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.

Perioperative management including dual cell salvage in a Jehovah's Witness patient undergoing major urological surgery.

Complex surgery associated with major hemorrhage presents particular risks for Jehovah's Witnesses who do not accept transfusion of blood products. Intraoperative use of two cell saver machines simultaneously can maximize the yield of salvaged blood from both the operative field and from washed surgical swabs and can potentially be life-saving.

Hexylaminolaevulinate fluorescence cystoscopy in patients previously treated with intravesical bacille Calmette-Guérin.

OBJECTIVE To determine if hexylaminolaevulinate fluorescence cystoscopy (HAL-FC) has the potential to improve the diagnosis of bladder cancer in patients who have been treated with bacille Calmette-Guérin (BCG). PATIENTS AND METHODS Patients scheduled for rigid cystoscopy after BCG therapy were recruited prospectively between April 2005 and February 2006. Patients received HAL (Hexvix, PhotoCure ASA, Oslo, Norway) and the D-light system (Storz, Tuttlingen, Germany) was used to detect fluorescence. The bladder was mapped and biopsies taken under white light and then using HAL-FC. The main outcome was the frequency and nature of additional pathology detected by HAL-FC. Twenty-seven patients (21 men and six women; median age 70 years, range 49-82) underwent 32 HAL-FC. RESULTS Recurrent bladder cancer was detected in 11 of the 32 (34%) examinations. HAL-FC detected additional pathology in five of the 27 (19%) patients. In two of these cases the additional pathology was clinically significant (one pT4G3 intraprostatic transitional cell carcinoma and one intravesical pT1G2 + carcinoma in situ), whereas in three cases the pathology was hyperplasia/dysplasia. Overall, the false-positive biopsy rate with HAL-FC was 63%. In the presence of positive voided urine cytology six of eight patients had recurrent bladder tumour and the false-positive biopsy rate was only 34%. Urine cytology was positive in four of five of the patients in whom additional pathology was detected by HAL-FC. CONCLUSIONS Clinically significant occult pathology can be detected using HAL-FC after BCG therapy, but in <10% of cases. The rate of false-positive biopsies is high but in our hands appears to be lower than with white-light guided biopsies after BCG. Our pragmatic approach is to use HAL-FC after BCG when clinical suspicion is high, and when the preoperative voided urine cytology is positive.

Hexylaminolevulinate photodynamic diagnosis for multifocal recurrent nonmuscle invasive bladder cancer.

OBJECTIVE: To determine the potential for hexylaminolevulinate (HAL) photodynamic diagnosis (PDD) to improve the management of multifocal recurrent nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients with a history of NMIBC and with at least two suspected papillary recurrences were enrolled in this prospective study between April 2005 and October 2006. The photosensitizer was hexylaminolevulinate (HAL) (PhotoCure, Norway), and the Storz D-light system was used to detect fluorescence. The bladder was mapped initially under white light and then using HAL-photodynamic diagnosis (PDD). The number and types of additional lesions detected by HAL-PDD over white light cystoscopy were measured. RESULTS: Eighteen patients (11 men), median age 74 years (range 35-84 yrs), underwent HAL-PDD. The median HAL instillation time was 109 minutes (range 60-250 min). Recurrent bladder cancer was confirmed histologically in 14/18 (78%) patients. Additional pathology was detected in 8/14 (57%) patients with confirmed recurrence and confirmed histologically in 6 of these. Additional pathology was papillary in 5/6 (83%) patients, and flat pathology was found in all six patients with additional foci. Carcinoma in situ (CIS) was detected in 4/6 (67%) patients with additional foci, three of whom were subsequently treated with intravesical bacille Calmette-Guérin (BCG). The sensitivity of HAL-PDD for the detection of tumor was 97.8%, compared with 69.6% for white light cystoscopy. The false-positive fluorescence-guided biopsy rate was 18/63 (29%). CONCLUSION: HAL-PDD allows more complete management of bladder tumor in patients with multifocal recurrence. The high frequency of additional lesions detected and the rate of detection of CIS suggest that HAL-PDD should be the standard of care.

