Publications by authors named "James Wykes"

26 Publications

  • Page 1 of 1

Dentoalveolar outcomes in maxillary reconstruction: A retrospective review of 85 maxillectomy reconstructions.

ANZ J Surg 2021 Jun 14. Epub 2021 Jun 14.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: Although microvascular free flaps are often used to reconstruct maxillary defects, dentoalveolar rehabilitation is arguably less common despite its importance to midface function and aesthetics. The aim of this study is to review the contemporary management of maxillary defects in a single quaternary referral institution to identify factors that assist or impede dentoalveolar rehabilitation.

Methods: A retrospective review of maxillary reconstructions performed between February 2017 and December 2020 was performed. Patient characteristics, defect classification, operative techniques, complications and dentoalveolar outcomes were recorded.

Results: A total of 85 maxillary reconstructions were performed in 73 patients. Of the 64 patients where dental rehabilitation was required, 31 received a functional denture (48%) with 24 (38%) being implant-retained. Significant predictors of successful rehabilitation included the use of virtual surgical planning (VSP; 86% vs. 25%, p < 0.001), preoperative prosthodontic assessment (82% vs. 21%, p < 0.001), prefabrication (100% vs. 40%, p = 0.002) and use of the zygomatic implant perforator flap technique (100% vs. 39%, p = 0.001). Preoperative prosthodontic consultation was associated with 21-fold increase in the odds of rehabilitation (odds ratio 20.9, 95% confidence interval 6.54-66.66, p < 0.005).

Conclusion: Preoperative prosthodontic evaluation, VSP and reconstructive techniques developed to facilitate implant placement are associated with increased dental rehabilitation rates. Despite using an institutional algorithm, functional dentures are frequently prevented by factors including soft tissue constraints, disease recurrence and patient motivation.
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http://dx.doi.org/10.1111/ans.17001DOI Listing
June 2021

Targeted ordering of investigations reduces costs of treatment for surgical inpatients.

Int J Qual Health Care 2021 May;33(2)

Department of Surgery, Wollongong Public Hospital, 252 Loftus Street, Wollongong, NSW 2500, Australia.

Background: Laboratory testing forms an important part of diagnostic investigation in modern medicine; however, the overuse of 'routine blood tests' can result in significant potential harm and financial cost to the patient and the healthcare system. In 2018, a new protocol targeting the ordering of investigations was implemented within the General Surgical Teams of Wollongong Hospital in New South Wales, an Australian tertiary referral hospital, to reduce the number of 'routine blood tests' as a quality improvement initiative.

Objective: To identify whether there was a reduction in the number of 'routine blood tests' and associated costs following implementation of the new protocol.

Methods: The protocol involved regular review of the laboratory investigations being ordered for the following day with a senior team member. The medical records of all patients admitted under the general surgery service at Wollongong Hospital were retrospectively reviewed over two 10-week periods in 2017 and 2018 (control and study, respectively). The casemix was categorized into Minor, Intermediate, Major or Unscored, depending on case complexity coding.

Results: A total of 838 patients were identified during the control period (2017) and 805 patients were identified during the study period (2018). Ten thousand and thirty tests were included in the control period, compared to 8610 over the study period, resulting in a 16% (or greater) reduction in 'routine blood tests' per patient, per day of admission and a 6% reduction in costs in the study group (P < 0.001).

Conclusion: Targeted ordering of investigations with personalized education and feedback to junior staff during review of clinical status of each patient as a part of normal workflow can reduce inappropriate ordering of 'routine blood tests' and associated costs to the patient and the healthcare system.
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http://dx.doi.org/10.1093/intqhc/mzab083DOI Listing
May 2021

Microvascular reconstruction of head and neck defects in the elderly.

ANZ J Surg 2021 05 6;91(5):969-974. Epub 2021 Apr 6.

Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney Head and Neck Cancer Institute, Sydney, New South Wales, Australia.

Background: Microvascular free-flap reconstruction of the head and neck is a common technique utilized across many ages. The purpose of this study was to identify if advanced age or comorbidity was associated with worse post-operative outcomes in patients undergoing free-flap reconstruction.

Methods: A retrospective analysis was performed on 344 consecutive patients undergoing free-flap surgery of the head and neck. Demographic, clinical and pathological factors were considered along with Charlson Comorbidity Index (CCI) scores and American Society of Anesthesiologists (ASA) status. Logistic regression analysis was used to investigate the association of age, CCI or ASA with post-operative complications.

