Brian Morse

Dual-Energy (Spectral) CT: Applications in Abdominal Imaging

Dual-energy imaging is a promising new development in computed tomography (CT) that has the potential to improve lesion detection and characterization beyond levels currently achievable with conventional CT techniques. In dual-energy CT (DECT), the simultaneous use of two different energy settings allows the differentiation of materials on the basis of their energy-related attenuation characteristics (material density). The datasets obtained with DECT can be used to reconstruct virtual unenhanced images as well as iodinated contrast material-enhanced material density images, obviating the standard two-phase (unenhanced and contrast-enhanced) scanning protocol and thus helping minimize the radiation dose received by the patient. Single-source DECT, which is performed with rapid alternation between two energy levels, can also generate computed monochromatic images, which are less vulnerable to artifacts such as beam hardening and pseudoenhancement and provide a higher contrast-to-noise ratio than polychromatic images produced by conventional CT. Familiarity with the capabilities of DECT may help radiologists improve their diagnostic performance.

The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society

Abstract Small bowel neuroendocrine tumors (SBNETs) have been increasing in frequency over the past decades, and are now the most common type of small bowel tumor. Consequently, general surgeons and surgical oncologists are seeing more patients with SBNETs in their practices than ever before. The management of these patients is often complex, owing to their secretion of hormones, frequent presentation with advanced disease, and difficulties with making the diagnosis of SBNETs. Despite these issues, even patients with advanced disease can have long-term survival. There are a number of scenarios which commonly arise in SBNET patients where it is difficult to determine the optimal management from the published data. To address these challenges for clinicians, a consensus conference was held assembling experts in the field to review and discuss the available literature and patterns of practice pertaining to specific management issues. This paper summarizes the important elements from these studies and the recommendations of the group for these questions regarding the management of SBNET patients.

PET/CT Fusion Scan Prevents Futile Laparotomy in Early Stage Pancreatic Cancer.

Background Surgical resection with negative margins is the only curative approach for pancreatic cancer. A paucity of data exists in using PET/CT scan as staging workup in resectable pancreatic cancer. The aim of this study is to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable or borderline resectable pancreatic cancer. Methods Patients were included using institutional PET/CT data base incorporating National Oncologic PET Registry with diagnosis of resectable or borderline resectable pancreatic cancer from 2005 to 2012. Clinical, radiographic, and pathologic characteristics were evaluated. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered secondary to PET/CT. Results We identified 285 patients with early stage pancreatic cancer who received PET/CT as part of initial staging workup. Upon initial workup (CT + EUS), 62% of patients were considered resectable, and 38% were borderline resectable. Addition of PET/CT scan changed the management in 10.9% (n = 31) of the patients (95% CI, 8%–15%). Metastatic lesions were confirmed with biopsy in 19 patients (61%). The proportion of change in treatment plan was significantly higher in patients who were initially considered to have borderline resectable compared with resectable malignancy (17% vs 7%, P = 0.019). In 199 patients who underwent surgery, 18.1% (n = 36) were found to have metastatic disease intraoperatively. Conclusions PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary surgery. The role of PET/CT scan should be validated in prospective study.

A phase II study of axitinib in advanced neuroendocrine tumors

Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29months, we observed a median PFS of 26.7months (95% CI, 11.4-35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4-45.3), and the median TTF was 9.6months (95% CI, 5.5-12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.

Cell-surface markers for colon adenoma and adenocarcinoma

Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

Treatment of Metastatic Neuroendocrine Tumors of the Thymus with Capecitabine and Temozolomide: A Case Series

Background: Metastatic neuroendocrine tumors of the thymus are exceedingly rare with an annual incidence of approximately 0.2 per 1,000,000. They are highly resistant to therapy and there have been no reports of an objective radiographic response to treatment. Materials and Methods: The authors retrospectively evaluated 3 patients with progressive, metastatic neuroendocrine tumors of the thymus who were treated with a combination of capecitabine and temozolomide. Radiographic scans were evaluated and response assessed using RECIST criteria. Results: One patient experienced a partial radiographic response, another patient experienced a minor response and the third patient experienced stable disease as the best response to treatment. Conclusion: The combination of capecitabine and temozolomide appears to be active in a rare neuroendocrine malignancy that is generally refractory to systemic therapy. Prospective multicenter trials are needed to validate this strategy.

Magnetic Resonance Imaging of Neuroendocrine Tumor Hepatic Metastases: Does Hepatobiliary Phase Imaging Improve Lesion Conspicuity and Interobserver Agreement of Lesion Measurements?

Objective The aim of this study was to determine if magnetic resonance imaging (MRI) performed with hepatobiliary phase imaging results in higher lesion conspicuity and produces lesion measurements with higher interobserver agreement than other MRI sequences when imaging neuroendocrine hepatic metastases. Methods Patients who had MRIs with both gadoxetate disodium and gadopentetate dimeglumine contrast within a 6-month span were identified, and 23 hepatic lesions were selected. Three radiologists and 1 oncologist measured the greatest diameter of each lesion on the following sequences: T2 weighted, T1 weighted, postcontrast (dynamic, delayed, and hepatobiliary phase), and diffusion weighted. Signal intensity ratio (SIlesion/SIliver) and contrast-to-noise ratio ([SIlesion – SIliver]/noise) were calculated for all lesions on each sequence. The interobserver agreement of measurements on each sequence was calculated using concordance correlation coefficient. Results Diffusion-weighted sequences had the highest signal intensity ratio ranging from 147% to 187% (vs other sequences range of 19.6%–130%). One hepatobiliary sequence had the highest contrast-to-noise ratio with a value of 41 (vs other sequences range of 3.2–28.1). Lesion measurements on all sequences showed high-interobserver agreement, with hepatobiliary sequences showing some of the highest levels of agreement. Conclusions Our results support the use of contrast agents with hepatobiliary excretion when imaging neuroendocrine tumors metastatic to liver.

