Primary Tumour Detection in Carcinoma of Unknown Primary with Transoral Robotic Surgery (TORS) Tongue Base Mucosectomy: A Meta-analysis.

BACKGROUND: Head and neck carcinoma of unknown primary (CUP) represents a challenging diagnostic process when standard work-up fails to identify the primary tumour site. The aim of this systematic review and meta-analysis was to evaluate the diagnostic utility and complication profile of transoral robotic surgery (TORS) tongue base mucosectomy (TBM) in the management of CUP. PATIENTS AND METHODS: An electronic database search was performed in the EMBASE, MEDLINE, PubMed and Cochrane databases. A meta-analysis of proportions was performed to obtain an estimate of the overall proportion for the detection and complication rates. RESULTS: Nine studies representing 235 patients with CUP who had TORS TBM were included in the final analysis. The overall pooled tumour detection rate was 66.2% [95% confidence interval (CI) 56.1-75.8]. The incidence of tumour detection in human papilloma virus (HPV)-positive cases (81.5%, 95% CI 60.8-96.4) was significantly higher than HPV-negative cases (2.3%, 95% CI 0.00-45.7). Weighted overall complication rate was 11.4% (95% CI 7.2-16.2). The majority were grade I or II (80%) according to the Clavien-Dindo classification. CONCLUSIONS: This meta-analysis suggests TORS to be safe and effective in localising the primary tumour site in patients with CUP. While the current data supports the use of TORS in patients who are HPV positive, larger numbers of HPV-negative cases are required to determine the true diagnostic effect with TORS before any valid conclusions can be inferred in this particular subgroup. Further research should focus on high quality prospective trials with stringent methodological work-up to minimise heterogeneity and allow for more accurate statistical analysis.

Quality of life outcomes comparing primary Transoral Robotic Surgery (TORS) with primary radiotherapy for early-stage oropharyngeal squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Transoral Robotic Surgery (TORS) and radiotherapy are considered oncologically equivalent primary treatment options for early-stage HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Quality of Life (QoL) and Patient Reported Outcome Measures (PROMs) are therefore imperative in supporting clinical decision-making and optimising patient-centred care. The aim of this article is to evaluate how these primary treatment modalities compare in terms of QoL. MATERIALS AND METHODS: Systematic review and meta-analysis of studies comparing primary TORS and primary radiotherapy for OPSCC using validated QoL tools. Swallowing and global QoL were the primary endpoints with secondary endpoints including all other QoL domains. An inverse variance random-effects model was employed to calculate the weighted estimate of the treatment effects across trials. RESULTS: A total of six studies collectively reporting on 555 patients were included (n = 236 TORS and n = 319 radiotherapy). Meta-analysis showed no significant difference for swallowing (mean difference = -0.24, p = 0.89) and global QoL (mean difference = 4.55, p = 0.14). For the remaining QoL domains (neck/shoulder impairment, neurotoxicity, voice, xerostomia, speech, and distress), the scarcity of data did not permit meta-analysis. However, the existing data showed no significant difference for any except for xerostomia where TORS appears favourable in the sole study reporting on this. CONCLUSIONS: TORS and radiotherapy appear to be comparable primary treatment options for early stage OPSCC when it comes to QoL. However, a substantial proportion of patients in the TORS group received adjuvant (chemo)radiotherapy rendering it difficult to establish the 'true' QoL outcomes following surgery alone. There are also minimal studies reporting QoL outcomes beyond swallowing and global QoL. Further research is therefore needed, including more randomised trials adequately powered to detect differences in QoL outcomes.

Successful Liver Retransplantation in a Patient With Disseminated Aspergillosis and Nocardiosis: A Case Report.

BACKGROUND: Clinical guidelines list active fungal infection and sepsis as contraindications to liver transplantation due to the risk of worsening infection with immunosuppression postoperatively. Mortality from systemic opportunistic infections in transplant recipients is high, approaching 100% for disseminated aspergillosis. However, the optimal duration of treatment required before transplant is unclear. Additionally, delaying surgery while the infection is treated risks death from hepatic decompensation and physical deconditioning, preventing progression to transplantation. CASE REPORT: Here, we present a patient who underwent successful repeat liver transplantation for recurrent autoimmune hepatitis and graft rejection while undergoing treatment for disseminated aspergillosis and nocardiosis. He had pulmonary, hepatic, and central nervous system involvement. He had received 2 months of antimicrobials but had ongoing radiologic evidence of infection when listed for retransplantation. He remains well and infection-free 1 year postoperatively. CONCLUSION: Few cases of successful liver transplantation in the setting of disseminated aspergillosis have been reported previously. To our knowledge, this is the first successful liver transplant in a patient with disseminated nocardial infection.

