Validation of the TNM-8 AJCC classification for HPV-positive oropharyngeal cancers in patients undergoing trans-oral robotic surgery.

High-risk human papillomaviruses (HPV) are associated with some oropharyngeal squamous cell carcinomas (OPSCC). HPV-OPSCC have better survival outcomes compared to HPV negative tumours. The new TNM-8 AJCC staging (2018) is based on ICON-S data with 98% of patients treated with primary chemoradiation. To validate the TNM-8 AJCC classification in HPV-OPSCC treated primarily with surgery (trans-oral robotic surgery or open). There were 102 patients with HPV-OPSCC treated between July 2009 and December 2014 at the Royal Adelaide Hospital. The median age was 57 years (range: 38-83) and mostly males (84.5%). 27.2% were active smokers and 50.5% reformed smokers. Early T-stage cancer in 72.8%. Primary treatment was surgery & adjuvant therapy (70%) while primary chemoradiation (30%). Survival analyses were performed for the 7th and 8th AJCC systems. The reclassification to the AJCC 8th edition staging system resulted in a change of 54 patients from stage 4 to stages 1 and 2. This was mainly an effect of changes with N2a and N2b nodal disease being reclassified to N1. Survival outcomes were comparable with the ICON-S data. The new TNM-8 classification is, therefore, validated in a cohort treated, predominantly, with primary surgery and adjuvant therapy.

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Transoral robotic narrow field oropharyngectomy for tumours of the parapharyngeal space.

The advent of transoral robotic surgery (TORS) has allowed transoral approaches for parapharyngeal space (PPS) tumours to be re-evaluated. It provides enhanced visualisation and instrument access for appropriate tumours. We describe a specific technique, TORS narrow-field oropharyngectomy, that is ideal for benign PPS tumours which have been violated by intra-oral biopsy or incision and drainage. This allows the contaminated, overlying oropharyngeal mucosa to be resected en-bloc with the PPS tumour, reducing the risk of local recurrence. This technique provides a window into the PPS, improving visualisation of underlying neurovascular structures as well as the tumour. This reduces the risk of tumour spillage and leads to superior vascular access and haemorrhage control. This technique is only applicable to PPS tumours that are appropriate for transoral approaches and is specifically designed for those selected patients that have been placed at risk of seeding or local scarring by intra-oral procedures prior to definitive resection. We present two such cases: a 38-year-old male with a PPS inflammatory cyst and a 66-year-old female with a PSS pre-styloid Schwannoma.

How I do it: transnasal retraction during transoral robotic oropharyngeal resection.

Collapse of the resection plane presents a frustrating problem during transoral robotic resection, in a situation already typified by limited vision and access for instruments. We present a quick and cost-effective retraction technique to effectively mitigate this issue and increase the ease and reliability of robotic oropharyngeal resection. This technique utilises a simple transnasal apparatus to create greater exposure of the resection plane. A Y-suction catheter is inserted into the oropharynx via the nasal cavity. A silk suture is then used to attach it to the oropharyngeal resection specimen. When pulled from the nasal cavity, this apparatus adds a non-intrusive, tremor-free fixation point that pulls the resected specimen along a unique cephalo-posterior vector. This significantly improves access and vision of the desired dissection plane. The entire process takes approximately 1-2 min per side to properly execute. It can be adapted for various pathologies and subsites of the oropharynx. This transnasal technique is a simple, minimally invasive, and inexpensive method for improving wound tension during transoral oropharyngeal resection.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

Elective neck dissection for the node-negative neck during salvage laryngectomy: an analysis of survival outcomes and complication rates.

OBJECTIVES: This study aimed to evaluate the effect of neck dissection on survival and complication rates in patients with no clinical or radiological evidence of cervical nodal disease (N0) undergoing salvage laryngectomy. METHODS: A retrospective study was conducted of patients with squamous cell carcinoma of the larynx following primary radiotherapy that required salvage laryngectomy. Disease-free and overall survival rates were compared over three years using Kaplan-Meier analysis. Pharyngocutaneous fistula rate, hospitalisation length and the requirement for further surgical intervention were also compared across cohorts. RESULTS: Twenty-three cases met the inclusion criteria (17 neck dissections, 6 undissected). No significant differences in survival outcomes were identified. One patient who underwent neck dissection for advanced, recurrent transglottic squamous cell carcinoma showed evidence of occult lymph node metastases. Fistula rates did not differ significantly between dissected and non-dissected groups; however, two patients required surgical repair of post-operative pharyngocutaneous fistula following neck dissection. CONCLUSION: In this study, elective neck dissection did not appear to alter survival outcomes or complication rates during salvage laryngectomy. Given the small but significant risk of occult neck metastases, its true value remains unclear.

The acceptance and adoption of transoral robotic surgery in Australia and New Zealand.

