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.

Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma.

BACKGROUND: When comparing the efficacy of surgical and non-surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so-called average treatment effect (ATE). METHODS: To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment. RESULTS: A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin-bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037). CONCLUSION: ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.

HLA-DRB1*15 association with multiple sclerosis is confirmed in a multigenerational Italian family.

Environmental and genetic factors seem to play a pathogenetic role in multiple sclerosis (MS). The genetic component is partly suggested by familial aggregation of cases; however, MS families with affected subjects over different generations have rarely been described. The aim of this study was to report clinical and genetic features of a multigenerational MS family and to perform a review of the literature on this topic. We describe a multigenerational Italian family with six individuals affected by MS, showing different clinical and neuroradiological findings. HLA-DRB1* typing revealed the presence of the DRB1*15:01 allele in all the MS cases and in 4/5 non-affected subjects. Reports on six multigenerational MS families have previously been published, giving similar results. The HLA-DRB1*15:01 allele was confirmed to be linked to MS disease in this family; moreover, its presence in non-affected subjects suggests the involvement of other susceptibility factors in the development and expression of the disease, in accordance with the complex disease model now attributed to MS.

The Long-Term Benefit of Liver Transplantation for Hepatic Metastases From Neuroendocrine Tumors.

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty-eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan-NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long-term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow-up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time-to-progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4-23.0; p = 0.001). Adjusted transplant-related survival benefit was 6.82 months (95% CI: 1.10-12.54; p = 0.019) and 38.43 months (95% CI: 21.41-55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long-term outcome. Transplant-related survival benefit increases over time and maximizes after 10 years.

Radioembolization of hepatocarcinoma with (90)Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology.

PURPOSE: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on (99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. METHODS: We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50% and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on (99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of (99m)Tc-MAA and (90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for (90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. RESULTS: MAA and (90)Y biodistributions were not different (71% of cases), different in 23% and uncertain in 6%. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50%) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14%, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD50 was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD15 ≈ 75 Gy. CONCLUSION: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.

Malignant pheochromocytoma and paraganglioma: future considerations for therapy.

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Knowledge about such neoplasms ameliorated in the last 10-15 years with the discovery of increasing number of germ line mutations even in apparently sporadic cases. Seemingly, genetic tests are going to be an integral part of diagnostic procedures. Standard therapies (advanced surgery, radiometabolic therapy, chemotherapy and radiotherapy) have revealed suboptimal results in tumor size reduction and survival. Currently, there is no standard therapeutic protocol and thus some patients end up with overtreatment while others are undertreated. An effective molecular target therapy aiming at permanent control of these highly complex neoplasms should be the aim of future efforts. In clinical setting investigatory trials with multiple drug therapies targeting a variety of different parallel pathways should be available. Successful management requires a multidisciplinary teamwork.

A dosimetric treatment planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres.

AIM: Our goal was to limit liver toxicity and to obtain good efficacy by developing a dosimetric treatment planning strategy. While several dosimetric evaluations are reported in literature, the main problem of the safety of the treatment is rarely addressed. Our work is the first proposal of a treatment planning method for glass spheres, including both liver toxicity and efficacy issues. METHODS: Fifty-two patients (series 1) had been treated for intermediated/advanced hepatocellular carcinoma (HCC) with glass spheres, according to the Therasphere® prescription of 120 Gy averaged on the injected lobe. They were retrospectively evaluated with voxel dosimetry, adopting the local deposition hypothesis. Regions of interest on tumor and non tumor parenchyma were drawn to determine the parenchyma absorbed dose, averaged also on non irradiated voxels, excluding tumor voxels. The relationship between the mean non tumoral parenchyma absorbed dose D and observed liver decompensation was analyzed. RESULTS: Basal Child-Pugh strongly affected the toxicity incidence, which was 22% for A5, 57% for A6, 89% for B7 patients. Restricting the analysis to our numerically richest class (basal Child-Pugh A5 patients), D median values were significantly different between toxic (median 90 Gy) and non toxic treatments (median 58 Gy) at a Mann-Withney test, (P=0.033). Using D as a marker for toxicity, the separation of the two populations in terms of area under ROC curve was 0.75, with 95% C.I. of [0.55-0.95]. The experimental Normal Tissue Complication Probability (NTCP) curve as a function of D resulted in the following values: 0%, 14%, 40%, 67% for D interval of [0-35] Gy, [35-70] Gy, [70-105] Gy, [105-140] Gy. DISCUSSION: A limit of about 70 Gy for the mean absorbed dose to parenchyma was assumed for A5 patients, corresponding to a 14% risk of liver decompensation. This result is applicable only to our administration conditions: glass spheres after a decay interval of 3.75 days. Different safety limit (40 Gy) are published for resin spheres, characterized by higher number of particle per GBq (more uniform irradiation, bigger biological effect for the same absorbed dose). CONCLUSION: As result of this study we suggest a constraint of about 70 Gy mean absorbed dose to liver non tumoral parenchyma, corresponding to about 15% probability of radioinduced liver decompensation while still aiming at achieving an absorbed of several hundreds of Gy to lesions.

CT-guided percutaneous cryoablation of renal masses in selected patients.

PURPOSE: We analysed our experience with computed tomography (CT)-guided percutaneous cryoablation (PCA) in patients who were not surgical candidates or refused surgery for small to medium-sized renal masses. MATERIALS AND METHODS: Two freezing cycles were applied and separated by a passive warming cycle using 1.7- and 2.4-mm cryoprobes under either general anaesthesia or sedation based on patient positioning and respiratory status. Postoperative monitoring included haematological and biochemistry evaluation and CT scan 24 h after PCA. Follow-up consisted of a multislice CT scan at 1 month and every 3 months in the first year then every 6 months thereafter. RESULTS: Thirty-seven patients (38 lesions) underwent 40 PCA procedures; 5/37 (13.5%) had a solitary kidney. Median mass size was 35 (range 12-70) mm. No complications occurred during the procedure. Clavien grade ≥2 anaemia occurred in two patients (5.4 %): one patient required 1 U of packed red blood cells; the other required an arterial embolisation. Serum creatinine did not increase in any case. Two patients showed persisting or recurrent disease at 1 and 9 months, respectively, and both could be re-treated with PCA. All other patients showed a hypodense mass 3 months after PCA, with no contrast enhancement. Subsequent examinations showed that lesion sizes decreased and CT densitometry remained stable or increased minimally, also with no contrast enhancement. CONCLUSIONS: PCA proved relatively easy and safe and could be considered an effective alternative for patients who are not surgical candidates or refuse surgery, as well as in patients with medium-sized lesions.

Vatalanib for metastatic gastrointestinal stromal tumour (GIST) resistant to imatinib: final results of a phase II study.

BACKGROUND: Vatalanib (PTK787/ZK 222584) inhibits a few tyrosine kinases including KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs). We report efficacy and safety results of vatalanib in advanced gastrointestinal stromal tumour (GIST) resistant to imatinib or both imatinib and sunitinib. PATIENTS AND METHODS: Forty-five patients whose metastatic GIST had progressed on imatinib were enrolled. Nineteen (42.2%) patients had received also prior sunitinib. Vatalanib 1250 mg was administered orally daily. RESULTS: Eighteen patients (40.0%; 95% confidence interval (CI), 25.7-54.3%) had clinical benefit including 2 (4.4%) confirmed partial remissions (PR; duration, 9.6 and 39.4 months) and 16 (35.6%) stabilised diseases (SDs; median duration, 12.5 months; range, 6.0-35.6+ months). Twelve (46.2%) out of the 26 patients who had received prior imatinib only achieved either PR or SD compared with 6 (31.6%, all SDs) out of the 19 patients who had received prior imatinib and sunitinib (P=0.324). The median time to progression was 5.8 months (95% CI, 2.9-9.5 months) in the subset without prior sunitinib and 3.2 (95% CI, 2.1-6.0) months among those with prior imatinib and sunitinib (P=0.992). Vatalanib was generally well tolerated. CONCLUSION: Vatalanib is active despite its narrow kinome interaction spectrum in patients diagnosed with imatinib-resistant GIST or with imatinib and sunitinib-resistant GIST.

Need, feasibility and convenience of dosimetric treatment planning in liver selective internal radiation therapy with (90)Y microspheres: the experience of the National Tumor Institute of Milan.

