Intraoperative intraorbital bleeding: considerations from a collaborative and retrospective Italian study with a management algorithm proposal.

BACKGROUND: Intraoperative intraorbital bleeding is a rare but potentially catastrophic event that can lead even to blindness, if not treated promptly. The goal of surgery is to quickly reduce intraorbital pressure thus restoring normal visual function. Aim of our work is to propose a practical algorithm helping the surgeon in the setting of this critical event. METHODOLOGY: An Italian multi-institutional retrospective study was conducted. All the cases of intraoperative intra-orbital bleeding requiring at least some form of surgical management were analyzed. Cases simply managed conservatively were excluded from this analysis. RESULTS: Sixteen cases were collected. Of these, 12 were initially treated with a medial wall orbital decompression, while 4 were treated via a lateral canthotomy and inferior cantholysis (LCC). Ten patients recovered completely. Four patients presented post-op sequelae (diplopia, enophthalmous and/or eyelid malpositioning). Two major negative outcomes (blindness) were observed. CONCLUSIONS: Timely surgical intervention is critical. According to the setting in which the bleeding occurs, different options are available. LCC is probably the most rapid maneuver that can be done to reduce intraorbital pressure. Anyway, if the patient is still in the OR and a complete ethmoidectomy yet done we advise, as first step, to perform a medial orbital wall decompression.

Endoscopic management of frontal sinus diseases after frontal craniotomy: a case series and review of the literature.

PURPOSE: To evaluate frontal sinus complications developed after previous external craniotomies requiring frontal sinus reconstruction and their treatment with an endoscopic approach. METHODS: We retrospectively evaluated 22 patients who referred to Sant'Orsola-Malpighi University Hospital and Bellaria Hospital (Bologna, Italy) between 2005 and 2017. All patients presented with frontal sinus disease after frontal craniotomy with sinus reconstruction performed to treat various pathological conditions. We reported our experience in the endoscopic management of such complications and we reviewed the current literature concerning the endoscopic treatment of these conditions. RESULTS: In total, 14 frontal mucoceles, 4 cases of chronic frontal sinusitis, 2 mucopyoceles and 2 fungus ball of the frontal sinus were identified. Endoscopic surgical treatment included 7 DRAF IIa, 1 DRAF IIb, 11 DRAF III and 3 DRAF IIc (modified DRAF III) approaches. The success rate of the surgical procedure was 86% (19/22 patients). Recurrence of the initial pathology occurred in three patients (14%) requiring a conversion of previous frontal sinusotomy into a DRAF III sinusotomy. CONCLUSION: Frontal sinusopathy can be a long-term complication following craniotomies and may lead to potentially severe pathological conditions, such as mucoceles and frontal sinus inflammation. Its management is still debated and requires recovery of the patency of nasal-frontal route. Our study confirms that the endoscopic endonasal approach may offer a valid solution with low morbidity avoiding re-opening of the craniotomic access. For selected cases, endoscopic approach could also be performed simultaneously to craniotomy as a combined surgery to reduce the risk of short- and long-term complications. Long-term follow-up is mandatory in patients with a history of opened and reconstructed frontal sinus and should include imaging and endoscopic outpatient evaluation.

Results and predictors of outcome of endoscopic endonasal surgery in Cushing's disease: 20-year experience of an Italian referral Pituitary Center.

PURPOSE: To assess outcomes and predictors of early and long-term remission in patients with Cushing's disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA). METHODS: This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected. RESULTS: 151 patients (107 F) were included; 88.7% were naïve for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12-237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size < 1 cm (p = 0.045) increased the chance of disease remission; cavernous sinus invasion was a negative predictor of outcome (p = 0.002). Twenty-seven patients developed diabetes insipidus and 18 hypopituitarism. Surgery repetition increased the risk of hypopituitarism (p = 0.03), but not of other complications, which included epistaxis (N = 2), cerebrospinal fluid leakage (1), pneumonia (3), myocardial infarction (1), and pulmonary embolisms (2). CONCLUSIONS: Selective adenomectomy via EEA performed by experienced surgeons, supported by a multidisciplinary dedicated team, allows long-term remission in the vast majority of CD patients with low complication rate.

Sialendoscopy for salivary stones: principles, technical skills and therapeutic experience.

