A phase 2 pilot study of water irrigation after transurethral resection of bladder tumor (WATIP) demonstrating safety, feasibility and activity.

PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) can recur, partly due to seeding of free tumour cells after transurethral resection of bladder tumour (TURBT). Intravesical chemotherapy post-TURBT can reduce the risk but is used infrequently and inconsistently due to cost, complexity and side effects. The objective of this study was to prospectively assess continuous bladder irrigation using water, which may be a safer and easier alternative with comparable effectiveness. METHODS: WATIP was a prospective, single-arm phase 2 study of water irrigation during and for at least 3 h after TURBT for bladder tumours noted on imaging or flexible cystoscopy. Participants were assessed clinically for adverse effects and with blood tests within 24 h for sodium, haemoglobin and lactate dehydrogenase. The primary endpoints were safety (defined as < 10% adverse events of CTCAE grade ≥ 3), and feasibility (defined as the intervention being delivered as planned in > 90% of cases) and secondary endpoint was recurrence-free rates (RFR). RESULTS: Water irrigation was delivered as planned in 29 (97%) of 30 participants (median age 67 years, 25 (83%) males). The only adverse event (grade 2) was clot retention in one (3.3%) participant. Water irrigation significantly reduced urothelial cell counts in catheter effluent over time, unlike saline irrigation which did not. RFR was 56.2% (9/16 participants with low-risk NMIBC) at first cystoscopy (median interval 108 days) and 62.5% (5/8 evaluable low-risk NMIBC) at 12 months. CONCLUSION: Water irrigation during and after TURBT is feasible and safe. Prospective assessment of its effect on NMIBC recurrence compared to post-TURBT intravesical chemotherapy is needed before recommending its use in routine clinical practice. Trial registration ANZCTR registration ID ACTRN12619000517178 on 1 April 2019.

Acute medical stabilisation of adults with anorexia nervosa: experience of a defined interdisciplinary model of care.

BACKGROUND: Patients with anorexia nervosa (AN) are vulnerable to physiological decompensation and often require inpatient management by an eating disorders unit. AIMS: Patients admitted to an Australian tertiary medical centre for medical stabilisation of AN were assessed as part of quality assurance. Analysis included: (i) medical complications during acute inpatient stabilisation; (ii) predictors of refeeding syndrome; (iii) predictors governing length of stay (LOS); and (iv) outcomes pre- and post-implementation of multidisciplinary treatment guidelines. METHODS: A retrosepctive analysis of 95 consecutive admissions (60 individual patients) between November 2011 and August 2017 was performed. RESULTS: Patients had a median LOS of 9.6 days (interquartile range 5.8-19.7) and a mean weight gain of 1.4 kg (standard deviation 2.9). Medical complications included the following: hypoglycaemia (11.6%) and refeeding electrolyte derangement (26.3%). Advancing age (odds ratio (OR) 1.06 per year, P = 0.019), nasogastric tube requirement (OR 3.4, P = 0.014) and Code Grey(s) (security calls) (OR 7.1, P = 0.010) were associated with refeeding electrolyte derangement. Parameters associated with increased LOS included the following: lower body mass index (P = 0.029), Code Grey(s) (P = 0.029) and tachycardia (P = 0.013). Following multivariate analysis, the post-guidelines implementation group required less intravenous fluid and electrolyte replacement, though had lower rates of refeeding electrolyte derangement (OR 0.33 (0.11-0.99)). CONCLUSION: Patients with moderate to severe AN are at risk of dangerous medical complications, and older patients may have heightened predisposition to refeeding electrolyte derangement. Early identification of medically high-risk patients is imperative to implement timely, life-saving interventions.

Lytic effects of water on cancer cells: Implications for post-operative irrigation.