In most centres, the choice of the optimal activity to be administered in selective intra-arterial radioembolization with microspheres is nowadays based on empirical models which do not take into account the evaluation of tumour and non tumour individual absorbed dose, despite plenty of published data which showed that local efficacy is correlated to tumour absorbed dose, and that the mean absorbed dose is a toxicity risk factor. A pitfall of the crudest, empirical tumour involvement method are 20 deaths in a single centre which adopted it to administer the whole liver, or the need of systematic 25% subjective reduction of activity prescribed with body surface area method. In order to develop a possibly safer and more effective strategy based on real individual dosimetry, we examine first external beam liver radiation therapy results. The half century experience has something to be borrowed: the volume effect, according to which the smaller the fraction of the irradiated liver volume, the higher the tolerated dose. Different tolerance for different underlying disease or previous non radiation treatment is to be expected. Radiobiological models experience also has to be inherited, but not their dose reference values. Then we report the published dosimetric experience about (90)Y microsphere radioembolization of primary and metastatic liver tumours. In addition we also present original data from our growing preliminary experience of more refined (99m)Tc MAA SPECT based calculations in hepatocarcinoma patients. This overcame the mean dose approach in favour of the evaluation of dose distribution at voxel level. An insight into dosimetry issues at microscopic level (lobule level) is also provided, from which the different radiobiological behaviour between resin and glass spheres can be understood. For tumour treatment, an attenuation corrected (99m)Tc- SPECT based treatment planning strategy can be proposed, although quantitative efficacy thresholds should be differentiated according to the kind of pathology and previous treatment. For non tumour liver parenchyma, data in favour of a relationship between absorbed dose and dangerous effects are encouraging. Unfortunately in hepato-cellular carcinoma, some confounding factors may hamper the adequate estimation of the risk of toxicity. First there is a lack of consensus about the exact definition of toxicity after (90)Y microsphere radioembolization. Second, for HCC patients, progression of both cancer and cirrhosis can simulate a radioinduced toxicity, making the analysis more complex.

Corticosteroids for the long-term treatment in multiple sclerosis.

BACKGROUND: Short term high dose corticosteroid treatment improves symptoms and short term disability after an acute exacerbation of multiple sclerosis (MS) but it is unknown whether its long-term use can reduce the accumulation of disability. OBJECTIVES: To determine the efficacy and safety of long-term corticosteroid use in MS. SEARCH STRATEGY: We searched the following bibliographic databases: CENTRAL (Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and one pharmaceutical company. SELECTION CRITERIA: We considered controlled, randomised trials (RCTs), with or without blinding, of long term treatment (i.e. longer than 6 months) of any type of corticosteroid in MS, irrespective of disease course. DATA COLLECTION AND ANALYSIS: Reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Three trials, all classified at high risk of bias, contributed to this review (Miller 1961; BPSM 1995; Zivadinov 2001) resulting in a total of 183 participants (91 treated). Corticosteroid therapy did not reduce the risk of being worse at the end of follow-up (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.26 to 1.02) but there was a substantial heterogeneity between studies (I(2): 78.4%). I. v. periodic high dose methylprednisolone (MP) was associated with a significant reduction in the risk of disability progression at 5 years in relapsing-remitting (RR) MS (OR 0.26, 95% CI 0.10 to 0.66), while oral continuous low dose prednisolone was not associated with any risk reduction in disability progression at 18 months (OR 1.23, 95% CI 0.43 to 3.56). Risk of experiencing at least one exacerbation at end of follow-up was not significantly reduced with corticosteroid treatment (OR 0.36; 95% CI 0.10 to 1.25). Only one study recorded adverse events: in one patient i. v. MP was discontinued after the fourth pulse when he developed acute glomerulonephritis; a second patient was removed from the study after the fifth i. v. MP pulse because of severe osteoporosis. AUTHORS' CONCLUSIONS: There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.

Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate.

BACKGROUND: We evaluated safety and efficacy of PTK787/ZK222584 (PTK/ZK), a novel tyrosine kinase inhibitor of KIT, platelet-derived growth factor receptors and vascular endothelial cell growth factor receptors (VEGFRs), in patients with imatinib-resistant gastrointestinal stromal tumor (GIST). This is the first study of PTK/ZK in this population. PATIENTS AND METHODS: Patients with metastatic GIST that had progressed after >/= 4-week treatment with imatinib mesylate were eligible. Prior VEGFR-2 inhibitor therapy was not permitted. PTK/ZK 1250 mg orally once-daily was administered to 15 patients (accrued as a two-stage procedure), most of whom (n = 11) had been unsuccessfully treated with imatinib 800 mg daily, until treatment failure. Patients were monitored at 4- to 8-week intervals. RESULTS: All 15 patients enrolled were eligible; two (13%) achieved partial response (PR), eight (53%) had stable disease (SD) >/=3 months, and five (33%) progressed. The clinical benefit rate (PR + SD) was 67% (95% CI 38% to 86%). Median time to progression was 8.5 months (range 0.9-24.8+ months). Three patients had not progressed at the time of analysis, including one PR at 24.8 months and two SDs at 16.6 and 18.6 months on treatment. PTK/ZK was generally well tolerated. CONCLUSION: PTK/ZK 1250 mg p.o. once daily is active and well tolerated in patients with imatinib-resistant GIST.