Results: Elderly patients (≥75 years) had a higher overall complication rate (odds ratio (OR) 1.7, P = 0.04) that was restricted to medical complications (OR 2.1, P = 0.05) and not surgical complications (OR 1.4, P = 0.14). Reconstructions of defects from cutaneous malignancy predominated in the elderly cohort (48% versus 29%, P < 0.01), but there was no difference in complication rate when cutaneous or mucosal subgroups were separated by age. ASA IV status was weakly associated with surgical complications (OR 3.89, P = 0.053), but CCI and elderly age were not associated with any outcome. Median length of stay was similar between age groups.

Conclusion: Free-flap reconstruction in older patients was associated with increased medical complications, and surgical complications were weakly associated with ASA status. Advanced age or comorbidity should not preclude microvascular reconstruction, but comorbid status should be optimized pre-operatively and factors predisposing to medical complications minimized where possible.
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http://dx.doi.org/10.1111/ans.16771DOI Listing
May 2021

Tracheostomy in free-flap reconstruction of the oral cavity: can it be avoided? A cohort study of 187 patients.

ANZ J Surg 2021 06 6;91(6):1246-1250. Epub 2021 Apr 6.

Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: Head and neck surgeons are moving away from routine tracheostomy in free-flap reconstruction. We reviewed prophylactic tracheostomy use in patients undergoing oral cavity or oropharynx free-flap reconstruction to identify patient groups who avoided tracheostomy. Secondary aims were to describe complications associated with and without tracheostomy.

Methods: A retrospective cohort study was undertaken, using a prospectively maintained database. Inclusion criteria was free-flap reconstruction for an oral cavity or oropharyngeal defect, excluding partial or total laryngectomy. Variables collected included demographics, comorbidity, American Society of Anesthesiologists grade, Charlson Comorbidity Index, tumour site and subsite, extent of resection, surgery duration, tracheostomy, complications, return to theatre and re-intubation.

Results: A total of 344 head and neck free-flap reconstructions were performed between January 2017 and July 2019. A total of 164 (87.7%) oral cavity and 23 (12.3%) oropharyngeal reconstructions were included totalling 187 free flaps. A total of 107 (57.2%) were males and 80 (42.8%) females, mean age 62.4 years (range 21-89). Of 187 patients, 100 (53.5%) underwent prophylactic tracheostomy at time of reconstruction. Longer operative time (P < 0.001), resection site (P < 0.001), number of subsites resected (P = 0.007), segmental mandibulectomy (P = 0.04), lip-split (P = 0.05), floor of mouth resection (P < 0.001), lingual release (P = 0.007), glossectomy (P < 0.001), extent of tongue resection (P < 0.001), extent of hard palate resection (P = 0.04), soft palate resection (P < 0.001) and double free-flap reconstruction (P = 0.04) were associated with tracheostomy use.

Conclusion: A personalized approach to postoperative airway management allowed almost half of our cohort to avoid tracheostomy. In high-volume institutions with the necessary expertise and support, appropriately selected patients may be safely managed without routine tracheostomy.
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http://dx.doi.org/10.1111/ans.16762DOI Listing
June 2021

Validated specialty-specific models for multi-disciplinary microsurgery training laboratories: a systematic review.

ANZ J Surg 2021 06 15;91(6):1110-1116. Epub 2021 Mar 15.

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Background: Laboratory simulation is increasingly important for teaching microsurgical skills. Training microsurgeons of different specialties within the same simulation laboratory increases efficiency of resource use. For maximal benefit, simulations should be available for trainees to practice specialty-specific, higher-order skills. Selection of appropriate simulations requires knowledge of the efficacy and validity of the numerous described laboratory models. Here we present a systematic review of validated training models that may serve as useful adjuncts to achieving competency in specialty elements of microsurgery, and appraise the evidence behind them.

Methods: In setting up a multi-disciplinary microsurgery training course, we performed a systematic review according to preferred reporting items for systematic reviews and meta-analyses guidelines. EMBASE, MEDLINE, Cochrane and PubMed databases were searched for studies describing validated, microscope-based, specialty-specific simulations, and awarded a level of evidence and level of recommendation based on a modified Oxford Centre for Evidence-Based Medicine classification.

Results: A total of 141 papers describing specialty-specific microsimulation models were identified, 49 of which included evidence of validation. Eleven were in the field of neurosurgery, 21 in otolaryngology/head and neck surgery, two in urology/gynaecology and 15 plastic and reconstructive surgery. These papers described synthetic models in 19 cases, cadaveric animals in 10 cases, live animals in 12 cases and human cadaveric material in 10 cases.

