Endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea is becoming a common procedure. The pur... more Endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea is becoming a common procedure. The purpose of this study was to perform a literature analysis centering cases of treatment failure and to review our 31 cases with a 1-year minimum follow-up. An extensive search of the literature was conducted, which focused on success rate, follow-up, diagnostic techniques, graft material used, failure rate, and comments on failures. A retrospective analysis of our 31 patients was carried out, and all cases were treated with the endoscopic approach with a 1-year minimum follow-up. From the literature analysis, the median success rate at the first endoscopic attempt is 90%. Our success rate was 87.1%. Failures were analyzed. A unique protocol for CSF leak diagnosis does not exist; we suggest our diagnostic algorithm. Graft material used depends on the authors' experience, and based on this review of cases to date, did not significantly influence the success rate. The analysis of cases of ...
The dependence of autofluorescence properties on the metabolic and functional engagement and on t... more The dependence of autofluorescence properties on the metabolic and functional engagement and on the transformation condition was studied on single cells. Normal Galliera rat fibroblasts at low subculture passage (cell strain), at high subculture passage (stabilized cell line), and transformed cell line derived from a rat sarcoma were used as a cell model. The study was performed by microspectrofluorometric and fluorescence imaging technique. The autofluorescence properties of cells were studied by excitation at two wavelengths, namely 366 nm and 436 nm, that are known to favor the emission of different fluorophores. Spectral shape analysis indicated that under excitation at 366 nm autofluorescence is ascribable mainly to coenzyme molecules, particularly to reduced pyridine nucleotides, while under excitation at 436 nm, flavin and lipopigment emission is favored. The energetic metabolic engagement of the different cell lines was analyzed in terms both of parameters related to anaerob...
Operative Techniques in Otolaryngology-Head and Neck Surgery, 2006
... Battaglia MD a , Davide Locatelli MD b , Giovanni Delù MD a , Federica Sberze MD a and Mauriz... more ... Battaglia MD a , Davide Locatelli MD b , Giovanni Delù MD a , Federica Sberze MD a and Maurizio Bignami MD a. a Department of Otorhinolaryngology, University of Insubria, Varese, Azienda Ospedaliera Universitaria Ospedale di Circolo e Fondazione Macchi, Varese, Italy. ...
Objective: Endoscopic repair of cerebrospinal fluid (CSF) leaks is a recognized technique. We con... more Objective: Endoscopic repair of cerebrospinal fluid (CSF) leaks is a recognized technique. We consider our experience and evaluate the outcomes in patients who underwent endoscopic repair of CSF leaks. Methods: A retrospective case note review of 135 patients who underwent anterior cranial repairs of CSF leaks between August 1995 and December 2004 at a tertiary referral center. We describe the technical details and outcomes of care by purely endoscopic procedures. Results: Thirteen patients had combined transcranial and endonasal repairs and 122 patients had their repairs using an endoscopic approach only. There were 64 males and 71 females with ages that ranged from 1 to 75 years (mean age 42 years, median age 44 years). The success rate for first attempt only was 93.4%. Eight of the 122 patients (6.6%) needed a second surgical repair. In one patient a bicoronal approach was necessary while in the other cases a revision endoscopic procedure was appropriate. The period of follow-up ranged from 2 months to 9 years (mean 5 years, median 39 months). Conclusions: Our experience confirmed that endoscopic surgery is an effective and safe method of treatment for most CSF leaks. A variety of different endoscopic techniques allowed CSF leaks to be repaired in almost every site of the anterior skull base with very few exceptions.
