Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.

BACKGROUND/AIM: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body autoradiography. MATERIALS AND METHODS: In vitro [18F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions. Post transplantation of My1/De cells under the left renal capsule of Long-Evans rats, primary My1/De tumorigenesis, and metastatic propagation were investigated using [18F]F-FDG PET imaging, whole-body autoradiography and phosphorimage analyses. To assess the organ uptake profile of the tumor-carrying animals we accomplished ex vivo biodistribution studies. RESULTS: The tracer accumulation in the My1/De culture cells exceeded that of both the tumorous and the healthy bone marrow suspensions (p<0.01). Based on in vivo imaging, the subrenally transplanted My1/De cells resulted in the development of leukemia in the abdominal organs, and metastasized to the mesenterial and thoracic parathymic lymph nodes (PTLNs). The lymphatic spread of metastasis was further confirmed by the significantly higher %ID/g values of the metastatic PTLNs (4.25±0.28) compared to the control (0.94±0.34). Cytochemical staining of the peripheral blood, autopsy findings, and wright-Giemsa-stained post-mortem histological sections proved the leukemic involvement of the assessed tissues/organs. CONCLUSION: The currently established My1/De model appears to be well-suited for further leukemia-related therapeutic and diagnostic investigations.

Concomitant [18F]F-FAZA and [18F]F-FDG Imaging of Gynecological Cancer Xenografts: Insight into Tumor Hypoxia.

BACKGROUND/AIM: Herein we assessed the feasibility of imaging protocols using both hypoxia-specific [18F]F-FAZA and [18F]F-FDG in bypassing the limitations derived from the non-specific findings of [18F]F-FDG PET imaging of tumor-related hypoxia. MATERIALS AND METHODS: CoCl2-generated hypoxia was induced in multidrug resistant (Pgp+) or sensitive (Pgp-) human ovarian (Pgp- A2780, Pgp+ A2780AD), and cervix carcinoma (Pgp- KB-3-1, Pgp+ KB-V-1) cell lines to establish corresponding tumor-bearing mouse models. Prior to [18F]F-FDG/[18F]F-FAZA-based MiniPET imaging, in vitro [18F]F-FDG uptake measurements and western blotting were used to verify the presence of hypoxia. RESULTS: Elevated GLUT-1, and hexokinase enzyme-II expression driven by CoCl2-induced activation of hypoxia-inducible factor-1α explains enhanced cellular [18F]F-FDG accumulation. No difference was observed in the [18F]F-FAZA accretion of Pgp+ and Pgp- tumors. Tumor-to-muscle ratios for [18F]F-FAZA measured at 110-120 min postinjection (6.2±0.1) provided the best contrasted images for the delineation of PET-oxic and PET-hypoxic intratumor regions. Although all tumors exhibited heterogenous uptake of both radiopharmaceuticals, greater differences for [18F]F-FAZA between the tracer avid and non-accumulating regions indicate its superiority over [18F]F-FDG. Spatial correlation between [18F]F-FGD and [18F]F-FAZA scans confirms that hypoxia mostly occurs in regions with highly active glucose metabolism. CONCLUSION: The addition of [18F]F-FAZA PET to [18F]F-FGD imaging may add clinical value in determining hypoxic sub-regions.

Esthetic and functional reconstruction of large mandibular defects using free fibula flap and implant-retained prosthetics - a case series with long-term follow-up.

BACKGROUND: The reconstructive and rehabilitative management of large mandibular defects with basal continuity is challenging in many respects, especially in the vertical dimension. The free fibula flap is an under-utilised but efficient approach in this indication. The aim of this case series is to demonstrate its use and long-term success. CASE PRESENTATION: Three cases are presented, where the patient had a large bone defect (at least 5 cm in length and 1 cm in the vertical dimension), but the continuity of the mandible was maintained. Two cases were related to pathological fracture and one was a large defect due to oncological surgery. Vertical augmentation with free microvascularised fibula flap was carried out, followed by implant-retained prosthetic therapy. Clinical status has been followed up for 5 to 6 years, with special attention to the condition of the peri-implant tissues and any radiographically detectable alterations or complications. No complications occurred during the follow-up. Function and esthetics have remained unchanged throughout. CONCLUSIONS: Free microvascularised fibula flap reconstruction combined with implant-retained prosthetics allows a lasting functional and esthetic solution in the discussed indication.

Vertical mandibular bone augmentation by the osteodistraction of the transplanted fibula free flap: A case series with long-term follow-up.

Vertical augmentation of the mandible to prepare dental implant therapy is still a challenge, especially with large mandible defects. Reconstruction with fibula free flap is a regularly applied approach in such cases, but it does not always yield optimal results: the resulting crestal height might differ significantly from the crestal height of the patient's intact bone, which makes esthetic and functional rehabilitation difficult. Osteodistraction of the integrated flap is a known but rarely discussed approach where the already integrated flap undergoes additional distraction. Through the four cases reported here, we would like to demonstrate that the osteodistraction of the transplanted fibula free flap is a useful and efficient method of secondary augmentation for cases where the flap itself fails to produce the desired crestal height, and no other method is applicable. The cases show that the method allows outcomes that are highly satisfactory, both in the functional and esthetic sense.