Three to six tissue specimens for histopathological analysis are most accurate for diagnosing periprosthetic joint infection.

AIMS: The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). METHODS: In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. RESULTS: Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). CONCLUSION: Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue.Cite this article: Bone Joint J 2023;105-B(2):158-165.

Results in the surgical treatment of aneurysmal bone cysts - A retrospective data analysis.

BACKGROUND: Aneurysmal bone cysts (ABC) are benign tumors mostly occurring in children and young adults. Different open and minimal invasive surgical approaches have been proposed for the treatment of ABCs and yet no consensus is defined to date. The aim of this study was to retrospectively review data of a large single center series of ABCs with patients treated by open curettage with or without filling of the cavity or en-bloc resection. Questions/purposes We asked: (1) What was the local recurrence rate of ABC after surgical treatment at our institution? (2) What were positive or negative predictors for local recurrence? (3) Was there a benefit from adjuvant burring, phenolization or filling, respectively? (4) Where there changes in recurrence free survival in different time periods of primary surgery? METHODS: By retrospective data analysis of the Vienna Bone and Soft Tissue Tumor Registry, 123 patients surgically treated for primary aneurysmal bone cysts were identified. After exclusion of 33 patients (27%) due to a postoperative follow up below one year, 90 patients who were treated for primary ABCs between 1986 and 2009 were evaluated. These included 50 males and 40 females with a mean age of 16 years (SD 10 years; range: 2 to 51 years). The mean follow-up was 99 months. (SD 72 months, range: 13 to 329 months) RESULTS: Curettage was performed in 84 patients, while 45 patients received adjuvant phenolization. Local recurrence occurred in 28 patients after a mean time of 16 months, with a corresponding local recurrence free survival (RFS) of 83% after one year, 77% after 2 years and 66% after 5 years. ABCs located in hands and feet (p=0.044) showed a superior RFS, while younger patients (p=0.001) displayed an inferior RFS. Regarding adjuvant surgical techniques, mechanical cavity burring (p=0.004) and filling with autologous cancellous bone graft (p=0.024) showed protective effects on RFS. Patients treated between 1986 and 1999 (n=47) had a higher RFS than patients treated between 2000 and 2009 (n=43, p=0.011), as surgeons and surgical indications changed over time. CONCLUSION: Although curettage, burring, phenolization and reconstruction with bone grafts came with a relatively high risk of local recurrence, open surgery is still justified in aggressively growing ABCs of critical localizations. LEVEL OF EVIDENCE: IV; therapeutic study.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries.

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Choice of High-Dose Intravenous Iron Preparation Determines Hypophosphatemia Risk.

BACKGROUND: Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM. AIM: To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort. METHODS: Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included. RESULTS: The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of ≥ 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation. CONCLUSION: Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

C-reactive protein as a prognostic factor in patients with chordoma of lumbar spine and sacrum--a single center pilot study.

STUDY DESIGN: This is a retrospective, diagnostic study, level IV. BACKGROUND: It appears to be necessary to identify prognostic markers for individual risk estimation for progression and survival in patients with chordoma, a rare disease. Are pre-operative serum levels of C-reactive protein (CRP) associated with disease progression and survival? METHODS: Survival rates of 24 patients (18 males, 6 females) (mean age 67 years (SD ± 16; range 20-85 years); minimum follow-up 2 years, mean follow-up 5 years (SD ± 5; range 2-19 years)) with chordoma of the lower spine and sacrum were assessed with a focus on pre-operative CRP levels. RESULTS: The survival rate of patients with pre-operative CRP level of >1.0 mg/dl was lower than that of patients with a CRP level <1.0 mg/dl (p = 0.01). The estimated 10-year survival of patients with pre-operative CRP values <1.0 and >1.0 mg/dl was 76 and 25%, respectively. CRP remained as an independent survival factor (p = 0.025; CI 95% 1.0-2.6) in multivariable analysis. CONCLUSIONS: Pre-operative CRP levels appear to be a biomarker for disease-specific survival in patients with chordoma of the lumbar spine and sacrum. A validation of our finding with larger cohorts and integration of putative risk factor would further elucidate CRP a surrogate for tumor progression.

Recurrence rate and progression of chondrosarcoma is correlated with heat shock protein expression.

