Differentiation Of Adenomas Research Articles

A practical contrast-enhanced ultrasound risk prediction of gallbladder polyp: differentiation of adenoma from cholesterol polyp lesion.

A practical contrast-enhanced ultrasound risk prediction of gallbladder polyp: differentiation of adenoma from cholesterol polyp lesion.

Contrast-Enhanced Ultrasound Qualitative and Quantitative Characteristics of Parathyroid Gland Lesions.

Background and Objectives: preoperative differentiation of enlarged parathyroid glands may be challenging in conventional B-mode ultrasound. The aim of our study was to analyse qualitative and quantitative characteristics of parathyroid gland lesions, using multiparametric ultrasound protocol—B-mode, Colour Doppler (CD), and contrast-enhanced ultrasound (CEUS)—and to evaluate correlation with morphology in patients with hyperparathyroidism (HPT). Materials and Methods: consecutive 75 patients with 88 parathyroid lesions and biochemically confirmed HPT prior to parathyroidectomy were enrolled in the prospective study. B-mode ultrasound, CD, and CEUS were performed with the subsequent qualitative and quantitative evaluation of acquired data. We used 1 mL or 2 mL of intravenous ultrasound contrast agent during the CEUS examination. Correlation with post-surgical morphology was evaluated. Results: seventy parathyroid adenomas were hypoechoic and well contoured with increased central echogenicity (44.3%), peripheral-central vascularization (47%), and polar feeding vessel (100%). Twelve hyperplasias presented with similar ultrasound appearance and were smaller in volume (p = 0.036). Hyperplasias had a tendency for homogenous, marked intense enhancement vs. peripherally enhanced adenomas with central wash-out in CEUS after quantitative analysis. No significant difference was observed in contrasting dynamics, regardless of contrast media volume use (1 mL vs. 2 mL). We achieved 90.9% sensitivity and 72.7% specificity, 93% positive predictive value (PPV), 87.3% negative predictive value (NPV), and 87.3% accuracy in the differentiation of parathyroid lesions prior to post-processing. In a quantitative lesion analysis, our sensitivity increased up to 98%, specificity 80%, PPV 98%, and NPV 80% with an accuracy of 96.4%. Conclusions: CEUS of parathyroid lesions shows potential in the differentiation of adenoma from hyperplasia, regardless of the amount of contrast media injected. The quantitative analysis improved the sensitivity and specificity of differentiation between parathyroid lesions. Hyperplasia was characterized by homogeneous enhancement, fast uptake, and homogeneous wash-out appearance; adenoma—by peripheral uptake, central wash-out, and reduced hemodynamics. The use of CEUS quantification methods are advised to improve the ultrasound diagnostic role in suspected parathyroid lesions.

Abstract 1276: Differentiation of human colon adenomas in an enteroid culture: A treatment comparison

