- A model of breast cancer meningeal metastases: characterization with in vivo molecular imaging. [Journal Article]
- CGCancer Gene Ther 2018 Nov 13
- Meningeal metastasis is a fatal complication of breast cancer which affects 8-15% of patients who experience severe neurological complications of cranial nerves, cerebrum, and spinal cord. Survival o...
Meningeal metastasis is a fatal complication of breast cancer which affects 8-15% of patients who experience severe neurological complications of cranial nerves, cerebrum, and spinal cord. Survival once diagnosed is less than 4 months. Currently there is no cure. Aggressive multimodal radiation, intra-CSF, or systemic chemotherapy is palliative. Investigation of urgently needed new treatment modalities is hindered by the lack of suitable animal models to effectively study tumor growth kinetics. We present a model of meningeal metastases where tumor growth and associated neurological symptoms have been characterized over 3 weeks by sequential molecular imaging, tumor growth kinetics, and histopathology. Meningeal metastases were induced by stereotaxic injection of human breast cancer cells (MDA-MB-231-Rluc) into the lateral ventricle. Tumor identified by Gd-MRI and Rluc-bioluminescence depict growth in 3 phases, namely lag, exponential, and plateau phase. Invasive tumor growth was highlighted by changes in contrast distribution in the meninges, ventricle and brain compartments over time where moderate contrast uptake in the early growth phase gave rise to a heavy tumor burden in the base of the brain in the latter phases. Tumor growth was accompanied with debilitating neurological symptoms and change in body mass. Tumor was confirmed by ex vivo histology. The reliability of the model to study novel therapeutics was confirmed by oncolytic virus delivered into the lateral ventricle showed potential for treatment. This effective and reliable model resembles human disease progression and is ideally suited to investigate novel treatments.
- Thyroid Carcinoma Presenting as a Dural and Calvarial Metastasis Mimicking a Lipoma With Difficult Diagnosis of the Primary Lesion. [Case Reports]
- JCJ Craniofac Surg 2018; 29(7):e684-e686
- Calvarial and dural metastases of papillary thyroid carcinomas (PTC) are rarely reported in the medical literature. Most frequent calvarial metastases are seen to originate from lung, breast, and pro...
Calvarial and dural metastases of papillary thyroid carcinomas (PTC) are rarely reported in the medical literature. Most frequent calvarial metastases are seen to originate from lung, breast, and prostate cancers. Thyroid cancer metastases are generally well vascularized and cause destruction in the bone tissues. First choice of treatment in distant metastases of PTC is surgery and radioactive iodine treatment for the primary cause. Postsurgical radiotherapy is used in accepted and suitable patients.
- Local recurrence patterns after postoperative stereotactic radiation surgery to resected brain metastases: A quantitative analysis to guide target delineation. [Journal Article]
- PRPract Radiat Oncol 2018 Nov - Dec; 8(6):388-396
- CONCLUSIONS: Our quantitative analysis of recurrence patterns suggests that a larger 3 mm uniform expansion of the SRS target volume substantially increases coverage of the volume that is later occupied by the recurrent tumor and may provide improved local control. The extent of the preoperative tumor in the target volume or expanding the target volume from the meninges provides little benefit.
- Leukaemia hijacks a neural mechanism to invade the central nervous system. [Journal Article]
- NatNature 2018; 560(7716):55-60
- Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve th...
Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.
- Role of (myo)fibroblasts in the development of vascular and connective tissue structure of the C38 colorectal cancer in mice. [Journal Article]
- CCCancer Commun (Lond) 2018 07 05; 38(1):46
- CONCLUSIONS: Our data suggest that the desmoplastic host tissue response is induced by tumor-derived fibrogenic molecules acting on host tissue fibroblasts. We concluded that not only the host tissue characteristics but also the tumor-derived fibrogenic signals determine the vascular and connective tissue structure of tumors.
- Concurrent metastases of papillary thyroid carcinoma to the scalp and Meckel's cave. [Case Reports]
- BCBMJ Case Rep 2018 Jun 17; 2018
- We present the case of a 65-year-old man with severe headaches and unilateral facial weakness, seen in consultation by the dermatology service to rule out primary cutaneous melanoma after brain imagi...
