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Background: The 2015 American Thyroid Association (ATA) thyroid nodule guidelines recommend selecting nodules for biopsy based on a sonographic pattern classification. These patterns were developed based on features of differentiated thyroid cancer. This study aimed to evaluate the performance and the inter-observer agreement of this classification system in medullary thyroid carcinoma (MTC)., Methods: The medical records of all patients with MTC evaluated at the authors' institution between 1998 and 2014 were retrospectively reviewed. Only patients with presurgical thyroid ultrasound available for review were included in the study. Five independent reviewers assessed the stored ultrasound images for composition, echogenicity, margins, presence of calcifications, and extrathyroidal extension for each nodule. The presence of suspicious lymph nodes was also evaluated when presurgical lateral neck ultrasound was available for review. Each nodule was classified according to the ATA sonographic patterns. Inter-observer agreement was calculated for each sonographic feature and for the sonographic patterns. To validate the findings, a systematic review of the literature and meta-analysis on the sonographic features of MTC was conducted., Results: In this institutional cohort, the inter-observer agreement for individual sonographic features was moderate to good (κ = 0.45-0.71), and for the ATA classification it was good (κ = 0.72). Ninety-seven percent (29/30) of the MTCs were classified in the intermediate or high suspicion patterns. A total of 249 MTCs were included in the meta-analysis. Based on pooled frequencies for solid composition and hypoechogenicity, >95% of MTCs would be classified at least in the intermediate suspicion pattern, warranting the lowest-size threshold for biopsy (≥1 cm)., Conclusions: The sonographic patterns proposed by the ATA perform well in MTC, and inter-observer agreement is good to very good.

Unlabelled: In this study we developed 25 computed tomography descriptors among 117 patients with lung adenocarcinoma to semiquantitatively assess their association with overall survival. Pleural attachment was significantly associated with an increased risk of death and texture was most important for distinguishing histological subtypes. This approach has the potential to support automated analyses and develop decision-support clinical tools., Background: Computed tomography (CT) characteristics derived from noninvasive images that represent the entire tumor might have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival., Patients and Methods: An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n = 117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that might differentiate histological subtypes., Results: Characteristics significantly associated with overall survival included pleural attachment (P < .001), air bronchogram (P = .03), and lymphadenopathy (P = .02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.53-6.70) and among patients with lepidic predominant adenocarcinomas (HR, 5.85; 95% CI, 1.75-19.59), and lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR, 3.07; 95% CI, 1.09-8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the 2 subtypes., Conclusion: A subset of the semiquantitative characteristics described herein has prognostic importance and provides the ability to distinguish between different histological subtypes of lung adenocarcinoma., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Multiple myeloma (MM) remains an incurable cancer. Treatment often is initiated at the time patients experience a progressive increase in tumor burden. The authors of this report investigated magnetic resonance imaging of the bone marrow (BM-MRI) as a novel approach to quantify disease burden and validated a staging system by correlating BM-MRI with common clinical and laboratory parameters., Methods: The extent of bone marrow involvement was evaluated by BM-MRI. Clinical and laboratory parameters were assessed in patients with active MM, and correlations between variables were assessed statistically. Bone marrow involvement by BM-MRI was defined as stage A (0%), stage B (<10%), stage C (10%-50%), and stage D (>50%)., Results: In total, 170 consecutive patients were evaluated (77 women and 93 men), including 144 patients who had active MM. The median age was 61 years (age range, 35-83 years). Advance stage disease (stage >I) based on Durie-Salmon (DS) staging or International Staging System (ISS) criteria was observed in 122 patients (84%) and 77 patients (53%), respectively. Lytic bone disease was noted in 120 patients (83%). There was a significant association between BM-MRI involvement and DS stage (P = .0006), ISS stage (P = .0001), the presence of lytic bone disease (P < .0001) and mean beta-2 microglobulin levels (P < .0001). Among the patients with previously untreated MM, there was a significant association between BM-MRI stage and overall survival (OS) (univariate P = .013; multivariate P = .045). Plasmacytosis on bone marrow biopsy at diagnosis was not predictive of OS (P = .91)., Conclusions: BM-MRI is a novel approach for quantifying disease burden in patients with MM. The current investigation in a large cohort of nontransplantion MM patients demonstrated that the extent of bone marrow involvement determined by BM-MRI correlates accurately with other conventional parameters of disease burden and can independently predict survival in patients with MM at the time of initial diagnosis., (Copyright 2010 American Cancer Society.)

