ObjectiveAlthough image‐guided surgery (IGS) is considered a valuable tool, its impact on periope... more ObjectiveAlthough image‐guided surgery (IGS) is considered a valuable tool, its impact on perioperative morbidity for endoscopic sinus surgery (ESS) remains unclear. The evidence from reported literature is systematically reviewed with meta‐analysis.Data SourcesMEDLINE (1946 to September 14, 2012, week 2) and EMBASE (1974 to September 14, 2012, week 37).Review MethodsMEDLINE and EMBASE were searched using a search strategy for publications on IGS during ESS that reported original data on perioperative morbidity. PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analyses) guidelines were followed. Both comparative cohort studies with non‐IGS cases and case series were included. Primary outcome was major and total complications. Secondary outcomes were specific orbital and intracranial injury, major hemorrhage, ability to complete the operation, and revision surgery. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) i...
Background/ObjectivesPerineural invasion within keratinocyte cancer is a hallmark of tumour aggre... more Background/ObjectivesPerineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols.MethodsWe retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post‐definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion.ResultsThere was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves <0.1 mm were more commonly treated...
Background/ObjectivesBasal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) a... more Background/ObjectivesBasal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair‐skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non‐representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients.MethodsWe retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population‐based cohort of 43 794 Queensland residents recruited 2010–2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high‐risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012–2014.) We estimated the prevalence of perineural invasion (and 95% confid...
To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging ... more To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95...
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in regions of South... more Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in regions of South-East Asia, with incidence as high as 25-50 cases per 100,000 people in southern China. While current standard therapy is curative for a subset with stage I or II disease, a high proportion of patients relapse and many patients are still initially diagnosed with advanced stage III or IV disease, where overall 5-year survival is significantly reduced. EBV-specific immunotherapy has been successfully used in the treatment of post-transplant lymphomas and may have the potential application to improve outcomes in NPC patients. We have designed the AdE1-LMPpoly vector to promote rapid expansion of CD8+ T cells specific for the latent membrane proteins (LMP) 1&2 and EBV nuclear antigen 1 (EBNA1) expressed in NPC. We recruited a total of 52 NPC patients, including 42 patients with refractory stage IV NPC disease and 11 at-risk patients with no or minimal residual disease (referred to as N/MRD p...
Direct visualization and complete dissection of the recurrent laryngeal nerve (RLN) remain the go... more Direct visualization and complete dissection of the recurrent laryngeal nerve (RLN) remain the gold standard to avoid RLN palsy (RLNP). However, reported mean rates of temporary RLNP are 9.8%, and permanent RLNP, 2.3%. Further, a structurally intact RLN is not necessarily functionally preserved, and surgeon visualization will identify only approximately 1 in 10 injured RLNs. In this setting, intra-operative neural monitoring (IONM) enables function to be assessed, providing important additional information to that available visually. Pathological associations with RLNP include thyroid cancer, re-operative thyroid surgery, large goitres, retrosternal goitres, Graves’ disease and thyroiditis. Anatomical associations with RLNP include non-recurrent LNs, and branched RLNs. Injury most commonly occurs in the last 2 cm, ligament of Berry segment, of the RLN prior to entry into the larynx. Only 10–15% of RLNPs are recognized at surgery. Most RLNPs occur with intact nerves: division and crushing injuries are uncommon. Further, the majority of RLNPs recover rapidly, suggesting neurapraxia, probably due to stretch injury at the ligament of Berry segment of the RLN. Accurate data on RLNP rates depend on preoperative and postoperative laryngoscopy, but if not undertaken, RLNP rates are probably underestimated at least twofold. IONM of the RLN may be utilized as an adjunct to RLN visualization for neural mapping, an aid in dissection, an aid in identification of injury states and to predict post-operative RLN function. Different electrophysiological monitoring systems are utilized worldwide. However, the system commonly available in Australia is the Nerve Integrity Monitor (Medtronic, Minneapolis, MN, USA). The system utilizes an endotracheal tube that detects vocal cord (thyroarytenoid) depolarization upon stimulation of the RLN or the vagus nerve, which is visually produced as an electromyogram on a monitor, and may then be recorded. Contraction of the posterior cricoarytenoid is detected with a finger in the postcricoid space, known as the laryngeal twitch. The learning curve to solve equipment and setup problems, for both surgeon and anaesthetist, is significant. Guidelines for IONM produced by the International Intra-operative Neural Monitoring Study Group highlighted the importance of standards