Obstructive sialadenitis is the most common non-neoplastic disease of the salivary glands, and sialendoscopy is increasingly used in both diagnosis and treatment, associated in selected cases with endoscopic laser lithotripsy. Sialendoscopy is also used for combined minimally invasive external and endoscopic approaches in patients with larger and proximal stones that would require excessively long laser procedures. The present paper reports on the technical experience from the Ear, Nose and Throat Unit of the Sant'Orsola-Malpighi Hospital of Bologna, and from the Department of Otorhinolaryngology of the University Hospital of Cagliari, Italy, including the retrospective analysis of the endoscopic and endoscopic assisted procedures performed on 48 patients (26 females and 22 males; median age 45.3; range 8-83 years) treated for chronic obstructive sialadenitis at the University Hospital of Cagliari from November 2010 to April 2016. The results from the Sant'Orsola-Malpighi Hospital of Bologna have been previously published. The technical aspects of sialendoscopy are carefully described. The retrospective analysis of the University Hospital of Cagliari shows that the disease was unilateral in 40 patients and bilateral in 8; a total of 56 major salivary glands were treated (22 submandibular glands and 34 parotids). Five patients underwent bilateral sialendoscopy for juvenile recurrent parotitis. 10 patients were treated for non-lithiasic obstructive disease. In 33 patients (68.75%) the obstruction was caused by salivary stones (bilateral parotid lithiasis in 1 case). Only 8 patients needed a sialectomy (5 submandibular glands and 3 parotids). The conservative approach to obstructive sialadenitis is feasible and can be performed either purely endoscopically or in a combined modality, with a high percentage of success. The procedure must be performed with dedicated instrumentation by a skilled surgeon after proper training since minor to major complications can be encountered. Sialectomy should be the "extrema ratio" after failure of a conservative approach.

Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review.

Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7-11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.

Outcomes of interventional sialendoscopy for obstructive salivary gland disorders: an Italian multicentre study.

Interventional sialendoscopy has become the predominant therapeutic procedure for the management of obstructive salivary disorders, but only a few multicentre studies of large series of patients with a long-term follow-up have been published. This Italian multicentre study involved 1152 patients (553 females; mean age 50 years) who, after at least a clinical and ultrasonographic evaluation, underwent a total of 1342 diagnostic and interventional sialendoscopies, 44.6% of which involved the parotid gland. 12% (n = 138) of patients underwent multiple treatments. The procedure was successful in 1309 cases. In 33 cases (2.4%) the procedure could not be concluded mainly because of complete duct stenosis (21 cases). Salivary stones were the main cause of obstruction (55%), followed by ductal stenosis and anomalies (16%), mucous plugs (14.5%) and sialodochitis (4.7%). Complete therapeutic success was obtained in 92.5% of patients after one or more procedures, and was ineffective in < 8%. Untoward effects (peri and postoperative complications) were observed in 5.4% of cases. Sialendoscopy proved to be an effective, valid and safe procedure in the diagnostic and therapeutic management of non-neoplastic obstructive salivary gland diseases.

Sialoendoscopy: state of the art, challenges and further perspectives. Round Table, 101(st) SIO National Congress, Catania 2014.

This draft of the Official Round Table held during the 101(st) SIO National Congress is an updated review on sialoendoscopy, a technique used for diagnosis and treatment of obstructive pathologies of salivary glands in a minimally invasive fashion. This review treats many aspects of salivary gland endoscopy, starting from anatomy to deal with the more advanced surgical techniques and analyses the main decisional algorithms proposed in the literature. In addition, particular attention was directed to the current limitations of this technique and to the potential developments that sialoendoscopy could have in the near future.

Learning curve in diagnostic and interventional sialendoscopy for obstructive salivary diseases.