Skull base lesions are challenging to treat and may be managed using several approaches each with... more Skull base lesions are challenging to treat and may be managed using several approaches each with its own advantages and limitations. In selected cases a modular, combined, multiportal approach could overcome the limits of a single approach and respond well to the needs of the patient. We report a preclinical study on five cadaveric specimens and four preliminary clinical experiences with the combined multiportal transnasal transorbital endoscopic approach for the management of selected complex skull base pathologies. The technical feasibility and safety of this combined approach were evaluated in the pre-clinical study. The applicability in vivo of such an approach, together with early and late complications, specific morbidity and hospitalization time were analyzed in the preliminary clinical experiences herein presented. The transnasal endoscopic extended approach combined with the transorbital endoscopic approach offered greater visualization and tissue handling than a single approach alone could. The multiportal combined transorbital transnasal endoscopic approach was used effectively in vivo to resect one case of malignant Schwannoma arising from V2 and three cases of spheno-orbital meningioma without significant complications and with minimal morbidity for the patients. The multiportal combined transorbital transnasal endoscopic approach is a safe and effective procedure for the management of selected complex skull base lesions able to capitalize on the advantages and overcome the limitations of each single approach. This combined approach offers a multi-perspectival view of the spaces and, allows for a more synergized procedure, especially when dealing with multi-compartmental lesions.
International Journal of Pediatric Otorhinolaryngology, 2009
Skull base encephaloceles are difficult to diagnose and to treat. Traditionally, they are approac... more Skull base encephaloceles are difficult to diagnose and to treat. Traditionally, they are approached externally via craniotomic routes. Endoscopic management of skull base defects is the standard treatment in adults. Our aim is to evaluate the efficacy and safety of endoscopic endonasal repair of basal encephaloceles in the paediatric population. Retrospective evaluation of paediatric encephaloceles managed endoscopically at a tertiary referral centre. Eleven subjects fitted the criteria of the study. Mean age at surgery was 6.1+/-4.6 SD years, while mean follow-up was 46.5+/-28 SD months. Most of the defects were located in the anterior cranial fossa. All patients were managed successfully with no complications. Endonasal endoscopic management of congenital encephaloceles is feasible in paediatric patients. Meticulous pre-op neuroimaging is of paramount importance when dealing with such cases.
Data from several centers worldwide have demonstrated that transnasal endoscopic surgery performe... more Data from several centers worldwide have demonstrated that transnasal endoscopic surgery performed with or without a transcranial approach is capable of achieving radical resection of selected sinonasal malignancies. We report our experience with endoscopic management of sinonasal cancers, with emphasis on naso-ethmoidal malignancies encroaching on the anterior skull base. Major series reporting results concerning the endoscopic endonasal approach with or without craniectomy for treatment of sinonasal and anterior skull base cancers were reviewed. Preoperative work-up, indications and exclusion criteria, surgical techniques, postoperative management, and adjuvant therapy are reported. In the 2 largest series analyzed, the most common malignancies were adenocarcinoma (28%), olfactory neuroblastoma (14.5%), and squamous cell carcinoma (13.5%). The 5-year disease-specific survival rate ranged from 81.9%-87%, with no major differences in the mean follow-up time (34.1 months vs. 37 month...
Management of cerebrospinal fluid leaks or encephaloceles of Sternberg&am... more Management of cerebrospinal fluid leaks or encephaloceles of Sternberg's canal is challenging. Transnasal visualization of this area is difficult, especially when large pneumatization is present. External approaches to this region involve aggressive surgery and are often associated with significant morbidity. The aim of the study was to assess the real effectiveness of an endoscopic endonasal approach for treating cerebrospinal fluid leaks of the lateral recess of the sphenoid sinus. The authors conducted a retrospective evaluation. Clinical charts of patients with cerebrospinal fluid leaks and/or encephaloceles of Sternberg's canal treated at our institution were retrospectively reviewed. All these patients were managed with an endonasal endoscopic procedure. Fifteen patients (9 female and 6 male) were included in this study. Nine patients underwent a transethmoidal-pterygoidal-sphenoidal approach with a multilayer reconstructive technique. No cerebrospinal fluid leak recurrences were observed during follow up (mean follow up 37.6 +/- 21.7 standard deviation months) The transethmoidal-pterygoidal-sphenoidal approach provides a wide, safe, and direct route to the lateral recess of the sphenoid sinus. Multilayered reconstruction of the skull base defects must be considered the first option for this kind of lesion.
