A novel two-stage approach to the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome.

OBJECTIVE: To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. PATIENTS AND METHODS: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. RESULTS: Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. CONCLUSION: While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Metformin may offer no protective effect in men undergoing external beam radiation therapy for prostate cancer.

OBJECTIVES: To assess whether metformin reduces radio-resistance and increases survival in men undergoing external beam radiation therapy (EBRT) for prostate cancer (PCa), and to determine its effect on hypoxia inducible factor 1-α (HIF1α). PATIENTS AND METHODS: All patients treated with curative intent with EBRT for PCa at a major cancer centre between 2000 and 2007 were included in this study. The outcome measures of time to biochemical failure (BF), metastasis, PCa-specific mortality and overall survival (OS) were analysed in those taking metformin vs those not, using competing risk and Cox regression models. To determine metformin's effect on HIF1α expression and survival in vitro, PC3 cells with high basal HIF1α levels were subjected to increasing doses of metformin after H2 O2 -induced oxidative stress. RESULTS: A total of 2055 eligible cases, including 113 who were on metformin, were identified, with a median follow-up of 95.7 months. There were no differences in age, initial prostate-specific antigen level, Gleason score, T-stage, D'Amico risk class or duration of androgen deprivation therapy (ADT) between patients who were or were not on metformin. Treatment with metformin did not result in any apparent improvement in time to BF, time to metastasis detection or OS, but there was a 1.5-fold increase in PCa-specific deaths (P = 0.045) in patients on metformin and ADT when adjusted for cancer risk and comorbidities. When comparing patients on high-dose metformin (>1 g/d) with those on low-dose metformin (≤1 g), there was no difference in either time to metastases or time to BF. In vitro metformin at a high concentration of 100 µM did not reduce HIF1α expression, nor did metformin affect the PC3 cell survival when exposed to oxidative stress (H2 O2 ). CONCLUSIONS: No association was found between the use of metformin and time to metastasis detection, time to BF or OS in patients undergoing radiation therapy with or without ADT for PCa. In vitro, low therapeutic concentrations of metformin had no effect on HIF1α, and this observation could explain the conflicting evidence for the effectiveness of metformin in men undergoing EBRT for PCa. Higher, more toxic doses of metformin may be required to inhibit the mammalian target of rapamycin-HIF1α pathway in this patient group.

Bilateral obstructing ureteric calculi in pregnancy: a rare cause of acute renal failure.

Bilateral obstructing ureteric calculi is a rare cause of acute renal failure. Although urolithiasis in later pregnancy is not uncommon, the development of bilateral obstruction secondary to ureteric calculi in the first trimester is rare and poses difficulty to diagnosis and management. Symptoms of diseases and physiological changes associated with pregnancy can obscure diagnosis of urolithiasis and obstructive uropathy. Advances in minimally invasive endourology afford intervention with reduced risk to fetal health. We present the second case of acute renal failure caused by bilateral obstructing ureteric calculi in a pregnant patient and discuss current management algorithms for this group.

Outpatient transperineal prostate biopsy under local anaesthesia is safe, well tolerated and feasible.

BACKGROUND: Transperineal biopsy (TPB) of the prostate has been increasingly utilized as it has reduced infection risks. Traditionally however, it is performed under general anaesthesia, thus it carries a differing set of risks. Recently, new studies have performed TPB under local anaesthesia with success. In the present study, we explored our experience of performing TPB under local anaesthesia in an Australian cohort. METHODS: In this prospective study based at a metropolitan outpatient clinic, patients were provided with TPB under local anaesthesia. We assessed prostate cancer detection rates, complication rates and patient tolerability. Pain tolerability was assess using patient reported pain score on the visual analogue scale. Follow up data was collected at days 7 and 30 post-biopsy via telephone interview. RESULTS: A total of 48 patients were enrolled in this study between June 2020 and March 2021. Median age was 65.5 years and median PSA was 6.95 ng/mL. Clinically significant prostate cancer was detected in 58% of patients. During the procedure, pain scores were rated the highest during infiltration of local anaesthetic agent with a median score of 5. By the conclusion of the procedure, median pain score was 1. Vast majority of patients (85.4%) would opt for a repeat TPB under local anaesthesia should the need for prostate biopsy arise again. Two of our patients experienced infectious complications, and one experienced urinary retention. CONCLUSION: Our data is in line with currently available data and confirms that TPB under local anaesthesia can be achieved in a safe and tolerable manner.

Evaluating the diagnostic role of in-bore magnetic resonance imaging guided prostate biopsy: a single-centre study.

