Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function.

Blindness caused by advanced stages of inherited retinal diseases and age-related macular degeneration are characterized by photoreceptor loss. Cell therapy involving replacement with functional photoreceptor-like cells generated from human pluripotent stem cells holds great promise. Here, we generated a human recombinant retina-specific laminin isoform, LN523, and demonstrated the role in promoting the differentiation of human embryonic stem cells into photoreceptor progenitors. This chemically defined and xenogen-free method enables reproducible production of photoreceptor progenitors within 32 days. We observed that the transplantation into rd10 mice were able to protect the host photoreceptor outer nuclear layer (ONL) up to 2 weeks post transplantation as measured by full-field electroretinogram. At 4 weeks post transplantation, the engrafted cells were found to survive, mature, and associate with the host's rod bipolar cells. Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents. At 20 weeks post transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses. Post-transplanted rabbit model also provided congruent evidence for synaptic connectivity with the degenerated host retina. The results may pave the way for the development of stem cell-based therapeutics for retina degeneration.

Xanthogranulomatous pyelonephritis: a systematic review of treatment and mortality in more than 1000 cases.

OBJECTIVES: To systematically review the current demographics, treatment and mortality rate associated with xanthogranulomatous pyelonephritis (XGP) and to test the hypothesis that the weighted pooled peri-operative mortality rate will be <10%. METHODS: Searches were performed of the Cochrane, Embase and Medline databases and the grey literature for studies published during the period 1 January 2000 to 30 August 2021. Eligible studies reported cohorts of ≥10 predominantly adult patients with XGP and described either average patient age or mortality rate. RESULTS: In total, 40 eligible studies were identified, representing 1139 patients with XGP. There were 18 deaths, with a weighted pooled peri-operative mortality rate of 1436 per 100 000 patients. The mean age was 49 years, 70% of patients were female and 28% had diabetes mellitus. The left kidney was more commonly affected (60%). Four patients had bilateral XGP, and all of whom survived. Renal or ureteric stones were present in 69% of patients, including 48% with staghorn calculi. Urine culture was positive in 59% of cases. Fistulae were present in 8%. Correct preoperative diagnosis occurred in only 45% of patients. Standard treatment continues to comprise a short cause of antibiotics and open radical (total) nephrectomy. Preoperative decompression occurred in 56% of patients. When considered at all, laparoscopic nephrectomy was performed in 34% of patients. Partial nephrectomy was conducted in 2% of patients. CONCLUSIONS: Xanthogranulomatous pyelonephritis has a lower mortality rate than historically reported. A typical patient is a woman in her fifth or sixth decade of life with urolithiasis. While open radical nephrectomy remains the most common treatment method, laparoscopic, and to a lesser degree partial nephrectomy, are feasible in well selected patients.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

OBJECTIVE: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011-2020) at a population level within a clinical quality cancer registry. PATIENTS AND METHODS: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state-wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. RESULTS: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36-23%, with commensurate rises in GG 2 (31-36%), GG 3 (14-17%) and GG 5 (9.3-14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56-35%, compared to patients aged 55-64 (41-31%), 65-74 (31-21%), and ≥75 years (12-10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. CONCLUSION: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods.

Systematic review of urological injury during caesarean section and hysterectomy.

INTRODUCTION AND HYPOTHESIS: We aim to review iatrogenic bladder and ureteric injuries sustained during caesarean section and hysterectomy. METHODS: A search of Cochrane, Embase, Medline and grey literature was performed using methods pre-published on PROSPERO. Eligible studies described iatrogenic bladder or ureter injury rates during caesarean section or hysterectomy. The 15 largest studies were included for each procedure sub-type and meta-analyses performed. The primary outcome was injury incidence. Secondary outcomes were risk factors and preventative measures. RESULTS: Ninety-six eligible studies were identified, representing 1,741,894 women. Amongst women undergoing caesarean section, weighted pooled rates of bladder or ureteric injury per 100,000 procedures were 267 or 9 events respectively. Injury rates during hysterectomy varied by approach and pathological condition. Weighted pooled mean rates for bladder injury were 212-997 events per 100,000 procedures for all approaches (open, vaginal, laparoscopic, laparoscopically assisted vaginal and robot assisted) and all pathological conditions (benign, malignant, any), except for open peripartum hysterectomy (6,279 events) and laparoscopic hysterectomy for malignancy (1,553 events). Similarly, weighted pooled mean rates for ureteric injury were 9-577 events per 100,000 procedures for all hysterectomy approaches and pathologies, except for open peripartum hysterectomy (666 events) and laparoscopic hysterectomy for malignancy (814 events). Surgeon inexperience was the prime risk factor for injury, and improved anatomical knowledge the leading preventative strategy. CONCLUSIONS: Caesarean section and most types of hysterectomy carry low rates of urological injury. Obstetricians and gynaecologists should counsel the patient for her individual risk of injury, prospectively establish risk factors and implement preventative strategies.

Strategies for success: a multi-institutional study on robot-assisted partial nephrectomy for complex renal lesions.

