145 research outputs found
Systematic evaluation of the features influencing the accuracy of third order measurements
The aims of this study were to evaluate the relationship of third order measurements on dental casts with those on lateral radiographs, and to identify those incisor features on radiographs which can best explain third order measurements on dental casts. Lateral cephalograms and corresponding dental casts were obtained from 39 untreated Caucasians (12 males, 27 females; mean age 19.5 years; standard deviation 3.7 years) with occlusal relationships considered to be ‘normal'. The upper (U1) and lower (L1) incisors were assessed with reference to the occlusal plane perpendicular which was established on the lateral radiographs, including third order angles (U1TR, L1TR) which were also derived from direct dental cast measurements (U1TA, L1TA). Both single regression and multiple linear regression analysis with stepwise variable selection were performed using third order measurements on casts as the dependent variable and crown axis (U1C, L1C), root axis (U1R, L1R), tip-apex connecting line (U1E, L1E), and radiographic third order measurements as independent variables. Single regression analysis indicated an overall difference of 0.02 degrees between radiographic third order inclination and cast assessment in the maxilla (mandible: −2.83 degrees). A change of 1 degree in radiographic third order inclination would produce a change of 0.65 degrees for U1TA and 0.86 degrees for L1TA assessments. Third order measurements on dental casts can best be explained by a linear combination of U1TR and U1E (maxilla) and of L1TR and L1C (mandible) measurements. This study demonstrates the functional enmeshment between two different third order assessments and the most common incisor features on lateral radiographs. Both methods of third order evaluation show sufficient reliability and are appropriate for routine orthodontic practic
Sarcomas of the extremities and the pelvis: comparing local recurrence after incisional and after core-needle biopsy
BACKGROUND The degree of contamination of healthy tissue with tumor cells during a biopsy in bone or soft tissue sarcomas is clearly dependant on the type of biopsy. Some studies have confirmed a clinically relevant contamination of the biopsy tract after incisional biopsies, as opposed to core-needle biopsies. The aim of our prospective study was to evaluate the risk of local recurrence depending on the biopsy type in extremity and pelvis sarcomas. METHODS We included 162 patients with a minimum follow-up of 6 months after wide resection of extremity sarcomas. All diagnostic and therapeutic procedures were performed at a single, dedicated sarcoma center. The excision of the biopsy tract after an incisional biopsy was performed as a standard with all tumor resections. All patients received their follow-up after the conclusion of therapy at our center by means of regional MRI studies and, at a minimum, CT of the thorax to rule out pulmonary metastatic disease. The aim of the study was the evaluation of the influence of the biopsy type and of several other clinical factors on the rate of local recurrence and on the time of local recurrence-free survival. RESULTS One hundred sixty-two patients with bone or soft tissue tumors of the extremities and the pelvis underwent either an incisional or a core-needle biopsy of their tumor, with 70 sarcomas (43.2%) being located in the bone. 84.6% of all biopsies were performed as core-needle biopsies. The median follow-up time was 55.6 months, and 22 patients (13.6%) developed a local recurrence after a median time of 22.4 months. There were no significant differences between incisional and core-needle biopsy regarding the risk of local recurrence in our subgroup analysis with differentiation by kind of tissue, grading of the sarcoma, and perioperative multimodal therapy. CONCLUSIONS In a large and homogenous cohort of extremity and pelvic sarcomas, we did not find significant differences between the groups of incisional and core-needle biopsy regarding the risk of local recurrence. The excision of the biopsy tract after incisional biopsy in the context of the definitive tumor resection seems to be the decisive factor for this result
Aneurysmal bone cyst: results of an off label treatment with Denosumab
Background
The treatment of aneurysmal bone cysts (ABCs) has evolved and less invasive methods have been tried. Denosumab is a monoclonal antibody which inhibits osteoclasts. It has been shown to be effective in giant cell tumour of bone (GCT) of bone and hence promises some effect also in ABC. We report on 6 patients treated with Denosumab and compare our results to the cases already published.
Methods
Data of 6 patients with ABCs and patients whose treatment included Denosumab were retrospectively analyzed. Denosumab was used at a dose of 120 mg on days 1, 8, 15 and 29, and every 4 weeks thereafter. In some of these patients the dose was reduced at the end of the treatment. Clinical and radiological responses were evaluated.
Results
In 4 female and 2 male patients with a mean age of 17 years (range: 6–30 years) the lesions were located in the sacrum (2), in distal radius, distal femur, talus and pelvis. One of the sacral lesions healed after 12 months and has stayed stable for 3 years since. The second patient received 2 years of therapy with recalcification, but recurred 1 year later and is under renewed therapy. The pelvic lesion improved but recurred. This patient has a 13-years history of intermittent therapy including surgery, two pregnancies and remains in a stable situation. The lesion of the talus did not improve with Denosumab after surgery and was complicated by destruction of the ankle joint with osteoarthritis. Recurrent lesions of the distal femur and the distal radius, previously treated by curettage and bone grafting healed under Denosumab and have remained stable for 2 and 3 years, respectively. One case of severe hypercalcemia was observed in a 7-year old child 6 months after discontinuation of Denosumab.
