Die Rolle von Zyklin D1 und Amino-terminal Enhancer of Split in der molekularen Pathogenese der Akuten Myeloischen Leukämie (AML)

Die Akute Myeloische Leukämie (AML) ist eine Erkrankung des hämatopoetischen Systems und gekennzeichnet durch das klonale Wachstum unreifer hämatopoetischer Vorläuferzellen. Typische genetischen Alterationen in der AML sind Mutationen der Rezeptortyrosinkinase FLT3 und chromosomale Translokationen. Es konnte gezeigt werden, dass das Fusionsprotein PML-RAR? und Flt3-ITD die Expression von Zyklin D1 induzieren. Die Induktion von Zyklin D1 durch Flt3-ITD geschieht über den PI3-Kinase/AKT Signalweg. Amino-terminal Enhancer of Split (AES), ein transkriptioneller De-Repressor, wird durch Fusionsproteine in der AML auf RNA- und Proteinebene heraufreguliert. Es wurde nachgewiesen, dass AES in immortalen Zellen und in Knochenmarkproben von AML Patienten überexprimiert wird. Eine Überexpression von AES in 32D Zellen führt zu gesteigerter Proliferation und Selbsterneuerungsfähigkeit. Eine Herunterregulation mündet in vermindertem Kolonienwachstum

Scar sarcoidosis on a finger mimicking a rapidly growing soft tissue tumour: a case report

Background: Scar sarcoidosis is a rare and uncommon but specific cutaneous manifestation of sarcoidosis. In general it arises in pre-existing scars deriving from mechanical traumas. As most surgeons dealing with scars might not be aware of cutaneous sarcoidosis and its different types of appearance the appropriate staging and treatment might be missed or at least delayed. To our knowledge this is the first case in literature of scar sarcoidosis on a finger. Case presentation: We present a case of a 33-year-old carpenter who developed scar sarcoidosis on his right index finger 4 years after the tendon of the long digital flexor got accidentally cut by an angle grinder. He was referred due to a swelling of the finger suspected to be a malignant soft tissue tumour. The circumference of the affected finger had almost doubled, adding up to 94 mm. Incision biopsy revealed typical noncaseating granulomas. Further investigation showed a systemic extent of the disease with involvement of the lung. A systemic treatment with oral steroids led to an almost full regression of the swelling with restoration of function and resolution of lung infiltrates. Conclusion: In case of a suspicious and/or progressive swelling a definite diagnosis should be achieved by biopsy within a short time to enable a proper treatment. If scar sarcoidosis is proven further investigation is necessary to exclude a systemical involvement. A surgical treatment of the swelling is not indicated.</p

Small sharp exostosis tip in solitary osteochondroma causing intermittent knee pain due to pseudoaneurysm

Background: Complications of solitary or multiple osteochondromas are rare but have been reported in recent literature. Most reported complications arose in patients with multiple and/or sizable osteochondromas. Case presentation: A 22-year-old, female, Caucasian patient with obesity presented with intermittent knee pain and hematoma of the right calf. The MRI depicted a small, sharp exostosis tip of the dorsal distal femur with a surrounding soft-tissue mass. After profuse bleeding occurred during biopsy of the soft tissue mass, angiography revealed a pseudoaneurysm of the right popliteal artery. In a second-stage surgery the exostosis tip and pseudoaneurysm were resected. Conclusion: Complications can also arise in small, seemingly harmless osteochondromas. Surgical resection should be considered as a preventive measure when exostoses form sharp tips close to neurovascular structures regardless of total osteochondroma size.<br

Short-stem reconstruction for megaendoprostheses in case of an ultrashort proximal femur

Background: Tumors of the distal femur and diaphysis with proximal metaphyseal extension into the femur present a challenge for limb salvage. The conventional treatment consists of limb salvage with total femur replacement. This case study aims to present preliminary results and experience with short-stem reconstruction, focusing on the mechanical stability of the procedure. Methods: Sixteen short stems were implanted in 15 patients. The patients’ mean age was 33,3 years (range 11–73). In 10 patients, the stem was used for distal femur reconstruction, in one patient for diaphyseal reconstruction, and in four for a stump lengthening procedure. All of the patients had a primary sarcoma in their history. The mean follow-up period was 37 months (range 5–95 months). The clinical and functional follow-up data were analyzed. Results: Ten patients (67%) were still alive at the time of evaluation. Three complications associated with the stem were noted. In one case, there was aseptic loosening after 58 months; in another, aseptic loosening occurred because the diameter of the stem had initially been too small; and in one case, there was breakage of the fixation screw, without any clinical symptoms. The average Musculoskeletal Tumor Society score for all patients was 23 (range 9–28). The mean result for the distal femur replacement was 24 (range 22–28). None of the surviving patients with distal femur replacements needed any crutches or had a Trendelenburg limp. Both living patients who underwent a stump lengthening procedure were able to walk with an exoprosthesis. Conclusions: The short stem is a good solution that can prevent or delay proximal femur resection in patients with tumors extending into the proximal metaphyseal femur. Additional risks of proximal femur resection, such as dislocation, opening of another oncological compartment, Trendelenburg limp, and chondrolysis can be avoided.<br

Modular tumor endoprostheses in surgical palliation of long-bone metastases: A reduction in tumor burden and a durable reconstruction

Background: Surgical treatment of bone metastases has become increasingly important as patients live longer with metastatic cancer and one of the main aims is a long-lasting reconstruction which survives the patient. Conventional osteosynthesis may not be able to achieve this objective in the context of modern day cancer care. Methods: This study evaluates the oncological outcomes, treatment-related complications, and function after resection of metastases and reconstruction with modular tumor endoprostheses in 80 patients. All patients who underwent surgical treatment with modular tumor prostheses for bone metastases from 1993 to 2008 were traced by our tumor database and clinical information was recorded from patient case. Results: Mean age was 63 years. The most common primary tumors were renal cell (47%), breast (21%), and lung (8%). The proximal femur was affected in 45%, proximal humerus in 26%, and the distal femur in 17% of cases. In 22 cases, the tumor prosthesis was implanted during a revision operation. Mean overall survival after surgery was 2.9 years. Overall survival rate was 70% at one year and 20% at five years. Implant survival was 83% after one year and 74% at five years. Overall rate of operative revision was 18%. Conclusions: Our data collectively suggest that despite higher costs, implantation of modular tumor endoprostheses may be a suitable treatment for bone metastases with a low complication rate and rapid improvement in function in appropriately selected patients.<br

Reconstruction after wide resection of the entire distal fibula in malignant bone tumours

In this study we present a series of patients (n = 11) with resection of the entire distal fibula in the case of sarcoma or metastasis. Moreover, we describe a new method to restore ankle stability with a tibiotalocalcaneal arthrodesis using a retrograde hindfoot nail (n = 4) in contrast to tibiotalar arthrodesis with screws (n = 5). The screw fixation failed in two patients due to osteopoenic bone. The crucial benefits of an arthrodesis with a retrograde nail are a stable arthrodesis, intramedullary stabilisation of the tibia and avoidance of extrinsic material in the wound area. An arthrodesis with a retrograde nail is a good alternative for reconstruction after a wide distal fibula resection. The additional arthrodesis of the subtalar joint was not associated with worse functional results in the MSTS and TESS scores

Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H??????? and H???ZZ*???4??? Decay Channels at s\sqrt{s}=8??????TeV with the ATLAS Detector

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3~fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb-1 of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ*→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σpp→H=33.0±5.3 (stat)±1.6 (syst)  pb. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions