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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Detection of BK virus in urine from renal transplant subjects by mass spectrometry.
BACKGROUND: The diagnosis and management of BK virus (BKV) reactivation following renal transplantation continues to be a significant clinical problem. Following reactivation of latent virus, impaired cellular immunity enables sustained viral replication to occur in urothelial cells, which potentially leads to the development of BKV-associated nephropathy (BKVAN). Current guidelines recommend regular surveillance for BKV reactivation through the detection of infected urothelial cells in urine (decoy cells) or viral nucleic acid in urine or blood. However, these methods have variable sensitivity and cannot routinely distinguish between different viral subtypes. We therefore asked whether mass spectrometry might be able to overcome these limitations and provide an additional non-invasive technique for the surveillance of BKV and identification of recipients at increased risk of BKVAN. RESULTS: Here we describe a mass spectrometry (MS)-based method for the detection of BKV derived proteins directly isolated from clinical urine samples. Peptides detected by MS derived from Viral Protein 1 (VP1) allowed differentiation between subtypes I and IV. Using this approach, we observed an association between higher decoy cell numbers and the presence of the VP1 subtype Ib-2 in urine samples derived from a cohort of 20 renal transplant recipients, consistent with the hypothesis that certain viral subtypes may be associated with more severe BKVAN. CONCLUSIONS: This is the first study to identify BK virus proteins in clinical samples by MS and that this approach makes it possible to distinguish between different viral subtypes. Further studies are required to establish whether this information could lead to stratification of patients at risk of BKVAN, facilitate distinction between BKVAN and acute rejection (AR), and ultimately improve patient treatment and outcomes.
Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: Results for 778 patients from a hospital haematuria clinic
OBJECTIVES: • To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible cystoscopy and voided urine cytology for diagnosing bladder cancer. • To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS: • The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age > 40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and flexible cystoscopy examinations for analysis. • On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer. • The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21-66 months. RESULTS: • The prevalence of bladder cancer in the clinical cohort was 20% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98-1.00), specificity was 0.94 (95% CI 0.91-0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73-0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99-1.00). • For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.83 (95% CI 0.80-0.86), the PPV was 0.58 (95% CI 0.52-0.64), and the NPV was 0.98 (95% CI 0.97-0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94-0.99), specificity was 0.94 (95% CI 0.92-0.96), the PPV was 0.80 (95% CI 0.73-0.85) and the NPV was 0.99 (95% CI 0.99-1.0). • For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98-1.0), specificity was 0.94 (95% CI 0.91-0.95), the PPV was 0.80 (95% CI 0.73-0.85), and the NPV was 1.0 (95% CI 0.99-1.0). • For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.93 (95% CI 0.87-0.96), and the NPV was 0.99 (95% CI 0.97-0.99). • For voided urine cytology, if scores of 0-3 were classified as negative and 4-5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31-0.45), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.82 (95% CI 0.72-0.88) and the NPV was 0.84 (95% CI 0.81-0.87). CONCLUSIONS: • There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. • Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. • The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy. © 2011 BJU International.
Developing a stone database for clinical practice
Purpose: Our objective was to design an intranet-based database to streamline stone patient management and data collection. Materials and Methods: The system developers used a rapid development approach that removed the need for laborious and unnecessary documentation, instead focusing on producing a rapid prototype that could then be altered iteratively. By using open source development software and website best practice, the development cost was kept very low in comparison with traditional clinical applications. Information about each patient episode can be entered via a user-friendly interface. Results: The bespoke electronic stone database removes the need for handwritten notes, dictation, and typing. From the database, files may be automatically generated for clinic letters, operation notes. and letters to family doctors. These may be printed or e-mailed from the database. Data may be easily exported for audits, coding, and research. Conclusions: Data collection remains central to medical practice, to improve patient safety, to analyze medical and surgical outcomes, and to evaluate emerging treatments. Establishing prospective data collection is crucial to this process. In the current era, we have the opportunity to embrace available technology to facilitate this process. The database template could be modified for use in other clinics. The database that we have designed helps to provide a modern and efficient clinical stone service. © Copyright 2011, Mary Ann Liebert, Inc.
Evaluation of multidetector computed tomography urography and ultrasonography for diagnosing bladder cancer.
