Cross-over septal flap technique for choanal atresia surgery in two centres: how I do it.

BACKGROUND: Choanal atresia is a congenital obstruction of the posterior nasal aperture. Endoscopic endonasal surgery has led to successful choanal atresia repair. This paper describes our surgical technique using septal mucosal flaps without the need for stenting. METHODS: This study comprised a multicentre retrospective review of patient notes. A cross-over septal technique is described, whereby bilateral vertical mucosal incisions are made at the posterior third of the septum, and the atretic plate and posterior vomer are removed. One flap is pedicled superiorly and rotated over the bare skull base and sphenoid bone; the contralateral flap is pedicled inferiorly to cover the exposed vomer remnant and hard palate. RESULTS: There were 12 patients from 2013 to 2020, aged 0.07-50 years, with a male to female ratio of 1:5. Ten patients had unilateral and two had bilateral choanal atresia. Nine patients had bony choanal atresia, with the remainder mixed. CONCLUSION: The cross-over technique for choanal atresia has low morbidity and 100 per cent success in our series. The use of mucoperiosteal flaps to cover exposed bone and minimal instrumentation to the lateral nasal wall reduce post-operative stenosis.

Frontal sinus ablation (Riedel-Mosher’s procedure): indications and role in the endonasal endoscopic era.

BACKGROUND: The aim of this article is to describe the Riedel-Mosher’s surgical technique and identify its current role in the endoscopic endonasal era based on the experience of a tertiary care medical centre. It also provides a brief excursus on materials available for frontal reconstruction. METHODS: A retrospective review of patients submitted to Riedel-Mosher’s procedure from 2005 to 2018 at a single tertiary care centre was carried out. Details of the surgical technique along with data on frontal reconstruction timing and materials used were collected. RESULTS: A total of 21 patients (16 males and 5 females) underwent the Riedel-Mosher’s procedure. The age of the patients ranged from 15 to 84 years. The underlying pathology was represented mainly by chronic osteitis of the frontal bone (17 cases), followed by benign tumours (3 cases) and malignancy (1 case). Perioperative complications occurred in 3 patients. Cranioplasty was carried out only on 16 cases and delayed by an average time of 10 months. Materials for reconstruction included titanium, ceramic, plastic and free flap . CONCLUSIONS: Nowadays, Riedel-Mosher’s procedure is still indicated in selected cases of benign and malignant pathologies of the frontal sinus and/or frontal bone. Surgical expertise is key to approach the frontal sinus safely. Its reconstruction requires proper planning and a wide variety of materials to perform it is now available.

From modeling to remodeling of upper airways: Centrality of hyaluronan (hyaluronic acid).

After traumatic events (accidental or surgical), the respiratory tract activates specific and prolix repairing mechanisms which tend to claw back the primitive differentiated state. The attempt of reactivation of the normal tissue functions is called 'remodeling' and its aim is to reinstate the modeling mechanisms that existed before the damaging event or the pathology's establishment. Endoscopic sinus surgery represents the gold standard treatment for inflammatory, malformative, benign, and, in selected cases, malignant diseases. The surgical technique is commonly described as minimally invasive as the nostrils are used as an access route and therefore does not leave any external scars. Currently, the surgical procedures, even though minimally invasive regarding the way in, are in fact widely destructive towards the surgical target. The healing process and re-epithelialization will depend on the amount of bony tissue that has been exposed and it will be important to stratify the different surgical typologies in order to foresee the increasing difficulty of mucosal healing process. As far as upper inflammatory diseases are concerned, recent studies demonstrated how intranasal hyaluronic acid can positively regulate mucosal glands secretion and modulate inflammatory response, being a useful tool for the improvement of remodeling after endoscopic sinus surgery. Acid has shown to be able to regulate mucosal glands secretion and modulate the inflammatory response.

Endoscopic endonasal management of non-functioning pituitary adenomas with cavernous sinus invasion: a 10- year experience.