Conclusion: Numerous specialty-specific models for use in the microscope laboratory are available, but the quality of evidence for them is poor. Provision of models that span numerous specialties may encourage use of a microscope lab whilst still enabling more specific skills training over a 'one-size-fits-all' approach.
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http://dx.doi.org/10.1111/ans.16721DOI Listing
June 2021

Oligometastases in head and neck carcinoma and their impact on management.

ANZ J Surg 2021 Feb 26. Epub 2021 Feb 26.

Department of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Historically, patients with head and neck squamous cell carcinoma (HNSCC) with distant metastases were regarded as palliative. Oligometastasis (OM) refers to patients with a limited number of distant metastatic deposits. Treatment of patients with OMs has been reported in patients with lung, colon, breast, prostate and brain malignancies. Selected patients with oligometastatic HNSCC have a higher probability of durable disease control and cure and these patients should be treated aggressively. Treatment options for patients with HNSCC OMs include single or combinations of the three arms of cancer treatment, that is surgery, radiotherapy and chemotherapy/immunotherapy. To date, there are limited studies reporting the management of OM with head and neck malignancy. This review will give insights into the management of OMs in HNSCC.
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http://dx.doi.org/10.1111/ans.16622DOI Listing
February 2021

Maxillofacial reconstruction with prefabricated prelaminated osseous free flaps.

ANZ J Surg 2021 03 6;91(3):430-438. Epub 2021 Jan 6.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: The prefabricated fibula flap is an advanced method of occlusal-based reconstruction that combines placement of osseointegrated dental implants with prelamination, using a split skin graft on the fibula, weeks prior to the definitive reconstruction. This approach is resource intensive but has several advantages including eliminating the delay from reconstruction to dental rehabilitation.

Methods: A retrospective cohort study of all prefabricated fibula flaps used for mandible and maxillary reconstruction from 2012 to 2020 was performed. Outcome measures were implant survival, implant utilization and functional dental rehabilitation.

Results: A total of 17 prefabricated fibula flaps were performed including two analogue and 15 digital plans. There were nine maxillary and eight mandibular reconstructions, of which 11 were primary and seven were secondary. There were no free flap failures. A total of 65 implants were placed (average 3.8, median 3 implants). There was one implant failure at 6 years giving a 1.5% failure rate. There was 91% implant utilization and 94% functional dental rehabilitation.

Conclusion: The prefabricated fibula flap provides outstanding dental rehabilitation in well-selected patients.
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http://dx.doi.org/10.1111/ans.16541DOI Listing
March 2021

Transoral robotic free flap inset in oropharyngeal cancer.

Clin Otolaryngol 2021 May 9;46(3):642-644. Epub 2021 Jan 9.

Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

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http://dx.doi.org/10.1111/coa.13696DOI Listing
May 2021

Occlusal-based planning for dental rehabilitation following segmental resection of the mandible and maxilla.

ANZ J Surg 2021 03 27;91(3):451-452. Epub 2020 Nov 27.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Reconstruction of the maxilla and mandible incorporating a dental prosthesis supported by dental implants is a complex process but has tremendous benefit to patient rehabilitation following ablative procedures. This study presents a protocol that can be used to aid other institutions to provide the highest standard of reconstruction.
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http://dx.doi.org/10.1111/ans.16441DOI Listing
March 2021

Nodal metastasis size predicts disease-free survival in cutaneous head and neck squamous cell carcinoma involving the parotid but not cervical nodes.

ANZ J Surg 2020 12 11;90(12):2537-2542. Epub 2020 Nov 11.

Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.

Background: The 8th edition American Joint Committee on Cancer nodal (N) staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is largely based on lymph node metastasis size, despite conflicting data in the literature. This study aimed to investigate the prognostic significance of largest node size in cSCCHN.

Methods: Retrospective analysis of 94 patients undergoing curative-intent treatment for nodal cSCCHN with surgery ± radiotherapy at Liverpool Hospital, Sydney, Australia was conducted. Survival outcomes were assessed using multivariate Cox regression. The primary end point was disease-free survival (DFS). Objective measures of model performance were used in exploratory analyses to identify optimal size thresholds for predicting survival.

Results: Nodal metastasis size significantly predicted DFS on multivariate analysis (hazard ratio 1.24; 95% confidence interval 1.06-1.46; P = 0.008). This prognostic impact occurred predominantly in parotid metastases (hazard ratio 1.27; 95% confidence interval 1.07-1.51; P = 0.006); each 1 cm increase in size increased the risk of recurrence or death by 27%, irrespective of the number of involved nodes. In parotid metastases, size thresholds of ≤3, 3-4.5 and >4.5 cm optimized prognostic discrimination. Extranodal extension (ENE) was associated with decreased DFS in nodes ≤3 cm in size (P = 0.025), but not in those >3 cm (P = 0.744).

