Publications by authors named "Claudio Guastella"

27 Publications

  • Page 1 of 1

The "Parachute" Technique for the Endoscopic Repair of High-Flow Anterior Skull-Base CSF Leaks.

World Neurosurg 2021 May 8. Epub 2021 May 8.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; "Aldo Ravelli" Research Center, Milan, Italy; Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, Milan, Italy.

Objective: This study aims to assess the feasibility and reliability of our endoscopic trans-nasal technique for the repair of cribriform and sellar high-flow cerebrospinal fluid (CSF) leaks.

Methods: A comparison between patients suffering from high-flow rhinorrhea and treated through a free grafting endoscopic technique or the "parachute" technique, our nasal packing proposal, was performed.

Results: Thirty-three patients were included. The mean age was 52 years (range: 36-68 years). The etiology of the CSF leaks was iatrogenic in 16 cases (48.5%), traumatic in 5 cases (15.2%), spontaneous in 11 cases (33.3%), and related to anterior skull base tumors in 1 case (3%). The bone defect affected the sphenoidal sinus in 20 cases (60.6%), the cribriform plate of the ethmoid in 10 cases (30.3%), and both the sphenoid and ethmoid in 3 cases (9.1%). The mean size of bone defects was 8.5 ± 3.9 mm. The median follow-up was 28 (64) months. A CSF leak recurrence occurred in no cases treated with the parachute technique and in 3 cases that underwent conventional endoscopic treatments. The CSF leak recurrences were associated with 2 iatrogenic and 1 post-traumatic fistula. All the CSF leak recurrences underwent the parachute technique, not showing second recurrences.

Conclusions: Our results suggest that the parachute technique is simple, safe, and effective. We recommend it as an alternative treatment to vascular flaps for the treatment of high-flow and recurrent fistulas.
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http://dx.doi.org/10.1016/j.wneu.2021.05.006DOI Listing
May 2021

Efficacy Profile and Safety of Very Low-Dose Rituximab in Patients with Graves' Orbitopathy.

Thyroid 2021 May 31;31(5):821-828. Epub 2021 Mar 31.

Department of Clinical Sciences and Community Health, Graves' Orbitopathy Center, Endocrinology, Milan, Italy.

Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled. Disease activity was assessed with the clinical activity score (CAS) and severity with a composite ophthalmic score. Long-term surgical treatment and quality of life were also assessed, as well as treatment-related adverse events. Mean baseline CAS was 4.56 ± 0.96 and decreased to 1.25 ± 1.14 at 24 weeks ( = 0.001). Disease inactivation occurred within 24 weeks in >90% of patients and was unrelated to disease duration. Severity improved in about 60% of patients, with no relapses. All patients showed peripheral depletion of CD20 and CD19 cells at the end of RTX infusion (60 minutes). Two patients required surgical orbital decompression because of optic neuropathy (ON). Among adverse events observed, there was one patient who developed a cytokine release syndrome. A dose of 100 mg RTX is effective in patients with active moderate-severe GO. Low doses are better tolerated, expose patients to immune suppression for a shorter period of time, and are extremely cost effective, compared with higher doses. This dose, consistently with all other immunosuppressants, does not prevent the progression of GO to dysthyroid ON.
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http://dx.doi.org/10.1089/thy.2020.0269DOI Listing
May 2021

Quantification of Global Ocular Motility Impairment in Graves' Orbitopathy by Measuring Eye Muscle Ductions.

Thyroid 2021 02 22;31(2):280-287. Epub 2020 Oct 22.

Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

The overall changes of ocular motility in Graves' orbitopathy (GO) are not easily quantifiable with the methods currently available, especially in clinical studies. The aim of the present study was to calculate parameters that quantify the changes of ocular motility in GO in relation to the Gorman score for diplopia. We studied 100 GO patients (Group 1) and 100 controls (Group 2). We also included 30 patients treated with intravenous methylprednisolone (iv-MP), assessed at baseline and after 12 and 24 weeks (Group 3), and 66 patients submitted to squint surgery, assessed at baseline and after 12 weeks (Group 4). Ocular ductions were measured in four gaze directions by a perimeter arc and were used to calculate a total motility score (TMS) as the sum of ductions in each direction; a biocular TMS (b-TMS) as the sum of the TMS of two eyes; and an asymmetry ratio (AR) as the sum of the differences of the corresponding ductions between the two fellow eyes divided by the mean difference found in controls. Quality of life was accessed by a specific questionnaire (Graves' orbitopathy quality of life [GO-QoL] questionnaire). TMS and b-TMS were lower, while AR was higher, in Group 1 compared with controls ( < 0.001). In Group 1, TMS and b-TMS were inversely correlated with the Gorman score ( < 0.001) and AR was higher in patients with constant diplopia compared with the others ( < 0.001). In Group 3, TMS and b-TMS increased after treatment in responders to iv-MP ( < 0.001). In Group 4, TMS and b-TMS improved in all patients after surgery ( < 0.01), while AR and GO-QoL score improved only in those without residual constant diplopia ( < 0.001). We describe a quantitative method to assess eye motility dysfunction in any stage of GO to be used as an outcome measure in clinical studies.
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http://dx.doi.org/10.1089/thy.2020.0165DOI Listing
February 2021

