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Peter Petrow

Publications and source records attributed to Peter Petrow.

16 recordsLinked to original sources

Intercomparison of treatment concepts for MR image assisted brachytherapy of cervical carcinoma based on GYN GEC-ESTRO recommendations.

PURPOSE: To perform a multicentre intercomparison study of treatment concepts for MRI assisted brachytherapy of cervix cancer based on recommendations of the Gynaecological GEC-ESTRO Working Group. METHODS: Each participating centre (IGR Paris, University Hospital Leuven, Medical University of Vienna) contributed data of one patient with comparable clinical features. GTV, High Risk CTV (HR CTV), Intermediate Risk CTV (IR CTV) and organ walls of bladder, rectum and sigmoid colon were delineated at the time of each brachytherapy fraction on axial MR images with the applicator in place. Dose-volume histograms were calculated to evaluate doses to tumour, target volumes and organs at risk. Dose values were biologically normalised to equivalent doses in 2 Gy fractions (EQD(2), equivalent to 50 cGy/h low dose rate) applying the linear-quadratic model. RESULTS: Total doses to point A from external beam therapy plus brachytherapy ranged from 85 to 91 Gy and were close to the dose covering 90% of HR CTV (D90=85-87 Gy). D90 of IR CTV was within 69-73 Gy. Doses to organs at risk were comparable. CONCLUSIONS: This study indicates the feasibility of the GEC-ESTRO recommendations. Despite different treatment concepts, biologically normalised total doses to tumour, target volumes and organs at risk were comparable.

Brachytherapy↗

Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology.

The second part of the GYN GEC ESTRO working group recommendations is focused on 3D dose-volume parameters for brachytherapy of cervical carcinoma. Methods and parameters have been developed and validated from dosimetric, imaging and clinical experience from different institutions (University of Vienna, IGR Paris, University of Leuven). Cumulative dose volume histograms (DVH) are recommended for evaluation of the complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to 90 and 100% of the respective volume: D90, D100. The volume, which is enclosed by 150 or 200% of the prescribed dose (V150, V200), is recommended for overall assessment of high dose volumes. V100 is recommended for quality assessment only within a given treatment schedule. For Organs at Risk (OAR) the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cm3; optional 5 and 10 cm3. Underlying assumptions are: full dose of external beam therapy in the volume of interest, identical location during fractionated brachytherapy, contiguous volumes and contouring of organ walls for >2 cm3. Dose values are reported as absorbed dose and also taking into account different dose rates. The linear-quadratic radiobiological model-equivalent dose (EQD2)-is applied for brachytherapy and is also used for calculating dose from external beam therapy. This formalism allows systematic assessment within one patient, one centre and comparison between different centres with analysis of dose volume relations for GTV, CTV, and OAR. Recommendations for the transition period from traditional to 3D image-based cervix cancer brachytherapy are formulated. Supplementary data (available in the electronic version of this paper) deals with aspects of 3D imaging, radiation physics, radiation biology, dose at reference points and dimensions and volumes for the GTV and CTV (adding to [Haie-Meder C, Pötter R, Van Limbergen E et al. Recommendations from Gynaecological (GYN) GEC ESTRO Working Group (I): concepts and terms in 3D image-based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235-245]). It is expected that the therapeutic ratio including target coverage and sparing of organs at risk can be significantly improved, if radiation dose is prescribed to a 3D image-based CTV taking into account dose volume constraints for OAR. However, prospective use of these recommendations in the clinical context is warranted, to further explore and develop the potential of 3D image-based cervix cancer brachytherapy.

Brachytherapy↗

[Retroperitoneal sarcomas imaging].

Retroperitoneal sarcomas are rare neoplasms. The aim of this article is to expose imaging protocols and useful radiological signs, to show the core biopsy technique for diagnosis, to precise imaging key points before treatment and for survey.

Biopsy, Needle↗

Intra-articular injections of high-molecular-weight hyaluronic acid have biphasic effects on joint inflammation and destruction in rat antigen-induced arthritis.