AIM: To evaluate and compare the diagnostic accuracy of multidetector computed tomography urography (CTU) and ultrasonography (US) for diagnosing bladder cancer. MATERIALS AND METHODS: A consecutive series of 143 patients over 40-years of age, presenting with macroscopic haematuria and without urinary tract infection underwent same-day CTU, US, and flexible cystoscopy. CTU and US were independently rated on a five-point scale for the presence of bladder cancer without knowledge of the reference standard of flexible or rigid cystoscopy and/or biopsy results. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis and likelihood ratios. RESULTS: For CTU, a rating of 5 (definitely tumour) was highly specific for bladder cancer (96.5%, 95%CI: 91.3-99%), effectively confirming diagnosis (positive likelihood ratio 25.6, 95%CI: 9.7-67.4). For US, specificity was also high (94.7%, 95%CI: 88.9-98%) with a positive likelihood ratio of 13.1 (95%CI: 5.8-29.6). Sensitivity at this rating was substantially higher for CTU (89.7%, 95%CI: 72.7-97.8%) than US (69%, 95%CI: 49.2-84.7%). Standardized partial area (Az) under the ROC curve between 95-100% specificity, representing the average sensitivity in this range, was significantly greater (0.88 versus 0.61, p<0.05) for CTU than US. CONCLUSION: The specificities of CTU and US for the diagnosis of bladder cancer were similar, but CTU was more sensitive. Although the sensitivity of CTU was not high enough to replace flexible cystoscopy in the diagnostic pathway, the high specificity enables direct referral to rigid cystoscopy, bypassing flexible cystoscopy and expediting diagnosis and treatment in those patients testing positive.
The type 1 insulin-like growth factor receptor is over-expressed in bladder cancer.
OBJECTIVE: To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin-like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis. MATERIALS AND METHODS: Formalin-fixed specimens of bladder cancer (40 whole-mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12). RESULTS: Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q-RT-PCR showed significantly higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta-T4) than in normal bladder (P < 0.05), indicating up-regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta-T1) or invasive (T2-4) tumours; only the latter showed significant IGF1R over-expression at the RNA level (P < 0.05 vs normal bladder). CONCLUSION: The IGF1R is up-regulated in bladder cancer compared with non-malignant bladder, and might contribute to a propensity for invasion.
Developing a stone database for clinical practice.
PURPOSE: Our objective was to design an intranet-based database to streamline stone patient management and data collection. MATERIALS AND METHODS: The system developers used a rapid development approach that removed the need for laborious and unnecessary documentation, instead focusing on producing a rapid prototype that could then be altered iteratively. By using open source development software and website best practice, the development cost was kept very low in comparison with traditional clinical applications. Information about each patient episode can be entered via a user-friendly interface. RESULTS: The bespoke electronic stone database removes the need for handwritten notes, dictation, and typing. From the database, files may be automatically generated for clinic letters, operation notes. and letters to family doctors. These may be printed or e-mailed from the database. Data may be easily exported for audits, coding, and research. CONCLUSIONS: Data collection remains central to medical practice, to improve patient safety, to analyze medical and surgical outcomes, and to evaluate emerging treatments. Establishing prospective data collection is crucial to this process. In the current era, we have the opportunity to embrace available technology to facilitate this process. The database template could be modified for use in other clinics. The database that we have designed helps to provide a modern and efficient clinical stone service.
Computed tomography urography for diagnosing bladder cancer.
OBJECTIVE: To evaluate the use of computed tomography urography (CTU) for diagnosing bladder tumours in patients with macroscopic haematuria and aged >40 years. PATIENTS AND METHODS: In all, 200 consecutive patients attending a fast-track haematuria clinic were assessed using 'same-day' CTU and flexible cystoscopy. Patients were aged >40 years and had macroscopic haematuria with no urine infection. CTU studies were reported by one uroradiologist and scored on a 3-point scale to quantify the probability of bladder cancer. All flexible cystoscopies were performed by the same cystoscopist with no knowledge of the findings of CTU, and scored using a 3-point scale. Cystoscopy, pathological findings and CTU were then compared. RESULTS: The prevalence of bladder tumours was 24%; when CTU was compared with the histopathological findings, there was one false-positive and three false-negative diagnoses, indicating a sensitivity of 0.93 and a specificity of 0.99, with a 0.98 positive and 0.97 negative predictive value for detecting bladder cancer. A review of the three false-negative cases showed that one was missed on original CTU reporting, the second had the appearance of prostate cancer on CTU and the third was a squamous metaplasia. CONCLUSION: CTU is an accurate method of detecting bladder tumours in the present patients, and is reliable and accurate for assessing the bladder. Our results support the use of CTU as a first-line screening tool for this high-risk group, the use of which will obviate the need for flexible cystoscopy in patients with a negative CTU and allow those with an obvious tumour to be referred directly for rigid cystoscopy and resection. The remaining patients should be referred for flexible cystoscopy. Such a pathway would accelerate patient assessment by using fewer tests and provide a true 'one-stop' clinic, allowing a comprehensive evaluation with a single test for the upper and lower urinary tract.
Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic.
UNLABELLED: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Haematuria clinics with same day imaging and flexible cystoscopy are an efficient way for investigating patients with haematuria. The principal role of haematuria clinics with reference to bladder cancer is to determine which patients are 'normal' and may be discharged, and which patients are abnormal and should undergo rigid cystoscopy. It is well recognised that CT urography offers a thorough evaluation of the upper urinary tract for stones, renal masses and urothelial neoplasms but the role of CT urography for diagnosing bladder cancer is less certain. The aim of the present study was to evaluate the diagnostic accuracy of CT urography in patients with visible haematuria aged >40 years and to determine if CT urography has a role for diagnosing bladder cancer. This study shows that the optimum diagnostic strategy for investigating patients with visible haematuria aged >40 years with infection excluded is a combined strategy using CT urography and flexible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid flexible cystoscopy. The number of flexible cystoscopies required therefore may be reduced by 17%. The present study also shows that the diagnostic accuracy of voided urine cytology is too low to justify its continuing use in a haematuria clinic using CT urography and flexible cystoscopy. OBJECTIVES: To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible cystoscopy and voided urine cytology for diagnosing bladder cancer. To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS: The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age >40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and flexible cystoscopy examinations for analysis. On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer. The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21-66 months. RESULTS: The prevalence of bladder cancer in the clinical cohort was 20% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98-1.00), specificity was 0.94 (95% CI 0.91-0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73-0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99-1.00). For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.83 (95% CI 0.80-0.86), the PPV was 0.58 (95% CI 0.52-0.64), and the NPV was 0.98 (95% CI 0.97-0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94- 0.99), specificity was 0.94 (95% CI 0.92-0.96), the PPV was 0.80 (95% CI 0.73-0.85) and the NPV was 0.99 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98-1.0), specificity was 0.94 (95% CI 0.91-0.95), the PPV was 0.80 (95% CI 0.73-0.85), and the NPV was 1.0 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.93 (95% CI 0.87-0.96), and the NPV was 0.99 (95% CI 0.97-0.99). For voided urine cytology, if scores of 0-3 were classified as negative and 4-5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31-0.45), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.82 (95% CI 0.72-0.88) and the NPV was 0.84 (95% CI 0.81-0.87). CONCLUSIONS: There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy.
Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks.
BACKGROUND AND PURPOSE: IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair. METHODS: We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry. RESULTS: We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30-40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses. CONCLUSIONS: These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.
Multidetector computed tomography urography for diagnosing upper urinary tract urothelial tumour.
OBJECTIVE: To evaluate multidetector computed tomography urography (MDCTU) for diagnosing upper urinary tract (UUT) urothelial tumour by comparison with retrograde ureteropyelography (RUP). PATIENTS AND METHODS: MDCTU and RUP were used in a selected series of adult patients presenting with haematuria. Entry criteria were based on findings on intravenous urography and were chosen to ensure a high prevalence of UUT urothelial tumour to allow a valid retrospective comparison of the diagnostic techniques. MDCTU and RUP studies were scored for the presence and absence of UUT urothelial tumour by two radiologists, retrospectively and independently, and while unaware of the demographic and clinical information. The reference standards were the histopathology and clinical follow-up. RESULTS: MDCTU and RUP were used in 106 patients over a 24-month period. RUP was attempted in 151 of 212 UUTs; the corresponding MDCTU for each UUT was reviewed. MDCTU was a true-positive (TP) for urothelial tumour in 31, true-negative (TN) in 111, false-positive (FP) in eight and false-negative (FN) in one UUT, giving a sensitivity of 0.97, a specificity of 0.93, a positive predictive value (PPV) of 0.79 and a negative PV (NPV) of 0.99. RUP was technically successful and diagnostic in 96% of the UUTs (143/151). For diagnosing urothelial tumour, RUP was TP in 26, TN in 112, FP in four and FN in one UUT, giving a sensitivity of 0.97, specificity of 0.93, a PPV of 0.79 and NPV of 0.99. CONCLUSION: This study validates quantitatively the use of MDCTU for diagnosing UUT urothelial tumour.
