To assess the safety of laparoscopy in patients with CSF catheters draining distally into the abdomen.

PURPOSE: This study evaluates the safety of laparoscopic procedures in patients with cerebrospinal fluid (CSF) catheters draining distally into the abdomen. METHODS: A systematic search across PubMed, Scopus, and Ovid databases using pertinent keywords yielded 47 relevant papers, encompassing 197 cases, for analysis. RESULTS: In the pediatric cohort (n = 129), male (49.6%) and female (34.1%) cases were reported, while gender remained unspecified in 16.3%. Shunt indications included unspecified (126 cases) and Meningomyelocele (3 cases). Laparoscopic procedures encompassed gastric (72.1%), urologic (21.7%), and other (6.2%) indications. Peri-operative shunt management included subcostal incision and clamping (1), ICP monitoring and drainage (2), and distal shunt flow confirmation (1). The prevalent complication was mechanical obstruction (10.1%), followed by pseudocyst formation (1.5%) and infection (2.3%). In the adult cohort (n = 61), males (60.6%) and females (39.3%) with a median age of 55 years were observed. Management strategies encompassed sponge packing and mobilization (11), distal shunt flow confirmation (2), shunt clamping (3), Transcranial Doppler monitoring (2), and no manipulation (30). Shunt infection emerged as the primary complication (2). Overall, 24 patients encountered VP shunt-related complications post-laparoscopy. CONCLUSION: This study underscores the safety of laparoscopic interventions in patients with ventriculoperitoneal or lumboperitoneal shunts when facilitated by interdisciplinary cooperation. A meticulous preoperative assessment for shunt track localization, intraoperative visualization of shunt tip with CSF flow, vigilant perioperative anesthetic monitoring, and shunt dysfunction surveillance are crucial for favorable outcomes in laparoscopic procedures for these patients.

Traumatic pneumorrhachis: systematic review and an illustrative case.

Pneumorrhachis (PR) refers to free air in the spinal canal. We aim to describe a case report and conduct a systematic review focused on the clinical presentation, diagnosis, and management of traumatic PR. We conducted a language-restricted PubMed, SciELO, Scopus, and Ovid database search for traumatic PR cases published till June 2019. Categorical variables were assessed by Fisher's exact test. In addition to our reported index case, there were 82 articles (96 individual cases) eligible for meta-analysis according to our inclusion/exclusion criteria. Eighty per cent of patients had blunt trauma, while 17% had penetrating injuries. Thirty-four per cent of cases were extradural PR, 21% intradural PR, and unreported PR type in 43%. Nine per cent of patients presented with symptoms directly attributed to PR: sensory radiculopathy (2%), motor radiculopathy (1%), and myelopathy (6%). CT had a 100% sensitivity for diagnosing PR, MRI 60%, and plain radiograph 48%. Concurrent injuries reported include pneumocephalus (42%), pneumothorax (36%), spine fracture (27%), skull fracture (27%), pneumomediastinum (24%), and cerebrospinal fluid leak (14%). PR was managed conservatively in every case, with spontaneous resolution in 96% on follow-up (median = 10 days). Prophylactic antibiotics for meningitis were given in 13% PR cases, but there was no association with the incidence of meningitis (overall incidence: 3%; prophylaxis group (0%) vs non-prophylaxis group (4%) (p = 1)). Occasionally, traumatic PR may present with radiculopathy or myelopathy. Traumatic PR is almost always associated with further air distributions and/or underlying injuries. There is insufficient evidence to support the use of prophylactic antibiotic in preventing meningitis in traumatic PR patients.

Analysis of cervical sagittal alignment change following correction of thoracic and thoracolumbar Scheuermann's kyphosis.

