Differentiating Transition Zone Cancers From Benign Prostatic Hyperplasia by Quantitative Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to evaluate the value of quantitative diffusion and perfusion parameters to aid in discriminating between transition zone carcinomas and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Twenty-four transition zone cancers and BPH nodules were contoured on T2-weighted magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) maps, and raw dynamic contrast-enhanced (DCE) MRI. Benign prostatic hyperplasia nodules were then stratified into 2 groups based on the presence or absence of a capsule. Apparent diffusion coefficient values, per-voxel Ktrans, kep, vp, and ve were all compared across all groups. RESULTS: Average ADCs (×10 mm/s) were 1019.22, 1338.11, and 1272.46 for cancer, encapsulated BPH, and nonencapsulated BPH, respectively. Both subgroups of BPH were found to be significantly different than that of cancer (P < 0.05). No individual DCE-MRI parameter was significantly different between cancer and either BPH group. The area under the curve for ADC alone was 0.83, and no individual DCE imaging parameter improved the area under the curve of ADC. CONCLUSIONS: Apparent diffusion coefficient may play a role in distinguishing TZ cancers from non-encapsulated BPH nodules that closely resemble cancer.

Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [99mTc] (AH-113018) or Cy 5** (AH-112543) Labeled Peptide.

Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIs). A peptide targeting Met labeled with [(99m)Tc] had high affinity in vitro (Kd = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [(99m)Tc]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using single-photon emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [(99m)Tc]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [(99m)Tc]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [(99m)Tc] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [(99m)Tc] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications.

Recent advances in image-guided targeted prostate biopsy.

Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques.

Immuno-PET imaging of tumor endothelial marker 8 (TEM8).

Tumor endothelial marker 8 (TEM8) is a cell surface receptor that is highly expressed in a variety of human tumors and promotes tumor angiogenesis and cell growth. Antibodies targeting TEM8 block tumor angiogenesis in a manner distinct from the VEGF receptor pathway. Development of a TEM8 imaging agent could aid in patient selection for specific antiangiogenic therapies and for response monitoring. In these studies, L2, a therapeutic anti-TEM8 monoclonal IgG antibody (L2mAb), was labeled with (89)Zr and evaluated in vitro and in vivo in TEM8 expressing cells and mouse xenografts (NCI-H460, DLD-1) as a potential TEM8 immuno-PET imaging agent. (89)Zr-df-L2mAb was synthesized using a desferioxamine-L2mAb conjugate (df-L2mAb); (125)I-L2mAb was labeled directly. In vitro binding studies were performed using human derived cell lines with high, moderate, and low/undetectable TEM8 expression. (89)Zr-df-L2mAb in vitro autoradiography studies and CD31 IHC staining were performed with cryosections from human tumor xenografts (NCI-H460, DLD-1, MKN-45, U87-MG, T-47D, and A-431). Confirmatory TEM8 Western blots were performed with the same tumor types and cells. (89)Zr-df-L2mAb biodistribution and PET imaging studies were performed in NCI-H460 and DLD-1 xenografts in nude mice. (125)I-L2mAb and (89)Zr-df-L2mAb exhibited specific and high affinity binding to TEM8 that was consistent with TEM8 expression levels. In NCI-H460 and DLD-1 mouse xenografts nontarget tissue uptake of (89)Zr-df-L2mAb was similar; the liver and spleen exhibited the highest uptake at all time points. (89)Zr-L2mAb was highly retained in NCI-H460 tumors with <10% losses from day 1 to day 3 with the highest tumor to muscle ratios (T:M) occurring at day 3. DLD-1 tumors exhibited similar pharmacokinetics, but tumor uptake and T:M ratios were reduced ∼2-fold in comparison to NCI-H460 at all time points. NCI-H460 and DLD-1 tumors were easily visualized in PET imaging studies despite low in vitro TEM8 expression in DLD-1 cells indicating that in vivo expression might be higher in DLD-1 tumors. From in vitro autoradiography studies (89)Zr-df-L2mAb specific binding was found in 6 tumor types (U87-MG, NCI-H460, T-47D MKN-45, A-431, and DLD-1) which highly correlated to vessel density (CD31 IHC). Westerns blots confirmed the presence of TEM8 in the 6 tumor types but found undetectable TEM8 levels in DLD-1 and MKN-45 cells. This data would indicate that TEM8 is associated with the tumor vasculature rather than the tumor tissue, thus explaining the increased TEM8 expression in DLD-1 tumors compared to DLD-1 cell cultures. (89)Zr-df-L2mAb specifically targeted TEM8 in vitro and in vivo although the in vitro expression was not necessarily predictive of in vivo expression which seemed to be associated with the tumor vasculature. In mouse models, (89)Zr-df-L2mAb tumor uptakes and T:M ratios were sufficient for visualization during PET imaging. These results would suggest that a TEM8 targeted PET imaging agent, such as (89)Zr-df-L2mAb, may have potential clinical, diagnostic, and prognostic applications by providing a quantitative measure of tumor angiogenesis and patient selection for future TEM8 directed therapies.

The critical importance of a vascularized flap in preventing recurrence after endoscopic repair of spontaneous cerebrospinal fluid leaks and meningoencephaloceles.