To assess the potential use of hyaluronic acid (HA) as adjuvant therapy in rheumatoid arthritis, the anti-inflammatory and chondroprotective effects of HA were analysed in experimental rat antigen-induced arthritis (AIA). Lewis rats with AIA were subjected to short-term (days 1 and 8, n = 10) or long-term (days 1, 8, 15 and 22, n = 10) intra-articular treatment with microbially manufactured, high-molecular-weight HA (molecular weight, 1.7 x 10(6) Da; 0.5 mg/dose). In both tests, 10 buffer-treated AIA rats served as arthritic controls and six healthy animals served as normal controls. Arthritis was monitored by weekly assessment of joint swelling and histological evaluation in the short-term test (day 8) and in the long-term test (day 29). Safranin O staining was employed to detect proteoglycan loss from the epiphyseal growth plate and the articular cartilage of the arthritic knee joint. Serum levels of IL-6, tumour necrosis factor alpha and glycosaminoglycans were measured by ELISA/kit systems (days 8 and 29). HA treatment did not significantly influence AIA in the short-term test (days 1 and 8) but did suppress early chronic AIA (day 15, P < 0.05); however, HA treatment tended to aggravate chronic AIA in the long-term test (day 29). HA completely prevented proteoglycan loss from the epiphyseal growth plate and articular cartilage on day 8, but induced proteoglycan loss from the epiphyseal growth plate on day 29. Similarly, HA inhibited the histological signs of acute inflammation and cartilage damage in the short-term test, but augmented acute and chronic inflammation as well as cartilage damage in the long-term test. Serum levels of IL-6, tumour necrosis factor alpha, and glycosaminoglycans were not influenced by HA. Local therapeutic effects of HA in AIA are clearly biphasic, with inhibition of inflammation and cartilage damage in the early chronic phase but with promotion of joint swelling, inflammation and cartilage damage in the late chronic phase.

Adjuvants, Immunologic↗

Role of computed tomography in the follow-up of hepatic and peritoneal metastases of GIST under imatinib mesylate treatment: a prospective study of 54 patients.

PURPOSE: To prospectively analyze the evolution of hepatic and peritoneal unresectable metastases from gastrointestinal stromal tumors (GIST) under imatinib mesylate, a new targeted treatment, which induces changes in lesion structure. MATERIALS AND METHODS: 54 patients with metastases from GIST underwent an abdominal and pelvic computed tomography examination without and with contrast enhancement, before and during treatment with imatinib mesylate. The number and size of lesions and contrast enhancement were noted before treatment and every 2 weeks for the first 2 months, then every 2 months for the first year of treatment and every 3 months thereafter. RESULTS: 27 patients presented with both hepatic and peritoneal metastases, 14 had only peritoneal and 13, only hepatic disease. On baseline imaging, all metastases were hypodense heterogeneous lesions with progressive, concentric enhancement. After treatment (mean duration of follow-up: 23 months) metastases decreased in size number and enhancement in 35/54 patients, remained stable in 2 patients and increased in 14 patients. In 13/39 patients with hepatic metastases a cyst-like appearance was noted. Reactivation after a partial response appeared first as a focal, peripheral, solid nodule in the wall of a cystic lesion, or an increase in lesion density, before size regrew. CONCLUSION: Besides the classic size criterion, a decrease in density and in contrast enhancement with stable "near cystic" lesions signifies a good response. A more aggressive approach (surgery or radiofrequency ablation) may be indicated for initially focal recurrences with a stable size.

Adult↗

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV.

BACKGROUND AND PURPOSE: Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used. METHODS: In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience. CONCLUSIONS: As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV(D), CTV(D) and at time of BT GTV(B), CTV(B). Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.

Brachytherapy↗

Identification of the receptor for advanced glycation end products in synovial tissue of patients with rheumatoid arthritis.

OBJECTIVES: Generation of advanced glycation end products (AGE) is an inevitable process in vivo and can be accelerated under pathologic conditions such as oxidative stress, e.g. in rheumatoid arthritis (RA). This process is mediated by the AGE-specific receptor (RAGE). In this study we analysed the presence of RAGE in RA and osteoarthritic (OA) synovial tissue using immunohistology. METHODS: Frozen synovial tissue samples from 11 RA patients and 12 OA patients were treated with goat anti-RAGE immunoglobulin G (IgG) and rabbit antigoat IgG. Immunostaining was visualised with streptavidin horse radish peroxidase (chromogen amino-ethyl-carbazole). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: In 9/11 RA and 8/12 OA synovial specimens, RAGE was detected in synovial lining, sublining, and stroma. In RA, many T cells (CD45RO(+)) and some macrophages (CD68(+)) showed positive immunostaining for RAGE, whereas B cells were mostly negative. We found no difference in staining patterns between the RA and OA samples. CONCLUSIONS: We detected RAGE in RA and OA synovial tissue. The presence of RAGE on macrophages, T cells, and some B cells suggests its role in the pathogenesis of inflammatory joint disease.

