Marcel-Philipp Henrichs

AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein

The most frequent translocation t(8;21) in acute myeloid leukemia (AML) generates the chimeric AML1/ETO protein, which blocks differentiation and induces self-renewal in hematopoietic progenitor cells. The underlying mechanisms mediating AML1/ETO-induced self-renewal are largely unknown. Using expression microarray analysis, we identified the Groucho-related amino-terminal enhancer of split (AES) as a consistently up-regulated AML1/ETO target. Elevated levels of AES mRNA and protein were confirmed in AML1/ETO-expressing leukemia cells, as well as in other AML specimens. High expression of AES mRNA or protein was associated with improved survival of AML patients, even in the absence of t(8;21). On a functional level, knockdown of AES by RNAi in AML1/ETO-expressing cell lines inhibited colony formation. Similarly, self-renewal induced by AML1/ETO in primary murine progenitors was inhibited when AES was decreased or absent. High levels of AES expression enhanced formation of immature colonies, serial replating capacity of primary cells, and colony formation in colony-forming unit-spleen assays. These findings establish AES as a novel AML1/ETO-induced target gene that plays an important role in the self-renewal phenotype of t(8;21)-positive AML.

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.

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

BackgroundComplications 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 presentationA 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.ConclusionComplications 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.

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

BackgroundScar 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 presentationWe 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.ConclusionIn 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.

Stump Lengthening Procedure with Modular Endoprostheses — the Better Alternative to Disarticulations of the Hip Joint?

We report outcomes of 28 patients after stump-lengthening procedures (SLPs) with modular tumor endoprostheses following high-thigh amputation and hip disarticulation over 11years. Mean follow up was 41.3months (range 7.4 to 133.6months). Mean Musculoskeletal Tumour Society Score was 56% (n=11); ten out of eleven patients alive used an exoprosthesis regularly. Complications occurred in 15 patients with infection being most common. In 2 cases, the prostheses had to be explanted. Our data suggest that SLP facilitates post-operative rehabilitation and prosthesis usage. Modular endoprostheses for stump-lengthening allow optimization of remnant soft-tissue envelope, reducing the risk of stump perforation.

Analysis of surgical and oncological outcome in internal and external hemipelvectomy in 34 patients above the age of 65 years at a mean follow-up of 56 months

BackgroundWith an increasing life expectancy and improved treatment regimens for primary or secondary malignant diseases of soft tissue or bone, hemipelvectomy will have to be considered more often in elderly patients in the future. Scientific reviews concerned with the surgical and oncological outcome of elderly patients undergoing hemipelvectomy are scarce. Therefore, it is the purpose of this study to review the outcome of patients treated with that procedure at our hospital and investigate the feasibility of such extensive procedures at an increased age.MethodsA retrospective analysis of thirty-four patients who underwent hemipelvectomy at an age of 65 years or older was performed to determine their surgical and oncological outcome. The Kaplan-Meier method was used to calculate the cumulative probability of survival using the day of tumor resection as a starting point. Univariate analysis was carried out to investigate the influence of a particular single parameter.ResultsThe mean age at operation was 70.2 years. Thirty patients were treated for intermediate- to high-grade sarcoma and 81.8% of tumors were larger than or equal to 10 cm in the longest diameter. Thirteen patients underwent internal hemipelvectomy and nine patients external hemipelvectomy as a primary procedure. Twelve patients were treated with external hemipelvectomy after failed local tumor control at primary operation. Wound infection occurred in 61.7% of cases. Three patients underwent amputation for non-manageable infection after internal hemipelvectomy. Hospital mortality was 8.8%. Clear resection margins were obtained in 88% of patients; in another 6% of patients planned intralesional resections were performed. Local recurrence occurred in 8.8% of patients at a mean time of 26 months after operation. Eleven patients are alive with no evidence of disease and 23 patients died of disease or other causes. Patients with pulmonary metastases had a mean survival period after operation to DOD of 22 months compared to 37 months in the curative group.ConclusionDespite an elevated rate in hospital mortality and wound infection, this study suggests that hemipelvectomy is feasible in elderly patients, although requiring long hospitalization periods and causing a limited functional outcome.