Sialendoscopy is a new diagnostic and surgical tool for management of salivary gland diseases that offers the opportunity to treat selected pathologies less invasively and with better results compared to previous techniques. As with any new technique, an adequate training programme involving a gradual learning curve is mandatory to quickly obtain results similar to those reported in the literature. This includes an appropriate diagnostic programme, correct patient selection and knowledge of possible pitfalls. In this retrospective study, the outcomes of the first 141 procedures (74 on the parotid gland and 67 on the submandibular gland) performed with this technique in our Department from 2009 to 2013 were compared with those reported in the literature. Patients were divided into three groups: Group A (the first 49 procedures performed), Group B (the next 50 procedures), and Group C (the last 42 procedures). There were no statistically significant differences relative to mean procedure times, recurrence of symptomatology after treatment, need for further treatments and rates of minor complications between groups. No major complications were seen. The increase in experience resulted in an increased number of interventional sialendoscopies performed under local anaesthesia instead of general anaesthesia (51% vs 18% vs 14%). In only three of 130 glands treated (2.3%) was gland resection required. We also evaluated which technique had been used for stone removal and rate of failure, which was similar in all groups (13.6% vs 15% vs 15%). Our results do not substantially differ from those reported in the literature. Initial difficulties in catheterising the papilla could be overcome with practise on fresh human specimens or fresh pig heads. Lack of precision regarding diagnostic imaging techniques was remedied by improving the competence of the surgeon in performing pre- and postoperative ultrasound. The creation of specialised centres capable of treating up to 1 to 2 million people would be desirable in order to better stratify pathologies, validate the investment in equipment and gain the necessary experience in the various surgical techniques.

Risks and medico-legal aspects of endoscopic sinus surgery: a review.

The aim of this study was to perform a systematic literature review of risks and medico-legal aspects of endoscopic sinus surgery. The development of sophisticated technologies and instruments for endoscopic sinus surgery (ESS) has caused a dramatic increase in the number of otolaryngologists performing sinus surgery and the number of cases performed. This expansion was accompanied by an increase in malpractice lawsuits. Over the past 20 years, rhinology claims represented 70 % of the total indemnity compensation for otolaryngology claims and ESS was the surgical procedure most often involved. Only then will a careful analysis and assessment of the possible and potential risk factors of ESS, which may mislead the surgeon, allow a correct clinical risk management, with activities and procedures aimed at reducing the possibility of complications that may expose the physician to a malpractice suit.

The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.

Nasopharyngeal mucoepidermoid carcinoma in children.

Salivary gland tumours represent 1-4% of all human neoplasms and less than 5% occur in children and adolescents. Malignant salivary gland tumours only represent 0.08% of all childhood tumours and mucoepidermoid carcinoma (MEC) is the most common histological type. The majority of MECs in the paediatric group are histologically classified as low or intermediate grade of malignancy, favouring a good prognosis. Complete excision of the lesion with free surgical margins is the treatment of choice and the one that offers the best local control of the disease. Experience with minor salivary gland carcinoma arising specifically within the nasopharynx is limited because nasopharyngeal MEC is an extremely rare malignancy and there is controversy regarding its optimal treatment. We hereby report a case of mucoepidermoid carcinoma arising from the nasopharynx in a 7-year-old girl, which was managed via an endonasal endoscopic procedure. To our knowledge the case we describe is the second case of nasopharyngeal MEC in paediatric age reported in literature and is the only one occurred in the first decade of life.

Extended endoscopic transplanum-transtuberculum approach for pituitary adenomas.

Few pituitary adenomas require removal through a transcranial route. This may be associated with more significant morbidity and mortality, compared to the transsphenoidal approach. An endoscopic, extended, transplanum-transtuberculum approach (ETTA) in selected pituitary adenomas may offer an alternative to the transcranial route. We describe our technique and experience of ETTA in pituitary adenomas over 10 years. Between 2000 and 2010, we performed 700 endoscopic endonasal procedures for pituitary adenomas. Nineteen patients (13 men; mean age, 48 years; range, 22-76 years) underwent 22 ETTAs. Thirteen patients had non-functioning adenomas. Three tumor groups were identified: (1) tumors developing in or around the pituitary stalk; (2) tumours with sub- frontal extension and (3) tumours with a major extrasellar component. Mean follow-up was 37 months (range 6-72 months). Gross total resection was achieved in 11 procedures (no recurrences), with partial tumour resection in 11 procedures. Of the 12 patients with visual symptoms, ten improved. Of eight patients with hormonal hypersecretion four were cured. Complications included CSF leak (14%), haemorrhage (9%), hemiplegia (5%). There were no mortalities. Experience using the ETTA for pituitary adenomas is limited because it is indicated in highly selected cases (3.1% of our series). An absolute indication is represented by ectopic secreting pituitary stalk/peri-stalk adenomas. ETTA is a useful option in midline frontal adenomas and adenomas with a major extrasellar component, but has a higher morbidity than that seen in the standard transsphenoidal approach. A study comparing ETTA versus transcranial resection is highly desirable.

