Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control.

BACKGROUND: Current data on the use of irreversible electroporation (IRE) in the treatment of prostate cancer (PCa) is limited. We aim to evaluate the safety, short-term functional and oncological outcomes of focal IRE in low-intermediate risk PCa. METHODS: Between February 2013 and May 2014, 32 consecutive men underwent IRE at a single centre. Patients with low-intermediate risk PCa who had not received previous PCa treatment were included for analysis. The tumour was ablated using 3-6 electrodes, ensuring a minimum 5-mm safety margin around the visible magnetic resonance imaging (MRI) lesion. Follow-up included recording Clavien complications, Expanded Prostate Cancer Index Composite (EPIC) questionnaires (baseline, 1.5, 3, 6 months), 6-month multi-parametric MRI (mp-MRI) and 7-month biopsy. Findings on mp-MRI and biopsy were sub-divided into infield, adjacent or outfield of the treatment zone. RESULTS: Twenty-five men were included for final analysis. Safety follow-up revealed one Clavien Grade 3 complication and five Grade 1 complications. Functional follow-up confirmed no significant change in American Urological Association urinary symptom score, sexual or bowel function. Infield, there were no suspicious findings on mp-MRI (n=24) or biopsy (n=21) in all patients. Adjacent to the treatment zone, five (21%) had suspicious findings on mp-MRI with four (19%) proving to be significant on biopsy. Outfield, there were two (8%) with suspicious findings on mp-MRI and one (5%) significant finding on biopsy. For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance. CONCLUSIONS: In selected patients with low-intermediate risk PCa, focal IRE appears to be safe with minimal morbidity. There were no infield recurrences and 76% of patients were histologically free of significant cancer at 8 months. Almost all recurrences were adjacent to the treatment zone, and this was addressed by widening the treatment margins.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PURPOSE: We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. MATERIALS AND METHODS: A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. RESULTS: Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). CONCLUSIONS: In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers.

Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer.

BACKGROUND: To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. METHODS: We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. RESULTS: Overall, 34 patients with a mean age of 65 years (s.d. = ± 6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR) = 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR = 5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR = 1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment. CONCLUSIONS: Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.

The relationship between knee adduction moment and cartilage and meniscus morphology in women with osteoarthritis.

OBJECTIVE: The aim of this cross-sectional study is to investigate the relationship between knee adduction moment and knee adduction angular impulse and meniscus, cartilage and bone morphology in women with knee osteoarthritis (OA). METHOD: Forty-five women aged >40 years with OA in at least one knee, according to American College of Rheumatology clinical criteria were studied. The knee joint loading was assessed by three-dimensional motion analysis system during gait. Three Tesla magnetic resonance imaging (MRI) with a coronal T2-weighted spin echo sequence was used for evaluating meniscus pathology, and a coronal T1-weighted gradient echo sequence for quantifying cartilage morphology and bone surface size. Cartilage thickness, denuded area and subchondral area in the femorotibial joint was measured using custom software. RESULTS: A higher peak knee adduction moment was observed in participants with medial compared to those with lateral tears (2.92+/-1.06 vs -0.46+/-1.7, P<0.001). Participants with a higher knee adduction moment displayed a larger medial meniscus extrusion (r=0.532, P<0.001) and a lower medial meniscus height (r=-0.395, P=0.010). The inverse relationship was observed for the lateral meniscus. A higher knee adduction moment was also associated with a higher ratio of the medial to lateral tibial subchondral bone area (r=0.270, P=0.035). By contrast, cartilage thickness and denuded areas in the femur and tibia were not related to the knee adduction moment. Similar results were found for the relationship between knee adduction angular impulse and meniscus, cartilage and bone morphology. CONCLUSIONS: Dynamic knee joint loading is significantly related to meniscus pathology and bone size, but not to cartilage thickness in women with OA.

A growth in bipolar disorder?

