Temporary treatment cessation versus continuation of first-line tyrosine kinase inhibitor in patients with advanced clear cell renal cell carcinoma (STAR): an open-label, non-inferiority, randomised, controlled, phase 2/3 trial.

BACKGROUND: Temporary drug treatment cessation might alleviate toxicity without substantially compromising efficacy in patients with cancer. We aimed to determine if a tyrosine kinase inhibitor drug-free interval strategy was non-inferior to a conventional continuation strategy for first-line treatment of advanced clear cell renal cell carcinoma. METHODS: This open-label, non-inferiority, randomised, controlled, phase 2/3 trial was done at 60 hospital sites in the UK. Eligible patients (aged ≥18 years) had histologically confirmed clear cell renal cell carcinoma, inoperable loco-regional or metastatic disease, no previous systemic therapy for advanced disease, uni-dimensionally assessed Response Evaluation Criteria in Solid Tumours-defined measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) at baseline to a conventional continuation strategy or drug-free interval strategy using a central computer-generated minimisation programme incorporating a random element. Stratification factors were Memorial Sloan Kettering Cancer Center prognostic group risk factor, sex, trial site, age, disease status, tyrosine kinase inhibitor, and previous nephrectomy. All patients received standard dosing schedules of oral sunitinib (50 mg per day) or oral pazopanib (800 mg per day) for 24 weeks before moving into their randomly allocated group. Patients allocated to the drug-free interval strategy group then had a treatment break until disease progression, when treatment was re-instated. Patients in the conventional continuation strategy group continued treatment. Patients, treating clinicians, and the study team were aware of treatment allocation. The co-primary endpoints were overall survival and quality-adjusted life-years (QALYs); non-inferiority was shown if the lower limit of the two-sided 95% CI for the overall survival hazard ratio (HR) was 0·812 or higher and if the lower limit of the two-sided 95% CI of the marginal difference in mean QALYs was -0·156 or higher. The co-primary endpoints were assessed in the intention-to-treat (ITT) population, which included all randomly assigned patients, and the per-protocol population, which excluded patients in the ITT population with major protocol violations and who did not begin their randomisation allocation as per the protocol. Non-inferiority was to be concluded if it was met for both endpoints in both analysis populations. Safety was assessed in all participants who received a tyrosine kinase inhibitor. The trial was registered with ISRCTN, 06473203, and EudraCT, 2011-001098-16. FINDINGS: Between Jan 13, 2012, and Sept 12, 2017, 2197 patients were screened for eligibility, of whom 920 were randomly assigned to the conventional continuation strategy (n=461) or the drug-free interval strategy (n=459; 668 [73%] male and 251 [27%] female; 885 [96%] White and 23 [3%] non-White). The median follow-up time was 58 months (IQR 46-73 months) in the ITT population and 58 months (46-72) in the per-protocol population. 488 patients continued on the trial after week 24. For overall survival, non-inferiority was demonstrated in the ITT population only (adjusted HR 0·97 [95% CI 0·83 to 1·12] in the ITT population; 0·94 [0·80 to 1·09] in the per-protocol population). Non-inferiority was demonstrated for QALYs in the ITT population (n=919) and per-protocol (n=871) population (marginal effect difference 0·06 [95% CI -0·11 to 0·23] for the ITT population; 0·04 [-0·14 to 0·21] for the per-protocol population). The most common grade 3 or worse adverse events were hypertension (124 [26%] of 485 patients in the conventional continuation strategy group vs 127 [29%] of 431 patients in the drug-free interval strategy group); hepatotoxicity (55 [11%] vs 48 [11%]); and fatigue (39 [8%] vs 63 [15%]). 192 (21%) of 920 participants had a serious adverse reaction. 12 treatment-related deaths were reported (three patients in the conventional continuation strategy group; nine patients in the drug-free interval strategy group) due to vascular (n=3), cardiac (n=3), hepatobiliary (n=3), gastrointestinal (n=1), or nervous system (n=1) disorders, and from infections and infestations (n=1). INTERPRETATION: Overall, non-inferiority between groups could not be concluded. However, there seemed to be no clinically meaningful reduction in life expectancy between the drug-free interval strategy and conventional continuation strategy groups and treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma. FUNDING: UK National Institute for Health and Care Research.

Long-term outcomes of image-guided ablation and laparoscopic partial nephrectomy for T1 renal cell carcinoma.