Does iodine concentration affect the diagnostic efficacy of biphasic spiral CT in patients with hepatocellular carcinoma?

BACKGROUND: We investigated the effect of iodinated contrast medium concentration on increased neoplastic lesion enhancement and its direct relation to diagnostic efficacy in biphasic spiral computed tomography for detection of hepatocellular carcinoma. METHODS: A pilot, single-center, randomized, double-blind, crossover, comparative study was performed and included 22 participants. Each patient underwent two separate biphasic contrast-enhanced spiral computed tomographic examinations. Scans were performed with iomeprol containing 400 (iomeprol 400) or 300 (iomeprol 300) mg of iodine per milliliter (Iomeron, Bracco Imaging SpA, Milan, Italy) with a 2- to 12-day window scan; patients were given an equal total dose of 45 g of iodine at a fixed injection rate of 4 mL/s. Comparison included assessment of quantitative and qualitative parameters. RESULTS: Lesion density and lesion-to-liver contrast increased more markedly with the higher concentration of contrast medium during the arterial phase (p = 0.0016 and 0.0005, respectively). There was no significant difference in any parameter between the two concentrations during the portal phase. Number of lesions detected during the arterial phase increased from 37 with iomeprol 300 to 42 with iomeprol 400; in the portal phase, the respective numbers were 34 and 36. CONCLUSION: Even though a small number of patients was examined, our study suggests that, in patients with cirrhosis, an increased concentration of iodine improves liver-to-lesion contrast and may improve the detection of hepatocellular carcinoma.

Visual evoked potentials in migraine.

Migraine is a chronic disorder. Visual symptoms and hypersensitivity to light stimuli are common. The aim of this study is the analysis of visual system in migraineurs by visual evoked potentials (VEP). We studied 53 migraineurs (21 with prophylactic migraine treatment and 32 without preventive therapy) and 20 healthy control subjects. We found lower P100 latencies in migraineurs without therapy compared to controls. In treated patients, P100 latencies showed the same trend seen in the control group. We speculate a different responsiveness of the visual system in migraineurs probably due to a dysmodulation of sensor input leading to facilitation of visual processing.

Optic neuritis: diagnostic criteria application in clinical practice.

Optic neuritis (ON) refers to any inflammatory optic neuropathy. In clinical practice ON is mainly diagnosed by ophthalmologists and less frequently by neurologists. ON diagnostic criteria are included in the Classification of International Headache Society (IHS) and in other classification systems, both in neurological and ophthalmologic fields. The aims of this study were to verify the application of IHS ON diagnostic criteria in clinical practice and the role of the ocular pain qualitative aspects. We performed a partially retrospective (140 cases) and prospective (43 cases) study analysing the clinical characteristics of patients with ON. We observed retro orbital pain in a huge percentage of patients; it was provoked or spontaneous and worsened by eye movements. We found that the new IHS classification criteria (IHS 2004) do not fully satisfy the requirements for ON diagnosis. Further study is necessary to validate the diagnostic criteria of ON in clinical practice.

An unusual case with relapsing neuromyelitis optica associated with undifferentiated connective tissue disease.

A case is presented with attacks of optic neuritis followed by severe myelitis 15 years later, in coincidence with a severe stressful life event. This female patient was also affected by undifferentiated connective tissue disease. This case presents some unusual and atypical findings such as: the association of a relapsing neuromyelitis optica with an undifferentiated connective tissue disease, a very long interval between optic neuritis and myelitis, and the important role of a stressful event in developing a relapse.

Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase I study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity.

