Role of Bowel Ultrasound in the Diagnosis and Follow-up of Patients with Crohn's Disease

Crohn's disease (CD) is an inflammatory chronic bowel disorder; it can involve the whole gastrointestinal tract, but its localization in the ileum or colon is most common. The reference standard for the diagnosis of CD is ileocolonoscopy with histologic assessment. The reference standard for the detection of any complications is surgery. However, imaging techniques have an important role both in the detection/localization of CD and in the follow-up of CD patients. In the last few years, the technical development of ultrasound equipment, the advent of new technologies such as elastography and mostly the increased expertise of sonographers have boosted the role of bowel ultrasound in assessment of the gastrointestinal tract. In fact, bowel ultrasound is particularly attractive thanks to its widespread availability, non-invasiveness, low cost and good reproducibility, as it can be easily repeated during follow-up. The aim of this article is to provide an extensive overview of the actual role of bowel ultrasound in the detection and follow-up of patients with CD.     

Contrast-enhanced computed tomography and ultrasound-guided liver biopsy to diagnose dysplastic liver nodules in cirrhosis

BackgroundDysplastic nodules in cirrhosis herald a very high risk of transition to hepatocellular carcinoma. A better understanding of the relationships between dysplastic nodules and hepatocellular carcinoma development may help refining strategies of enhanced follow-up.MethodsAll consecutive cirrhotics with a histologically proven de novo dysplastic nodule, were retrospectively identified and underwent alternating abdominal ultrasound and contrast-computed tomography every 3 months. An ultrasound-guided liver biopsy was the diagnostic gold standard, whereas surveillance and recall policies were according to current guidelines.ResultsAmong 36 patients with dysplastic nodule (21 low-grade, 15 high-grade, 17.4 ± 2.6 mm), 17 (47%) showed arterial wash-in, 15 (42%) portal/venous hypodensity whereas 4 (11%) had neither pattern. During 6–128 (median 36) months, 21 patients developed a hepatocellular carcinoma at a rate of 13.8% per year, intranodular = 8.7% vs extranodular = 7.1% per year. Hepatocellular carcinoma occurred more frequently in high-grade than low-grade dysplastic nodules (32.2% vs 9.3% per year, p = 0.0039); the maximum time to hepatocellular carcinoma transformation was 27 months for intranodular vs 67 months for extranodular tumours (p = 0.025). No contrast-computed tomography pattern predicted neoplastic transformation of dysplastic nodules.ConclusionThe histological examination of liver nodules in cirrhosis lacking the imaging hallmark of hepatocellular carcinoma improves both prognostication and outcome of surveillance, since it dictates the intensity of the radiological follow-up.     

Helper strategy in tumor immunology: Expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy

Two main kinds of immune strategy are possible against neoplasia. The first potentiates a selected effector arm. In vitro culture with exogenous interleukin-2 (IL-2) increases the activity of natural killer cells and leads to the expansion of T cytotoxic lymphocytes. Systemic reinfusion of both of these cells with high doses of IL-2 mediates the regression of a variety of murine and human tumors. In an alternative strategy, a few regulatory lymphocytes turn on immune reactivity by triggering a cascade of interconnected effector functions. The efficacy of this strategy rests on the repertoire of effector mechanisms moved to action. An effective immunoregulatory maneuver is the addition of helper determinants on the surface of tumor cells. Its power can be further increased by the pre-induction of helper T lymphocytes specific to the helper determinants. This approach can be achieved in mice by coupling muramyl dipeptides to tumor cells, along with eliciting T lymphocytes specifically reactive to Bacillus Calmette-Guerin. Noncytotoxic T helper lymphocytes produce factors which recruit nonspecific (macrophages) as well as specific (cytolytic T lymphocytes) anti-tumor attacking cells. In this way protection can be afforded against primary tumors and metastases, as well as leukemia cells. As the activity of helper lymphocytes rests mostly on lymphokine release, the use of molecularly defined lymphokines mimicking T-helper functions has also been attempted. In a few experimental models, the association of low doses of IL-2 with non-reactive lymphocytes from tumor-bearing mice promotes an effective anti-tumor reaction in the host. Moreover, the combination of distinct lymphokines can also build a molecularly defined helper system able to activate in sequence non-specific and specific anti-tumor reactions in vivo. Trials intended to evaluate the clinical impact of these helper approaches in the management of human tumors are being started or are already under way.     

Severity of bone marrow involvement in patients with Gaucher's disease evaluated by scintigraphy with 99mTc-sestamibi.

