Laser-induced thermotherapy (LITT) of liver metastases: MR-guided percutaneous insertion of an MRI-compatible irrigated microcatheter system using a closed high-field unit

PURPOSE: To evaluate the efficacy and safety of a new MRI-compatible irrigated laser microcatheter system for thermal ablation of liver metastases. MATERIAL AND METHODS: The new microcatheter system consists of a titanium needle with a diameter of 1.5 mm and a surrounding Teflon catheter with an outer diameter of 1.8 mm (5.5 F). In vitro laser-induced coagulation of bovine liver tissue was performed to determine the optimal perfusion rate of cooling saline flow, maximum laser energy, and ablation time. Laser-induced thermotherapy using the new microcatheter system, an Nd:YAG laser (Dornier), and a flexible laser light guide (Somatex GmbH, Berlin, Germany) was performed in 28 patients with liver metastases. Percutaneous insertion and positioning of multiple microcatheters in the lesion and monitoring of therapy was performed with a closed high-field MRI scanner using T1-weighted gradient-echo sequences during breath-hold. RESULTS: A perfusion rate of 0.75 mL/minute, a laser energy of 15 W, and an ablation time of 20 minutes were found suitable to achieve safe and sufficient ablation of metastatic tissue. The mean volume of induced coagulation in vitro was 23.9 mL. Ablation of liver metastases in patients was technically and clinically successful. CONCLUSION: The new microcatheter system allows for both catheter placement and monitoring of therapy using a single imaging modality. This shortens the procedure and enables more precise puncture and therapy of liver metastases. Due to the miniaturized design of the catheter and the real-time monitoring, the procedure is minimally invasive and very well tolerated by patients. This new technique seems to be a safe and feasible alternative in treating liver metastases.     

Prospective evaluation of contrast-enhanced MRI in the depiction of peritoneal spread in primary or recurrent ovarian cancer

The purpose of this study was to assess the accuracy of MRI in the staging of intra-abdominal tumor seeding of ovarian carcinoma. Fifty-seven patients with suspected primary or recurrent ovarian carcinoma were included in this study. All patients received laparotomy within 8 weeks after MRI. The MRI protocol included fat-saturated T1-weighted spin-echo (SE) sequences pre- and post i.v. application of gadopentetate dimeglumine. The criteria for tumor manifestation was contrast enhancement of intra-abdominal soft tissue lesions or peritoneum. The image review was performed by a blinded radiologist, a specialist in gynecological and abdominal MR imaging. Results were compared with findings during laparotomy. Sensitivity, specificity, positive and negative predictive values, and corresponding 95% confidence intervals were calculated for single intra-abdominal locations and for groups of locations defined according to surgical strategies for intra-abdominal cytoreduction. Laparotomy and histopathology confirmed 251 abdominal tumor locations. Sensitivity was high in lower pelvis locations (73–83%) except for ureter or bladder infiltration (40%). Bowel or mesentery locations displayed sensitivity values from 73 to 77%. Sensitivity was very low for pelvic lymph nodes (28%), greater omentum (38%), and lesser sac (43%). Magnetic resonance imaging based on contrast-enhanced fat-saturated T1 SE sequences improves planning of cytoreduction preceding chemotherapy in advanced primary or relapsed ovarian carcinoma. Electronic Publication     

Imaging of large vessel vasculitis with <Superscript>18</Superscript>FDG PET: illusion or reality? A critical review of the literature data

Fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of ¹⁸FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the ¹⁸FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging.T. Belhocine and D. Blockmans contributed equally to this review article.     

AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain

INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by ACE inhibitors has been demonstrated to reduce total mortality in cardiovascular diseases. This advantage was attributed in part to changes of autonomic cardiovascular control, exemplified by an increase of heart rate variability (HRV) and baroreflex gain (BRG). We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG. MATERIALS AND METHODS: In a double-blind randomized cross-over design 25 young males took eprosartan (600 mg/day) and placebo each for a period of 7 days with a wash-out period of at least 4 weeks in between. At the end of the intake phases simultaneous recordings of arterial blood pressure (AP; Finapres) and electrocardiogram (ECG) were taken. Power spectra of HRV and arterial blood pressure variability (APV) were calculated by fast Fourier transform (FFT) and served to calculate BRG. Ang-II levels were measured by radioimmunoassay. RESULTS: Eprosartan tended to lower mean AP, it slightly increased heart rate (HR) (p<0.05), and markedly increased circulating Ang-II levels (p<0.01). Eprosartan diminished the total power of HRV (p<0.05) and the BRG (p<0.01). The low/high frequency (LF/HF) ratio of HRV and the APV were not altered. CONCLUSIONS: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. We speculate that these findings are due to the marked increase in circulating angiotensin II (Ang II). Further studies are needed to clarify whether angiotensin type 1 (AT1) blockers with potential actions inside the blood-brain barrier (BBB) may have different effects on HRV and BRG.     