Transoral robotic surgery (TORS) provides improved access to head and neck subsites resulting in well-validated functional and oncological outcomes, but access to and cost of robotic platforms can limit their use. Evidence suggests TORS is increasingly being adopted globally, but there is a paucity of data on the adoption and diffusion of TORS in Australia and New Zealand. A cross-sectional analysis was performed. An online survey was distributed to otolaryngologists and head and neck surgeons through three different Australian and New Zealand specialty membership databases. A 5-point Likert scale based on a Unified Theory of Acceptance and Use of Technology (UTAUT) model was incorporated to assess barriers and facilitators to adoption. 77 respondents completed the survey. 43.6% of head and neck surgeons had performed TORS. The most common cases were lateral oropharyngectomy (35.9%), base of tongue resection (33.3%), tongue base mucosectomy (28.2%), supraglottic laryngectomy (15.4%) and TORS for obstructive sleep apnoea (12.8%). Perceived barriers to adoption were high costs, access to and availability of the robotic platform and limited training opportunities. This study provides evidence of adoption of TORS in Australia and New Zealand; however, there is a perception that significant barriers to adoption persist. Results from this study may help guide decisions on how we train and license surgeons in the era of this technology.

Reviewing indications for panendoscopy in the investigation of head and neck squamous cell carcinoma.

BACKGROUND: The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer. METHOD: A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.

A comparison of oncological outcomes between transoral surgical and non-surgical treatment protocols in the management of oropharyngeal squamous cell carcinoma.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes. METHODS: This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated. RESULTS: Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group. CONCLUSION: This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Surgical anatomy of the spinal accessory nerve: review of the literature and case report of a rare anatomical variant.

OBJECTIVE: To evaluate the prevalence of variations in the anatomical route of the spinal accessory nerve from the base of the skull to the point where it enters the trapezius muscle. A case report is used to demonstrate an example of a rare but clinically important anatomical variant of this nerve. METHODS: An independent review of the literature using Medline, PubMed and Q Read databases was performed using combinations of terms including 'spinal accessory nerve', 'anatomy', 'surgical anatomy', 'anatomical variant', 'cranial nerve XI' and 'shoulder syndrome'. RESULTS: Our report demonstrates marked variation in spinal accessory nerve anatomy. At the point of crossing over the internal jugular vein, the spinal accessory nerve passes most commonly laterally (anterior) to the internal jugular vein. The reported incidence of this lateral relationship varies from 67 to 96 per cent. The nerve can also pierce the internal jugular vein, as demonstrated in our case study, with incidence ranging from 0.48 to 3.3 per cent. CONCLUSION: Anatomical variations of the spinal accessory nerve are not uncommon, and it is important for the surgeon to be aware of such variations when undertaking surgery in both the anterior and posterior triangles of the neck.

Phenotype analysis impacts testing strategy in patients with Currarino syndrome.

Currarino syndrome (OMIM 175450) presents with sacral, anorectal, and intraspinal anomalies and presacral meningocele or teratoma. Autosomal dominant loss-of-function mutations in the MNX1 gene cause nearly all familial and 30% of sporadic cases. Less frequently, a complex phenotype of Currarino syndrome can be caused by microdeletions of 7q containing MNX1. Here, we report one familial and three sporadic cases of Currarino syndrome. To determine the most efficient genetic testing approach for these patients, we have compared results from MNX1 sequencing, chromosomal microarray, and performed a literature search with analysis of genotype-phenotype correlation. Based on the relationship between the type of mutation (intragenic MNX1 mutations vs 7q microdeletion) and the presence of intellectual disability, growth retardation, facial dysmorphism, and associated malformations, we propose a testing algorithm. Patients with the classic Currarino triad of malformations but normal growth, intellect, and facial appearance should have MNX1 sequencing first, and only in the event of a normal result should the clinician proceed with chromosomal microarray testing. In contrast, if growth delay and/or facial dysmorphy and/or intellectual disability are present, chromosomal microarray should be the first method of choice for genetic testing.

Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.

Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions and the associated human psychopathology, 22 individuals with genomic disruption of MBD5 (translocation, point mutation and deletion) were identified through whole-genome sequencing or cytogenomic microarray at 11 molecular diagnostic centers. The genomic impact ranged from a single base pair to 5.4 Mb. Parents were available for 11 cases, all of which confirmed that the rearrangement arose de novo. Phenotypes were largely indistinguishable between patients with full-segment 2q23.1 deletions and those with intragenic MBD5 rearrangements, including alterations confined entirely to the 5'-untranslated region, confirming the critical impact of non-coding sequence at this locus. We identified heterogeneous, multisystem pathogenic effects of MBD5 disruption and characterized the associated spectrum of psychopathology, including the novel finding of anxiety and bipolar disorder in multiple patients. Importantly, one of the unique features of the oldest known patient was behavioral regression. Analyses also revealed phenotypes that distinguish MBD5 disruptions from seven well-established syndromes with significant diagnostic overlap. This study demonstrates that haploinsufficiency of MBD5 causes diverse phenotypes, yields insight into the spectrum of resulting neurodevelopmental and behavioral psychopathology and provides clinical context for interpretation of MBD5 structural variations. Empirical evidence also indicates that disruption of non-coding MBD5 regulatory regions is sufficient for clinical manifestation, highlighting the limitations of exon-focused assessments. These results suggest an ongoing perturbation of neurological function throughout the lifespan, including risks for neurobehavioral regression.

Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype.

The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion.

Molecular studies of segmental aneusomy: FISHing for the atypical cry in del(5)(p15.3).

We report a newborn male with multiple congenital anomalies including growth retardation, hypotonia, dysmorphic facies, widely-spaced nipples, micropenis, cryptorchidism, optic nerve hypoplasia, heart disease, and a striking, high-pitched cry. Chromosome analysis revealed de novo partial trisomy 11q due to a der(5)t(5;11)(p15.3;q22). Fluorescence in situ hybridization (FISH) showed loss of the 5p telomere signal on the der(5) chromosome, indicating the infant has partial monosomy 5p in addition to partial trisomy 11q. Among cases involving trisomy 11q, an unusual cry has only been documented in the presence of a der(5)t(5p;11q). This apparent dependence of the abnormal cry on monosomy 5p suggested the same genetic mechanism that occurs in Cri du chat syndrome (CDCS) may be responsible for the atypical cry in der(5)t(5p;11q) individuals. Neither a commercial CDCS probe (LSI D5S23, D5S721) nor a series of BAC clones encompassing distal regions implicated in the CDCS-associated cat-cry were deleted in our patient. These results suggest a second cry-modifying locus maps telomeric to BAC RP11-94J21 in band 5p15.33. This locus may not only cause the abnormal cry in individuals with a der(5)t(5p;11q) but could also contribute to the phenotypic variability and discordant mapping studies observed for CDCS.

Cementoplasty and the oncologic population.

The first and only description of percutaneous cementoplasty, to date, has been described in the French medical literature in 1994. In this series of 12 cases, radiologists successfully instilled a cement derivative into the acetabulum under fluoroscopic control. As in these cases, the major indication for cementoplasty is to provide pain control and stabilization of an osteolytic lesion. Potential complications include physical or thermal damage to the adjacent neurovascular structures, either during needle positioning or from cement leakage, respectively. Although no absolute contraindications exist, one should proceed cautiously in patients with coagulopathies. Results may be suboptimal as well in patients with pathologic fractures.

The incidence of sacroiliac joint disease in patients with low-back pain.

PURPOSE: The clinical presentation of intervertebral disc, facet joint, nerve root, and sacroiliac (SI) joint diseases are often indistinguishable. SI joint arthritis likely accounts for a significant proportion of what is called "low-back pain" or "sciatica." Our goal was to determine the incidence of SI joint arthritis in patients with this presentation. METHODS: Computed tomographic (CT) scans of the lumbosacral spine (LSS) of patients referred with low-back pain, sciatica, spinal stenosis or disc pathology were gathered over a 3-month period. Scans were retrospectively reviewed by 2 independent readers for SI joint arthritis. When there was disagreement, the 2 readers reviewed the case and reached a concensus opinion. SI joint arthritis was considered to be present if subchondral sclerosis, osteophytosis, or cartilage loss was noted on the CT scan. RESULTS: The SI joint(s) were visualized by both readers on 64 LSS CT scans performed in 29 women and 35 men, mean age 52 years. By the aforementioned criteria, 16 SI joints (25%) were considered normal by both readers. In 48 cases (75%), there was evidence of osteoarthritis. The diagnosis of osteoarthritis was made by concensus opinion in 8 of these 48 cases (16%). CONCLUSION: There is a relatively high incidence of SI joint arthritis in patients undergoing evaluation for "low-back pain" or "sciatica." Hence, SI joint arthritis should be considered a possible diagnosis in these patients.

Clinics in diagnostic imaging (40). Iliotibial band syndrome.

A 51-year-old male cyclist presented with a mass over the lateral portion of his knee. MR scans showed a cystic collection deep to the iliotibial band (ITB). Diagnosis of the ITB syndrome and its differentiation from other cause of painful lateral knee masses, such as meniscal cyst, lateral collateral ligament injury and Segond fracture, are discussed.

Bilateral radial head and neck fractures.

Isolated radial head and neck fractures comprise 1-2% of all fractures seen by physicians. Although bilateral distal radial fractures have been documented, primarily in gymnasts, no literature is present on bilateral radial head or neck fractures. This article presents two such patients who sustained nondisplaced bilateral radial head or neck fractures resulting from falls on outstretched hands. The detection, classification, and treatment options of radial head fractures is reviewed.