BACKGROUND: To evaluate the role of in-bore MRI-guided biopsy (IB-MRGB) in the diagnosis of clinically significant prostate cancer (csPCa). METHODS: In this tertiary single centre study, a total of 125 consecutive patients receiving IB-MRGB over a three-year period were evaluated, including 73 patients who had prior biopsies and 52 biopsy-naïve patients. We assessed cancer detection rate of patients according to the degree of suspicion based on mpMRI findings. Histopathological data were reviewed by experienced uropathologists. RESULTS: The mpMRI was suspicious for PCa (PI-RADS 4/5) in 77% (96/125) and equivocal (PI-RADS 3) in 23% (29/125). The detection rate for csPCa was 54.2% (52/96) and 20.7% (6/29) for suspicious lesions (PI-RADS 4/5) and equivocal lesions (PI-RADS 3), respectively. In subgroup analysis, patients with previous negative biopsy, overall positive biopsy rate and csPCa detection rate were 48.3% (19/35) and 34.5% (13/35), respectively. In patients on AS, 36/44 (81.8%) and 21/44 (47.8%) had PCa and csPCa respectively. In biopsy-naïve patients 34/52 (65.4%) and 27/52 (51.92%) had PCa and csPCa respectively. Of the patients on AS, 18/44 (41.6%) upgraded from ISUP 1 to ISUP 2 PCa, and 4/44 (9.1%) upgraded from ISUP 1 to ISUP 3 PCa on IB-MRGB. A total of 14 Clavien-Dindo≤2 complications occurred in 14 patients (11.2%) that were directly related to the biopsy. No Clavien-Dindo≥3 complications occurred. CONCLUSION: MRI-targeted biopsy is suitable for assessment of csPCa. Given the favourable complications profile, its use may be considered in both the initial biopsy and re-biopsy settings.

Local versus general anesthesia transperineal prostate biopsy: Tolerability, cancer detection, and complications.

Objectives: To compare data on transperineal template biopsy (TPTB) under general anesthesia (GA) compared with local anesthesia (LA) procedures using the PrecisionPoint™ Transperineal Access System (PPTAS) in relation to tolerability, cancer detection rate, complications, and cost. Methods: A prospective pilot cohort study of patients undergoing transperineal biopsy was performed. Patients were excluded if they had concurrent flexible cystoscopy or language barriers. Patients had a choice of GA or LA. A prospective questionnaire on Days 0, 1, 7, and 30 was applied. The primary outcome was patient tolerability. Secondary outcomes were cancer detection rate, complication rate, and theater utilization. Results: This study included 80 patients (40 GA TPTB and 40 LA PPTAS). Baseline characteristics including age, prostate-specific antigen (PSA), digital rectal examination (DRE), findings, and prostate volume were comparable between the groups (p = 0.3790, p = 0.9832, p = 0.444, p = 0.3939, respectively). Higher median prostate imaging-reporting and data system (PI-RADS) score of 4 (interquartile range [IQR] 2) versus 3 (IQR 1) was noted in the LA group (p = 0.0326). Pain was higher leaving recovery in the GA group however not significantly (p = 0.0555). Median pain score at LA infiltration was 5/10 (IQR 3), with no difference in pain at Days 1, 7, or 30 (p = 0.2722, 0.6465, and 0.8184, respectively). For GA versus LA, the overall cancer detection rate was 55% versus 55% (p = 1.000) with clinically significant cancer in 22.5% versus 35% (p = 0.217). Acute urinary retention (AUR) occurred in 5% of GA and 2.5% of LA patients (p = 1.000). The GA cohort spent longer in theater and in recovery with a median of 93.5 min versus 57 min for the LA group (p = <0.0001). Conclusion: This study demonstrates that transperineal biopsy is safely performed under LA with no difference between the cohorts in relation cancer detection or AUR. LA biopsy also consumed less theater and recovery resources. A further larger prospective randomized controlled trial is required to confirm the findings of this study.

Ureteral intramural metastatic deposit of prostate cancer with ureteric obstruction.

True metastatic ureteric lesions are exceptionally rare when sourced from any primary tumour. Primary prostatic cancer metastasis to the ureter is understandably even more atypical with very few cases reported in current literature. True intramural ureteric metastatic disease deposited from prostate cancer is an even rarer occurrence. We present a case of a man in his mid-60s with left-sided hydronephrosis in the setting of biochemical recurrence of Gleason 9 prostate cancer. Initially misdiagnosed as obstruction secondary to mass effect from a large trigonal lesion, subsequent investigation revealed solid intramural metastatic deposit of prostate primary tumour in the distal ureter. We detail current hypotheses regarding the subsequent pathophysiology of the disease and its common clinical presentations. Our case highlights that prostatic metastasis should be considered as a differential in coexisting prostate cancer and ureteric obstruction despite its low incidence.

Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.

Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+ and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+ in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total and free Zn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+ treatment on proliferation and survival were measured in vitro using MTT assays and in vivo using mouse xenografts. The ability of Zn2+ to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+ concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+ than PNT1A cells (p < 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+ than PC3 cells. Exposure to 10 µM Zn2+ over 72 hours significantly reduces PC3 cell proliferation in vitro but not in vivo. Zn2+ increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+ dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival.