BACKGROUND: Intraoperative tumour spillage can be concerning during cancer excisions, given it can lead to tumour-cell re-implantation and local recurrence. Examples include bladder tumour recurrences post-transurethral resection, or peritoneal spillage during laparotomy/laparoscopy for bowel and ovarian cancers. One approach to reducing implantation is mechanical wash out of free-floating tumour cells. Irrigation with water may have additional effectiveness compared to iso-osmotic irrigants (e.g. saline) by causing osmotic cytolysis, but this is not well-characterised. This in vitro study aimed to ascertain the time-course of osmotic effects of water on various cancer cell lines to provide guidance for clinical usage. METHODS: Assays were conducted on six cancer cell lines (bladder [HT1197, HT1376], colon [KM12, LIM2405], kidney [SKRC52], and ovarian [COV434]). Cells were exposed to water or 0.9% saline and cell counts were performed using a haemocytometer at 10, 20, 40, 60, 120 and 180 min. Cell viability was determined using Trypan Blue exclusion. RESULTS: In all cell lines, exposure to water led to 100% cell lysis within a median time of 40 min (range 10-180 min), while exposure to saline led to a gradual decline in cell viability (median 50.2%, range 6.7%-100.0%) over 3 h, and did not result in complete cell lysis. An increase in osmotic gradient equivalent to a concentration of 5% NaCl was sufficient to impede the effects of water-mediated cell lysis. CONCLUSION: Our studies suggest that water has a rapid osmolytic effect on cancer cells. The required exposure time to reach 0% cell viability varied between individual cell lines.

Continuous bladder irrigation after transurethral resection of non-muscle invasive bladder cancer for prevention of tumour recurrence: a systematic review.

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) can recur despite transurethral resection of bladder tumour (TURBT) that clears macroscopic disease, partly from re-implantation of exfoliated cells. Immediate instillation of intravesical chemotherapy (IC) can reduce recurrence, is guideline-recommended but is under-utilized. Continuous bladder irrigation (CBI) immediately post-TURBT is postulated to prevent re-implantation, and may provide a simple, cheap and practical alternative. We undertook a systematic review to assess the effect of CBI on NMIBC recurrence. METHODS: Following PRISMA guidelines, relevant publications were identified by online search of databases, including Ovid Medline and EMBASE (1980-2019). All published prospective randomized controlled trials comparing CBI post-TURBT to a control group were included. The primary end-point was recurrence. RESULTS: Our search yielded 514 studies, of which six met inclusion criteria. Two studies (935 participants), albeit without peer-reviewed publication, comparing CBI to no CBI both showed a reduction in recurrence at 2 years. Four publications from three trials (331 participants) compared CBI to IC, showing similar recurrence rates at 1 year (odds ratio 1.29, 95% confidence interval 0.78-2.13) but a lower risk of adverse events (6-34% versus 27-48%). CONCLUSION: CBI post-TURBT appears to yield 1-year recurrence rates of NMIBC comparable to immediate IC. However, existing studies are small and of heterogenous design, precluding definitive conclusions. Further trials are required to determine if CBI can be implemented routinely to reduce NMIBC recurrence, as well as the optimal irrigant, volume and duration.

Nephron-sparing surgery for the management of upper tract urothelial carcinoma: an outline of surgical technique and review of outcomes.

Upper tract urothelial carcinoma (UTUC) often occurs in elderly patients with multiple co-morbidities including renal impairment. As such, nephron sparing surgery (NSS) often needs to be considered. This article reviews the available NSS techniques for UTUC, including ureteroscopy, percutaneous approaches and segmental ureterectomy. PubMed and OvidMEDLINE reviews of available case series from the last 10 years demonstrated that recurrence was highly variable between studies and occurred in 19-90.5% of ureteroscopic cases, 29-98% of percutaneous resections and in 10.2-31.4% of patients who underwent segmental ureterectomy. The small number of included studies and variable follow up periods made comparison between techniques difficult. NSS is a necessary alternative for patients with significant comorbidities or renal impairment who cannot undergo radical nephro-ureterectomy. However, there is significant variation in oncological outcomes, with an increased risk of progression or death from cancer-salvage by radical surgery may sometimes be required.