PURPOSE: To analyse pre-operative and post-operative changes of cervical sagittal alignment (CSA) in Scheuermann's kyphosis (SK) patients. METHODS: 64 SK and 33 control patients were retrospectively reviewed. Whole spine X-rays obtained at pre-op, 3 months post-op and at latest follow-up were reviewed and ten separate CSA radiological parameters were measured. Patients were divided in three groups: thoracic SK (TK group, apex T6-T9, n = 40), thoracolumbar SK (TLK group, apex T10-T12, n = 24), and controls. RESULTS: Pre-operative C2-C7 lordosis was 21.1° ± 8.1°(TK), 6.1° ± 5.0°(TLK), and 11.4° ± 8.3° in control group and correlated significantly with T1 slope in both SK groups (r = 0.640, r = 0.772). Pre-operative T1 slope was dependent on deformity type, thoracic kyphosis (TK, ß = 0.445), and lumbar lordosis (LL, ß = -0.354). At final follow-up C2-C7 lordosis decreased to 15.7° ± 5.5° in TK, and increased to 12.1° ± 4.1° in TLK group. C2-C7 lordosis changes linearly correlated with T1 slope changes post-operatively (r = 0.721). Post-operative T1 slope showed linear correlation with post-operative changes in TK (ß = 0.728) and pelvic tilt (PT, ß = 0.539) in TK, and LL (ß = -0.669), thoracolumbar kyphosis (TLK, ß = -0.434), and PT (ß = 0.760) in TLK group. CONCLUSIONS: Our study suggests that SK is not a homogenous group of patients. Two patterns of pre- and post-operative CSA are demonstrated in TK and TLK groups. T1 slope is the most important parameter in determining pre-operative CSA and correlates with other regional anatomical parameters (TK and LL). Post-operative CSA adaptations also correlate with T1 slope post-operative changes. However, post-surgical T1 slope correlates with different parameters in the two SK groups (TK and PT in TK group; TLK, LL, and PT in TLK group).

The Nottingham Expectation and Complication score following Surgery (NECS): an universal scale for surgical outcome audit and peer comparison.

BACKGROUND: Consultant Outcomes Publication (COP) is an NHS England initiative for promoting improvements in quality of care. However, at present outcomes are commonly expressed as mortality rates which do not necessarily reflect the performance of surgeons. We developed the Nottingham Expectation and Complication score following Surgery (NECS) to determine the success of surgical treatment from both the clinical perspective and the practical expectations agreed between surgeons and patients during the consent process. METHOD: This was a pilot study to trial the use of the NECS score. It is a simple expression of overall outcome comprising three clinical domains: S - surgical outcome, T - surgical/technical complications and M - medical complications recorded by the treating clinician, and practical outcome determined by a joint clinical/patient assessment. 107 elective neurosurgical patients were included in this prospective study. 95 completed questionnaires were included. RESULTS: 75% patients achieved the best possible treatment score (S3T3M4). Of the 25% of patients who did not achieve this ideal outcome, the most common cause was either medical deterioration 18%, or technical complications of surgery discussed during the consent process 17%, or both. Surgeons rated their outcomes as expectations exceeded in 2% of cases, met in 92%, partially met in 5% and failed in 1%. Patients rated their outcomes as expectations exceeded in 37%, met in 37%, partially met in 18%, and 5% reported that their expectations were not met or they were worse than before the operation. Bivariate correlation analysis (Pearson's r coefficient) between overall 'expectation score' of patients and surgeons showed moderate correlation with r = .25 (p = .014). CONCLUSION: NECS score can be used as an indicator to assess technical performance and patient satisfaction. It provides a more balanced quality indicator of the surgical service delivery than COP. It also offers additional advantages for auditing/planning improving care and may serve as an appraisal/revalidation tool.

Clinical outcome and safety study of a newly developed instrumented French-door cervical laminoplasty technique.