Urolithiasis Treatment in Australia: The Age of Ureteroscopic Intervention.

INTRODUCTION: The incidence of urolithiasis is increasing in the Western population. Significant advances in ureteroscopy and stone fragmentation energy sources have resulted in a paradigm shift in urolithiasis management. We aimed to assess the current state of urolithiasis management in Australia over the last 15 years using population-based data. METHODS: Medicare Australia databases were accessed and Medicare rebate codes pertaining to ureteroscopy, extracorporeal shockwave lithotripsy (SWL), and percutaneous nephrolithotomy (PCNL) were extracted per state, year, and gender between 2001 and 2015. Population data were extracted from the Australian Bureau of Statistics website and provided the "population at risk" denominator to calculate incidence proportions. RESULTS: From January 2001 to December 2015, 114,789 ureteroscopy or pyeloscopy procedures for stone extraction in adult patients were performed in Australia. During the same period, 48,209 SWL and 6956 PCNL procedures were performed. Ureteroscopy and pyeloscopy procedures have been increasing by an average of 9.3% year-on-year, population adjusted, while SWL has decreased by 3.5% and PCNL by 6.4% every year over the same period. In absolute terms, scope procedures have increased yearly by an average of 3.9 per 100,000 of population (confidence interval [95% CI]: 3.2, 4.5), while SWL has changed by -0.77 (95% CI: -0.88, -0.65) and PCNL by -0.16 (95% CI: -0.17, -0.14). CONCLUSION: Over the past 15 years in Australia, the total number of stone treatment procedures has increased significantly. Considerable increases in ureteroscopy were observed with relative and absolute reductions in SWL and PCNL. Regional variations in urolithiasis management strategies highlight the need for consensus on stone treatments within Australia.

Sensitivity, Specificity, and Predictors of Positive 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease. 68Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for 68Ga-PSMA PET-positive scans. OBJECTIVE: A systematic review and meta-analysis of reported predictors of positive 68Ga-PSMA PET and corresponding sensitivity and specificity profiles. EVIDENCE ACQUISITION: We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS: Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19-64%) for primary staging and 76% (95% CI 66-85%) for biochemical recurrence (BCR). Positive 68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0-0.2, 0.2-1, 1-2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased 68Ga-PSMA PET positivity. On per-patient analysis, the summary sensitivity and specificity were both 86%. On per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. CONCLUSIONS: In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques. PATIENT SUMMARY: Positron emission tomography using 68Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer.

Patients' perspectives of accessibility and digital delivery of factual content provided by official medical and surgical specialty society websites: a qualitative assessment.

BACKGROUND: Health care websites provide a valuable resource of health information to online consumers, especially patients. Official surgical and medical society websites should be a reliable first point of contact. OBJECTIVE: The primary aim of this study was to quantitatively assess medical and surgical society websites for content and highlight the essential features required for a high-quality, user-friendly society website. METHODS: Twenty specialty association websites from each of the regions, Australia, UK, Canada, Europe, and the USA were selected for a total of 100 websites. Medical and surgical specialities were consistent across each region. Each website was systematically and critically analysed for content and usability. RESULTS: The average points scored per website was 3.2 out of 10. Of the total (N=100) websites, 12 scored at least 7 out of 10 points and 2 scored 9 out of 10. As well, 35% (35.0/100) of the websites had an information tab for patients on their respective homepages while 38% (38.0/100) had download access to patient information. A minority of the websites included different forms of multimedia such as pictures and diagrams (24.0/100, 24%) and videos (18.0/100, 18%). CONCLUSIONS: We found that most society websites did not meet an adequate standard for delivery of information. Half of the websites were not patient accessible, with the primary focus being for health professionals. As well, most required logins for information access. Specialty health care societies should create patient-friendly websites that would be beneficial to all online consumers.

Advances in ureteroscopy.

Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.

Spermatocytic seminoma with sarcoma: an indication for adjuvant chemotherapy in localized disease.

Spermatocytic seminoma (SCS) with sarcoma is an extremely rare testicular tumor with only 11 cases previously described in the literature. We present the 12th case of SCS with sarcoma in a 29-year-old male. SCS itself is an uncommon germ cell tumor with a relatively indolent clinical course that mostly affects males around the fifth decade of life. Sarcomatous differentiation of SCS occurs in 5% to 6% of cases and correlates with a higher possibility of metastatic disease and a poor prognosis. Clinically, this tumor manifests as a slow-growing testicular mass often with an accelerated period of secondary growth. After a concise review of the literature, we conclude that SCS with sarcoma should be treated by radical inguinal orchidectomy with strong consideration given to adjuvant chemotherapy.