Hexylaminolaevulinate 'blue light' fluorescence cystoscopy in the investigation of clinically unconfirmed positive urine cytology.

OBJECTIVE: To investigate the value of photodynamic diagnosis (PDD) using hexylaminolaevulinate (Hexvix, PhotoCure, Oslo, Norway) in the investigation of patients with positive urine cytology who have no evidence of disease after standard initial investigations. PATIENTS AND METHODS: Twenty-three patients referred with positive urine cytology but no current histological evidence of cancer were investigated between April 2005 and January 2007 with PDD, using Hexvix and the D-light system (Karl Storz, Tuttlingen, Germany) to detect fluorescence. The bladder was mapped initially under white light and then under 'blue-light'. Biopsies were taken from abnormal urothelium detected by white light, fluorescence, or both. All cytological specimens were reviewed by a reference cytopathologist unaware of the result of the PDD. RESULTS: Twenty-five PDD-assisted cystoscopies were carried out on 23 patients (20 men/3 women; median age 64 years, range 24-80 years). Of the 23 patients, 17 (74%) were previously untreated for transitional cell carcinoma (TCC), whilst six were under surveillance for previous TCC. Nineteen of the 23 (83%) cytology specimens were confirmed as suspicious or positive by the reference pathologist. TCC of the bladder or preneoplastic lesions were diagnosed in six patients, i.e. six (26%) of those investigated and six of 19 (32%) with confirmed positive cytology. Four of the six were under surveillance for previous bladder tumour. Additional pathology was detected by fluorescence in five of the six patients, including two carcinoma in situ (CIS), one CIS + G3pT1 tumour, and two dysplasia. Diagnoses in PDD-negative cases included one upper tract TCC and four patients with stones. In addition, one patient had CIS diagnosed on both white light and PDD 6 months later. CONCLUSION: Additional pathology was detected by HAL fluorescence cystoscopy in 32% of patients with confirmed positive urinary cytology. PDD is a key step in the management of patients with positive urinary cytology and no evidence of disease on conventional tests.

Robotic-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion: initial experience.

BACKGROUND: The use of robotic technology for laparoscopic prostatectomy is now well established. The same cannot yet be said of robotic-assisted laparoscopic radical cystectomy (RARC), which is performed in just a few centres worldwide. OBJECTIVE: We present our technique and experience of this procedure using the da Vinci surgical system. DESIGN, SETTING, AND PARTICIPANTS: From 2004 to 2007, 23 patients underwent RARC and urinary diversion at our institution. SURGICAL PROCEDURE: We report the development of our technique for RARC, which involves posterior dissection, lateral pedicle control, anterior dissection, and lymphadenectomy prior to either ileal conduit urinary diversion or Studer pouch reconstruction performed extracorporeally. MEASUREMENTS: Demographic and perioperative data were recorded prospectively. Oncologic and functional outcomes were assessed at 3- to 6-mo intervals. RESULTS AND LIMITATIONS: To date, 23 patients have undergone this procedure at our institution. Of those, 19 had ileal loop urinary diversion and 4 were suitable for Studer pouch reconstruction. Mean total operative time plus or minus (+/-) standard deviation (SD) was 397+/-83.8min. Mean blood loss +/-SD was 278+/-229ml with one patient requiring a blood transfusion. Surgical margins were clear in all patients with a median +/-SD of 16+/-8.9 lymph nodes retrieved. The complication rate was 26%. At a mean follow-up +/-SD of 17+/-13 (range 4-40) mo, one patient had died of metastatic disease and one other is alive with metastases. The remaining 21 patients are alive without recurrence. CONCLUSIONS: RARC remains a procedure in evolution in the small number of centres carrying out this type of surgery. Our initial experience confirms that it is feasible with acceptable morbidity and good short-term oncologic results.

The importance of palliative care in urology.

