Mural Crohn disease: correlation of dynamic contrast-enhanced MR imaging findings with angiogenesis and inflammation at histologic examination--pilot study.

PURPOSE: To determine mural perfusion dynamics in Crohn disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to correlate these with histopathologic markers of inflammation and angiogenesis. MATERIALS AND METHODS: Ethical permission was given by the University College London Hospital ethics committee, and informed consent was obtained from all participants. Eleven consecutive patients with Crohn disease (eight female patients, three men; mean age, 39.5 years; range, 16.4-66.6 years) undergoing elective small-bowel resection were recruited between July 2006 and December 2007. Harvey-Bradshaw index, C-reactive protein (CRP) level, and disease chronicity were recorded. Preoperatively, dynamic contrast-enhanced MR imaging was performed through the section of bowel destined for resection, and slope of enhancement, time to maximum enhancement, enhancement ratio, the volume transfer coefficient K(trans), and the extracellular volume fraction v(e) were calculated for the affected segment. Ex vivo surgical specimens were imaged to facilitate imaging-pathologic correlation. Histopathologic sampling of the specimen was performed through the imaged tissue, and microvascular density (MVD) was determined, together with acute and chronic inflammation scores. Correlations between clinical, MR imaging, and histopathologic data were made by using the Kendall rank correlation and linear regression. RESULTS: Disease chronicity was positively correlated with enhancement ratio (correlation coefficient, 0.82; P = .002). Slope of enhancement demonstrated a significant negative correlation with MVD (correlation coefficient, -0.86; P < .001). There was a negative correlation between CRP level and slope of enhancement (correlation coefficient, -0.77; P = .006). Neither acute nor chronic inflammation score correlated with any other parameter. CONCLUSION: Certain MR imaging-derived mural hemodynamic parameters correlate with disease chronicity and angiogenesis in Crohn disease, but not with histologic and clinical markers of inflammation. Data support the working hypothesis that microvessel permeability increases with disease chronicity and that tissue MVD is actually inversely related to mural blood flow.

Mural inflammation in Crohn disease: location-matched histologic validation of MR imaging features.

PURPOSE: To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference. MATERIALS AND METHODS: Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate. RESULTS: AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS. CONCLUSION: Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.

Clinical-radiological scoring system for enhanced diagnosis of acute appendicitis.

INTRODUCTION: Acute appendicitis is the most common surgical condition in industrialized countries. However, diagnosis in borderline cases is often cumbersome and requires follow-up examinations, and/or a Computed Tomography examination. Therefore, our aim was to develop a combined clinical and sonographic score to enhance prediction of acute appendicitis. PATIENTS AND METHODS: The modified Alvarado score and various established sonographic criteria were investigated in 132 patients with suspected acute appendicitis. Two models were computed accounting for missing values. After analysis of sensitivity and specificity for the modified Alvarado score, logistic regression analysis was performed to identify significantly contributing sonographic features. RESULTS: The threshold of the logistic regression analysis of the two models resulted in the formula: modified Alvarado score+axial Appendix diameter [mm]. When the Appendix diameter is>8mm, 1 point/mm is added, while for a diameter<8mm, 1 point/mm is subtracted. The cut-off value is≥13 for acute appendicitis with a sensitivity 91.4% and a specificity of 100%, compared to a sensitivity of 90% and a specificity of 84.4% for the modified Alvarado score in our cohort. CONCLUSION: The established modified Alvarado score for diagnosis of acute Appendicitis can be improved by adding the axial diameter of the Appendix in a sonographic examination.

Frequency and spectrum of cancers in the Peutz-Jeghers syndrome.

BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

Essential requirements of a CT colonography service.

There are many potential challenges to developing a high quality, efficient CT colonography service. Some are clear and predictable, for example creating CT capacity and securing financial resources, but some are less obvious, such as harnessing local support or changing referral practice amongst clinical colleagues. Notwithstanding, such barriers will need to be overcome to deliver a well-resourced, successful CT colonography programme. This article utilises the authors' experience of developing their own CT colonography service from scratch (now examining >1200 patients per annum) and relevant published articles on 'Standards' of practice and training to recommend how others might provide CT colonography in their own patient communities. We offer a practical guide and will emphasise the need for a multi-disciplinary approach with locally agreed protocols and service objectives.

High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors.

BACKGROUND: Desmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery. METHODS: Since 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP-associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR). RESULTS: Of the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP-associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoing surgery at other institutions. Of these, two patients had SD and two patients had a PR to CR. CONCLUSIONS: The patients with desmoid tumors who were managed conservatively with high-dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP-associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high-dose tamoxifen and sulindac as the primary treatment for patients with FAP-associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined.