophylactic surgery.

[Can molecular genetic knowledge from studies of hereditary carcinoma be applied to sporadic colorectal carcinoma?]. / Können die molekulargenetischen Kenntnisse aus dem Studium des erblichen Karzinoms auf das sporadische kolorektale Karzinom übertragen werden?

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.

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.

[Surgery of hereditary colorectal carcinoma]. / Die Chirurgie der hereditären kolorektalen Karzinome.

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.

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.

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.

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.

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.

Clinical consequences of molecular diagnosis in families with mismatch repair gene germline mutations.

Hereditary nonpolyposis colorectal cancer (HNPCC), clinically defined by the Amsterdam criteria, is associated with mismatch repair gene germline mutations. This study was performed to evaluate the efficiency of combined clinical and molecular diagnostics in identifying carriers of a mutated gene in families meeting criteria of the Bethesda guidelines and to examine the influence of molecular diagnosis on clinical decision-making in carriers and noncarriers. Seventy-two patients meeting criteria of the Bethesda guidelines were tested for microsatellite instabilities (MSI). MSI-H tumors were found in 38 (52.8%) index patients. Complete sequencing of hMLH1 and hMSH2 in 38 MSI-H patients and of hMSH6 in one of these patients revealed 15 pathogenic germline mutations, including three novel mutations, and three novel unclassified germline variants. Twelve of the 15 pathogenic mutations were found in patients fulfilling the Amsterdam I/II criteria. Surgical and genetic counseling was offered to the affected families; as a result of molecular diagnosis in the 15 families, 26 index patients and affected carriers and 8 asymptomatic carriers of a mutated mismatch repair gene were included in the surveillance program, and 26 noncarriers were excluded from this program. Although germline mutations are detected in only 20.8% of patients fulfilling criteria of the Bethesda guidelines, family history and MSI-H tumor classification are both strong indicators for germline mutations in hMSH2, hMLH1, and hMSH6 genes, resulting in a 51.9% mutation detection rate. Identification of individual mutation status allows clear-cut decisions on whether or not inclusion in surveillance programs is indicated.

[Preventive surgery of inherited colorectal cancer identified through molecular diagnosis]. / Präventive Chirurgie des vererbten colorectalen Carcinoms als Folge molekularer Diagnostik.

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.