Erik K. Paulson

Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison.

BACKGROUND The usefulness of currently available colon imaging tests, including air contrast barium enema (ACBE), computed tomographic colonography (CTC), and colonoscopy, to detect colon polyps and cancers is uncertain. We aimed to assess the sensitivity of these three imaging tests. METHODS Patients with faecal occult blood, haematochezia, iron-deficiency anaemia, or a family history of colon cancer underwent three separate colon-imaging studies--ACBE, followed 7-14 days later by CTC and colonoscopy on the same day. The primary outcome was detection of colonic polyps and cancers. Outcomes were assessed by building an aggregate view of the colon, taking into account results of all three tests. FINDINGS 614 patients completed all three imaging tests. When analysed on a per-patient basis, for lesions 10 mm or larger in size (n=63), the sensitivity of ACBE was 48% (95% CI 35-61), CTC 59% (46-71, p=0.1083 for CTC vs ACBE), and colonoscopy 98% (91-100, p<0.0001 for colonoscopy vs CTC). For lesions 6-9 mm in size (n=116), sensitivity was 35% for ACBE (27-45), 51% for CTC (41-60, p=0.0080 for CTC vs ACBE), and 99% for colonoscopy (95-100, p<0.0001 for colonoscopy vs CTC). For lesions of 10 mm or larger in size, the specificity was greater for colonoscopy (0.996) than for either ACBE (0.90) or CTC (0.96) and declined for ACBE and CTC when smaller lesions were considered. INTERPRETATION Colonoscopy was more sensitive than other tests, as currently undertaken, for detection of colonic polyps and cancers. These data have important implications for diagnostic use of colon imaging tests.

Efficacy, Safety, and Biomarkers of Neoadjuvant Bevacizumab, Radiation Therapy, and Fluorouracil in Rectal Cancer: A Multidisciplinary Phase II Study

PURPOSE To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. PATIENTS AND METHODS In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. RESULTS Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. CONCLUSION Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA.

BACKGROUND Studies have suggested an increased risk of peritoneal seeding in patients with pancreatic cancer diagnosed by percutaneous FNA. EUS-FNA is an alternate method of diagnosis. The aim of this study was to compare the frequency of peritoneal carcinomatosis as a treatment failure pattern in patients with pancreatic cancer diagnosed by EUS-FNA vs. percutaneous FNA. METHODS Retrospective review of patients with non-metastatic pancreatic cancer identified 46 patients in whom the diagnosis was made by EUS-FNA and 43 with the diagnosis established by percutaneous FNA. All had neoadjuvant chemoradiation. Patients underwent restaging CT after completion of therapy, followed by attempted surgical resection if there was no evidence of disease progression. RESULTS There were no significant differences in tumor characteristics between the two study groups. In the EUS-FNA group, one patient had developed peritoneal carcinomatosis compared with 7 in the percutaneous FNA group (2.2% vs. 16.3%; p<0.025). No patient with a potentially resectable tumor in the EUS-FNA group had developed peritoneal carcinomatosis. CONCLUSIONS Peritoneal carcinomatosis may occur more frequently in patients who undergo percutaneous FNA compared with those who have EUS-FNA for the diagnosis of pancreatic cancer. A concern for peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS-guided FNA is recommended as the method of choice for diagnosis in patients with potentially resectable pancreatic cancer.

Dual-energy multidetector CT: how does it work, what can it tell us, and when can we use it in abdominopelvic imaging?

Dual-energy CT provides information about how substances behave at different energies, the ability to generate virtual unenhanced datasets, and improved detection of iodine-containing substances on low-energy images. Knowing how a substance behaves at two different energies can provide information about tissue composition beyond that obtainable with single-energy techniques. The term K edge refers to the spike in attenuation that occurs at energy levels just greater than that of the K-shell binding because of the increased photoelectric absorption at these energy levels. K-edge values vary for each element, and they increase as the atomic number increases. The energy dependence of the photoelectric effect and the variability of K edges form the basis of dual-energy techniques, which may be used to detect substances such as iodine, calcium, and uric acid crystals. The closer the energy level used in imaging is to the K edge of a substance such as iodine, the more the substance attenuates. In the abdomen and pelvis, dual-energy CT may be used in the liver to increase conspicuity of hypervascular lesions; in the kidneys, to distinguish hyperattenuating cysts from enhancing renal masses and to characterize renal stone composition; in the adrenal glands, to characterize adrenal nodules; and in the pancreas, to differentiate between normal and abnormal parenchyma.

Pneumatosis intestinalis in the adult: benign to life-threatening causes.

OBJECTIVE The frequency of detection of pneumatosis intestinalis (PI) appears to be increasing. This increase may be the result of increased CT use. New medications and surgical procedures have been reported to be associated with an increase in the incidence of PI. The purpose of this review is to provide an update on the imaging features and clinical conditions associated with PI. CONCLUSION This article illustrates the imaging findings of PI due to benign and life-threatening causes, with emphasis placed on describing newly associated conditions and also the imaging appearance on CT.

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

AbstractBackground: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT. Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.

