Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Comparison between magnetic resonance imaging and rigid rectoscopy in the preoperative identification of intra- and extraperitoneal rectal cancer.

AIM: Accurate preoperative discrimination between extra- and intraperitoneal rectal cancer has important treatment implications. Our main objective was to compare the diagnostic performance of MRI with rigid rectoscopy (RRS) in assessing the location of rectal cancers above or below the peritoneal reflection (PR), using the findings obtained during abdominal surgery for treatment of the cancer as the reference standard. We also compared the accuracy of MRI and RRS in assessing the level of the lower border of the tumour from the anal verge. METHOD: Patients with rectal carcinoma awaiting surgery underwent MRI and RRS. The MRI images were reviewed by two abdominal radiologists who determined the location of the inferior border of the tumour in relation to the PR. Receiver-operating characteristics (ROC) curve analysis was performed to determine the diagnostic performance of RRS at different cut-off values. RESULTS: The sensitivity and specificity were 98.15% and 100%, respectively, for MRI, and 100% and 76.92%, respectively, for RRS at a cut-off value of < 10 cm. The mean level of the lower border of the tumour from the anal verge was 68 ± 44.3 mm on RRS and 73.5 ± 42.4 mm on MRI (P = 0.25), with a trend towards overestimation with MRI. CONCLUSION: RRS is still the main means of assessing the level of a rectal tumour from the anal verge, but MRI has value in determining the level of the tumour in relation to the PR, which cannot be seen on endoscopy.

Intestinal anti-tissue transglutaminase antibodies in potential coeliac disease.

Anti-tissue transglutaminase 2 (anti-TG2) antibodies are present in the serum of the great majority of untreated coeliac disease (CD) patients. They are produced and deposited in the small intestinal mucosa. Potential CD patients present serum anti-TG2 antibodies higher than cut-off, but a normal duodenal mucosa where mucosal deposits of anti-TG2 are not always detectable. The aim of our work was to investigate the presence of anti-TG2 intestinal antibodies in patients with potential CD, and identify the most sensitive test to detect them. Twelve active CD patients, 28 potential CD patients and 39 non-CD controls were enrolled. Biopsy fragments from all patients were analysed by double immunofluorescence to detect mucosal deposits of anti-TG2 antibodies. Fragments from the same subjects were also cultured for 24 h with medium in the presence or absence of gliadin peptides. Anti-TG2 autoantibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay. All active CD, 68% of potential CD patients and 20% of non-CD controls showed mucosal deposits of immunoglobulin (Ig)A anti-TG2; at the same time 100, 96 and 8% of active CD, potential CD and non-CD control patients secreted these antibodies in culture supernatants, respectively. Our data showed that, to detect intestinal anti-TG2 antibodies, the measurement of antibodies secreted into culture supernatants has higher sensitivity and specificity (97·5 and 92·3%, respectively) than the detection of mucosal deposits (77·5 and 80·0%, respectively). The measurement of intestinal anti-TG2 antibodies may prove useful in clinical practice to predict evolution towards mucosal atrophy in potential coeliac patients and identify patients with gluten sensitivity.

Crohn's disease: prevalence of intestinal and extraintestinal manifestations detected by computed tomography enterography with water enema.

