Percutaneous image-guided thermal ablation of lung cancer: What is the evidence?

Thermal ablation techniques have now been used for more than twenty years in the treatment of primary lung tumours, predominantly non-small cell lung cancer (NSCLC). Although primarily used for the treatment of early-stage disease in non-surgical patients, thermal ablation is now also being used in selected patients with oligometastatic and oligoprogressive disease. This review discusses the techniques available for thermal ablation, the evidence for use of thermal ablation in primary lung tumours in early- and advanced-stage disease and compares thermal ablation to alternative treatment strategies.

Nodal and systemic recurrence following observation of a positive sentinel lymph node in melanoma.

BACKGROUND: Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone. METHODS: All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995-2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed. RESULTS: Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up. CONCLUSION: Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma.

A rare late complication of traumatic diaphragmatic hernia repair.

We report a case of sudden cardiovascular collapse several weeks following surgical repair of a traumatic diaphragmatic hernia. The patient presented with features of circulatory shock without a clear diagnosis, therefore an urgent computed tomography scan of the chest and abdomen was undertaken, which revealed a pericardial effusion with evidence of cardiac tamponade. Ultrasound-guided needle pericardiocentesis with aspiration of blood from the pericardial sac in the Emergency Department provided an immediate response and her cardiac output improved. On review of the imaging, it is likely a surgically-placed permanent metallic fixation device, sitting near the pericardium, caused bleeding into the pericardial sac due to local trauma as a delayed postoperative complication.

Testicular Microlithiasis: Is Sonographic Surveillance Necessary? Single Centre 14 Year Experience in 442 Patients with Testicular Microlithiasis.

PURPOSE: Increased prevalence of germ cell tumour (GCT) is seen with testicular microlithiasis (TM) suggesting TM is a premalignant condition with US surveillance advocated. We present a cohort of patients with TM followed up in a single centre and deliberate on the value of US surveillance. MATERIALS AND METHODS: A retrospective analysis of subjects with underlying US diagnosis of TM between 1998 and 2012. One-yearly US follow-up was offered to all patients with TM and a database maintained. Any co-existing tumour at presentation with TM was recorded. TM was divided into limited (< 5 microliths/field), classical (≥ 5 microliths/field) and florid ('snowstorm' appearance). Patient demographics, follow-up details and the development of any scrotal abnormalities were recorded. The radiological and histological findings were documented when a testicular lesion occurred during the follow-up period. RESULTS: 20 224 patients were examined: 867/20 224 (4.3 %) had TM. 21/867 (2.4 %) patients had histology proven malignant tumours at presentation. All TM patients consented to follow-up with 442/867 (51.0 %) achieving this and entering into a follow-up program (mean duration 28 months, range 8 - 165 months). Two patients developed primary GCT during the follow up period. One patient (limited TM) had undergone a previous orchiectomy for contralateral GCT and developed a palpable mass at follow up month 21. The other (limited TM) had an atrophic testis; a tumour was found on US at follow up month 62. CONCLUSION: Two patients of 442 (0.5 %) followed up for all forms of TM in a single centre developed a GCT over a mean duration of 28 months, both had independent risk factors for the development of GCT. These findings suggest that US surveillance is not required when TM is the only abnormality in the absence of any clinical risk factors for the development of GCT.

Age-related auditory deficits in temporal processing in F-344 rats.