Pearls and pitfalls of response evaluation criteria in solid tumors (RECIST) v1.1 non-target lesion assessment

Oncologic imaging is an important facet of abdominal imaging that radiologists encounter nearly every day. Many oncology clinical trials utilize response evaluation criteria in solid tumors (RECIST) version 1.1 which divides tumor sites into target and non-target lesions. Although RECIST v1.1 provides clear instructions regarding the use of imaging in clinical trials, errors in response assessment still occur using these criteria. This is especially true of response assessment with regards to non-target lesions which involve rules which are less well-defined and somewhat subjective. This pictorial essay will review RECIST v1.1 guidelines and common non-target lesion errors which can occur at baseline and follow-up response assessment.

Congenital Anomaly Detected During Work-up of Cystic Pancreatic Lesion.

Question: A 60-year-old man presented to an internal medicine physician to establish care and the initial workup revealed mildly elevated liver function tests (LFTs). CT of the abdomen was performed to evaluate the elevated LFTs and found a 4.4-cm cystic lesion in the uncinate process of the pancreas (Figure A). Further workup, which included endoscopic ultrasound-guided fine-needle aspiration, diagnosed the lesion as a side branch intraductal papillary mucinous neoplasm. He was referred to our institution for further management. At initial evaluation, the patient’s LFTs had normalized (aspartate aminotransferase, 45 IU/L; alanine aminotransferase, 39 IU/L; alkaline phosphatase, 102 IU/L; total bilirubin, 0.40 mg/dL). His hemogram and routine chemistry tests were normal with the exception of mildly elevated glucose (serum glucose, 111mg/dL). The patient was obese with a body mass index of 34 kg/m. The physical examination was otherwise unremarkable. A maximum intensity projection reformatted image from the patient’s CT in the coronal plane (Figure B) shows the relevant anatomy (A, main portal vein; B, superior mesenteric vein; C, splenic vein; D, inferior vena cava; E, hepatic vein). Another maximum intensity projection reformatted image from a CT in the coronal plane of a normal patient is shown in Figure C for comparison (A, main portal vein; B, superior mesenteric vein; C, splenic vein; D, inferior vena cava; E, hepatic vein). What is the incidentally detected congenital anomaly in this patient? Look on page 34 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Contents Vol. 97

D.H. Abbott, Madison, Wisc. E. Arzt, Buenos Aires A.V. Babwah, London, Ont. T. Bartness, Atlanta, Ga. C.L. Bethea, Beaverton, Oreg. D.W. Brann, Augusta, Ga. B. Canny, Monash, Vic. M. Caplin, London K. Catt, Bethesda, Md. A. Chodobski, Providence, R.I. S.L. Dickson, Gothenburg J. Drouin, Montreal, Que. P.J. Enriori, Monash, Vic. W. Farrell, Keele M. Freeman, Tallahasse, Fla. A.C. Gore, Austin, Tex. K. Grove, Beaverton, Oreg. T. Harmar, Edinburgh A. Herbison, Dunedin J. Herman, Cincinnati, Ohio J.J. Hirst, Callaghan, N.S.W. T. Hökfelt, Stockholm U. Kaiser, Boston, Mass. K. Kim, Seoul J.Z. Kiss, Geneva A.C. Latronico, São Paulo G. Leng, Edinburgh J. Levine, Evanston, Ill. C. Libertun, Buenos Aires C. Llorens-Cortes, Paris A. Lomniczi, Beaverton, Oreg. A. Loudon, Manchester Z.-L. Lu, Edinburgh G. Martinez de la Escalera, Querétaro R. Melcangi, Milano I. Modlin, New Haven, Conn. Z. Naor, Tel Aviv M. Palkovits, Budapest I. Parhar, Kuala Lumpur D.W. Pfaff, New York, N.Y. T.M. Plant, Pittsburgh, Pa. J. Reul, Bristol R. Reynolds, Edinburgh E. Rissman, Charlottesville, Va. J.L. Roberts, San Antonio, Tex. I. Robinson, London P. Ruszniewski, Clichy W. Schlegel, Geneva D. Skinner, Laramie, Wyo. M. Sleeman, Clayton, Vic. J. Smith, Perth, W.A. E. Spinedi, La Plata R. Steiner, Seattle, Wash. E. Terasawa, Madison, Wisc. A. Tilbrook, Roseworthy, S.A. E. Wagner, Pomona, Calif. B. Walker, Edinburgh H. Watanobe, Chiba M. Watt, Clayton, Vic. M. Wierman, Denver, Colo. J. Wingfield, Seattle, Wash. S. Wray, Bethesda, Md. International Journal for Basic and Clinical Studies on Neuroendocrine Relationships