BACKGROUND: Computed tomography enterography (CTE) may detect the presence, severity, and extent of bowel inflammation in patients with Crohn's disease (CD). The aim of our study was to assess, among a cohort of 22 histologically proven CD patients, the prevalence of disease distribution, behavior, anastomotic recurrence and extraintestinal manifestations detected by an original CTE technique. METHODS: Two radiologists reviewed 221 CTEs performed providing both small and large bowel distension by oral administration of neutral contrast material and trans-rectal introduction of a water enema (CTE-WE). RESULTS: Ileal CD was detected in 116 CTE-WEs (52.4%), including 71/116 (61.2%) non-stricturing/non-penetrating, 17/116 (14.6%) stricturing, and 28/116 (24.1%) penetrating forms. Colonic CD was appreciable in 35 (15.8%) patients, including 18/35 (51.4%) non-stricturing/non-penetrating, 6/35 (17.1%) stricturing, and 11/35 (31.4%) penetrating forms. Ileocolic CD was present in 52 (23.5%) CTE-WEs, including 30/52 (57.7%) non-stricturing/ non-penetrating; 3/52 (5.7%) stricturing, and 19/52 (36.5%) penetrating forms. In 10/221 patients (4.5%), upper gastrointestinal involvement (UGI) was present. Perianal disease was observed in 17/221 patients (7.7%). Fistulas were present in 52 (23.5%) and abscesses in 24 (10.8%) CTE-WEs, respectively. Among 57/221 (25.8%) patients who had undergone a disease-related intestinal resection, in 30/57 cases (52.6%) CD recurrence at the anastomosis was present. 4/221 patients (1.8%) with a histologically confirmed intestinal neoplastic stenosis were observed. Sacroiliitis (24%) was found to be prevalent over hepatic steatosis (10.8%), cholelithiasis (8.6%), and nephrolithiasis (4%). CONCLUSIONS: CTE-WE represents a comprehensive imaging technique which may demonstrate bowel inflammation and CD extraintestinal manifestations. A peculiar prevalence of UGI involvement and neoplastic strictures were observed. In our study the prevalence of sacroiliitis resulted higher than previously reported.

Multimodality imaging of intraosseous ganglia of the wrist and their differential diagnosis.

Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within the carpus and is often an incidental finding on radiographs obtained for other reasons. Two types of IOG have been described: an "idiopathic" form (or type I), the pathogenesis of which has not been completely clarified, and a "penetrating" form (or type II), caused by the intrusion of juxtacortical material (often a ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment. The differential diagnosis for IOG is wide-ranging and complex, including lesions of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial proliferative lesions), ischaemic (Kienböck's disease or avascular osteonecrosis of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs is a useful diagnostic tool that provides complete morphological characterisation and differentiation from other intraosseous cystic abnormalities of the carpus. Thin-slice multidetector computed tomography (MDCT) can provide high-spatial-resolution images of the cortical and cancellous bone compartments, allowing detection of morphological findings helpful in characterising bone lesions, whereas magnetic resonance (MR) imaging can simultaneously visualise bone, articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments, along with intra- and periarticular soft tissues.

Imaging studies of crystalline arthritides.

Gout, calcium pyrophosphate dihydrate (CPPD) deposition disease, and calcium hydroxyapatite deposition disease (HADD) are the three most common crystal-induced arthropathies. Multimodality imaging may help in their diagnosis, and is useful for a precise and comprehensive assessment and grading of the related osteoarticular damage. Plain film radiography, due to its low cost and wide availability, is the first imaging technique to be used in crystal deposition diseases, providing well-known and specific findings for CPPD deposition disease and HADD, while it may undergrade the early osteoarticular lesions in gouty patients. Ultrasonography (US) is a radiation-free approach that accurately depicts crystal deposits in cartilage, peri- and intra-articular soft tissues, but it does not give a panoramic view of the affected joints. Cross-sectional imaging techniques can examine crystal deposits in the spine and axial joints. CT has the potential to distinguish monosodium urate (MSU) crystals from calcium containing crystals, due to their different attenuation values. MRI may demonstrate synovitis, erosions and bone marrow edema in gouty patients and it may differentiate tophi from other soft tissue nodules due to its high contrast resolution and power of tissue characterization.

Imaging of tophi with an extremity-dedicated MRI system.