BACKGROUND: Standard laminectomy for treatment of cervical myelopathy is associated with secondary instability and kyphosis, while laminectomy combined with fusion puts adjacent segments at risk of degeneration. Single- and double-door laminoplasty techniques have been developed to overcome these limitations. More recently, complications related to bone graft dislodgment have fostered development of hardware-augmented laminoplasty techniques. The aim of this study is to review the clinical safety and effectiveness of a newly developed technique of instrumented French-door laminoplasty for treatment of cervical myelopathy. MATERIALS AND METHODS: A series of 25 consecutive myelopathic patients were treated with a novel instrumented cervical French-door laminoplasty technique, whereby the enlarged posterior arch was held open with maxillofacial plates and screws. Patients had pre- and postoperative assessments with the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) Score, Visual Analogue Score and radiographs. Minimum follow-up was 40 months, with regular interval assessments. RESULTS: There were 18 males with a mean age of 45 years. The mean operative time was 145 min. The average hospital stay was 2.4 days and the mean follow-up was 56.5 months (40-72). All patients reported neurological improvements and there was a 35% improvement in NDI, and JOA score improved by 4.8 points. No postoperative hardware-related complications were noted and only one case of temporary C5 palsy, which completely resolved by the one-year follow-up. CONCLUSIONS: Our data and clinical experience demonstrate that this hardware-augmented laminoplasty technique is safe and effective. We observed no hardware-related complications in our series. The use of readily available maxillofacial titanium miniplates and ease of surgical procedure means that this technique can be easily adopted into clinical practice. LEVEL OF EVIDENCE: Level IV.

Selective dorsal rhizotomy as an alternative to intrathecal baclofen pump replacement in GMFCS grades 4 and 5 children.

BACKGROUND: Conventionally, selective dorsal rhizotomy (SDR) has been reserved for ambulant children and implantation of intrathecal baclofen (ITB) pump for non-ambulant children with cerebral palsy. Rather than replacing the ITB pump in selected Gross Motor Function Classification System (GMFCS) grades 4 and 5 children, we elected to undertake SDR instead. We discuss the rationale and outcomes. OBJECTIVES: To assess if children with severe spasticity treated with long-term ITB pump would benefit from SDR as alternative procedure to replacement of ITB pump. METHOD: This study is a prospective review of ten children with severe spasticity. Indications for ITB pump replacement in 3/10 children were previous ITB pump infection and the remaining seven were nearing depletion of drug delivery system. Pre- and post-SDR mean modified Ashworth scores, assessment of urological function and survey of parent/carer satisfaction were undertaken. RESULT: Mean Ashworth score reductions post-SDR in the lower limbs and upper limbs were 2.4 and 1.70, respectively. An improvement in urological function was also noticed in 27% of patients. Overall, 90% of parents/carers felt that functional outcome with SDR was improved compared with that of ITB. CONCLUSION: SDR in comparison to ITB in this subgroup is cheaper, less intrusive by avoiding refills/replacement and found to be more effective than ITB in reducing spasticity and providing ease for nursing care. We therefore suggest that consideration should be given to SDR as an alternative in patients previously implanted with ITB systems complicated by infection or nearing end of battery life.

Combined selective dorsal rhizotomy and scoliosis correction procedure in patients with cerebral palsy.

UNLABELLED: Intrathecal baclofen (ITB) therapy for spasticity has been suggested to accelerate the development of scoliosis. We present the case of a 17-year-old female patient with cerebral palsy who had ITB therapy from the age of 11 years. During this period, she developed a severe scoliosis measuring 86° from T11 to L4, with pain due to costo-pelvic impingement. Her baclofen pump had reached its end of life and required replacement if ITB therapy was to continue. This coincided with plans for scoliosis corrective surgery. METHODS: We performed scoliosis correction along with removal of baclofen pump and selective dorsal rhizotomy (SDR), as a single combined procedure. SDR was performed instead of ITB pump replacement for management of spasticity. RESULTS: Following surgery, scoliosis improved to 24°. At 6 month follow-up, there was significant improvement in spasticity and quality of life. CONCLUSIONS: This report illustrates the feasibility of a combined procedure to correct scoliosis and manage spasticity with SDR. We present the case details, our management and review of the published literature regarding the factors influencing treatment of scoliosis and spasticity.

Subarachnoidal pleural fistula after resection of intradural thoracic disc herniation and multimodal treatment with noninvasive positive pressure ventilation (NPPV).

