R J Shaw

Aintree University Hospital NHS Foundation Trust, Liverpool, England, United Kingdom

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Publications (39)95.89 Total impact

  • British Journal of Oral and Maxillofacial Surgery 10/2014; 52(8):e45. · 2.72 Impact Factor
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    ABSTRACT: Background:Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available.Methods:In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis.Results:Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%).Conclusion:A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.British Journal of Cancer advance online publication 30 September 2014; doi:10.1038/bjc.2014.500 www.bjcancer.com.
    British journal of cancer. 09/2014;
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    ABSTRACT: Aims and background. In breast cancer (BC) there are different therapies available with different side effects affecting the health-related quality of life (HRQOL) of patients. Here we report a novel tool, the BC-specific Patient Concerns Inventory (PCI). This work includes a survey that is part of the validation process to allow a larger cohort and comparisons with clinical characteristics. We report the concerns that BC patients would like to discuss in the outpatient clinic - using the PCI - and also their choice of multidisciplinary team members they would like to see. Methods and study design. We carried out a cross-sectional survey - using the BC-specific PCI, the EORTC QLQ-C30 and the EORTC BC QLQ-BR23 - of patients who had completed their initial treatment and were attending a review outpatient clinic. 249 patients were recruited from February to July 2012. Results. Survey responses were obtained from 80% (200/249). The three most frequent items were fear of cancer coming back (62%, 124), breast sensitivity/pain (46%, 92), and fatigue/tiredness and low energy levels overall (46%, 92). The most frequently selected members of the multidisciplinary team that patients wished to see were the breast care nurse (46%, 92), the medical oncologist (28%, 55) and the psychologist (20%, 40). Conclusions. The PCI provides the opportunity for multiprofessional engagement across a range of issues specific to BC. It can identify issues relating to physical, psychological, sexual and social functioning, as well as issues relating to body image and lifestyle.
    Tumori 06/2014; · 0.92 Impact Factor
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    ABSTRACT: In head and neck microvascular reconstruction, a proportion of patients are at a higher risk of flap failure. These include salvage surgery after chemoradiotherapy, reconstruction for osteoradionecrosis and when difficulty is encountered in achieving flap perfusion intraoperatively. Several studies have shown that the Cook-Swartz Doppler (Cook Medical Inc, Bloomington, USA) enabled earlier detection of a compromised flap. We retrospectively reviewed microvascular reconstructions monitored with the Cook-Swartz implantable Doppler (2006-2012) and included patients' characteristics, comorbidity (American Society of Anesthesiologists' (ASA) grade), indication for operation, type of reconstruction, and indication for implantable Doppler. We also included details of surgical exploration, free flap salvage, and outcomes of flap salvage. These outcomes were compared with a group of low-risk patients (2005-2009) whose flaps were monitored clinically. A total of 75 free flaps in 73 patients were monitored with the implantable Doppler: 40 (53%) were in cases which required reconstruction following previous surgery/radiotherapy or flap perfusion difficulties, 10 (13%) buried flaps, 13 (17%) as routine flap monitors and 12 (17%) for other indications. The false negative rate was 5%, sensitivity 67%, the false positive rate was 25%, and specificity was 95%. Higher risk flaps monitored with the doppler had a higher return to theatre rate, 21% compared with 4% (p<0.001) and flap failure rate, 7% compared with 1% (p=0.002). Salvage rates for free flaps were similar in both groups (62% compared with 60%, p=1.0). There is not enough evidence to suggest that the implantable doppler reduces the rate of failed flaps in routine low-risk cases, and its value in monitoring high-risk reconstructions require evaluation in a prospective randomised study.
