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.

[Effect of equal temperature bladder irrigation in patients with transurethral resection of prostate: A meta-analysis].

OBJECTIVE: To evaluate the effect of equal temperature bladder irrigation on bladder spasm, postoperative bleeding, vital signs and discomfort of chills in patients of transurethral resection of prostate using meta-analysis. METHODS: Several electronic databases included Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM) were searched systematically for published randomized controlled trial about equal temperature bladder irrigation in patients with transurethral resection of prostate before November 20, 2019. Two reviewers selected independently the literature in the light of the inclusion and exclusion criteria, assessed the risk of bias by quality assessment and extracted data which were consisted of clinical efficacy indexes, such as incidence of bladder spasm, severity of bladder spasm, incidence of tube plugging, amount of bladder flushing fluid, time of bladder flushing, heart rate, systolic pressure, diastolic pressure, and incidence of chills. Data were pooled using fixed-effects model or random-effects model, and the summary effect measure was calculated by risk ratio (RR) or mean difference (MD) and 95% confidence interval (95%CI). Meta-analysis was performed by Review Manager 5.3 Software. RESULTS: In the study, 13 randomized controlled trails met the requirement with a total of 2 033 patients of transurethral resection of prostate were included, of whom 1 015 were carried out with equal temperature bladder irrigation and 1 018 with room temperature bladder irrigation. The results of meta-analysis showed that incidence of bladder spasm [RR=0.51, 95%CI (0.45, 0.57), P < 0.001], severity of bladder spasm [MD=-1.61, 95%CI (-2.00, -1.23), P < 0.001], incidence of urinary blockage [RR=0.29, 95%CI (0.19, 0.44), P < 0.001], dosage of bladder irrigation [MD=-6.75, 95%CI (-7.33, -6.17), P < 0.001], time of bladder rinse [MD=-7.60, 95%CI (-11.91, -3.29), P < 0.001], heart rate [MD=-13.68, 95%CI (-15.19, -12.17), P < 0.001], systolic pressure [MD=-29.26, 95%CI (-31.92, -26.59), P < 0.001], diastolic pressure [MD=-29.36, 95%CI (-31.75, -26.98), P < 0.001], incidence of chills and discomfort [MD=0.37, 95%CI (0.31, 0.44), P < 0.001] in equal temperature group of the patients with transurethral resection of prostate had significantly statistical difference compared with room temperature group. CONCLUSION: Based on current available evidence, equal temperature bladder irrigation reduced the incidence of bladder spasm and urinary blockage, relieved bladder spasm, reduced dosage and time of bladder irrigation, and hardly affected normal vital signs and increased the patient' s comfort.

In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection.

PURPOSE: Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination. METHODS: Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated. RESULTS: The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 105 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly. CONCLUSION: A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells. TRIAL REGISTRATION: The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.

Predicting long-term outcomes of ultrasound-guided percutaneous irrigation of calcific tendinopathy with the use of machine learning.

OBJECTIVE: To evaluate the performance of two machine learning models in predicting the long-term complete pain resolution in patients undergoing ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT). MATERIALS AND METHODS: Within a 3-year period, 100 consecutive patients who underwent US-PICT for rotator cuff disease were prospectively enrolled. The location, maximum diameter, and type of each calcification were recorded. The degree of calcium retrieval was graded as complete or incomplete. Shoulder pain was assessed with the visual analogue scale (VAS) at baseline, 1-week, 1-month, and 1-year post-treatment. Measurements related to procedural details, patient, and calcification characteristics were used to construct a machine learning model for the prediction of pain at 1-year post-US-PICT. Two distinct models were built, one including VAS data at 1 week and another additionally including pain data at 1-month post-treatment. Variable importance analysis was performed for the 1-week model. Model performance was evaluated by using receiver operating characteristics (ROC) curves and the respective areas under the curve (AUC). RESULTS: The model exhibited an AUC of 69.2% for the prediction of complete pain resolution at 1 year. The addition of VAS scores at 1 month did not significantly alter the performance of the algorithm. Age and baseline VAS scores were the most important variables for classification performance. CONCLUSION: The presented machine learning model exhibited an AUC of almost 70% in predicting complete pain resolution at 1 year. Pain data at 1 month do not appear to improve the performance of the algorithm.

Ultrasound-guided percutaneous irrigation of calcific tendinopathy: redefining predictors of treatment outcome.