For most solid neoplasms, medical imaging is a vital component of tumor staging and surveillance. Imaging strategies vary according to the type and grade of primary neoplasm, tumor stage at diagnosis, tumor markers, previous therapies, and patient symptoms. In this article, we address imaging of individual organs (lung, liver, adrenals) and outline imaging strategies for specific types of neoplasms.

In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.

The combination of computed tomographic (CT) venography and pulmonary angiography (CTVPA) was initially described in 1998 as a single comprehensive noninvasive imaging examination for suspected thromboembolic disease. It allowed the identification of pulmonary embolism as well as deep venous thrombosis (DVT) in the abdomen, pelvis, thighs, and calves. The venographic portion of CTVPA has now been studied by multiple researchers and has been shown to be an accurate imaging study for the thigh veins in comparison with lower extremity sonography. In contrast to sonography, however, CTVPA readily and rapidly permits evaluation of the inferior vena cava, the pelvic veins, the calf veins, and all of the superficial venous system. Complex venous anatomy can be surveyed, an additional sonographic study is not required, and only a few extra minutes and images are required over and above CT pulmonary angiography. A review of 957 recent cases of suspected pulmonary embolism examined with CTVPA revealed an overall 10.5% frequency of DVT, with a nearly equal distribution of thrombosis at the common femoral, superficial femoral, popliteal, and deep calf veins. Although a variety of protocols for CTVPA may be implemented, including a contiguous helical acquisition, obtaining 5- or 10-mm-thick images every 4 cm provides a high degree of accuracy and decreases overall radiation dose., (Copyright RSNA, 2002)

Objective: Combined CT venography and helical pulmonary angiography is a new diagnostic test that permits radiologists to check both the pulmonary arteries for embolism and the deep veins of the abdomen, pelvis, and legs for thrombosis in a single examination. The purpose of this study was to determine the degree of venous enhancement routinely obtained using this combined CT examination., Materials and Methods: We identified all patients at a single institution who, during a 29-month period, had symptoms suggestive of pulmonary embolism and who underwent CT venography and helical pulmonary angiography. The examinations were performed after the patients received a rapid (3--5 mL/sec) IV injection of 150 mL of nonionic contrast medium (240 mg I/mL). CT venography of the abdomen, pelvis, and lower extremities was performed as follows: Beginning 3 min after the start of contrast medium infusion for helical CT pulmonary angiography, 1-cm axial images obtained at 5-cm intervals were acquired from an area ranging from the diaphragm to the calves. Patients who had evidence of deep venous thrombosis on CT scans were excluded from further analysis. The venous portions of the remaining 429 examinations were retrospectively reviewed at a CT console or workstation by one of two radiologists, and Hounsfield unit measurements were recorded from the inferior vena cava as well as from the right and left external or internal iliac, common femoral, superficial femoral, and popliteal veins. A single Hounsfield unit measurement was obtained from the center of each vessel using a region of interest that was approximately half the diameter of the vessel. Mean Hounsfield unit measurements were then calculated for these venous stations., Results: Mean Hounsfield unit measurements at the inferior vena cava and at the right and left external or internal iliac veins were 97, 95, and 95 H, respectively. Mean measurements at the common femoral veins were 95 H for both the right and left; the mean measurements at the superficial femoral veins were 91 H for both the right and left, and those at the popliteal veins were 97 H for the right and 94 H for the left., Conclusion: CT venography of the abdomen, pelvis, and lower extremities begun 3 min after the start of contrast medium infusion for helical CT pulmonary angiography routinely produced high mean levels of venous enhancement.

Purpose: To determine the frequency and location of deep venous thrombosis at computed tomographic (CT) venography after CT pulmonary angiography in a large series of patients clinically suspected of having pulmonary embolism and to compare the accuracy of CT venography with lower-extremity venous sonography., Materials and Methods: Venous phase images were acquired from the diaphragm to the upper calves after completion of CT pulmonary angiography in 650 patients (373 women, 277 men; age range, 18-99 years; mean age, 63 years) to determine the presence and location of deep venous thrombosis. Results of CT venography were compared with those of bilateral lower-extremity venous sonography in 308 patients., Results: A total of 116 patients had pulmonary embolism and/or deep venous thrombosis, including 27 patients with pulmonary embolism alone, 31 patients with deep venous thrombosis alone, and 58 patients with both. Among 89 patients with deep venous thrombosis, thrombosis was bilateral in 26, involved the abdominal or pelvic veins in 11, and was isolated to the abdominal or pelvic veins in four. In patients in whom sonographic correlation was available, CT venography had a sensitivity of 97% and a specificity of 100% for femoropopliteal deep venous thrombosis., Conclusion: Combined CT venography and pulmonary angiography can accurately depict the femoropopliteal deep veins, permitting concurrent testing for venous thrombosis and pulmonary embolism. CT venography also defines pelvic or abdominal thrombus, which was seen in 17% of patients with deep venous thrombosis.