OBJECTIVE: This case report suggests that screening of patients with psychiatric symptoms using modern neuroimaging can help identify organic causes of mental illness. METHOD: A single case study was reported. RESULTS: We report the case of a 25-year-old woman with a recent diagnosis of bipolar II disorder having an magnetic resonance imaging (MRI) scan as part of a research project that reveals an intraventricular brain tumour. The latter is most likely the cause of her irritability and 'hypomanic' symptoms and is defined anatomically using diffusion tensor imaging and structural and functional imaging using MRI and positron emission tomography. CONCLUSION: The lesion in this individual case most probably produces mood symptoms by impinging upon the fornix, a component of the limbic system. However, more generally, the increase in diagnosis of bipolar disorder has to be tempered against alternate causes of similar symptoms and necessitates vigilance of potential organic mechanisms.

Degenerative meniscus tears and mobility impairment in women with knee osteoarthritis.

OBJECTIVE: Meniscus tears are often presumed to be associated with a traumatic event, but they can also occur as a result of the cartilage degeneration process in osteoarthritis (OA). The aim of this paper is to describe the prevalence and clinical correlates of degenerative meniscus tears in women with knee OA. METHOD: The subjects were women screened for a double-blind, sham-exercise controlled clinical trial for women over 40 years of age with OA in at least one knee, according to American College of Rheumatology (ACR) clinical criteria. The presence of meniscus tears was assessed via a 3T Intera (Philips Medical Systems) magnetic resonance image (MRI). Clinical examination included a history of arthritis onset and physical examination of the lower extremities. Physical assessments included body composition, muscle strength, walking endurance, gait velocity, and balance. In addition, pain and disability secondary to OA, physical self-efficacy, depressive symptoms, habitual physical activity level and quality of life were assessed via questionnaires. RESULTS: Almost three-quarters (73%) of the 41 subjects had a medial, lateral, or bilateral meniscus tear by MRI. Walking endurance and balance performance were significantly impaired in subjects with a degenerative meniscus tear, compared to subjects without tears, despite similar OA duration, symptoms, and disability, body composition, and other clinical characteristics. CONCLUSION: Meniscus tears, diagnosed by MRI, are very common in older women with knee OA, particularly in the medial compartment. These incidentally discovered tears are associated with clinically relevant impairments of balance and walking endurance relative to subjects without meniscus tears. The explanation for this association requires further study.

Utility of magnetic resonance imaging in diagnosing ulnar neuropathy at the elbow.

OBJECTIVE: Magnetic resonance imaging (MRI) of the ulnar nerve is being increasingly employed in the diagnosis of ulnar neuropathy at the elbow (UNE). Our aims were to: (i) assess the sensitivity of MRI in diagnosing UNE, especially in cases where neurophysiologic studies were non-localizing, (ii) determine the spectrum of MRI abnormalities in patients presenting with symptoms and signs of ulnar neuropathy, (iii) assess whether MRI findings differ between grades of UNE severity, and (iv) to see if MRI findings give an input into the pathological mechanisms of UNE. METHODS: Clinical, neurophysiologic, and radiologic (MRI) records were reviewed in 52 patients with symptoms and signs of ulnar neuropathy. Ulnar nerve MRI studies were assessed by an unblinded observer. RESULTS: The sensitivity of MRI at diagnosing UNE was higher than conventional nerve conduction studies, 90 versus 65%, respectively. In patients with non-localizing neurophysiologic studies (n=19), MRI disclosed changes consistent with UNE in 16 (84%) cases. The most frequent MRI findings included a combination of high signal intensity and nerve enlargement (63%), followed by nerve compression (27%) and isolated high signal intensity (23%), and isolated nerve enlargement (2%). There was no significant difference between patients with localizing and non-localizing neurophysiologic testing. Lastly, there were no differences between different grades of UNE, suggesting that UNE may be a neurophysiologically heterogeneous disorder. CONCLUSIONS: MRI studies proved to be more sensitive than conventional nerve conduction studies at diagnosing UNE. In addition, the MRI studies were highly sensitive in patients with non-localizing UNE. SIGNIFICANCE: Our study shows that MRI of the ulnar nerve should be used in patients with clinical features of UNE especially in those with non-localizing neurophysiologic testing.

Power Doppler 'blanching' after the application of transducer pressure.