Abscess of the clivus in an adolescent with complicated acute rhinosinusitis: a case report.

Ital J Pediatr 2020 Jul 14;46(1):97. Epub 2020 Jul 14.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35,20122, Milan, Italy.

Background: Complications of acute sinusitis affecting multiple sites are very uncommon, and generally develop for a delayed diagnosis of the primary infection, with possible severe and life-threatening evolution. Patients can have variable presentations according to the site and extent of the infection. Multiple forms generally include the coexistence of orbital manifestations and intracranial infections. We here present a case with unusual multiple sites locations (i.e.: intraorbital intraconic abscess, sigmoid sinus thrombosis, preclival abscess, multiple splanchnocranium osteomyelitic processes).

Case Presentation: A 13-year-old male presented at our hospital with right progressive orbital oedema with eyesight worsening and signs of meningitis. Computed tomography and magnetic resonance (MRI) demonstrated right intraorbital intraconic abscess, left sphenoidal sinusitis, transverse and sigmoid sinus thrombosis. Ophthalmologic evaluation documented a right optic nerve sufferance. Endoscopic and superior right trans-palpebral surgical decompression was performed, and the abscess was drained. Microbiological analysis revealed the presence of multi-sensitive Streptococcus Intermedius. Subsequent prolonged antibiotic and anti-thrombotic treatments were started. In the following two-weeks the sinusal and ophthalmologic clinical conditions improved, whereas the patients complained of mild to moderate cervical pain and suffered from intermittent pyrexia. Control MRI documented clival abscess extending up to preclival soft tissues posterior to the nasopharynx, associated with mandible osteomyelitis, occipital condyles and anterior part of the temporal bone hyper intensity. Endoscopic trans-nasal surgical approach to the clival compartment with neurosurgery navigation-guided achieved preclival abscess drainage. Complete clinical and radiological recovery was achieved after 45 days of medical treatment.

Conclusions: Multiple sites complicated rhinosinusitis is uncommon, and its management is challenging. A proper history and thorough clinical examination along with a radiological evaluation are key factors in the final diagnosis of patients with complicated multiple sites acute rhinosinusitis. A quick multidisciplinary approach is always necessary to avoid unwanted life-threatening complications.
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http://dx.doi.org/10.1186/s13052-020-00863-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362412PMC
July 2020

The suprasellar volume of nonfunctioning pituitary adenomas: a useful tool for predicting visual field deficits.

Pituitary 2020 Oct;23(5):552-557

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza, 20122, Milan, Italy.

Purpose: The aim of the present study is to assess the predictive value of the suprasellar volume (SSV) of nonfunctioning pituitary adenomas (NFPAs) for visual field (VF) impairment in order to guide clinical decision-making and improve neurosurgical management.

Methods: Two independent samples of patients with NFPAs (exploratory population N = 50, testing population N = 98) were included in the present study. In the first phase, we determined the optimal cut-off value of the SSV correlating with VF deficits in the exploratory population. In the second phase, we then studied the accuracy of identified cut-off in predicting a VF deficit in the testing population.

Results: In the exploratory population, the optimal cut-off value of the SSV to determine the presence of a VF deficit was 1.5 mL. Sensitivity and specificity of the cut-off were 81.3 and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 100 and 75%, respectively. When we checked the identified cut-off score on the testing population, we found a sensitivity of 71% and a specificity of 100%. The PPV and NPV were 100 and 59.2%, respectively. In six cases with VF defects and SSV inferior to 1.5 mL, the displacement of optic chiasm was in superior position.

Conclusion: The SSV may represent an accurate method in routinely clinical practice for predicting VF deficit in patients affected by NFPA.
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http://dx.doi.org/10.1007/s11102-020-01060-0DOI Listing
October 2020

Prevention of Orbitopathy by Oral or Intravenous Steroid Prophylaxis in Short Duration Graves' Disease Patients Undergoing Radioiodine Ablation: A Prospective Randomized Control Trial Study.

