Publications by authors named "Pietro Mortini"

190 Publications

Advanced Imaging Techniques for Radiotherapy Planning of Gliomas.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Radiation Oncology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy.

The accuracy of target delineation in radiation treatment (RT) planning of cerebral gliomas is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Conventional magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, represents the current standard imaging modality for target volume delineation of gliomas. However, conventional sequences have limited capability to discriminate treatment-related changes from viable tumors, owing to the low specificity of increased blood-brain barrier permeability and peritumoral edema. Advanced physiology-based MRI techniques, such as MR spectroscopy, diffusion MRI and perfusion MRI, have been developed for the biological characterization of gliomas and may circumvent these limitations, providing additional metabolic, structural, and hemodynamic information for treatment planning and monitoring. Radionuclide imaging techniques, such as positron emission tomography (PET) with amino acid radiopharmaceuticals, are also increasingly used in the workup of primary brain tumors, and their integration in RT planning is being evaluated in specialized centers. This review focuses on the basic principles and clinical results of advanced MRI and PET imaging techniques that have promise as a complement to RT planning of gliomas.
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http://dx.doi.org/10.3390/cancers13051063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959155PMC
March 2021

Surgical and Radiologic Prognostic Factors in Intramedullary Spinal Cord Lesions.

World Neurosurg 2021 Mar 19. Epub 2021 Mar 19.

Department of Neurosurgery and Gamma Knife Radiosurgery, I.R.C.C.S. San Raffaele Hospital, Milan, Italy. Electronic address:

Objective: The present study aimed to perform a comprehensive data analysis of 47 consecutive patients treated in 8 years and to observe how clinical, radiologic, and surgical factors affect early and long-term outcomes, recurrence rate, and survival.

Methods: Clinical, radiologic, and surgical data were collected retrospectively from the review of a prospectively collected database. The neurologic disability was evaluated according to the modified Rankin Scale (mRS). Radiologic data were obtained by direct measurement performed on magnetic resonance imaging (MRI). Univariate and multivariate statistical analysis was performed.

Results: From 2008 to 2016, 47 consecutive patients underwent microsurgical resection of intramedullary lesions (28 males and 19 females; mean age, 41.2 years). Ependymoma (53.2%), astrocytoma (14.9%), hemangioblastoma (14.9%), and cavernous angioma (6.4%) were the most frequent tumor histology. The mean follow-up duration was 69.3 months. Gross total tumor resection was performed in 80.8% of cases. Forty-two patients (89.4%) were alive at last follow-up. Five-year overall survival and recurrence-free survival were 92% and 82%, respectively.

Conclusions: Among the examined variables, age seemed to strongly correlate with outcomes; better chances of recovery and a good postoperative outcome were observed in younger patients. Surfacing lesions had a better early functional outcome than did intramedullary located lesions. Patients' preoperative neurologic and functional status (mRS score ≤2) had a significant impact on late neurologic outcome. Progression-free survival correlated with the extent of tumor resection. Surgery should probably be performed before patients' neurologic decline, aiming to achieve maximal resection without compromising patients' quality of life.
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http://dx.doi.org/10.1016/j.wneu.2021.03.061DOI Listing
March 2021

Therapeutic cannabis for pain management in a patient with chiari malformation type i during concomitant SARS-COV-2 infection.

J Neurosurg Sci 2021 Mar 11. Epub 2021 Mar 11.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

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http://dx.doi.org/10.23736/S0390-5616.21.05322-4DOI Listing
March 2021

Endoscope-Assisted Neuroportal Transcerebellar Approach to the Fourth Ventricle: An Anatomical Study.

J Neurol Surg A Cent Eur Neurosurg 2021 Mar 9. Epub 2021 Mar 9.

Department of Neurosurgery and Gamma Knife Radiosurgery, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background And Study Aims:  Minimally invasive approaches to deep-seated lesions still represent a fundamental issue in modern neurosurgery. Tubular retractors allow to enhance the operability of intraventricular lesions, minimizing the risk of damages to brain parenchyma. Increasing interest for portal devices has been mainly focused on supratentorial pathologies, while transportal approaches in the posterior cranial fossa have been rarely described. In the present study, the authors aimed to investigate the surgical exposure and operability obtained with a microsurgical neuroportal transcerebellar approach targeting the fourth ventricle, assisted by endoscopic exploration.

Material And Methods:  Six cadaveric specimens were provided for anatomical microsurgical dissection and Vycor ViewSite Brain Access System was used as tubular retractor. Surgical feasibility of the neuroportal transcerebellar approach was demonstrated through a definable and measurable parameter, the operability score.