Abstract Introduction: Previous murine studies have demonstrated that dietary Aquamin®, a calcium-rich, multi-mineral natural product, suppressed colon polyp formation and transition to invasive tumors more effectively than calcium alone when provided over the lifespan of the animals. Methods: In the present study, we compared Aquamin® to calcium for modulation of growth and differentiation in human colon adenomas in enteroid culture. Adenoma growth and differentiation were assessed at the light and electron microscopic levels and by immunostaining. Image quantitation of immunohistochemical markers was performed using Aperio Imagescope to compare these interventions. A proteomic assessment was done to compare protein expression patterns in treated cultures as compared to cultures maintained under control conditions (calcium 0.15 mM). Enteroids established from normal colonic tissue were examined in parallel. Results: Both calcium and Aquamin® provided at 1.5 mM calcium fostered differentiation in the adenoma enteroid cultures as compared to control, but Aquamin® was more effective. Even at a concentration providing only 0.15 mM calcium, Aquamin® induced differentiation in some individual enteroids. Aquamin® was more effective than calcium in inducing upregulation of proteins. There were 35 proteins upregulated with Aquamin as compared to 20 with calcium 1.5mM at 1.8-fold change or above (in 3 colonic adenomas) with less than 2% FDR. Both calcium and Aquamin® induced differences in the expression pattern of proteins known to be involved in differentiation (table). In addition, several keratins and histones, as well as merlin and Olfactomedin-4 were upregulated. Conclusion: These findings support that i) calcium (1.5 mM) has the capacity to modulate growth and differentiation in large human colon adenomas and ii) the additional trace elements provided along with calcium in Aquamin® can have effects on proliferation and differentiation at lower levels than observed with calcium at 1.5mM. Expression of Immunohistochemical Markers in enteroid cultures of Human Adenomas (Fold-Changes)IHC MarkersCalcium 0.15mMAquamin 0.15mMCalcium 1.5mMAquamin 1.5mMKi6710.750.59*0.49*CK2012.13*2.36*2.35*E-Cadherin11.051.57*1.57*NF2 (Merlin)12.44*#1.012.56*#Occludin11.23*1.25*1.29**reflects significance as compared to Ca 0.15mM. #reflects significance as compared to Ca 1.5mM Citation Format: Shannon D. McClintock, Justin A. Colacino, Durga Attili, Michael K. Dame, Areeba H. Rizvi, Aliah Richter, Anusha R. Reddy, Venkatesha Basrur, D. Kim Turgeon, James Varani, Muhammad N. Aslam. Differentiation of human colon adenomas in an enteroid culture: A treatment comparison [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1276.

Characterization of Adrenal Adenoma by Gaussian Model-Based Algorithm

We confirmed that computed tomography (CT) attenuation values of pixels in an adrenal nodule approximate a Gaussian distribution. Building on this and the previously described histogram analysis method, we created an algorithm that uses mean and standard deviation to estimate the percentage of negative attenuation pixels in an adrenal nodule, thereby allowing differentiation of adenomas and nonadenomas. The institutional review board approved both components of this study in which we developed and then validated our criteria. In the first, we retrospectively assessed CT attenuation values of adrenal nodules for normality using a 2-sample Kolmogorov-Smirnov test. In the second, we evaluated a separate cohort of patients with adrenal nodules using both the conventional 10HU unit mean attenuation method and our Gaussian model-based algorithm. We compared the sensitivities of the 2 methods using McNemar's test. A total of 183 of 185 observations (98.9%) demonstrated a Gaussian distribution in adrenal nodule pixel attenuation values. The sensitivity and specificity of our Gaussian model-based algorithm for identifying adrenal adenoma were 86.1% and 83.3%, respectively. The sensitivity and specificity of the mean attenuation method were 53.2% and 94.4%, respectively. The sensitivities of the 2 methods were significantly different (P value < 0.001). In conclusion, the CT attenuation values within an adrenal nodule follow a Gaussian distribution. Our Gaussian model-based algorithm can characterize adrenal adenomas with higher sensitivity than the conventional mean attenuation method. The use of our algorithm, which does not require additional postprocessing, may increase workflow efficiency and reduce unnecessary workup of benign nodules.

BRAF(V600E) Mutation, RET/PTC1 and PAX8-PPAR Gamma Rearrangements in Follicular Epithelium Derived Thyroid Lesions - Institutional Experience and Literature Review.