Heat shock proteins (HSPs) are involved in tumour immunity, and are correlated with survival and drug resistance in numerous types of cancer. The present study investigated the expression of HSPs and multiple drug resistance (MDR) in human chondrosarcoma. HSP and P-glycoprotein (the MDR1 gene product) expression was evaluated by immunohistochemical analysis of paraffin-embedded sections obtained from 37 patients with chondrosarcoma (19 male and 18 female; aged 33-85 years; mean age, 48.5 years). HSP73 and 90 were significantly overexpressed in patients with local recurrence: HSP73 was expressed in 7/7 patients (100%) with local recurrence and 9/18 patients (50%) without recurrence (P<0.02), while HSP90 was expressed in all patients with recurrence but only 8/18 (44%) without recurrence (P<0.02). A marked association was also identified between HSP expression and survival. HSP72 and 73 were significantly overexpressed in tumours from patients who succumbed to the disease (all positive for HSP72 and 73; P<0.05). No differences were observed between HSP27, 73 or 90-positive or -negative tumours according to age or gender. In addition, HSP72 expression was correlated with differentiation of the tumours (P<0.02). These results indicate that HSP72, 73 and 90 may function as novel prognostic markers for chondrosarcoma, and initiate further studies regarding the use of such markers for the identification of patients with poor prognosis.

Impact of RANK signalling on survival and chemotherapy response in osteosarcoma.

The receptor activator of NF-κB (RANK) signalling pathway represents a promising target for the therapy of bone-related tumours. In the present study we evaluated the impact of the expression of RANK and its ligand (RANKL) on survival and response to chemotherapy in osteosarcoma patients.Expression of RANK and RANKL was examined in 91 human osteosarcomas by immunohistochemistry using formalin fixed, paraffin embedded (FFPE) tumour samples. Results of the stainings were correlated with clinicopathological parameters and patient survival.Sixty-three osteosarcomas (69.2%) expressed RANK, whereas only eight cases (8.8%) showed expression of RANKL. Expression of RANK was significantly associated with shorter disease-free survival by Kaplan-Meier analysis (p=0.031). We further observed worse response to chemotherapy in RANK expressing tumours, which was statistically not significant (p=0.099). RANKL expression was significantly more frequent in osteosarcoma of the lower extremity than in any other location. Analysis of RANKL expression did not reveal any statistically significant correlation with disease-free or osteosarcoma-specific survival.In our study, we identified RANK expression as a negative prognostic factor regarding disease-free survival in osteosarcoma. Moreover, RANK might modulate response of human osteosarcoma to chemotherapy. Therefore, RANK signalling cascade is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

Bcl-2 correlates with localization but not outcome in human osteosarcoma.

bcl-2 is a member of the bcl-2 family that inhibits apoptosis, plays a crucial role in cell viability and is expressed in various types of tumors. With respect to inconsistent results in previous studies, the aim of the present study was to generate a clear hypothesis with regards to the value of bcl-2 expression as a predictive or prognostic factor in human osteosarcoma. The expression of bcl-2 was examined immunohistochemically in 49 patients with high-grade osteosarcoma and the results were correlated with localization, histological response to chemotherapy, survival and the occurrence of metastases. In patients with osteosarcoma, 21/49 cases (43%) were positive for bcl-2 expression and the remaining cases were negative. A significantly higher expression of bcl-2 was observed in central tumors located in the pelvis (83 vs. 37% positive; P<0.05). The bcl-2 expression status revealed no statistically significant correlation with response to chemotherapy, with 57% of patients with bcl-2-positive tumors showing a good response and 43% showing a poor response. No significant difference was observed when comparing survival or occurrence in bcl-2-positive and -negative tumors. In conclusion, the results of the present study indicate that, despite higher bcl-2 expression in central osteosarcoma, the expression in high-grade osteosarcoma is not a reliable prognostic or predictive marker.

Altered matrix mineralization in a case of a sclerosing osteosarcoma.