Results:  The neuroport provided a surgical corridor away from eloquent structures to target the whole fourth ventricle cavity, preventing injury to cerebellar nuclei and white matter pathways and, potentially, minimizing the risk of surgical morbidity. Maximal operability was reached in the pontomedullary junction and medullary area of the ventricular floor. Transportal endoscopic assistance contributed to a further extension of surgical exposure in blind spots, corresponding to the ipsilateral lateral recess, the uppermost part of the fourth ventricle, and the obex.

Conclusion:  The neuroportal transcerebellar approach represents a viable alternative route to the fourth ventricle, avoiding vermian splitting or subarachnoid dissection of the cerebellomedullary cistern. Endoscopic assistance enhances the exposure of the surgical field and accomplishes a valid instrument for intraventricular orientation to ease microsurgical procedures.
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http://dx.doi.org/10.1055/s-0040-1719107DOI Listing
March 2021

Combined, Rib-Sparing, Bilateral Approach to the Ventral Mid and Low Thoracic Spine: Study on Comparative Anatomy and Surgical Feasibility.

World Neurosurg 2021 Mar 4. Epub 2021 Mar 4.

Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

Background: Pathologies of the ventral thoracic spine represent a challenge, igniting arguments about which should be the ideal surgical approach to access this area. Anterior transthoracic thoracotomy and a number of posterolateral routes have been developed. Among the latter, costotransversectomy has demonstrated to provide good ventral exposure with a lower, but not negligible, morbidity. The optimal approach should be the one minimizing surgical morbidity on both neural and extraneural structures while optimizing exposure.

Methods: The authors described the combined, rib-sparing, bilateral approach (CRBA) to the ventral mid/low-thoracic spine. The technique combines a transfacet pedicle partially sparing approach on one side and a transpedicular with transverse process resection on the contralateral one. A laboratory investigation was conducted. The technique was applied in a surgical setting, and a case was reported.

Results: CRBA is rib-sparing, completely extracavitary, and does not require pleural exposure and paraspinal muscle splitting, thus minimizing potential morbidity. The combination of 2 corridors ensures the greatest exposure compared with standard posterolateral approaches. The only blind corner is limited to a small area just in front of the dural sac. A bimanual approach optimizes control during surgical manipulation, even if the area of maneuverability and cross-section areas of surgical corridors are slightly limited compared to traditional costotransversectomy due to the minimally invasive nature of the procedure.

Conclusions: CRBA represents a safe and effective option to access the ventral mid/low thoracic spine. It provides great exposure and bimanual manipulation of the surgical target, minimizes potential morbidity, and avoids entrance into the thoracic cavity and paraspinal muscle splitting.
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http://dx.doi.org/10.1016/j.wneu.2021.02.105DOI Listing
March 2021

Predictive factors of radio-induced complications in 194 eyes undergoing gamma knife radiosurgery for uveal melanoma.

Acta Ophthalmol 2021 Feb 26. Epub 2021 Feb 26.

Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background And Purpose: To report the factors predictive of radio-induced complications (i.e. radiation retinopathy [RR], radiation papillopathy [RP] and neovascular glaucoma [NVG]) in uveal melanoma (UM) patients undergoing gamma knife radiosurgery (GKR).

Materials And Methods: Longitudinal cohort study on patients with UM treated at the Ocular Oncology Service, San Raffaele Scientific Institute, Milan, between June 1994 and November 2018. Data were retrospectively reviewed. Rates of GKR-related complications were reported. Variables associated with each complication were investigated using multivariable Cox models and confirmed by logistic regression analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were reported for significant associations.

Results: One hundred ninety-four patients (99 males, 51%) were included, and 184 tumours were primarily located in the choroid (95%). Median follow-up was 57 months (range 6-286). Local control was achieved in 182 eyes (94%), and 152 eyes (78%) experienced at least one radiation-induced complication. Radiation retinopathy was documented in 67 eyes (35%) after a median of 23 months. Older age (HR = 0.97, 95% CI = 0.95-0.99, p = 0.02) had a protective effect for RR. Radiation papillopathy was diagnosed in 35 eyes (18%) after a median of 14 months after GKR. Macular or peripapillary location (HR = 3.06, 95% CI = 1.52-6.16, p = 0.002) was associated with increased risk of RP, while older age was protective (HR = 0.95, 95% CI = 0.93-0.98, p = 0.001). New-onset NVG was found in 53 eyes (27%), and median onset was 28 months. Tumour thickness (HR = 4.41, 95% CI = 2.23-8.72, p < 0.001) and peripapillary location (HR = 2.78, 95% CI = 1.46-5.27, p = 0.002) were the main risk factors associated with NVG.

Conclusion: Understanding factors predictive for radiation-related complications in patients undergoing GKR might help for better counselling and treatment planning.
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http://dx.doi.org/10.1111/aos.14814DOI Listing
February 2021

MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study.

Br J Haematol 2021 Feb 23. Epub 2021 Feb 23.

Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
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http://dx.doi.org/10.1111/bjh.17357DOI Listing
February 2021

MIS removal of extraforaminal lumbar spine schwannoma using MAS-TLIF retractor: technical note.

Br J Neurosurg 2021 Feb 20:1-3. Epub 2021 Feb 20.

Department of Neurosurgery and Gamma Knife Radiosurgery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Background: To report the use of Nuvasive MAS-TLIF retractor for the removal of lumbar spine schwannomas.

Methods: A 47-year-old man with 1-year history of back pain with progressive left sciatica underwent surgical resection of a left extraforaminal lumbar schwannoma (type IV according to Eden's classification) using the MAS-TLIF retractor.

Results: The patient completely recovered from the preoperative symptoms and was discharged three days after surgery. The MRI acquired 6 months postoperatively showed complete tumour removal, with no signs of instability. The MAS-TLIF retractor allows for an optimal paraspinal tissues retraction, improving the area of exposure and the manoeuverability angle. Moreover, the stability of the retraction is guaranteed by the positioning of the two transpedicular screws. Spinal fusion is not necessary because the posterior tension band is not jeopardised.

Conclusions: MAS-TLIF retractor allows for a minimally invasive and safe surgical removal of LSS maximising surgical exposure and avoiding spinal fusion.
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http://dx.doi.org/10.1080/02688697.2021.1888872DOI Listing
February 2021

Efficacy of Gamma Knife radiosurgery in the management of multiple sclerosis-related trigeminal neuralgia: a systematic review and meta-analysis.

Neurosurg Rev 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurosurgery and Gamma Knife Radiosurgery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Trigeminal neuralgia (TN) is the most frequent craniofacial pain condition, which commonly affects patients suffering from multiple sclerosis (MS). Stereotactic radiosurgery, especially Gamma Knife radiosurgery (GKRS), represents a safe and effective treatment for TN, and it has been adopted also for MS-TN, with a lower success rate. Therefore, we aimed to analyze the outcome of GKRS for MS-TN. PubMed, Web of Science, and Google Scholar and the reference list of relevant articles were searched for GKRS in MS-TN. Two investigators independently identified the articles, assessed the study quality, and extracted the data. Endpoints of interest were initial pain responders, successful treatments at the end of follow-up, and factors influencing the outcome. Data analyses were performed using R software. Twelve articles involving 646 patients met our inclusion criteria. Pooled proportion of patients who experienced an initial response to GKRS treatment was 83% (CI 74-90%). The cumulative proportion of successful treatments at the end of follow-up was 47% (CI 33-60%). No variables were found to have a significant contribution to heterogeneity regarding the initial response outcome. The only variable significantly explaining the heterogeneity found in the proportion of successful treatments was the length of the follow-up, with a negative b coefficient (- 0.0051, p value = 0.0047). Regarding the efficacy of GKRS in MS-TN, the initial pain response rate was 83%, which dramatically decreases to 47% during follow-up. GKRS still represents a valuable option for MS-TN; however, its long-term efficacy should be always considered.
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http://dx.doi.org/10.1007/s10143-021-01507-3DOI Listing
February 2021

Long term follow-up in advanced Parkinson's disease treated with DBS of the subthalamic nucleus.

J Neurol 2021 Feb 17. Epub 2021 Feb 17.

Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been an approved treatment for PD for more than 30 years, but few data are available regarding its long-term effectiveness.

Objective: The aim of this study is to evaluate patients' outcome, both from a motor and non-motor perspective, 9 to 14 years after DBS implantation. We have investigated patients with advanced PD and treated with STN-DBS, in relation to key clinical features of PD.

Methods: 18 patients were assessed both retrospectively and prospectively. They underwent motor examination, neuropsychological evaluation and questionnaires on the quality of life, preoperatively, as well as 1, 9 and 14 years after DBS surgery. All patients were implanted with STN-DBS at San Raffaele Hospital between 2004 and 2010.

Results: 13 males and five females underwent DBS implantation with a mean PD duration of 11 years. Stimulation significantly improved med-off/stim-on condition up to 9 years, compared to the preoperative off state, and med-on/stim-on condition at 14 years, compared to med-on/stim-off state. Long term improvement specifically involved tremor and rigidity, as well as dopaminergic daily dose. At the same time, STN-DBS had no long-lasting effect on axial symptoms and cognitive functions.

Conclusions: STN-DBS remains an effective therapy for advanced PD, also over the years. Despite the underlying progression of the disease, this treatment extends the period in which the overall quality of life is still acceptable.
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http://dx.doi.org/10.1007/s00415-021-10430-yDOI Listing
February 2021

Endoscopic sublabial transmaxillary approach to the inferior orbit: pearls and pitfalls-A comparative anatomical study.