Conclusion: Size is an important prognostic factor in cSCCHN with parotid metastases, with optimal thresholds of ≤3, >3-4.5 and >4.5 cm. The prognostic impact of ENE was seen only in nodal metastases ≤3 cm in size. These results may have important implications for node size thresholds and inclusion of ENE in the American Joint Committee on Cancer N staging categories.
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http://dx.doi.org/10.1111/ans.16413DOI Listing
December 2020

Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma.

ANZ J Surg 2020 09 5;90(9):1727-1732. Epub 2020 Aug 5.

Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.

Background: Lymphovascular invasion (LVI) is an established adverse prognostic factor in many cancers, however, there are few studies assessing its significance in papillary thyroid carcinoma (PTC). We aimed to determine if LVI is an independent prognostic factor in PTC.

Methods: We conducted a single institution retrospective analysis of 610 patients with PTC treated between 1987 and 2016. LVI was defined as the presence or absence of cancer cells in blood vessels and/or lymphatics on histopathology. Multivariate Cox regression analysis was used to evaluate the association between LVI and recurrence-free survival (RFS).

Results: The study cohort included 481 (78.9%) females and 129 (21.1%) males, with a median age of 47.6 years and median follow-up of 3.4 years. LVI was present in 56 (9.2%) patients and was associated with nodal metastases (P < 0.001), extrathyroidal extension (P < 0.001), extranodal extension (P < 0.001), multifocality (P = 0.018) and microscopic positive margins (P < 0.001). On univariate analysis, LVI was associated with reduced RFS (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.3-4.3; P = 0.007). However, after adjusting for nodal stage (pN0, pN1a, pN1b) there was no association between LVI and RFS (HR 1.3; 95% CI 0.7-2.5; P = 0.398). Similar results were obtained in full multivariate models adjusting for additional prognostic factors (HR 1.2; 95% CI 0.6-2.4; P = 0.627).

Conclusion: LVI is strongly associated with other adverse prognostic factors in PTC, particularly the presence and extent of nodal metastases. However, after adjusting for these, LVI is not an independent predictor of recurrence.
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http://dx.doi.org/10.1111/ans.16202DOI Listing
September 2020

Sentinel Node Biopsy in 105 High-Risk Cutaneous SCCs of the Head and Neck: Results of a Multicenter Prospective Study.

Ann Surg Oncol 2019 Dec 3;26(13):4481-4488. Epub 2019 Oct 3.

Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia.

Background: Regional nodal metastases from cutaneous squamous cell carcinoma (cSCC) is strongly associated with a poor prognosis, but these metastases are difficult to predict clinically. Sentinel node biopsy (SNB) has been used for a wide range of malignancies to assess for regional nodal metastasis, but is not widely used for cSCC.

Methods: Patients presenting with high-risk cSCC of the head and neck with clinically N0 necks were offered SNB at the time of primary cSCC excision or secondary wide local excision. Patients with positive sentinel nodes were offered completion lymph node dissection, and all the patients were followed up at regular intervals for up to 5 years.

Results: In this study, 105 lesions underwent SNB, and 10 sentinel nodes (9.5%) were positive. In an additional five patients, regional recurrence developed after a negative sentinel node, with a total subclinical nodal metastasis rate of 14.3%. Nodal metastases were significantly associated with reduced disease-specific survival. The significant predictors of metastasis were four or more high-risk features or tumors with a concurrent invasion deeper than 5 mm and PNI.

Conclusion: For high-risk cSCC, SNB is a safe and feasible staging technique. The total number of high risk features and certain combinations of high-risk features predicted metastasis better than individual high-risk features.
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http://dx.doi.org/10.1245/s10434-019-07865-zDOI Listing
December 2019

The extent of extrathyroidal extension is a key determinant of prognosis in T4a papillary thyroid cancer.

J Surg Oncol 2019 Nov 26;120(6):1016-1022. Epub 2019 Aug 26.

Department of Head and Neck Surgery, Liverpool Hospital, NSW, Australia.

Background And Objectives: In papillary thyroid cancer (PTC), the adverse prognostic impact of extrathyroidal extension (macro-ETE) invading the subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a disease) is well established. We investigated whether the extent of macro-ETE, defined as "limited" with single structure involvement (lim-ETE) and "extensive" with multiple structures involved (ext-ETE), influences prognosis in T4a PTC.

Methods: A retrospective analysis of 610 patients with PTC identified 39 with T4a disease, including 26 with lim-ETE and 13 with ext-ETE. Univariate Cox regression was used to assess the relationship between the extent of macro-ETE and recurrence-free survival (RFS).