Subarachnoid pleural fistula (SPF) is a type of cerebrospinal fluid (CSF) fistula that can arise as a complication following transthoracic resection of intervertebral disc herniation in the thoracic spine. It is an abnormal communication between the subarachnoid and pleural space. Negative intrapleural pressure promotes CSF leak due to a suction effect into the pleural cavity, with little chance of spontaneous closure. Due to the risk of severe complications with CSF leak into the thoracic cavity, early diagnosis and treatment are mandatory. However, management can be challenging. We report a case of a 72-year-old woman who underwent anterior thoracic surgery to treat thoracic myelopathy caused by an ossified intradural disc herniation. The postoperative period was complicated by a subarachnoidal pleural fistula. We describe our successful treatment of this using noninvasive positive pressure ventilation and lumbar CSF drainage and review other methods reported in the literature.

Socio-economic characteristics of patients with glioblastoma multiforme.

The incidence of glioblastoma multiforme (GBM) varies across the world and also within subpopulations within each nation. Many cancers show correlation with socioeconomic status and we hypothesised that incidence of GBM also does the same. We performed a retrospective analysis of all patients treated with brain tumours at a single hospital over a 6-year period. For these patients we examined markers of socioeconomic status and reviewed their histopathological diagnosis. A total of 2859 patients had surgery between April 2006 and April 2012. Of these 880 had histological diagnosis of GBM. Records for all patients were reviewed. Based on postcodes, socioeconomic data was obtained at ward level from government sources. Markers were: average weekly household income, percentage unemployed, population density, indices of deprivation and percentage of households with no car. Data was analysed for trends between incidence per ward and socio-economic markers. Increasing incidence of GBM was associated with increasing wage (p = 0.044), less unemployment (p = 0.0002), Indices of Multiple Deprivation (p = 0.05), lower population density (p = 0.0015) and greater ownership of cars (p = 0.0005). There are unique socioeconomic characteristics for patients with GBM. Although a link to aetiology cannot be established from this limited epidemiological study, these results identify issues that these patients are more likely to face. These should be taken into account when planning support services and patient care following surgery.

A simple method to ease insertion and removal of vertebral body distractor pins in anterior cervical surgery.

Soft tissue injuries and visceral perforation are rare but potentially lethal complications of anterior cervical spine surgery. We describe a cheap and simple technique for guarding para-vertebral soft tissues, making insertion and removal of vertebral body distractor screws easier and safer with or without an assistant.

Clival Mucocele: A Rare Yet not Forgotten Pathology.

Primary clival mucoceles are a rare clinical entity that usually represents an incidental finding on computed tomography or magnetic resonance imaging scanning. There are only a few reports in the literature of patients who presented with vague symptoms such as headaches, facial paresthesia, and numbness. Clival mucoceles can also be secondary, by extension of a sphenoid mucocele to the clivus. We present a case of primary clival mucocele, aiming to highlight the importance of a multidisciplinary approach.

Cervical catheter placement for intrathecal baclofen test dose: is it safe?

INTRODUCTION: Intrathecal baclofen testing is usually performed via a catheter inserted at the lumbar spine. However, in patients with scoliosis, the distorted anatomy and bone fusion from corrective spinal surgery obviates access at the lumbar spine. PATIENTS AND METHODS: We report a method for inserting the intrathecal catheter via a posterior cervical approach and discuss our outcome. We describe our experience in 20 patients in whom intrathecal baclofen test catheter was inserted at the lower cervical spine. Data was collected prospectively. DISCUSSION: The procedure was successful in all 20 patients. There were no complications as a result of surgery or from baclofen test dose administration via a cervical catheter. Of the 20 patients, 15 went on to have baclofen pump implantation via a cervical catheter. In one patient, subsequent pump implantation procedure was unsuccessful due to presence of extradural scar tissue. In the remaining four patients pump implantation was declined due impending corrective spinal surgery or social reasons. CONCLUSION: Our experience shows that low cervical catheter insertion for administration of a test dose of intrathecal baclofen and feasible and safe to perform via the method described.

Pituitary haemorrhage and infarction: the spectrum of disease.