Thyroid 2019 12;29(12):1828-1833

Graves' Orbitopathy Center, Endocrinology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Radioiodine (RAI) is a known risk factor for activation or occurrence of Graves' orbitopathy (GO). Several studies demonstrated that GO can be prevented by glucocorticoids (GCs) in patients with pre-existing GO. We have previously shown that Graves' disease duration (GDd) <5 years is a risk factor for RAI-induced GO. We studied the effect of prophylaxis with either oral GCs (OGCs) or intravenous GCs (IVGCs) on GO activation in patients with GDd. In total, 99 hyperthyroid patients without GO or with pre-existing inactive GO with GDd <5 years were randomized to receive IVGCs ( = 49) or OGCs ( = 50) before RAI; 22 patients with GDd >5 did not receive steroids and were studied as controls. All patients underwent ophthalmological assessment before and 45, 90, 180 days and for a 5-year follow-up after RAI. Serum thyrotropin (TSH) receptor antibodies (TRAbs), thyroid hormones, and thyroid volume (TV) were also measured in response to RAI therapy and steroid prophylaxis. No patient on prophylaxis developed GO after RAI. One woman of the control group, without steroid prophylaxis, and who had a marked elevation of her TSH, showed transient reactivation of GO, which spontaneously improved after restoring euthyroidism. On follow-up at 12 and 20 months after RAI, two patients developed overt optic neuropathy. A smaller TV was associated with a higher prevalence of RAI-induced hypothyroidism. Serum TRAbs increased significantly after RAI ( < 0.0001) but less in patients receiving steroids than in those without prophylaxis at 45 days ( < 0.01). The risk of RAI-induced GO can be prevented in all patients with GDd <5 years by steroids. Such treatment may not be necessary in patients with GDd >5 years. The blunting of TRAb elevation after RAI may be related to the prophylactic effect of steroids.
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http://dx.doi.org/10.1089/thy.2019.0150DOI Listing
December 2019

Review of Systemic Antibiotic Treatments in Children with Rhinosinusitis.

J Clin Med 2019 Aug 3;8(8). Epub 2019 Aug 3.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20100, Italy.

Antibiotic treatment in paediatric rhinosinusitis is still a matter of debate, as the current guidelines have been drafted mainly based on clinical studies published before 2013. Recent modifications in the epidemiological basis of the disease might mean that current treatments are not completely adequate considering the evolving microbiological profile of the disease. The present paper reviews the role of systemic antibiotics in children with acute (ARS), chronic (CRS), recurrent (RARS), and complicated acute (CoARS) rhinosinusitis. A total of 14 studies (including 3 prospective non-randomised studies, 8 retrospective studies, and 3 prospective randomised studies) of the 115 initially identified papers were included in this review, corresponding to 13,425 patients. Five papers dealt with ARS, four papers with RARS or CRS, and five papers with CoARS; the remaining papers included patients with either ARS or CRS. Data about the effectiveness of antibiotic treatment in children with ARC, CRS, and CoARS is scarce, as only three randomised controlled trials have been published in the last decade, with contrasting results. There is an urgent need for dedicated controlled trials not only to test the actual clinical benefits deriving from the routine use of systemic antibiotics in different categories of patients but also to compare the effectiveness of various therapeutic protocols in terms of the type of antibacterial molecules and the duration of treatment.
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http://dx.doi.org/10.3390/jcm8081162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723210PMC
August 2019

Surgical Treatment of Paediatric Chronic Rhinosinusitis.

J Clin Med 2019 May 15;8(5). Epub 2019 May 15.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Rhinosinusitis (RS) is a common disease in children, significantly affecting their quality of life. Chronic rhinosinusitis (CRS) is frequently linked to other respiratory diseases, including asthma. Children affected by CRS may be candidates for surgery in the case of failure of maximal medical therapy comprising three to six weeks of broad-spectrum systemic antibiotics with adjunctive therapies. Although endoscopic sinus surgery (ESS) is the surgical treatment of choice in adult patients with CRS, different surgical procedures are scheduled for refractory paediatric CRS and include adenoidectomy, paediatric ESS (PESS), and balloon catheter sinuplasty (BCS). The present paper discusses the indications and limitations of each treatment option in children with CRS. Given the amount of current evidence, it is reasonable to suggest that, in young and otherwise healthy children with refractory CRS, an adenoidectomy (eventually combined with BCS) should be offered as the first-line surgical treatment. Nevertheless, this approach may be considered ineffective in some patients who should be candidates for traditional ESS. In older children, those with asthma, or in the case of peculiar conditions, traditional ESS should be considered as the primary treatment.
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http://dx.doi.org/10.3390/jcm8050684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571701PMC
May 2019

An Unusual Hypopharyngeal Foreign Body Causing Dyspnea After Vertebroplasty.