Results: Ext-ETE was associated with a five times increased risk of recurrence compared to lim-ETE (HR 5.0, P < .030), with or without adjustment for radioactive iodine administration and after adjustment for margin status (HR 4.7; P = .041). A low-risk subset of T4a disease comprising of patients aged less than 55 years with lim-ETE and clear margins accounted for one-third of the cohort and demonstrated an excellent 5-year RFS of 92%.

Conclusions: The extent of macro-ETE appears to be an important determinant of prognosis in T4a PTC. A low-risk subset of T4a disease exists with an excellent prognosis.
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http://dx.doi.org/10.1002/jso.25683DOI Listing
November 2019

Number of nodal metastases and prognosis in metastatic cutaneous squamous cell carcinoma of the head and neck.

ANZ J Surg 2019 07 11;89(7-8):863-867. Epub 2019 Apr 11.

Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.

Background: Existing prognostic systems for metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) do not discriminate between the number of involved nodes beyond single versus multiple. This study aimed to determine if the number of metastatic lymph nodes is an independent prognostic factor in metastatic cSCCHN and whether it provides additional prognostic information to the American Joint Committee on Cancer (AJCC) staging.

Methods: We retrospectively analysed 101 patients undergoing curative intent treatment for metastatic cSCCHN to parotid and/or neck nodes by surgery +/- radiotherapy at Liverpool Hospital, Sydney, Australia. The impact of number of nodal metastases on disease-free survival (DFS) and risk of distant metastases was assessed using multivariate Cox regression.

Results: The mean number of nodal metastases was 2.5 (range 1-12). On multivariate analysis, increasing number of nodal metastases significantly predicted reduced DFS (hazard ratio 1.17; 95% confidence interval 1.05-1.30; P = 0.004), with a 17% increased risk of recurrence or death for each additional node. This remained significant in multivariate models adjusted for AJCC 8th edition nodal and TNM stages. Number of nodal metastases was also associated with risk of distant metastatic failure (hazard ratio 1.21; 95% confidence interval 1.05-1.39; P = 0.009).

Conclusion: Increasing number of nodal metastases is associated with decreased DFS and increased risk of distant metastases in metastatic cSCCHN, with a cumulative risk increase with each additional node. It provides additional prognostic information to the AJCC staging, which may be improved by incorporating information on the number of nodal metastases beyond the current single versus multiple distinction.
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http://dx.doi.org/10.1111/ans.15086DOI Listing
July 2019

Microscopic positive margins strongly predict reduced disease-free survival in pT4a papillary thyroid cancer.

Head Neck 2019 08 12;41(8):2549-2554. Epub 2019 Mar 12.

Department of Head and Neck Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia.

Background: Although microscopic positive margins appear to have no independent prognostic impact in papillary thyroid cancer (PTC), this may not be the case in pT4a tumors.

Methods: Retrospective analysis of 610 patients with PTC, 39 with pT4a tumors, to determine if microscopic positive margins impact disease-free survival (DFS) in pT4a PTC.

Results: On univariate analysis, microscopic positive margins were not associated with reduced DFS in patients with no extrathyroidal extension (ETE) (hazard ratio [HR], 1.7; P = 0.32), microscopic ETE (HR, 1.6; P = 0.36), or macroscopic ETE limited to strap muscles (HR, 1.2; P = 0.87). In contrast, microscopic positive margins were associated with reduced DFS in T4a disease (HR, 4.1; P = 0.04). Disease recurrence was nodal, distant, or biochemical, and did not occur directly at the site of positive margins.

Conclusion: Although microscopic positive margins do not influence DFS in the majority of patients with PTC, they are associated with a fourfold increased risk of recurrence in pT4a disease.
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http://dx.doi.org/10.1002/hed.25730DOI Listing
August 2019

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck.

Head Neck 2019 06 19;41(6):1591-1596. Epub 2019 Jan 19.

Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.

Background: The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases.

Methods: Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease-specific and overall survival (OS) using the proportion of variation explained and Harrell's C-index.

Results: In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease-specific survival for both N and TNM stages, and OS by TNM stage.

Conclusions: The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.
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http://dx.doi.org/10.1002/hed.25599DOI Listing
June 2019

Response to Re: Microscopic positive margins in papillary thyroid cancer do not impact disease recurrence.

ANZ J Surg 2018 11;88(11):1212-1213

Department of Breast, Endocrine, Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/ans.14799DOI Listing
November 2018

The Prognostic Impact of Tumor Size in Papillary Thyroid Carcinoma is Modified by Age.