Open partial nephrectomy: outcomes from two UK centres.
OBJECTIVE: To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. PATIENTS AND METHODS: We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2-9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of < or = 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTS: In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSION: OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.
Audiovisual distraction reduces pain perception during shockwave lithotripsy.
BACKGROUND AND PURPOSE: Lithotripsy is an established method to fragment kidney stones that can be performed without general anesthesia in the outpatient setting. Discomfort and/or noise, however, may deter some patients. It has been demonstrated that audiovisual distraction (AV) can reduce sedoanalgesic requirements and improve patient satisfaction in nonurologic settings, but to our knowledge, this has not been investigated with lithotripsy. This randomized controlled trial was designed to test the hypothesis that AV distraction can reduce perceived pain during lithotripsy. PATIENTS AND METHODS: All patients in the study received identical analgesia before a complete session of lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter. Patients were randomized to two groups: One group (n=61) received AV distraction via a wall-mounted 32″ (82 cm) television with wireless headphones; the other group (n=57) received no AV distraction. The mean intensity of treatment was comparable in both groups. Patients used a visual analogue scale (0-10) to record independent pain and distress scores and a nonverbal pain score was documented by the radiographer during the procedure (0-4). RESULTS: In the group that received AV distraction, all measures of pain perception were statistically lower. The patient-reported pain score was reduced from a mean of 6.1 to 2.4 (P<0.0001), and the distress score was reduced from a mean of 4.4 to 1.0 (P=0.0001). The mean nonverbal score recorded by the radiographer was reduced from 1.5 to 0.5 (<0.0001). CONCLUSIONS: AV distraction significantly lowered patients' reported pain and distress scores. This correlated with the nonverbal scores reported by the radiographer. We conclude that AV distraction is a simple method of improving acceptance of lithotripsy and optimizing treatment.
Serial analysis of resected prostate cancer suggests up-regulation of type 1 IGF receptor with disease progression.
OBJECTIVE: • To compare immunostaining protocols using different antibodies for the type 1 insulin-like growth factor receptor (IGF-1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF-1R expression varies with time in serial prostate cancer specimens from individual patients. METHODS: • We studied IGF-1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart. • Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate-specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation. • After an optimization process using three commercially-available IGF-1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips. RESULTS: • Santa Cruz antibody sc713 gave positive staining in IGF-1R null R- cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R- cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively. • There was significant correlation of IGF-1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF-1R staining scores generated by the CS antibody were used to analyze the clinical data. • Most patients (six of seven) with falling IGF-1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen-independence between procedures, IGF-1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF-1R staining scores. CONCLUSION: • The present study is the first to assess changes in IGF-1R expression in serial prostate cancer samples. The results obtained indicate that IGF-1R expression usually remains high throughout the course of histologically-proven disease progression in serial specimens, suggesting that the IGF-1R remains a valid treatment target for advanced prostate cancer.
Trends in urological stone disease.
OBJECTIVE: To summarize the changes in prevalence and treatment of upper urinary tract stone disease in the UK over the last 10 years. METHODS: Data from the Hospital Episode Statistics (HES) website (http://www.hesonline.nhs.uk) were extracted, summarized and presented. RESULTS: The number of upper urinary tract stone hospital episodes increased by 63% to 83,050 in the 10-year period. The use of shock wave lithotripsy (SWL) for treating all upper tract stones increased from 14,491 cases in 2000-2001 to 22,402 cases in 2010 (a 55% increase) with a 69% increase in lithotripsy for renal stones. There was a 127% increase in the number of ureteroscopic stone treatments from 6,283 to 14,242 cases over the 10-year period with a 49% increase from 2007/2008 to 2009/2010. There was a decline in open surgery for upper tract stones from 278 cases in 2000/2001 to 47 cases in 2009/2010 (an 83% reduction). Treatment for stone disease has increased substantially in comparison with other urological activity. In 2009/2010, SWL was performed almost as frequently as transurethral resection of the prostate or transurethral resection of bladder tumour, ureteroscopy for stones was performed more frequently than nephrectomy, radical prostatectomy and cystectomy combined, and percutaneous nephrolithotomy was performed more frequently than cystectomy. CONCLUSIONS: The present study highlights the increase in prevalence and treatment of stone disease in the UK over the last 10 years. If this trend continues it has important implications for workforce planning, training, service delivery and research in the field of urolithiasis.