Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

PI-RADS version 2.1: one small step for prostate MRI.

Multiparametric (mp) prostate magnetic resonance imaging (MRI) is playing an increasingly prominent role in the diagnostic work-up of patients with suspected prostate cancer. Performing mpMRI before biopsy offers several advantages including biopsy avoidance under certain clinical circumstances and targeting biopsy of suspicious lesions to enable the correct diagnosis. The success of the technique is heavily dependent on high-quality image acquisition, interpretation, and report communication, all areas addressed by previous versions of the Prostate Imaging-Reporting and Data System (PI-RADS) recommendations. Numerous studies have validated the approach, but the widespread adoption of PI-RADS version 2 has also highlighted inconsistencies and limitations, particularly relating to interobserver variability for evaluation of the transition zone. These limitations are addressed in the recently released version 2.1. In this article, we highlight the key changes proposed in PI-RADS v2.1 and explore the background reasoning and evidence for the recommendations.

Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

PSMA PET/CT with Glu-urea-Lys-(Ahx)-[68Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer.

PURPOSE: PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) in the setting of recurrent prostate cancer. METHODS: All PET/CT images were acquired 60 ± 10 min after intravenous injection of (68)Ga-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined. RESULTS: The mean volume of (68)Ga-PSMA-11-positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters >8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters <8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, (68)Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. CONCLUSION: (68)Ga-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting.

PI-RADS version 2: what you need to know.

Prostate cancer is the second most prevalent cancer in men worldwide and its incidence is expected to double by 2030. Multi-parametric magnetic resonance imaging (MRI) incorporating anatomical and functional imaging has now been validated as a means of detecting and characterising prostate tumours and can aid in risk stratification and treatment selection. The European Society of Urogenital Radiology (ESUR) in 2012 established the Prostate Imaging-Reporting and Data System (PI-RADS) guidelines aimed at standardising the acquisition, interpretation and reporting of prostate MRI. Subsequent experience and technical developments have highlighted some limitations, and a joint steering committee formed by the American College of Radiology, ESUR, and the AdMeTech Foundation have recently announced an updated version of the proposals. We summarise the main proposals of PI-RADS version 2, explore the evidence behind the recommendations, and highlight key differences for the benefit of those already familiar with the original.

Head-to-head Intra-individual Comparison of [68Ga]-FAPI and [18F]-FDG PET/CT in Patients with Bladder Cancer.

AIM/PURPOSE: Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [18F]FDG PET/CT. 68Ga-labeled fibroblast activation protein inhibitor-([68Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [18F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [68Ga]FAPI in patients with bladder cancer. MATERIAL AND METHODS: This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [68Ga]FAPI and [18F]FDG PET/CT scans with a median time interval of 5 days (range 1-20 days). Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool. RESULTS: Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [68Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [68Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [18F]FDG PET/CT with higher mean SUVmax (8.2 vs. 4.6; p = 0.01). Furthermore, [68Ga]FAPI detected additional 30% (n = 9) lesions, missed by [18F]FDG. TBR demonstrated favorable uptake for [68Ga]FAPI in comparison to [18F]FDG. Significant differences were determined with regard to metastasis/blood pool ([68Ga]FAPI 5.3 vs [18F]FDG 1.9; p = 0.001). CONCLUSION: [68Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [18F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies.

Preparation and characterization of a magnetic and optical dual-modality molecular probe.

Multi-modality imaging probes combine the advantages of individual imaging techniques to yield highly detailed anatomic and molecular information in living organisms. Herein, we report the synthesis and characterization of a dual-modality nanoprobe that couples the magnetic properties of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with the near infrared fluorescence of Cy5.5. The fluorophore is encapsulated in a biocompatible shell of silica surrounding the iron oxide core for a final diameter of approximately 17 nm. This silica-coated iron oxide nanoparticle (SCION) has been analyzed by transmission electron microscopy, dynamic light scattering, and superconducting quantum interference device (SQUID). The particle demonstrates a strong negative surface charge and maintains colloidal stability in the physiological pH range. Magnetic hysteresis analysis confirms superparamagnetic properties that could be manipulated for thermotherapy. The viability of primary human monocytes, T cells, and B cells incubated with the particle has been examined in vitro. In vivo analysis of agent leakage into subcutaneous A431 tumors in mice was also conducted. This particle has been designed for diagnostic application with magnetic resonance and fluorescence imaging, and has future potential to serve as a heat-sensitive targeted drug delivery platform.

Impact of Primary Staging with Fibroblast Activation Protein Specific Enzyme Inhibitor (FAPI)-PET/CT on Radio-Oncologic Treatment Planning of Patients with Esophageal Cancer.