BACKGROUND: The management of Non-Functioning Pituitary Adenoma (NFPA) invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy. METHODS: We undertook a retrospective review of 56 cases of NFPA with CS invasion treated through an endoscopic endonasal approach (EEA) between 2000 and 2010. The Knosp classification was adopted to describe CS involvement using information from preoperative MRI and intraoperative findings. Extent of resection and surgical outcomes were evaluated on the basis of postoperative contrast-enhanced MRI. Endocrinological improvement and visual outcomes were assessed according to the most recent consensus criteria. RESULTS: EEA was performed using direct para-septal, trans-ethmoidal-sphenoidal or trans-ethmoidal-pterygoidal-sphenoidal approach. Visual outcomes improved in 30 (81%) patients. Normalization or at least improvement of previous hypopituitarism was obtained in 55% of cases. A gross total resection was achieved in 30.3% of cases. The recurrence-free survival was 87.5%, with a mean follow-up of 61 months (range, 36-166 months). No major intraoperative or postoperative complications occurred. DISCUSSION: EEA is a minimally-invasive, safe and effective procedure for the management of NFPA invading the CS. The extent of CS involvement was the main factor limiting the degree of tumor resection. The EEA was able to resolve the mass effect, preserving or restoring visual function, and obtaining adequate long-term tumor control.

Post-traumatic optic neuropathy: our surgical and medical protocol.

Post-traumatic optic neuropathy (TON) is a rare, but very much feared event. It is a traumatic injury of the optic nerve at any level along its course (often inside the optic canal), with partial or total loss of visual acuity, temporarily or permanently. Until now, an univocal treatment strategy does not exist. The clinical records of 26 patients, treated from 2002 to 2013, were reviewed. The most frequent cause of injury was road traffic accident (63%), followed by iatrogenic damage, work injuries, sport or home accidents. All patients underwent pre-operative ophthalmological evaluation, neuro-imaging (angio-CT or angio-MRI scans) and systemic corticosteroid therapy. All patients required a surgical treatment, due to poor response to medical therapy; it consisted of an endonasal endoscopic decompression of the intracanalicular segment of the optic nerve, performed by removing the bony wall of the optical canal and releasing the perineural sheath. Improvement of visual acuity was reached in 65% of cases. No minor or major complication occurred intra- or post-operative, with a maximum follow-up time of 41 months. An improvement in visual acuity was achieved, although very limited in some cases, when surgery was performed as close as possible to the traumatic event. In the literature, there is no evidence-based data evaluating both of the two main treatment options (medical therapy versus surgical decompression), to state which is the gold standard in the treatment for TON. We discuss the pro and cons of our protocol: medical endovenous steroid treatment, within 8 h of injury, and endoscopic surgical decompression within 12-24 since the beginning of medical therapy, represent the best solution in terms of risk-benefit ratio for the patients.

The WRN and MUS81 proteins limit cell death and genome instability following oncogene activation.

Oncogene-induced replication stress is recognized as the primary cause of accumulation of DNA damage and genome instability in precancerous cells. Although the molecular mechanisms responding to such type of replication perturbation are not fully characterized, it has been speculated that their dysfunction may enhance genome instability and accelerate tumor progression. Here, we show that the WRN protein, a member of the human RecQ helicases, is necessary to sustain replication fork progression in response to oncogene-induced replication stress. Loss of WRN affects cell cycle progression and results in enhanced accumulation of double-strand breaks and instability at common fragile sites in cells experiencing oncogene-induced replication stress. Moreover, we demonstrate that double-strand breaks, observed upon oncogene over-expression, depend on the MUS81 endonuclease, which represents a parallel pathway collaborating with WRN to prevent cell death. Overall, our findings give insights into the mechanisms protecting replication forks in cells experiencing oncogene-induced replication stress, and identify factors that, when mutated or dysfunctional, may enhance genome instability in precancerous cells. In addition, because concomitant depletion of WRN and MUS81 causes synthetic sickness in cells growing under oncogene-induced replication stress, our results support the possibility of targeting cancer cells with an impaired replication fork recovery pathway by a specific inactivation of the other parallel pathway.

Loss of MUTYH function in human cells leads to accumulation of oxidative damage and genetic instability.