    British Journal of Oral and Maxillofacial Surgery 04/2014; · 2.72 Impact Factor
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    ABSTRACT: In head and neck microvascular reconstruction, a proportion of patients are at a higher risk of flap failure. These include salvage surgery after chemoradiotherapy, reconstruction for osteoradionecrosis and when difficulty is encountered in achieving flap perfusion intraoperatively. Several studies have shown that the Cook-Swartz Doppler (Cook Medical Inc, Bloomington, USA) enabled earlier detection of a compromised flap. We retrospectively reviewed microvascular reconstructions monitored with the Cook-Swartz implantable Doppler (2006–2012) and included patients’ characteristics, comorbidity (American Society of Anesthesiologists’ (ASA) grade), indication for operation, type of reconstruction, and indication for implantable Doppler. We also included details of surgical exploration, free flap salvage, and outcomes of flap salvage. These outcomes were compared with a group of low-risk patients (2005–2009) whose flaps were monitored clinically. A total of 75 free flaps in 73 patients were monitored with the implantable Doppler: 40 (53%) were in cases which required reconstruction following previous surgery/radiotherapy or flap perfusion difficulties, 10 (13%) buried flaps, 13 (17%) as routine flap monitors and 12 (17%) for other indications. The false negative rate was 5%, sensitivity 67%, the false positive rate was 25%, and specificity was 95%. Higher risk flaps monitored with the doppler had a higher return to theatre rate, 21% compared with 4% (p < 0.001) and flap failure rate, 7% compared with 1% (p = 0.002). Salvage rates for free flaps were similar in both groups (62% compared with 60%, p = 1.0). There is not enough evidence to suggest that the implantable doppler reduces the rate of failed flaps in routine low-risk cases, and its value in monitoring high-risk reconstructions require evaluation in a prospective randomised study.
    British Journal of Oral and Maxillofacial Surgery 01/2014; · 2.72 Impact Factor
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    ABSTRACT: Multidisciplinary team (MDT) meetings have an important role in the management of head and neck cancer. Increasing incidence of the disease and a drive towards centralised meetings on large numbers of patients mean that effective discussions are pertinent. We aimed to evaluate new cases within a single high volume head and neck cancer MDT and to explore the relation between the time taken to discuss each case, the number of discussants, and type of case. A total of 105 patients with a new diagnosis of head and neck malignancy or complex benign tumour were discussed at 10 head and neck cancer MDT meetings. A single observer timed each discussion using a stopwatch, and recorded the number of discussants and the diagnosis and characteristics of each patient. Timings ranged from 15 to 480s (8min) with a mean of 119s (2min), and the duration of discussion correlated closely with the number of discussants (rs=0.63, p<0.001). The longest discussions concerned patients with advanced T stage (p=0.006) and advanced N stage (p=0.009) disease, the elderly (p=0.02) and male patients (p=0.05). Tumour site and histological findings were not significant factors in the duration of discussion. Most discussions on patients with early stage tumours were short (T1: 58% less than 60s, mean 90) and fewer people contributed. Many patients, particularly those with early stage disease, require little discussion, and their treatment might reasonably be planned according to an agreed protocol, which would leave more time and resources for those that require greater multidisciplinary input. Further studies may highlight extended discussions on patients with head and neck cancer, which may prompt a review of protocols and current evidence.
    British Journal of Oral and Maxillofacial Surgery 11/2013; · 2.72 Impact Factor
  • M W Ho, J S Brown, R J Shaw
    British Journal of Oral and Maxillofacial Surgery 09/2013; · 2.72 Impact Factor
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    ABSTRACT: Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.
    British Journal of Oral and Maxillofacial Surgery 04/2013; · 2.72 Impact Factor
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    ABSTRACT: Background:Human papillomavirus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC) is now advocated. Demonstration of transcriptionally active high-risk HPV (HR-HPV) in fresh tumour tissue is considered to be the analytical 'gold standard'. Clinical testing has focused on formalin-fixed paraffin-embedded (FFPE) tissue at the expense of sensitivity and specificity. Recently, a novel RNA in situ hybridisation test (RNAscope) has been developed for the detection of HR-HPV in FFPE tissue; however, validation against the 'gold standard' has not been reported.Methods:A tissue microarray comprising FFPE cores from 79 OPSCC was tested using HR-HPV RNAscope. Analytical accuracy and prognostic capacity were established by comparison with the reference test; qRT-PCR for HR-HPV on matched fresh-frozen samples.Results:High-risk HPV RNAscope had a sensitivity and specificity of 97 and 93%, respectively, against the reference test. Kaplan-Meier estimates of disease-specific survival (DSS, P=0.001) and overall survival (OS, P<0.001) by RNAscope were similar to the reference test (DSS, P=0.003, OS, P<0.001) and at least, not inferior to p16 immunohistochemistry +/- HR-HPV DNA-based tests.Conclusion:HR-HPV RNAscope demonstrates excellent analytical and prognostic performance against the 'gold standard'. These data suggest that the test could be developed to provide the 'clinical standard' for assigning a diagnosis of HPV-related OPSCC.British Journal of Cancer advance online publication, 14 February 2013; doi:10.1038/bjc.2013.63 www.bjcancer.com.
