Third-line treatment of colorectal liver metastases using DEBIRI chemoembolization.

To evaluate safety, efficacy of drug-eluting beads with irinotecan (DEBIRI) on local response and survival of patients affected by colorectal liver metastases (CRLM) progressing during or after second line was evaluated. Sixty-two patients, with colorectal liver metastases, not suitable for surgery or thermal ablation treatments, progressing during or within 6 month from the end of second-line chemotherapy, were treated with DEBIRI chemoembolization between February 2009 and July 2014. CRLM were histologically confirmed. Exclusion criteria were considered. The DEBIRI technique consists in intrahepatic embolization of metastases with non-absorbable beads (75-150 µm and 100-300 µm) preloaded with irinotecan, carried near tumour using a selective catheterization of the right or of the left hepatic artery. To control pain associated with treatment, we use a specific schedule. Efficacy of treatment, defined as lack of disease progression and reduction in size of metastasis according to RECIST 1.1 criteria, was evaluated after two treatments with contrast-enhanced computed tomography (CT) at 4 months. If necessary, more treatments are repeated. A total of 191 procedures were performed. No intra-/peri-procedural death occurred. Pain and post-embolization syndrome were generally controlled by medications. Overall, the efficacy of treatment, evaluated in terms of stability and remission of the disease, was 37.1%. In our experience, DEBIRI technique results as a safe and effective procedure, with good intra- and peri-procedural tolerability.

Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum.

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

The clinical effects of deep brain stimulation of the pedunculopontine tegmental nucleus in movement disorders may not be related to the anatomical target, leads location, and setup of electrical stimulation.

BACKGROUND: The pedunculopontine tegmental nucleus (PPTg) is a novel target for deep brain stimulation (DBS) in movement disorders. OBJECTIVE: To clarify the relationships between the individual anatomic variations of the brainstem, the site in which the PPTg DBS is applied, and the clinical outcome in a relatively large number of patients affected by Parkinson disease or progressive supranuclear palsy. METHODS: Magnetic resonance images have been used to evaluate brainstem anatomy and the relationships between lead position and specific brainstem landmarks. All data were matched on atlas representations of the PPTg and were correlated with Unified Parkinson Disease Rating Scale III (UPDRS III), subitems 27 to 30 of UPDRS III and the Hoehn and Yahr evaluations. RESULTS: A high variance of brainstem parameters was evident, affecting the relationships between the position of the nucleus and lead contacts. According to the contacts giving the best clinical outcome, patients could be distinguished between those who required the use of 2 adjacent contacts and those who required stimulation through 2 nonadjacent contacts. Furthermore, in the former group the target coordinates were more lateral and deeper compared with the latter group. CONCLUSION: Individual PPTg-DBS planning is required to overcome the inconsistencies linked to the high variability in the brainstem anatomy of patients. The lack of correlations between lead position, contact setup, and clinical outcome indicate that the benefits of PPTg DBS may not be strictly linked to the site of stimulation within the PPTg area, and may not depend upon the neurons still surviving in this region in Parkinson disease or progressive supranuclear palsy.

The deep brain stimulation of the pedunculopontine tegmental nucleus: towards a new stereotactic neurosurgery.

The application of deep brain stimulation (DBS) to the pedunculopontine tegmental nucleus (PPTg) has required profound modifications of classic neurosurgical techniques and of the criteria for evaluation of clinical results. This review analyzes a novel method of targeting the PPTg, based on angio-computerized tomography (angio-CT) scans and the tridimensional reconstruction of nuclei and cerebral vessels, and considers the advantages of applying these methods in comparison to the more traditional approach based on reference points obtained through the evaluation of the bicommessural line. Validation of the results obtained following unilateral PPTg DBS through neurophysiological recordings and objective measurements of functional parameters suggests that the PPTg may be considered as an initial target for the treatment of motor symptoms in selected patients affected by idiopathic Parkinson's disease (PD), which, if required, could be followed by DBS of other target areas. Moreover, on the basis of the observations derived from stimulating the PPTg, the potential utility attributed up to date to intraoperative neurophysiological recordings for identifying neurosurgical targets should be revisited, and the need for changes in the intraoperative management of patients has arisen from the body of evidence accumulated over recent years. The results obtained by different groups following PPTg DBS in parkinsonian patients are not uniform, most likely due to a cautious acceptance of this methodology, the experience progressively acquired, the criteria for patient selection and to subtle differences in target location. Although the role of PPTg in PD and/or in other pathologies remains to be clarified, pursuing the traditional approach on classical basal ganglia targets may limit the perspective of DBS based on multiple implantations.

The deep brain stimulation of the pedunculopontine tegmental nucleus.

Objective. The aim of the present study was to describe the surgical and clinical outcomes of the implantation and stimulation of the pedunculopontine tegmental nucleus in humans. Materials and Methods. Fourteen patients affected by movement disorders (12 Parkinson's disease and 2 progressive supranuclear palsy) underwent surgery for bilateral or monolateral implantation of stimulating electrodes in the pedunculopontine tegmental nucleus. The correct placement of electrodes was established and verified by combining angio-CT scans with magnetic resonance imaging. Intraoperative and postoperative evaluations were made to assess the clinical effectiveness of stimulation according to different Unified Parkinson's Disease Rating Scale items and neurophysiologic parameters. Results. No major complications occurred following the insertion of electrodes into the pedunculopontine tegmental nucleus. Neuroimaging showed that the electrode contacts were always correctly placed below the ponto-mesencephalic line. Stimulation of the pedunculopontine tegmental nucleus improved gait, posture, and speech, and modulated reflexes integrated at spinal or pontine levels. Conclusions. The surgical targeting of the pedunculopontine tegmental nucleus requires a careful adaptation of the traditional stereotactic approaches owing to the high variability of brainstem anatomy from one patient to another. The insertion of the leads in the pedunculopontine tegmental nucleus as well as their activation did not appear to induce serious adverse effects. The correct positioning of stimulating electrodes in pontine structures such as the pedunculopontine nucleus may be ascertained not only through neuroimaging techniques but also through clinical neurophysiology. The evolution of the surgical planning that we have developed emphasizes the limited value of single-unit recordings to identify the pedunculopontine tegmental nucleus and highlights the opportunities offered by functional evaluations of neurophysiologic parameters. As far as the clinical efficacy is concerned, our data suggest a promising outcome for simultaneous implantations of different basal ganglia nuclei in Parkinsonian and in progressive supranuclear palsy patients as well.