The DNA glycosylase MUTYH (mutY homolog (Escherichia coli)) counteracts the mutagenic effects of 8-oxo-7,8-dihydroguanine (8-oxodG) by removing adenine (A) misincorporated opposite the oxidized purine. Biallelic germline mutations in MUTYH cause the autosomal recessive MUTYH-associated adenomatous polyposis (MAP). Here we designed new tools to investigate the biochemical defects and biological consequences associated with different MUTYH mutations in human cells. To identify phenotype(s) associated with MUTYH mutations, lymphoblastoid cell lines (LCLs) were derived from seven MAP patients harboring missense as well as truncating mutations in MUTYH. These included homozygous p.Arg245His, p.Gly264TrpfsX7 or compound heterozygous variants (p.Gly396Asp/Arg245Cys, p.Gly396Asp/Tyr179Cys, p.Gly396Asp/Glu410GlyfsX43, p.Gly264TrpfsX7/Ala385ProfsX23 and p.Gly264TrpfsX7/Glu480del). DNA glycosylase assays of MAP LCL extracts confirmed that all these variants were defective in removing A from an 8-oxoG:A DNA substrate, but retained wild-type OGG1 activity. As a consequence of this defect, MAP LCLs accumulated DNA 8-oxodG in their genome and exhibited a fourfold increase in spontaneous mutagenesis at the PIG-A gene compared with LCLs from healthy donors. They were also hypermutable by KBrO3--a source of DNA 8-oxodG--indicating that the relatively modest spontaneous mutator phenotype associated with MUTYH loss can be significantly enhanced by conditions of oxidative stress. These observations identify accumulation of DNA 8-oxodG and a mutator phenotype as likely contributors to the pathogenesis of MUTYH variants.

Endoscopic transnasal resection of anterior skull base malignancy with a novel 3D endoscope and neuronavigation.

The surgical treatment of sinonasal malignancies is in continuous evolution. In selected patients, endoscopic resection has become a sound alternative to traditional external approaches. Further improvements are necessary to enhance the possibilities of endoscopic transnasal resection of sinonasal malignancies. We present a case of intestinal-type adenocarcinoma of the left nasal fossa eroding the skull base that affected a 56-year-old male. The patient was surgically-treated by means of a four-hand binarial endoscopic transnasal resection using a 3D endoscopic system and neuronavigation. Surgery was completed in 5 hours without significant complications. Surgeons were able to recognize and manage anatomical structures, and to control bleeding easily thanks to the bimanual technique and 3D visualization. The new 3D scopes and the bimanual technique under the guidance of a navigation system represent an interesting solution that can overcome the traditional limits of the traditional set up currently used.

The RAD9-RAD1-HUS1 (9.1.1) complex interacts with WRN and is crucial to regulate its response to replication fork stalling.

The WRN protein belongs to the RecQ family of DNA helicases and is implicated in replication fork restart, but how its function is regulated remains unknown. We show that WRN interacts with the 9.1.1 complex, one of the central factors of the replication checkpoint. This interaction is mediated by the binding of the RAD1 subunit to the N-terminal region of WRN and is instrumental for WRN relocalization in nuclear foci and its phosphorylation in response to replication arrest. We also find that ATR-dependent WRN phosphorylation depends on TopBP1, which is recruited by the 9.1.1 complex in response to replication arrest. Finally, we provide evidence for a cooperation between WRN and 9.1.1 complex in preventing accumulation of DNA breakage and maintaining genome integrity at naturally occurring replication fork stalling sites. Taken together, our data unveil a novel functional interplay between WRN helicase and the replication checkpoint, contributing to shed light into the molecular mechanism underlying the response to replication fork arrest.

Subdural haematoma after endoscopic skull base surgery: case report and lesson learned.

We report a case of a left fronto-temporo-parietal subdural haematoma that emerged as a complication of an endonasal endoscopic resection of a sinonasal adenocarcinoma of the left ethmoidal region. During the first surgical intervention, following oncological principles, the dura mater above the ethmoidal plate was removed and a skull base plasty was performed. In the post-operative phase a massive cerebrospinal fluid leak was observed and a revision duraplasty was performed the following day. Subsequently the patient was discharged on day 8 with no signs of CSF leakage. At the three month follow-up MR examination a subdural haematoma was observed and then treated by the neurosurgeon in a standard fashion. The collection was quite asymptomatic and discovered accidentally. We strongly advise the role of early post-op neuroimaging in every patient undergoing skull base procedures. We maintain that a massive CSF leak, that causes a significant reduction of intracranial pressure, should be managed as a surgical emergency, in order to reduce the risk of subdural haematoma.

Transnasal approach to the medial intraconal space: anatomic study and clinical considerations.

BACKGROUND: The aim of this study was to illustrate the anatomy of the medial compartment of the orbit by comparing the endoscopic transnasal perspective with the external ones. METHODS: 8 orbits from 5 double-injected heads were carefully dissected. An endoscopic anterior transconjunctival dissection was performed in one orbit while an endoscopic transnasal intraconal dissection was conducted in 3 orbits. External dissections (from medial, superior and anterior perspective) were also performed. RESULTS: The role of the medial rectus muscle is emphasised. It represents the first important landmark encountered, covering all the other structures during transnasal approaches. By displacing it, the medial intraconal space with its contents becomes visible: the ophthalmic artery and related branches, the superior ophthalmic vein, the nasociliary nerve and, in the deepest part of the medial compartment, the optic nerve. CONCLUSION: The medial compartment of the orbit can be addressed transnasally. By displacing the medial rectus muscle, it is possible to gain adequate space for the instruments and to control all of the medial compartment, including the medial aspect of the optic nerve.