Neurosurg Rev 2021 Feb 10. Epub 2021 Feb 10.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Objective: Although orbital surgery has always represented a challenge for neurosurgeons, keyhole and endoscopic techniques are gradually surging in popularity maximizing functional and esthetic outcomes. This quantitative anatomical study first compared the surgical operability achieved through three endoscopic approaches within the inferior orbit: the endoscopic sublabial transmaxillary (ESTMax), the endoscopic endonasal transethmoidal (EETEth), and the endoscope-assisted lateral orbitotomy (ELO).

Methods: Each of these approaches was performed bilaterally on five specimens. We described the ESTMax step-by-step, underlining its advantages and pitfalls in comparison with EETEth and ELO. Then, we assessed surgical measurements and operability in ESTMax, EETEth, and ELO.

Results: The ESTMax provided the most favorable operative window (278.9 ± 43.8 mm; EETEth: 240.8 ± 21.5 mm, p < 0.001; ELO: 263.1 ± 19.8 mm, p = 0.006), the broadest surgical field area (415.9 ± 26.4 mm; EETEth: 386.7 ± 30.1 mm, p = 0.041; ELO: 305.2 ± 26.3 mm, p < 0.001), surgical field depths significantly shorter than EETEth (p < 0.001) but similar to ELO, the widest surgical angles of attack (45°-65°; EETEth: 20°-30°, p < 0.001; ELO: 25°-50°, p < 0.001), and the greatest surgical mobility areas (EETEth: p < 0.001; ELO: p < 0.001). Furthermore, the ESTMax allowed multi-angled exposure and handy maneuverability around all the inferior intraorbital targets. Small anterior antrostomy, blunt intraorbital dissections, direct targets' approach, orbital floor reconstruction, and maxillary bone flap replacement may limit the ESTMax morbidity rates.

Conclusions: The ESTMax is a minimally invasive "head-on" orbital approach that exploits endoscopic surgery advantages avoiding the cranio-orbital and trans-nasal approach limitations and possible complications. It represents a promising alternative to EETEth and ELO because of its optimal operability for resecting lesions extending into the entire inferior orbit.
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http://dx.doi.org/10.1007/s10143-021-01494-5DOI Listing
February 2021

Hemorrhagic Suprasellar Central Nervous System Embryonal Tumor in an Adult: Uncommon Features of an Extremely Rare Neoplasm.

J Neurol Surg A Cent Eur Neurosurg 2021 Jan 21. Epub 2021 Jan 21.

Department of Neurosurgery and Gamma Knife Radiosurgery, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background:  Occurrences of suprasellar central nervous system (CNS) embryonal tumors in adults are extremely rare. Hemorrhagic onset is further uncommon, with only anecdotic cases reported in the literature. The authors describe the case of a 57-year-old man affected by a suprasellar CNS embryonal tumor, with hemorrhagic onset and a unique diffusion pattern along the optic pathways.

Material And Methods:  A 57-year-old man presenting with acute visual acuity worsening and left homonymous hemianopia was referred to our hospital. Neuroradiologic studies demonstrated an infiltrating, high-grade lesion involving the optic chiasm and right retrochiasmatic pathways with a hemorrhagic area in the ipsilateral pulvinar.

Results:  The patient underwent microsurgical biopsy. Pathologic assessment confirmed the diagnosis of CNS embryonal tumor, not otherwise specified (NOS) according to the 2016 World Health Organization (WHO) classification of CNS tumors. The patient was referred to a multimodal adjuvant treatment; he eventually died 4 months after surgery. Competent literature has been systematically reviewed in the light of the relevant changes made in the last version of the WHO classification.

Conclusion:  Embryonal tumors should be considered in the differential diagnosis for sellar and suprasellar space-occupying lesions, despite the rarity of the disease and the uncommon features at time of presentation. As per our knowledge, this is the first case ever described of hemorrhagic suprasellar embryonal tumor with a diffusion pattern along white matter fibers. Histogenesis, biomolecular and neuroradiologic features, and classification of embryonal tumors are an open field of research, with considerable implications for the definition of better diagnostic pitfalls and therapeutic regimens.
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http://dx.doi.org/10.1055/s-0040-1721022DOI Listing
January 2021

Factors affecting long-lasting pain relief after Gamma Knife radiosurgery for trigeminal neuralgia: a single institutional analysis and literature review.

Neurosurg Rev 2021 Jan 12. Epub 2021 Jan 12.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute and Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy.