Thyroid 2018 08 30;28(8):991-996. Epub 2018 Jul 30.

1 Department of Head and Neck Surgery, Liverpool Hospital , New South Wales, Sydney, Australia .

Background: Although the importance of tumor size in papillary thyroid cancer (PTC) is well established, there is no research investigating whether age modifies the impact of tumor size, and there is conflicting evidence regarding optimal size thresholds for prognostic discrimination. We aimed to verify that tumor size is an independent prognostic factor in PTC, investigate the impact of patient age, and identify optimal size cutoffs for risk stratification using objective measures of model performance.

Methods: A retrospective analysis of 574 patients with PTC, using multivariate Cox regression models to test the impact of tumor size on recurrence-free survival (RFS). Subgroup analyses were performed in patients aged <55 and ≥55 years. Exploratory analyses to identify optimal size cutoffs for prognostic discrimination were performed using the proportion of variation explained (PVE) and Harrell's C-index.

Results: Tumor size predicted RFS on multivariate analysis in the overall study cohort (hazard ratio [HR] 1.16; [95% confidence interval (CI)1.01-1.34]; p = 0.038). In subgroup analysis, there was no association between tumor size and RFS in patients aged <55 years (HR 1.11; [CI 0.89-1.38]; p = 0.362). In contrast, size was an independent predictor of RFS in patients aged ≥55 years (HR 1.52; [CI 1.11-2.07]; p = 0.009). In this subgroup, an optimal size threshold of >2 cm versus ≤2 cm (HR 5.24; [CI 2.30-11.92]; p < 0.001; PVE: 36%; C-index: 0.66) provided the greatest prognostic discrimination. There was no incremental improvement in prognostic value by further stratification of size.

Conclusion: In our PTC cohort, the impact of tumor size on RFS was limited to patients aged ≥55 years. A single size threshold of 2 cm maximized prognostic discrimination with tumors >2 cm associated with a five times higher risk of recurrence than those ≤2 cm. These findings need to be validated in independent large cohorts and the potential management and staging implications further studied.
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http://dx.doi.org/10.1089/thy.2017.0607DOI Listing
August 2018

Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients.

BMC Cancer 2018 Jun 1;18(1):624. Epub 2018 Jun 1.

Sydney Medical School, The University of Sydney, Sydney, Australia.

Background: This study examined the prognostic significance of microtubule-associated protein light chain 3B (LC3B) expression in oropharyngeal and oral cavity squamous cell carcinoma (SCC). The prognostic significance of LC3B expression in relation to human papillomavirus (HPV) status in oropharyngeal SCC was also examined.

Methods: Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded oropharyngeal (n = 47) and oral cavity (n = 95) SCC tissue blocks from patients with long-term recurrence and overall survival data (median = 47 months). LC3B expression on tumour was assessed by immunohistochemistry and evaluated for associations with clinicopathological variables. LC3B expression was stratified into high and low expression cohorts using ROC curves with Manhattan distance minimisation, followed by Kaplan-Meier and multivariable survival analyses. Interaction terms between HPV status and LC3B expression in oropharyngeal SCC patients were also examined by joint-effects and stratified analyses.

Results: Kaplan-Meier survival and univariate analyses revealed that high LC3B expression was correlated with poor overall survival in oropharyngeal SCC patients (p = 0.007 and HR = 3.18, 95% CI 1.31-7.71, p = 0.01 respectively). High LC3B expression was also an independent prognostic factor for poor overall survival in oropharyngeal SCC patients (HR = 4.02, 95% CI 1.38-11.47, p = 0.011). In contrast, in oral cavity SCC, only disease-free survival remained statistically significant after univariate analysis (HR = 2.36, 95% CI 1.19-4.67, p = 0.014), although Kaplan-Meier survival analysis showed that high LC3B expression correlated with poor overall and disease-free survival (p = 0.046 and 0.011 respectively). Furthermore, oropharyngeal SCC patients with HPV-negative/high LC3B expression were correlated with poor overall survival in both joint-effects and stratified presentations (p = 0.024 and 0.032 respectively).

Conclusions: High LC3B expression correlates with poor prognosis in oropharyngeal and oral cavity SCC, which highlights the importance of autophagy in these malignancies. High LC3B expression appears to be an independent prognostic marker for oropharyngeal SCC but not for oral cavity SCC patients. The difference in the prognostic significance of LC3B between oropharyngeal and oral cavity SCCs further supports the biological differences between these malignancies. The possibility that oropharyngeal SCC patients with negative HPV status and high LC3B expression were at particular risk of a poor outcome warrants further investigation in prospective studies with larger numbers.
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http://dx.doi.org/10.1186/s12885-018-4536-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984815PMC
June 2018

Microscopic positive margins in papillary thyroid cancer do not impact disease recurrence.