Delivering a net zero National Health Service: where does otorhinolaryngology - head and neck surgery stand?

OBJECTIVE: The National Health Service (NHS) recognised the risk to public health brought by climate change by launching the Greener NHS National Programme in 2020. These organisational changes aim to attain net zero direct carbon emissions. This article reviews the literature on initiatives aimed at mitigating the environmental impact of ENT practice. METHOD: Systematic review of the literature using scientific, healthcare and general interest (public domain) databases. RESULTS: The initiatives reviewed can be broken down into strategies for mitigating the carbon footprint of long patient stay, use of operative theatres and healthcare travel. The carbon footprint of in-patient stay can be mitigated by a shift towards day-case surgery. The ENT community is currently focused on the reduction of theatre waste and the use of disposable instruments. Furthermore, supply chains and healthcare delivery models are being redesigned to reduce travel. CONCLUSION: Future areas of development include designing waterless theatre scrubs, waste-trapping technologies for anaesthetic gases and a continuing investment in virtual healthcare.

Liver fibrosis quantified by image morphometry predicts clinical outcomes in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Liver fibrosis predicts adverse clinical outcomes, such as liver-related death (LRD) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the accuracy of semi-automated quantification of collagen proportionate area (CPA) as an objective new method for predicting clinical outcomes. METHOD: Liver biopsies from patients with NAFLD underwent computerized image morphometry of Sirius Red staining with CPA quantification performed by ImageScope. Clinical outcomes, including total mortality, LRD, and combined liver outcomes (liver decompensation, HCC, or LRD), were determined by medical records and population-based data-linkage. The accuracy of CPA for predicting outcomes was compared with non-invasive fibrosis tests (Hepascore, FIB-4, APRI). RESULTS: A total of 295 patients (mean age 50 years) were followed for a median (range) of 9 (0.2-25) years totalling 3253 person-years. Patients with CPA ≥ 10% had significantly higher risks for total death [hazard ratio (HR): 5.0 (1.9-13.2)], LRD [19.0 (2.0-182.0)], and combined liver outcomes [15.6 (3.1-78.6)]. CPA and pathologist fibrosis staging (FS) showed similar accuracy (AUROC) for the prediction of total death (0.68 vs. 0.70), LRD (0.72 vs. 0.77) and combined liver outcomes (0.75 vs. 0.78). Non-invasive serum markers Hepascore, APRI, and FIB-4 reached higher AUROC; however, they were not statistically significant compared to that of CPA except for Hepascore in predicting total mortality (0.86 vs. 0.68, p = 0.009). CONCLUSION: Liver fibrosis quantified by CPA analysis was significantly associated with clinical outcomes including total mortality, LRD, and HCC. CPA achieved similar accuracy in predicting outcomes compared to pathologist fibrosis staging and non-invasive serum markers.

Predicting liver-related events in NAFLD: A predictive model.

BACKGROUND AND AIMS: Management of NAFLD involves noninvasive prediction of fibrosis, which is a surrogate for patient outcomes. We aimed to develop and validate a model predictive of liver-related events (LREs) of decompensation and/or HCC and compare its accuracy with fibrosis models. APPROACH AND RESULTS: Patients with NAFLD from Australia and Spain who were followed for up to 28 years formed derivation (n = 584) and validation (n = 477) cohorts. Competing risk regression and information criteria were used for model development. Accuracy was compared with fibrosis models using time-dependent AUC analysis. During follow-up, LREs occurred in 52 (9%) and 11 (2.3%) patients in derivation and validation cohorts, respectively. Age, type 2 diabetes, albumin, bilirubin, platelet count, and international normalized ratio were independent predictors of LRE and were combined into a model [NAFLD outcomes score (NOS)]. The NOS model calibrated well [calibration slope, 0.99 (derivation), 0.98 (validation)] with excellent overall performance [integrated Brier score, 0.07 (derivation) and 0.01 (validation)]. A cutoff ≥1.3 identified subjects at a higher risk of LRE, (sub-HR 24.6, p < 0.001, 5-year cumulative incidence 38% vs 1.0%, respectively). The predictive accuracy at 5 and 10 years was excellent in both derivation (time-dependent AUC,0.92 and 0.90, respectively) and validation cohorts (time-dependent AUC,0.80 and 0.82, respectively). The NOS was more accurate than the fibrosis-4 or NAFLD fibrosis score for predicting LREs at 5 and 10 years ( p < 0.001). CONCLUSIONS: The NOS model consists of readily available measures and has greater accuracy in predicting outcomes in patients with NAFLD than existing fibrosis models.

Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. METHODS: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3-4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. RESULTS: In 271 NAFLD patients, 83 (31%) had F3-4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). CONCLUSIONS: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.

Synchronous mucoepidermoid carcinoma and papillary microcarcinomas of the thyroid gland.

Thyroid mucoepidermoid carcinoma (MEC) is a rare thyroid malignancy first documented in 1977. The majority of thyroid MECs are indolent, low-grade tumours with excellent prognosis. A woman in her 60s presented with an ongoing sensation of a lump in the left neck. There were no swallowing, voice or airway concerns. Ultrasound of the neck showed an enlarged thyroid with U5 and U3 features on the right and left lobes, respectively. Right fine needle aspiration cytology (FNAC) demonstrated certain features of Hurthle cell or anaplastic carcinoma (Thy5). Left FNAC showed Hurthle cell changes with atypical cells and prominent nucleoli (Thy3a). Following total thyroidectomy, histopathology revealed synchronous right low-grade MEC and left papillary thyroid microcarcinomas (pT2(m) N0 M0) on a background of Hashimoto's thyroiditis. This case adds to the literature and details the key histopathological features for a rare but important differential in patients with thyroid carcinoma due to synchronous histological types.

Liver Transplant for Adult Recurrent Hepatic Mesenchymal Hamartoma and a Feasible Treatment Modality: A Case Report and Literature Review.

BACKGROUND: Adult hepatic mesenchymal hamartoma (HMH) is an extremely rare hepatic tumor. Recurrence following complete resection is uncommon. Liver transplantation (LT) is described as a possible treatment option in nonresectable HMH. We conducted a systematic review investigating LT in adult HMH followed by a case report describing evidence of extensive recurrence following complete resection of large right-sided HMH requiring LT. CASE REPORT: A 46-year-old woman with symptomatic large right-hepatic HMH underwent right hemi-hepatectomy with histologic evidence of complete resection. Two and a half years postresection, she presented with abdominal pain and distension; imaging revealed large multi-septated hepatic cystic lesions within the liver suggestive of extensive recurrence of disease with concerns of malignant sarcomatous transformation. After a multidisciplinary team discussion, the lesion was deemed unresectable and the patient was referred for LT. Findings on transplantation included giant multiple hepatic cystic lesions occupying the entire abdomen and histopathological analysis confirmed recurrent HMH with no malignancy. The 6-month follow-up was unremarkable with no signs of postoperative complications or rejection. CONCLUSION: We identified only 3 reported adult unresectable HMH cases in the English literature requiring LT, with good clinical outcome and no rejection on a 1-year follow-up. To our knowledge, we report the first recurrent HMH that required LT in the English literature. Current evidence suggests possible malignant sarcomatous transformation of those lesions. No guidelines exist on postresection surveillance for HMH; however, given their malignant potential, we suggest a benefit of imaging-based surveillance following HMH resection. Offering LT for nonresectable or recurrent HMH is a feasible treatment modality with a reported good outcome.

Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS).

Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

Serum Fibrosis Tests Guide Prognosis in Metabolic Dysfunction-Associated Fatty Liver Disease Patients Referred From Primary Care.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is managed predominately in primary care, however, there is uncertainty regarding how to best identify patients for specialist referral. We examined the accuracy of noninvasive tests as screening tools for the prediction of outcomes in MAFLD patients referred from primary care. METHODS: Patients with MAFLD referred by primary care for specialist review to Sir Charles Gairdner Hospital (cohort 1, n = 626) or tertiary centers within Western Australia (cohort 2, n = 246) were examined. Hepascore, aspartate aminotransferase to platelet ratio, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score performed at baseline were examined for their accuracy in predicting liver-related death (LRD), decompensation, and hepatocellular carcinoma. Outcomes were collected from hospital records and data linkage. RESULTS: The median follow-up period was 5.0 years (range, 0.1-13.0 y) and 3.8 years (range, 0.1-10.0 y) in cohorts 1 and 2, respectively. In both cohorts, Hepascore and FIB-4 had the highest area under the curve for the prediction of LRD (0.90-0.95 and 0.83-0.94, respectively), decompensation (0.86-0.91 and 0.86-0.87, respectively), and hepatocellular carcinoma (0.75-0.90 and 0.67-0.85, respectively). The sensitivity and negative predictive values were high (>90%) for Hepascore (cut-off value, 0.60), FIB-4 (cut-off value, 1.30), and nonalcoholic fatty liver disease fibrosis score (cut-off value, -1.455) for all outcomes in cohort 1, and for predicting LRD in cohort 2. Hepascore had the highest specificity, classified the greatest proportion of patients as low risk, and was favored by decision curve analysis as providing the greatest net benefit. CONCLUSIONS: Serum noninvasive tests accurately stratify risk of liver-related outcomes in MAFLD patients and can be used as a screening tool for patients referred for specialist review by primary care.

