Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound.

Several thermal-therapy strategies such as thermal ablation, hyperthermia-triggered drug delivery from temperature-sensitive liposomes (TSLs), and combinations of the above were investigated in a rhabdomyosarcoma rat tumor model (n = 113). Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) was used as a noninvasive heating device with precise temperature control for image-guided drug delivery. For the latter, TSLs were prepared, coencapsulating doxorubicin (dox) and [Gd(HPDO3A)(H2O)], and injected in tumor-bearing rats before MR-HIFU treatment. Four treatment groups were defined: hyperthermia, ablation, hyperthermia followed by ablation, or no HIFU. The intratumoral TSL and dox distribution were analyzed by single-photon emission computed tomography (SPECT)/computed tomography (CT), autoradiography, and fluorescence microscopy. Dox biodistribution was quantified and compared with that of nonliposomal dox. Finally, the treatment efficacy of all heating strategies plus additional control groups (saline, free dox, and Caelyx) was assessed by tumor growth measurements. All HIFU heating strategies combined with TSLs resulted in cellular uptake of dox deep into the interstitial space and a significant increase of tumor drug concentrations compared with a treatment with free dox. Ablation after TSL injection showed [Gd(HPDO3A)(H2O)] and dox release along the tumor rim, mirroring the TSL distribution pattern. Hyperthermia either as standalone treatment or before ablation ensured homogeneous TSL, [Gd(HPDO3A)(H2O)], and dox delivery across the tumor. The combination of hyperthermia-triggered drug delivery followed by ablation showed the best therapeutic outcome compared with all other treatment groups due to direct induction of thermal necrosis in the tumor core and efficient drug delivery to the tumor rim.

A Case of Infantile Large Parapharyngeal Rhabdomyosarcoma Followed Up for More Than 20 Years.

Rhabdomyosarcomas in the parapharyngeal space are quite rare. We report herein on the case of a 14-month-old boy who was hospitalized with a 2-month history of stridor. On admission, right peritonsillar swelling was noted. CT demonstrated the presence of a large tumor in the right parapharyngeal space. MRI findings showed a right parapharyngeal tumor, 6-cm in diameter. Histopathologic evaluation of the tumor revealed embryonal rhabdomyosarcoma. The clinical staging of the Intergroup Rhabdomyosarcoma Study Group (IRSG) was classified as group III. According to regimen 35 of the IRSG III treatment protocol, radiochemotherapy was started, comprising combination therapy with vincristine, actinomycinD, cyclophosphamide, adriamycin, and carboplatin. The patient tolerated the therapy, but with severe pancytopenia and fever. His sedation during irradiation was difficult. After he received a total dose of 10 Gy and had undergone 9 cycles of chemotherapy, an operation for the rhabdomyosarcoma was performed, resulting in successful removal of the tumor. Doses of 20 Gy were intraoperatively administered. After surgery, residual chemotherapy and irradiation was resumed. The evaluation of the response to therapy was complete remission. After 4 years from the start of therapy, all chemotherapy was halted. At present there is no evidence of recurrence or metastasis, and the patient is a well-developed college student. His sequela following therapy consisted of facial asymmetry, dental abnormalities, and pigmentation of the neck. No adriamycin cardiomyopathy was found.

Efficacy and Safety of Limited-Margin Conformal Radiation Therapy for Pediatric Rhabdomyosarcoma: Long-Term Results of a Phase 2 Study.

PURPOSE: Our purpose was to assess disease outcomes and late toxicities in pediatric patients with rhabdomyosarcoma treated with conformal photon radiation therapy (RT). METHODS AND MATERIALS: Sixty-eight patients (median age, 6.9 years) were treated with conformal photon RT to the primary site on a prospective clinical trial. Target volumes included a 1-cm expansion encompassing microscopic disease. Prescribed doses were 36 Gy to this target volume and 50.4 Gy to gross residual disease. Chemotherapy consisted of vincristine/dactinomycin (n = 6), vincristine/dactinomycin/cyclophosphamide (n = 37), or vincristine/dactinomycin/cyclophosphamide-based combinations (n = 25). Patients were evaluated with primary-site magnetic resonance imaging, whole-body [18F]fluorodeoxyglucose positron emission tomography, and chest computed tomography for 5 years after treatment. RESULTS: Five-year disease-free survival was 88% for low-risk (n = 8), 76% for intermediate-risk (n = 37), and 36% for high-risk (n = 23) patients (P ≤ .01 for low risk/intermediate risk vs high risk). The cumulative incidence of local failure (LF) at 5 years for the entire cohort was 10.4%. Tumor size at diagnosis was a significant predictor of LF (P < .01). Patients with head and neck primary tumors (n = 31) had a 35% cumulative incidence of cataracts; the risk correlated with lens dose (P = .0025). Jaw dysfunction was more severe when the pterygoid and masseter muscles received a mean dose of >20 Gy (P = .013). Orbital hypoplasia developed more frequently after a mean bony orbit dose of >30 Gy (P = .041). Late toxicity in patients with genitourinary tumors included microscopic hematuria (9 of 14), bladder-wall thickening (10 of 14), and vaginal stenosis (2 of 5). CONCLUSIONS: Long-term LF rates were low, and higher rates correlated with larger tumors. Treatment-related toxicities resulting in measurable functional deficits were not infrequent, despite the conformal RT approach.

The mannose 6-phosphate receptor targeted with porphyrin-based periodic mesoporous organosilica nanoparticles for rhabdomyosarcoma theranostics.

Porphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO-AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observed.

[Differential diagnosis of cystic and cystic-like lesions of the jaw]. / Differentialdiagnose zystischer und zystenähnlicher Läsionen der Kiefer.