OBJECTIVES: To describe the MRI features of gout tophi in the soft-tissues or joints of the limbs by low-field extremity-dedicated MRI. METHODS: Nine consecutive patients, 8M/1W, affected by chronic tophaceous gout were studied. Mean patients' age was 71.3±11.5 years, mean disease duration 98.1±44.9 months, and mean serum uric acid concentration 9.2±2.8 mg/L. Diagnosis was based on the ACR classification criteria for gout, and by identification of MSU crystals in the tophi and synovial fluid. Conventional radiograms and MRI with an extremity-dedicated system were obtained of the joint areas involved by tophi. RESULTS: At T1 weighted MRI images, all tophi showed a homogeneous intermediate signal intensity, similar to that of muscle. Conversely, in T2 weighted images, a wide spectrum of signal intensity patterns was observed. The pattern of contrast enhancement was variable from intense homogeneous to peripheral and heterogeneous. Capsulo-ligamentous structures were often thickened and degenerated and, on occasion, could be recognised as inhomogeneous, hypointense ribbon-shaped elements in the context of the tophus. In only two cases, tendons were infiltrated by tophaceous matter. Bone marrow oedema (BME) and erosions were seen in 8 out of 10 bones adjacent to tophi. CONCLUSIONS: The MRI appearance of gout tophi using an extremity-dedicated machine is similar to that described in the literature using whole body machines. BME adjacent to the tophus was a frequent finding. This technique may occasionally help in the differential diagnosis of nodules and in the follow-up of the disease. It also represents a useful tool to investigate the pathogenesis of gout and to better understand its clinical progression.

[Multimodal imaging in the differential diagnosis of soft tissue calcinosis]. / Imaging multimodale nella diagnosi differenziale della calcinosi dei tessuti molli.

Soft tissue calcinosis is a common radiographic finding, which may be related to different types of pathological processes. Multimodality imaging, combined with analysis of clinical and laboratory data, plays an important role for the differential diagnosis of these conditions. Conventional radiography is considered the first line approach to soft tissue calcinosis; CT and MRI may provide further information to better characterize calcified deposits. Imaging may help to distinguish metabolic calcification, such as primary tumoral calcinosis and the secondary one (associated with acquired disorders of calcium or phosphate regulation), from dystrophic calcification, which is associated to normal blood values of phosphate. The sedimentation sign typical of tumoral calcinosis has been demonstrated by plain film radiography, CT, MRI, and, more recently, by ultrasonography. Other types of soft tissue calcinosis may have a degenerative, metaplastic or neoplastic origin, and their characterization strongly relies on multimodality imaging.

High density of intraepithelial gammadelta lymphocytes and deposits of immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of coeliac patients with IgA deficiency.

The diagnosis of coeliac disease (CD) represents a special challenge in selective immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti-tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2 antibodies in the jejunal mucosa of IgAD patients with and without CD. Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and nine without CD). Sixteen immunologically intact children without CD represented the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+) IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No significant differences were noted between IgAD subjects without CD and those with potential CD. Furthermore, IgAD patients without CD showed a higher TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2 antibody deposits were present in six of seven of the IgAD patients with untreated CD, one of seven with potential CD and none of those without CD. Most of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti-TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and immunohistochemical markers do not discriminate between IgAD and potential CD with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very important for the diagnosis of CD in IgAD.

[Multimodality imaging of chronic tophaceous gout]. / Imaging integrato nella gotta cronica tofacea.

The diagnosis of gout is usually based on clinical presentation and laboratory findings. Imaging plays a role in the assessment and grading of articular damage related to chronic, long-standing disease, which is characterized by granulomatous synovitis, tophi, and erosions. Multimodality imaging of chronic tophaceous gout may be useful in clinical practice for a variety of purposes, including assessment of disease-related anatomical changes and monitoring of articular and soft-tissue lesions over time, especially in response to urate-lowering therapy. Radiography remains the primary imaging technique. Ultrasonography may detect monosodium urate crystals on cartilage, is helpful to assess small joint effusion, to guide to joint aspiration, and to evaluate the volume of tophi. Computed tomography is considered to be more sensitive than plain radiography in the detection and evaluation of cortical bone erosions associated with tophi. MRI represents the only imaging modality which provides visualization of bone marrow oedema associated with erosions and may be useful to characterize and distinguish tophi from other soft tissue nodules.

Parotid glands tumours: overview of a 10-year experience with 282 patients, focusing on 231 benign epithelial neoplasms.