OBJECTIVES: To identify prognostic factors affecting the clinical outcome in patients treated with rotator cuff ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT), by evaluating the degree of calcium removal, the size and consistency of calcific deposits, and baseline level of shoulder pain and functionality. METHODS: From January 2017 to December 2019, 79 patients (23 males, 56 females; mean age, 45.7 years) who underwent US-PICT were prospectively enrolled. The calcifications' location, consistency, and size were evaluated. For US-PICT, local anesthesia, lavage of calcific material, and intrabursal steroid injection were performed. The degree of calcium removal was graded as total/partial. Shoulder pain and functionality were assessed with the visual analogue scale (VAS) in all and Constant score (CS) in a subset of patients, respectively, at 4 time-points. Mann-Whitney U test, Fisher's test, and linear and binary logistic regression were utilized for analysis. RESULTS: Pain improvement correlated with the presence of larger calcifications and lower baseline VAS score, at 1 week (p = 0.001, p < 0.001, respectively) and 1 year (p < 0.001, p = 0.002, respectively). Improved functionality correlated with total calcification retrieval, higher baseline CS, and fluid/soft calcific consistency at 1 week (p = 0.013, p = 0.003, p = 0.019, respectively). Increased calcification size, cystic appearance, and lower baseline VAS scores independently predicted complete pain resolution at 1 year. CONCLUSION: Large calcifications and low-grade pain at baseline correlated with short- and long-term pain improvement. The degree of calcium removal did not impact pain or functional improvement beyond 1 week. Increased calcification size, cystic appearance, and low-grade baseline pain predicted complete pain recovery at 1 year. KEY POINTS: • The presence of larger calcifications and lower-grade baseline pain appear to correlate with pain improvement at 1 week and 1 year after ultrasound-guided irrigation of rotator cuff calcific tendinopathy (US-PICT). • Total calcification retrieval, less affected baseline shoulder functionality, and presence of fluid/soft consistency of calcific deposits appear to correlate with improved shoulder functionality at 1 week post-treatment. • Baseline pain intensity and calcifications' morphologic characteristics, but not the degree of calcium retrieval, represent predictors of complete pain recovery at 1 year after US-PICT.

A New Appendicostomy Technique to Prevent Stomal Stenosis.

PURPOSE: Stomal stenosis has been reported to occur in 12% to 45% of patients following Malone antegrade continence enema and Mitrofanoff appendicostomy. The standard stoma technique entails excision of the distal appendix. We evaluated a novel technique with preservation of the appendiceal tip and vessels, and opening the lumen in a more proximal and vascular area to determine whether the incidence of stenosis would be decreased. MATERIALS AND METHODS: Medical records of patients who underwent appendicostomy for Malone antegrade continence enema or urinary diversion were retrospectively evaluated. We included cases with a minimum of 1 year of followup and those in which the distal portion of a complete appendix was oriented for use as the stomal end in the umbilicus. Variables such as age, gender, body mass index, antegrade continence enema or urinary diversion, open or laparoscopic approach, cecal and appendiceal adhesions, retrocecal position, cecal imbrication, technique and stenosis were recorded. Cox proportional hazards analyses were performed to determine association of covariates. RESULTS: A total of 123 patients met inclusion criteria. The incidence of stenosis following standard stoma technique was 13% (12 of 93 patients) with a median followup of 9.4 years. Of these cases 75% occurred within 1 year of surgery. Stomal stenosis did not occur after the new stoma technique in 30 patients with a median followup of 3.3 years. Only technique cohort (standard vs new) was associated with stenosis (p=0.04). CONCLUSIONS: Stomal stenosis of appendicostomy may be lessened by preservation of the distal appendiceal vasculature and tip, and opening the lumen in a more proximal location.

Tolerability and effectiveness of povidone-iodine or mupirocin versus saline sinus irrigations for chronic rhinosinusitis.

OBJECTIVES: The role of topical anti-infectives in acute exacerbations of chronic rhinosinusitis is controversial. Povidone-iodine is an anti-bacterial and anti-viral that is affordable and available over-the-counter and may demonstrate advantages over mupirocin as a sinus irrigation therapy. The objective was to compare povidone-iodine or mupirocin versus saline sinus irrigations for sinusitis exacerbations in post-surgery subjects as well as to assess tolerability of povidone-iodine sinus irrigations. MATERIALS AND METHODS: This was a prospective single-blinded (clinician only) randomized controlled trial. Subjects were post-surgery with acute exacerbations of chronic rhinosinusitis and gram-positive bacteria on culture. They received povidone-iodine, mupirocin, or saline sinus irrigations, twice daily for 30 days. Outcomes were post-treatment culture negativity (primary) and Sinonasal Outcome Test-20 and Lund-Kennedy endoscopic score change (secondary). RESULTS: Of the 62 subjects analyzed, post-treatment culture negativity rate was higher in the MUP (14/20, 70%) group compared to the PI (9/21, 43%) and SAL (9/19, 47%) groups, although this was not significant (p = 0.29). Povidone-iodine sinus irrigations at the 1% concentration were very well-tolerated, similar to saline irrigations. There were no significant differences in Sinonasal Outcome Test-20 score (povidone-iodine -0.3 [-0.6, 0.05] vs. mupirocin -0.3 [-0.7, 0.05] vs. saline -0.4 [-0.8, 0.05]; p = 0.86) or Lund-Kennedy endoscopic score (povidone-iodine -3.5 [-7, -0.5] vs. mupirocin -2 [-4, 2] vs. saline -3 [-5, 0]; p = 0.45) change. No serious adverse effects were reported. CONCLUSIONS: In patients who have had prior sinus surgery with acute exacerbations of CRS and gram-positive bacteria on culture, mupirocin sinus irrigations achieved a better post-treatment culture "control" rate compared to saline and povidone-iodine. In addition, 1% povidone-iodine solution was well-tolerated as a sinus irrigation and may represent a feasible method for temporarily disinfecting the sinonasal cavity of bacteria and viruses such as COVID-19.