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.

Background: Oncologic literature cites many different definitions of critical response measurements., Patients and Methods: Response criteria (RC) for non-Hodgkin's lymphoma (NHL) were developed by lymphoma experts, endorsed by international lymphoma clinicians, and applied to a 166-patient rituximab (Rituxan, MabThera) trial by a third-party, blinded panel of NHL experts (LEXCOR). Retrospectively, we analyzed this data using variations of the original RC and comparing with recently published RC., Results: The definition of a 'normal' lymph node affected the complete response (CR) rate (< or = 1.0 x 1.0 cm, 6%; < or = 1.5 x 1.5 cm, 18%; < or = 2.0 x 2.0 cm, 28%); overall response rate (ORR) was not affected. CR rates increased progressively without > or = 28 days response confirmation: 12% vs. 6% (< or = 1.0 x 1.0 cm), 26% vs. 18% (< or = 1.5 x 1.5 cm), and 36% vs. 28% (< or = 2.0 x 2.0 cm). CR rate and duration of response (DR) were unaffected when only the six largest, rather than all lesions, were measured. When the new RC were applied, CR rate (32%) was higher and DR (13.9 months) and time to progression (15.6 months) were shorter in complete responders., Conclusions: Standard RC must be consistently and rigorously applied for accurate comparisons between studies.

A growing consensus is that pulmonary embolism and thrombosis represent different aspects of the same disease, and a single study that accurately defines both pulmonary emboli and deep venous thrombosis would be a desirable examination. The purpose of this pictorial review is to demonstrate the extra-thoracic findings on the venous phase of such a study, which combines computed tomographic venography and pulmonary angiography.

Objective: Combined CT venography and pulmonary angiography is a new diagnostic test that evaluates both pulmonary embolism and deep venous thrombosis (DVT) in a single study. Our purpose was to compare the CT venous findings with lower extremity venous sonography., Subjects and Methods: Seventy-one consecutive patients with suspected pulmonary embolism underwent helical CT pulmonary angiography during rapid i.v. infusion of contrast medium. Axial scans at 5-cm intervals from the patient's upper calves to the diaphragm were generated 3.5 min after the beginning of contrast medium injection. CT venous phase images were interpreted prospectively and compared with subsequent bilateral lower extremity venous sonography performed within 12 hr., Results: DVT was revealed by CT venous phase images in 19 patients, 12 of whom also had pulmonary embolism. CT and sonographic findings correlated exactly in the femoropopliteal deep venous system, where most pulmonary emboli originate. CT venous phase images also revealed pelvic extension of DVT in six patients and isolated vena cava thrombus in one patient., Conclusion: CT venous phase imaging at the time of CT pulmonary angiography is comparable with venous sonography in the evaluation of femoropopliteal DVT. The iliac veins and vena cava, vessels poorly shown on sonography but sometimes the source of significant pulmonary emboli, are also depicted by CT venography.

Occult primary breast carcinoma presenting as isolated ipsilateral axillary lymph node metastases in patients with normal mammograms and normal physical exams accounts for less than 1% of all breast carcinomas. Contrast-enhanced magnetic resonance imaging (MRI) may identify the site of primary breast carcinoma and effect management of these patients. We report on eight consecutive women evaluated in our multidisciplinary clinic who had biopsy-proven metastatic adenocarcinomas to axillary lymph nodes and occult primary carcinomas. Each patient underwent MRI at 1.5 T with a volumetric fast-spoiled gradient-echo (3D FSPGR) pulse sequence before and after injection of gadopentetate dimeglumine. Wire localization of suspicious areas of enhancement was performed under MRI or mammography guidance followed by surgical excision. Seven (88%) of the eight normal mammograms showed dense (>50%) breast parenchyma. In two (25%) of the eight patients, suspicious focal or regional enhancement was seen on MRI. Following wire localization and excision, pathologic exam showed an invasive ductal carcinoma and ductal carcinoma in situ with invasion corresponding to the MRI enhancement in the two cases. Breast MRI can identify the primary tumor site and influence management of patients presenting with clinically and mammographically occult primary breast carcinomas.