Thyroid cancers are the most frequently occurring endocrine malignancy worldwide. In Turkey, thyroid cancers are ranked 2(nd) on the incidence list in women, with a rate of 16.2%, but they are not included among the top 10 cancer types in men. To identify the contribution of the BRAF(V600E) mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements in the diagnosis and differential diagnosis of follicular epithelial-derived thyroid lesions. Retrospective clinical and molecular genetic study. A total of 86 thyroid cases diagnosed between 2001 and 2012 at the Department of Pathology were included in the retrospective study group. Samples best representing the lesion and comprising capsules were chosen in the selection of paraffin blocks pertaining to the cases. The BRAF(V600E) mutation, and the RET/PTC1 and PAX8-PPARγ rearrangements were investigated in all cases. The BRAF(V600E) mutation was observed in 12 out of 37 papillary carcinoma cases (32.4%), in 1 out of 15 follicular carcinoma cases (6.6%), and in 1 out of 7 undifferentiated carcinoma cases (14.3%). No mutation was detected in benign lesions. The RET/PTC1 rearrangement was detected in 2 out of 7 undifferentiated carcinoma cases (28.6%), and in 1 out of 15 follicular carcinoma cases (6.6%). No gene rearrangement was detected in benign lesions. The PAX8-PPARγ rearrangement was detected in 5 out of 15 follicular thyroid carcinoma cases (33.3%) and in 1 out of 15 follicular adenoma cases (6.6%). The BRAF(V600E) mutation and RET/PTC1 rearrangement were effective in distinguishing the follicular epithelium-derived benign and malignant lesions of the thyroid in the resection materials. The BRAF(V600E) mutation was rather specific to papillary carcinoma in the thyroid, and in cases where the BRAF(V600E) mutation was detected, multi-centricity, lymph node metastasis and capsular invasion findings were observed more frequently compared to cases in which no mutation was observed. The PAX8-PPARγ rearrangement was observed to be more effective in the differentiation of adenomas and carcinomas in follicular neoplasms of the thyroid, whereas the RET/PTC1 analysis contributed to the differential diagnosis of papillary carcinoma histogenesis at a frequency of 29% in undifferentiated thyroid carcinomas.

Development and validation of a training module on the use of narrow-band imaging in differentiation of small adenomas from hyperplastic colorectal polyps

Experts are accurate in differentiating small adenomas from hyperplastic polyps at colonoscopy by using narrow-band imaging (NBI). To prospectively evaluate the effectiveness of an NBI training module on individuals with varying colonoscopy experience. Prospective educational evaluation study. Academic endoscopy unit. Twenty-one participants of varying colonoscopy experience (novices, trainees, and experienced gastroenterologists) and 5 experts in NBI. Participants completed a computer-based test module consisting of 30 NBI polyp images. No feedback was given. They then completed a computer-based training module on the use of NBI in the differentiation of adenomas and hyperplastic polyps. The test module was then completed a second time. Construct validity (the difference in baseline accuracy on the test module between different groups of participants) and content validity (difference in accuracy achieved on the test module before and after training) of the training module. There was a significant difference in the baseline accuracy (P < .001) between experts (0.95; 95% confidence interval [CI], 0.92-0.97), experienced colonoscopists (0.68; 95% CI, 0.68-0.74), trainees (0.75; 95% CI, 0.67-0.82), and novices (0.62; 95% CI, 0.46-0.77). Accuracy increased significantly (P < .001) for all 3 groups after training (novices 0.84; 95% CI, 0.78-0.88, trainees 0.90; 95% CI, 0.84-0.93, and experienced colonoscopists 0.84; 95% CI, 0.76-0.89). After training, the agreement was moderate at least (κ = 0.56 for novices, κ = 0.70 for trainees, and κ = 0.54 for experienced colonoscopists). This study did not assess the accuracy of optical diagnosis in routine clinical practice. A short, computer-based training module can improve the diagnostic accuracy and interobserver agreement for the use of NBI to differentiate adenomas from hyperplastic polyps and could be used for the initial training in optical diagnosis.