Older human listeners demonstrate perceptual deficits in temporal processing even when audibility has been controlled. These age-related auditory deficits in temporal processing are thought to originate in the central auditory pathway. Precise temporal processing is necessary to detect and discriminate auditory cues such as modulation frequency, modulation depth and envelope shape which are critical for perception of speech and environmental sounds. This study aims to further understanding of temporal processing in aging using non-invasive electrophysiological measurements. Amplitude modulation following responses (AMFRs) and frequency modulation following responses (FMFRs) were recorded from aged (92-95-weeks old) and young (9-12-weeks old) Fischer-344 (F-344) rats for sinusoidally amplitude modulated (sAM) tones, sinusoidally frequency modulated (sFM) tones and ramped and damped amplitude modulation (AM) stimuli which differ in their envelope shapes. The modulation depth for the sAM and sFM stimuli and envelope shape for the ramped and damped stimuli were systematically varied. There was a monotonic decrease in AMFR and FMFR amplitudes with decreases in modulation depth across age for sAM and sFM stimuli. There was no significant difference between the response amplitudes of the young and aged animals for the largest modulation depths. However, a reduction in modulation depth resulted in a significant decrease in the response amplitudes and higher modulation detection thresholds for sAM and sFM stimuli with age. The aged animals showed significantly lower response amplitudes for ramped stimuli but not for damped stimuli. Cross correlating the responses with the ramped, symmetric, or damped stimulus envelopes revealed a decreased fidelity in encoding envelope shapes with age. These results indicate that age related temporal processing deficits become apparent only with reduced modulation depths or when discriminating envelope shapes. This has implications for psychophysical or diagnostic testing as well as for constraining potential cellular and network mechanisms responsible for these deficits.

Acute hyperammonemic encephalopathy in adults: imaging findings.

BACKGROUND AND PURPOSE: Acute hyperammonemic encephalopathy has significant morbidity and mortality unless promptly treated. We describe the MR imaging findings of acute hyperammonemic encephalopathy, which are not well-recognized in adult patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical and imaging data and outcome of consecutive patients with documented hyperammonemic encephalopathy seen at our institution. All patients underwent cranial MR imaging at 1.5T. RESULTS: Four patients (2 women; mean age, 42 ± 13 years; range, 24-55 years) were included. Causes included acute fulminant hepatic failure, and sepsis with a background of chronic hepatic failure and post-heart-lung transplantation with various systemic complications. Plasma ammonia levels ranged from 55 to 168 µmol/L. Bilateral symmetric signal-intensity abnormalities, often with associated restricted diffusion involving the insular cortex and cingulate gyrus, were seen in all cases, with additional cortical involvement commonly seen elsewhere but much more variable and asymmetric. Involvement of the subcortical white matter was seen in 1 patient only. Another patient showed involvement of the basal ganglia, thalami, and midbrain. Two patients died (1 with fulminant cerebral edema), and 2 patients survived (1 neurologically intact and the other with significant intellectual impairment). CONCLUSIONS: The striking common imaging finding was symmetric involvement of the cingulate gyrus and insular cortex in all patients, with more variable and asymmetric additional cortical involvement. These specific imaging features should alert the radiologist to the possibility of acute hyperammonemic encephalopathy.

Classification of carotid stenosis by millimeter CT angiography measures: effects of prevalence and gender.

BACKGROUND AND PURPOSE: Previous studies quantifying moderate and severe carotid stenosis by direct millimeter measures on CT angiography (CTA) did not consider how prevalence and gender may influence classification cutoff values. MATERIALS AND METHODS: Three hundred nineteen carotid arteries were evaluated in consecutive patients with known or suspected carotid artery disease. Millimeter measures were obtained of the stenotic carotid bulb lumen and distal internal carotid artery (ICA). Interclass correlation coefficients (ICC) defined interobserver and intraobserver agreement. North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style percent stenosis ratios were calculated per carotid artery and used in linear regression and receiver operating characteristic (ROC) curve analysis to define equivalent millimeter quantification and classification values. Likelihood ratios and prevalence-specific positive/negative predictive values (PPV/NPV) were calculated to determine the most appropriate millimeter cutoff values to classify stenosis. RESULTS: Interobserver agreement was excellent for stenosis measures (0.90) and good for distal ICA measures (0.79). Gender-specific regression curves and ROC curves indicated that millimeter stenosis is an excellent tool to quantify and classify carotid stenosis. Assuming a 10% prevalence of severe stenosis, we found that the cutoff value maximizing NPV and PPV was 1.1 mm for both genders (female: PPV = 86.2, NPV = 97.7; male: PPV = 83.2, NPV = 95.9). Assuming a 40% prevalence of moderate stenosis, we found that the cutoff values differed between genders: female = 2.0 mm (PPV = 91.3, NPV = 91.5), male = 2.1 mm (PPV = 91.6, NPV = 92.4). Specific millimeter cutoffs will vary depending upon the clinical scenario, prevalence, and gender. CONCLUSIONS: Direct millimeter stenosis measures are an excellent tool to classify moderate and severe carotid artery stenosis. Millimeter classification cutoff values that best approximate NASCET classifications vary depending on prevalence and gender.