Background: The proximity of a hepatic tumor to major vessels and bile ducts limits the use of cryotherapy because of the potential damage to these structures. However, the effects of cryotherapy on major hepatic vessels and bile ducts are not well understood., Methods: Nine pigs underwent laparotomy and intraoperative ultrasound to identify hepatic vessels larger than 5.0 mm. Cryotherapy consisting of two freeze-thaw cycles was performed, incorporating the identified vessel. In four pigs the Pringle maneuver was performed to determine the effects of partial vascular occlusion on the hepatic parenchyma and structures undergoing cryotherapy. The animals were sacrificed 30 days postoperatively, and the livers were processed for histologic examination., Results: Eight of the nine livers had vessels larger than 5.0 mm incorporated into the iceball, with all vessels having evidence of infarction but remaining patent. All the livers had major bile ducts incorporated in the iceball, with eight having evidence of infarction. The Pringle maneuver had no real effect on the degree of vessel and bile duct infarction. There was no incidence of hepatic bleeding, liver fracture, bile leak, or hemobilia., Conclusions: Cryotherapy results in the infarction of major hepatic vessels and bile ducts but can be safely performed in the porcine model. Proximity of tumors to major vascular and biliary structures may not be a contraindication to the use of cryotherapy. Further studies are necessary to determine whether cryotherapy can be used in humans.

We sought to determine how rates of sonographically detected deep venous thrombosis correlate with presenting symptoms in cancer patients. We performed venous sonography in 588 cancer patients with clinically suspected lower extremity deep venous thrombosis. Results were correlated with clinical findings. Deep venous thrombosis was diagnosed in 32% of patients with unilateral lower extremity symptoms and in 17% of patients with bilateral symptoms. Patients with unilateral symptoms of pain and swelling, swelling alone, or pain alone had significantly different rates of deep venous thrombosis (47%, 31%, and 16%, respectively). In patients with bilateral leg symptoms, deep venous thrombosis was significantly more likely when symptoms were not bilaterally symmetric.

Purpose: To determine whether dynamic magnetic resonance (MR) imaging enhancement parameters are associated with vessel density of malignant and benign breast lesions., Materials and Methods: Forty-five patients with 48 breast lesions underwent gadolinium-enhanced spoiled gradient-recalled echo (SPGR) MR imaging followed by excisional biopsy and Factor VIII staining and vessel density measurement in the lesions., Results: The vessel densities were not significantly different in 25 malignant breast lesions as compared to 23 benign breast lesions. Among all 48 lesions, greater MR enhancement showed an association with increased vessel density. Seventy-four percent of all lesions with MRI enhancement amplitude greater or equal to three times post-precontrast ratio had vessel densities greater than the median of 172 as compared to 34% of lesions with enhancement amplitude less than three times, p = 0.02. The rate and washout of MR enhancement showed no significant association with vessel density., Conclusion: Although there is an overall significant association between greater MRI enhancement amplitude and vessel density, MRI gadolinium enhancement of breast lesions is not an accurate predictor of vessel density.

Our purpose was to determine whether the expression of cathepsin D, a proteolytic enzyme implicated in basement membrane degradation, is associated with dynamic magnetic resonance imaging (MRI) enhancement of breast lesions. Forty-five patients with 48 breast lesions underwent gadolinium-enhanced spoiled gradient recalled echo MRI followed by excisional biopsy and cathepsin D staining and semiquantitative measurement in the lesions. There was no significant difference in cathepsin D staining of 25 malignant and 23 benign breast lesions. A significant association was seen between high cathepsin D staining and positive axillary lymph nodes in invasive carcinomas. Nine of nine (100%) node-positive carcinomas had high cathepsin D, as compared to three of seven (43%) node-negative carcinomas (P = 0.02). No significant associations were observed between cathepsin D staining and MRI enhancement amplitude, rate, or washout. Cathepsin D has no effect upon MRI gadolinium enhancement of malignant and benign breast lesions but is associated with positive axillary lymph nodes in invasive carcinomas.

Background: There is little information regarding associations between magnetic resonance imaging (MRI) enhancement and biologic parameters of breast carcinoma. A prospective study was undertaken to correlate MRI dynamic contrast enhancement features with cell proliferative activity, as determined by DNA S-phase percentage., Methods: Seventeen patients with invasive breast cancer underwent MRI at 1.5 tesla using a dynamic gadolinium-enhanced spoiled gradient recall echo technique. DNA analysis of samples of the excised lesions was then performed using flow cytometry., Results: Invasive carcinomas with high DNA S-phase percentages (> or = 6.9%, the median value in this study), a measure of increased cell proliferation, were associated with a peripheral MRI enhancement pattern in 4 of 6 (67%) lesions compared with 0 of 11 carcinomas with lower DNA S-phase percentages (< or = 6.9%) (P = 0.006). There was no significant association between a high DNA S-phase percentage and greater MRI enhancement amplitude, rate, or washout. There was no significant association between aneuploid DNA content and any MRI enhancement feature., Conclusions: Increased cell proliferation in invasive breast carcinoma, as determined by high DNA S-phase percentage, is significantly associated with a peripheral MRI enhancement pattern but unrelated to greater MRI enhancement amplitude, rate, or washout.