The influence both of overexpression of multidrug transporter proteins and of phenotype changes o... more The influence both of overexpression of multidrug transporter proteins and of phenotype changes occurring in cells developing spontaneous resistance on the accumulation of photosensitizer molecules was studied on two tumor-derived cell lines (B16, A2780) expressing the MDR-1 phenotype. Rhodamine 123, Rose Bengal acetate (a fluorogenic substrate that is restored to the native active molecule by specific enzyme activity inside cells) and Photofrin ® were considered. The two resistant variants accumulate Rhodamine 123 to a lesser extent than the respective wild types. Treatment with verapamil markedly enhances Rhodamine 123 accumulation in resistant cells, blocking the drug's extrusion. The amount of Rose Bengal is larger in resistant cells than in wild type cells. Verapamil does not affect drug accumulation, although it significantly impairs the efflux process. The results are explained by the enhancement of both membrane traffic and esterase activity resulting in intracellular Rose Bengal production that counterbalances the increased ability in the outward transport of resistant cells. Photofrin ® is accumulated to a lower degree in resistant than in wild type cells. Verapamil does not alter the drug accumulation, although the release process is somewhat affected. Different intracellular turnovers of Photofrin ® take place in the cell variants, and the release of the monomeric fluorescent fractions is greater in resistant than in wild type cells.
To describe surgical endoscopic experience in the repair of cerebrospinal fluid leaks treated by ... more To describe surgical endoscopic experience in the repair of cerebrospinal fluid leaks treated by transnasal approaches. Different surgical approaches and techniques in the repair of cranial base defects are reviewed in a series of 135 patients. Success rate at first attempt was 93.3%. Only 9 patients (6.7%) needed a second surgical repair, and in one patient, a coronal approach with frontal craniotomy was necessary. In the other eight cases, an endoscopic procedure was chosen. Two patients needed a third endonasal endoscopic surgical repair, with successful outcome. The target of endoscopic endonasal technique in the repair of cerebrospinal fluid leaks is to ensure a stable duraplasty with the least invasive approach avoiding craniotomy. A correct diagnosis surely allows the choice of the best treatment, surgical approach, graft, and technique. Our multidisciplinary approach to this pathology during these years has been essential to gain our challenging results.
The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two di... more The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow- up.
Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length surv... more Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length survival of motor neuron protein, the main product of the disease gene SMN1. Axonal SMN (a-SMN) is an alternatively spliced isoform of SMN1, generated by retention of intron 3. To study a-SMN function, we generated cellular clones for the expression of the protein in mouse motoneuron-like NSC34 cells. The model was instrumental in providing evidence that a-SMN decreases cell growth and plays an important role in the processes of axon growth and cellular motility. In our conditions, low levels of a-SMN expression were sufficient to trigger the observed biological effects, which were not modified by further increasing the amounts of the expressed protein. Differential transcriptome analysis led to the identification of novel a-SMN-regulated factors, i.e. the transcripts coding for the two chemokines, C-C motif ligands 2 and 7 (CCL2 and CCL7), as well as the neuronal and myotrophic factor, insulin-like growth factor-1 (IGF1). a-SMN-dependent induction of CCL2 and IGF1 mRNAs resulted in increased intracellular levels and secretion of the respective protein products. Induction of CCL2 contributes to the a-SMN effects, mediating part of the action on axon growth and random cell motility, as indicated by chemokine knockdown and re-addition studies. Our results shed new light on a-SMN function and the underlying molecular mechanisms. The data provide a rational framework to understand the role of a-SMN deficiency in the etiopathogenesis of spinal muscular atrophy.
The objective of the study is to present our multicentric experience on intraorbital lesions mana... more The objective of the study is to present our multicentric experience on intraorbital lesions managed by means of an endonasal endoscopic approach. The study design used was multi-institutional retrospective review. We collected data on 16 intraorbital medially-located lesions, all managed by means of an endonasal route, treated in four different skull base centers. We retrospectively reviewed the technical details, complications, histology, and general outcome. The endoscopic endonasal approach was effective in removing completely intraorbital extra-intraconal tumors in 8 cases, in performing biopsies for histological diagnosis in 6 intraorbital intraconal tumors, and in draining 1 extraconal abscess. No major complications were observed; in particular, there was no optic nerve damage. Minor, temporary complications (diplopia) were seen in 3 cases; only 2 patients experienced a permanent diplopia related to medial rectus muscle impairment, in 1 case associated with enophthalmos. Our preliminary multi-centric clinical experience suggests that medially located intraorbital lesions, and in particular the infero-medial ones, can be successfully and safely managed by such an approach. The well-known advantages of the endoscopic techniques, namely the lack of external scars, less bleeding, shorter hospital stay, and fewer complications, are confirmed.