BACKGROUND: Pituitary apoplexy is an acute syndrome of haemorrhage or infarction into the pituitary. The condition is relatively well-described. Less well-described is sub-acute presentation of the same condition. OBJECTIVE: To compare the clinical presentation and natural history of subacute pituitary haemorrhage/infarction with pituitary apoplexy (acute). METHOD: Retrospective analysis of a consecutive cohort of 55 patients (33 with pituitary apoplexy, 22 with subacute disease) presenting to University Hospital Plymouth between 1994 and 2019. Comparison of the clinical, endocrinological and radiological features at presentation. Comparison of clinical treatment and subsequent outcomes for the two groups. RESULTS: There were no significant differences in predisposing factors for the two groups. Acute headache was more frequent in the acute group. Chronic headache was common in both groups prior to presentation. Low sodium was more common at presentation in the acute group (11/26 vs 2/19 P = 0.02) otherwise there were no differences in endocrine deficit at presentation. A significant proportion showed an improvement in endocrine function at follow up (acute 8/31, subacute 5/21 P = 1.0). MRI characteristics were variable at presentation and follow up in both groups. Ring enhancement with contrast was more frequent in acute (14/20 vs 3/11 P = 0.03). This appearance resolved at follow up in the majority. CONCLUSIONS: Pituitary apoplexy has a characteristic and dramatic presentation. Subacute pituitary haemorrhage/infarction shows similar natural history and outcome. These conditions would appear to represent a spectrum of the same condition.

The expression of neural cell adhesion molecule and the microenvironment of pituitary neuroendocrine tumours.

The neural cell adhesion molecule (NCAM) has previously been studied in pituitary neuroendocrine tumours (PitNETs), but its role in tumour biology and aggressiveness remains controversial, and its relationship with the tumour microenvironment remains unknown. We aimed to characterise NCAM expression in PitNETs, to correlate this with clinico-pathological features, and to assess the role of various microenvironment components on NCAM expression. NCAM and immune cells were investigated by immunohistochemistry in 16 human non-functioning-PitNETs (NF-PitNETs) and eight somatotrophinomas, including macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20), and neutrophils (neutrophil elastase). Five normal pituitaries were included for comparison. The cytokine secretome from these PitNETs and from PitNET-derived tumour-associated fibroblasts (TAFs) were assessed on culture supernatants using a multiplex immunoassay panel. There were no significant NCAM expression differences between PitNETs and normal pituitary, and no difference between types of pituitary tumours (NF-PitNETs vs. somatotrophinomas). There was no association between NCAM expression and different clinico-pathological features, including cavernous sinus invasion and Ki-67, nor with serum hormone levels. NCAM immunoreactivity correlated negatively with PitNET-derived CXCL10 (rho = -0.417; p = .042) and CX3CL1 (rho = -0.423; p = .040) levels. NCAM immunoreactivity was negatively correlated with TAF-derived fibroblast growth factor (FGF)-2 (rho = -0.632; p = .009), but not with other TAF-derived cytokines. Within the PitNET cohort, there were no correlations between NCAM immunoreactivity and immune infiltrates or ratios, although, within NF-PitNETs, NCAM expression was higher in tumours with more FOXP3+ cells. NCAM expression does not differ between PitNETs and normal pituitary, and does not appear to relate to tumour invasiveness or proliferation. However, our data suggest a possible role for cytokines in the modulation of NCAM expression in PitNETs, particularly CXCL10, CX3CL1 and FGF-2, but not for immune cell infiltrates.

Isolated Intracranial Rosai-Dorfman Disease: Case Report and Review of the Literature.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare idiopathic benign proliferative disorder of histiocytes, predominantly affecting the lymph nodes. RDD can also present in extranodal tissues and is occasionally found within the central nervous system. CASE DESCRIPTION: We report the case of a 52-year-old man presenting with a short episode of dizziness. Imaging identified a right frontal, extraaxial, dural-based lesion, suspicious for a meningioma. The patient underwent a craniotomy for tumor resection and, although not entirely typical, the pathology was consistent with RDD. No other evidence of RDD was identified. CONCLUSIONS: RDD should be considered as a differential diagnosis of dural-based lesions, more commonly meningiomas.

The role of the tumour microenvironment in the angiogenesis of pituitary tumours.