OBJECTIVE: To compare long-term outcomes and peri-operative outcomes of image-guided ablation (IGA) and laparoscopic partial nephrectomy (LPN). MATERIAL AND METHODS: This is a retrospective cohort study of localised RCC (T1a/bN0M0) patients undergoing cryoablation (CRYO), radio-frequency ablation (RFA), or LPN at our institution from 2003 to 2016. Oncological outcomes were compared using Cox regression and log-rank analysis. eGFR changes were compared using Kruskal-Wallis and Wilcoxon-rank tests. RESULTS: A total of 296 (238 T1a, 58 T1b) consecutive patients were identified; 103, 100, and 93 patients underwent CRYO, RFA, and LPN, respectively. Median follow-up time was 75, 98, and 71 months, respectively. On univariate analysis, all oncological outcomes were comparable amongst CRYO, RFA, and LPN (p > 0.05). On multivariate analysis, T1a patients undergoing RFA had improved local recurrence-free survival (LRFS) (HR 0.002, 95% CI 0.00-0.11, p = 0.003) and metastasis-free survival (HR 0.002, 95% CI 0.00-0.52, p = 0.029) compared to LPN. In T1a and T1b patients combined, both CRYO (HR 0.07, 95% CI 0.01-0.73, p = 0.026) and RFA (HR 0.04, 95% CI 0.03-0.48, p = 0.011) had improved LRFS rates. Patients undergoing CRYO and RFA had a significantly smaller median decrease in eGFR post-operatively compared to LPN (T1a: p < 0.001; T1b: p = 0.047). Limitations include retrospective design and limited statistical power. CONCLUSIONS: IGA is potentially as good as LPN in oncological durability. IGA preserves kidney function significantly better than LPN. More studies with larger sample size should be performed to establish IGA as a first-line treatment alongside LPN. KEY POINTS: • Ablative therapies are alternatives to partial nephrectomy for managing small renal cell carcinomas. • This study reports long-term outcomes of image-guided ablation versus partial nephrectomy. • Ablative therapies have comparable oncological durability and better renal function preservation compared to partial nephrectomy.

The changing trends of image-guided biopsy of small renal masses before intervention-an analysis of European multinational prospective EuRECA registry.

OBJECTIVES: To evaluate the use of pre-cryoablation biopsy for small renal masses (SRMs) and the effects of increasing uptake on histological results of treated SRMs. METHODS: From 2015 to 2019, patients with sporadic T1N0M0 SRMs undergoing percutaneous, laparoscopic, or open cryoablation from 14 European institutions within the European Registry for Renal Cryoablation (EuRECA) were included for the retrospective analysis. Univariate and multivariate logistic models were used to evaluate the trends, histological results, and the factors influencing use of pre-cryoablation biopsy. RESULTS: In total, 871 patients (median (IQR) age, 69 (14), 298 women) undergoing cryoablation were evaluated. The use of pre-cryoablation biopsy has significantly increased from 42% (65/156) in 2015 to 72% (88/122) in 2019 (p < 0.001). Patients treated for a benign histology are significantly more likely to have presented later in the trend, where pre-cryoablation biopsy is more prevalent (OR: 0.64, 95% CI 0.51-0.81, p < 0.001). Patients treated for undiagnosed histology are also significantly less likely to have presented in 2018 compared to 2016 (OR 0.31, 95% CI 0.10-0.97, p = 0.044). Patients aged 70+ are less likely to be biopsies pre-cryoablation (p < 0.05). R.E.N.A.L. nephrometry score of 10+ and a Charlson Comorbidity Index > 1 are factors associated with lower likelihood to not have received a pre-cryoablation biopsy (p < 0.05). CONCLUSION: An increased use of pre-cryoablation biopsy was observed and cryoablation patients treated with a benign histology are more likely to have presented in periods where pre-cryoablation biopsy is not as prevalent. Comparative studies are needed to draw definitive conclusions on the effect of pre-cryoablation biopsy on SRM treatments. KEY POINTS: • The use of biopsy pre-ablation session has increased significantly from 42% of all patients in 2015 to 74% in 2019. • Patients are less likely to be treated for a benign tumour if they presented later in the trend, where pre-cryoablation biopsy is more prevalent, compared to later in the trend (OR 0.64, 95% CI 0.51-0.81, p < 0.001). • Patients with comorbidities or a complex tumour (R.E.N.A.L. nephrometry score > 10) are less likely to not undergo biopsy as a separate session to cryoablation.