in equipment, anaesthesia, intra-operative monitoring technique, management of signal loss and the importance of vagal stimulation. Vagal stimulation at the start of thyroidectomy ensures set-up of equipment is satisfactory, and at the conclusion demonstrates the entire RLN is functioning. The negative predictive value of an intact signal of the RLN at the conclusion of thyroidectomy is approximately 98%. However, the positive predictive value of loss of the RLN signal can be as low as 37%. Possible reasons include equipment problems, misplacement of the endotracheal tube and early (even intra-operative) resolution of temporary neurapraxia. Perhaps one of the greatest utilities of IONM is to help prevent bilateral RLNP. Neural stimulation at the completion of lobectomy can be used to determine the safety of proceeding to contralateral surgery, and has been associated with a reduction of bilateral paralysis when loss of signal occurs on the first side. Only one randomized control trial has compared direct visualization of RLN to direct visualization and use of IONM and demonstrated a reduction in temporary but not permanent RLNP. The reduction in temporary RLNP was greatest in cancer and re-operative cases. A meta-analysis of 64 699 RLNs at risk, in one randomized trial, seven comparative trials and 34 case series, did not show a significant difference in temporary or permanent RLNP rates. Are there any circumstances where IONM is of value? Monitoring would appear to be of value in thyroid cancer, re-operative surgery – for both benign and malignant conditions, large goitres, retrosternal goitres, Graves’ disease and thyroiditis, bilateral thyroid surgery and surgery on the side of the only functioning nerve. It is also of value where the RLN is distorted and adherent to a thyroid lobe either de novo or due to cancer or scar tissue. Further, it is of value when unexpected findings occur, such as branched nerves – where the anterior branch contains all the motor fibres to the larynx, non-recurrent nerves and a difficult posteriorly situated thyroid cancer in close proximity to the terminal portion of the RLN. However, due to the need for surgeons and anaesthetists to develop and maintain expertise, the possibility of unexpected anatomical and pathological findings, and the inability to predict when it will be of particular use, we suggest there is considerable value in employing routine use of IONM for all thyroid surgery.
Genomic instability underlies the transformation of host cells toward malignancy, promotes develo... more Genomic instability underlies the transformation of host cells toward malignancy, promotes development of invasion and metastasis and shapes the response of established cancer to treatment. In this review, we discuss recent advances in our understanding of genomic stability in squamous cell carcinoma of the head and neck (HNSCC), with an emphasis on DNA repair pathways. HNSCC is characterized by distinct profiles in genome stability between similarly staged cancers that are reflected in risk, treatment response and outcomes. Defective DNA repair generates chromosomal derangement that can cause subsequent alterations in gene expression, and is a hallmark of progression toward carcinoma. Variable functionality of an increasing spectrum of repair gene polymorphisms is associated with increased cancer risk, while aetiological factors such as human papillomavirus, tobacco and alcohol induce significantly different behaviour in induced malignancy, underpinned by differences in genomic sta...
Objective: Endoscopic transnasal approaches to the skull base and intracranial disease are an eme... more Objective: Endoscopic transnasal approaches to the skull base and intracranial disease are an emerging subspecialty. The limits of this approach are often dictated by exposure and blood loss. Cell salvage techniques are widely used in other surgical fields. However, in otolaryngology, questions remain regarding its safety because work is performed in a contaminated field. In this literature review, we present the evidence for perioperative cell saver blood transfusion in potentially contaminated fields and the need for further investigation of its use in endonasal surgery.Data Sources: MEDLINE and Evidence Based Medicine Reviews databases were searched for relevant articles.Review Methods: All English articles discussing autologous blood transfusion in endonasal surgery were reviewed.Results: Despite a wide search pattern, no articles that discuss this topic were found in the English literature. Therefore, we went on to present data on the general use of cell saver blood in contamin...
ObjectiveAlthough image‐guided surgery (IGS) is considered a valuable tool, its impact on periope... more ObjectiveAlthough image‐guided surgery (IGS) is considered a valuable tool, its impact on perioperative morbidity for endoscopic sinus surgery (ESS) remains unclear. The evidence from reported literature is systematically reviewed with meta‐analysis.Data SourcesMEDLINE (1946 to September 14, 2012, week 2) and EMBASE (1974 to September 14, 2012, week 37).Review MethodsMEDLINE and EMBASE were searched using a search strategy for publications on IGS during ESS that reported original data on perioperative morbidity. PRISMA (Preferred Reporting Items for Systematic reviews and Meta‐Analyses) guidelines were followed. Both comparative cohort studies with non‐IGS cases and case series were included. Primary outcome was major and total complications. Secondary outcomes were specific orbital and intracranial injury, major hemorrhage, ability to complete the operation, and revision surgery. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) i...