Craniopharyngiomas are tumours of the central nervous system of dysontogenetic origin. They are m... more Craniopharyngiomas are tumours of the central nervous system of dysontogenetic origin. They are most commonly localized in the sellar region and appear to originate from an embryogenetic defect of the Rathke cleft. It is universally accepted that radical surgery should be performed as first surgery because surgery after relapses usually causes more difficulty due to tighter adhesion to surrounding structures. It is essential when relapses occur to evaluate which technique to use for treatment. For this reason, any new approach is welcomed in order to have as many alternatives as possible. In this paper we present the treatment, with a minimum follow-up of 4 years, of 5 paediatric patients affected by cystic craniopharyngiomas who went through first traditional surgery in other institutions and suffered relapses in various anatomical structures. One had a second successful endoscopic attempt at total gross resection. In 3 cases we endoscopically implanted a stent in the cystic cavity draining the cystic liquid out from the cystic cavity of the craniopharyngioma to the sphenoid sinus in order to form an accessory sinus. In 1 case a multiphase treatment has been undertaken. All patients treated using a transsphenoidal endoscopic approach are still living, without relapses and no postoperative complications. In particular, there where no episodes of vasospasm (a common complication reported in the literature when the "motor oil" comes into contact with the subarachnoid space) or infections. The patient treated using the multiphase approach recovered but suffered a recurrence 2 years later due to hypothalamic infiltration. Craniopharyngioma relapse needs different treatments. Many alternative approaches have been reported but none of them is the first choice alternative. We believe endoscopic stent placement in the cystic cavity is an alternative method for the treatment of cystic relapses.
Endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea is becoming a common procedure. The pur... more Endoscopic repair of cerebrospinal fluid (CSF) rhinorrhea is becoming a common procedure. The purpose of this study was to perform a literature analysis centering cases of treatment failure and to review our 31 cases with a 1-year minimum follow-up. An extensive search of the literature was conducted, which focused on success rate, follow-up, diagnostic techniques, graft material used, failure rate, and comments on failures. A retrospective analysis of our 31 patients was carried out, and all cases were treated with the endoscopic approach with a 1-year minimum follow-up. From the literature analysis, the median success rate at the first endoscopic attempt is 90%. Our success rate was 87.1%. Failures were analyzed. A unique protocol for CSF leak diagnosis does not exist; we suggest our diagnostic algorithm. Graft material used depends on the authors' experience, and based on this review of cases to date, did not significantly influence the success rate. The analysis of cases of ...
The dependence of autofluorescence properties on the metabolic and functional engagement and on t... more The dependence of autofluorescence properties on the metabolic and functional engagement and on the transformation condition was studied on single cells. Normal Galliera rat fibroblasts at low subculture passage (cell strain), at high subculture passage (stabilized cell line), and transformed cell line derived from a rat sarcoma were used as a cell model. The study was performed by microspectrofluorometric and fluorescence imaging technique. The autofluorescence properties of cells were studied by excitation at two wavelengths, namely 366 nm and 436 nm, that are known to favor the emission of different fluorophores. Spectral shape analysis indicated that under excitation at 366 nm autofluorescence is ascribable mainly to coenzyme molecules, particularly to reduced pyridine nucleotides, while under excitation at 436 nm, flavin and lipopigment emission is favored. The energetic metabolic engagement of the different cell lines was analyzed in terms both of parameters related to anaerob...
Operative Techniques in Otolaryngology-Head and Neck Surgery, 2006
... Battaglia MD a , Davide Locatelli MD b , Giovanni Delù MD a , Federica Sberze MD a and Mauriz... more ... Battaglia MD a , Davide Locatelli MD b , Giovanni Delù MD a , Federica Sberze MD a and Maurizio Bignami MD a. a Department of Otorhinolaryngology, University of Insubria, Varese, Azienda Ospedaliera Universitaria Ospedale di Circolo e Fondazione Macchi, Varese, Italy. ...