Irreversible electroporation (IRE) in renal cell carcinoma (RCC): a mid-term clinical experience.

OBJECTIVES: To evaluate the safety and efficacy of CT-guided IRE of clinical T1a (cT1a) renal tumours close to vital structures and to assess factors that may influence the technical success and early oncological durability. METHODS: CT-guided IRE (2015-2020) was prospectively evaluated. Patients' demographics, technical details/success, Clavien-Dindo (CD) classification of complications (I-V) and oncological outcome were collated. Statistical analysis was performed to determine variables associated with complications. The overall 2- and 3-year cancer-specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates are presented using the Kaplan-Meier curves. RESULTS: Thirty cT1a RCCs (biopsy-proven/known VHL disease) in 26 patients (age 32-81 years) were treated with IRE. The mean tumour size was 2.5 cm and the median follow-up was 37 months. The primary technical success rate was 73.3%, where 22 RCCs were completely IRE ablated. Seven residual diseases were successfully ablated with cryoablation, achieving an overall technical success rate of 97%. One patient did not have repeat treatment as he died from unexpected stroke at 4-month post-IRE. One patient had CD-III complication with a proximal ureteric injury. Five patients developed > 25% reduction of eGFR immediately post-IRE. All patients have preservation of renal function without the requirement for renal dialysis. The overall 2- and 3-year CS, LRF and MF survival rates are 89%, 96%, 91% and 87%. CONCLUSION: CT-guided IRE in cT1a RCC is safe with acceptable complications. The primary technical success rate was suboptimal due to the early operator's learning curve, and long-term follow-up is required to validate the IRE oncological durability. KEY POINTS: • Irreversible electroporation should only be considered when surgery or image-guided thermal ablation is not an option for small renal cancer. • This non-thermal technique is safe in the treatment of small renal cancer and the primary technical success rate was 73.3%. • This can be used when renal cancer is close to important structure.

The utility of magnetic resonance imaging in addition to computed tomography scans in the evaluation of cervical spine injuries: a study of obtunded blunt trauma patients.

PURPOSE: Evidence guiding the use of CT and MRI scans in blunt trauma patients who are obtunded remains controversial. This study aims to determine and predict if computed tomography (CT) scans alone can be performed without risking oversight of substantial injuries found on follow-up magnetic resonance imaging (MRI). METHODS: This is a retrospective cohort study of 63 blunt trauma patients with a Glasgow Coma Scale of < 8. Data were collated from electronic medical records and included patient demographics, premorbid mobility, mechanism of injury, suspected level of injury and neurological examination findings. Patients were urgently evaluated using CT scans, followed by non-contrast MRI scans within 48 h of admission. The accuracy of CT scan was evaluated using MRI as a reference. Adjusted multivariable analysis was also performed to identify predictors for findings detected on MRI but not on CT. RESULTS: The mean age of patients was 42.3 years and 90.5% were males. CT scans had a high specificity of 100% and sensitivity of 87.2%. Predictors of MRI abnormalities include females, patients with relatively milder mechanisms of injury, patients with suspected thoracic spine injury, and CT scan findings of facet dislocation and intracranial haemorrhage. There was no predictor for spinal cord oedema. CONCLUSIONS: MRI should be performed in the presence of the aforementioned predictive factors and in the presence of neurological deficits. Otherwise, patients can be treated medically without the fear of missing a substantial cervical injury.

The accuracy of magnetic resonance imaging (MRI) in predicting the invasion of the tunica albuginea and the urethra during the primary staging of penile cancer.

OBJECTIVES: To assess the accuracy of magnetic resonance imaging (MRI) in predicting invasion of the tunica albuginea (TA) and the urethra during the primary staging of penile cancer. PATIENTS AND METHODS: In all, 104 consecutive patients with clinical T1-T3 penile cancer had a penile MRI as a part of local staging protocol. An artificial erection was induced before MRI by injecting alprostadil (prostaglandin E1 ). Four men with poor quality MRI images were excluded from the study. The preoperative MRI was compared with final histology to assess its accuracy in predicting the invasion of the TA and urethra. RESULTS: Data of 100 patients who underwent penile MRI before definitive surgery for invasive penile carcinoma were available for analysis. The mean age was 65 years and number of patients with pathological stage T1, T2 and T3 was 32, 52, and 16, respectively. The sensitivity and specificity of MRI in predicting the invasion of TA and urethra was 82.1% and 73.6%, and 62.5% and 82.1%, respectively. There were no MRI-related complications. CONCLUSIONS: This study shows that penile MRI is an accurate method for assessing TA invasion but is less sensitive in assessing urethral invasion. These results support the use of MRI in the local staging of penile cancer.