Ear Nose Throat J 2019 Jul 28;98(6):321-323. Epub 2019 Mar 28.

1 Department of Otorhinolaryngology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

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http://dx.doi.org/10.1177/0145561319837457DOI Listing
July 2019

Sinonasal-Related Orbital Infections in Children: A Clinical and Therapeutic Overview.

J Clin Med 2019 Jan 16;8(1). Epub 2019 Jan 16.

Otolaryngological Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

Sinonasal-related orbital infections (SROIs) are typically pediatric diseases that occur in 3⁻4% of children with acute rhinosinusitis. They are characterised by various clinical manifestations, such as peri-orbital and orbital cellulitis or orbital and sub-periosteal abscesses that may develop anteriorly or posteriorly to the orbital septum. Posterior septal complications are particularly dangerous, as they may lead to visual loss and life-threatening events, such as an intracranial abscess and cavernous sinus thrombosis. Given the possible risk of permanent visual loss due to optic neuritis or orbital nerve ischemia, SROIs are considered ophthalmic emergencies that need to be promptly recognised and treated in an urgent-care setting. The key to obtaining better clinical outcomes in children with SROIs is a multi-disciplinary assessment by pediatricians, otolaryngologists, ophthalmologists, radiologists, and in selected cases, neurosurgeons, neurologists, and infectious disease specialists. The aim of this paper is to provide an overview of the pathogenesis, clinical manifestations, diagnosis, and treatment of pediatric SROIs, and to make some practical recommendations for attending clinicians.
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http://dx.doi.org/10.3390/jcm8010101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351922PMC
January 2019

Aneurysmal bone cyst in the inferior nasal turbinate in a pediatric patient: A case report.

Turk J Pediatr 2018 ;60(6):747-750

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinica, University of Milan, Milan, Italy.

Torretta S, Di Pasquale D, Carioli D, Guastella C, Ibba T, Marchision P, Pignataro L. Aneurysmal bone cyst in the inferior nasal turbinate in a pediatric patient: A case report. Turk J Pediatr 2018; 60: 747-750. Aneurysmal bone cysts (ABCs) are non-neoplastic, highly vascularised bone lesions that rarely involve the craniofacial complex. We describe the first case of an ABC involving the inferior turbinate in a 17-month-old boy who attended our Pediatric Emergency Department because of recurrent epistaxis, and discuss the diagnostic and therapeutic work-up in children with nasal masses.
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http://dx.doi.org/10.24953/turkjped.2018.06.019DOI Listing
January 2018

Is Complex Sphenoidal Sinus Anatomy a Contraindication to a Transsphenoidal Approach for Resection of Sellar Lesions? Case Series and Review of the Literature.

World Neurosurg 2017 Apr 5;100:173-179. Epub 2017 Jan 5.

Unit of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: The transsphenoidal approach is considered the gold standard for resection of pituitary adenomas and other sellar region lesions. This approach is guided by a few fundamental anatomic landmarks that conduct the surgeon toward the sellar floor. Some anatomic structures may vary a lot (e.g., intrasphenoidal septa, intercarotid distance) and may be difficult to identify. Pneumatization and conformation of the sphenoidal sinus (SS) plays a key role in accessing the floor of the sella and other skull base structures. A poorly pneumatized SS may be a relative contraindication to the transsphenoidal approach. We analyzed outcome and complications in transsphenoidal surgery for sellar lesions with a difficult SS.

Methods: We analyzed 243 consecutive patients who underwent a transsphenoidal approach for sellar lesions. Patients with poor pneumatization of the SS were included. Neurosurgical and endocrinologic outcomes were reported.

Results: Successful treatment using a transsphenoidal approach with neuronavigation and Doppler ultrasound was achieved in 15 patients with a low degree of pneumatization of the SS. A pituitary adenoma was present in 13 of 15 patients. Endocrinologic and neurosurgical outcomes were similar to patients with normal pneumatization of the SS, showing a cure of disease in 6 of 9 patients with functioning adenomas and an improvement of symptoms in cases of nonfunctioning adenomas.

Conclusions: Patients with a poorly pneumatized SS can be treated safely with a transsphenoidal approach using image guidance techniques to avoid major neurovascular complications.
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http://dx.doi.org/10.1016/j.wneu.2016.12.123DOI Listing
April 2017

Oral pyogenic granuloma gravidarum: A case report describing a large bleeding lingual lesion.