The difficulties in the differential diagnosis of jaw cysts are demonstrated by 10 selected case studies. Panorama radiographies are basic for radiodiagnosis. Supplementary radiographs, including CT, are often necessary. In general, the final diagnosis can be given after synopsis of clinical, radiographic and patho-histological findings.

Concomitant reconstruction of infrarenal aorta and inferior vena cava after en bloc resection of retroperitoneal rhabdomyosarcoma.

Adult paratesticular rhabdomyosarcoma (PRMS) with invasion of the retroperitoneum and involvement of the infrarenal aorta and inferior vena cava (IVC) is rare. We describe a 23-year-old male diagnosed with PRMS in 2008, previously treated with right orchiectomy, chemotherapy, and radiation, who presented with new onset of lower back pain. Computed tomography (CT) scan revealed a 4.8 × 4.2 cm mass involving both the infrarenal aorta and the IVC. We resected the tumor en bloc with in situ reconstruction of the aorta utilizing a Dacron graft and the IVC with a bovine pericardium roll graft. His postoperative period was uneventful, and he was discharged on postoperative day 6 in stable condition. At 2-month follow-up, the patient recovered well from the surgery, patent grafts on CT scan with no clinical signs of lower extremity ischemia or edema, and he continues to receive cycles of chemotherapy.

Design and optimization of coin-shaped microreactor chips for PET radiopharmaceutical synthesis.

UNLABELLED: An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. METHODS: The unique architecture of the device is centered around a 5-microL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. RESULTS: The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. CONCLUSION: The reactor has the potential to produce multiple human doses of (18)F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment.

Rhabdomyosarcoma: report of a case with involvement of the angle of the mandible.

The most common signs of a malignancy in the region of the head and neck are evidence of a mass or symptoms arising from it. In this report a patient is described with rhabdomyosarcoma of the mandible. An incidental x-ray taken some 3 months prior to the onset of clinical symptoms showed no evidence of bone involvement of the mandible. The onset of bone destruction of the angle and ascending ramus of the mandible as seen on a subsequent x-ray can be placed somewhere in this period of time.

Use of computed tomography for the fabrication of a custom brachytherapy carrier: a clinical report.

Early methods of fabricating customized radiation carriers for inaccessible areas, such as the nasopharyngeal space, normally required the patient to be under conscious sedation or general anesthesia to allow impressions for indirect processing techniques. This article describes the use of computed tomography to design and fabricate a carrier for the intracavity application of iodine 125 seeds for a patient with rhabdomyosarcoma of the nasopharynx. With tomography printed copies, a wax pattern was formed, flasked, boiled out, and eventually replaced with silicone material. The patient had to be available only for a conventional thin-cut computed tomography scan without contrast; no fitting appointments or anesthesia were necessary. The indirect procedure eliminated discomfort from impression making and allowed for precise fabrication of the nasopharyngeal carrier. The described technique can be used for other intracavitary radiation applications.

Rhabdomyosarcoma of pterygoid fossa. Resection for cure utilizing an innervated facial flap and craniofacial reconstruction.

Tumors of the pterygoid fossa are often regarded as unresectable because of their anatomic inaccessibility. The rapidly developing techniques of craniofacial surgery have advanced sufficiently to now allow safe ablative surgery in this area and yet preserve the functional status and cosmetic appearance of the patient. A technique utilizing a bicoronal incision that is extended to the angle of the mandible on the involved side is described. This allows wide exposure of the bony structures at the lateral base of the skull while maintaining the integrity of the facial nerve within the cutaneous flap. Temporary removal of the zygomatic arch achieves direct access to and visualization of the contents of the temporal and pterygoid fossae. Skull, mandibular, and maxillary bone adjacent to tumor can easily and safely be resected to obtain complete tumor-free margins. Craniectomy bone is harvested and split into inner and outer tables to reconstruct the bony defects. This approach was successfully utilized in a 5-year-old boy with a Group III rhabdomyosarcoma with residual tumor following combined chemo- and radiotherapy. He remains tumor-free at 15 months, postoperation. The technique can be adapted for a variety of mass lesions located at the anterior base of the skull, both intra- and extracranially. Morbidity and mortality should be minimal with an experienced craniofacial team.

A case of head and neck kaposiform hemangioendothelioma simulating a malignancy on imaging.

Kaposiform hemangioendothelioma (KH) is an endothelial-derived spindle cell neoplasm often associated with Kasabach-Merritt syndrome. Most cases arise in infancy and childhood and are soft-tissue tumors. The tumor displays an appearance between capillary hemangioma and Kaposi's sarcoma. We report a case of KH in a 1-year-old girl involving a mass that showed abnormal enhancement of soft tissue superficial to the right temporal bone with partial destruction of the temporal bone, the temporomandibular joint, mandibular condyle, and occipital bone. The physical finding of a discolored mass led clinicians to consider a hemangiomatous lesion, whereas the radiological picture suggested a more aggressive diagnosis of rhabdomyosarcoma and aggressive fibromatosis.

Presentation and diagnosis of unilateral maxillary swelling in children.

Facial asymmetry secondary to pathologic processes involving the maxillary sinus and its surrounding structures presents a challenge for the clinician. An organized approach to evaluate these patients is essential in order to differentiate inflammatory sinus pathology from disease processes primarily involving the surrounding maxilla, parotid gland, orbital contents, and dental structures. In addition to a thorough history and physical examination, appropriate imaging studies must be obtained to localize the pathologic processes and develop a meaningful differential diagnosis. Once this is accomplished, specific treatment modalities can be developed. Representative cases will be presented to illustrate this organized approach to unilateral maxillary swelling, including soft tissue and osseous masses, fibro-osseous lesions, osseous cysts and inflammatory lesions.