The aim of this study was to determine if transducer pressure modifies power Doppler assessments of rheumatoid arthritis synovium at the metacarpophalangeal joints and metatarsophalangeal joints. Five rheumatoid arthritis patients of varying degrees of 'disease activity' and damage were assessed with power Doppler ultrasound scanning of the dominant hand second to fifth metacarpophalangeal joints. Two rheumatoid arthritis patients had their dominant foot first to fifth metatarsophalangeal joints assessed with power Doppler ultrasound. Ultrasonography was performed with a high frequency transducer (14 MHz) with a colour mode frequency of 10 Mhz, and a standard colour box and gain. In the joint that showed the highest power Doppler signal, an image was made. A further image was taken after transducer pressure was applied. In all patients, there was increased flow to at least one joint. After pressure was applied, power Doppler signal intensity markedly reduced in all images and in some there was no recordable power Doppler signal. Increased transducer pressure can result in a marked reduction or obliteration in power Doppler signal. This power Doppler 'blanching' shows the need for further studies to evaluate sources of error and standardization before power Doppler ultrasound becomes a routine measure of 'disease activity' in rheumatoid arthritis.

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the metacarpophalangeal joints.

This paper presents the metacarpophalangeal (MCP) joint magnetic resonance images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. The illustrations include synovitis in the MCP joints (OMERACT RA magnetic resonance imaging scoring system (RAMRIS), grades 0-3), bone oedema in the metacarpal head and the phalangeal base (grades 0-3), and bone erosion in the metacarpal head and the phalangeal base (grades 0-3, and examples of higher grades). The presented reference images can be used to guide scoring of MCP joints according to the OMERACT RA MRI scoring system.

Pitfalls in scoring MR images of rheumatoid arthritis wrist and metacarpophalangeal joints.

This paper outlines the most important pitfalls which are likely to be encountered in the assessment of magnetic resonance images of the wrist and metacarpophalangeal joints in patients with rheumatoid arthritis. Imaging artefacts and how these can be recognised using various sequences and views are discussed. Normal structures such as interosseous ligaments and nutrient foramina may appear prominent on certain images and need to be identified correctly. Pathological change in the rheumatoid hand involves many tissues and when substantial damage has occurred, it may be difficult to identify individual structures correctly. Bone erosion, bone oedema, synovitis, and tenosynovitis frequently occur together and in close proximity to each other, potentially leading to false positive scoring of any of these. Examples are given to illustrate the various dilemmas the user of this atlas may face when scoring the rheumatoid hand and suggestions are made to assist correct interpretation of what can be very complex images.

The development of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas.

Based on a previously developed rheumatoid arthritis MRI scoring system (OMERACT 2002 RAMRIS), the development team agreed which joints, MRI features, MRI sequences, and image planes would best illustrate the scoring system in an atlas. After collecting representative examples for all grades for each abnormality (synovitis, bone oedema, and bone erosion), the team met for a three day period to review the images and choose by consensus the most illustrative set for each feature, site, and grade. A predefined subset of images (for example, for erosion--all coronal slices through the bone) was extracted. These images were then re-read by the group at a different time point to confirm the scores originally assigned. Finally, all selected images were photographed and formatted by one centre and distributed to all readers for final approval.

Dural arteriovenous fistulae causing pseudotumour cerebri syndrome in an elderly man.

The clinical presentation of dural arteriovenous fistulae (DAVF) is dependent on their location and the nature of their venous drainage. The latter plays a critical part in determining whether or not the fistula gives rise to intracranial hypertension, which is present in only a minority of cases. We present a case of the pseudotumour cerebri syndrome in an elderly man with bilateral intracranial DAVF supplied by the occipital arteries. Cerebral angiography was required for definitive diagnosis, and to characterise the abnormal venous drainage. The pathophysiology of intracranial hypertension in DAVF is discussed.

Nocturnal blood pressure predicts left ventricular mass index in normotensive elderly.