Gamma Knife radiosurgery (GKRS) is a well-established safe and effective treatment for trigeminal neuralgia (TN) with high initial success rate (80-90%). Why the pain relief is progressively decreased with time is a matter of considerable debate. To investigate factors related to long-lasting pain relief, the authors conducted a retrospective analysis focusing on anatomical and radiosurgical related parameters, chosen according to literature review. One hundred and twelve patients with classical trigeminal neuralgia and follow-up longer than 12 months were selected from our institutional consecutive series of patients treated by GKRS. Patients were followed for a mean period of 61.5 ± 3.5 months (range, 12-126 months) to evaluate, as endpoints, long-term pain relief and hypoesthesia onset. The median maximum radiation dose was 80 Gy (range 70-90 Gy). Factors related to poor long-term pain relief were prescription dose < 80 Gy (p = 0.038), calibration dose rate < 2.5 Gy/min (p = 0.018), and distance between isocenter and trigeminal nerve emergence > 8 mm (p < 0.001). When analyzing patients who received 80 Gy as maximum dose without any sector blocking, we notice that ID < 2.7 mJ was predictive for longer period of pain control (p = 0.043). It was experienced also among patients in which a small volume of the nerve (< 35%) received more than 80% of the maximal dose, compared to those in which a larger volume of the nerve was irradiated with maximal dose (p 0.034). This last result was significant if the shot was 8 mm or less from the pons. Several single-patient anatomical and radiosurgical parameters should be considered to improve GKRS effectiveness.
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http://dx.doi.org/10.1007/s10143-021-01474-9DOI Listing
January 2021

Results from ACROCOVID: an international survey on the care of acromegaly during the COVID-19 era.

Endocrine 2021 02 7;71(2):273-280. Epub 2021 Jan 7.

Pituitary Center, Oregon Health and Science University, Portland, OR, USA.

With most global healthcare resources focused on COVID-19, altered resource allocation is disrupting the continuum of care for chronic endocrine conditions, including acromegaly. In order to assess the effects of COVID-19 on care of patients with acromegaly, we conducted an international online survey of endocrinologists. The questionnaire was drafted by a Steering Committee of acromegaly experts and covered both respondent demographics, contact and communication with patients, and patient care. Respondent awareness was generated through social media campaigns and the survey completed online using Google forms. The majority of endocrinologists who responded (N = 84) were based in Europe (67.9%) and were female (58.3%). Slightly more than half of respondents worked in a specialized pituitary center (52.4%) and a large minority cared for more than 50 acromegaly patients (47.6%). Most respondents (85.7%) indicated surgery was their first-line treatment, with only 14.3% indicating medical therapy as a first-choice treatment option. One-third (33.3%) of respondents reported having delayed a planned surgery due to a lack of COVID-19 testing provision and 54.8% due to a lack of surgical provision; 19.1% indicated that a lack of personal protective equipment had reduced their ability to treat patients with acromegaly. Just 21.4% of respondents reported no negative effects from the pandemic on diagnostic practice patterns, and just 19.1% reported no negative effect on patient follow-up practices. Many respondents (55.9%) indicated that remote methods had improved their ability to communicate with their patients and 69.0% indicated that they would continue to use methods of consultation necessitated by the COVID-19 pandemic. Our data suggest the COVID-19 pandemic is substantially affecting the care of acromegaly. However, these results also suggest that endocrinologists are embracing aspects of the 'new normal' to create a novel continuum of care better suited to the presumed post-COVID-19 environment. The goal of these changes must be both to improve care while shielding patients from more severe involvement in concomitant acute illnesses such COVID-19.
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http://dx.doi.org/10.1007/s12020-020-02565-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790473PMC
February 2021

Nerve Compression Injuries After Prolonged Prone Position Ventilation in Patients With SARS-CoV-2: A Case Series.

Arch Phys Med Rehabil 2021 03 25;102(3):359-362. Epub 2020 Nov 25.

Department of Rehabilitation and Functional Recovery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute University, Milan.

Background: Prone positioning improves oxygenation in adult respiratory distress syndrome. This procedure has been widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, this procedure can also be responsible for nerve damage and plexopathy.

Methods: We retrospectively reviewed a series of 7 infectious patients with coronavirus disease 2019 who underwent prone positioning ventilation at the San Raffaele Hospital of Milan, Italy, during the SARS-CoV-2 pandemic.

Results: Clinical and neurophysiological data of 7 patients with nerve compression injuries have been reported.

Conclusions: Health care workers should take into consideration the risk factors for prone positioning-related plexopathy and nerve damage, especially in patients with coronavirus disease 2019, to prevent this type of complication.
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http://dx.doi.org/10.1016/j.apmr.2020.10.131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685952PMC
March 2021

A reappraisal on botulinum toxin-A in trigeminal neuralgia.

J Neurosurg Sci 2020 Sep 28. Epub 2020 Sep 28.

Department of Neurosurgery and Gamma Knife Radiosurgery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

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http://dx.doi.org/10.23736/S0390-5616.20.05125-5DOI Listing
September 2020

Transcortical endoportal subchoroidal endoscope-assisted approach to the third ventricle: from virtual reality to anatomical laboratory.