Salivary gland tumours are uncommon, representing less than 6% of head and neck neoplasm. Pleomorphic adenoma is the most common benign epithelial salivary gland neoplasm, comprising 50%-74% of all parotid tumours. It is followed by Warthin's tumour (4-14%). The authors retrospectively reviewed 282 eligible patients surgically treated for parotid gland tumours in the last 10 years, focusing on 231 benign epithelial neoplasms. Clinical and diagnostic findings, surgical treatment and surgical outcome were discussed. The diagnosis of a parotid gland neoplasm must be considered in any patient presenting with a lump near the mandible. Smoking habit is important in Warthin's tumour pathogenesis. Fine needle aspiration citology (FNAC) can't lead alone to histological diagnosis. Only surgery can give histological certainty of benignity, thus preventing malignant degeneration, lump infection or risk of size-dependent surgical complications. Conservative formal parotidectomy appears to be the treatment of choice. Tumour pseudopodia and capsule ruptures are recognised factors involved in pleomorphic adenoma recurrences but also tumour multicentricity might play an important role.

Anatomic relationship between trigeminal nerve and temporomandibular joint.

Temporomandibular joint disorders (TMD) is a collective term used to describe pathologic conditions involving temporomandibular joint (TMJ), masticatory muscles and associated structures. Common related complaints include local pain, limited mouth opening and TMJ noises whereas symptoms often associated to TMD with debated pathogenesis enclose earache, headaches, tinnitus and trigeminal-like symptoms such as atypical orofacial pain. In particular, TMD trigeminal associated symptoms are intricate, difficult to treat and exert a great impact on everyday life of the patients thus invoking a complex multidisciplinary treatment. In this paper, the authors analyze the anatomic and topographic relationships between the mandibular branch of the trigeminal nerve and the medial aspect of the TMJ capsule in 8 fresh adult cadavers thus resuming a pathologic relationship between atypical trigeminal symptoms and TMD.

Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology.

PURPOSE: To evaluate the role of (18)F-flurodeoxiglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in predicting malignancy of thyroid nodules with indeterminate cytology. PATIENTS AND METHODS: We analysed 87 patients who have been scheduled to undergo surgery for thyroid nodule with indeterminate cytology. All patients underwent (18)F-FDG-PET/CT, multiparametric neck ultrasonography (MPUS), and (99m)Tc-methoxyisobutylisonitrile scintigraphy ((99m)Tc-MIBI-scan). Histopathology was the standard of reference. We compared the sensitivity (SE), specificity (SP), accuracy (AC), positive (PPV) and negative predictive (NPV) values of (18)F-FDG-PET/CT with those of (99m)Tc-MIBI-scan and MPUS in detecting cancer. Univariate and multivariate analyses evaluated the association between each diagnostic tool and histopathology. RESULTS: On histopathology, 69 out of 87 nodules were found to be benign and 18 to be malignant. The SE, SP, AC, PPV and NPV of (18)F-FDG-PET/CT were 94, 58, 66, 37 and 98% respectively. The SE, AC and NPV of (18)F-FDG-PET/CT were significantly higher than those of MPUS and (99m)Tc-MIBI-scan. The association of both positive (18)F-FDG-PET/CT and MPUS (FDG+/MPUS+) showed significantly lower SE (61% vs 94%) and NPV (88% vs 98%) than (18)F-FDG-PET/CT alone, but significantly higher SP (77% vs 58%). On univariate analysis, (18)F-FDG-PET/CT and the combination of FDG+/MPUS+ and of FDG+/MIBI- were all significantly associated with histopathology. On multivariate analysis, only FDG+/MIBI- was significantly associated with histopathology. CONCLUSION: The AC of (18)F-FDG-PET /CT in detecting thyroid malignancy is higher than that of (99m)Tc-MIBI-scan and MPUS. A negative (18)F-FDG-PET/CT correctly predicts benign findings on histopathology. The association of FDG+/MPS+ is significantly more specific than (18)F-FDG-PET/CT alone in identifying differentiated thyroid cancer. A positive (18)F-FDG-PET/CT is significantly associated with malignancy when qualitative (99m)Tc-MIBI-scan is rated as negative.

18F-FDG PET/CT is a prognostic biomarker in patients affected by bone metastases from breast cancer in comparison with 18F-NaF PET/CT.