Little is known about the tumor matrix mineralization of highly sclerotic osteosarcoma. We used quantitative backscattered electron imaging (qBEI) to determine the Bone mineralization density distribution (BMDD) of a highly sclerosing osteosarcoma of the proximal tibia as well as adjacent normal bone of a 10-year-old girl following chemotherapy according to the EURAMOS-1 protocol. Data were compared to recently published normative reference data for young individuals. Backscattered electron imaging of the tumor region revealed a dense accumulation of mineralized tumor bone matrix (up to 90% of the medullar space). The BMDD was shifted tremendously towards higher matrix mineralization (CaMean +18.5%, CaPeak +22.5%, CaHigh +100 fold) compared to normal bone. Additionally the BMDD became much wider, indicating a higher heterogeneity in mineralization (CaWidth +40%). In contrast to lamellar bone, which mineralizes via a mineralization front, the mineralization of the tumor matrix starts by randomly distributed spots of mineral clusters fusing together to a highly mineralized non-lamellar bone matrix. We also found an altered BMDD of the patient's normal bone when compared with the reference BMDD of young individuals. In conclusion this high radiodensity region of the sclerosing sarcoma is not only due to the high amount of tumor matrix but also to its high mineralization density. Chemotherapy may lead to altered matrix mineralization of normal bone due to suppression of bone turnover. The mechanism of matrix mineralization in a sclerosing osteosarcoma warrants further studies.

Survival of patients with pathologic T0N+ oral and oropharyngeal cancer after neoadjuvant therapy and surgery: the minority report.

OBJECTIVES: Treatment outcome of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) achieving complete pathologic response at the primary site (ypT0) but incomplete response in loco-regional lymph nodes after preoperative chemoradiation (ypN+) is poorly described in the literature. This study's objective was to assess the survival of patients with OOSCC with ypT0N+ disease. STUDY DESIGN: 176 patients with primary locally advanced OOSCC undergoing preoperative chemoradiotherapy were stratified according to the pathologic TNM classification into 6 groups: ypT0N0M0 (46%), ypT0N+M0 (10%), ypTNM I (24%), ypTNM II (4%), ypTNM III (6%), and ypTNM IV (10%). RESULTS: Three-year overall survival (OS) and recurrence-free survival (RFS) rates for the ypT0N+M0 group were both 61.8% and were similar to those of the ypTNM I group (OS 62.4%; RFS rate of 59.2%). CONCLUSIONS: Survival analyses showed that patients with OOSCC with ypT0N+ disease have a similar prognosis to those with pathologic TNM stage I.

Impact of elective neck dissection on regional recurrence and survival in cN0 staged oral maxillary squamous cell carcinoma.

To evaluate the impact of elective neck dissection (END) on regional recurrence and survival in cN0 staged patients with maxillary squamous cell carcinoma (SCC). Eighty-six patients with maxillary SCC and clinically staged N0 cervical lymph-nodes were evaluated in this single center retrospective study. Seventy-four of 86 patients were included in this analysis, of which 36 patients were treated with END, 38 without END. Following END, pathohistologically verified regional lymph-nodes in the initially cN0 neck were found in three (8%) patients. In both the +END and non-END group regional recurrences occurred exclusively in patients with T4 primaries. The overall regional recurrence rate was 17% in the +END and 18% in the non-END group, respectively. The 5-year overall survival rate for all tumor stages combined (T1-T4) was 86% in the +END group and 82% in the -END group. Within the patients groups with T4 tumors, 5-year overall survival was 81% for the +END group and 56% for the -END group. Over all tumor stages combined (T1-T4), END did not significantly improve overall survival rates and did not prevent the rate of regional recurrence in cN0 staged patients with maxillary alveolar, gingival and palatal SCC. However, in the subgroup of patients with locally advanced T4 tumors, their seemed to be a clear tendency towards improvement of overall survival in the END group. END can therefore be recommended for these patients.

Factors influencing surgical treatment of bisphosphonate-related osteonecrosis of the jaws.

BACKGROUND: Bisphosphonates are known to be associated with osteonecrosis of the jaw. We assess factors underlying the success of surgical treatment in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: Fifty-eight patients were investigated 6 months after having surgery. Outcome variables included the stage of disease. Factors underlying the success of surgery such as age, sex, dental procedures, underlying disease, and bisphosphonate therapy were subjected to statistical analysis. RESULTS: In all, 41 patients after surgery could be followed up. Twenty-four patients (58.5%) had an intact mucosa after surgical treatment. A statistically significant improvement was registered between preoperative and postoperative staging (p < .01). Routine dental procedures and the underlying illness influenced the outcome of surgery (p < .05). Patients with osteoporosis and multiple myeloma improved to a greater extent by surgery than those with cancer. Discontinuation of bisphosphonates was found to improve the outcome (p < .05). CONCLUSIONS: Surgery is more successful in patients with osteoporosis or multiple myeloma than in those with solid tumors. Discontinuation of bisphosphonate therapy favored the surgical outcome.