PURPOSE: Angiogenesis has been studied in pituitary neuroendocrine tumours (PitNETs), but the role of the tumour microenvironment (TME) in regulating PitNET angiogenesis remains unknown. We aimed to characterise the role of TME components in determining the angiogenetic PitNET profile, focusing on immune cells and tumour-derived cytokines. METHODS: Immune cells were studied by immunohistochemistry in 24 human PitNETs (16 non-functioning-PitNETs (NF-PitNETs) and 8 somatotrophinomas): macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitaries (NP) were included for comparison. Microvessel density and vascular morphology were estimated with ImageJ. The cytokine secretome from these PitNETs were assessed on culture supernatants using a multiplex immunoassay panel. RESULTS: Microvessel density/area was higher in NP than PitNETs, which also had rounder and more regular vessels. NF-PitNETs had vessels of increased calibre compared to somatotrophinomas. The M2:M1 macrophage ratio correlated with microvessel area. PitNETs with more CD4+ T cells had higher microvessel area, while tumours with more FOXP3+ cells were associated with lower microvessel density. PitNETs with more B cells had rounder vessels. Of the 42 PitNET-derived cytokines studied, CCL2, CXCL10 and CX3CL1 correlated with microvessel density and vessel architecture parameters. CONCLUSIONS: M2 macrophages appear to play a role in PitNET neovascularisation, while B, CD4+ and FOXP3+ lymphocytes, as well as non-cellular TME elements such as CCL2, CXCL10 and CX3CL1, may also modulate the angiogenesis of PitNETs.

Correlation Between Cost of Publication and Journal Impact. Comprehensive Cross-sectional Study of Exclusively Open-Access Surgical Journals.

OBJECTIVES: As open-access journals have become increasingly common, it has provided more options for researchers to publish their work and improved access of information to the public. However, some open-access journals charge the authors processing fee on submission. In certain cases, this can be rather expensive. This study is the first study to specifically assess the cost of publishing in exclusively open-access, peer-reviewed surgical journals, and their correlation with journal impact, in the form of 6 bibliometrics. DESIGN AND SETTING: This is a cross-sectional study. A list of journals is compiled using the SCImago Journal & Country Rank and Directory of Open Access Journals. 6 indices are measured - impact factor, SCOPUS h-index, SCImago journal rank indicator (SJR), Eigenfactor, Article Influence Score and Google h5 index. The cost of publication (in USD$) of a research article (maximum of 6 pages) is used as a baseline. RESULTS: 89 research journals are included. The median cost of publication is USD$100 (range [0-2580]). 47% are free of charge. 13% can cost more than USD$2000 per article. SJR and Google h5 index appear to be the only indices that correlate linearly with the cost (p = 0.015 and 0.041, respectively), although the correlations are weak. 3 indices, namely impact factor, SJR and Article Influence Score appear to have very strong correlations with each other (Pearson coefficient > 0.90). CONCLUSIONS: From this study, the cost of publishing in open-access journals bears little correlation to their impact; this poses a dilemma for researchers without significant funding. Therefore, authors and funders must consider cautiously when submitting to these journals.

Chemokines modulate the tumour microenvironment in pituitary neuroendocrine tumours.