Purpose: To prospectively correlate dynamic contrast enhancement at magnetic resonance (MR) imaging with mammographic and pathologic features of suspect breast lesions., Materials and Methods: Forty-nine patients with 51 breast lesions underwent gadolinium-enhanced spoiled gradient-recalled echo (SPGR) MR imaging at 1.5 T, as well as excisional biopsy or cyst aspiration., Results: Twenty-two of 22 (100%) invasive carcinomas 8 mm or more in diameter, including three (12%) not evident on dense mammograms, enhanced 2.0 or more times the unenhanced intensity. One of three predominantly ductal carcinomas in situ and 10 of 26 (38%) benign lesions enhanced 2.0 or more times. Time-intensity curves were not statistically significantly different among enhancing carcinomas, fibroadenomas, or other benign lesions and showed no statistically significant correlations with pathologic size, nodal status, or hormone receptor status of invasive carcinomas., Conclusion: MR imaging enhancement of 2.0 or more times had high sensitivity (100%) for invasive carcinomas 8 mm or more in diameter, with moderate specificity (65%). Time-intensity curves showed no significant difference between enhancement of benign and malignant lesions.

Purpose: To determine whether hepatosplenomegaly was a reproducible finding in seven neonates who were being treated with extracorporeal membrane oxygenation (ECMO) for respiratory failure., Materials and Methods: The authors measured splenic and hepatic dimensions with ultrasound (US) at the time ECMO was initiated and then every 24-48 hours until decannulation. Splenic volume and the index of hepatic size were calculated by using published formulas., Results: Splenic volume increased in all seven patients from 8.3 cm3 +/- 1.7 to 16.4 cm3 +/- 4.4 (P < or = .001). Hepatic size did not change markedly., Conclusion: Hemolysis, leukopenia, and platelet activation occur during ECMO. Rapid splenic enlargement may be secondary to sequestration of red cells, platelets, and other hematologic elements that have been damaged in the ECMO circuit. Since the liver does not also increase in size, the splenic enlargement is unlikely to be the result of passive congestion.

Antibodies to the basement membrane proteoglycan produced by the EHS tumor were used to immunoprecipitate [35S]sulfate-labeled protoglycans produced by PYS-2 cells. The immunoprecipitated proteoglycans were subsequently fractionated by CsCl density gradient centrifugation and Sepharose CL-4B chromatography. The culture medium contained a low-density proteoglycan eluting from Sepharose CL-4B at Kav = 0.18, containing heparan sulfate side chains of Mr = 35-40,000. The medium also contained a high-density proteoglycan eluting from Sepharose CL-4B at Kav = 0.23, containing heparan sulfate side chains of Mr = 30,000. The corresponding proteoglycans of the cell layer were all smaller than those in the medium. Since the antibodies used to precipitate those proteoglycans were directed against the protein core, this suggests that these proteoglycans share common antigenic features, and may be derived from a common precursor which undergoes modification by the removal of protein segments and a portion of each heparan sulfate chain.

Wider application of positron emission tomography would be facilitated by the availability of positron-emitting radiopharmaceuticals labeled with nuclides, like 62Cu, that are available from parent/daughter generator systems. Using a longer-lived copper isotope (67Cu) we have examined three derivatives of copper(II) pyruvaldehyde bis(thiosemicarbazone) as potential tracers for evaluation of cerebral and myocardial blood flow: Cu(PTS), Cu(PTSM), and Cu(PTSM2) (where PTS = pyruvaldehyde bis(thiosemicarbazone), PTSM = pyruvaldehyde bis(N4-methylthiosemicarbazone), and PTSM2 = pyruvaldehyde bis(N4-dimethylthiosemicarbazone). All three lipophilic radiocopper complexes were obtained in high yield via a procedure that could be adapted to a "kit" formulation. In animal model systems Cu(PTSM) and Cu(PTSM2) show excellent uptake in the brain and heart following i.v. injection. These tracers differ in that Cu(PTSM) exhibits microsphere-like retention in the brain and heart, whereas Cu(PTSM2) substantially clears from these organs. The relative cerebral pharmacokinetics of [67Cu]Cu(PTSM) and [67Cu]Cu(PTSM2) are consistent with their known reactivity towards intracellular sulfhydryl groups.