Local delivery therapies as adjuvants to non-surgical periodontal treatment of periodontitis grade C: a systematic review.

OBJECTIVES: The aim of this article was to perform a systematic review on the effectiveness of local adjuvant therapies in the treatment of aggressive periodontitis (AgP), now reported as periodontitis grade C. MATERIALS AND METHODS: The authors selected randomized clinical trials of AgP patients who received local therapy as adjuvants to non-surgical periodontal with a duration of at least 90 days. Seven databases were searched up to January 2020. The gain in clinical attachment level (CAL) and reduction of probing depth (PD) were the outcomes of interest. RESULTS: Of the 3583 studies found, only five articles were included in the qualitative analysis. Among the substances analyzed, only 1.2 mg of simvastatin gel (SMV) (1.2 mg/0.1 ml), 1% of alendronate gel (ALN) (10 mg/ml), and 25% metronidazole gel (MTZ) (Elyzol@) showed a significant decrease in the probing depth when compared with their respective control groups. The gain CAL was shown using 1.2 mg SMV gel (1.2 mg/0.1 ml) and 1% ALN gel (10 mg/ml). CONCLUSION: Although 1.2 mg SMV gel (1.2 mg/0.1 ml), 1% ALN gel (10 mg/ml), and 25% MTZ gel (Elyzol) have shown better results, local therapies adjuvant to SRP the data found were limited. Future clinical studies with appreciable methodological quality should be conducted. CLINICAL RELEVANCE: Despite some benefits of local delivery therapy, up to now, it has not been possible to prove the efficacy of local therapy as an adjunct to standard treatment of AgP (periodontitis grade C).

Continuous saline bladder irrigation for two hours following transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer does not prevent recurrence or progression compared with intravesical Mitomycin-C.

BACKGROUND: Intravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT. METHODS: We retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed. RESULTS: 205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk. CONCLUSIONS: Postoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone.

Analysis of the effects of several decalcifying agents alone and in combination with sodium hypochlorite on the chemical composition of dentine.

AIM: To investigate the effects of several decalcifying agents alone and in combination with sodium hypochlorite (NaOCl) on the organic and inorganic components of dentine using attenuated total reflectance in Fourier transform infrared spectroscopy (ATR-FTIR). METHODOLOGY: Dentine slices from bovine teeth were submitted to (n = 5) the following: 0.9% saline, 9% and 18% etidronic acid (HEDP), 5% and 10% tetrasodium EDTA (EDTANa4 ), 17% trisodium EDTA (EDTAHNa3 ), and 0.5% and 2.0% peracetic acid (PAA) for 0.5-10 min; and to the combinations: G1 - mixture 5% NaOCl + 18% HEDP (5 and 10 min); G2 - mixture 5% NaOCl + 10% EDTANa4 (5 and 10 min); G2 - 2.5% NaOCl (5 min) + 17% EDTAHNa3 (1 min); G3 - 2.5% NaOCl (5 min) + 0.5% PAA (1 min); G4 - 2.5% NaOCl (5 min) + 9% HEDP (5 min). Specimens of G2, G3 and G4 received final flushes with 2.5% NaOCl for 0.5-10 min. Amide III/phosphate and carbonate/phosphate ratios of the spectra collected from the dentine specimens before and after immersion in the solutions were determined. Data were submitted to one-way repeated measures and one-way anova. RESULTS: For the same decalcifying agent, the higher the concentration and immersion time the greater the removal of phosphate, exposure of collagen matrix and consequently the increases in amide III/phosphate ratio. However, significant differences were found only between the two concentrations of PAA (P < 0.05). PAA caused greater increases in this ratio, followed by EDTAHNa3 , EDTANa4 and HEDP, and this order was retained in the combinations with NaOCl. This ratio was significantly reduced in G1 (P < 0.05) and not altered in G2 (P > 0.05). Due to collagen degradation, the amide III/phosphate ratio reduced significantly after the use of NaOCl in G3, G4 and G5 (P < 0.05). NaOCl required approximately 0.5 s to deproteinate the collagen matrix exposed after phosphate removal by EDTAHNa3 and PAA. The carbonate of dentine was removed more rapidly than phosphate by all decalcifying agents alone and in G3, G4 and G5. In the combinations with NaOCl, the last irrigant used defined the dentine amide III/phosphate and carbonate/phosphate ratios. CONCLUSIONS: HEDP and EDTANa4 caused minor whilst EDTAHNa3 and PAA caused greater demineralization of dentine; both effects were time and concentration dependent. NaOCl degraded the dentine organic matrix more rapidly when it was exposed. Combinations of NaOCl and decalcifying agents can be used to create dentine surfaces with varying compositions for interaction with endodontic sealers.