J Obstet Gynaecol 2017 May 26;37(4):537-538. Epub 2016 Dec 26.

a Department of Otolaryngology, Department of Clinical Sciences and Community Health , Fondazione I.R.C.C.S. Ca' Granda, Ospedale Maggiore Policlinico, University of Milan , Milan , Italy.

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http://dx.doi.org/10.1080/01443615.2016.1256957DOI Listing
May 2017

Titanium Exposure Outcome in Facial Plastic and Reconstructive Surgery.

Plast Reconstr Surg 2017 01;139(1):310e

Italian Association for Metals and Biocompatibility Research Milan, Italy.

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http://dx.doi.org/10.1097/PRS.0000000000002867DOI Listing
January 2017

Efficacy of B-cell targeted therapy with rituximab in patients with active moderate to severe Graves' orbitopathy: a randomized controlled study.

J Clin Endocrinol Metab 2015 Feb 15;100(2):422-31. Epub 2014 Dec 15.

Graves' Orbitopathy Center, Endocrinology Unit, Departments of Clinical Sciences and Community Health (M.S., G.V., I.C., D.C., P.B.-P.), Ophthalmology (N.C., S.S.), Otolaryngology (C.G., L.P.), and Neuroradiology (S.A.), Fondazione Cà Granda Istituto di Ricovero e Cura a Carattere Scientifico and University of Milan, I-20122 Milan, Italy; and Division of Internal Medicine (D.D.), Ospedale di Fidenza, I-43036 Fidenza, Italy.

Background: Preliminary studies have shown that rituximab (RTX) is effective in the treatment of active Graves' orbitopathy (GO).

Methods: We conducted a double-blind, randomized trial (European Clinical Trials Database [EudraCT] 2007-003910-33) to compare RTX with iv methylprednisolone (ivMP) in patients with active moderate to severe GO. Thirty-two patients were randomized to receive either ivMP (7.5 g) or RTX (2000 or 500 mg). The primary end point was the decrease of the clinical activity score of 2 points or to less than 3 at week 24. Changes of proptosis, lid fissure, diplopia and eye muscle motility, and quality of life score were secondary end points. The number of therapeutic responses, disease reactivation, and surgical procedures required during follow-up and the patients' quality of life were also assessed.

Results: The clinical activity score decreased with both treatments but more after RTX at 16, 20, and 24 weeks (P < .04, P < .02, P < .006, respectively), whether 1000 mg RTX twice or 500 mg RTX once was used (P = NS). At 24 weeks 100% of RTX patients improved compared with 69% after ivMP (P < .001). Disease reactivation was never observed in RTX patients but was observed in five after ivMP. Patients treated with RTX scored better motility at 52 weeks in both the right (P = .014) and the left eye (P = .026). Overall rehabilitative surgical procedures carried out during follow-up (at 76 wk) were 12 in 16 ivMP patients and 5 in 15 RTX patients (P = .049).

Conclusions: The results of this trial confirm preliminary reports on a better therapeutic outcome of RTX in active moderate to severe GO, when compared with ivMP, even after a lower RTX dose. The better eye motility outcome, visual functioning of the quality of life assessment, and the reduced number of surgical procedures in patients after RTX seem to suggest a disease-modifying effect of the drug.
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http://dx.doi.org/10.1210/jc.2014-3014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318899PMC
February 2015

Therapeutic outcomes of high-dose intravenous steroids in the treatment of dysthyroid optic neuropathy.

Thyroid 2014 May 6;24(5):897-905. Epub 2014 Mar 6.

1 Unit of Ophthalmology, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca' Granda , Ospedale Maggiore Policlinico, Milan, Italy .

Background: While pulsed intravenous methylprednisolone (iv-MP) has been shown to be effective and well tolerated in moderate to severe Graves' orbitopathy (GO), limited data are available on dysthyroid optic neuropathy (DON). The objective of this retrospective study was to investigate the efficacy of iv-MP in the treatment of DON and to seek parameters predictive of response.

Methods: Twenty-four DON patients (40 eyes) treated with iv-MP from 2007 to 2012 were included in the study. Concurrent neurological or ophthalmologic diseases or signs of corneal exposure were considered as exclusion criteria. Iv-MP was administered daily for three consecutive days and repeated the following week. At six months, eyes not requiring surgery to preserve visual function were considered as responsive to treatment. Visual acuity, color sensitivity, visual field, and optic discs were analyzed at two and four weeks, and at 3, 6, and 12 months after treatment. Activity of GO was graded using a clinical activity score (CAS). Visual and clinical characteristics of the eyes responsive to iv-MP were studied by comparison to those of nonresponsive eyes.