PURPOSE: Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. METHODS: Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. RESULTS: Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. CONCLUSION: FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.

First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging.

INTRODUCTION: Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status. METHODS: 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions. RESULTS: No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h). CONCLUSION: 111In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.

Multiparametric MRI/ultrasound fusion-guided biopsy decreases detection of indolent cancer in African-American men.

BACKGROUND: Analysis of systematic 12-core biopsies (SBx) has shown that African-American (AA) men tend to harbor higher risk prostate cancer (PCa) at presentation relative to other races. Multiparametric magnetic resonance imaging (mpMRI) and MRI-ultrasound fusion-guided biopsy (FBx) have been shown to diagnose more intermediate- and high-risk PCa in the general population; however, the efficacy in AA remains largely uncharacterized. We aim to evaluate the utility of FBx in an AA patient cohort. METHODS: Men suspected of PCa underwent an mpMRI and FBx with concurrent SBx from 2007 to 2015 in this institutional review board-approved prospective cohort study. Patient demographics, imaging and fusion biopsy variables were collected. χ2, Mann-Whitney U-test and McNemar's tests were performed to compare proportions, means and paired variables, respectively. Clinically significant PCa (CSPCa) was defined as Gleason score ⩾3+4. RESULTS: Fusion biopsy demonstrated exact agreement with SBx risk categories in 64% of AA men. There was no statistically significant difference in the detection of CSPCa between FBx vs SBx (68 vs 62 cases, P=0.36). However, FBx detected 41% fewer cases of clinically insignificant PCa (CIPCa) compared with SBx (FBx 30 vs SBx 51 cases, P=0.0004). The combined FBx/SBx biopsy approach detected significantly more cases of CSPCa (FBx/SBx 80 vs SBx 62 cases, P=0.004) while detecting comparable number of cases of CIPCa (FBx/SBx 45 vs SBx 51 cases, P=0.37) compared with SBx alone. FBx/SBx also detected more CSPCa in patients with a history of prior negative SBx (FBx/SBx 28 vs 19 cases, P=0.003). CONCLUSIONS: FBx when used in combination with SBx detected more cases of CSPCa while not significantly increasing the diagnosis of CIPCa in AA men. Future multicenter studies will be needed to validate ultimately the clinical implications of FBx in AA patients.

The prostate cancer prevention trial risk calculator 2.0 performs equally for standard biopsy and MRI/US fusion-guided biopsy.

BACKGROUND: The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) is a widely used risk-based calculator used to assess a man's risk of prostate cancer (PCa) before biopsy. This risk calculator was created from data of a patient cohort undergoing a 6-core sextant biopsy, and subsequently validated in men undergoing 12-core systematic biopsy (SBx). The accuracy of the PCPTRC has not been studied in patients undergoing magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy (FBx). We sought to assess the performance of the PCPTRC for straitifying PCa risk in a FBx cohort. METHODS: A review of a prospective cohort undergoing MRI and FBx/SBx was conducted. Data from consecutive FBx/SBx were collected between August 2007 and February 2014, and PCPTRC scores using the PCPTRC2.0R-code were calculated. The risk of positive biopsy and high-grade cancer (Gleason ⩾7) on biopsy was calculated and compared with overall and high-grade cancer detection rates (CDRs). Receiver operating characteristic curves were generated and the areas under the curves (AUCs) were compared using DeLong's test. RESULTS: Of 595 men included in the study, PCa was detected in 39% (232) by SBx compared with 48% (287) on combined FBx/SBx biopsy. The PCPTRC AUCs for the CDR were similar (P=0.70) for SBx (0.69) and combined biopsy (0.70). For high-grade disease, AUCs for SBx (0.71) and combined biopsy (0.70) were slightly higher, but were not statistically different (P=0.55). CONCLUSIONS: In an MRI-screened population of men undergoing FBx, PCPTRC continues to represent a practical method of accurately stratifying PCa risk.

Comparing nonrigid registration techniques for motion corrected MR prostate diffusion imaging.

PURPOSE: T2-weighted magnetic resonance imaging (MRI) is commonly used for anatomical visualization in the pelvis area, such as the prostate, with high soft-tissue contrast. MRI can also provide functional information such as diffusion-weighted imaging (DWI) which depicts the molecular diffusion processes in biological tissues. The combination of anatomical and functional imaging techniques is widely used in oncology, e.g., for prostate cancer diagnosis and staging. However, acquisition-specific distortions as well as physiological motion lead to misalignments between T2 and DWI and consequently to a reduced diagnostic value. Image registration algorithms are commonly employed to correct for such misalignment. METHODS: The authors compare the performance of five state-of-the-art nonrigid image registration techniques for accurate image fusion of DWI with T2. RESULTS: Image data of 20 prostate patients with cancerous lesions or cysts were acquired. All registration algorithms were validated using intensity-based as well as landmark-based techniques. CONCLUSIONS: The authors' results show that the "fast elastic image registration" provides most accurate results with a target registration error of 1.07 ± 0.41 mm at minimum execution times of 11 ± 1 s.

Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma.

In primary hyperaldosteronism, discriminating bilateral adrenal hyperplasia (BAH) from an aldosterone-producing adenoma (APA) is important because adrenalectomy, which is usually curative in APA, is seldom effective in BAH. We analyzed the results from our most recent 7-yr series to evaluate the predictive value of preoperative noninvasive tests compared with adrenal vein sampling (AVS). Forty-eight patients with hypertensive hyperaldosteronism underwent bedside testing, computed tomography (CT) imaging, and AVS. Those in whom the results of AVS indicated APA underwent adrenalectomy. Twelve (30%) and 14 (34%) of 41 patients with APA had paradoxical falls with ambulation in plasma aldosterone concentration (PAC) and 18-hydroxycorticosterone (18-OH-B), respectively. Twenty-nine (70%) and 26 (65%) APA patients had a rise in PAC and 18-OH-B, respectively, as did all 8 BAH patients. Significant identifiers of BAH were supine PAC values less than 15 ng/dL (P: = 0.04), an increase greater than 60% (P: = 0.02) in PAC with ambulation, and supine 18-OH-B values less than 60 ng/dL (P: = 0.04). CT imaging alone was not predictive for BAH or APA. In our population, patients with a positive bedside test result (e.g. a fall in PAC and/or 18-OH-B) and a unilateral adrenal nodule on CT (10 of 41 patients) could have proceeded directly to adrenalectomy for APA. However, a positive bedside test result with a negative CT or a negative bedside test result regardless of CT findings required AVS to confirm the diagnosis and site of disease.

Central nervous system involvement in Von Hippel-Lindau disease.

Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.

Magnetic resonance angiography of the kidney.

Magnetic resonance angiography (MRA) of the kidneys has become a clinical standard for detecting renal artery stenosis. This test is performed by injecting a bolus of a gadolinium chelate and scanning with a three-dimensional volumetric data collection sensitized to the T1 shortening effects of gadolinium. In addition to displaying the renal arterial anatomy, atherosclerosis within the aorta and iliac arteries is commonly depicted. MRA is a time efficient and safe test when compared with conventional arteriography. Gadolinium-enhanced MRA has proven to have a high sensitivity for detecting stenoses in main and accessory renal arteries. Although false-negative studies are rare, overestimation of the degree of renal stenosis is problematic and may lead to false-positive diagnosis. To some extent this tendency to overestimate stenoses can be compensated for by performing phase contrast MRA, a type of MRA based on accumulated phase differences. As with conventional angiography, MRA is still only an anatomic test which provides little information about the functional significance of a stenosis. It is highly accurate in determining the number of renal arteries, the size of the kidneys, and the presence of any anatomic variants. Ultimately, MRA, needs to be combined with a functional test similar in concept to captopril renography. This test, termed MR renography together with MRA may replace the current multimodalitiy approach to the work-up of renovascular hypertension.

Determination of serum creatinine level before intravenous administration of iodinated contrast medium. A survey.

RATIONALE AND OBJECTIVES: To study the practice of obtaining serum creatinine before administering intravenous iodinated contrast medium and the costs associated with this practice. MATERIALS AND METHODS: In June 1993, a questionnaire was sent to 217 physicians who are members of the Society of Uroradiology or the Society of Computed Body Tomography/Magnetic Resonance. There were 149 respondents who completed a total of 70 questionnaires, providing a response rate of 69% (149/217). RESULTS: The percentage of institutions that always require a serum creatinine before administering intravenous contrast medium for excretory urography, body computed tomography, and head computed tomography was 13%, 20%, and 14%, respectively. In institutions where routine serum creatinine is not required, approximately 60% request a serum creatinine in either insulin-dependent or juvenile type 1 diabetes. The mean maximal acceptable time between the serum creatinine value and contrast administration is 29 days. It takes a mean of 69 minutes to get the results of a stat serum creatinine and costs a mean of 15 dollars for the test. In patients with no risk factors, the mean for the highest serum creatinine value at which respondents still gave contrast was 2.1 mg/dL; in patients with risk factors, the mean was 1.9 mg/dL. There was no correlation between the use of serum creatinine and the number of studies performed in the institution or the type of contrast used. CONCLUSIONS: The practice of requiring a pretest serum creatinine and its interpretation regarding the use of contrast media are quite variable. In view of this disparity in opinion, development and acceptance of a list of patients who are at increased risk for contrast-induced nephropathy may be desirable.