    British Journal of Cancer 02/2013; · 5.08 Impact Factor
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    ABSTRACT: Background:There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs.Methods:DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival.Results:Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series.Conclusion:Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.British Journal of Cancer advance online publication 3 January 2013; doi:10.1038/bjc.2012.568 www.bjcancer.com.
    British Journal of Cancer 01/2013; · 5.08 Impact Factor
  • British Journal of Oral and Maxillofacial Surgery 06/2012; 50:S34. · 2.72 Impact Factor
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    ABSTRACT: While the size and clinical appearance are known risk factors for malignant transformation of potentially malignant oral the importance of site, grade of dysplasia and exposure to environmental carcinogens remains controversial. We aim to report the clinical determinants of malignant progression in a series of patients with histopathologically graded oral epithelial dysplasia (OED). We recruited patients with a histopathological diagnosis of OED to a longitudinal observational study in a tertiary oral dysplasia clinic. Clinical, histopathological and risk factor data were recorded at baseline. One of three clinical endpoints were determined: malignant transformation, progression of dysplasia grade, remission/stable dysplasia grade. Ninety-one patients meeting the criteria gave consent for inclusion to the cohort, with outcomes reported after a median follow up of 48months. An estimated 22% (SE 6%) of patients underwent malignant transformation within 5years, with significant predictors being: non-smoking status (χ(2)=15.1, p=0.001), site (χ(2)=15.3, p=0.002), non-homogeneous appearance (χ(2)=8.2, p=0.004), size of lesion >200mm(2) (χ(2)=4.7, p=0.03) and, of borderline significance, high grade (χ(2)=5.8, p=0.06). Gender, age, number of lesions and alcohol history did not predict for malignant transformation. Although a number of these clinical determinants have previously been associated with higher malignant transformation in OED, the high-risk nature of lesions in non-smokers is of particular note and requires a greater emphasis and recognition amongst clinicians dealing with OED. It suggests that those non-smokers with OED, have an inherited or acquired predisposition and should be treated more aggressively; these should form the focus for further investigation.
    Oral Oncology 05/2012; 48(10):969-76. · 2.70 Impact Factor
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    ABSTRACT: Improved disease-free survival for oral squamous cell carcinoma (SCC) with the use of postoperative radiotherapy (PORT) has to be balanced against the risk of recurrence, the relative morbidity of radiotherapy, reduced options for treatment, and survival with recurrent disease. In the absence of randomised trials, a review of current evidence is timely because of increasing differences in outcome and response to treatment for cancers of the larynx, oropharynx, and oral cavity. From a search of 109 papers, 25 presented relevant data in tabular form, and reported local, regional, and total recurrence, and overall survival. Most data come from non-randomised studies that compared the effects of interventions with previous or historical information. A summary of the results shows local recurrence of 11%, 17%, and 15% for early, late, and all stages after operation alone, compared with 13%, 16%, and 19% after PORT. Regional recurrence is reported as 13%, 12%, and 11% for early, late, and all stages after operation alone compared with 6%, 11%, and 9% after PORT. Overall survival is reported as 76%, 74%, and 77% for operation alone compared with 65%, 62%, and 62% for early, late and all stages of oral SCC, respectively. It is acknowledged that this is a weak level of evidence as patients who have PORT probably have a high pathological-stage of disease. Knowing that PORT increases morbidity and reduces salvage rates and options for treating recurrent disease, this difference in overall survival emphasises the need for randomised studies or a re-evaluation of our current protocols.
    British Journal of Oral and Maxillofacial Surgery 12/2011; 50(6):481-9. · 2.72 Impact Factor
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    A G Schache, R J Shaw
    Clinical Oncology 09/2011; 23(10):718. · 2.86 Impact Factor
  • British Journal of Oral & Maxillofacial Surgery - BRIT J ORAL MAXILLOFAC SURG. 01/2011; 49.
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    ABSTRACT: Reconstruction of surgical defects in the head and neck using microvascular free tissue transfer is reliable with success rates in excess of 95%. Our previous audit (1992-1998) showed that 16% of patients required an early return to theatre, and the overall free flap salvage rate was 73%. The medical records of 37 patients who had required early return to theatre (within 7 days) after free tissue transfer were analysed to ascertain the indication for reoperation, and whether surgical intervention had been successful, taking into account the timing and cause of compromise. The results of a retrospective re-audit (1999-2004 and 2005-2009) showed that the return to theatre rate had reduced to 4% overall because of a reduction in the number of cases: those that required evacuation of a neck haematoma, and venous compromise of fasciocutaneous or perforator free flaps. Salvage of flaps was most successful when done within the first 24h, and in cases of venous compromise. Three percent of free flaps failed without attempted salvage; most were late failures. Overall survival (1992-2009) for composite free flaps (93%) was lower than for fasciocutaneous or perforator free flaps (96%). Between 2005 and 2009 our overall free flap survival rate was 98%.