Gaucher's disease is a lysosomal storage disorder due to a genetically transmitted deficiency of the enzyme glucocerebrosidase. In the most common form of the disease (type 1), accumulation of glucosylceramide in the reticuloendothelial cells of liver, spleen, and bone marrow leads to visceromegaly, anemia, thrombocytopenia, and osteopenia. Skeletal manifestations secondary to infiltration of the bone marrow by Gaucher's cells are detectable by radiography only in advanced stages. Imaging of bone marrow involvement can be performed indirectly by magnetic resonance techniques or by bone marrow scintigraphy with radiocolloids. However, both procedures lack specificity because the normal bone marrow, rather than the pathologic process, is imaged. The aim of this study was to assess the reliability of (99m)Tc-sestamibi scintigraphy for direct evaluation of bone marrow involvement. METHODS: Seventy-two patients with type 1 and 2 patients with type 3 Gaucher's disease (35 males, 39 females) were enrolled in the study. The mean age +/- SD was 31.9 +/- 16.5 y (range, 3-76 y), and the average duration of the disease manifestations when performing scintigraphy was 12.95 y (median, 10.5 y; range, 0-44 y). Forty-three of 74 patients had never received enzyme replacement therapy (ERT), whereas 31 patients were already being treated with ERT. (99m)Tc-Sestamibi was injected intravenously (6-8 MBq/kg of body weight) and imaging was recorded at the lower limbs 30 min after injection, at the plateau of tracer accumulation in the involved bone marrow. The scans were evaluated visually, assigning a semiquantitative score based on the extension and intensity of uptake in the bone marrow of the lower limbs (0 = no uptake; 8 = maximum uptake). The scintigraphic score was entered into complex statistical analysis, which included a series of clinical and blood chemistry parameters defining overall severity of the disease. RESULTS: (99m)Tc-Sestamibi scintigraphy showed that 71 of 74 patients had some degree of bone marrow involvement. The scintigraphic score was highly correlated with an overall clinical severity score index (SSI) and with various parameters contributing to the SSI, either positively or negatively. The highest correlation of the scintigraphic score was found with an overall biochemical marker of disease severity (serum chitotriosidase). ERT-naive patients showed high correlation of the scintigraphic score with the clinical SSI, with a radiographically based score, and with serum chitotriosidase. In the ERT-treated patients, the scintigraphic score was correlated with the clinical SSI, with hepatomegaly, and with hemoglobin. CONCLUSION: (99m)Tc-Sestamibi uptake reliably identifies bone marrow infiltration by Gaucher's cells. The scintigraphic score is helpful for defining the severity of bone marrow involvement and for comparing patients. (99m)Tc-Sestamibi scintigraphy, which provides topographic information about the sites involved by the disease, is highly correlated with other parameters of disease severity and appears to correlate with response to ERT.     

Transient elastography identifies liver recipients with nonviral graft disease after transplantation: a guide for liver biopsy

Transient elastography (TE) reliably predicts the severity of recurrent hepatitis C virus after orthotopic liver transplantation (OLT); however, its accuracy in evaluating nonviral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients [37 for hepatitis B virus/hepatitis D virus (recurrence-free), 20 for autoimmune/cholestatic liver disease, 6 for alcoholic liver disease, and 6 for mixed etiologies] underwent protocol/on-demand liver biopsy (LB) and concomitant TE. A histological diagnosis of graft disease was made according to criteria defined by the Banff working group. Sixty-five patients (94%) had reliable TE examinations during a median post-OLT follow-up of 18 months (range = 7-251 months). LB samples (median length = 35 mm) showed graft damage in 28 patients (43%): idiopathic chronic hepatitis (11), steatohepatitis (3), rejection (3), cholangitis (2), and autoimmune/cholestatic recurrence (9). Patients with graft damage had significantly higher serum liver enzyme levels and TE results (median = 7.8 kPa, range = 5.4-27.4 kPa) than the 37 patients without graft damage (median = 5.3 kPa, range = 3.1-7.4 kPa, P < 0.001). By a receiver operating characteristic curve analysis, 2 TE cutoffs for the diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. The pretest probability of graft damage was 43%; in patients with TE values ≤5.3 kPa, the posttest probability of graft damage fell to 0%, but in patients with TE results >7.4 kPa, the posttest probability increased to 100%. In conclusion, the dual TE cutoff allows accurate discrimination between the absence and presence of nonviral liver graft damage and improves the clinical management of OLT recipients in terms of the selection of patients most in need of LB.