Gadopentetate dimeglumine clearance in renal insufficiency in rabbits.

The total body clearance of gadopentetate dimeglumine (Gd-DTPA) was evaluated in 17 normal rabbits and 11 rabbits with renal insufficiency induced by angioinfarction. Serial measurements of the serum spin lattice relaxation rate (1/T1) were compared with actual gadolinium concentrations as determined by mass spectroscopy. Gadopentetate dimeglumine concentrations measured by both mass spectroscopy and magnetic resonance (MR) relaxometry decreased by two logs in both normals and rabbits with renal impairment by 24 hours and were highly correlated with each other (r = .98). The estimated total body clearance of gadopentetate dimeglumine was 14.1 +/- 0.56 cc/minute for the normal animals and 3.78 +/- 0.19 cc/minute for the impaired rabbits. These results indicate that gadopentetate dimeglumine is excreted rapidly, usually within 24 hours, even in the presence of renal insufficiency.

Enhanced pancreatic CT imaging utilizing a geometric magnification technique.

Computed tomography (CT) using a geometric magnification technique was found to improve spatial resolution in phantom studies when compared with conventional third-generation geometry images. The clinical feasibility of using geometric magnification, small focal spot size, and dynamic contrast enhancement was studied in 143 patients referred to CT for clinically suspected pancreatic disease. This population included 46 patients with a normal pancreas and 36 patients subsequently proven to have primary pancreatic carcinoma. Using this new technique in conjunction with dynamic contrast enhancement resulted in high quality pancreatic images. Despite the limitations in tube current associated with a small focal spot size and low total heat capacity of the system, clinical imaging was not adversely affected. Use of the geometric magnification technique is recommended in departments where it is technically feasible.

Pancreatic neuroendocrine tumors associated with von Hippel Lindau disease: diagnostic and management recommendations.

BACKGROUND: von Hippel Lindau disease (VHL) is an inherited syndrome characterized by tumors of the kidney, adrenal, central nervous system, and pancreas. The incidence and natural history of pancreatic neuroendocrine tumors occurring in VHL are not known. METHODS: From December 1988 through November 1997, 256 patients with VHL were screened with imaging studies, and these data were reviewed from a prospective database. RESULTS: Thirty (12%) of 256 patients had solid pancreatic lesions consistent with neuroendocrine tumors. Fourteen patients underwent resection, and 4 with metastases on imaging studies underwent biopsy only. Of the 14 patients who underwent resection, 11 remain free of disease, 2 have experienced recurrence, and 1 has died of unrelated causes (mean follow-up, 25 months; range, 3 to 73 months). The size of the primary tumor (median, 5 cm; range, 3 to 8 cm) in patients with liver metastases was significantly larger than the size of the primary tumor (median, 2 cm; range, 1 to 5 cm) in patients without liver metastases (P = .0013). CONCLUSIONS: Solid pancreatic lesions were detected in 12% of patients with VHL. Larger primary tumors were associated with liver metastases. Pancreatic imaging to identify neuroendocrine tumors and resection when they reach 2 to 3 cm may prevent the development of hepatic metastases.

Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease.

BACKGROUND: Patients with von Hippel-Lindau disease (VHL) may develop pancreatic neuroendocrine tumors (PNETs), which can behave in a malignant fashion. We prospectively evaluated size criteria for resection of lesions and the role of genotype/phenotype analysis of germline VHL mutations in predicting clinical course. METHODS: From December 1988 through December 1999 we screened 389 patients with VHL. The diagnosis of PNET was made by pathologic analysis of tissues or by radiographic appearance. Germline mutations were determined by quantitative Southern blotting, fluorescence in situ hybridization and complete gene sequencing. RESULTS: Forty-four patients with PNETs have been identified; 25 have undergone surgical resection, 5 had metastatic disease, and 14 are being monitored. No patient who has undergone resection based on tumor size criteria has developed metastases. Patients with PNETs were more likely to have missense mutations (58%), and 4 of 5 patients (80%) with metastatic disease had mutations in exon 3 compared with 18 of 39 (46%) patients without metastatic disease. CONCLUSIONS: Imaging for detection and surgical resection based on size criteria have resulted in the successful management of VHL patients with PNETs. Analysis of germline mutations may help identify patients at risk for PNET and which patients may benefit from surgical intervention.