Results: At six months, 17 of 40 (42.5%) eyes had complete visual recovery and were spared from surgical decompression. At two weeks, visual acuity, color sensitivity, and visual field improved significantly in almost all eyes, but GO inactivated (CAS<4) only in the eyes that permanently responded to iv-MP (p<0.01). The CAS at two weeks was a good predictor of response (cutoff ≥4; 66.7% sensitivity, 76.9% specificity). Optic disc swelling at diagnosis was highly predictive for unresponsiveness to iv-MP (34% sensitivity, 100% specificity). At baseline, high CAS (cutoff >5; 40.2% sensitivity, 94.1% specificity) and severely altered visual field mean defect (cutoff ≤6.31 dB; 73.9% sensitivity, 58.8% specificity) were associated with unresponsiveness to steroids. No major side effects were observed.

Conclusions: High-dose iv-MP was effective in permanently restoring visual function in about 40% of the eyes treated. When successful, it generally induced inactivation of the orbital disease within two weeks and normalization of visual function within one month. The presence of optic disc swelling at diagnosis and persistent active disease at two weeks were good predictors of unresponsiveness to steroids.
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http://dx.doi.org/10.1089/thy.2013.0445DOI Listing
May 2014

A quantitative method for assessing the degree of axial proptosis in relation to orbital tissue involvement in Graves' orbitopathy.

Ophthalmology 2013 May 8;120(5):1092-8. Epub 2013 Feb 8.

Endocrinology, Department of Clinical Sciences and Community Health, Graves' Orbitopathy Center, Università degli Studi di Milano, Fondazione Cà Granda, IRCCS Milan, Italy.

Purpose: To define a method of quantifying axial proptosis in patients with Graves' orbitopathy (GO) and to validate a score that correlates with the orbital involvement and helps determine the degree of proptosis correction for elective orbital decompression.

Design: Retrospective, case series.

Participants: The study included 50 patients (group A) and 29 control subjects who underwent orbital computed tomography (CT). The method was then validated in another group of 21 patients with GO (group B).

Methods: The orbital area (OA) was measured manually on the central axial section of the CT scan at a level where the lens is visualized. The OA intersects the projection of the globe and delimitates the chord of an arch (globe chord [OC]). The area of the circular sector under the chord (CA) represents the portion of the globe within the orbit.

Main Outcome Measures: A CA-to-OA ratio was calculated to reduce the error due to variability of the measurements and to perform correlations with some of the clinical parameters of GO.

Results: Measurement error was low (<2%). We did not observe significant differences in the mean OA of patients with GO (783.6 ± 12.1 mm(2)) and controls (758.5 ± 20.4 mm(2); P = not significant). The OC value in patients with GO was 130.2 ± 11.5 mm(2), significantly lower than in controls (281.8 ± 9.7 mm(2); P<0.0001). The CA-to-OA ratio also was lower in patients with GO than in controls (0.16 ± 0.01 vs. 0.38 ± 0.01; P<0.0001). A significant correlation was found in patients with GO between the CA-to-OA ratio and proptosis (P<0.001), lid fissure (P = 0.004), and intraocular pressure (P<0.001). In group B, the CA-to-OA ratio was 0.18 ± 0.02, significantly different from that of controls (P<0.0001) and inversely correlated with proptosis (P<0.0001) and lid fissure (P<0.045).

Conclusions: By measuring the CA-to-OA ratio, we were able to quantify the degree of axial proptosis in patients with GO. The significant correlation of CA/OA with some orbital parameters confirms that this parameter also may be used as a measure of orbital involvement in GO.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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http://dx.doi.org/10.1016/j.ophtha.2012.10.041DOI Listing
May 2013

Transphenoidal surgery in acromegalic patients: anatomical considerations and potential pitfalls.

Acta Neurochir (Wien) 2013 Jan 25;155(1):125-30; discussion 130. Epub 2012 Nov 25.

Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milano, Via Francesco Sforza 35, 20122, Milano, MI, Italy.

Background: Transphenoidal surgery is an effective treatment for acromegalic patients with growth hormone (GH) producing pituitary adenomas. Since acromegaly is a systemic disease which causes multiple bony alterations, we hypothesized that it could affect the sphenoid sinus anatomy. The aim of the study was to determine whether acromegalic patients have sphenoid sinus alterations with potential surgical impact.