Conclusion
Denosumab provides a treatment option for ABCs in anatomically critical locations. Adjuvant application might reduce the rate of local recurrence. In young patients, severe rebound hypercalcemia months after discontinuation of Denosumab may occur
Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier
Aims: p16(INK4a) is an important factor in carcinogenesis, and its expression is linked to oncogene-induced senescence. Very recently it was shown that upregulation and downregulation of p16 indicates a senescence barrier in the serrated route of colorectal cancer. However, in soft tissue sarcoma (STS), the senescence mechanism is still not understood. In this study, we analysed a well characterised cohort of STS for p16(INK4a) expression and correlated the results with clinicopathological parameters including survival.
Methods: Tissue microarrays (TMA) of 183 soft tissue and bone tumours were analysed immunohistochemically. Furthermore, mRNA expression of p16(INK4a) was evaluated in four sarcoma cell lines, and a demethylation test was performed by treatment with 5-aza-2 \grq-deoxycytide.
Results: On protein level, expression of p16(INK4a) was observed in undifferentiated pleomorphic sarcoma (UPS) in 69.1%, leiomyosarcoma in 85.7%, synovial sarcoma in 77.8%, liposarcoma in 88.9%, angiosarcoma in 60.9% and MPNST in 22.2%. Loss of p16(INK4a) was observed in high grade sarcomas and showed a significant correlation with reduced patient survival (p=0.032). On DNA level, one out of four sarcoma cell lines exhibited a methylated p16(INK4a) promoter analysed by methylation-specific PCR. p16(INK4a) mRNA and protein expression was restored after demethylation using 5-aza-2′-deoxycytide.
Conclusions: Upregulation of p16(INK4a) might be associated with the induction of senescence and indicates a senescence barrier. Downregulation of p16(INK4a) is found in malignant progression, and is significantly correlated with reduced patient survival. Downregulation of p16(INK4a) may be explained by DNA-hypermethylation in sarcoma cells
Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier
Aims: p16(INK4a) is an important factor in carcinogenesis, and its expression is linked to oncogene-induced senescence. Very recently it was shown that upregulation and downregulation of p16 indicates a senescence barrier in the serrated route of colorectal cancer. However, in soft tissue sarcoma (STS), the senescence mechanism is still not understood. In this study, we analysed a well characterised cohort of STS for p16(INK4a) expression and correlated the results with clinicopathological parameters including survival.
Methods: Tissue microarrays (TMA) of 183 soft tissue and bone tumours were analysed immunohistochemically. Furthermore, mRNA expression of p16(INK4a) was evaluated in four sarcoma cell lines, and a demethylation test was performed by treatment with 5-aza-2 \grq-deoxycytide.
Results: On protein level, expression of p16(INK4a) was observed in undifferentiated pleomorphic sarcoma (UPS) in 69.1%, leiomyosarcoma in 85.7%, synovial sarcoma in 77.8%, liposarcoma in 88.9%, angiosarcoma in 60.9% and MPNST in 22.2%. Loss of p16(INK4a) was observed in high grade sarcomas and showed a significant correlation with reduced patient survival (p=0.032). On DNA level, one out of four sarcoma cell lines exhibited a methylated p16(INK4a) promoter analysed by methylation-specific PCR. p16(INK4a) mRNA and protein expression was restored after demethylation using 5-aza-2′-deoxycytide.
Conclusions: Upregulation of p16(INK4a) might be associated with the induction of senescence and indicates a senescence barrier. Downregulation of p16(INK4a) is found in malignant progression, and is significantly correlated with reduced patient survival. Downregulation of p16(INK4a) may be explained by DNA-hypermethylation in sarcoma cells
Hematopoietic islands mimicking osteoblastic metastases within the axial skeleton
Background
Hyperplasia of the hematopoietic bone marrow in the appendicular skeleton is common. In contrast, focal hematopoietic islands within the axial skeleton are a rare entity and can confuse with osteoblastic metastases. This study aimed to characterize typical MRI and CT findings of hematopoietic islands in distinction from osteoblastic metastases to help both radiologists and clinicians, on the one hand, not to overdiagnose this entity and, on the other hand, to decide on a reasonable work-up.
Methods
We retrospectively analyzed the imaging findings of 14 hematopoietic islands of the axial skeleton in ten patients (nine females, median age = 65.5 years [range, 49–74]) who received both MRI and CT at initial diagnosis between 2006 and 2020. CT-guided biopsy was performed in five cases to confirm the diagnosis, while the other five patients received long-term MRI follow-up (median follow-up = 28 months [range, 6–96 months]). Diffusion-weighted imaging was available in three, chemical shift imaging respectively 18 F- fluorodeoxyglucose PET/CT in two, and Technetium 99 m skeletal scintigraphy in one of the patients.