The value of SPET/CT in chronic osteomyelitis

Immunoscintigraphy with technetium-99m labelled anti-granulocyte antibodies (AGA) is an equivalent technique to imaging with in vitro-labelled leucocytes, which is now considered state of the art in the diagnostic work-up of patients with suspected post-traumatic chronic osteomyelitis. In this study, we evaluated the use of a combined single-photon emission tomography/computed tomography (SPET/CT) device to improve detection and anatomical definition of inflammatory bone lesions. Twenty-seven patients with 29 sites of suspected bone infection underwent immunoscintigraphy with 750 MBq ^99mTc-labelled AGA. Planar scans were acquired immediately, 4 h and 24 h after injection, and combined SPET/CT was performed using a dual-head multifunctional gamma camera equipped with a low-power X-ray system. Accumulation of AGA in inflammatory lesions was quantitated, comparing uptake at 4 and 24 h after injection. The validation was based on culture data derived from surgical or biopsy samples (20 lesions in 18 patients) or clinical follow-up without further therapy for more than 6 months (nine lesions). On a lesion-by-lesion basis 19 true positive, one false positive and nine true negative findings were obtained. SPET/CT correctly identified the location of all positive foci in the appendicular skeleton and that of a cold lesion in the axial skeleton. It also enabled differentiation between soft tissue infection, septic arthritis and osteomyelitis, as well as between cortical, corticomedullary and subperiosteal foci. Sensitivity was identical for SPET and SPET/CT (100%), whereas specificity was improved from 78% to 89% by the use of SPET/CT. Combined SPET/CT improves the accuracy of immunoscintigraphy by allowing correct differentiation between soft tissue infection and bone involvement. This technique may gain clinical relevance in the selection of patients for surgical therapy.     

Benefit of anatomical-functional image fusion in the diagnostic work-up of neuroendocrine neoplasms

The aim of this prospective study was to evaluate anatomical-functional image fusion using the new technology of combined transmission and emission tomography (SPET/CT) in patients with neuroendocrine tumours (NET). Fifty-four patients with known or suspected NET prospectively underwent both tumour scintigraphy with (111)In-octreotide (n=43) or (123)I-MIBG (n=11) and contrast-enhanced high-end spiral CT. Scintigraphy was performed using a gamma camera (Millennium VG & Hawkeye, GE) with an integrated X-ray tube for combined transmission and emission tomography. SPET and high-end CT were interpreted blinded with regard to localisation and classification of lesions. Analysis of fused images (SPET/CT) was done on a lesion-by-lesion basis, followed by re-evaluation of SPET and high-end CT by consensus. The standard of reference for confirming the presence or absence of malignancy was either histopathology or clinical and imaging follow-up data. A total of 120 lesions were identified by CT and/or scintigraphy. This group included four patients with negative SPET but eight liver lesions on CT that were proven to be metastases. We excluded from the analysis two patients with no evidence of tumour on either modality, two lesions that lacked comparison with the standard of reference and two patients, each with two lesions, who were lost to follow-up. In 56 of the 114 evaluated lesions (49%), the results of SPET and CT were concordant; all lesions were interpreted as malignant. In 58 of 114 lesions (51%), consensus reading of fused images changed the image interpretation of 39 CT scans and 19 SPET studies: 31 lesions previously interpreted as equivocal (n=10) or benign (n=21) were re-classified as malignant and 27 lesions previously interpreted as equivocal (n=19) or malignant (n=8) were re-evaluated as benign. The highest accuracy (99%) in classifying NET lesions was achieved by combined analysis of SPET/CT ("hawkeye") and high-end CT. The specificity of SPET/CT was significantly higher than that of CT alone (P=0.0026) and slightly higher than that of SPET alone, but the accuracy of SPET/CT was inferior to that of side-by-side analysis of SPET and high-end CT (P=0.013) or visual correlation of SPET/CT and high-end CT (P<0.0001). Therapy was changed in 14 of 50 patients (28%) owing to the results of image fusion: in five patients tumour could be excluded, three patients were spared unnecessary surgery because of additional lesions indicating systemic tumour spread, in four patients the surgical approach was changed owing to precise tumour localisation and minimising of the surgical field, and in two patients medical and radiopeptide therapy was changed. Anatomical-functional image fusion allows for improved localisation and characterisation of NET with resultant alteration of the treatment approach in a substantial proportion of patients.     