Neural coding of temporal information in auditory thalamus and cortex.

How the brain processes temporal information embedded in sounds is a core question in auditory research. This article synthesizes recent studies from our laboratory regarding neural representations of time-varying signals in auditory cortex and thalamus in awake marmoset monkeys. Findings from these studies show that 1) the primary auditory cortex (A1) uses a temporal representation to encode slowly varying acoustic signals and a firing rate-based representation to encode rapidly changing acoustic signals, 2) the dual temporal-rate representations in A1 represent a progressive transformation from the auditory thalamus, 3) firing rate-based representations in the form of monotonic rate-code are also found to encode slow temporal repetitions in the range of acoustic flutter in A1 and more prevalently in the cortical fields rostral to A1 in the core region of marmoset auditory cortex, suggesting further temporal-to-rate transformations in higher cortical areas. These findings indicate that the auditory cortex forms internal representations of temporal characteristics of sounds that are no longer faithful replicas of their acoustic structures. We suggest that such transformations are necessary for the auditory cortex to perform a wide range of functions including sound segmentation, object processing and multi-sensory integration.

Neural coding of temporal information in auditory thalamus and cortex.

How the brain processes temporal information embedded in sounds is a core question in auditory research. This article synthesizes recent studies from our laboratory regarding neural representations of time-varying signals in auditory cortex and thalamus in awake marmoset monkeys. Findings from these studies show that 1) the primary auditory cortex (A1) uses a temporal representation to encode slowly varying acoustic signals and a firing rate-based representation to encode rapidly changing acoustic signals, 2) the dual temporal-rate representation in A1 represent a progressive transformation from the auditory thalamus, 3) firing rate-based representations in the form of a monotonic rate-code are also found to encode slow temporal repetitions in the range of acoustic flutter in A1 and more prevalently in the cortical fields rostral to A1 in the core region of the marmoset auditory cortex, suggesting further temporal-to-rate transformations in higher cortical areas. These findings indicate that the auditory cortex forms internal representations of temporal characteristic structures. We suggest that such transformations are necessary for the auditory cortex to perform a wide range of functions including sound segmentation, object processing and multi-sensory integration.

Diagnosing carotid stenosis near-occlusion by using CT angiography.

BACKGROUND/PURPOSE: Identification of carotid near-occlusion is essential before calculation of percent stenosis because stroke risk is lower than other severe stenosis and the treatment benefit is less. Calculations with reduced distal diameters are fallacious. CT angiography (CTA) is convenient and accurately quantifies internal carotid artery (ICA) stenosis. METHODS: In a blinded protocol, 268 carotid artery CTAs for known or suspected carotid disease were independently evaluated by 2 neuroradiologists. All carotid arteries were measured in millimeters at the narrowest diameter of the stenotic bulb, distal ICA well beyond the tapering bulb, and distal external carotid artery (ECA). Near-occlusions were independently identified, with disagreements settled by consensus meeting. Receiver operating characteristic (ROC) curve analysis defined the threshold values that best predicted near-occlusion according to (1) ICA stenosis, (2) distal ICA, (3) distal ICA: contralateral distal ICA, and (4) distal ICA: ECA. Paired permutations of variables were evaluated. RESULTS: Forty-two near-occlusion distal ICAs were identified. The ROC-derived threshold values determined near-occlusion carotid stenosis with a sensitivity range, 90.2-97.3; specificity, 84.1-89.9; positive predictive value (PPV), 61.3-66.7; and negative predictive value (NPV), 96.7-99.4. Ranges for paired permutations were also determined: sensitivity, 82.9-91.9; specificity, 95.4-96.8; PPV, 78.6-85.7; and NPV, 96.3-98.4. CONCLUSIONS: Threshold values provide guidelines for CTA interpretation when assessing carotid artery disease and the presence of near-occlusion. Ultimate identification of near-occlusion requires the interpreter's judgment, with attention to the following criteria: (1) notable stenosis of the ICA bulb and (2) distal ICA caliber reduction compared with (A) expected size, (B) contralateral ICA, and (C) ipsilateral ECA. Near-occlusion distal ICAs can be reliably identified on CTA.