Results
All lesions were small (mean size = 1.72 cm 2 ) and showed moderate hypointense signals on T1- and T2-weighted MRI sequences. They appeared isointense to slightly hyperintense on STIR images and slightly enhanced after gadolinium administration. To differentiate this entity from osteoblastic metastases, CT provides important additional information, as hematopoietic islands do not show sclerosis.
Conclusions
Hematopoietic islands within the axial skeleton can occur and mimic osteoblastic metastases. However, the combination of MRI and CT allows for making the correct diagnosis in most cases
Neoadjuvant or adjuvant sirolimus for malignant metastatic or locally advanced perivascular epithelioid cell tumors: two case reports
Perivascular epithelioid cell tumors (PEComas) are very rare mesenchymal tumors, characterized by the presence of perivascular epithelioid cells. Despite their often benign nature, malignant variants with a locally aggressive growth pattern and even distant metastases are known. We describe two cases of malignant PEComas. The first patient had an extensive peritoneal spread and a history of multiple resections, and received the mechanistic target of rapamycin inhibitor sirolimus in a postoperative setting as maintenance therapy. The second patient presented with locally advanced disease in the iliac fossa and was treated with sirolimus in a neoadjuvant setting and achieved complete remission. Both patients have been under treatment for 18 and 52 months, respectively, and are currently in complete remission. These two cases indicate that mechanistic target of rapamycin inhibition for malignant PEComas could be a safe and successful treatment strategy in a neoadjuvant setting with an acceptable toxicity profile
Survival and prognostic factors in conventional G1 chondrosarcoma
Background
Chondrosarcoma is the second most frequent malignant bone tumor. Grade I chondrosarcoma (syn.: atypical cartilaginous tumor) is classified as an intermediately and locally aggressive neoplasm and typically is treated less aggressively (i.e., by intralesional curettage). Does the data regarding local recurrence (LR) and metastatic disease justify this?
Methods
From 1982 to 2014, 37 consecutive patients with G1 chondrosarcoma had been resected or curetted. The margin was defined as R0 (wide resection) or R1 (marginal resection). All patients were followed for evidence of local recurrence or metastatic disease. Overall and recurrence-free survival were calculated, and various potentially prognostic factors were evaluated.
Results
In 23 patients (62%), the tumor was widely (R0) resected, whereas in 14 patients, (38%) the resection was marginal (R1). Overall survival was 97% after 5 years, 92% after 10 years, and 67% after 20 years. Five-year local recurrence-free survival was 96%. Ten-year local recurrence-free survival was 83%. Local recurrence-free survival showed a significant correlation to margin status but no correlation to location or age. None of the patients with local recurrence died during the follow-up. One patient had metastatic disease at initial presentation, and a further five patients developed metastatic disease during follow-up. Metastatic disease proofed to be a highly significant factor for survival but was not correlated to local recurrence.
Conclusions
There was no significant correlation between the outcome and the primary tumor location. Marginal resection was a risk factor for LR, but there was no significant difference in the overall survival in patients with or without LR. Metastatic disease (16%) was more common than expected from the literature and a significant predictor for poor overall survival
Distinct expression patterns of VEGFR 1-3 in gastroenteropancreatic neuroendocrine neoplasms: supporting clinical relevance, but not a prognostic factor
Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are an increasing tumor entity. Since many patients are diagnosed at an advanced stage, treatment is still challenging and dependent on many tumor and patient specific factors. Therefore, the aim of the present study was to elucidate the expression rates and the prognostic value of vascular endothelial growth factor receptor (VEGFR) 1-3 in GEP-NENs. A potential association to immune checkpoint markers was further investigated. Material and Methods: The expression levels of VEGFR 1-3 were analyzed by immunohistochemistry and correlated with the expression of the checkpoint markers PD-1 and PD-L1. Furthermore, the tumor samples of 249 GEP-NEN patients were studied and correlated with overall survival rates and clinicopathological features. Kaplan–Meier analyses and the log rank test were used for survival analyses. Categorical variables were compared by the χ2 test. Results: The most common primary tumor site was the small intestine (50.6%), followed by the pancreas (25.7%). VEGFR 1 was highly expressed in 59%, VEGFR 2 in 6.4%, and VEGFR 3 in 61.8% of the analyzed samples. The expression of VEGFR 1-3 was not significantly associated with survival rates. Pancreatic NENs had the highest expression of VEGFR 1 and 3 in 80% of the cases. VEGFR 1-3 positivity correlated with the expression levels of immune checkpoint markers. Discussion: VEGFR 1-3 show a distinct expression pattern in different subgroups of neuroendocrine neoplasias indicating a conceivable target. Moreover, there was a substantial association between VEGFRs andimmune checkpoint markers. Taken together, anti-VEGFR therapy represents a promising therapeutic approach in GEP-NEN patients and should be addressed in future studies
- …