Non-tumoural cells within the tumour microenvironment (TME) influence tumour proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary neuroendocrine tumours (PitNETs). We aimed to characterise the role of TME in the aggressive behaviour of PitNETs, focusing on immune cells and cytokines. The cytokine secretome of 16 clinically non-functioning PitNETs (NF-PitNETs) and 8 somatotropinomas was assessed in primary culture using an immunoassay panel with 42 cytokines. This was correlated with macrophage (CD68, HLA-DR, CD163), T-lymphocyte (CD8, CD4, FOXP3), B-lymphocyte (CD20), neutrophil (neutrophil elastase) and endothelial cells (CD31) content, compared to normal pituitaries (NPs, n = 5). In vitro tumour-macrophage interactions were assessed by conditioned medium (CM) of GH3 (pituitary tumour) and RAW264.7 (macrophage) cell lines on morphology, migration/invasion, epithelial-to-mesenchymal transition and cytokine secretion. IL-8, CCL2, CCL3, CCL4, CXCL10, CCL22 and CXCL1 are the main PitNET-derived cytokines. PitNETs with increased macrophage and neutrophil content had higher IL-8, CCL2, CCL3, CCL4 and CXCL1 levels. CD8+ T-lymphocytes were associated to higher CCL2, CCL4 and VEGF-A levels. PitNETs had more macrophages than NPs (p < 0.001), with a 3-fold increased CD163:HLA-DR macrophage ratio. PitNETs contained more CD4+ T-lymphocytes (p = 0.005), but fewer neutrophils (p = 0.047) with a 2-fold decreased CD8:CD4 ratio. NF-PitNETs secreted more cytokines and had 9 times more neutrophils than somatotropinomas (p = 0.002). PitNETs with higher Ki-67 had more FOXP3+ T cells, as well as lower CD68:FOXP3, CD8:CD4 and CD8:FOXP3 ratios. PitNETs with "deleterious immune phenotype" (CD68hiCD4hiFOXP3hiCD20hi) had a Ki-67 ≥ 3%. CD163:HLA-DR macrophage ratio was positively correlated with microvessel density (p = 0.015) and area (p < 0.001). GH3 cell-CM increased macrophage chemotaxis, while macrophage-CM changed morphology, invasion, epithelial-to-mesenchymal transition and secreted cytokines of GH3 cells. PitNETs are characterised by increased CD163:HLA-DR macrophage and reduced CD8:CD4 and CD8:FOXP3 T cell ratios. PitNET-derived chemokines facilitate macrophage, neutrophil and T cell recruitment into the tumours which can determine aggressive behaviour.

Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness.

Tumour-associated fibroblasts (TAFs) are key elements of the tumour microenvironment, but their role in pituitary neuroendocrine tumours (PitNETs) has been little explored. We hypothesised that TAF-derived cytokines may play a role in tumour aggressiveness and that their release can be inhibited by somatostatin analogues. TAFs were isolated and cultured from 16 PitNETs (11 clinically non-functioning tumours and 5 somatotropinomas). The fibroblast secretome was assessed with a 42-plex cytokine array before and after multiligand somatostatin receptor agonist pasireotide treatment. Angiogenesis and epithelial-to-mesenchymal transition pathway assessment included CD31, E-cadherin and ZEB1 expression. GH3 cells treated with TAF- or skin fibroblast-conditioned medium were assessed for migration, invasion and cell morphology changes. PitNET TAFs secreted significant amounts of cytokines including CCL2, CCL11, VEGF-A, CCL22, IL-6, FGF-2 and IL-8. TAFs from PitNETs with cavernous sinus invasion secreted higher IL-6 levels compared to fibroblasts from non-invasive tumours (P = 0.027). Higher CCL2 release from TAFs correlated with more capillaries (r = 0.672, P = 0.004), and TAFs from PitNETs with a higher Ki-67 tended to secrete more CCL2 (P = 0.058). SST1 is the predominant somatostatin receptor in TAFs, and pasireotide decreased TAF-derived IL-6 by 80% (P < 0.001) and CCL2 by 35% (P = 0.038). GH3 cells treated with TAF-conditioned medium showed increased migration and invasion compared to cells treated with skin fibroblast-conditioned medium, with morphological and E-cadherin and ZEB1 expression changes suggesting epithelial-to-mesenchymal transition. TAF-derived cytokines may increase PitNET aggressiveness, alter angiogenesis and induce epithelial-to-mesenchymal transition changes. Pasireotide's inhibitory effect on TAF-derived cytokines suggest that this effect may play a role in its anti-tumour effects.

A Case of Invasive Sinonasal Carcinosarcoma: The Importance of Early Detection.

Sinonasal carcinosarcomas represent rare neoplasms, with aggressive character and unfavourable prognosis. We present a case of extensive sinonasal carcinosarcoma extending into the anterior cranial fossa and into the orbit and also a review of the current international literature regarding this rare yet aggressive neoplasm. There is currently a lack of specific guidelines on the optimal management of sinonasal carcinosarcoma and the treatment represents a challenge for the clinician. The key message that we would like to disseminate to our colleagues is the importance of suspicion and early detection, as well as the necessity to adopt a holistic approach when counselling patients.