Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Contrast-enhanced CT in 100 clear cell renal cell cancers - an analysis of enhancement, tumour size, and survival.

AIM: To investigate the relationship between computed tomography (CT) contrast enhancement of clear cell renal tumours and clinicopathological measures including tumour size, stage, grade, presence of necrosis, and disease-specific survival (DSS). MATERIALS AND METHODS: Patients who had radical nephrectomy for clear cell renal cell carcinoma (RCC) in the period 2004-2007 and who underwent contrast-enhanced (CE)CT at diagnosis were included. Pathological records and radiological imaging were reviewed. Maximum contrast enhancement (MACE) in Hounsfield units (HU) was calculated as the difference between the highest value on pre-contrast and post-contrast imaging in at least three regions of interest within the tumour. MACE was correlated with histopathological measures (size, stage, grade, necrosis) and 5 year DSS. RESULTS: In total, 100 patients with clear cell RCC (median follow-up 40 months) were included with median age of 64 years. MACE values ranged from 21-155 HU with a median of 60.5 HU. There was weak negative correlation between increasing tumour size and MACE (r=-0.2, p=0.045). Patients with necrosis on pathology had lower MACE (71.3 versus 57.5 HU, p=0.03). There was no significant correlation between tumour grade or stage and MACE. Kaplan-Meier plots showed significant survival differences with 5 year DSS for MACE <50 HU 100% versus 5 year DSS for MACE >50 HU 82% (log rank p=0.025). CONCLUSION: MACE decreased with increasing tumour size and was associated with tumour necrosis. MACE >50 HU was associated with a worse 5 year DSS.

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism: a systematic review by the EAU Sexual and Reproductive Health Guidelines panel.

Surgical treatments for ischemic priapism (IP) include shunts or penile implants. Non-ischemic priapism (NIP) is usually the result of penile/perineal trauma causing an arterial fistula and embolisation may be required. We conducted a systematic review on behalf of the EAU Sexual and Reproductive health Guidelines panel to analyse the available evidence on efficacy and safety of surgical modalities for IP and NIP. Outcomes were priapism resolution, sexual function and adverse events following surgery. Overall, 63 studies (n = 923) met inclusion criteria up to September 2021. For IP (n = 702), surgery comprised distal (n = 274), proximal shunts (n = 209) and penile prostheses (n = 194). Resolution occurred in 18.7-100% for distal, 5.7-100% for proximal shunts and 100% for penile prostheses. Potency rate was 20-100% for distal, 11.1-77.2% for proximal shunts, and 26.3-100% for penile prostheses, respectively. Patient satisfaction was 60-100% following penile prostheses implantation. Complications were 0-42.5% for shunts and 0-13.6% for IPP. For NIP (n = 221), embolisation success was 85.7-100% and potency 80-100%. The majority of studies were retrospective cohort studies. Risk of bias was high. Overall, surgical shunts have acceptable success rates in IP. Proximal/venous shunts should be abandoned due to morbidity/ED rates. In IP > 48 h, best outcomes are seen with penile prostheses implantation. Embolisation is the mainstay technique for NIP with high resolution rates and adequate erectile function.

SDH-deficient renal cell carcinoma: a clinicopathological analysis highlighting the role of genetic counselling.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) accounts for 0.05-2% of all RCCs. The majority of patients have germline mutations, most frequently in the SDHB gene. People with these mutations are predisposed to developing paragangliomas, phaeochromocytomas and gastrointestinal stromal tumours. Patients should be referred to genetic services for further workup and close surveillance imaging due to the risk of development of further tumours. We present a woman with SDH-deficient RCC and review the literature associated with this uncommon entity.

Correction: The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance.

The original version of this article contained an error in Fig. 5a where the colours of the labels representing the Hinge and LBD of the AR were incorrect and did not match the corresponding exons. The corrected version of this Figure now appears in the article. The conclusions of this paper were not affected. The authors apologise for this error and any confusion caused.

The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance.

Stem cell characteristics have been associated with treatment resistance and poor prognosis across many cancer types. The ability to induce and regulate the pathways that sustain these characteristic hallmarks of lethal cancers in a novel in vitro model would greatly enhance our understanding of cancer progression and treatment resistance. In this work, we present such a model, based simply on applying standard pluripotency/embryonic stem cell media alone. Core pluripotency stem cell master regulators (OCT4, SOX2 and NANOG) along with epithelial-mesenchymal transition (EMT) markers (Snail, Slug, vimentin and N-cadherin) were induced in human prostate, breast, lung, bladder, colorectal, and renal cancer cells. RNA sequencing revealed pathways activated by pluripotency inducing culture that were shared across all cancers examined. These pathways highlight a potential core mechanism of treatment resistance. With a focus on prostate cancer, the culture-based induction of core pluripotent stem cell regulators was shown to promote survival in castrate conditions-mimicking first line treatment resistance with hormonal therapies. This acquired phenotype was shown to be mediated through the upregulation of iodothyronine deiodinase DIO2, a critical modulator of the thyroid hormone signalling pathway. Subsequent inhibition of DIO2 was shown to supress expression of prostate specific antigen, the cardinal clinical biomarker of prostate cancer progression and highlighted a novel target for clinical translation in this otherwise fatal disease. This study identifies a new and widely accessible simple preclinical model to recreate and explore underpinning pathways of lethal disease and treatment resistance.