Evaluation of Relative Wash-In Ratio of Adrenal Lesions at Early Biphasic CT

The purpose of this study was to retrospectively evaluate the accuracy of unenhanced attenuation and relative percentage wash-in ratio in early, that is, arterial and portal venous phase, biphasic CT in differentiating adrenal adenomas from metastatic lesions. One hundred seven adrenal masses in 86 consecutively registered patients (45 men, 41 women; mean age, 56 years) were evaluated. Diagnosis was achieved with percutaneous biopsy (n = 6), surgery (n = 13), and at least 1 year of imaging follow-up (n = 88). Unenhanced, arterial phase, and portal phase scans were obtained. Diameter and absolute attenuation values in each phase of CT were measured in a region of interest covering one to two thirds of a lesion. Relative percentage wash-in ratio was calculated. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in differentiation of adenomas from metastatic lesions were calculated for unenhanced attenuation and for wash-in ratio. A value of p < 0.05 was considered significant. The final diagnosis was metastasis in 51 cases and adenoma in 56 cases. A significant difference was found between benign and malignant lesions in regard to diameter (p = 0.001), unenhanced CT attenuation (p = 0.001), and relative percentage wash-in ratio from the arterial to the portal venous scan (p = 0.014). In the differentiation of benign from malignant lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of unenhanced CT attenuation (at an 11-HU threshold) were 98%, 86%, 86%, 98%, and 92%, and those of relative percentage wash-in ratio from the arterial to the portal venous phase were 94%, 77%, 79%, 93%, and 85%. Relative percentage wash-in ratio may help in differentiating adenoma from metastasis and in guiding the decision to perform CT directed at the adrenal glands when unenhanced CT is not available.

Colorectal Cancer Prevention

Purpose: Narrow band imaging has been successfully used in diff erentiating adenomatous from hyperplastic polyps when used with or without optical magnifi cation. Th ere is little published information regarding teaching tools, and there are few data on interobserver variation in identifi cation of histology for either experts or non-experts. Real time histology has been proposed as a means to decrease costs and risks of colonoscopy by not removing small distal colon hyperplastic polyps. We tested whether medical residents with no prior training in endoscopy (n=12), gastroenterology fellows with varying levels of endoscopic training (n=12) and gastroenterology attendings who were all experienced endoscopists (n=12) could learn and apply endoscopic criteria for diff erentiation of adenomas from hyperplastic polyps aft er a short didactic session.

Hyperplastic polyposis syndrome: a pilot study for the differentiation of polyps by using high-resolution endoscopy, autofluorescence imaging, and narrow-band imaging

Endoscopic differentiation and removal of potentially premalignant sessile serrated adenomas (SSAs) may be important steps in preventing the development of colorectal cancer in hyperplastic polyposis syndrome (HPS). To assess the value of high-resolution endoscopy, autofluorescence imaging (AFI), and narrow-band imaging (NBI) for differentiating polyps in HPS. A prospective polyp series. Single tertiary referral center. Seven patients with HPS underwent colonoscopy with endoscopic trimodal imaging, which incorporates high-resolution endoscopy, AFI, and NBI in 1 system. All detected polyps were analyzed with AFI for color and with NBI for Kudo pit pattern and vascular pattern intensity. The accuracy, sensitivity, and specificity of AFI and NBI in differentiating detected polyps were determined by using histology as the criterion standard. A total of 19 hyperplastic polyps (HPs), 32 SSAs, and 15 adenomas were detected. For differentiating SSAs from HPs, AFI color, Kudo pit pattern, and vascular pattern intensity resulted in a diagnostic accuracy of 55%, 55%, and 52%, respectively. For differentiating adenomas from HPs, the accuracy was 65%, 94%, and 90%, respectively. Macroscopically, the combination of a size of 3 mm or larger and a proximal location resulted in the highest accuracy (76%) for differentiating SSAs from HPs. Small sample size. Endoscopic differentiation between HPs and SSAs by using endoscopic trimodal imaging proved unsatisfactory. Differentiation of adenomas from HPs was possible with NBI but not with AFI.