Blood pressure (BP) predictors of left ventricular mass index (LVMI) were studied in 40 healthy normotensive (71.4 +/- 4.4 years) and 31 hypertensive (73.5 +/- 4.8 years) elderly community-dwelling subjects using short-axis cardiac cine magnetic resonance imaging and 24-h ambulatory BP monitoring. Mean night-time BPs were calculated from the average of readings during sleep and mean daytime BPs were calculated from the remaining recordings. The hypertensive subjects were all receiving anti-hypertensive therapy with angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, beta-blockers or diuretics. Nocturnal systolic BP was a strong predictor of LVMI in both normotensive (beta = 0.38, p = 0.02) and treated hypertensive (beta = 0.39, p = 0.03) subjects. By contrast, daytime systolic BP was a weaker predictor of LVMI in the treated hypertensives (beta = 0.36, p = 0.04) and did not predict LVMI in the normal subjects (beta = 0.27, NS). Nocturnal BP may partly explain the increase in LVMI with ageing in subjects thought to be normotensive on the basis of daytime clinic BP recordings.

A case of neurosyphilis with a florid Jarisch-Herxheimer reaction.

A 37 year old man with a 2 year history of progressive cognitive decline, unilateral tinnitus and deafness presented with complex partial seizures and a fever. On examination there was a sluggish right pupillary response but no other abnormal findings. Serum and CSF syphilis serology were both strongly positive. High dose intravenous penicillin therapy was complicated by a severe Jarisch-Herxheimer reaction (JHR) characterised by fever, obtundation, fluctuating upper motor neuron signs and complex visual and auditory hallucinations. These symptoms resolved over three days and the course of penicillin was completed. At discharge the patient's cognitive functioning was unchanged from the pretreatment state. He made gradual improvement over the following months but remains unable to live alone or work. Clinical, pathologic and radiologic findings of neurosyphilis are reviewed, as is the JHR, a self-limiting, systemic febrile response related to massive cytokine release that can occur in response to treatment of a number of bacterial infections. The similarities in pathophysiology of the JHR and the Septic Shock Syndrome are discussed, with particular reference to use of the JHR as a potential model for therapeutic agents in the treatment of septic shock.

Prospective evaluation of magnetic resonance imaging and physical examination findings in patients with greater trochanteric pain syndrome.

OBJECTIVE: This study examined patients with greater trochanteric pain syndrome (GTPS) to determine the prevalence of gluteus medius pathology by utilizing magnetic resonance imaging (MRI), and to evaluate the presence of Trendelenburg's sign, pain on resisted hip abduction, and pain on resisted hip internal rotation as predictors of a gluteus medius tear in this group of patients. METHODS: Twenty-four subjects with clinical features consistent with GTPS were recruited. A standard physical assessment was performed at study entry, including assessment of the 3 specific physical signs. Following this initial assessment, MRI of the affected hip was performed. A 1.5T whole body MRI system was utilized, with T1 and T2 fast spin-echo sequences performed in the coronal and axial planes. All MR images were reviewed in random order by a single radiologist. In 12 patients, the 3 physical signs were assessed at study entry and at 2 months by the same observer and the intraobserver reliability for each of the signs was calculated. RESULTS: All subjects were women (median age 58 years, range 36-75 years). The median duration of symptoms was 12 months (range 12-60 months). MRI findings were as follows: 11 patients (45.8%) had a gluteus medius tear, 15 patients (62.5%) had gluteus medius tendinitis (pure tendinitis in 9 patients and tendinitis with a tear in 6 patients), 2 patients had trochanteric bursal distension, and 1 patient had avascular necrosis of the femoral head. Trendelenburg's sign was the most accurate of the 3 physical signs in predicting a tendon tear, with a sensitivity of 72.7% and a specificity of 76.9%. Moreover, Trendelenburg's sign was the most reliable measure, with a calculated intraobserver kappa of 0.676 (95% confidence interval 0.270-1.08). CONCLUSION: The results support the hypothesis that gluteus medius tendon pathology is important in defining GTPS. In this series, trochanteric bursal distension was uncommon and did not occur in the absence of gluteus medius pathology. The physical findings suggest that Trendelenburg's sign is the most sensitive and specific physical sign for the detection of gluteus medius tears, with an acceptable intraobserver reliability. Further delineation with MRI, especially in patients with a positive Trendelenburg's sign, is recommended prior to any consideration of surgery in this group of patients. Finally, with the pathology of this condition defined, the challenge will be to devise and assess, by randomized controlled trial, an appropriate treatment strategy for this group of patients.