Objective: Endoscopic repair of cerebrospinal fluid (CSF) leaks is a recognized technique. We con... more Objective: Endoscopic repair of cerebrospinal fluid (CSF) leaks is a recognized technique. We consider our experience and evaluate the outcomes in patients who underwent endoscopic repair of CSF leaks. Methods: A retrospective case note review of 135 patients who underwent anterior cranial repairs of CSF leaks between August 1995 and December 2004 at a tertiary referral center. We describe the technical details and outcomes of care by purely endoscopic procedures. Results: Thirteen patients had combined transcranial and endonasal repairs and 122 patients had their repairs using an endoscopic approach only. There were 64 males and 71 females with ages that ranged from 1 to 75 years (mean age 42 years, median age 44 years). The success rate for first attempt only was 93.4%. Eight of the 122 patients (6.6%) needed a second surgical repair. In one patient a bicoronal approach was necessary while in the other cases a revision endoscopic procedure was appropriate. The period of follow-up ranged from 2 months to 9 years (mean 5 years, median 39 months). Conclusions: Our experience confirmed that endoscopic surgery is an effective and safe method of treatment for most CSF leaks. A variety of different endoscopic techniques allowed CSF leaks to be repaired in almost every site of the anterior skull base with very few exceptions.
Skull base lesions are challenging to treat and may be managed using several approaches each with... more Skull base lesions are challenging to treat and may be managed using several approaches each with its own advantages and limitations. In selected cases a modular, combined, multiportal approach could overcome the limits of a single approach and respond well to the needs of the patient. We report a preclinical study on five cadaveric specimens and four preliminary clinical experiences with the combined multiportal transnasal transorbital endoscopic approach for the management of selected complex skull base pathologies. The technical feasibility and safety of this combined approach were evaluated in the pre-clinical study. The applicability in vivo of such an approach, together with early and late complications, specific morbidity and hospitalization time were analyzed in the preliminary clinical experiences herein presented. The transnasal endoscopic extended approach combined with the transorbital endoscopic approach offered greater visualization and tissue handling than a single approach alone could. The multiportal combined transorbital transnasal endoscopic approach was used effectively in vivo to resect one case of malignant Schwannoma arising from V2 and three cases of spheno-orbital meningioma without significant complications and with minimal morbidity for the patients. The multiportal combined transorbital transnasal endoscopic approach is a safe and effective procedure for the management of selected complex skull base lesions able to capitalize on the advantages and overcome the limitations of each single approach. This combined approach offers a multi-perspectival view of the spaces and, allows for a more synergized procedure, especially when dealing with multi-compartmental lesions.
International Journal of Pediatric Otorhinolaryngology, 2009
Skull base encephaloceles are difficult to diagnose and to treat. Traditionally, they are approac... more Skull base encephaloceles are difficult to diagnose and to treat. Traditionally, they are approached externally via craniotomic routes. Endoscopic management of skull base defects is the standard treatment in adults. Our aim is to evaluate the efficacy and safety of endoscopic endonasal repair of basal encephaloceles in the paediatric population. Retrospective evaluation of paediatric encephaloceles managed endoscopically at a tertiary referral centre. Eleven subjects fitted the criteria of the study. Mean age at surgery was 6.1+/-4.6 SD years, while mean follow-up was 46.5+/-28 SD months. Most of the defects were located in the anterior cranial fossa. All patients were managed successfully with no complications. Endonasal endoscopic management of congenital encephaloceles is feasible in paediatric patients. Meticulous pre-op neuroimaging is of paramount importance when dealing with such cases.