Correlation of carotid stenosis diameter and cross-sectional areas with CT angiography.

PURPOSE: Carotid stenosis quantification traditionally uses measurements of narrowest stenosis diameter. The stenotic carotid lumen, however, is often irregularly shaped. New PACS workstation tools allow for more precise calculation of carotid geometry. We compare the narrowest stenosis diameter with 2D area stenosis measurements, with the hypothesis that the narrowest diameter is a good predictor of the more precise area measurement. METHODS: Two neuroradiologists evaluated 178 stenosed carotids in a blinded protocol. Carotid artery bulb stenosis was identified on axial CT angiography and measured in millimeters at its narrowest diameter. An AGFA Impax 4.5 Volume Tool (VT) using Hounsfield units was used to estimate the cross-sectional area of the contrast luminogram. Pearson correlation coefficients were calculated between the millimeter stenosis and the VT area, as well as between the VT area and the calculated area (radius based on narrowest diameter). Regression analysis was performed with the VT area and narrowest diameter datasets. RESULTS: Excellent interobserver correlation (correlation coefficients, 0.71-0.85; 2-tailed significance = .01) permitted averaging of measurement data. There is excellent correlation between the VT area and the narrowest diameter (correlation coefficient, 0.88; n = 176). The VT area was generally greater than the calculated area by an average of 2.77 mm2. There was excellent correlation between the VT area and the calculated area (correlation coefficient, 0.87; n = 176). Regression analysis shows the ability of the diameter measurements to predict corresponding area stenosis. CONCLUSION: Although some carotid stenoses are irregularly shaped and noncircular, measurement of the narrowest stenosis is a reasonably reliable predictor of the cross-sectional area.

Quantification of carotid stenosis on CT angiography.

PURPOSE: Carotid artery stenosis quantification uses percent diameter ratios from conventional angiography. Multidetector high-speed CT angiography (CTA) allows direct millimeter measurement of carotid stenosis. We hypothesize a linear relationship between millimeter stenosis measurements and derived percent, alleviating cumbersome ratio calculations. METHODS: Two neuroradiologists separately reviewed CTAs of 268 carotid arteries, blinded to other information. The narrowest portion of each carotid stenosis was measured in millimeters from axial source images. Distal internal carotid arteries (ICAs) were measured beyond the bulb, where walls are parallel. North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style ratios were calculated for each ICA, except for suspected near-occlusions. Interobserver agreement was calculated for all measurements. Correlation coefficients were calculated comparing millimeter and derived percent stenosis, followed by regression analysis. Sensitivity and specificity values tested validity. RESULTS: Interobserver agreement correlations were excellent, from 0.78 to 0.89 (2-tailed P

Chasing "chasing the dragon" with MRI: leukoencephalopathy in drug abuse.

UNLABELLED: Spongiform leukoencephalopathy is a rare complication from inhalation of heated heroin vapour, a practice called "chasing the dragon". The MRI findings are considered pathognomonic, making MRI important for diagnosis. This is especially true in busy urban emergency departments where a variety of patients may present obtunded, unable or unwilling to provide a useful history. Even though the MR pattern of "chasing" toxicity is considered pathognomonic, there are mimickers. We compare the MRI findings of two classic cases of chasing leukoencephalopathy with one case of mimickery from cocaine exposure only. All three cases had diffuse symmetrical white matter changes. MR spectroscopy (MRS) in chasing patients showed increased lactic acid and myo-inositol, decreased N-acetyl aspartate and creatine, normal to slightly decreased choline, and normal lipid peak. MRS in the cocaine exposure patient showed marked increase in lactic acid and lipids. MR perfusion in one chasing patient was normal. IN CONCLUSION: (1) All three cases have MR findings suggestive of spongiform leukoencephalopathy. MRS may help differentiate toxicity due to inhaled heroin from other non-heroin related toxicities. (2) Discordance between perfusion and spectroscopy in one chasing patient adds evidence that the disease is due to impaired energy metabolism at the cellular level. (3) MR findings of spongiform leukoencephalopathy secondary to chasing heroin can progress despite apparent abstinence of the drug and during clinical improvement, suggesting the MR changes may represent an evolving injury.