J Neurosurg Sci 2020 Sep 28. Epub 2020 Sep 28.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Background: Surgical approaches to the third ventricle (TV) have always represented a technical challenge in neurosurgery. Virtual reality (VR) is attaining increasing relevance in training programs and preoperative planning. The aim of this study is to demonstrate the worthwhile mutual contribution of VR simulations and specimen dissections to develop a new surgical approach to the TV.

Methods: The transcortical endoportal subchoroidal endoscope-assisted (TEPSEA) approach was planned and simulated thanks to VR (Surgical Theater©, LLC, Cleveland, Ohio), and then implemented on cadaver specimens by using the VBAS portal system (Viewsite™ Brain Access System TC Model, Vycor Medical™ Inc). We assessed anthropometric measurements during VR planning and evaluated surgical operability during anatomical dissections.

Results: Surgical field depths measured between 75.6 and 85.3 mm to mammillary bodies and habenular commissure, which were in mean 20.2 mm away. An 18-mm movement was estimated for 15°-posterior tilting of a 70-mm long VBAS. Excellent exposure and maneuverability were achieved within the TV through a 2.47 cm2 portal working area. The 30°-endoscope assistance expanded the access towards the anterior and posterior walls of the TV particularly to the infundibular recess, mammillary bodies, habenular commissure and pineal recess.

Conclusions: We documented the utility of a step-by-step VR planning and simulation followed by anatomical dissections to study surgical approaches to deep brain areas. The TEPSEA exploits the portal system and endoscopic assistance to access the entire TV minimizing cortical and white matter manipulation.
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http://dx.doi.org/10.23736/S0390-5616.20.05122-XDOI Listing
September 2020

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Rehabilitative of COVID-19 patients with acute lower extremity Ischemia and amputation.

J Rehabil Med 2020 Sep 2;52(9):jrm00094. Epub 2020 Sep 2.

Department of Rehabilitation and Functional Recovery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy. E-mail:

Objective: To evaluate the clinical characteristics and rehabilitation management of patients who undergo amputation for COVID-19-associated coagulopathy.

Methods: Clinical and laboratory data for 3 patients were analysed and their rehabilitative management discussed.

Results: The medical records of 3 patients who had undergone amputation due to acute lower extremity ischaemia and who were provided with rehabilitation in our COVID-19 unit were reviewed.

Conclusion: Coagulation changes related to SARS-CoV-2 may complicate recovery from this devastating disease. The rehabilitation management of amputated patients for COVID-19 acute lower extremity ischaemia is based on a multilevel approach for clinical, functional, nutritional and neuropsychological needs. Based on this limited experience, a dedicated programme for this specific group of patients seems advantageous to warrant the best functional outcome and quality of life.
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http://dx.doi.org/10.2340/16501977-2714DOI Listing
September 2020

Normal Insulin-like Growth Factor 1 During Somatostatin Receptor Ligand Treatment Predicts Surgical Cure in Acromegaly.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Neurosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.

Context: Treatment with somatostatin receptor ligands (SRLs) is often given before pituitary surgery to patients with acromegaly.

Objective: To study whether the response to treatment with SRLs is predictive of surgical outcome.

Design: Retrospective, observational study.

Setting: Tertiary care center.

Patients: We investigated 272 patients with acromegaly who had been treated with an SRL between 1990 and 2018.

Intervention: All patients underwent pituitary surgery performed by a skilled neurosurgeon.

Main Outcome Measure: Outcome of pituitary surgery in patients who had normalization of insulin-like growth factor 1 (IGF-1) levels during SRL therapy in comparison with patients who did not normalize IGF-1 levels.

Results: Normalization of IGF-1 levels during SRL treatment occurred in 62 patients (22.8%) and was similar for the 3 different types of SRL (P = .88). Surgical remission occurred in 59.6% of the patients. Patients who normalized IGF-1 levels during SRL treatment had a higher probability of surgical cure than patients without IGF-1 normalization (83.9% vs 52.4%, respectively; P < .001). Multivariate analysis confirmed that lack of cavernous sinus invasion, small maximum tumor diameter, and IGF-1 normalization during SRL therapy were the only factors independently associated with a favorable surgical outcome.

Conclusions: Our study demonstrates that the normalization of IGF-1 levels during treatment with SRLs is an independent predictive factor of a favorable surgical outcome. The underlying mechanisms remain unclear, but an optimal response to medical therapy may be a characteristic of less aggressive tumors that are more likely to be entirely removed at surgery.
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http://dx.doi.org/10.1210/clinem/dgaa424DOI Listing
September 2020

Combined Technique of Temporal Muscle Augmentation for Muscle Reconstruction in Case of Small to Medium Anatomic Defects.