Data from several centers worldwide have demonstrated that transnasal endoscopic surgery performe... more Data from several centers worldwide have demonstrated that transnasal endoscopic surgery performed with or without a transcranial approach is capable of achieving radical resection of selected sinonasal malignancies. We report our experience with endoscopic management of sinonasal cancers, with emphasis on naso-ethmoidal malignancies encroaching on the anterior skull base. Major series reporting results concerning the endoscopic endonasal approach with or without craniectomy for treatment of sinonasal and anterior skull base cancers were reviewed. Preoperative work-up, indications and exclusion criteria, surgical techniques, postoperative management, and adjuvant therapy are reported. In the 2 largest series analyzed, the most common malignancies were adenocarcinoma (28%), olfactory neuroblastoma (14.5%), and squamous cell carcinoma (13.5%). The 5-year disease-specific survival rate ranged from 81.9%-87%, with no major differences in the mean follow-up time (34.1 months vs. 37 month...
Management of cerebrospinal fluid leaks or encephaloceles of Sternberg&am... more Management of cerebrospinal fluid leaks or encephaloceles of Sternberg's canal is challenging. Transnasal visualization of this area is difficult, especially when large pneumatization is present. External approaches to this region involve aggressive surgery and are often associated with significant morbidity. The aim of the study was to assess the real effectiveness of an endoscopic endonasal approach for treating cerebrospinal fluid leaks of the lateral recess of the sphenoid sinus. The authors conducted a retrospective evaluation. Clinical charts of patients with cerebrospinal fluid leaks and/or encephaloceles of Sternberg's canal treated at our institution were retrospectively reviewed. All these patients were managed with an endonasal endoscopic procedure. Fifteen patients (9 female and 6 male) were included in this study. Nine patients underwent a transethmoidal-pterygoidal-sphenoidal approach with a multilayer reconstructive technique. No cerebrospinal fluid leak recurrences were observed during follow up (mean follow up 37.6 +/- 21.7 standard deviation months) The transethmoidal-pterygoidal-sphenoidal approach provides a wide, safe, and direct route to the lateral recess of the sphenoid sinus. Multilayered reconstruction of the skull base defects must be considered the first option for this kind of lesion.
The influence both of overexpression of multidrug transporter proteins and of phenotype changes o... more The influence both of overexpression of multidrug transporter proteins and of phenotype changes occurring in cells developing spontaneous resistance on the accumulation of photosensitizer molecules was studied on two tumor-derived cell lines (B16, A2780) expressing the MDR-1 phenotype. Rhodamine 123, Rose Bengal acetate (a fluorogenic substrate that is restored to the native active molecule by specific enzyme activity inside cells) and Photofrin ® were considered. The two resistant variants accumulate Rhodamine 123 to a lesser extent than the respective wild types. Treatment with verapamil markedly enhances Rhodamine 123 accumulation in resistant cells, blocking the drug's extrusion. The amount of Rose Bengal is larger in resistant cells than in wild type cells. Verapamil does not affect drug accumulation, although it significantly impairs the efflux process. The results are explained by the enhancement of both membrane traffic and esterase activity resulting in intracellular Rose Bengal production that counterbalances the increased ability in the outward transport of resistant cells. Photofrin ® is accumulated to a lower degree in resistant than in wild type cells. Verapamil does not alter the drug accumulation, although the release process is somewhat affected. Different intracellular turnovers of Photofrin ® take place in the cell variants, and the release of the monomeric fluorescent fractions is greater in resistant than in wild type cells.
To describe surgical endoscopic experience in the repair of cerebrospinal fluid leaks treated by ... more To describe surgical endoscopic experience in the repair of cerebrospinal fluid leaks treated by transnasal approaches. Different surgical approaches and techniques in the repair of cranial base defects are reviewed in a series of 135 patients. Success rate at first attempt was 93.3%. Only 9 patients (6.7%) needed a second surgical repair, and in one patient, a coronal approach with frontal craniotomy was necessary. In the other eight cases, an endoscopic procedure was chosen. Two patients needed a third endonasal endoscopic surgical repair, with successful outcome. The target of endoscopic endonasal technique in the repair of cerebrospinal fluid leaks is to ensure a stable duraplasty with the least invasive approach avoiding craniotomy. A correct diagnosis surely allows the choice of the best treatment, surgical approach, graft, and technique. Our multidisciplinary approach to this pathology during these years has been essential to gain our challenging results.
The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two di... more The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow- up.
Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length surv... more Spinal muscular atrophy is a fatal genetic disease of motoneurons due to loss of full-length survival of motor neuron protein, the main product of the disease gene SMN1. Axonal SMN (a-SMN) is an alternatively spliced isoform of SMN1, generated by retention of intron 3. To study a-SMN function, we generated cellular clones for the expression of the protein in mouse motoneuron-like NSC34 cells. The model was instrumental in providing evidence that a-SMN decreases cell growth and plays an important role in the processes of axon growth and cellular motility. In our conditions, low levels of a-SMN expression were sufficient to trigger the observed biological effects, which were not modified by further increasing the amounts of the expressed protein. Differential transcriptome analysis led to the identification of novel a-SMN-regulated factors, i.e. the transcripts coding for the two chemokines, C-C motif ligands 2 and 7 (CCL2 and CCL7), as well as the neuronal and myotrophic factor, insulin-like growth factor-1 (IGF1). a-SMN-dependent induction of CCL2 and IGF1 mRNAs resulted in increased intracellular levels and secretion of the respective protein products. Induction of CCL2 contributes to the a-SMN effects, mediating part of the action on axon growth and random cell motility, as indicated by chemokine knockdown and re-addition studies. Our results shed new light on a-SMN function and the underlying molecular mechanisms. The data provide a rational framework to understand the role of a-SMN deficiency in the etiopathogenesis of spinal muscular atrophy.
The objective of the study is to present our multicentric experience on intraorbital lesions mana... more The objective of the study is to present our multicentric experience on intraorbital lesions managed by means of an endonasal endoscopic approach. The study design used was multi-institutional retrospective review. We collected data on 16 intraorbital medially-located lesions, all managed by means of an endonasal route, treated in four different skull base centers. We retrospectively reviewed the technical details, complications, histology, and general outcome. The endoscopic endonasal approach was effective in removing completely intraorbital extra-intraconal tumors in 8 cases, in performing biopsies for histological diagnosis in 6 intraorbital intraconal tumors, and in draining 1 extraconal abscess. No major complications were observed; in particular, there was no optic nerve damage. Minor, temporary complications (diplopia) were seen in 3 cases; only 2 patients experienced a permanent diplopia related to medial rectus muscle impairment, in 1 case associated with enophthalmos. Our preliminary multi-centric clinical experience suggests that medially located intraorbital lesions, and in particular the infero-medial ones, can be successfully and safely managed by such an approach. The well-known advantages of the endoscopic techniques, namely the lack of external scars, less bleeding, shorter hospital stay, and fewer complications, are confirmed.
Craniopharyngiomas are tumours of the central nervous system of dysontogenetic origin. They are m... more Craniopharyngiomas are tumours of the central nervous system of dysontogenetic origin. They are most commonly localized in the sellar region and appear to originate from an embryogenetic defect of the Rathke cleft. It is universally accepted that radical surgery should be performed as first surgery because surgery after relapses usually causes more difficulty due to tighter adhesion to surrounding structures. It is essential when relapses occur to evaluate which technique to use for treatment. For this reason, any new approach is welcomed in order to have as many alternatives as possible. In this paper we present the treatment, with a minimum follow-up of 4 years, of 5 paediatric patients affected by cystic craniopharyngiomas who went through first traditional surgery in other institutions and suffered relapses in various anatomical structures. One had a second successful endoscopic attempt at total gross resection. In 3 cases we endoscopically implanted a stent in the cystic cavity draining the cystic liquid out from the cystic cavity of the craniopharyngioma to the sphenoid sinus in order to form an accessory sinus. In 1 case a multiphase treatment has been undertaken. All patients treated using a transsphenoidal endoscopic approach are still living, without relapses and no postoperative complications. In particular, there where no episodes of vasospasm (a common complication reported in the literature when the "motor oil" comes into contact with the subarachnoid space) or infections. The patient treated using the multiphase approach recovered but suffered a recurrence 2 years later due to hypothalamic infiltration. Craniopharyngioma relapse needs different treatments. Many alternative approaches have been reported but none of them is the first choice alternative. We believe endoscopic stent placement in the cystic cavity is an alternative method for the treatment of cystic relapses.
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Papers by D. Locatelli