Lactobacilli attenuate bacteremia and endotoxemia associated with severe intra-abdominal infection

BACKGROUND: Systemic administration of antibiotics or selective decontamination is frequently used in the prophylaxis and treatment of infections originating from the gastrointestinal flora. In this study, we wanted to compare the protective effect of enteral administration of lactobacilli to gentamicin against severe intra-abdominal infection. METHODS: Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP). Rats were pretreated with saline, Lactobacillus R2LC, and gentamicin. Bacterial growth and endotoxin levels in the blood, reticuloendothelial system (RES)-function, and intestinal transit were determined up to 24 hours after CLP. RESULTS: CLP-provoked bacteremia was significantly reduced by 48% and 55% in lactobacilli- and gentamicin-treated rats, respectively. Notably, CLP-induced endotoxemia was abolished at 12 hours, and reduced by 47% at 24 hours, in rats pretreated with lactobacilli. Gentamicin reduced endotoxin levels provoked by CLP by 86% at 12 hours, but had no effect at 24 hours. Lactobacilli had no effect on the clearance of Escherichia coli (E coli) from the blood, whereas intestinal transit was increased in lactobacilli-treated animals, suggesting that the beneficial effect of Lactobacillus R2LC is not related to an increase of phagocytic capacity but may rather be partly attributable to an enhanced intestinal motility. CONCLUSION: Enteral administration of Lactobacillus R2LC attenuates bacteremia and endotoxemia associated with intra-abdominal infection in rats.     

Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study

Purpose The safety and efficacy of oral metronomic low-dose treosulfan chemotherapy in combination with the cyclooxygenase-2 (COX-2) inhibitor rofecoxib as a compound with antiangiogenic potential, a therapeutic regimen optimally targeting endothelial cells instead of tumor cells, were assessed in pretreated advanced melanoma patients.Methods Endothelial cells were analyzed for proliferation, apoptosis and cytotoxicity in response to increasing concentrations of treosulfan, either in the absence or presence of COX-2 inhibitor, to determine whether inhibition of COX-2 enhanced the effect of treosulfan on cell function. In a clinical pilot study, 12 consecutive patients with pretreated advanced melanoma, meeting the eligibility criteria were enrolled. Patients received combined daily treosulfan chemotherapy (500 mg) with rofecoxib (25 mg). Metastatic lesions were assessed every 12 weeks. Patients with responsive or stable disease were eligible for a further 12-week treatment period. Response criteria according to the WHO handbook for reporting results of cancer treatment were applied. Side effects were classified according to the National Cancer Institute's Common Toxicity Criteria v2.0.Results At noncytotoxic concentrations, treosulfan inhibited endothelial cell proliferation in a dose-dependent fashion. Simultaneous inhibition of COX-2 significantly increased the extent to which treosulfan suppressed cell proliferation, without inducing cytotoxicity. In the pilot study in which 12 patients were treated, toxicity was mild; only hematologic toxicity of grade II was seen. An objective response was noted in one patient, and four patients showed stabilization of their disease for 24 weeks (one) and 36 weeks (three). The patient who had a partial response subsequently showed stable disease for 48 weeks. The median survival time was 13 months.Conclusions As increases in response rates following polychemo- or biochemotherapy have not been shown to correlate with prolongation in overall survival, more durable control of metastatic melanoma represents an attractive therapeutic goal. Thus, regimens scheduled to primarily target endothelial cells may potentially provide a palliative alternative that preserves quality of life in the absence of significant treatment-related toxicity.