Hepatocellular carcinoma: modern image-guided therapies.

The most common primary malignancy of the liver and the third leading cause of cancer mortality worldwide is hepatocellular carcinoma (HCC), which presents a major global health problem due to its increasing incidence. Most cases of HCC are secondary to either infection (hepatitis B or C) or cirrhosis (alcohol being the most common cause). Clinical presentation is variable and the tumour can be an incidental finding. Treatment options for HCC and prognosis are dependent on many factors but most importantly tumour size and staging. The last two decades have revolutionised the treatment of HCC using image-guided techniques. The concepts of imaging and image-guided techniques are still young and not well described in standard textbooks and hence an up to date review article is essential. The clinical subspecialities may lack familiarity with image-guided techniques but are responsible for management of these patients before and after the treatment by interventional radiologists. This article reviews current image-guided techniques, evidence and outcomes and provides educational highlights and question and answers. The article provides an overview in a simple understandable manner to enable readers from various levels of practice and training to benefit from and apply in their practice.

Radiofrequency ablation (RFA) of renal cell carcinoma (RCC): experience in 200 tumours.

OBJECTIVES: To evaluate our clinical experience with percutaneous image-guided radiofrequency ablation (RFA) of 200 renal tumours in a large tertiary referral university institution. PATIENTS AND METHODS: Image-guided RFA (ultrasonography or computed tomography [CT]) of 200 renal tumours in 165 patients from June 2004 to 2012 was prospectively evaluated. Institutional Review Board approval was granted. The treatment response and technical success were defined by absence of contrast enhancement within the tumour on contrast enhanced CT or magnetic resonance imaging. Both major and minor complications, glomerular filtration rate (GFR) before and after RFA, the management and outcomes of the complications, as well as oncological outcome were prospectively documented. Multivariate analysis was used to determine variables associated with major complications and also the percentage GFR change after RFA. The overall (OS), 5-year cancer-specific (CSS), local recurrence-free (LRFS) and metastasis-free survival (MFS) rates are presented using the Kaplan-Meier curves. RESULTS: In all, 200 tumours were RF ablated with a mean (range) tumour size of 2.9 (1-5.6) cm and the mean (range) patient age was 67.7 (21-88.6) years with a mean follow-up period of 46.1 months. The primary technical and overall technical success rate was 95.5% and 98.5%, respectively. Two independent predictors of successful RFA in a single sitting were tumour size (<3 cm) and exophytic location in multivariate logistic regression analysis. Major complications included ureteric injury (six patients), calyceal-cutaneous fistula (one), acute tubular necrosis (one) and abscess (two). Two independent predictors of ureteric injury were central location and lower pole position. Within this cohort of patients, only four patients developed significant renal function deterioration i.e. >25% decreased in GFR. In all, 161 (98%) patients of the 165 patients have preservation of renal function. Any change in renal function after RFA was not influenced by tumour factors or solitary kidney status. In our clinical series, this yielded a 5-year OS, CSS, LRFS and MFS rates of 75.8%, 97.9%, 93.5% and 87.7% respectively. CONCLUSIONS: Image-guided RFA is a safe, nephron sparing and effective treatment for small renal cell carcinoma (RCC) tumours with a low rate of recurrence and has good 5-year CSS and MFS rates.

Image-Guided Ablation of Renal Masses: Challenges to Produce High-Quality Evidence and Future Directions.

Image-guided ablation (IGA) is a rapidly developing field in interventional oncology. There is some evidence suggesting IGA's non-inferiority compared with partial or radical nephrectomy for the treatment of small renal masses (SRM). However, these are mostly limited to retrospective cohort studies. This review article outlines the evidence comparing IGA to partial nephrectomy by collating the different survival measures and evaluates the challenges of producing clinical trials and high-quality evidence. The main challenges are due to the heterogeneity of SRM, patient selection bias, unstandardized endpoint and outcomes, and the lack of global practice standards. Despite the evidence thus far demonstrating that IGA stands as a non-inferior treatment modality for SRMs, exhibiting favorable short- and long-term outcomes, further robust research is needed to integrate ablation techniques into routine clinical practice with a multidisciplinary approach. There is emerging evidence that suggests randomized controlled trial in SRMs is possible, and technologies such as histotripsy as well as artificial intelligence are used in IGA.