Aged↗

MR imaging in the evaluation of isolated limb perfusion: a prospective study of 18 cases.

PURPOSE: To prospectively evaluate the use of MRI with dynamic sequences during isolated limb perfusion (ILP) for soft tissue sarcomas, an aggressive local treatment using very high-dose chemotherapy and tumor necrosis factor aimed at avoiding limb amputation. DESIGN AND PATIENTS: Twenty-six patients were referred for ILP over one and a half years; eight were excluded as the lesions were either too proximal or suspicious inflammatory changes without tumor were found on the initial MRI, or the vascular status was poor. The indications for ILP were: vessel nerve involvement (13), multiple lesions (8), tumor size (4) or the presence of pulmonary metastases (2). MRI was performed 1 and 2 months after ILP, immediately prior to surgery and histological analysis. The MR examinations included T1-weighted SE and fast SE T2-weighted fat-saturated sequences, as well as dynamic sequences (T1-weighted SE repeated six times every 40 s), displaying the maximum intensity slope in each pixel. RESULTS: The tumor had disappeared in three patients. One patient still had histologically proven isolated widespread tumor cells without a mass. The tumor size had increased in two patients. In six patients, the size of the tumor had not changed but it had become completely necrotic, with a thin wall. In three patients, after an initially good result MRI demonstrated that the tumor wall had become thickened from 1 to 2 months after ILP. Dynamic MRI was mainly useful during the initial examination, demonstrating two patients with inflammatory changes without tumor. Three amputations and a second ILP were proposed based on poor results. Conservative limb-sparing surgery was successful in the other cases. CONCLUSION: MRI proved valuable in demonstrating the variable responses to ILP.

Adult↗

Cooperation of Ras- and c-Myc-dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis.

OBJECTIVE: To study the specific contribution of MAP kinase activator c-Raf-1 and one of its downstream transcription factors, c-Myc, to the growth and invasive behavior of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: RASFs were transduced with retroviral constructs expressing dominant-negative mutants of c-Raf-1 or c-Myc (DN c-Raf-1 or DN c-Myc, respectively) or with the mock vector. The expression of wild-type and mutant proteins was confirmed by Western blotting. Growth curves of RASFs were recorded, and apoptosis was measured by flow cytometry. Invasiveness of RASFs was assessed in the SCID mouse model of RA. Immunohistochemistry was used to study the effects of DN c-Raf-1 on phosphorylated c-Jun and matrix metalloproteinase 1 (MMP-1) in RASFs implanted into SCID mice. The phosphorylation of ERK and JNK in DN c-Raf-1- and mock-transduced RASFs was determined in vitro by Western blotting. The levels of MMPs in these cells were measured by quantitative polymerase chain reaction (PCR). RESULTS: Neither DN c-Raf-1 alone nor DN c-Myc alone significantly altered proliferation or apoptosis of RASFs, but both mutants together rapidly induced apoptosis. Inhibition of c-Raf-1 or c-Myc significantly reduced the invasiveness of RASFs in the SCID mouse model. DN c-Raf-1 decreased the phosphorylation of ERK and JNK in vitro and reduced the in vivo expression of phosphorylated c-Jun as well as the expression of disease-relevant MMPs. As determined by quantitative PCR, the inhibition was most pronounced for MMP-1 and MMP-3. CONCLUSION: The data demonstrate that Ras- and c-Myc-dependent signaling events cooperate to regulate the growth and invasiveness of RASFs. Targeting of both c-Raf-1 and c-Myc may constitute an interesting therapeutic approach in RA.

Animals↗

Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01).

PURPOSE: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done. RESULTS: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. CONCLUSION: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.

Adult↗

Synovial fibroblasts and synovial macrophages from patients with rheumatoid arthritis and other inflammatory joint diseases show chromosomal aberrations.