ANZ J Surg 2018 11 27;88(11):1193-1197. Epub 2018 Apr 27.

Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.

Background: The prognostic significance of microscopic positive margins in papillary thyroid carcinoma (PTC) remains unclear. The aim of this study was to determine if microscopic positive margins are associated with increased risk of disease recurrence.

Methods: This is a retrospective analysis of 610 patients with PTC using multivariate Cox regression to evaluate the association between microscopic positive margins and disease-free survival.

Results: Microscopic positive margins were found in 67 (11%) patients and associated with extrathyroidal extension (P < 0.001), multifocality (P < 0.001), nodal metastases (P < 0.001), lymphovascular invasion (P < 0.001), age ≥55 years (P = 0.048), administration of radioactive iodine (RAI) therapy (P = 0.001) and a trend towards larger tumour size (18 versus 15 mm; P = 0.074). After a median follow-up of 3.4 years, there were 83 recurrences. Although involved margins were associated with increased risk of recurrence on univariate analysis (hazard ratio 2.6, 95% confidence interval 1.5-4.6; P = 0.001), there was no association after adjusting for age, nodal metastases, tumour size and extrathyroidal extension on multivariate analysis (hazard ratio 1.5, 95% confidence interval 0.8-2.9; P = 0.242). Similar results were obtained after adjusting for RAI and if margins were analysed as focal versus widely positive. In our study cohort, patients with involved margins generally had other indications for RAI. However, in the nine patients who did not receive RAI, there was no recurrence in the thyroid bed.

Conclusion: Despite a strong association between microscopic positive margins and other adverse prognostic factors in PTC, there is no independent association with disease recurrence on multivariate analysis. Microscopic positive margins are rare (1.1%) in the absence of other indications for RAI.
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http://dx.doi.org/10.1111/ans.14490DOI Listing
November 2018

An Analysis of The American Joint Committee on Cancer 8th Edition T Staging System for Papillary Thyroid Carcinoma.

J Clin Endocrinol Metab 2018 06;103(6):2199-2206

Department of Head and Neck Surgery, Liverpool Hospital, New South Wales, Australia.

Background: The American Joint Committee on Cancer (AJCC) removed microscopic extrathyroidal extension (ETE) from the 8th edition T staging for papillary thyroid cancer (PTC) based on increasing evidence that it is not an independent prognostic factor.

Objectives: We compared the prognostic performance of AJCC 7th (pT7) and 8th (pT8) edition T stage systems, particularly in patients ≥55 years old without macroscopic ETE or distant metastases in whom T classification affects AJCC Tumor Node Metastasis (TNM) stage.

Method: A retrospective analysis of disease-free survival (DFS) in 577 patients with PTC comparing pT8 vs pT7 using the Akaike information criterion (AIC), Harrell's C-index, and Proportion of Variation Explained (PVE).

Results: Of 105 patients with AJCC7 T3 disease, 74 were down-staged. Overall, the prognostic performance of pT7 and pT8 was similar. However, in patients ≥55 years old without macroscopic ETE or distant metastases, pT8 was inferior to pT7 on the basis of higher AIC, lower C-index (0.67 vs 0.76), and lower PVE (30% vs 45%). In this subset, microscopic ETE was associated with multiple other adverse prognostic features and reduced DFS (hazard ratio, 2.8; 95% confidence interval, 1.5 to 5.2; P = 0.002), irrespective of tumor size.

Discussion: In our cohort, pT8 was inferior to pT7 in patients ≥55 years old without macroscopic ETE or distant metastases in whom T classification affects TNM stage. Microscopic ETE was strongly associated with other adverse prognostic factors and reduced DFS in this patient subgroup and may be an effective surrogate for disease biology in PTC, irrespective of whether it is an independent prognostic factor.
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http://dx.doi.org/10.1210/jc.2017-02551DOI Listing
June 2018

Examining clinicians' perceptions of head and neck cancer (HNC) information.

Asia Pac J Clin Oncol 2018 Oct 2;14(5):e428-e433. Epub 2018 Mar 2.

Sydney Medical School, University of Sydney, NSW, Australia.

Background: Providing appropriate educational resources to patients with head and neck cancer (HNC) is important but challenging. The aim of this study was to determine Australian clinicians' perceptions of currently used HNC information resources.

Methods: A purpose-designed questionnaire was disseminated electronically to clinician members of the Australian and New Zealand Head and Neck Cancer Society (ANZHNCS) and The Australian Society of Otolaryngology Head and Neck Surgery (ASOHNS).