AIM: To compare 18F-FDG PET/CT and 18F-NaF PET/CT with respect to disease prognostication and outcome in patients affected by bone metastases from breast cancer (BC). PATIENTS, METHODS: We retrospectively investigated 32 women with BC and documented bone metastases. Semi-quantitative parameters were applied to 18F-FDG PET/CT and 18F-Na PET/CT in order to evaluate disease extent and tumour metabolism. We used time-to-event analyses (Kaplan Meier and COX proportional hazard methods) to estimate progression-free (PFS) and overall survival (OS) in order to assess the independent prognostic value of 18F-FDG PET/CT and 18F-Na PET/CT. RESULTS: The sensitivity of 18F-NaF PET/CT (100%) was higher (p < 0.05) than that of 18F-FDG PET/CT (72% and 72%). None of the 18F-FDG PET/CT-negative patients showed disease progression at the end of follow-up. After adjustment for age, Ki-67 levels, presence of visceral metastases, hormone therapy, duration of bone disease and response to first-line therapy, only 18F-FDG SUV mean [HR 15.7, 95% confidence interval (CI) 1.15-214.5] and 18F-FDG whole-body bone metabolic burden (WB-B-MB) (HR 16.9; 95%CI 1.87-152.2) were independently and significantly associated with OS. None of the 18F-NaF PET/CT parameters were associated with OS. None of the conventional clinical prognostic parameters remained significantly associated with OS after the inclusion of PET/CT parameters in the model. CONCLUSION: 18F-FDG PET/CT is independently associated with OS in BC patients with bone metastases and its prognostic impact seems to be higher than conventional clinical and biological prognostic factors. Although 18F-NaF PET/CT has a higher diagnostic sensitivity than 18F-FDG PET/CT, it is not independently associated with OS.

Transglutaminase 1 gene mutations in Italian patients with autosomal recessive lamellar ichthyosis.

We analyzed the transglutaminase 1 gene locus in patients from six unrelated Italian families affected by autosomal recessive lamellar ichthyosis. In two families we identified a novel mutation (E520G) in the gene coding region, a previously reported splicing mutation (A3447G), and the mis-sense mutations S272P and V518M. The latter mutation, hitherto considered disease causing, was found to be a simple polymorphism. Linkage to transglutaminase 1 gene was excluded in two of the other four families examined. Single strand conformational polymorphism analysis of the transglutaminase 1 gene in the remaining two families did not reveal any alteration in the coding region. This finding confirms the genetic heterogeneity of the disease.

Pure pancreatic juice collection over 24 consecutive hours.

We collected pure pancreatic juice during an entire day and examined pancreatic secretory changes induced by ordinary meals in a male patient having an external drainage of the main pancreatic duct. The ingestion of breakfast, lunch, and dinner each caused a marked increase in pancreatic secretion above basal levels. The increase in both bicarbonate and protein output was very prolonged. The highest secretory outputs induced by meals were slightly higher than those produced by exogenous administration of submaximal doses of secretin and cerulein. The profile and magnitude of bicarbonate and protein secretion were similar.

Treatment of giardiasis reverses "active" coeliac disease to "latent" coeliac disease.

In patients with coeliac disease, a regression of intestinal damage without a gluten-free diet is a very rare event. We describe a young child with diarrhoea, intestinal mucosa atrophy and positive serum anti-endomysial and anti-tissue transglutaminase (anti-tTG) antibodies during intestinal giardiasis infection. He showed normal intestinal mucosa architecture and negative anti-endomysial and anti-tTG antibodies after his giardiasis was cured, although he continued to assume a normal diet. Re-evaluations on a 6-monthly basis showed that he was symptom free, and all haemato-chemical parameters were within normal limits. Three years after the initial diagnosis, a third intestinal biopsy showed: normal mucosa architecture; an increase in the intra-epithelial CD3+ and gamma/delta+ lymphocyte counts; and immunoglobulin-A anti-endomysial antibody detection in the supernatant of the intestinal mucosa culture incubated with gliadin. An active coeliac disease status, with intestinal mucosa atrophy, may regress to a latent coeliac disease status with normal intestinal mucosa histology after removal of the environmental factors that have presumably precipitated mucosa damage. Serum anti-endomysial and anti-tTG antibody behaviour is not a permanent, life-long feature and this must recommend the repetition of anti-endomysial or anti-tTG antibody assays in the same patient whenever coeliac disease diagnosis is again suspected, irrespective of previous negativity.