Staging and grading as prognostic factors in maxillary squamous cell carcinoma.

PURPOSE: This retrospective study was performed to present our long-term results in the treatment of maxillary squamous cell carcinoma and evaluate especially the influence of T staging and grading on patients' survival. PATIENTS AND METHODS: We performed a retrospective analysis of 93 consecutive patients with alveolar, gingival, or palatal maxillary SCC treated at our clinic with surgical resection and/or radiation therapy. Data were obtained from chart review and patients' records and were analyzed statistically using the log-rank test and Kaplan-Meier survival curves. The male:female ratio was 2:1 and the mean age was 63 years (range 35 to 94 yrs). Most patients showed a T4 stage (66%) and the most frequent staging was T4N0M0 (42%). The most common histopathological grading was G2 (57%), followed by G3 (22%) and G1 (21%). The 5-year overall survival rate was 71%, and the recurrence rate was 37%. Advanced T stage (T4) and grading did not significantly influence the cumulative survival rates. CONCLUSIONS: T-stage and grading do not have a significant impact on patients' long-term survival. The most crucial factor for recurrence prevention and therefore survival are free resection margins.

Expression of platelet-derived growth factor-alpha receptor in human osteosarcoma is not a predictor of outcome.

AIMS: The aims of this study were to examine the prognostic relevance of platelet-derived growth factor-α receptor (PDGFRA) expression in human osteosarcomas and to evaluate the mutation status of exon 12 and exon 18 of the PDGFRA gene. METHODS: PDGFRA expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 12 and 18 of the PDGFRA gene. RESULTS: Ninety-six osteosarcomas showed PDGFRA expression ranging from 4% to 90% (mean 40%, median 37.5%, SD 27.11%). Furthermore, DNA sequence of exon 12 and exon 18 of the PDGFRA gene were not altered in 40 tumours with high PDGFRA expression. Overall and disease-free survival analysis did not reveal any differences between osteosarcoma patients with high PDGFRA expression and patients with low PDGFRA expression. CONCLUSIONS: The protein expression is not linked to mutations in exon 12 or exon 18 of PDGFRA gene. Therefore, treatment modalities based on the suppression of PDGFRA tyrosine kinase activity may need further investigation. PDGFRA expression is not a prognostic marker for osteosarcoma patients.

Expression of platelet-derived growth factor-alpha receptor and c-kit in giant cell tumours of bone.

AIMS: Platelet-derived growth factor-alpha receptor (PDGFRA) and c-kit are tyrosine kinase receptors expressed in many neoplasms. We investigated protein expression in 34 giant cell tumours of bone and two specimens of lung metastases. METHODS: The expression of PDGFRA and c-kit was analysed by immunohistochemistry. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene. RESULTS: PDGFRA expression was detected in all specimens and all cellular components such as reactive osteoclast-like giant cells and neoplastic stromal cells. C-kit expression was found in six cases of giant cell tumour and one specimen of lung metastasis in all cellular components ranging from 5 to 50% (mean 4.8%, SD 12.4). A further 13 cases showed labelling of osteoclast-like giant cells. DNA sequence of exons 12 and 18 of the PDGFRA gene and exons 9 and 11 of the c-kit gene were not altered in these tumours. CONCLUSION: PDGFRA and c-kit play a functional role in the growth of giant cell tumours of bone but genetic changes of therapeutically relevant exons of the PDGFRA gene and the c-kit gene are not seen in these tumours.

Expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor in ameloblastomas.