We present the case of a 65-year-old man with severe headaches and unilateral facial weakness, seen in consultation by the dermatology service to rule out primary cutaneous melanoma after brain imaging identified an enlarging mass within the right trigeminal (Meckel's) cave. Examination revealed only a pair of erythematous papules on the scalp, for which biopsy demonstrated metastatic papillary thyroid carcinoma. Further evaluation and subsequent thyroidectomy confirmed the origin of widespread internal disease, followed by definitive excision of scalp lesions and multimodal management of systemic involvement. Whereas presentation of metastasis to the skin is highly variable, a low threshold for biopsy may allow for histological identification of internal disease not otherwise considered in the clinical differential.
- Tumor-to-Lesion Metastasis: Case Report of Carcinoma Metastasis to Multiple Sclerosis Lesion. [Case Reports]
- WNWorld Neurosurg 2018; 116:14-17
- CONCLUSIONS: The carcinoma-hosting MS lesions are unlike typical active lesions but recapitulate the CNS metastatic niche. Our observations suggest that metastasis-hosting MS lesions might require a distinct immune microenvironment to be permissive to the seeding and growth of metastatic tumors.
- Epidemiology and national trends in prevalence and surgical management of metastatic spinal disease. [Journal Article]
- JCJ Clin Neurosci 2018; 53:183-187
- Surgical treatment for spinal metastasis has benefited from improvements in surgical techniques. However, the trends in treatment and outcomes for spinal metastasis surgery have not been well-establi...
Surgical treatment for spinal metastasis has benefited from improvements in surgical techniques. However, the trends in treatment and outcomes for spinal metastasis surgery have not been well-established in a pediatric population. Patients <20 years old with metastatic spinal tumors undergoing spinal surgery were identified in the KID database. Trends for spinal metastases treatment and patient outcomes were analyzed using weight-adjusted ANOVAs. 333 patients were identified in the KID database. The top five primary diagnoses were metastatic brain/spinal cord tumor (19.8%), metastatic nervous system tumor (15.9%), metastatic bone cancer (13.2%), spinal cord tumor (4.2%), and tumor of ventricles (3.0%). There was an increased incidence of spinal metastasis diagnoses from 2003 to 2012 (88.5-117.9 per 100,000; p < 0.001) and an increased trend in the incidence of surgical treatment for spinal metastasis from 2003 to 2012 (p = 0.014). The average age was 10.19 ± 6.33 years old and 38.4% were female. The average length of stay was 17.34 ± 24.36 days. Average CCI increased over time (2003: 7.87 ± 1.40, 2012: 8.44 ± 1.39; p = 0.006). The most common surgeries were excision of spinal cord/meninges lesions (69.1%) and decompression of spinal canal (38.1%). Length of hospital stay and in-hospital mortality did not change over time (17.34-18.04 days, p = 0.337; 1.6%-2.9%, p = 0.801). 10.5% of patients underwent a posterior fusion and 22.2% had at least one complication (nervous system, respiratory, dysphagia, infection). The overall complication rate remained stable over time (23.4%-21.8%, p = 0.952). Surgical treatment for spinal metastasis in the last decade has increased, though the complication rates, in-hospital mortality, and length of stay have remained stable.
- Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity. [Case Reports]
- WNWorld Neurosurg 2018; 114:235-240
- CONCLUSIONS: To the best of our knowledge, this is the first reported case of metastatic epidural spread of pheochromocytoma without concomitant subdural or intraparenchymal extension.
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- A dural metastatic small cell carcinoma of the gallbladder as the first manifestation: a case report. [Case Reports]
- WJWorld J Surg Oncol 2018 Mar 16; 16(1):57
- CONCLUSIONS: To the best of our knowledge, this is the first case of a dural metastasis of gallbladder small cell carcinoma. A systemic examination is essential for clinicians when atypical findings of meningioma are observed, suggesting a meningioma mimic. We present this rare case with a review of the literature.