Endonasal endoscopic approach for intracranial nasal dermoid sinus cysts in children.

Nasal dermoid sinus cysts are the most common congenital midline nasal lesions. The frequency of intracranial extensions varies from 5% to 45%. Complete surgical excision of nasal dermoid cyst and any associated sinus tract is essential for cure and any residual ectodermal elements result in a high rate of recurrence and complicated infections. Many different approaches have been described for the removal of nasal dermoids in the past two decades, ranging from a simple extracranial excision to complex procedures in which a combined extracranial-intracranial approach is required. We hereby report two cases of nasal dermoid sinus cysts in children with intracranial extension which were managed with an endonasal endoscopic procedure. We describe the technique we implemented for this procedure and for the reconstruction of the skull base defect.

[Sinonasal carcinoma and exposure to wood and leather dust: analysis of 36 cases]. / Neoplasie naso-sinusali da esposizione occupazionale a polveri di legno e cuoio: analisi retrospettiva di 36 casi.

In order to define the best strategies of prevention and diagnosis of sinonasal cancer, the aim of our study was the investigation of the etiological and prognostic factors related to 36 cases. The enrolled cases were composed mostly of men working in the footwear industry, with a mean age of 63.7 years and mean exposure of 34.6 years. The period between the start of exposure and the appearance of the neoplasm was of 44.6 years, the time between the onset of symptoms and diagnosis was of 10.8 months. Our results suggest that a diagnosis within 6 months after the onset of symptoms is associated with a lower tumor stage, a better survival and to a lower rate of recurrence. Nasal obstruction (58.3%) and epistaxis (52.7%) are the main initial symptoms. In order to obtain an early diagnosis, in addition to periodic clinical controls, a proper information of workers is required.

Surgical repair of persisting CSF leaks following standard or extended endoscopic transsphenoidal surgery for pituitary tumor.

INTRODUCTION: In this article, the aim of the authors is to discuss their experience with skull base reconstruction in endoscopic transsphenoidal and extended transsphenoidal surgery for pituitary tumor resection. METHODS: Between January 1997 and January 2008, 665 patients underwent either transnasal transsphenoidal endoscopic or extended transsphenoidal surgery for pituitary tumors. In patients without intraoperative CSF leak, we prefer to pack the surgical cavity with absorbable material, such as collagen sponge (Gelfoam), or, in the case of thin diaphragma sellae and postoperative risk of rupture with abdominal fat. In patients with minimal CSF oozing, but without any visible diaphragma sellae defect or only a small dural defect with leak, we pack the surgical cavity with abdominal fat. In case of a leak from an anterior face of the diaphragma sellae defect we prefer to reconstruct the defect by means of mucoperiosteum taken from the resected middle turbinate. Patients with larger sellar or supradiaphragmatic defects were treated with a multilayer reconstruction. RESULTS: 529 patients (79.5%) did not require any repair besides a packing of the surgical cavity with absorbable material such as collagen sponge, while 128 patients (19.2%) required an endoscopic skull base repair at the end of the procedure for an overt CSF leak. 8 patients (1.2%) required repair because of overt thin diaphragma sellae without a visible CSF leak but with a postoperative risk of rupture. Out of the latter two groups (n = 136) only 11 patients (8 %) developed persistent postoperative CSF leaks requiring revision multilayer reconstruction. CONCLUSIONS: More complex defects after pituitary surgery should be repaired with a multilayer technique, using autologous materials such as fat, fascia lata, bone and mucoperiosteum taken from the middle turbinate. This type of autologous material is generally reliable in more complex defects, and it appears to be easy to harvest and handle for repair.

Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency.

In an expanded newborn screening program for inborn errors of metabolism by LC-MS/MS in Tuscany, six newborns out of 169,000 showed decreased blood citrulline levels. In one of them, molecular analysis of the OTC gene identified the known p.Trp265Leu mutation, which is correlated with late-onset ornithine transcarbamylase deficiency (OTCD). Hypocitrullinemia is not a reliable marker for OTCD newborn screening, especially for late-onset forms that may exhibit normal citrulline levels. However, when hypocitrullinemia is detected in a newborn in whom intestinal dysfunction and prematurity have been excluded, OTCD should be investigated first because of the OTCD incidence (1:14,000) and the small size of the OTC gene coding sequence.