Renal Stone Assessment with Dual-Energy Multidetector CT and Advanced Postprocessing Techniques: Improved Characterization of Renal Stone Composition—Pilot Study

PURPOSE To prospectively evaluate the capability of noninvasive, simultaneous dual-energy (DE) multidetector computed tomography (CT) to improve characterization of human renal calculi in an anthropomorphic DE renal phantom by introducing advanced postprocessing techniques, with ex vivo renal stone spectroscopy as the reference standard. MATERIALS AND METHODS Fifty renal calculi were assessed: Thirty stones were of pure crystalline composition (uric acid, cystine, struvite, calcium oxalate, calcium phosphate, brushite), and 20 were of polycrystalline composition. DE CT was performed with a 64-detector CT unit. A postprocessing algorithm (DECT(Slope)) was proposed as a pixel-by-pixel approach to generate Digital Imaging and Communications in Medicine dataset gray-scale-encoding ratios of relative differences in attenuation values of low- and high-energy DE CT. Graphic analysis, in which clusters of equal composition were identified, was performed by sorting attenuation values of color composition-encoded calculi in an ascending sequence. Multivariate general linear model analysis was used to determine level of significance to differentiate composition on native and postprocessed DE CT images. RESULTS Graphic analysis of native DE CT images was used to identify clusters for uric acid (453-629 HU for low-energy CT, 443-615 HU for high-energy CT), cystine (725-832 HU for low-energy CT, 513-747 HU for high-energy CT), and struvite (1337-1530 HU for low-energy CT, 1007-1100 HU for high-energy CT) stones; high-energy clusters showed attenuation value overlap. Polycrystalline calcium oxalate and calcium phosphate calculi were found throughout the entire spectrum, and dense brushite had attenuation values of more than 1500 HU for low-energy CT and more than 1100 HU for high-energy CT. The DE CT algorithm was used to generate specific identifiers for uric acid (77-80 U(Slope), one outlier), cystine (70-71 U(Slope)), struvite (56-60 U(Slope)), calcium oxalate and calcium phosphate (17-59 U(Slope)), and brushite (4-15 U(Slope)) stones. Statistical analysis showed that all compositions were identified unambiguously with the DECT(Slope) algorithm. CONCLUSION DE multidetector CT with advanced postprocessing techniques improves characterization of renal stone composition beyond that achieved with single-energy multidetector CT acquisitions with basic attenuation assessment.

Computerized tomographic colonography: Performance evaluation in a retrospective multicenter setting

BACKGROUND & AIMS No multicenter study has been reported evaluating the performance and interobserver variability of computerized tomographic colonography. The aim of this study was to assess the accuracy of computerized tomographic colonography for detecting clinically important colorectal neoplasia (polyps >or=10 mm in diameter) in a multi-institutional study. METHODS A retrospective study was developed from 341 patients who had computerized tomographic colonography and colonoscopy among 8 medical centers. Colonoscopy and pathology reports provided the standard. A random sample of 117 patients, stratified by criterion standard, was requested. Ninety-three patients were included (47% with polyps >or=10 mm; mean age, 62 years; 56% men; 84% white; 40% reported colorectal symptoms; 74% at increased risk for colorectal cancer). Eighteen radiologists blinded to the criterion standard interpreted computerized tomography colonography examinations, each using 2 of 3 different software display platforms. RESULTS The average area under the receiver operating characteristic curve for identifying patients with at least 1 lesion >or=10 mm was 0.80 (95% lower confidence bound, 0.74). The average sensitivity and specificity were 75% (95% lower confidence bound, 68%) and 73% (95% lower confidence bound, 66%), respectively. Per-polyp sensitivity was 75%. A trend was observed for better performance with more observer experience. There was no difference in performance across software display platforms. CONCLUSIONS Computerized tomographic colonography performance compared favorably with reported performance of fecal occult blood testing, flexible sigmoidoscopy, and barium enema. A prospective study evaluating the performance of computerized tomography colonography in a screening population is indicated.

Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

BackgroundNeoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. MethodsSince 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.ResultsThe estimated overall survival (median ± SE) in the entire group of patients undergoing resection was 23 ± 4.2 months, with an estimated 3-year survival of 37% ± 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.ConclusionsHistological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Radiation Dose to the Female Breast from 16-MDCT Body Protocols

OBJECTIVE The objective of our study was to determine the radiation dose to the female breast from current 16-MDCT body examinations. MATERIALS AND METHODS Metal oxide semiconductor field effect transistor (MOSFET) detectors were placed in four quadrants of the breast of a female-configured anthropomorphic phantom to determine radiation dose to the breast. Imaging was performed on a 16-MDCT scanner (LightSpeed, GE Healthcare) using current clinical protocols designed to assess pulmonary embolus (PE) (140 kVp, 380 mA, 0.8-sec rotation, 16 x 1.25 mm collimation), appendicitis (140 kVp, 340 mA, 0.5-sec rotation, 16 x 0.625 mm collimation), and renal calculus (140 kVp, 160 mA, 0.5-sec rotation, 16 x 0.625 mm collimation). RESULTS Radiation dose to the breast ranged from 4 to 6 cGy for the PE protocol and up to 1-2 cGy in the inferior aspect of the right breast and lateral aspect of the left breast for the appendicitis protocol. The renal calculus protocol yielded less than 150 microGy absorbed breast dose. CONCLUSION Current clinical chest and abdomen protocols result in vairable radiation doses to the breast. The magnitude of exposure may have implications for imaging strategies.