Rodrigo Salgado

Platelet number and interleukin-6 correlate with VEGF but not with bFGF serum levels of advanced cancer patients

SummaryWe have compared the platelet number and the serum concentration of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and interleukin-6 (IL-6) in 80 blood samples of 50 patients with advanced cancer. We have also measured the mitogenic effect of patient sera on endothelial cells in vitro in order to estimate the biological activity of serum VEGF. Serum VEGF concentration correlated with platelet number (r = 0.61; P < 10–4). Serum IL-6 levels correlated with platelet count (r = 0.36; P < 10–3), with serum VEGF levels (r = 0.55; P < 10–4) and with the calculated load of VEGF per platelet (r = 0.4; P = 3 × 10–4). Patients with thrombocytosis had a median VEGF serum concentration which was 3.2 times higher (P < 10–4) and a median IL-6 serum level which was 5.8 times higher (P = 0.03) than in other patients. Serum bFGF did not show an association with any of the other parameters. Patient sera with high VEGF and bFGF content stimulated endothelial cell proliferation significantly more than other sera (P = 4 × 10–3). These results support the role of platelets in the storage of biologically active VEGF. Platelets seem to prevent circulating VEGF from inducing the development of new blood vessels except at sites where coagulation takes place. IL-6, besides its thrombopoietic effect, also seems to affect the amount of VEGF stored in the platelets. This is in accordance with the indirect angiogenic action of IL-6 reported previously. The interaction of IL-6 with the angiogenic pathways in cancer might explain the stimulation of tumour growth occasionally observed during IL-6 administration. It also conforms to the worse outcome associated with high IL-6 levels and with thrombocytosis in several tumour types and benign angiogenic diseases.

Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia

Although angiogenesis is a prerequisite for the growth of most human solid tumours, alternative mechanisms of vascularisation can be adopted. We have previously described a non-angiogenic growth pattern in liver metastases of colorectal adenocarcinomas (CRC) in which tumour cells replace hepatocytes at the tumour–liver interface, preserving the liver architecture and co-opting the sinusoidal blood vessels. The aim of this study was to determine whether this replacement pattern occurs during liver metastasis of breast adenocarcinomas (BC) and whether the lack of an angiogenic switch in such metastases is due to the absence of hypoxia and subsequent vascular fibrinogen leakage. The growth pattern of 45 BC liver metastases and 28 CRC liver metastases (73 consecutive patients) was assessed on haematoxylin- and eosin-stained tissue sections. The majority of the BC liver metastases had a replacement growth pattern (96%), in contrast to only 32% of the CRC metastases (P<0.0001). The median carbonic anhydrase 9 (CA9) expression (M75 antibody), as a marker of hypoxia, (intensity × % of stained tumour cells) was 0 in the BC metastases and 53 in the CRC metastases (P<0.0001). There was CA9 expression at the tumour–liver interface in only 16% of the BC liver metastases vs 54% of the CRC metastases (P=0.002). There was fibrin (T2G1 antibody) at the tumour-liver interface in only 21% of the BC metastases vs 56% of the CRC metastases (P=0.04). The median macrophage count (Chalkley morphometry; KP-1 anti-CD68 antibody) at the interface was 4.3 and 7.5, respectively (P<0.0001). Carbonic anhydrase 9 score and macrophage count were positively correlated (r=0.42; P=0.002) in all metastases. Glandular differentiation was less in the BC liver metastases: 80% had less than 10% gland formation vs only 7% of the CRC metastases (P<0.0001). The liver is a densely vascularised organ and can host metastases that exploit this environment by replacing the hepatocytes and co-opting the vasculature. Our findings confirm that a non-angiogenic pattern of liver metastasis indeed occurs in BC, that this pattern of replacement growth is even more prevalent than in CRC, and that the process induces neither hypoxia nor vascular leakage.

Magnetic Resonance Imaging of the Brain

Magnetic resonance imaging (MRI) examinations of the brain can be performed with several coil types, depending on the design of the MRI unit and the information required. Traditionally, MRI examinations of the brain are performed with quadrature (i.e., circularly polarized) head coils. These volume coils are closely shaped around the head of the patient and usually present a so-called “bird-cage” configuration. Many coils are split in half, for easier patient access and positioning. Recently, phased-array head coils have become the standard of practice for state-of-the-art high-resolution MRI of the brain. Phased-array head coils contain multiple small coil elements, which are arranged in an integrated design which surrounds the head (e.g., 8-, 12- or even 32-channel head coils). Data from the individual coils are integrated by special software to compensate for the nonuniform distribution of the signal-to-noise ratio (SNR) between the peripheral and central parts of the brain. The major advantage of a multichannel, phased-array head coil is that it allows the application of parallel acquisition techniques (PAT), which can be used to speed up MRI. The concept is to reduce the number of phase-encoding steps by switching a field gradient for each phase-encoding step. Skipping, for example, every second phase-encoding line accelerates the acquisition speed by a factor of two. This is called the acceleration or PAT factor. The trade-off for this increased imaging speed is a decrease in SNR. Image reconstruction with PAT techniques is more complicated, and several algorithms have been described, depending on whether image reconstruction takes place before (SMASH, GRAPPA (generalized autocalibrating partially parallel acquisition)) or after (SENSE) Fourier transform of the image data.

Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer

The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis.