Radical prostatectomy for locally advanced and metastatic prostate cancer.

The management of advanced prostate cancer remains challenging. Traditionally, radical prostatectomy was discouraged in patients with locally advanced or node positive disease owing to the increased complication rate and treatment related morbidity. However, technical advances and refinements in surgical techniques have enabled the outcomes for patients with high risk prostate cancer to be improved. More recently, the concept of cytoreductive prostatectomy has been described where surgery (often Combined with an extended lymph node dissection) is performed in the setting of metastatic disease. Indirect evidence suggests an advantage using the cytoreductive approach. Hypothetical explanations for this observed benefit include decreased tumour burden, immune modulation, improved response to secondary treatment and avoidance of secondary complications attributable to local tumour growth. Nevertheless, prospective trials are required to investigate this further.

Intraoperative and surgical specimen (ex vivo) ultrasound in the assessment of margins at partial nephrectomy.

PURPOSE: To correlate the accuracy of intraoperative and surgical specimen (ex vivo) ultrasound (US) with pathological margin status at partial nephrectomy. MATERIALS AND METHODS: Patients undergoing partial nephrectomy for T1 renal tumours in the period May 2010-January 2014 at a single institution who had intraoperative specimen US were included. PN was performed by standardised technique with intraoperative tumour localisation. Following excision, surgical specimen (ex vivo) US was performed and the margin status was compared to the final histopathological analysis. The specificity of US to identify margin status was calculated as was the correlation between the ultrasonographic and final pathological margin. RESULTS: Forty-five patients were included (median age 61 years). Mean tumour size was 28.1 ± 10 mm, and 89 % were renal cell carcinomas with the remainder being oncocytomas. Forty-four cases had negative surgical margins on pathological analysis, and US had a specificity of 100 %. There was a strong correlation between the margin as measured on US and final analysis (Pearson's r = 0.86, p < 0.001). CONCLUSION: Results show that intraoperative, surgical specimen (ex vivo) US control of resection margins in patients undergoing PN is feasible and efficient. It represents a promising tool to ensure margin negativity during PN.

Adenoid cystic carcinoma of the breast: case report and review of literature.

We report the case of a patient who presented with a painful breast lump that turned out to be an adenoid cystic carcinoma of the breast. The literature is reviewed, highlighting the good prognosis associated with this rare condition and the current preferred treatment modalities.

Accuracy of the revised 2010 TNM classification in predicting the prognosis of patients treated for renal cell cancer in the north east of England.

BACKGROUND: The TNM classification for renal cell cancer (RCC) should accurately predict and assign prognostic information for patients. In this study the recent 2010 revision to the TNM classification was compared with the previous 2002 classification with regard to survival outcomes. METHODS: All patients having radical nephrectomy for RCC in the 5-year period 2004-8 at a tertiary referral centre were included. Pathological and radiological records were reviewed to identify TNM stage (2002 and 2010 classification) and survival data were captured. RESULTS: 345 patients with RCC were identified. Based on the 2002 TNM staging system and using outcomes in T1 staged tumours as a baseline, statistically significant differences in disease-specific survival were noted between patients with T1 and T3b tumours (log rank p<0.001) but not between those with T1 and T3a tumours (p=0.33). However, when tumour stage was reassigned according to the 2010 classification, patients with T3a tumours were also found to do statistically worse than T1 staged disease (p<0.001). CONCLUSION: In our cohort, the new 2010 TNM reclassification of T3 tumours showed better correlation with predicting worsening outcomes compared with localised disease.

Safety and efficacy of percutaneous nephrolithotomy for the treatment of paediatric urolithiasis.

INTRODUCTION: Paediatric percutaneous nephrolithotomy (PCNL) has revolutionised the treatment of paediatric nephrolithiasis. Paediatric PCNL has been performed using both adult and paediatric instruments. Stone clearance rates and complications vary according to the technique used and surgeon experience. We present our experience with PCNL using adult instruments and a 28Fr access tract for large renal calculi in children under 18 years. METHODS: All patients undergoing PCNL at our institution between 2000 and 2009 were reviewed. Demographics, surgical details and post-operative follow-up information were obtained to identify stone clearance rates and complications. RESULTS: PCNL was performed in 32 renal units in 31 patients (mean age: 10.8 years). The mean stone diameter was 19mm (range: 5-40mm). Twenty-six cases required single puncture and six required multiple tracts. Overall, 11 staghorn stones, 10 multiple calyceal stones and 11 single stones were treated. Twenty-seven patients (84%) were completely stone free following initial PCNL. Two cases had extracorporeal shock wave lithotripsy for residual fragments, giving an overall stone free rate of 91% following treatment. There was no significant bleeding or sepsis encountered either during the operation or in the post-operative setting. No patient required or received a blood transfusion. CONCLUSIONS: Paediatric PCNL can be performed safely with minimal morbidity using adult instruments for large stone burden, enabling rapid and complete stone clearance.