J Craniofac Surg 2020 Oct;31(7):1933-1936

Department of Neurosurgery and Gamma Knife Radiosurgery, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

Inadequate temporal muscle (TM) reconstruction after surgery may hesitate in potentially severe functional and aesthetic sequelae, making it of paramount importance to carefully consider TM reconstruction even in case of small deformities.The authors describe the combined temporal muscle augmentation technique (CTMA), an innovative technique for TM augmentation for muscle reconstruction in case of small to medium substance loss.A cadaver study was conducted as preclinical validation of the technique for the assessment of CTMA coverage capability. CTMA consists in a combination of 2 techniques for muscle surface coverage (MSC) increase: the radial (RA) and the longitudinal augmentation (LA), which enables to harvest a radial (RF) and a longitudinal flap (LF), respectively.Each flap derives from a different muscle-bundle, spearing TM segmentation and functional performance, and are supplied by a specific neuro-vascular peduncle, which makes flaps functionally independent.A surgical case is reported to demonstrate the feasibility of the technique.Combined temporal muscle augmentation technique provides an overall coverage surface of 6.5 ± 0.6 cm, which corresponds to a gap distance of 2.5 ± 0.2 cm, with RF providing a statistically significant larger surface of coverage compared to LF (×2.1; P = 0.0001).Combined temporal muscle augmentation technique is easy and fast to perform displaying a good reconstructive capability with complete preservation of temporal muscle anatomic compartmentalization and segmental vasculature. It might be considered as a safe and effective alternative in the reconstruction of small-to medium TM defects.
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http://dx.doi.org/10.1097/SCS.0000000000006702DOI Listing
October 2020

Gamma Knife Radiosurgery for Trigeminal Neuralgia: Role of Trigeminal Length and Pontotrigeminal Angle on Target Definition and on Clinical Effects.

World Neurosurg 2020 10 26;142:e140-e150. Epub 2020 Jun 26.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.

Objective: Gamma Knife radiosurgery (GKRS) is a well-defined treatment for trigeminal neuralgia. The aim of this study was to determine how the GKRS planning might change on the basis of the patient's own anatomy and how to best choose the target location.

Methods: Trigeminal cisternal length, pontotrigeminal angle, and distance between middle of the shot and emergence were evaluated in 112 consecutive GKRS plans for trigeminal neuralgia. Correlations with pain outcomes and facial hypoesthesia were analyzed.

Results: The mean angle was 29° ± 4.4° and 37° ± 0.9°, respectively, in patients developing and not developing severe hypoesthesia (P = 0.045), despite no significant difference on brainstem dose (11.9 ± 0.8 and 10.5 ± 0.3 Gy; P = 0.22). The length of the nerve was not relevant on clinical outcomes but the shot-emergence distance (mean 8.1 ± 0.2 mm) depended on both trigeminal length and angle (P = 0.01). At constant prescription dose, 6-month cumulative rates of pain relief and control without therapy were 52.9% when the shot-emergence distance was ≤8 mm, whereas 25% when this distance was >8 mm (P = 0.017). The maintenance of good pain control was more long lasting in the first group (49.5 ± 6.6 vs. 25.4 ± 5 months; P = 0.006) with a 5-year cumulative rate of 70% and 26%, respectively (P < 0.001).

Conclusions: The pontotrigeminal angle and the shot-emergence distance should be considered during GKRS planning: the first as a potential risk factor for hypoesthesia, and the second should not exceed 8 mm.
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http://dx.doi.org/10.1016/j.wneu.2020.06.147DOI Listing
October 2020

COVID-19 rehabilitation units are twice as expensive as regular rehabilitation units.

J Rehabil Med 2020 Jun 30;52(6):jrm00073. Epub 2020 Jun 30.

Department of Rehabilitation and Functional Recovery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

Objective: The COVID-19 pandemic has caused significant motor, cognitive, psychological, neurological and cardiological disabilities in many infected patients. Functional rehabilitation of infectious COVID-19 patients has been implemented in the acute care wards and in appropriate, ad hoc, multidisciplinary COVID-19 rehabilitation units. However, because COVID-19 rehabilitation units are a clinical novelty, clinical and organizational benchmarks are not yet available. The aim of this study is to describe the organizational needs and operational costs of such a unit, by comparing its activity, organization, and costs with 2 other functional rehabilitation units, in San Raffaele Hospital, Milan, Italy.

Methods: The 2-month activity of the COVID-19 Rehabilitation Unit at San Raffaele Hospital, Milan, Italy, which was created in response to the emergency need for rehabilitation of COVID-19 patients, was compared with the previous year's activity of the Cardiac Rehabilitation and Motor Rehabilitation Units of the same institute.

Results: The COVID-19 Rehabilitation Unit had the same number of care beds as the other units, but required twice the amount of staff and instrumental equipment, leading to a deficit in costs.