Endoscopic, endonasal management of sinonasal haemangiopericytoma: 12-year experience.

AIM: To report our experience with endoscopic, endonasal management of sinonasal haemangiopericytoma. MATERIALS AND METHODS: Retrospective review of the medical records of 10 patients undergoing endoscopic, endonasal surgery for sinonasal haemangiopericytoma of the nose and paranasal sinuses, between 1997 and 2008. RESULTS: Five men and five women were included. Their mean age at surgery was 59 years. All patients underwent endoscopic, endonasal resection of their tumour. Major post-operative complications were encountered in only one patient (stroke). Local recurrence was diagnosed in only one patient (10 per cent), who subsequently underwent a combined resection (endoscopic and external) with orbital exenteration. CONCLUSIONS: Sinonasal haemangiopericytomas are rare tumours that are usually benign. The mainstay of treatment is wide surgical excision with free resection margins. Nowadays, the great majority of patients can be treated using a purely endoscopic, endonasal approach.

Nasopharyngeal endoscopic resection in the management of selected malignancies: ten-year experience.

OBJECTIVE: To evaluate the feasibility of endoscopic surgery in the management of selected nasopharyngeal cancers. Three different types of nasopharyngeal endoscopic resections (NER) are described. METHOD OF STUDY: From January 1997 to October 2008, 17 consecutive patients (mean age: 50 years) with previously untreated (5) or recurrent nasopharyngeal tumours (12) were treated with curative intent by pure endoscopic resection. The extent of surgical resection was classified as follows: type I NER: resection limited to the postero-superior nasopharyngeal wall; type 2 NER: resection superiorly extended to the sphenoid sinus; type 3 NER: resection with lateral extension including the cartilaginous portion of the Eustachian tube and parapharyngeal space. RESULTS: Type 1 NER was performed in 4 cases, type 2 in 6, and type 3 in 7. No intra- or post-operative complications were observed. Mean hospitalization time was 4 days (range: 1-7). Follow-up ranged from 10 to 138 months (mean: 41.2±38). At the time of writing, 12 (71/%) patients were free of disease, 3 (17%) alive with disease, and 2 (12%) dead of disease. CONCLUSIONS: NER is a feasible surgical technique that can be tailored in relation to tumour extension. Larger series and longer follow-up are needed to further validate the long-term results.

Endoscopic transnasal anatomy of the infratemporal fossa and upper parapharyngeal regions: correlations with traditional perspectives and surgical implications.

BACKGROUND: The aim of this study was to illustrate the endoscopic surgical anatomy of the infratemporal fossa (ITF) and upper parapharyngeal space and to provide useful landmarks by comparing transnasal perspectives with external ones. MATERIALS AND METHODS: 6 fresh double injected heads were dissected. External lateral dissection was performed through a pre-auricular skin incision while external anterior dissection started with a modified Weber-Ferguson incision. External medial to lateral dissection was performed starting from the rhinopharyngeal and pterygoid regions, after cutting the specimen in 2 halves passing through the nose. Endoscopic dissection was performed through an endonasal approach (0° and 45° scopes). RESULTS: Among all the structures identified during the dissection, the most useful landmark when dissecting the ITF in a lateral to medial direction is the lateral pterygoid muscle. In anterior approaches (mostly endoscopic) the role of the lateral pterygoid muscle is less important and the Eustachian tube (ET) represents the most important landmark to point out the upper portion of the parapharyngeal internal carotid artery (ICA). The role of the ET, in lateral dissection is, on the contrary, by far less important given the fact that it is very deep in the surgical field and that the ICA is encountered earlier during surgical approaches. Another crucial landmark during anterior endoscopic surgery is the vidian nerve because it points to the anterior genu of the internal carotid artery. CONCLUSION: The complex 3-dimensionality of the ITF and the upper parapharyngeal space needs a sound knowledge of the surgical anatomy. The role of the same landmarks changed in different approaches. The ability to orientate oneself in this complex area is related to an accurate knowledge of its anatomy through comparison of endoscopic and external perspectives.

A rare case of oncocytic Schneiderian papilloma with intradural and intraorbital extension with notes of operative techniques.