Background/ObjectivesPerineural invasion within keratinocyte cancer is a hallmark of tumour aggre... more Background/ObjectivesPerineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols.MethodsWe retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post‐definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion.ResultsThere was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves <0.1 mm were more commonly treated...
Background/ObjectivesBasal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) a... more Background/ObjectivesBasal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair‐skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non‐representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients.MethodsWe retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population‐based cohort of 43 794 Queensland residents recruited 2010–2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high‐risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012–2014.) We estimated the prevalence of perineural invasion (and 95% confid...
To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging ... more To determine whether the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) for HPV associated oropharyngeal carcinoma (HPV+OPC) is a better discriminator of overall survival (OS), compared with the 7th edition (7th Ed) AJCC/UICC TNM staging following curative radiotherapy (RT). The 5-year OS for all patients with non-metastatic (M0) p16-confirmed OPC treated between 2005 and 2015 was determined and grouped based on the 7th Ed AJCC/UICC TNM and ICON-S staging. A total of 279 patients met the inclusion criteria. The 5-year OS with the 7th Ed TNM classification were Stage I/II 88.9% (95% CI; 70.6-100%), Stage III 93.8% (95% CI; 85.9-100%), Stage IVa 86.4% (95% CI; 81.6-91.5%) and Stage IVb 62.3% (95% CI; 46.8-82.8%). On multivariate Cox regression analysis there was no statistically significant OS difference when comparing Stage I/II with, Stage III (p=0.98, HR=0.97, 95% CI; 0.11-8.64), IVa (p=0.67, HR=1.56, 95% CI; 0.2-11.94) and IVb (p=0.11, HR=5.54, 95...
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in regions of South... more Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in regions of South-East Asia, with incidence as high as 25-50 cases per 100,000 people in southern China. While current standard therapy is curative for a subset with stage I or II disease, a high proportion of patients relapse and many patients are still initially diagnosed with advanced stage III or IV disease, where overall 5-year survival is significantly reduced. EBV-specific immunotherapy has been successfully used in the treatment of post-transplant lymphomas and may have the potential application to improve outcomes in NPC patients. We have designed the AdE1-LMPpoly vector to promote rapid expansion of CD8+ T cells specific for the latent membrane proteins (LMP) 1&2 and EBV nuclear antigen 1 (EBNA1) expressed in NPC. We recruited a total of 52 NPC patients, including 42 patients with refractory stage IV NPC disease and 11 at-risk patients with no or minimal residual disease (referred to as N/MRD p...
Direct visualization and complete dissection of the recurrent laryngeal nerve (RLN) remain the go... more Direct visualization and complete dissection of the recurrent laryngeal nerve (RLN) remain the gold standard to avoid RLN palsy (RLNP). However, reported mean rates of temporary RLNP are 9.8%, and permanent RLNP, 2.3%. Further, a structurally intact RLN is not necessarily functionally preserved, and surgeon visualization will identify only approximately 1 in 10 injured RLNs. In this setting, intra-operative neural monitoring (IONM) enables function to be assessed, providing important additional information to that available visually. Pathological associations with RLNP include thyroid cancer, re-operative thyroid surgery, large goitres, retrosternal goitres, Graves’ disease and thyroiditis. Anatomical associations with RLNP include non-recurrent LNs, and branched RLNs. Injury most commonly occurs in the last 2 cm, ligament of Berry segment, of the RLN prior to entry into the larynx. Only 10–15% of RLNPs are recognized at surgery. Most RLNPs occur with intact nerves: division and crushing injuries are uncommon. Further, the majority of RLNPs recover rapidly, suggesting neurapraxia, probably due to stretch injury at the ligament of Berry segment of the RLN. Accurate data on RLNP rates depend on preoperative and postoperative laryngoscopy, but if not undertaken, RLNP rates are probably underestimated at least twofold. IONM of the RLN may be utilized as an adjunct to RLN visualization for neural mapping, an aid in dissection, an aid in identification of injury states and to predict post-operative RLN function. Different electrophysiological monitoring systems are utilized worldwide. However, the system commonly available in Australia is the Nerve Integrity Monitor (Medtronic, Minneapolis, MN, USA). The system utilizes an endotracheal tube that detects vocal cord (thyroarytenoid) depolarization upon stimulation of the RLN or the vagus nerve, which is visually produced