Chromosomal aberrations were investigated in nuclei extracted from synovial tissue and first-passage synovial fibroblasts (P-1 SFB, 98% enrichment) or macrophages (P-1 Mphi) from patients with rheumatoid arthritis (n=10). The findings were compared with those in other rheumatic diseases (osteoarthritis, n=14; reactive arthritis, n=1), as well as with those in chronic obstructive pulmonary disease (n=8). Controls were paired peripheral blood lymphocytes from arthritic patients, synovial tissue or SFB/Mphi from joint trauma/normals (n=9), and peripheral blood monocytes from normal donors (n=10). GTG banding of metaphase chromosomes and interphase fluorescence in situ hybridization with centromere-specific probes were used. Comparable chromosomal aberrations were observed in synovial tissue and P-1 SFB of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis (polysomy 7 and aneusomies of chromosomes 4, 8, 9, 12, and 18). Notably, aneusomies of chromosomes 4, 6, 7, 8, 9, 11, 12, and/or X were also detected in P-1 synovial Mphi from rheumatoid arthritis (90% of the cases), osteoarthritis (93%), and reactive arthritis (1/1), as well as bronchial Mphi from chronic obstructive pulmonary disease (25%). No aberrations were detected in paired peripheral blood lymphocytes (except for one osteoarthritis case with a karyotype 45,X[10]/46,XX[17]), or in peripheral blood monocytes and synovial tissue of normals/joint trauma. Because Mphi aberrations were common to chronic joint and pulmonary disease, chronic inflammatory stress may induce chromosomal aberrations with potential functional relevance in local mesenchymal cells and infiltrating leukocytes in an organ-independent fashion.

Adult↗

Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis.

Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.

Antibodies, Antineutrophil Cytoplasmic↗

Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice.

OBJECTIVE: To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice. METHODS: Messenger RNA (mRNA) and protein expression of collagenase 3 and collagenase 1 were characterized in synovial and skin fibroblasts by Northern blot and Western blot analysis. The mRNA expression of both collagenases in cell-cartilage implants in NOD/SCID mice was investigated by in situ hybridization in combination with immunohistochemistry of human fibroblasts. RESULTS: Synovial fibroblasts coimplanted with normal cartilage in NOD/SCID mice deeply invaded adjacent cartilage tissue. In this in vivo system of cartilage destruction, collagenase 3 mRNA was induced in synovial fibroblasts at sites of cartilage erosion, while the expression of collagenase 1 mRNA could not be detected. Culture of synovial fibroblasts within 3-dimensional collagen gels was associated with a marked increase in collagenase 3 mRNA expression and proenzyme production. This stimulatory effect was 1 order of magnitude higher in comparison with a 2-4-fold increase upon treatment with interleukin-1beta or tumor necrosis factor a. In contrast, mRNA expression and proenzyme production of collagenase 1 were increased strongly, and to a similar extent, either by contact with 3-dimensional collagen or by proinflammatory cytokines. CONCLUSION: The expression of collagenase 3, in contrast to that of collagenase 1, is preferentially stimulated in synovial fibroblasts by 3-dimensional collagen rather than by proinflammatory cytokines. The induction of collagenase 3 by cell-matrix interactions represents a potential mechanism contributing to the invasive phenotype of synovial fibroblasts at sites of synovial invasion into cartilage in RA.

Animals↗

Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow-up.

PURPOSE: To describe the appearance of hepatic tumors treated with radio-frequency (RF) ablation on computed tomographic (CT) and magnetic resonance (MR) images and the pattern of residual tumor at the site of RF ablation and to assess prospectively the sensitivity, specificity, and positive and negative predictive CT and MR imaging values in the evaluation of RF treatment. MATERIALS AND METHODS: Thirty-one patients with 50 tumors (nine hepatocellular carcinomas and 41 metastases) treated with RF ablation underwent CT and MR imaging on the same day at 2, 4, and 6 months; CT was performed every 3 months thereafter. CT and MR findings were interpreted separately and prospectively by two reviewers with consensus. For both imaging techniques, appearance of the treated area, treatment efficacy, and complications were assessed at each time. Sensitivity and specificity were determined by using the McNemar test. RESULTS: After a mean follow-up of 19 months, nine tumors showed local regrowth. At 2 months, MR imaging depicted more local regrowths (eight of nine; sensitivity, 89%) than did CT (four of nine; sensitivity, 44%) but without significant differences (P =.12). In two cases, only T2-weighted imaging depicted local regrowth. All nine lesions became conspicuous at 4-month follow-up with both techniques. At 2 months, thin peripheral rim enhancement and arterioportal shunting were found in 24% and 12%, respectively, of the treated tumors. These findings disappeared thereafter and are not linked to tumor regrowth. CONCLUSION: Despite the small number of patients, CT and MR imaging may depicted all local regrowth at 4 months or sooner. MR imaging may have an edge over CT in the early detection of local regrowth.

Adult↗