Methods: Fourty-six consecutive patients (23 acromegalics-GH group, 23 non-acromegalics-nGH group) undergoing transphenoidal surgery were included in this study. Pre-operative volumetric CT scan of the head was used to assess the following anatomic characteristics: type of sphenoid sinus (sellar, pre-sellar, conchal); number of intrasphenoid septa; number of carotid-directed septa; intercarotid distance; depth of the sphenoid sinus; depth and size of the sella.

Results: The sphenoid sinus was of the pre-sellar/conchal type in 26 % of the patients with acromegaly (n = 23) versus 9 % of the patients of the nGH group (n = 23). The number of intrasphenoid septations was significantly higher in the GH group than in the nGH group (P = .03). Interestingly, the intercarotid distance was smaller in GH patients than in nGH displaying a trend toward significance (P = .05). The sphenoid bone was deeper in the GH group as compared to the nGH group (P = .01) but the distance sphenoid sinus-sella was reduced (P < .01). Finally, the sella was not deeper, nor larger in acromegalic patients.

Conclusions: The sphenoid sinus of acromegalic patients resulted in being deeper, characterized by more septa and by a reduced intercarotid distance. These alterations deserve special pre- and intraoperative care, being potentially responsible for surgical difficulties.
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http://dx.doi.org/10.1007/s00701-012-1527-6DOI Listing
January 2013

Serum BAFF concentrations in patients with Graves' disease and orbitopathy before and after immunosuppressive therapy.

J Clin Endocrinol Metab 2012 May 7;97(5):E755-9. Epub 2012 Mar 7.

Endocrine Unit, Department of Medical Sciences, University of Milan and Fondazione Cà Granda Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy.

Introduction: B cells are known to play a key role in the pathogenesis of autoimmune disease. B lymphocyte activating factor (BAFF), a member of TNF family, promotes autoantibody production by increasing B cell survival and proliferation. Serum BAFF concentrations have been found to be increased in systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome.

Objective: We have measured serum BAFF concentrations in patients with Graves' disease (GD) with or without Graves' orbitopathy (GO) and in active GO in relation to immunosuppressive treatment.

Methods: Forty-two patients and nine normal controls were studied. Thirty-four patients had GO, which was active in 23. Of these, nine were treated with rituximab (RTX) and 14 with i.v. methylprednisolone (MP). Serum BAFF concentrations were measured at baseline in all patients, at peripheral B cell depletion and repopulation after RTX, and after therapy with MP.

Results: Serum basal BAFF concentrations in GD patients were significantly higher when compared with normal controls (P = 0.0001), and no difference was observed in those with active or inactive GO. Serum BAFF concentrations were also significantly correlated with serum antithyroglobulin antibodies (P = 0.04) but not with sex, age, smoking habits, therapy for thyroid disease, and serum antithyroperoxidase antibodies and TSH receptor antibodies. After RTX, there was an increase of serum BAFF concentrations at the time of B cell depletion (P = 0.02) but also at B cell repopulation (P = 0.04). In patients treated with MP, serum BAFF concentrations decreased significantly after therapy (P < 0.01).

Conclusions: We report that serum BAFF concentrations are elevated in patients with GD, in whom hyperthyroidism is known to be based on a B-cell-driven pathophysiological mechanism. In active GO, BAFF further increases after therapy with RTX as a consequence of the B cell depletion per se. The decrease of serum BAFF after iv steroids suggests that MP may exert an immunosuppressive effect by modifying B-cell-derived immune reactions.
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http://dx.doi.org/10.1210/jc.2011-2614DOI Listing
May 2012

Endoscopic endonasal removal of a cavernous hemangioma of the orbital apex.

Surg Neurol Int 2011 28;2:58. Epub 2011 Apr 28.

Department of Neurosurgery, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milano, Via Francesco Sforza 35, Milano 20122, Italy.

Background: Cavernous hemangioma are the most common benign lesions of the orbit. Their surgical resection is still challenging and several surgical approaches have been proposed.

Case Description: We present the case of a 59-year-old woman with a cavernous hemangioma of the orbital apex, which was diagnosed incidentally. The hemangioma was extraconal and involved mainly the medial orbital apex; it also extended to the pterygoid fossa, to the middle fossa, to the maxillary and sphenoid sinuses. The surgical resection was performed by a pure endoscopic transphenoidal, transmaxillary, transethmoidal approach, achieving a total removal. The patient had a transient and incomplete paresis of the VI cranial nerve on the left side and did not experience other postoperative complications.

Conclusion: The endoscopic endonasal approach proved successful in the management of this case and it should be considered in the surgical management of extraconal orbital apex lesions with medial or inferior extension.
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http://dx.doi.org/10.4103/2152-7806.80123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114373PMC
July 2011

Anterior cranial base reconstruction following a complicated nasal septoplasty.