Results: Of the 648 clinicians invited, 112 responded to the survey (17.3% response rate). Overall, 85% utilized written information as their primary mode of patient education and 49% received information on treatment details. Areas for improvement include information provision, pain management, emerging risk factors, survivorship and side effects. The majority (66%) of clinicians had a preference for internet patient education materials.

Conclusions: Clinicians predominantly utilized written HNC information rather than multimedia or interactive resources. However, they expressed the desire to be able to deliver HNC information resources via an internet-based platform covering the psychosocial effects of treatment.
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http://dx.doi.org/10.1111/ajco.12858DOI Listing
October 2018

Perforator variability in the anterolateral thigh free flap: a systematic review.

Surg Radiol Anat 2017 Jul 30;39(7):779-789. Epub 2017 Jan 30.

Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.

Objectives: The use of free flaps greatly improves reconstruction options and quality of life for patients undergoing oncological resections. The anterolateral thigh (ALT) free flap is frequently used in the head and neck. The aim of this review was to provide a summary of published evidence assessing perforator anatomy of this flap.

Methods: A broad search was undertaken through the PubMed database using the terms "anterolateral thigh free flap" and "perforator". Search limits included English language and human subjects. Studies that examined more than or equal to ten patients were analysed.

Results: A total of 23 studies were identified, which included both clinical and cadaver studies. 1251 thighs were examined with the mean number of perforators ranging from 1.15 to 4.26. In the majority of cases, the descending branch of the lateral circumflex femoral artery was the dominant pedicle and took a musculocutaneous route. In some series, up to 5.4% of thighs were identified as having no cutaneous perforators. Venous data is limited with most studies reporting the presence of two concomitant veins of which the largest concomitant vein is selected for venous anastomoses.

Conclusions And Future Studies: The ALT free flap is a reconstruction option in head and neck cancer. Adequate perforators for reconstruction are identified in the majority of cases. Increased anatomical perforator knowledge may lead to further uptake of ALT free flap reconstruction and improved intraoperative troubleshooting. Further studies investigating those patients with no perforators in the ALT may lead to improved clinical outcomes.
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http://dx.doi.org/10.1007/s00276-016-1802-yDOI Listing
July 2017

Differences in survival outcome between oropharyngeal and oral cavity squamous cell carcinoma in relation to HPV status.

J Oral Pathol Med 2017 Sep 30;46(8):574-582. Epub 2016 Dec 30.

Cancer Pathology, Bosch Institute, The University of Sydney, Sydney, Australia.

Background: This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC).

Methods: Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation.

Results: Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC.

Conclusions: HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients.
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http://dx.doi.org/10.1111/jop.12535DOI Listing
September 2017

Diagnostic and prognostic utility of Mastermind-like 2 (MAML2) gene rearrangement detection by fluorescent in situ hybridization (FISH) in mucoepidermoid carcinoma of the salivary glands.

Oral Surg Oral Med Oral Pathol Oral Radiol 2016 May 9;121(5):530-41. Epub 2016 Jan 9.

Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia; Central Clinical School, The University of Sydney, Sydney, Australia; Chris O'Brien Lifehouse, Sydney, Australia. Electronic address:

Objective: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy, with a proportion harboring MAML2 rearrangement. This study evaluates the diagnostic and prognostic utility of MAML2 rearrangement in MEC.

Study Design: Salivary gland malignancies at a single institution (1989-2014) were reviewed to identify MECs. Histopathologic evaluation, immunohistochemistry, and fluorescent in situ hybridization (FISH) were performed.

Results: Forty-one cases of MEC were identified, with mean age of 47 years and mean tumor size of 21 mm. Seven locoregional recurrences and five MEC-related deaths were seen over a 22-year follow-up period. Thirty-eight cases were suitable for FISH, and 31 (82%) cases were positive for MAML2 rearrangement, including the oncocytic and clear cell variants of MEC. FISH was negative in the morphologic mimics of MEC. MAML2 rearrangement was significantly associated with longer survival.

Conclusions: MAML2 rearrangement is common and specific for MEC, which makes it a useful diagnostic tool. MAML2 rearrangement also predicts a favorable prognosis.
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http://dx.doi.org/10.1016/j.oooo.2016.01.003DOI Listing
May 2016

Laparoscopic repair of Morgagni hernia: an interesting case and complication.

ANZ J Surg 2013 Sep;83(9):688-9

Department of Surgery, Bankstown Hospital, New South Wales, Australia.

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http://dx.doi.org/10.1111/ans.12219DOI Listing
September 2013
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