BACKGROUND: Platelet-derived growth factor (PDGF)-AA isoform and its receptor, PDGF-alpha receptor (PDGFRA) regulate tooth development and growth. We investigated the expression of both proteins in ameloblastomas, to contribute the understanding of the potential role of the PDGF/PDGFR system in this odontogenic neoplasm. METHOD: Twenty-nine specimens of ameloblastoma were analyzed for PDGF-AA and PDGFRA expression using immunohistochemistry. The proliferation activity was investigated with the MIB-1 antibody. Additionally, capillary sequencing of genomic DNA was performed to search for mutations in therapeutically relevant exons 12 and 18 of the PDGFRA gene. RESULTS: PDGF-AA and PDGFRA expression were detectable in all cases with the exception of one tumor. However, protein expression levels did neither correlate with each other nor with MIB-1 expression. Unicystic ameloblastomas did not differ from solid tumors with regard to PDGF-AA, PDGFRA, and MIB-1 expression. One tumor revealed a somatic mutation of exon 12 of the PDGFRA gene. CONCLUSION: PDGF-AA and PDGFRA proteins are regularly expressed in variable levels in ameloblastomas, and somatic mutations of exon 12 and exon 18 of the PDGFRA gene are rare findings.

Diffusion-weighted magnetic resonance imaging of head and neck squamous cell carcinomas.

OBJECTIVE: To evaluate whether diffusion-weighted imaging (DWI) is a reliable technique to quantify microstructural differences between head and neck squamous cell carcinomas (SCC) and tumour-free soft tissue. MATERIALS AND METHODS: DWI was obtained from 20 patients with histologically proven, untreated head and neck SCC. DWI was acquired using a diffusion-weighted, navigated echo-planar imaging sequence with a maximum b-value of 800 s/mm2. For an objective assessment of image quality, the signal-to-noise ratio (SNR) was calculated. Microstructural differences between vital tumour tissue and tumour-free soft tissue were quantified by calculating the apparent-diffusion-coefficients (ADC) on a pixel by pixel method. RESULTS: Echo-planar DWI provided good image quality in all patients (mean SNR 18.4). The mean ADC of SCC, (0.64+/-0.28 x 10(-3) mm2/s), was significantly (P<0.0001) lower than that of the tumour-free soft tissue, (2.51+/-0.82 x 10(-3) mm2/s). CONCLUSION: DWI is a reliable diagnostic tool to quantify the microstructural differences between vital tumour tissue and tumour-free soft tissue in patients with head and neck SCC.

Expression of c-kit in human osteosarcoma and its relevance as a prognostic marker.

AIMS: To examine the prognostic relevance of c-kit expression in human osteosarcomas and to evaluate the mutation status in exon 9 and exon 11 of the c-kit gene. METHODS: c-kit expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 9 and 11 of the c-kit gene. RESULTS: 20 osteosarcomas showed c-kit expression ranging from 5% to 90% (mean 5.9%; SD 16.74%). Furthermore, DNA sequences of exon 9 and exon 11 of the c-kit gene were not altered in these tumours. Overall and disease free survival analysis did not reveal any differences between patients with osteosarcoma with c-kit expression and those with c-kit negative tumours. CONCLUSIONS: C-kit expression is not a prognostic marker in patients with osteosarcoma. The protein expression is not linked to mutations in exon 9 or exon 11 of the c-kit gene. Therefore, these exons may not function as targets for treatment modalities based on the suppression of c-kit tyrosine kinase activity.

Tissue reactions induced by different embolising agents in cerebral arteriovenous malformations: a histopathological follow-up.

AIMS: Comparative histopathological analysis was performed in 47 incompletely embolised and resected cerebral arteriovenous malformations (AVMs). METHODS: Thirty-three AVMs were embolised with n-butyl-cyanoacrylate (NBCA), four with iso-butyl-cyanoacrylate (IBCA), seven with polyvinyl alcohol particles (PVA), one with a fibrin mixture, one with silicon pellets, and one with microcatheter balloons. Maximum exposure time (MET) of the embolising agent (interval between embolisation and surgery) ranged from <24 hours to 80 months. All AVMs were investigated regarding angionecrosis, angiofibrosis, acute inflammation, chronic inflammation, foreign-body reactions, vascular calcification, blood admixture to embolising cast, and capillary recanalisation within the AVMs. These parameters were correlated with MET, comparing different embolising agents, age, and sex. RESULTS: A typical sequence of events depending on MET is observed in all embolised AVMs: acute inflammation with mural angionecrosis is soon replaced by prominent chronic granulomatous vasculitis, which remains stable and is detectable for a very long time, even in AVMs with a MET of more than 6 years. CONCLUSION: Capillary recanalisation is always present in incompletely embolised AVMs, detectable after 3 months of MET, irrespective of the embolising agent used. Age and sex does not influence pattern and time course of tissue lesions and recanalisation in incompletely embolised AVMs.