Hepascore predicts liver outcomes and all-cause mortality in long-term methotrexate users: A retrospective cohort study.

BACKGROUND AND AIM: Methotrexate (MTX) is routinely used for immunological disorders, and its long-term use is associated with hepatotoxicity. The aim of this study was to investigate whether a serum liver fibrosis test (Hepascore) predicted the risk of adverse liver-related outcomes and mortality. METHODS: A total of 92 patients in Western Australia who had a long-term MTX intake history,from 2004 to 2016, were recruited and followed up from the first Hepascore to death or end of the study. Clinical data, all deaths, and liver-related outcomes (liver-related death and decompensation) were obtained from hospital, PathWest, and WA Data Linkage Unit databases. RESULTS: Nine deaths and four adverse liver-related outcomes occurred during the follow up of 354 person-years. The 5-year survival was 86.1%. The liver-related outcome free survival was 95.6%. Baseline Hepascore ≥0.84 was associated with advanced fibrosis on liver biopsy (P = 0.025). A baseline Hepascore ≥0.84 was significantly associated with higher risks for adverse liver-related outcomes (P < 0.001) and all-cause mortality (P = 0.001). Cox regression demonstrated that only baseline Hepascore ≥0.84 was independently associated with the increased risk of all-cause mortality (7.91 [1.52-41.29], P = 0.014). Moreover, any Hepascore ≥0.84 found during follow up was independently associated with the increased risk of all-cause mortality (86.18 [4.03-1844.83], P = 0.007). CONCLUSIONS: This study demonstrated the potential importance of Hepascore monitoring in long-term MTX users. Patients with a Hepascore higher than 0.84 at any stage had increased mortality, but further studies are required to confirm this finding.

The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium-90 resin microsphere radioembolization.

BACKGROUND AND AIM: Yttrium-90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre-treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials. METHODS: Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child-Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups. RESULTS: One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2 months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End-Stage Liver Disease score (≤ 7), lower Alpha-fetoprotein (≤ 150 IU/L), higher serum Albumin (> 37 g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group = 0). Three survival prognostic groups were identified: good (median overall survival 25.0 months), average (15.3 months), and poor (6.3 months) (overall log-rank test, P < 0.001). CONCLUSION: The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.

The role of allied healthcare professionals in head and neck cancer surveillance: A systematic review.

OBJECTIVES: The roles of Allied Health Care Professionals (AHPs) in Head and Neck Cancer (HNC) are wide ranging but not clearly defined. Inter-regional variability in practice results from a lack of standardisation in approaches to the Multidisciplinary Team (MDT) make-up and structure. Traditionally, the follow-up of HNC patients is clinician led with multiple scheduled follow-up appointments. The increasing population of HNC patients provides logistical, monetary and efficiency challenges. This systematic review presents the roles of the multiple AHP sub-groups in HNC with the aim of presenting how their differing skill sets can be integrated to modernise our approach in follow-up. DESIGN: We searched MEDLINE, Embase, the Cochrane Library, NIHR Dissemination Centre, The Kings Fund Library, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify multiple subgroups of AHPs (Dentists, Speech and Language Therapists, Dieticians, Physiotherapists, Psychologists, Clinical Nurse Specialists) and evidence of their role in HNC follow-up. Evidence not directly relating to HNC follow-up was excluded. SETTING AND PARTICIPANTS: This Systematic Review was undertaken online by the Integrate (UK ENT Trainee National Collaborative) Head and Neck Subcommittee. MAIN OUTCOME MEASURES: Most evidence was of low-quality, and the broad nature of the protocol provided a wide variety of study models. Two authors screened the articles for relevance to the topic before final analysis. RESULTS: The main role identified was improvement in Quality of Life and symptom control rather than detecting recurrence. We also demonstrate that it is possible to stratify HNC follow-up patients using their received treatment modality and Distress Thermometers to identify groups who will require more intensive AHP input. CONCLUSIONS: HNC follow-up covers a broad group of patients with differing needs. As such, a blanket approach to this phase of treatment is likely to be less effective than a patient-led model where the group of AHPs are employed on a needs basis rather than at set time points. This will likely lead to greater patient satisfaction, earlier detection of recurrence and efficiency savings.