Radioembolization of hepatocarcinoma with 90Y glass microspheres: treatment optimization using the dose-toxicity relationship.

AIM: Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. METHODS: Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. RESULTS: A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/< 1.1 mg/dL. These results are valid for a 90Y glass microsphere administration 4 days after the reference time. CONCLUSION: Given the low predictive accuracy of 99mTc-MAA on lesion absorbed dose reported by several authors, an optimized TARE with 90Y glass microspheres with lobar injection 4 days after reference time should aim at an absorbed dose averaged over the whole non-tumoural liver of 50 Gy/90 Gy for basal bilirubin higher/lower than 1.1 mg/dL, respectively.

Is there a prognostic role for C-reactive protein in ischemic stroke?

OBJECTIVES: We investigated the relationship between C-reactive protein (CRP)-values in the acute phase of stroke and the risk of further fatal and non-fatal ischemic events. MATERIALS AND METHODS: We analysed 462 consecutive incident ischemic strokes. Patients were divided into two subgroups on the basis of a CRP cut-off level of 9 mg/l. Primary end points were any new vascular fatal and non-fatal event recorded during the follow-up period. RESULTS: During a follow-up of 2.27 years, in 132 patients occurred a primary end point. Patients with CRP values > or = 9 mg/l had more frequently primary end point. The hazard ratio (HR) for cardiovascular events was 3.59; 1.93 for cerebrovascular events; 7.43 for vascular deaths and 5.78 for death from any cause. Cox proportional hazard multivariate analysis identified CRP values > or = 9 (HR = 4.19, 95% CI: 1.85-9.50, P = 0.001), the lack of secondary prevention therapy at discharge (HR = 4.35, 95% CI: 1.87-10.1, P = 0.001), age >70 years (HR = 3.09, 95% CI: 1.04-9.24, P = 0.04) as independent predictors of fatal events. CONCLUSIONS: CRP levels > or = 9 mg/l, evaluated in incident ischemic stroke within 24 h, predict a higher risk of further ischemic events and mortality.

Long-term activation in a 15 MeV radiotherapy accelerator.

The high energy electrons produced by linear accelerators can generate several radioisotopes by means of photonuclear reactions. The activity produced in the head of a 15 MV Mevatron Siemens 77 medical linear accelerator was measured by high resolution gamma-ray spectrometry, during its decommissioning 1 year after the last clinical use. The activity of 54Mn, 57Co, 60Co, 181W, and 65Zn was measured while the activity of other radioisotopes which emit soft beta or gamma rays such as 59Ni, 63Ni, and 55Fe was inferred by appropriate scaling factors. The number of pieces requiring particular care is limited, their mass does not exceed some tens of kilograms, and their volume is of the order of some thousands of cm3. Moreover, these materials are metals and the emitted radiation can be easily shielded, so that storage should not create particular problems.

Clinical application of laser evoked potentials using the Nd:YAG laser.

The clinical interest of a new type of laser evoked potentials (LEPs) using Nd:YAG laser was assessed in the diagnosis of peripheral neuropathies affecting the small-diameter nerve fibres, and of spinal cord lesions, affecting the spinothalamic tract. Twelve patients aged from 26 to 79 years with sensory neuropathies (n = 6) or spinal cord lesions (n = 6) underwent neurophysiological examination of the lower limbs comprising quantitative sensory testing, i.e., the determination of vibratory and thermal thresholds (VT and TT), somatosensory evoked potentials (SEPs) to electrical stimulation and Nd:YAG LEPs. VT and SEPs were used to assess large-diameter afferent nerve fibres and the lemniscal pathways while TT and LEPs were used to assess small-diameter afferent nerve fibres and the spinothalamic tract. In addition, patients with peripheral neuropathy underwent also standard nerve conduction studies to explore large fibres and the recording of sympathetic skin responses (SSRs) to explore small fibres, whereas motor evoked potentials were performed in patients with spinal cord lesion. LEPs were absent bilaterally in all patients with polyneuropathy, even when TT remained within the normal limits and SSRs were present. LEPs were absent after stimulation of the affected limb in all patients with a spinal cord lesion, and allowed to detect subclinical contralateral lesion in two cases. LEPs following Nd:YAG laser stimulation are sensitive in the diagnosis of peripheral and/or central nervous system disorders and they give complementary information as compared to routine electrophysiological tests.

Frequency, distribution and characteristics of progressive supranuclear palsy in Italy: preliminary observations.

We report the number of pathologically proven cases of progressive supranuclear palsy, described in the Italian neurological literature from 1961 until now. A discussion of the diagnostic value of downward gaze palsy is made. A comparison with the number of similar cases described in the rest of the world and with the number of Parkinsonian patients who died in the same region in the corresponding year is attempted.

Long-term remyelination after optic neuritis: A 2-year visual evoked potential and psychophysical serial study.