Renal Function After CT-Guided Cryoablation of Small Renal Tumours in Patients with Solitary Kidney: An Analysis of European Multinational Prospective EuRECA Registry.

PURPOSE: Treatment of renal cell carcinoma (RCC) in patients with solitary kidneys remains challenging. The purpose of this multicentre cohort study was to explore how renal function is affected by percutaneous image-guided cryoablation in patients with solitary kidneys. MATERIAL AND METHODS: Data from the European Registry for Renal Cryoablation database were extracted on patients with RCC in solitary kidneys treated with image-guided, percutaneous cryoablation. Patients were excluded if they had multiple tumours, had received previous treatment of the tumour, or were treated with more than one cryoablation procedure. Pre- and post-treatment eGFR (within 3 months of the procedure) were compared. RESULTS: Of 222 patients with solitary kidneys entered into the database, a total of 70 patients met inclusion criteria. The mean baseline eGFR was 55.8 ± 16.8 mL/min/1.73 m2, and the mean 3-month post-operative eGFR was 49.6 ± 16.5 mL/min/1.73 m2. Mean eGFR reduction was - 6.2 mL/min/1.73 m2 corresponding to 11.1% (p = 0.01). No patients changed chronic kidney disease group to severe or end-stage chronic kidney disease (stage IV or V). No patients required post-procedure dialysis. CONCLUSION: Image-guided renal cryoablation appears to be safe and effective for renal function preservation in patients with RCC in a solitary kidney. Following cryoablation, all patients had preservation of renal function without the need for dialysis or progression in chronic kidney disease stage despite the statistically significant reduction in eGFR. LEVEL OF EVIDENCE 3: Observational study.

Percutaneous treatment of renal tumours.

Image-guided ablation is an accepted treatment option in the management of renal cell carcinoma. Percutaneous renal ablation offers the possibility of minimally invasive treatment while attempting to preserve renal function. Over the past several years there have been advances in tools and techniques that have improved procedure safety and patient outcomes. This article provides an updated comprehensive review of percutaneous ablation in the management of renal cell carcinoma.

A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER).

PURPOSE: Image-guided thermal ablation are established treatment options for non-surgical patients with primary and metastatic liver cancers. However, there are limitations with nonuniformity of cancer tissue destruction, heat sink effect and the risk of thermal ablative injury. The current non-thermal ablative techniques have high risk of local recurrence and are not widely adopted. Histotripsy is a treatment technology that destroys targeted tissue under ultrasound visualization via mechanical destruction through the precise application of acoustic cavitation and can offer the potential of non-invasive, non-thermal and non-ionizing radiation cancer treatment. The aim of this multi-centre non-randomized phase I/II trial is to assess the initial safety and efficacy of the prototype investigational 'System' in the treatment of primary and metastatic liver cancers. METHODS/DESIGN: All non-surgical patients with primary/metastatic liver cancers having had previous liver directed therapy, radiation therapy or image-guided ablation may be offered image-guided Histotripsy as per trial protocol. The co-primary endpoints are technical success and procedural safety. Technical success is determined, at ≤ 36 h post procedure, by evaluating the histotripsy treatment size and coverage. The procedural safety is defined by procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE version 5) grade 3 or higher toxicities, up to 30 days post procedure. This phase I/II trial has intended to recruit up to 45 patients to show safety and efficacy of image-guided histotripsy in liver cancers. TRAIL REGISTRATION: Clinicaltrials.gov identifier-NCT04573881; NIHR CRN CPMS-ID 47572.

The current status of interventional radiology in the undergraduate medical curriculum and the way forward.

Interventional radiology (IR) is underrepresented in undergraduate medical school curricula. Despite the introduction of a suggested undergraduate curriculum for IR by the British Society of Interventional Radiology (BSIR), current evidence suggests there is inadequate knowledge and awareness of IR amongst medical students. As a result of this, there is a lack of visibility of the subspeciality amongst medical students and junior doctors contributing to the shortage of IR trainees resulting in an IR workforce crisis in the UK. The uptake of the proposed undergraduate IR curriculum remains unclear, highlighting the need for a thorough audit and improvement of IR teaching in undergraduate medical education. In this commentary, we discuss the importance of including IR in the undergraduate curriculum, the evidence surrounding undergraduate IR education, the reasons for the potential lack of interest in IR from medical students and future steps to ensure optimal IR exposure in undergraduate medical school curricula.