Interreader agreement in the assessment of magnetic resonance images of rheumatoid arthritis wrist and finger joints--an international multicenter study.

Magnetic resonance imaging (MRI) allows direct visualization of inflammation and destruction in rheumatoid arthritis (RA) joints. However, MRI scoring methods have not yet been standardized or appropriately validated. Our aim was to examine interreader agreement for a simple system of scoring RA changes on MRI among 5 centers that had not undertaken intergroup calibration. MRI of RA wrist and metacarpophalangeal (MCP) joints were scored by experienced readers in 5 centers in different countries. In substudy 1, 5 sets of 2nd-5th MCP joints from UK [Technique A: 1.5 T, coronal and axial T1 and T2 spin-echo, -/+ fat saturation (FS), -/+ iv gadolinium (Gd)] were scored for synovitis (score 0-3) and bone lesions (0-3). In substudy 2, we evaluated 19 sets of 2nd-5th MCP joints [10 sets from UK (Technique A) and 9 sets from the US (Technique B: 1.5 T; coronal T1 spin-echo and T2* gradient-echo + FS, no Gd)] and 19 wrist joints [9 from the US (Technique B) and 10 from Denmark (Technique C: 1.0 T; coronal and axial T1 spin-echo, no FS, -/+ Gd)]. Synovitis (0-3), bone lesions (0-3), and joint space narrowing (JSN, 0-3) were scored in each MCP joint and in 3 different regions of the wrist. Bone erosions and lesions in each bone were scored 0-5. Substudy 1 served to test and redesign the score sheets. In substudy 2, the scores of synovitis and bone lesions by the 5 groups were the same or differed by only one grade in 73% and 85% of joints, respectively. On MRI that included 2 imaging planes and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa values were in the low to moderate range, generally lowest for JSN (< 0.20), better for synovitis and bone erosions, and best for bone lesions, being generally highest for MRI with 2 planes pre- and post-Gd and in MCPjoints compared with wrists. These preliminary results suggest that the basic interpretation of MRI changes in RA wrist and MCP joints is relatively consistent among readers from different countries and medical backgrounds, but that further training, calibration, and standardization of imaging protocols and grading schemes will be necessary to achieve acceptable intergroup reproducibility in assessing synovitis and bone destruction in RA multicenter studies.

Magnetic resonance imaging in rheumatoid arthritis: summary of OMERACT activities, current status, and plans.

Complementing the 3 papers that precede it, this paper explains the rationale for the activities of an OMERACT working party on magnetic resonance imaging (MRI) evaluation of rheumatoid arthritis (RA), sets out provisional recommendations for the acquisition and scoring of MRI of the hand and wrist in RA, and delineates some of the many residual problems that need to be addressed.

Questioning the sensitivity of magnetic resonance imaging in early septic spondylodiscitis.

Septic spondylodiscitis is an uncommon disease, but one with serious complications and potentially high morbidity and mortality. The diagnosis is sometimes delayed, particularly in those patients with an insidious mode of onset and nonspecific symptoms. Several imaging methods are available to facilitate the early diagnosis of septic spondylodiscitis, and of these methods magnetic resonance imaging (MRI) has been reported to be the most sensitive, revealing abnormalities earlier than plain x-ray, gallium scan and bone scan. We report a case of septic spondylodiscitis in which MRI did not demonstrate evidence of discitis after a symptom period of seven days. The diagnosis was later confirmed by bone scan and repeat MRI. We suggest that a negative or equivocal MRI cannot exclude infective spondylodiscitis, especially in the early stages of the disease process. In such cases, it is important to note that the addition of a short tau-inversion recovery sequence will increase the sensitivity of MRI, and, additionally, gadolinium should be administered if the magnetic resonance study is negative and a strong clinical suspicion of spondylodiscitis exists.