Mirna Abraham-Nordling

Cancer and diverticulitis of the sigmoid colon. Differentiation with computed tomography versus magnetic resonance imaging: preliminary experiences

Background Both colon cancer and diverticular disease are common in the Western world. A challenge when patients present with clinical findings is that both diseases can present with symptoms that may mimic the other. Purpose To determine whether magnetic resonance imaging (MRI) could be helpful to differentiate between diverticulitis and cancer of the sigmoid colon compared to the differentiation offered by evaluation of multidetector computed tomography (CT) in a clinical situation. Material and Methods Thirty patients were consecutively included. Fifteen patients were under work-up for a recently diagnosed sigmoid cancer and 15 patients had recently been treated in hospital due to first-time acute sigmoid diverticulitis. All patients underwent CT, T2-weighted MRI and diffusion-weighted MRI. Anonymized examinations were retrospectively presented in random order to one experienced radiologist. Results With contrast-enhanced CT, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 66.7% (10/15) and 93.3% (14/15), respectively. Using T2-weighted and diffusion-weighted MR images, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 100% (14/14) and 100% (14/14), respectively. Conclusion MRI provides information that may contribute to improve the differentiation between sigmoid cancer and diverticulitis that is offered by CT. These encouraging results need to be confirmed in a larger study.

Colonic amyloidosis, computational analysis of the major amyloidogenic species, Serum Amyloid A

Amyloidosis is characterized by misfolding of proteins. The clinical gastrointestinal manifestations of amyloidosis may mimic other disease, such as inflammatory bowel disease or colonic cancer. As these patients have a high risk for bleeding and poor wound healing following surgery it is important to diagnose them correctly and do a careful preoperative assessment. The most common form of colonic amyloidosis is caused by Serum Amyloid A (SAA), an acute phase protein of unknown function. It is expressed in response to inflammation and the increased levels may lead to amyloidosis. The main treatment is to suppress the acute phase response and thereby reduce production of SAA. As no structure for SAA is available we aim to perform an in silico assessment of its structural and fibrillation properties. In the paper we propose an ab initio model of the structure of SAA, which consists of a five membered helical bundle with a fold related to the tetratricopeptide repeat domain. As there are uncertainties relating to the packing of the helices, each helical region is subjected to triplicate molecular dynamics simulations to assess the integrity of the structural region. The first helix, stretching from residues 1 to 13, is the least stable according to the simulations; almost all of the helical conformation is lost during the 10 ns simulations, whereas the other helices maintain portions that remain in an helical conformation in at least 80% of the simulations. All helices are also subjected to a single 100 ns simulation to investigate how the secondary structure develops over time. In them helix 1 adopts a β-hairpin structure similar to other fibril forming proteins. The β-hairpin can in turn multimerise and form a mature fibril structure. The mechanism behind the conformational transition appears to be driven by interactions of side chains of charged residues, particularly Arginine 1. It exchanges interaction partners in the simulation and stabilizes intermediate conformations on the folding pathway to the final β-hairpin.

Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

BackgroundWe aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions.FindingsIn the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation.ConclusionsA model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.

The value of preoperative computed tomography combined with ultrasound in the investigation of small indeterminate liver lesions in patients with colorectal cancer

Background Computed tomography (CT) is used routinely for the preoperative detection of colorectal cancer (CRC) metastases. When small indeterminate focal liver lesions are detected that are too small to characterize (TSTC) on CT, additional imaging is usually needed, resulting in a potential delay in obtaining a complete diagnostic work-up. Purpose To determine the diagnostic accuracy of ultrasound (US) of the liver performed in direct conjunction to CT in the preoperative investigation among patients with newly diagnosed CRC when indeterminate liver lesions were found on CT. Material and Methods Preoperative investigations with CT and consecutive US where CT had shown at least one focal liver lesion in 74 patients diagnosed with CRC between June 2009 and February 2012 were retrospectively reviewed. Either histopathological findings or a combination of imaging and clinical follow-up one to three years after surgery was used as the reference. Results Liver metastases were diagnosed with CT/US in 13 out of 74 patients (17.6%). In one patient, a liver cyst was preoperatively regarded as liver metastasis by a combined CT/US. The sensitivity and specificity for the CT with consecutive US procedure was 100% (13/13) and 98.4% (60/61). Conclusion US performed in conjunction with CT in patients with indeterminate focal liver lesions on CT is an accurate work-up for detection of liver metastases in patients with newly diagnosed CRC. Although our results are promising, they cannot be considered safely generalizable to all hospitals.