Paediatric Crohn disease patients with stricturing behaviour exhibit ileal granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody production and reduced neutrophil bacterial killing and GM-CSF bioactivity.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies are associated with stricturing behaviour in Crohn disease (CD). We hypothesized that CD ileal lamina propria mononuclear cells (LPMC) would produce GM-CSF autoantibodies and peripheral blood (PB) samples would contain GM-CSF neutralizing capacity (NC). Paediatric CD and control PBMC and ileal biopsies or LPMC were isolated and cultured and GM-CSF, immunoglobulin (Ig)G and GM-CSF autoantibodies production were measured by enzyme-linked immunosorbent assay (ELISA). Basal and GM-CSF-primed neutrophil bacterial killing and signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation (pSTAT5) were measured by flow cytometry. GM-CSF autoantibodies were enriched within total IgG for LPMC isolated from CD ileal strictures and proximal margins compared to control ileum. Neutrophil bacterial killing was reduced in CD patients compared to controls. Within CD, neutrophil GM-CSF-dependent STAT5 activation and bacterial killing were reduced as GM-CSF autoantibodies increased. GM-CSF stimulation of pSTAT5 did not vary between controls and CD patients in washed PB granulocytes in which serum was removed. However, GM-CSF stimulation of pSTAT5 was reduced in whole PB samples from CD patients. These data were used to calculate the GM-CSF NC. CD patients with GM-CSF NC greater than 25% exhibited a fourfold higher rate of stricturing behaviour and surgery. The likelihood ratio (95% confidence interval) for stricturing behaviour for patients with elevation in both GM-CSF autoantibodies and GM-CSF NC was equal to 5 (2, 11). GM-CSF autoantibodies are produced by LPMC isolated from CD ileal resection specimens and are associated with reduced neutrophil bacterial killing. CD peripheral blood contains GM-CSF NC, which is associated with increased rates of stricturing behaviour.

Positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer.

Malignant tumors with high glucose metabolic rates accumulate [18F]-fluorodeoxyglucose (FDG), a positron emitting tracer. The aim of this study was to evaluate FDG positron emission tomography (PET) for detection and staging of human cholangiocarcinoma (CC). Patients with adenocarcinoma of the biliary tree (n = 26), with benign lesions of the bile ducts (n = 8), and 20 control patients underwent FDG-PET (370 MBq [18F]-FDG, Siemens ECAT EXACT HR(+)). In a blinded fashion, 4 independent experts evaluated the PET scans visually and semiquantitatively using the standardized uptake value and a tumor/non-tumor ratio. All adenocarcinomas and benign lesions (sclerosing cholangitis, bile duct adenoma, Caroli's disease) were histologically proven and imaged by magnetic resonance imaging and endoscopic retrograde cholangioscopy. True-positive PET scans were obtained in 24 of 26 CC and false-negative scans in the other 2 (sensitivity 92.3%). The PET scan was true-negative in 18 of 20 controls and in all 8 benign biliary lesions (specificity 92.9%). Visual and semiquantitative evaluation using tumor/non-tumor ratios were equally accurate (accuracy 92.6%) whereas evaluation by standardized uptake value revealed lower accuracy (P <.05). Regional or hepatoduodenal lymph node metastases were detected with PET in only 2 of 15 cases whereas distant metastases (peritoneal carcinomatosis, pulmonary metastases) were diagnosed in 7 of 10 cases. In conclusion, PET is highly sensitive and specific for the detection and localization of CC. It can be helpful for diagnosis of distant metastases but is not suitable for detection of regional lymph node metastases.

[18F-FDG positron-emission-tomography in cervical carcinoma: preliminary findings]. / 18F-FDG-Positronen-Emissions-Tomographie bei Zervixkarzinom: Erste Ergebnisse.

18F-Fluorodesoxyglucose-Positron-Emission-Tomography (18F-FDG-PET) is a novel imaging modality for malignancies. This study was initiated to define the efficiency of PET in detecting and characterizing metabolically the primaries and in preoperatively assessing of lymphonodal metastases of cervical cancer. 15 patients with histologically proven cervical carcinoma were studied with 18F-FDG-PET regarding 18F-FDG-uptake of primary tumor and evidence as well as extent of lymphonodal metastases. 18F-FDG-PET and histopathological results were compared after radical hysterectomy with pelvic and supplementary in 7 cases paraaortal lymphadenectomy. All primary tumours showed 18F-FDG accumulation and had a mean maximal standardized uptake value (SUV) of 8.0 +/- 5.3. 3/6 lymph node metastases were obtained with 18F-FDG-PET. Micrometastases (size of metastasis < or = 0.2 cm) were present in 2 patients with false negative PET results. Regarding the subgroup with paraaortal lymph node dissection, PET detected one patient with metastases, the other one had micrometastasis, while metastasis was not observed by PET. The accuracy of PET is 73% for assessment of pelvic lymph nodes and 86% for assessment of paraaortal lymph nodes. In conclusion 18F-FDG accumulates reliably in primaries of cervical cancer. Regarding assessment of lymph node metastases PET seems to be of potential use, offering metabolic information independent of the size of metastatic lymph nodes. An improvement of accuracy can be expected if combined evaluation of morphologic and metabolic images is performed.

Improvement of brain SPECT by stabilization of Tc-99m-HMPAO with methylene blue or cobalt chloride. Comparison with Tc-99m-ECD.

AIM: This present study was carried out to investigate whether stabilization of Tc-99m-HMPAO with methylene blue (MB) or cobalt chloride (CC) causes a sensible improvement in image quality and how cerebral to noncerebral activity ratios compare with those of Tc-99m-ECD. METHODS: 30 minutes after preparation 400-600 MBq unstabilized Tc-99m-HMPAO (N = 35 patients), Tc-99m-HMPAO added with MB (N = 24 patients), added with CC (N = 30 patients) or Tc-99m-ECD (N = 28 patients) were injected. Radiochemical stability was measured in vitro with three chromatographical methods. Image quality was assessed quantitatively using two ratios, one of them determined by count densities of brain/scalp (Os), the other one by count densities of brain/nose (QN). In addition, image quality (0 = bad, 3 = excellent) and background activity (0 = high, 3 = no) were visually assessed by three independent observers. RESULTS: In contrast to unstabilized Tc-99m-HMPAO the integrity of the complexes of MB-Tc-99m-HMPAO, CC-Tc-99m-HMPAO and Tc-99m-ECD decreased only by a few percent during a period of 2 hours after reconstitution (66.8 +/- 9.9 vs. 93.0 +/- 2.5, 91.8 +/- 1.9 and 96.9 +/- 1.4%, p < 0.001). Qs and Qn (m.v. +/- SD) differed significantly between studies using unstabilized Tc-99m-HMPAO (3.0 +/- 0.4 and 2.1 +/- 0.3), MB-Tc-99m-HMPAO (3.4 +/- 0.4 and 2.3 +/- 0.3), CC-Tc-99m-HMPAO (3.6 +/- 0.6 and 2.6 +/- 0.4) and those using Tc-99m-ECD (4.3 +/- 0.7 and 4.8 +/- 1.4, p < 0.05 and < 0.001). Stabilization with CC or MB resulted in significant higher scoring of image quality and lower scoring of background activity in comparison to that of unstabilized Tc-99m-HMPAO, without reaching the scores obtained with Tc-99m-ECD. CONCLUSIONS: It is concluded that stabilization of Tc-99m-HMPAO with MB or CC definitely improves image quality in rCBF-SPECT, without reaching that of Tc-99m-ECD. Improvement of image quality results from the reduction of the amount of decomposition products that contribute to considerable extracerebral activity.