as an electromyogram on a monitor, and may then be recorded. Contraction of the posterior cricoarytenoid is detected with a finger in the postcricoid space, known as the laryngeal twitch. The learning curve to solve equipment and setup problems, for both surgeon and anaesthetist, is significant. Guidelines for IONM produced by the International Intra-operative Neural Monitoring Study Group highlighted the importance of standards in equipment, anaesthesia, intra-operative monitoring technique, management of signal loss and the importance of vagal stimulation. Vagal stimulation at the start of thyroidectomy ensures set-up of equipment is satisfactory, and at the conclusion demonstrates the entire RLN is functioning. The negative predictive value of an intact signal of the RLN at the conclusion of thyroidectomy is approximately 98%. However, the positive predictive value of loss of the RLN signal can be as low as 37%. Possible reasons include equipment problems, misplacement of the endotracheal tube and early (even intra-operative) resolution of temporary neurapraxia. Perhaps one of the greatest utilities of IONM is to help prevent bilateral RLNP. Neural stimulation at the completion of lobectomy can be used to determine the safety of proceeding to contralateral surgery, and has been associated with a reduction of bilateral paralysis when loss of signal occurs on the first side. Only one randomized control trial has compared direct visualization of RLN to direct visualization and use of IONM and demonstrated a reduction in temporary but not permanent RLNP. The reduction in temporary RLNP was greatest in cancer and re-operative cases. A meta-analysis of 64 699 RLNs at risk, in one randomized trial, seven comparative trials and 34 case series, did not show a significant difference in temporary or permanent RLNP rates. Are there any circumstances where IONM is of value? Monitoring would appear to be of value in thyroid cancer, re-operative surgery – for both benign and malignant conditions, large goitres, retrosternal goitres, Graves’ disease and thyroiditis, bilateral thyroid surgery and surgery on the side of the only functioning nerve. It is also of value where the RLN is distorted and adherent to a thyroid lobe either de novo or due to cancer or scar tissue. Further, it is of value when unexpected findings occur, such as branched nerves – where the anterior branch contains all the motor fibres to the larynx, non-recurrent nerves and a difficult posteriorly situated thyroid cancer in close proximity to the terminal portion of the RLN. However, due to the need for surgeons and anaesthetists to develop and maintain expertise, the possibility of unexpected anatomical and pathological findings, and the inability to predict when it will be of particular use, we suggest there is considerable value in employing routine use of IONM for all thyroid surgery.
Genomic instability underlies the transformation of host cells toward malignancy, promotes develo... more Genomic instability underlies the transformation of host cells toward malignancy, promotes development of invasion and metastasis and shapes the response of established cancer to treatment. In this review, we discuss recent advances in our understanding of genomic stability in squamous cell carcinoma of the head and neck (HNSCC), with an emphasis on DNA repair pathways. HNSCC is characterized by distinct profiles in genome stability between similarly staged cancers that are reflected in risk, treatment response and outcomes. Defective DNA repair generates chromosomal derangement that can cause subsequent alterations in gene expression, and is a hallmark of progression toward carcinoma. Variable functionality of an increasing spectrum of repair gene polymorphisms is associated with increased cancer risk, while aetiological factors such as human papillomavirus, tobacco and alcohol induce significantly different behaviour in induced malignancy, underpinned by differences in genomic sta...
Objective: Endoscopic transnasal approaches to the skull base and intracranial disease are an eme... more Objective: Endoscopic transnasal approaches to the skull base and intracranial disease are an emerging subspecialty. The limits of this approach are often dictated by exposure and blood loss. Cell salvage techniques are widely used in other surgical fields. However, in otolaryngology, questions remain regarding its safety because work is performed in a contaminated field. In this literature review, we present the evidence for perioperative cell saver blood transfusion in potentially contaminated fields and the need for further investigation of its use in endonasal surgery.Data Sources: MEDLINE and Evidence Based Medicine Reviews databases were searched for relevant articles.Review Methods: All English articles discussing autologous blood transfusion in endonasal surgery were reviewed.Results: Despite a wide search pattern, no articles that discuss this topic were found in the English literature. Therefore, we went on to present data on the general use of cell saver blood in contamin...
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