Acta Neurochir (Wien) 2009 Jun 1;151(6):701-3; discussion 703. Epub 2009 Apr 1.

Unit of Neurosurgery, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Via Francesco Sforza 35, Milan 20122, Italy.

We present a 29 year old man who had unilateral visual loss and 3rd cranial nerve palsy after a nasal septoplasty. Nasal packing was extending from the right nasal cavity into the right frontal lobe passing through the right orbit. A combined trans-cranial and endoscopic endonasal approach was performed to safely remove the nasal packing and to achieve a leak-proof sealing of the anterior cranial base. This surgical technique proved successful in the management of this unique complication and should be considered in the surgical management of foreign body removal from the anterior cranial base.
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http://dx.doi.org/10.1007/s00701-009-0289-2DOI Listing
June 2009

Rituximab treatment in a patient with severe thyroid-associated ophthalmopathy: effects on orbital lymphocytic infiltrates.

Clin Immunol 2009 May 4;131(2):360-5. Epub 2009 Feb 4.

Department of Medical Sciences (Padiglione Granelli), University of Milan, Fondazione Ospedale Maggiore, IRCCS Via Sforza, Milan, Italy.

Rituximab (RTX) has been shown in previous work to improve thyroid-associated ophthalmopathy (TAO), but very little data is available on the effects of RTX in the target tissues. We studied the effects of RTX on peripheral lymphocytes and on the intra-orbital infiltrates in one patient with severe TAO who was treated with two cycles of therapy. Intra-orbital tissues derived at decompression from 3 patients with moderate-severe and 1 with severe TAO, treated with standard immunosuppression, were studied as controls. Peripheral blood lymphocytes were analyzed throughout the study period, while intra-orbital tissue lymphocytes at decompression. In the patient treated with RTX visual field and acuity improved in response to peripheral CD 20+ cell depletion, although there was a proportion of persisting CD 19+ cells. After RTX re-treatment the patient's optic nerve function improved only transiently. The number of CD 20+ cells was lower in orbital tissues (0-1%) than in the peripheral blood (3%). A greater percentage of CD 19+ was observed in the orbits compared to the periphery, most of which were CD 19+5+ (80%). By immunohistochemistry, orbital tissues from all control patients showed CD 20+ and CD 3+ cells, independently of the duration of TAO and of the treatment with either steroids or radiotherapy. This is the first report on the therapeutic effect of RTX in active, severe TAO associated to the depletion of intra-orbital CD 20+ lymphocytes. After RTX, CD 19+5+ lymphocytes were shown to be 2-3 times more prevalent in the orbital infiltrates, compared to CD 20+ cells. Persistence of autoreactive cells is believed to be related to TAO relapse.
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http://dx.doi.org/10.1016/j.clim.2008.12.005DOI Listing
May 2009

Invasive fungal sinusitis: an effective combined treatment in five haematological patients.

Leuk Lymphoma 2007 Aug;48(8):1577-86

U.O. Ematologia I, Centro Trapianti di Midollo, Università degli Studi di Milano & Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Mnagiagalli e Regina Elena, Milano, Italy.

Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.
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http://dx.doi.org/10.1080/10428190701457923DOI Listing
August 2007

Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study.

Eur J Endocrinol 2007 Jan;156(1):33-40

Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore IRCCS, Milan, Italy.

Introduction: Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO).

Methods: Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods.

Results: All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20+ depletion (P = NS). CAS values before RTX were 4.7 +/- 0.5 and decreased to 1.8 +/- 0.8 at the end of follow-up (P < 0.0001) and more significantly compared with IVGC (P < 0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P < 0.0001) and those with lid signs (ANOVA; P < 0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P < 0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients).

Conclusions: RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.
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http://dx.doi.org/10.1530/eje.1.02325DOI Listing
January 2007

Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression.

Eur J Endocrinol 2006 Apr;154(4):511-7

Institutes of Endocrine Sciences, University of Milan, Fondazione Ospedale Policlinico IRCCS, Italy.

One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. Hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score = 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed.
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http://dx.doi.org/10.1530/eje.1.02119DOI Listing
April 2006

Madelung's lipomatosis associated with head and neck malignant neoplasia: a study of 2 cases.

Otolaryngol Head Neck Surg 2002 Feb;126(2):191-2

Department of Scienze Otorinolaringologiche IRCCS Ospedale Maggiore Policlinico, Milano, Italy.

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http://dx.doi.org/10.1067/mhn.2002.122004DOI Listing
February 2002