Computed tomography findings in diseases of the adrenal gland

The adrenal gland is a common site of disease, with an abnormality prevalence as high as 9% in autopsy series. With the increasing use of CT, adrenal lesions are frequently found in the daily practice of radiology and are diagnosed in up to 5% of CT examinations performed for varied reasons. Imaging features on CT can establish a specific diagnosis of many of these lesions, including myelolipoma, hematoma and cysts. Once a diagnostic dilemma, now adenomas can be accurately diagnosed using unenhanced CT, chemical shift magnetic resonance imaging and CT contrast washout analysis. Because the adrenal gland is also a frequent site of metastasis, recent literature has focused on imaging characterization of adrenal masses for differentiation of adenomas from metastases. In patients without known malignancy, most adrenal lesions are benign and a specific diagnosis can now be made on the basis of imaging features. It is important to understand the prevalence of adrenal abnormalities because the gland is a common site of disorders, and the increased use of cross-sectional imaging has increased the frequency of detection of adrenal lesions. The prevalence of disease is important in predicting the risk of malignancy when an adrenal mass is discovered in a patient without known cancer. Detection of adrenal gland diseases has increased substantially with the advent and widespread use of imaging techniques. Although several imaging modalities can be used, CT has a central role in both detection and differential diagnosis of an adrenal lesion. The aim of this article is to review the CT findings of adrenal gland diseases.

Contrast-Enhanced Sonography of Adrenal Masses: Differentiation of Adenomas and Nonadenomatous Lesions

The aim of this proof-of-principle study was to evaluate contrast-enhanced sonography in the characterization of adrenal masses. Thirty-five consecutively registered patients with newly detected adrenal masses underwent hormonal evaluation and duplex and Doppler sonography followed by contrast-enhanced sonography and CT or MRI. The dynamics of contrast enhancement were analyzed with time-intensity curves. CT and MRI were used as the reference methods for the diagnosis of adenoma and myelolipoma. Metastasis was diagnosed with fine-needle biopsy, and all other adrenal masses were diagnosed at adrenalectomy. Fisher's exact test was used to evaluate the criteria for diagnosis of malignant adrenal masses. Size greater than 4 cm and hypervascularization were found significantly more often in malignant than in benign lesions (71% vs 21% for size; 57% vs 7% for hypervascularization). At contrast-enhanced sonography, early arterial or arterial contrast enhancement and rapid washout were seen in all patients with primary or secondary malignant lesions of the adrenal gland and in only 22% of patients with benign adrenal masses (p < 0.05). All primary malignant lesions were confirmed at histologic examination. In 32 of 35 patients (91%), findings at CT or MRI were congruent with those at contrast-enhanced sonography in regard to characterization of adenoma versus nonadenomatous lesion (p < 0.001). In two of the 35 cases, however, all imaging methods favored the diagnosis of nonadenomatous lesion, but the histologic result after adrenalectomy was adrenal adenoma. The sensitivity and specificity of contrast-enhanced sonography in the diagnosis of malignant adrenal mass were 100% and 82%. Contrast-enhanced sonography can be used to differentiate adenomas and nonadenomatous lesions with a sensitivity comparable with that of CT and MRI and may be a cost-effective method for preselection of patients with adrenal masses.

MRI of Hepatic Adenomatosis: Initial Observations with Gadoxetic Acid Contrast Agent in Three Patients

The purpose of our study was to describe the MR signal characteristics of histologically proven liver adenomatosis in three patients using gadoxetic acid, a newly developed liver-specific MR contrast agent. In all three patients, more than 100 liver adenomas revealed no metabolism of the new liver-specific contrast agent in the delayed phase. Because of absent or strongly reduced intracellular uptake of gadoxetic acid in all adenomas during delayed contrast-enhanced series, differentiation of adenomas from dysplastic or malignant lesions was not possible.

The optimal imaging of adrenal tumours: a comparison of different methods

Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [(131)I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [(123)I]- and [(131)I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.

Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells

The self-renewing epithelium of the small intestine is ordered into stem/progenitor crypt compartments and differentiated villus compartments. Recent evidence indicates that the Wnt cascade is the dominant force in controlling cell fate along the crypt-villus axis. Here we show a rapid, massive conversion of proliferative crypt cells into post-mitotic goblet cells after conditional removal of the common Notch pathway transcription factor CSL/RBP-J. We obtained a similar phenotype by blocking the Notch cascade with a gamma-secretase inhibitor. The inhibitor also induced goblet cell differentiation in adenomas in mice carrying a mutation of the Apc tumour suppressor gene. Thus, maintenance of undifferentiated, proliferative cells in crypts and adenomas requires the concerted activation of the Notch and Wnt cascades. Our data indicate that gamma-secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic benefit in colorectal neoplastic disease.

Hexaminolevulinate- Induced Fluorescence Endoscopy in Patients with Rectal Adenoma and Cancer

patients with colorectal polyps$2 cm resected in a general hospital from january 2001 to august 2003. Results: 118 large polyps were resected in 67 men and 39 women. 78 patients had an ER and 28 a SR. 43% of the ER were performed using endoscopic mucosal resection. An endoloop was necessary in 8% of cases, Argon plasma coagulation in 17% and clipping in 9%. 14% of SR were transanal, 14% laparoscopic and 71% open resections. A colectomy was necessary in 82% of SR. Polyp histology was similar in both groups. One perforation and one bleeding occurred in the ER group which required a surgical treatment and one of them died. No complication occurred in the SR group. 2 patients in the ER group had to be referred to surgery because a T1 carcinoma was diagnosed. A follow-up colonoscopy was performed in 26 patients of the ER group after a mean follow-up time of 6.5 months. Recurrence was detected in 9 patients : 6 had repeat ER and 3 were referred to surgery. Altogether 7 patients in the ER group had to be referred to surgery so that 33% of all patients had to be operated on. Whereas 14.6% of patients with pedunculated polyps had to be operated on, 45.2% of patients with sessile or flat polyps had to (p= 0.002). 44% of patients with polyps located in the right colon had to be operated on, whereas 24.1% of those with polyps in the left and transverse colon had to (p > 0.05). 24% of patients who had their colonoscopy performed by an expert endoscopist had to be operated on (20.7% of patients with benign polyps). 20 patients were referred to an expert endoscopist for a second attempt of ER and 75%were successful. 50% of patients in the SR group had not had an ER attempt by an expert endoscopist. Conclusions : one in three patients with a large colorectal polyp has to be operated on. The rate of referral to surgery may be decreased to one in five for benign polyps if an expert endoscopist gets involved. Referral to surgery is related to the size of polyps, their sessile or flat shape, their location in the right colon, their malignancy and to the lack of attempt of ER by an expert endoscopist. HexaminolevulinateInduced Fluorescence Endoscopy in Patients with Rectal Adenoma and Cancer Esther Endlicher, Cornelia Gelbmann, Ruth Knuechel, Alois Fuerst, Rolf-Marcus Szeimies, Stefan Goelder, Juergen Schoelmerich, Helmut Messmann Background and Aims: Fluorescence endoscopy is a promising new method for detection and therapy of premalignant and malignant lesions. The aim of the present pilot study was to investigate the feasibility of hexaminolevulinate based photodetection in patients with rectal adenoma and cancer, including safety, dosefinding and efficacy. Methods: 10 patients with known rectal adenoma and cancer were sensitised with 3.2 mM hexaminolevulinate (Photocure, Oslo, Norway). Fluorescence endoscopy was performed after an enema lasting for 30-60 minutes and a resting time of 0-30 minutes before endoscopy. Biopsies were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to investigate distribution of protoporphyrin IX (PPIX) fluorescence in different tissue layers. Adverse events were reported by open questioning in all patients while skin photosensitivity, serum transaminases, blood pressure, heart rate and gastric discomfort were recorded actively in 5 patients. Results: Hexaminolevulinate-induced fluorescence endoscopy led to selective fluorescence of all rectal adenoma containing intraepithelial neoplasia. In rectal cancer only a weak or even no fluorescence could be detected. No side effects related to hexaminolevulinatewere observed. In twopatients differentiation of adenoma and hyperplastic polyps was possible due to fluorescence. Conclusion: Hexaminolevulinate based fluorescence endoscopy using a 3.2 mM enema in patients with rectal cancer and adenoma was well tolerated and showed no significant skin sensitivity and other side effects. The optimal time of administration seems to be 30-45 minutes with a resting time of 30 minutes. Selective fluorescence of intraepithelial neoplasia containing adenoma indicates that hexaminolevulinatebased fluorescence endoscopy has the potential for the detection of premalignant lesions. Partially ulcerated surface, tumour necrosis and moderate differentiation are probably the reasons for lacking fluorescence in complete cancer after local sensitisation with hexaminolevulinate.