Epithelial cells of cylindrical cell papilloma are oncocytes, which arise from the sinonasal respiratory epithelium, hence the term Oncocytic Schneiderian papilloma.This is a rare and benign neoplasm of the nose and paranasal sinuses and it should be considered in the work-up of all unilateral nasal polypoid lesions. Clinically behaviour is comparable to inverted papillomas for local recurrence and malignancy coexistence. We report a case arisen from the nasoethmoidal space that extended to the anterior skull base through a bone dehiscence with intradural invasion and orbital space involvement. Surgical therapy is the treatment of choice, the endonasal endoscopic approach can be used in most of the cases and this surgical technique is safe and suitable also in presence of an extra nasal extension. We describe our experience for management of this kind of lesions and some notes on our operative technique.

Endoscopic endonasal management of petroclival cerebrospinal fluid leaks: anatomical study and preliminary clinical experience.

BACKGROUND: Endonasal management of most anterior cranial fossa cerebrospinal fluid leaks is a well established procedure, and even some middle cranial fossa cerebrospinal fluid leaks can be managed safely endonasally. Endonasal endoscopic management of leakages of the posterior cranial fossa represents an unique challenge. OBJECTIVE: The aim of this study was to assess the feasibility of an endoscopic endonasal approach for treating well-selected cerebrospinal fluid leaks of the petroclival region. METHODS: Clinical charts of patients with leakages of the petroclival region treated at our institution were retrospectively reviewed. Careful dissection of the petroclival region was performed, both endonasally and externally, in three fresh injected heads. RESULTS: Two patients presented a leakage of the petroclival region. Both the patients presented multiple skull base defects. The two patients underwent a supratubaric trans-spheno-petroclival approach; in one of these, it was performed in combination with a middle cranial fossa approach. Multilayer reconstruction was performed in both patients. No cerebrospinal fluid leak recurrences were observed during follow-up (17 and 19 months, respectively). CONCLUSIONS: Endonasal endoscopic management of well-selected petroclival cerebrospinal fluid leaks is feasible.

Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: Focus on DNA repair genes.

Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.

Drop attacks and vertical vertigo after transtympanic gentamicin: diagnosis and management.

Drop attacks represent a significant problem during the natural course of Meniere's disease. They are characterized by a sudden fall to the ground without loss of consciousness. Diagnosis is clinical and based on the typical description of the patient. Involvement of vertical canal is possible during Meniere's disease and also after gentamicin application. Treatment of drop attacks is still a matter of discussion; most cases have a benign course with spontaneous remission and no treatment is necessary. In severe cases, aggressive treatment (surgical or pharmacological) is necessary. A case of drop attack associated with vertical vertigo is presented. Vestibular tests were performed in order to assess the involvement of inner ear. Caloric test and ice water test reveal no response. Vestibular Evoked Myogenic Potentials are present even after high doses of gentamicin. Drop attacks and vertical vertigo can occur after transtympanic gentamicin and can be well managed with high doses of local gentamicin.

[Rational treatment of nasal polyposis]. / Trattamento ragionato della poliposi nasale.

Despite the therapeutical advances of the last decade, nasal polyposis represents still a problem for rhinology, practitioners. A number of hypotheses have been formulated about its etiopathogenesis, but no one is confirmed, so that nowadays therapy continues to be only symptomatic and does not cure definitively the underlying pathology. Recurrences are frequent and discourage both the practitioner and the patient. Purpose of this paper is to illustrate Authors' therapeutical rationale aimed to reestablish nasal flow, reduce rhinorrhea, improve olfaction, decrease rhinosinusinusal infection rate and maintain as long as possible such a symptomatic improvement. These targets are best achieved by a combination of medical and surgical treatments in order to optimize the results and reduce the side-effects of both the therapeutical options. Moreover the treatment should be tailored on each patient and follow up should be careful and performed at regular interval. Authors reviewed the clinical records of patients who underwent surgery for nasal polyposis between 2002 and 2004 at Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy, with a minimum follow-up of 12 months. All patients underwent the complete set of diagnostic work-up. The choice between surgical or medical options was based on both the kind of the polyposis and the staging of the pathology. The therapy was as more "personalized" as possible, but a homogeneity of treatment was maintained. The results show that a correct "staging" of the patient allows an appropriate therapy and reduces recurrence rate. In conclusion, authors report their experience and propose a scheme of diagnostic work-up in order to define grading/staging of the pathology and establish a "tailored" therapeutic protocol aimed to control a pathology which is rarely definitively treated.