Soft tissue aneurysmal bone cyst

A soft tissue aneurysmal bone cyst located in the right gluteus medius of a 21-year-old man is reported. On conventional radiography, the lesion demonstrated a spherically trabeculated mass with a calcific rim. On CT scan, it showed a well-organized peripheral calcification resembling a myositis ossificans. On MRI, it presented as a multilocular, cystic lesion with fluid-fluid levels. The lesion had no solid components except for intralesional septa. Although findings on imaging and histology were identical to those described in classical aneurysmal bone cyst, diagnosis was delayed because of lack of knowledge of this entity and its resemblance to the more familiar post-traumatic heterotopic ossification (myositis ossificans).

Preprocedural CT Evaluation of Transcatheter Aortic Valve Replacement: What the Radiologist Needs to Know

Aortic valve stenosis is the most common valvular heart disease in the Western world. When symptomatic, aortic valve stenosis is a debilitating disease with a dismal short-term prognosis, invariably leading to heart failure and death. Elective surgical valve replacement has traditionally been considered the standard of care for symptomatic aortic valve stenosis. However, several studies have identified various subgroups of patients with a significantly elevated risk for surgery-related complications and death. Thus, not every patient is a suitable candidate for surgery. Recent developments in transcatheter-based therapies have provided an alternative therapeutic strategy for the nonsurgical patient population known as transcatheter aortic valve replacement (TAVR) (also called transcatheter aortic valve implantation or percutaneous aortic valve replacement). In TAVR, the native aortic valve is replaced with a bioprosthetic valve via a nonsurgical endovascular, transaortic, or transapical pathway. Nevertheless, several anatomic and technical criteria must be met to safeguard patient eligibility and procedural success. Therefore, noninvasive imaging plays a crucial role in both patient selection and subsequent matching to a specific transcatheter valve size in an effort to ensure accurate prosthesis deployment and minimize peri- and postprocedural complications. The authors review the relevant anatomy of the aortic root, emphasizing the implications of anatomic pitfalls for correct reporting of imaging-derived measurements and important differences between findings obtained with different imaging modalities. They also discuss the evolving role of computed tomography and the role of the radiologist in patient triage in light of current viewpoints regarding patient selection, device size selection, and the preprocedural evaluation of possible access routes. Online supplemental material is available for this article.

Circulating Basic Fibroblast Growth Factor is Partly Derived from the Tumour in Patients with Colon, Cervical and Ovarian Cancer

In order to investigate whether the high bFGF serum levels encountered in cancer patients are derived from the tumour, we analysed serum bFGF levels in 18 untreated randomly selected patients with operable colorectal, cervical and ovarian cancer in the blood draining the tumour, i.e., in mesenteric and uterine veins, and compared these with arterial samples. No significantly elevated bFGF levels were found in the veins draining the tumours compared with arterial samples in our patient population. This suggests that, in contrast to what is generally presumed, serum bFGF levels might also be derived from other sources besides the tumour, e.g., platelets.

Development of acute schmorl nodes after discography.

We report the development of acute Schmorl nodes at the L3-L4 intervertebral disc level after discography in a 36-year-old man. Although a few cases of acute Schmorl nodes have been reported in the literature, they have not been described because of discography. We surmise that the herniation of disc material through the vertebral endplates, with the ensuing formation of Schmorl nodes, should be regarded as a potential, but fortunately rare, complication of discography.

An unusual case of traumatic pneumatocele in a nine-year-old girl: A bronchial tear with clear bronchial laceration

Post‐traumatic pneumatoceles (traumatic pulmonary pseudocysts) after blunt thoracic trauma are not frequently observed. It is widely accepted that pneumatoceles are caused by compression of the lung resulting in bursting parenchyma, followed by decompression of the chest with negative intrathoracic pressure. We present a case of post‐traumatic pneumatocele in a nine‐year‐old girl who was crushed under the tailboard of a horse hamper. A multislice CT of the thorax clearly demonstrated a bronchial laceration pointing to bronchial disruption as an additional causative mechanism. Pediatr Pulmonol. 2009; 44:826–828.

Transcatheter aortic valve replacement: postoperative CT findings of Sapien and CoreValve transcatheter heart valves.

Transcatheter aortic valve replacement represents one of the most exciting medical technical developments in recent years, offering a much-needed therapeutic alternative for patients with severe aortic valve stenosis who, due to comorbidities and advanced age, are considered to be inoperable or at high surgical risk. The efficacy of this procedure compared with standard surgical intervention has been properly validated in multicenter randomized controlled trials (PARTNER A and B trials), leading to widespread clinical implementation, with over 50,000 procedures currently being performed worldwide each year. Although much of the attention has rightly focused on the potential role of computed tomography (CT) in the preprocedural assessment of the aortic root and the establishment of imaging-guided valve-sizing algorithms, less is known regarding the postprocedural CT characteristics of transcatheter heart valves (THVs). However, given the increasing worldwide recognition and clinical implementation of these devices, they will no doubt be encountered with increasing frequency in patients referred for thoracic CT, either for postprocedural evaluation of the aortic root or for unrelated reasons. Familiarity with these devices and their CT characteristics will increase diagnostic confidence and the value of the radiology report. The authors describe the physical and imaging properties of the currently commercially available THVs, their normal postprocedural imaging appearances, and potential complications that can be detected at CT. In addition, they discuss the relative strengths and weaknesses of CT and echocardiography in this setting.