BACKGROUND: This study was designed to determine the feasibility, maximum tolerated dose, and toxicities of intraarterial administration of paclitaxel-albumin nanoparticles in patients with advanced head and neck and recurrent anal canal squamous cell carcinoma. Antitumor activity also was assessed. METHODS: Forty-three patients (31 with advanced head and neck and 12 with recurrent anal canal squamous cell carcinoma) were treated intraarterially with ABI-007 every 4 weeks for 3 cycles. In total, 120 treatment cycles were completed, 86 in patients with head and neck carcinoma (median, 3 cycles; range, 1-4) and 34 in patients with anal canal carcinoma (median, 3 cycles; range, 1-4). ABI-007 was compared preliminarily with Taxol for in vitro cytostatic activity. Increasing dose levels from 120 to 300 mg/m2 were studied in 18 patients. Pharmacokinetic profiles after intraarterial administration were obtained in a restricted number of patients. RESULTS: The dose-limiting toxicity of ABI-007 was myelosuppression consisting of Grade 4 neutropenia in 3 patients. Nonhematologic toxicities included total alopecia (30 patients), gastrointestinal toxicity (3 patients, Grade 2), skin toxicity (5 patients, Grade 2), neurologic toxicity (4 patients, Grade 2) ocular toxicity (1 patient, Grade 2), flu-like syndrome (7 patients, Grade 2; 1 patient, Grade 3). In total, 120 transfemoral, percutaneous catheterization procedure-related complications occurred only during catheterization of the neck vessels in 3 patients (2 TIA, 1 hemiparesis) and resolved spontaneously. CONCLUSIONS: Intraarterial administration of ABI-007 by percutaneous catheterization does not require premedication, is easy and reproducible, and has acceptable toxicity. The maximum tolerated dose in a single administration was 270 mg/m2. Most dose levels showed considerable antitumor activity (42 assessable patients with 80.9% complete response and partial response). The recommended Phase II dose is 230 mg/m2 every 3 weeks.

[Percutaneous implant of Denver peritoneovenous shunt: a new opportunity for the interventional radiologist]. / L'impianto percutaneo dello shunt peritoneo-venoso di Denver: Una nuova opportunità per il radiologo interventista.

PURPOSE: The study is aimed at presenting our experience in the implant of Denver peritoneovenous shunts. Medical treatment-resistant ascites, either neoplastic or related to hepatic failure, is highly symptomatic and its treatment is indicated in order to improve patients' quality of life. One of the most efficient methods of treatment consists in implanting a peritoneovenous shunt. The availability of this device and its percutaneous implantation provide Interventional Radiologists with the possibility of expanding their repertoire. MATERIAL AND METHODS: Thirteen shunts were implanted in 12 patients, 10 with neoplastic ascites and 2 with hepatic failure-related ascites. In 1 patient a second device had to be implanted. All the procedures were performed in the Interventional Radiology Department, under local anesthesia and mild sedation. The central venous access was by the subclavian vein in 7 cases and the internal jugular vein in 6 cases. The puncture kit is consists of 2 needles, 1 for venous puncture and 1 for peritoneal puncture, 2 angiographic J-guide wires, 2 peel-away introducers, and a chamber containing the double valve-pump connected with both the venous and the peritoneal catheters. The whole device is placed subcutaneously thus allowing fluids to flow from the peritoneum to the vein either spontaneously, if intra-abdominal pressure exceeds 3cm of water, or by manual compression exerted on the pump itself. RESULTS: All implants were successfully performed. One transient complication occurred consisting in a mild inflammatory reaction along the subcutaneous catheter route, which promptly solved by antibiotic therapy. So far a total of 1773 catheter/days have been accumulated. 7/10 of the neoplastic patients died from progressive disease after 915 catheter/days (median 120, range 30-180). In a cirrhotic patient the first shunt occluded after 430 days due to hemoperitoneum caused by hepatic biopsy: it was removed and a new one implanted. Five shunts are in now use, with a follow-up of 30, 48, 70, 120 and 160 days each. DISCUSSION: The implanting technique was well tolerated by all patients and it could be performed under local anesthesia. The central vein puncture was easy for both accesses but the introducer diameter (12F) and the possibility of clavicle pinch-off induced us to use the internal jugular approach in the last six cases, which provided a reduced risk of pneumothorax and a better catheter track. In the patients with neoplastic ascites we observed neither disease dissemination nor changes in the patients' changed related to the shunt. Our results show that the implant of Denver venous-peritoneal shunts is a relatively easy procedure, which can be performed by Interventional Radiologists on a regular basis.