INTRODUCTION: The aim of this study was to identify patients with advanced urological cancer who may benefit from specialist palliative care and to quantify the number of these patients, characterize their problems and to see if their needs were being met. METHODS: The study was divided into two parts over 4-month periods centred on a hospital trust in the UK with a catchment population of 850,000. Urology in-patients were observed prospectively and out-patients were observed retrospectively. Patients were included if they had unresectable, locally advanced or metastatic urological cancer. Patients with prostate cancer were included if they had advanced disease with hormone relapse, defined as three successive rises in PSA. RESULTS: 881 admissions to the urology ward were reviewed. A total of 24 patients with terminal malignancy had 27 admissions. Two patients died during their admission. The average length of stay was 16.6 days. Only 5 patients underwent surgical intervention. The majority of patients had general systemic symptoms of advanced malignancy. 2,482 out-patient visits were reviewed where 69 patients with terminal malignancy received 82 outpatient consultations, representing approximately 10% of all cancer visits. Seventy-five percent of the patients had specific problems or were generally unwell as a result of their disease and would have benefited from specialist palliative care. The remaining 25% were well at the time of their visit, but potential psychosocial problems arising from coping with advancing terminal disease were not addressed. CONCLUSION: Patients requiring palliative care place a heavy burden on in- and out-patient services. There is a case for a palliative care physician to be closely involved in urological cancer teams. Urologists need to be trained in palliative care, as this comprises a significant volume of their work.

Combined percutaneous radiofrequency ablation and ethanol injection of renal tumours: midterm results.

OBJECTIVES: To evaluate the safety and efficacy of combined percutaneous, image-guided, radiofrequency (RF) ablation and ethanol injection of renal tumours, and to present our midterm results. METHODS: Since February 2002, 27 consecutive patients (22 men, 5 women; age range: 39-84 yr; mean: 69) with 28 renal tumours (mean diameter: 2.87cm) were treated with combined percutaneous RF and ethanol ablation, and were prospectively evaluated. Twenty-five patients were considered nonsurgical candidates because of comorbid conditions (16 patients) or had previous nephrectomy (9 patients), and 2 had refused surgery. Thirty-three ablation sessions were performed, with computed tomography (26 sessions), ultrasound (6), or combined magnetic resonance imaging/fluoroscopic guidance in 1. Absolute ethanol (0.5-3ml; mean: 1.7) was injected into the tumour immediately before treatment with radiofrequency. Mean follow-up period was 18.6 mo (range: 3-56). RESULTS: Twenty-seven of the 28 tumours were completely ablated with either one (21 tumours) or two treatment sessions (6 tumours). One patient with residual disease refused further treatment. Only three minor complications, including a subcapsular haematoma and two patients with loin pain, occurred; all three patients were treated conservatively. None of the complications was related to the ethanol injection. During the follow-up period, no evidence of local recurrence or metastatic disease was seen. Creatinine levels have not changed significantly in any of the patients following ablation. CONCLUSIONS: Combined use of percutaneous RF and ethanol ablation is a safe and effective alternative treatment for selective patients with renal tumours.

Regulation of E-cadherin expression by VHL and hypoxia-inducible factor.

Mutations in von Hippel-Lindau tumor suppressor gene (VHL) underlie the VHL hereditary cancer syndrome and also occur in most sporadic clear cell renal cell cancers (CCRCC). Currently, the mechanism(s) by which VHL loss of function promotes tumor development in the kidney are not fully elucidated. Here, we show that VHL inactivation in precancerous lesions in kidneys from patients with VHL disease correlates with marked down-regulation of the intercellular adhesion molecule E-cadherin. Moreover, in VHL-defective cell lines (RCC4 and RCC10) derived from sporadic CCRCC, reexpression of VHL was found to restore E-cadherin expression. The product of the VHL gene has multiple reported functions, the best characterized of which is its role as the recognition component of an ubiquitin E3 ligase complex responsible for mediating oxygen-dependent destruction of hypoxia-inducible factor-alpha (HIF-alpha) subunits. We show that HIF activation is necessary and sufficient to suppress E-cadherin in renal cancer cells. Given the fundamental role of E-cadherin in controlling epithelial behavior, our findings give insight into how VHL inactivation/HIF activation may lead to kidney cancer and also indicate a mechanism by which reduced oxygenation could alter E-cadherin expression in other cancers and influence normal homeostasis in other epithelia.