Lipoplatin monotherapy: A phase II trial of second-line treatment of metastatic non-small-cell lung cancer.

Lipoplatin is a liposome encapsulated form of cisplatin. phase i studies on lipoplatin have demonstrated that the compound has an excellent toxicity profile. therefore we performed a phase ii trial in heavily pre-treated patients with advanced non-small-cell lung cancer (NSClC), performance status 0-2 in which the primary endpoint was response rate and secondary endpoints were safety and overall survival.Nineteen patients, average age 64 years old, with stage iV NSClC, were treated with lipoplatin 100 mg/m(2) every two weeks, as second line chemotherapy.We observed 1 partial remission (5.2%) and 3 stable diseases (15.9%). Time to progression (ttp) was 16 weeks and median overall survival (OS) was 31 weeks (7.2 months). We observed G1-G2 toxicity during chemotherapy, mainly gastrointestinal with nausea and vomiting (4 patients), asthenia (3 patients), mucositis (2 patients) and anemia (4 patients).Our phase ii study does not support a more extensive use of lipoplatin in phase III studies. An increase of dosage and a better selection of patients are mandatory to understand the real therapeutic activity of lipoplatin.

Thyrotropin-secreting pituitary tumours: significance of "atypical adenomas" in a series of 10 patients and association with Hashimoto thyroiditis as a cause of delay in diagnosis.

BACKGROUND: Thyrotropin-secreting adenomas (TSH-As) are rare and, according to the World Health Organization criteria (WHO 2004), a significant proportion of them present features of atypical adenomas at the time of diagnosis. AIMS: To determine the frequency of "atypical adenomas" and the significance of this definition as regards follow-up. To investigate their possible association with Hashimoto thyroiditis, leading to a delay in diagnosis. METHODS: Case notes for patients who underwent trans-sphenoidal surgery between 1992 and 2006 were retrieved. Follow-up ranged from 6 to 180 months. RESULTS: Ten cases of TSH-As out of 908 pituitary adenomas were selected. Before surgery, eight patients had hyperthyroidism, one was euthyroid and another one showed hypothyroidism associated with Hashimoto thyroiditis. All cases were macroadenomas; six of them were invasive. Three cases met the criteria for classification as atypical. In none of the cases, including the three "atypical adenomas", were clinical or radiological signs of recurrence observed. CONCLUSIONS: The three cases with features of atypical adenoma did not recur or metastasise, suggesting that, at least in the present series, a strict relationship between the morphological criteria for diagnosing atypical adenomas and biological behaviour may be sometimes lacking. Furthermore, the casual association of TSH-As with Hashimoto thyroiditis may led to an adjunctive delay in diagnosis, because of low thyroid hormone levels.

Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: update on methods to reduce false tests.

We report on our 6-year experience of expanded newborn screening by tandem mass spectrometry in Tuscany (Italy), the first Italian Region to screen all newborns for more than 40 inborn errors of metabolism: organization, diseases observed and updates on methods to reduce false-positive and false-negative tests are described. Blood collection is recommended between 48 and 72 h of life. Blood spots are sent daily by courier to laboratory. When a positive result occurs, two subsequent procedures are followed: for disorders with possible acute metabolic decompensation, the baby is immediately recalled and clinical examinations and confirmatory tests are performed; for the other disorders, the nursery provides for a second blood spot. If the test is positive, clinical examinations and confirmatory tests are performed. In both cases, if confirmatory tests are positive, a treatment and a follow-up programme are started. Up to now, spots from 160 000 infants have been analysed and 80 affected patients have been identified (disorders of amino acids, organic acids and fatty acids metabolism). We describe adjustments to cut-off values, the introduction of a second-tier test for propionic acidaemia and for methylmalonic aciduria, the inclusion of succinylacetone in the panel of metabolites, and protocols for premature infants and for newborns on parenteral nutrition or transfused. These changes resulted in a reduction in recalls from 1.37% to 0.32% and consequently of working time and parental stress. Avoiding false-negatives by using more specific markers and minimizing the false-positive rate with second-tier testing is important for a successful newborn screening programme.