Thirty-one patients were followed-up, at 3-month intervals for the first year and at 6-month intervals for the second year, after an episode of optic neuritis. The object was to confirm previous evidence for a progressive shortening of visual evoked potential (VEP) latencies and to determine whether this is associated with any change in the clinical ocular examination, visual fields or contrast sensitivity. VEP latencies were found to decrease significantly during both the first and (less strikingly) the second year, the most marked changes occurring between 3 and 6 months. Contrast sensitivity improved during the first 9 months, but subsequently tended (non-significantly) to deteriorate. A similarly transient improvement in central visual field sensitivity was seen in a subgroup of patients with clinically overt multiple sclerosis. In the data from the acutely unaffected fellow eyes, no significant changes in VEP parameters or functional indices were observed. The findings extend those of a previous study which showed significant shortening of VEP latencies between 6 months and 3 years without significant functional improvement. Over this period, a significant prolongation of VEP latencies occurred in the asymptomatic fellow eye, accompanied by contrast sensitivity deterioration. Taken in conjunction, the two studies suggest that recovery processes involving remyelination or, possibly, ion channel reorganization proceed for at least 2 years. The concurrent effects of insidious demyelination and/or axonal degeneration (also occurring in the fellow optic nerve) are initially masked by the recovery process, but gradually become more evident. The functional benefits of the long-term recovery process are relatively minor and are usually reversed within a few years. Nevertheless, it is suggested that long-term remyelination may perform an important role in protecting demyelinated axons from degeneration. Understanding the factors which promote long-term remyelination may have significant implications for therapy in multiple sclerosis.

Variation of visual evoked potential delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis.

OBJECTIVES: To compare the degree of visual evoked potential (VEP) delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis, to determine whether the differential involvement of parvocellular and magnocellular fibre types suggested by other studies is governed by retinotopic factors. METHODS: VEPs were recorded to reversal of 40' checks in the central (4 degrees radius) and the left and right surrounding regions of the visual field (as far as 10 degrees vertical and 14 degrees horizontal) in 30 patients recently recovered from the acute stage of optic neuritis, and in 17 age matched controls. RESULTS: In the control group, VEP latencies were similar to stimulation of the central and temporal regions of the macula, marginally shorter from the nasal region. In the patients with optic neuritis, VEPs were significantly more delayed from the central region, on average by about twice as much as from the nasal and temporal regions. Delays seen in some of the VEPs from the patients' fellow eyes tended to be more uniformly distributed. CONCLUSIONS: Although the central region of the macula is where the density of parvocellular innervation is greatest, there is no reason to suppose that the VEPs to stimulation of the nasal and temporal regions (almost all P100 activity arising from within the central 10 degrees ) are mediated by fibres of another type. Consequently it is suggested that the central fibres were most affected by demyelination, not on account of their belonging to the parvocellular type but because of their particular situation in the optic nerve. Centrally located fibres may experience greater exposure to factors causing demyelination, or fibres located closer to the edge of the plaque may undergo more effective remyelination in the first few weeks after the acute episode.

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study.

OBJECTIVES: Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects. METHODS: Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients. RESULTS: Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005). CONCLUSIONS: The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined.

Ante litteram description of atypical parkinsonian cases.

We have searched in the neurological literature for cases of atypical parkinsonism published before the epidemic encephalitis era. Some of these cases can be recognized. Therefore the epidemic encephalitis has no etiological importance in these clinical syndromes.

Long-term recovery and fellow eye deterioration after optic neuritis, determined by serial visual evoked potentials.

Twelve optic neuritis patients (part of a larger group in whom the effects of intravenous methylprednisolone treatment were previously reported), were followed-up 3 years from the onset of symptoms with visual evoked potentials (VEPs), contrast sensitivity and visual field examination. Findings from the previously "unaffected" eyes, none of which had had symptomatic optic neuritis, were also assessed. Between 6 months and 3 years after the onset of symptoms the VEPs of the affected eyes showed a significant shortening of mean latency (whole field, 131-123 ms; central field, 136-125 ms). Conversely, the responses of the previously unaffected eyes showed a contemporaneous latency prolongation (significant for the whole field, 110-113 ms) which exceeded the expected effect of aging. Contrast sensitivity tests showed no significant change in the affected eyes but a mild deterioration in the unaffected eyes, while the visual fields showed no overall pattern of improvement or deterioration. If the strong tendency for VEP latencies to shorten is due to ongoing remyelination, the lack of significant improvement in visual function may be because the visual deficit at 6 months is due to irreversible axonal loss rather than demyelination. The absence of functional deterioration in the affected eye, while VEPs and contrast sensitivity deteriorated in the unaffected eye, suggests that long-term remyelination may for a while counteract the effects of insidious demyelination and axonal degeneration which affect the visual pathway during clinical remission.

Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS).

PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N-shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning.

Effects of intravenous methylprednisolone on outcome in MRI-based prognostic subgroups in acute optic neuritis.