OBJECTIVE: Spontaneous CSF leaks into the anterior skull base nasal sinuses are often associated with meningoencephaloceles and occur in patients with idiopathic intracranial hypertension (IIH). Endonasal endoscopic repair has become the primary method of choice for repair. The authors sought to evaluate the success rate of endoscopic closure and to identify predictive factors for CSF leak recurrence. METHODS: A consecutive series of endonasally repaired anterior skull base meningoencephaloceles was drawn from a prospectively acquired database. Lumbar punctures were not performed as part of a treatment algorithm. All patients had at least 5 months of follow-up. Chart review and phone calls were used to determine the timing and predictors of recurrence. Demographic information and details of operative technique were correlated with recurrence. Two independent radiologists reviewed all preoperative imaging to identify radiographic markers of IIH, as well as the location and size of the meningoencephalocele. RESULTS: From a total of 54 patients there were 5 with recurrences (9.3%), but of the 39 patients in whom a vascularized nasoseptal (n = 31) or turbinate (n = 8) flap was used there were no recurrences (p = 0.0009). The mean time to recurrence was 24.8 months (range 9-38 months). There was a trend to higher BMI in patients whose leak recurred (mean [± SD] 36.6 ± 8.6) compared with those whose leak did not recur (31.8 ± 7.4; p = 0.182). Although the lateral recess of the sphenoid sinus was the most common site of meningoencephalocele, the fovea ethmoidalis was the most common site in recurrent cases (80%; p = 0.013). However, a vascularized flap was used in significantly more patients with sphenoid (78.3%) defects than in patients with fovea ethmoidalis (28.6%) defects (Fisher's exact test, p = 0.005). Radiographic signs of IIH were equally present in all patients whose leak recurred (75%) compared with patients whose leak did not recur (63.3%); however, an enlarged Meckel cave was present in 100% (2/2) of patients whose leaks recurred compared with 13.3% (4/30) of patients whose leaks did not recur (p = 0.03). The average meningoencephalocele diameter tended to be larger (1.73 ± 1.3 cm) in patients with recurrence compared to those without recurrence (1.2 ± 0.66 cm; p = 0.22). A ventriculoperitoneal shunt was already in place in 3 patients, placed perioperatively in 5, and placed at recurrence in 2, none of whose leaks recurred. CONCLUSIONS: Recurrence after endonasal repair of spontaneous CSF leaks from meningoencephaloceles can be dramatically reduced with the use of a vascularized flap. Although failures of endonasal repair tend to occur in patients who have higher BMI, larger brain herniations, and no CSF diversion, the lack of vascularized flap was the single most important risk factor predictive of failure.

Risk stratification of patients undergoing pulmonary metastasectomy for soft tissue and bone sarcomas.

OBJECTIVES: Our objective was to identify risk factors associated with survival in patients who underwent pulmonary metastasectomy for soft tissue or bone sarcoma and to create a risk stratification model. METHODS: A retrospective review of the prospectively maintained University of California Los Angeles Sarcoma Database was performed. Clinical, pathologic, and treatment variables were analyzed for overall survival and disease-free survival. Univariate and multivariate analyses were performed, and variables that were identified as significant were included to create a risk model. A total of 155 patients who underwent pulmonary metastasectomy for soft tissue sarcoma (n = 108 patients) or bone sarcoma (n = 47 patients) from 1994 to 2010 were identified. RESULTS: Multivariate analysis identified 7 factors associated with poor overall survival: age more than 45 years, disease-free interval less than 1 year, thoracotomy, synchronous disease, location and type of sarcoma (soft tissue vs bone sarcoma), and performance of a lobectomy. The number of factors present was associated with poor overall survival, which varied widely from 64% in patients with 2 factors to 3% in those with 5 factors. CONCLUSIONS: We have identified prognostic variables associated with overall survival after lung metastasectomy. Our model may be used as a risk stratification model to guide treatment decisions on the basis of the number of risk factors present. Although prospective studies are warranted to determine the benefit of surgical intervention in all cohorts compared with other local therapies or medical therapy, given the attendant dismal prognosis in patients with 5 or more risk factors, the benefit of surgical resection in this group is questioned.

Laryngomalacia presenting as recurrent croup in an infant.

Laryngomalacia is a common disease of infancy which can present with atypical symptoms and at an atypical age, causing the diagnosis to often be overlooked. We report a case of a male patient who was diagnosed with laryngomalacia at the age of three months. The patient's inspiratory stridor resolved within a year, but he went on to develop atypical croup. The patient was later diagnosed with severe laryngomalacia which complicated his "croup-like" symptoms. He subsequently underwent supraglottoplasty with complete resolution of symptoms.

Solitary fibrous tumor of the larynx: case report demonstrating the value of MRI in guiding surgical management.

A 74-year-old woman presented with persistent dysphagia, dysphonia, and throat gurgling. Prior intraoperative biopsies were negative, and outside imaging revealed supraglottic swelling. Magnetic resonance imaging (MRI) demonstrated a well-defined T1 and T2 hypointense, avidly enhancing hypopharyngeal mass. Deep intraoperative rebiopsies revealed a tumor with CD34+ tissue, diagnostic of a solitary fibrous tumor. A broad range of nonsquamous cell tumors should be considered when a submucosal laryngeal mass is encountered. MRI may be particularly helpful in guiding appropriate biopsy.