    British Journal of Oral and Maxillofacial Surgery 12/2010; 50(1):13-8. · 2.72 Impact Factor
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    ABSTRACT: potential epigenetic biomarkers for malignant transformation to carcinoma ex pleomorphic adenoma (Ca ex PSA) have been sought previously with and without specific comparison with the benign variant, pleomorphic salivary adenoma (PSA). Previous analysis has been limited by a non-quantitative approach. We sought to demonstrate quantitative promoter methylation across a panel of tumour suppressor genes (TSGs) in both Ca ex PSA and PSA. quantitative methylation-specific real-time polymerase chain reaction (qMSP) analysis of p16(INK4A), CYGB, RASSF1, RARβ, human telomerase reverse transcriptase (hTERT), Wilms' tumour 1 (WT1) and TMEFF2 gene promoters was undertaken on bisulphite-converted DNA, previously extracted from archival fixed tissue specimens of 31 Ca ex PSA and an unrelated cohort of 28 PSA. All target regions examined had formerly been shown to be hypermethylated in salivary and/or mucosal head and neck malignancies. the qMSP demonstrated abnormal methylation of at least one target in 20 out of 31 (64.5%) Ca ex PSA and 2 out of 28 (7.1%) PSA samples (P<0.001). RASSF1 was the single gene promoter for which methylation is shown to be a statistically significant predictor of malignant disease (P<0.001) with a sensitivity of 51.6% and a specificity of 92.9%. RARβ, TMEFF2 and CYGB displayed no apparent methylation, while a combinatory epigenotype based on p16, hTERT, RASSF1 and WT1 was associated with a significantly higher chance of detecting malignancy in any positive sample (odds ratio: 24, 95% CI: 4.7-125, P<0.001). we demonstrate the successful application of qMSP to a large series of historical Ca ex PSA samples and report on a panel of TSGs with significant differences in their methylation profiles between benign and malignant variants of pleomorphic salivary adenoma. qMSP analysis could be developed as a useful clinical tool to differentiate between Ca ex PSA and its benign precursor.
    British Journal of Cancer 11/2010; 103(12):1846-51. · 5.08 Impact Factor
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    ABSTRACT: We retrospectively reviewed 15 cases of pharyngolaryngectomy for advanced laryngeal carcinoma reconstructed with the anterolateral thigh (ALT) free flap. Thirteen patients had primary surgery and adjuvant treatment (radiotherapy or chemoradiotherapy), and two had salvage surgery. Thirteen had stage III or IV disease, and eight had cervical nodal extracapsular spread. In this series all the flaps survived, and at median follow-up of 14.5 months (range 3.7-31.2), 12 of the 15 patients were alive. One patient developed a chronic pharyngocutaneous fistula, and five required repeat balloon dilatations for late pharyngeal strictures. Six patients enjoyed restoration of full oral intake, seven were able to take a soft diet, and two were dependent on feeding by percutaneous endoscopic gastrostomy. Four patients developed adequate tracheo-oesophageal speech, and one successfully developed oesophageal speech. In this series many of the surgical problems associated with pharyngolaryngectomy reconstruction were addressed successfully by the ALT, but late dysphagia remained troublesome in an appreciable minority. While adjuvant radiotherapy could have contributed to this, future innovations will focus on the reduction of late strictures.
    British Journal of Oral and Maxillofacial Surgery 11/2010; 50(1):19-24. · 2.72 Impact Factor
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    British Journal of Oral and Maxillofacial Surgery 05/2010; 48. · 2.72 Impact Factor
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    ABSTRACT: The authors present a case of inferior alveolar nerve morbidity attributable to use of bone wax to control haemorrhage during third molar surgery. The patient presented after 11 symptom-free years with parasthesia and, eventually pain in the cutaneous distribution of the right inferior alveolar nerve. Radiographs revealed a 1cm radiolucency consistent with a neuroma. Pathological examination of the surgically resected lesion revealed a foreign body reaction to bone wax. The case illustrates the poor resorption qualities of bone wax and the need for other haemostatic agents to achieve haemostasis in dentoalveolar surgery.
    International Journal of Oral and Maxillofacial Surgery 04/2010; 39(5):511-3. · 1.52 Impact Factor