Treatment of acute optic neuritis with steroids has been shown to hasten visual recovery without affecting the final degree of recovery. However, MRI-clinical studies indicate that patients with long optic nerve lesions, particularly those that involve the nerve within the optic canal, may have a worse prognosis for recovery of vision. Partly because such lesions could lead to swelling and subsequent ischemic optic nerve damage, steroids could have a selective beneficial effect on this subgroup of patients. The present randomized trial was designed to test this possibility. Sixty-six patients with acute optic neuritis received IV saline or IV methylprednisolone. The clinical, psychophysical, electrophysiologic, and MRI outcomes were assessed after 6 months. Patients with short lesions presented earlier than those with long lesions (involving three or more 5-mm-thick slices of any part of the optic nerve, as well as its intracanalicular portion), and lesion length was significantly less in patients presenting within a week of onset of symptoms. Lesions also tended to lengthen during follow-up in individual patients. Treatment did not limit lesion length in either the long or short lesion subgroup and had no significant effect on final visual outcome. We conclude that steroids do not improve visual outcome or lesion length in patients with acute optic neuritis.

Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central, hemi- and peripheral fields.

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40' subtense reversed in the whole field (28 degrees x 20 degrees), alternatively in the left and right hemifields and alternately in the central (5 degrees radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4 degrees radius) and left and right hemisurround fields. In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes. In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields.(ABSTRACT TRUNCATED AT 250 WORDS)

[Stereotactic radiotherapy with linear accelerators. Dosage considerations on collimators and photon beam energy]. / La radioterapia stereotassica con acceleratori lineari. Considerazioni dosimetriche sui collimatori e sull'energia di fasci di fotoni.

The small X-ray beam profiles produced by linear accelerators and used in stereotactic radiosurgery were studied. Circular focusing and not-focusing beams outlined by additional collimators (diameter ranging 10 to 30 mm) and square field outlined by the jaws (field size 10 to 30 mm) were measured. 6 and 18-MV X-ray beams from a dual energy accelerator and 6 and 15-MV X-ray beams produced by 2 single-energy accelerators were used. Measurements were carried out with Kodak X Omat V films in a perspex phantom in the same conditions for all the fields. To study the profile characteristics we introduced the V80/V20 = (R80/R20)3 ratio where R80 and R20 are respectively the mean distance of the 80% and 20% isodose lines from the beams axis. Measurement results show that 6-MV X-ray beams have a higher V80/V20 ratio than the ones obtained with the other energies. There is no significant difference between the beams produced with focused collimators and those produced with not-focused collimators. Square fields outlined by the jaws have a V80/V20 ratio greatly dependent on the accelerator used. This ratio is generally worse than the ones obtained with beams outlined by additional collimators.

[Digital fluorography in gastroenterological radiology]. / La fluorografia digitale nella radiologia gastroenterologica.

The clinical value of two digital fluoroscopy systems not connected to a PACS was investigated and compared with that of conventional radiology. Some critical variables were considered: image intensifier diameter, image definition, examination time, acquisition speed, patient exposure and finally film consumption. The main problems in the use of the digital techniques consisted in the limited size of the examination fields, which was not big enough to demonstrate the whole colon during double contrast enema, and in the difficult representation of the actual size on the image printed on the laser films. Definition was considered as sufficient for GI examinations. The main advantages consisted in acquisition speed, allowing detailed examinations of cervical esophagus, cardias and fistulous tracts, reduced patient dose and finally the real time visualization of the acquired image on the TV monitor.

Evoked potentials obtained with tendon percussion in hemiplegic patients.

The purpose of this research was to verify in a group of hemiplegic subjects the usefulness of potentials obtained with tendon tap by evaluating the integrity of the proprioceptive area in relation to lesions in the middle cerebral artery territory. The healthy and paretic sides in 10 subjects affected by hemiplegia have been studied using the cerebral potential evoked by tendon tap. Two sets of 150 stimuli for each lower limb were applied at a standard repetition rate of 1 stimulus per 16 seconds. Data obtained shows a reduction of the amplitude of the P1-N1 cortical complex derived from the paretic side. This effect appears to be related to the entity of the kinaesthetic sensitivity impairment.

Some little-known aspects of spinal cord softening.

311 cases of spinal cord softening, were selected for review. The following points emerged from this study: 1) spinal cord softening is a rare occurrence; 2) while formerly syphilis was the most frequent cause, recently reports of cases secondary to aortic disease or to embolism with diffuse signs of arteriosclerosis and circulatory failure pointing to a different pathogenesis have become more frequent; 3) the site of softening rarely corresponds to the vascular spinal territories as defined by the anatomists, from which it may be argued that often several arterial territories may be involved simultaneously or, alternatively, that the arterial territories are not so rigidly defined as anatomical research has led us to suppose; 4) the few cases of multiple vascular lesions show that, as happens in the brain, the cord may be damaged contemporaneously or successively in several areas.