The effectiveness of ablative and non-surgical therapies for early hepatocellular carcinoma: Systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND & AIMS: Non-surgical therapies are frequently used for patients with early or very early hepatocellular carcinoma (HCC). The aim of this systematic review and network meta-analysis (NMA) was to evaluate and compare the effectiveness of ablative and non-surgical therapies for patients with small HCC. METHODS: Nine databases were searched (March 2021) along with clinical trial registries. Randomised controlled trials (RCTs) of any ablative or non-surgical therapy versus any comparator in patients with HCC ≤3 cm were eligible. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The effectiveness of therapies was compared using NMA. Threshold analysis was undertaken to identify which NMA results had less robust evidence. RESULTS: Thirty-seven eligible RCTs were included (including over 3700 patients). Most were from China (n = 17) or Japan (n = 7). Sample sizes ranged from 30 to 308 patients. The majority had a high RoB or some RoB concerns. No RCTs were identified for some therapies and no RCTs reported quality of life outcomes. The results of the NMA and treatment effectiveness rankings were very uncertain. However, the evidence demonstrated that percutaneous ethanol injection was worse than radiofrequency ablation for overall survival (hazard ratio [HR]: 1.45, 95% credible interval [CrI]: 1.16-1.82), progression-free survival (HR: 1.36, 95% CrI: 1.11-1.67), overall recurrence (relative risk [RR]: 1.19, 95% CrI: 1.02-1.39) and local recurrence (RR: 1.80, 95% CrI: 1.19-2.71). The threshold analysis suggested that robust evidence was lacking for some comparisons. CONCLUSIONS: It is unclear which treatment is most effective for patients with small HCC because of limitations in the evidence base. It is also not known how these treatments would impact on quality of life. Further high quality RCTs are needed to provide robust evidence but may be difficult to undertake.

Oncological and Peri-Operative Outcomes of Percutaneous Cryoablation of Renal Cell Carcinoma for Patients with Hereditary RCC Diseases-An Analysis of European Multi-Centre Prospective EuRECA Registry.

This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan-Meier method. Simple proportions, chi-squared tests, and t-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75-99%), 96.4% (95% CI 77-99%), 90.9% (95% CI 51-99%), and 90.9% (95% CI 51-99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation.

There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution from 2003 to 2016. A total of 203 patients were included in the analysis. In the multivariable analysis, patients with raised neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) pre-operatively, post-operatively and peri-operatively are associated with significantly worsened cancer-specific survival, overall survival and metastasis-free survival. Furthermore, an increased PLR pre-operatively is also associated with increased odds of a larger than 25% drop in renal function post-operatively. In conclusion, NLR and PLR are effective prognostic factors in predicting oncological outcomes and peri-operative outcomes; however, larger external datasets should be used to validate the findings prior to clinical application.

Protocol for a MULTI-centre feasibility study to assess the use of 99mTc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

Use of Activated Recombinant Factor VII in Severe Bleeding - Evidence for Efficacy and Safety in Trauma, Postpartum Hemorrhage, Cardiac Surgery, and Gastrointestinal Bleeding.

BACKGROUND: Uncontrolled bleeding continues to be a major cause of mortality in trauma, cardiac surgery, postpartum hemorrhage and liver failure. The aim of this paper is to assess the evidence supporting the efficacy of activated recombinant factor VII (rFVIIa) administration in these settings. METHODS: Electronic literature search. RESULTS: Numerous retrospective trials have mostly shown a decrease in blood transfusion requirements with no increase in thromboembolic events (TEE), but major limitations in trial design make generalization difficult. In most retrospective reports rFVIIa has been administered as a last-ditch attempt to control bleeding, when acidosis, hypothermia and coagulation factor depletion may not allow optimal rFVIIa effect. Prospective randomized controlled trials have not shown any effect of rFVIIa on mortality or TEE, although some have shown a reduction in RBC requirement. CONCLUSION: Stipulated transfusion protocols in prospective trials have reduced anticipated mortality among controls and make future trials for mortality effect unlikely in view of large sample size requirements. Establishment of these protocols and rapid hemostasis are likely to have greater benefits than administration of a single agent.