Discussion: The COVID-19 Rehabilitation Unit was twice as expensive as the 2 other units studied. World health systems are organizing to respond to the pandemic by expanding capacity in acute intensive care and sub-intensive care units. This study shows that COVID-19 rehabilitation units must be organized and equiped according to the clinical and rehabilitative needs of patients, following specific measures to prevent the spread of infection amongs patients and workers.
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http://dx.doi.org/10.2340/16501977-2704DOI Listing
June 2020

The optimal numerosity of the referral population of pituitary tumors centers of excellence (PTCOE): A surgical perspective.

Rev Endocr Metab Disord 2020 Dec;21(4):527-536

Division of Endocrinology, San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy.

Surgical experience is of paramount importance to reach therapeutic success and minimize operative complications. In the field of pituitary surgery, this led to the concept of Pituitary Center of Excellence (PTCOE) defined as a center where an interdisciplinary team works in collaboration and where surgeons can be trained appropriately to reach and keep excellence in daily practice. To review the literature to define the optimal referral population size to establish a PTCOE to optimize both training and specific field research. A review of the literature was performed about epidemiology. The time needed to observe 200 cases of PAs in a single PTCOE and to reach the minimal surgical experience threshold (MSET) was calculated for different referral population groups. The time needed to reach MSET decreased as population size increased. We defined a population as the optimal one to be served by a single PTCOE with a single dedicated neurosurgeon. PTCOEs should be established after an analysis of the referral population, number of cases suitable for surgical treatment and number of dedicated neurosurgeons.
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http://dx.doi.org/10.1007/s11154-020-09564-7DOI Listing
December 2020

Nutritional management of COVID-19 patients in a rehabilitation unit.

Eur J Clin Nutr 2020 Jun 20;74(6):860-863. Epub 2020 May 20.

Department of Rehabilitation and Functional Recovery, I.R.C.C.S. San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.

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http://dx.doi.org/10.1038/s41430-020-0664-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237874PMC
June 2020

Cumulative intracranial tumour volume prognostic assessment: a new predicting score index for patients with brain metastases treated by stereotactic radiosurgery.

Clin Exp Metastasis 2020 08 19;37(4):499-508. Epub 2020 May 19.

Department of Neurosurgery and Gamma Knife Radiosurgery, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Brain metastases (BM) represent the most common intracranial malignancy in adults. Limitations of existing prognostic models reduce their predictivity and clinical applicability. The aim of this study is to validate the cumulative intracranial tumour volume prognostic assessment (CITVPA) as a new prognostic score system for patients with BM treated by Stereotactic Radiosurgery (SRS). Between January 2001 and December 2015, 1894 patients underwent Gamma Knife SRS treatment. The CITVPA model was implemented and validated as follows: the CITV cut-offs were identified thanks to a receiver-operating characteristic (ROC) curve analysis; the survival predictive factors were selected through a Cox proportional hazard model; its prognostic power was compared to RPA, SIR and GPA through the Harrel concordance index (HCI). According to the ROC curve analysis, the CITV cut-off values were set at 1.5 and 4.0 cc. Based on the multivariate analysis, the CITVPA model included: age (OR 1.010, 95% CI 1.005-1.015, p < 0.001), KPS (OR 0.960, 95% CI 0.956-0.965, p < 0.001), extracranial metastases (OR 1.287, 95% CI 1.154-1.437, p < 0.001), BM number (OR 1.193, 95% CI 1.047-1.360, p = 0.008), and CITV (OR 1.028, 95% CI 1.020-1.036, p < 0.001). A score between 0 and 1 was attributed to each prognosticator; a global CITVPA score ranging from 0 to 5 was assigned with higher results corresponding to worse outcomes. The CITVPA (HCI = 0.64) exhibited a significantly (p < 0.001) higher prognostic power compared to RPA (HCI = 0.55), SIR (HCI = 0.55) and GPA (HCI = 0.61). The CITVPA represents a reliable prognostic system for patients with BM treated by SRS. However, further prospective and multicentric studies are necessary before its applicability in clinical practice.
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http://dx.doi.org/10.1007/s10585-020-10037-zDOI Listing
August 2020

How I do it: posterior transdural approach for central soft thoracic disk herniation.

Acta Neurochir (Wien) 2020 09 8;162(9):2051-2054. Epub 2020 May 8.

Department of Neurosurgery and Gamma Knife Radiosurgery, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina 60, 20132, Milan, Italy.

Background: Thoracic disc herniation (TDH) is a rare condition with severe neurological sequelae. Surgical management is still a matter of debate and challenging.

Method: We present a modification of the transdural approach for TDH. The approach has been described in a stepwise fashion, analysing pre-, peri-, and postoperative strategies to improve patients' management and reduce approach-related morbidity.

Conclusion: The modified posterior transdural approach represents an effective technique for TDH, minimizing the risk of spinal cord damages, which can dramatically affect the outcome.
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http://dx.doi.org/10.1007/s00701-020-04387-6DOI Listing
September 2020