Adrenal adenomas: relationship between histologic lipid-rich cells and CT attenuation number

Objective: To evaluate the relationship between lipid-rich cells of the adrenal adenoma and precontrast computed tomographic (CT) attenuation numbers in three clinical groups. Materials and Methods: Thirty-five surgically resected adrenal adenomas were used. The clinical diagnoses of the patients included 13 cases of primary aldosteronism, 15 cases of Cushing's syndrome, and 7 non-functioning tumors. The number of lipid-rich clear cells was counted using a microscopic eyepiece grid that contained 100 squares. The results were expressed as the percentages of lipid-rich areas. Results: There was a strong inverse linear relationship between the percentage of lipid-rich cells and the precontrast CT attenuation number ( R 2=0.724, P<0.0001). There were significantly more lipid-rich cells in the primary aldosteronism and non-functioning tumor cases compared to cases of Cushing's syndrome ( P=0.007 and 0.015, respectively). The CT attenuation numbers of the primary aldosteronism cases were significantly lower than those of Cushing's syndrome ( P=0.0052). Furthermore, the CT attenuation numbers of the non-functioning tumor cases were lower than those of Cushing's syndrome cases. Conclusion: We showed that adrenal adenomas in primary aldosteronism and non-functioning tumors contain significantly more lipid-rich cells than those in Cushing's syndrome. They also showed significantly lower attenuation than that in Cushing's syndrome on CT scans. Our results suggest that precontrast CT attenuation numbers may be helpful in the differentiation of adenomas from non-adenomatous lesions, which include malignancies.

Discerning malignancy in adrenocortical tumors: are molecular markers useful?

Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Discerning ACCs from benign adenomas histologically may be difficult if invasion into surrounding tissues or metastases are missing. In order to establish molecular markers for malignancy, we analyzed seven normal adrenals, three massive macronodular ACTH-independent adrenocortical hyperplasias (MMAHs), 30 adrenocortical adenomas (ACAs) and ten ACCs. All tissues were studied for the presence of alterations in the p53 tumor suppressor gene using the PAb 1801 antibody, which detects mutant p53 protein and the pYNZ22 microsatellite marker to show loss of heterozygosity (LOH) at 17p, for expression of the proliferation-associated antigen Ki67 using the MIB1 antibody, for the rate of apoptotic tumor cells with the TdT-mediated dUTP biotin nick end labeling (TUNEL) method, and for LOH of 11q13 (menin gene locus) with the D11S956 microsatellite marker. 0/3 MMAH, 1/28 ACA and 3/10 ACC revealed immunopositive staining for p53. LOH for pYNZ22 was observed in 1/3 MMAH, 1/23 informative ACA and 6/6 informative ACC. The rate of apoptotic cells was significantly higher in ACC (P<0.0001 by ANOVA) than in ACA but there was some overlap between groups. The Ki67 index (% immunopositive cells) was 1.9+/-1.30% (mean+/-s.d.) in normal adrenals, 3.47+/-1.37% in MMAH, and 2.11+/-1.01% in ACA. ACC had the highest Ki67 index of 11.94+/-7.58% distinguishing all ACC from the ACA and MMAH studied with a cut-off level of 5%. LOH for 11q13 was detected in 2/3 MMAH, 5/26 ACA and 6/8 ACC. We conclude that a Ki67 index above 5% is a sensitive and specific indicator of ACC and may be useful in the differentiation of adenomas from carcinomas.