The natural history of lower urinary tract dysfunction in men: the influence of detrusor underactivity on the outcome after transurethral resection of the prostate with a minimum 10-year urodynamic follow-up.

OBJECTIVES: To assess the long-term outcome of the efficacy of transurethral resection of the prostate (TURP) in men with detrusor underactivity (DUA), a cause of lower urinary tract symptoms (LUTS) in a significant minority of men. PATIENTS AND METHODS: Neurologically intact men with LUTS, who were investigated in our department between 1972 and 1986, diagnosed with DUA and who underwent surgical intervention, were invited for a repeat symptomatic and urodynamic assessment. Identical methods were used, allowing direct comparison of the results. RESULTS: In all, 224 men were initially diagnosed with DUA; 87 (39%) of these died in the interim and 22 followed had a TURP, with a mean follow-up since surgery of 11.3 years. There were no significantly sustained reductions in any symptoms. There was a small but significant reduction of questionable clinical significance in the bladder outlet obstruction index, but this did not translate into an improved flow rate. Comparison with 58 age-matched patients with DUA who remained untreated showed no significant advantage of surgical intervention in the long-term; on the contrary, there was more chronic retention in those who had had surgery. CONCLUSIONS: There are no long-term symptomatic or urodynamic gains from TURP in men shown to have DUA. The results of TURP in men with DUA are important, as urologists who surgically treat patients based on the symptoms and uroflowmetry alone will do so in a significant minority of men with DUA. These results strengthen the argument for a routine preoperative urodynamic assessment.

Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice.

Viral DNA vaccines encoding the glycoprotein B (gB) of cytomegalovirus provide partial protective immunity upon challenge with infectious virus. Although it is known that type I IFN can stimulate the adaptive immune response, their direct use in vaccines has been limited. Here we show that coimmunisation of type I IFN and gB CMV DNA constructs enhances protective immunity in mice. In vivo expression of IFN transgenes ranged from 1.2 to 2.0 x 10(4) IU/g tibialis anterior muscle. Viral titre in major target organs and the severity of acute CMV-induced myocarditis was reduced preferentially with either IFN-alpha 9 or IFN-beta, but not with IFN-alpha 6, coimmunisation. However, all IFN subtypes investigated markedly reduced chronic myocarditis in gB-vaccinated mice. The early antiviral IgG1 and IgG2a titres were enhanced with IFN-beta coimmunisation. TNF and IL-10 was increased in response to MCMV infection in mice coimmunised with IFN subtypes and viral gB DNA. Indeed T cells from IFN-inoculated mice reduced myocarditis upon in vivo transfer. These results suggest that select type I IFNs may act as a natural adjuvant for the immune response against CMV infection. Type I IFN DNA coimmunisation may provide increased efficacy for viral vaccines and subsequently modulate post-viral chronic inflammatory disorders.

Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body.

Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the second GABA(A) potential amplitude measured from the resting potential, but the GABA(B) amplitude was sensitive to the interstimulus interval. Train stimuli applied to collicular or cortical inputs generated intra-train responses that were often predicted by their paired-pulse behavior. Long-lasting responses following train stimulation of the collicular inputs were uncommon. In contrast, corticothalamic inputs often generated long-lasting depolarizing responses that were dependent on activation of a metabotropic glutamate receptor. Our results demonstrate that during repetitive afferent firing there are input-specific mechanisms controlling synaptic strength and membrane potential over short and long time scales. Furthermore, they suggest that there may be two classes of excitatory collicular input to medial geniculate neurons and a single class of small-terminal corticothalamic inputs, each of which has distinct features.