OBJECTIVE: To describe our technique, illustrated with images and videos, of robot-assisted partial nephrectomy (RAPN) for challenging renal tumours. PATIENTS AND METHODS: A study of 249 patients who underwent RAPN in multiple institutions was performed. Patients were identified using prospective RAPN databases. Complex renal lesion were defined as those with a RENAL nephrometry score ≥10. Data were analysed and differences among groups examined. RESULTS: A total of 31 (12.4%) RAPNs were performed for complex renal tumours. The median (interquartile range [IQR]) patient age was 57 (50.5-70.5) years and 21 patients (67.7%) were men. The median (IQR) American Society of Anesthesiologists score was 2 (2-3). The median (IQR) operating time was 200 (50-265) min, warm ischaemia time was 23 (18.5-29) min, and estimated blood loss was 200 (50-265) mL. There were no intra-operative complications. Two patients (6.4%) had postoperative complications. One patient (3.2%) had a positive surgical margin. The median (IQR) length of stay was 3.5 (3-5) days and the median (IQR) follow-up was 12.5 (7-24) months. There were no recurrences. RAPN resulted in statistically significant changes in renal function 3 months after RAPN compared with preoperative renal function (P < 0.001). CONCLUSION: Our results showed that RAPN was a safe approach for selected patients with complex renal tumours and may facilitate tumour resection and renorrhaphy for challenging cases, offering a minimally invasive surgical option for patients who may otherwise require open surgery.

The role of localised prostate cancer treatment in renal transplant patients: A systematic review.

Objective: To systematically review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients. Method: A systematic review was conducted adhering to PRISMA guidelines. Searches were performed in the Cochrane Library, Embase, Medline, the Transplant Library and Trip database for studies published up to September 2022. Risk of bias was assessed with the Cochrane Risk of Bias in Non-Randomised Studies of Interventions for non-randomised studies tool. Results: A total of 60 studies were identified describing 525 patients. The majority of studies were either retrospective non-randomised comparative or case series/reports of poor quality. The vast majority of studies were focussed on prostate cancer after renal transplantation. Overall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (high-intensity frequency ultrasound) and 21 patients were placed on active surveillance. The mean age was 61 years old, the mean PSA level at diagnosis was 9.6 ng/mL and the mean follow-up time was 31 months. The majority of patients had low-risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%). All prostate cancer mortality cases were in high-risk prostate cancer (≥Gleason 8). The cancer-specific survival results were similar between surgery and radiotherapy at 1 and 3 years. Conclusion: Localised prostate cancer treatment in renal transplant patients should be risk stratified. Surgery and radiation treatment for localised prostate cancer in renal transplant patients appear equally efficacious. Given the limitations of this study, future research should concentrate on developing a multicentre RCT with long-term registry follow-up.

The impact of health-policy-driven subsidisation of prostate magnetic resonance imaging on transperineal prostate biopsy practice and outcomes.

Background: From 1 July 2018, the Australian Medicare Benefits Schedule (MBS) introduced rebates for multi-parametric magnetic resonance imaging (mpMRI) for the workup for prostate cancer (PCa). We aimed to determine if subsidisation of mpMRI prior to transperineal biopsy altered our institution's prostate biopsy practice patterns and outcomes. Methods: All patients who underwent transperineal prostate biopsy at an Australian tertiary institution from 1 January 2017 to 1 January 2020 were identified. Patients with known PCa were excluded. Patients were stratified into two groups: a pre-subsidisation cohort comprising patients biopsied prior to the introduction of mpMRI subsidisation on 1 July 2018 and a post-subsidisation cohort comprising patients biopsied after 1 July 2018. Histopathological results were compared with further stratification based on mpMRI results. Clinically significant cancer was defined as ISUP Grade Group ≥ 2. Results: Six hundred and fifty men fulfilled the inclusion criteria. Three hundred and sixty-one patients were in the pre-subsidisation cohort and 289 in the post-subsidisation cohort. Of the patients in the pre-subsidisation group, 36.3% underwent a pre-biopsy mpMRI compared with 77.5% in the post-subsidisation group. Of the patients in the pre-subsidisation group, 59.6% had positive biopsies (p = 0.024) compared with 68.2% in the post-subsidisation group. The rate of clinically significant PCa was lower in the pre-subsidisation group (39.1%) compared with the post-subsidisation (49.5%, p = 0.008). The negative predictive value of mpMRI for clinically significant PCa was 86.5%. Conclusion: Our institution experienced a reduction of negative prostate biopsies and an increase in clinically significant PCa within transperineal biopsy specimens after the Australian healthcare system introduced financial subsidisation of mpMRI.

Renal Cell Carcinoma Follow-Up - Is it Time to Abandon Ultrasound?

BACKGROUND: We wished to compare the efficacy of ultrasound versus intravenous contrast-enhanced computed tomography (CT) for detecting recurrent renal cell carcinoma (RCC) by identifying patients presenting with such tumor burden and to evaluate the utility of these imaging modalities in these circumstances. METHODS: Patients who developed local and/or distant recurrences following surgical intervention for RCC were identified. The imaging regimen utilized during post-operative surveillance was analyzed to determine whether recurrent disease was identifiable on ultrasound or CT or both. RESULTS: Of the 22 patients with recurrent RCC, 16 had previously undergone radical nephrectomy and 6 had undergone partial nephrectomy. Median duration to RCC recurrence was 28.5 months (range 2-66 months). Fourteen patients (64%) underwent ultrasound during their follow-up surveillance protocol and 1 case of disease recurrence was detected by ultrasound before subsequent con-frmation with CT. All 22 patients underwent CT as a routine component of their follow-up surveillance protocol and all recurrences were detected by this modality. Six patients had recurrence in their ipsilateral kidney after partial nephrec-tomy - five had undergone ultrasound in their surveillance protocol and this modality failed to detect a recurrence in four of these patients. CONCLUSION: Ultrasound is inferior to CT for detecting recurrent RCC. CT should be recognized as the standard diagnostic modality during post-operative surveillance, in contradiction to what is recommended in many guidelines.