CT time-attenuation washout curves of adrenal adenomas and nonadenomas.

The purpose of this study was to analyze the CT contrast enhancement washout curves of adrenal masses and to determine the earliest time after initial enhancement that differentiation of adenomas from nonadenomas is possible. Contrast enhancement washout curves were generated after delayed contrast-enhanced CT scans of 52 adrenal adenomas and 24 nonadenomas. The optimal threshold value and corresponding sensitivity and specificity for the diagnosis of adenoma were determined according to attenuation values. Also, we calculated the percentage and relative percentage of enhancement washout at time delays from 5 to 45 min after initial enhancement. The mean percentage of enhancement washout for adrenal adenomas was 51% at 5 min and 70% at 15 min, compared with 8% and 20%, respectively, for nonadenomas. The sensitivity and specificity for the diagnosis of adenoma were both 96% at a threshold attenuation value of 37 H on the 15-min delayed enhanced scan. On CT, adrenal adenomas show a much earlier and more rapid washout of contrast enhancement than do nonadenomas. Adenomas and nonadenomas can be differentiated by attenuation values or the percentage or relative percentage of washout as early as 5-15 min after enhancement.

Adrenal venous sampling analysis of primary aldosteronism: value of ACTH stimulation in the differentiation of adenoma and hyperplasia

Adrenal venous blood samples drawn before and after stimulation with adrenocorticotropic hormone (ACTH) were analysed in 32 consecutive patients with primary aldosteronism. Twenty-six patients had aldosterone-producing adenomas and six patients had bilateral hyperplasia.

Scintigraphic studies in adrenal hypertension

Endocrine hypertension secondary to disorders of the adrenal glands is uncommon, but by no means rare. The importance of correct biochemical diagnosis and subsequent localization of the responsible lesion(s) lie in the fact that many of these syndromes occur in younger patients, may exhibit familial patterns of inheritance and are frequently amenable to surgical cure. The radiopharmaceuticals (131)1-6 beta-iodomethyl-19-norcholesterol (NP-59), a marker of adrenocortical cholesterol uptake, and (131)1- and (123)1-metaiodobenzylguanidine (MIBG), a norepinephrine (NE) analog and marker of energy-dependent NE storage vesicle accumulation, can be shown to accurately localize adrenal cortex and sympathoadrenal dysfunction, respectively. In Cushing's syndrome (CS) not only does the pattern of NP-59 uptake depict the adrenal dysfunction and its pathophysiologic basis, but the level of NP-59 accumulation reflects the degree of adrenocortical hyperfunction. Adrenocorticotrophin-independent CS is uniformly and accurately localized, especially in bilateral cortical nodular hyperplasia where even high resolution computed tomography (CT) may fail to depict the often subtle, asymmetric anatomic abnormalities. Dexamethasone suppression NP-59 adrenal scintigraphy has been shown to be highly sensitive and specific, and exceeds the efficacy of CT in the differentiation of adenoma and bilateral hyperplasia in primary aldosteronism. MIBG is useful as a sympathoadrenal imaging agent whose clinical utility has been demonstrated in the localization of pheochromocytoma, especially as a modality to screen the body for multiple and extraadrenal, recurrent, or metastatic lesions. Moreover, the extent of metastatic involvement from neuroblastoma can also be accurately depicted using MIBG. In this review we will examine the role of adrenal scintigraphy in the characterization of hypersecretory disorders of the adrenal cortex, medulla, and related conditions that produce hypertension as part of their symptom(s) complex. This approach, which is complementary to other anatomical modalities of imaging, can be used to advantage in the localization of functioning cortical and medulla adrenal diseases and other neoplasms of adrenergic origin.