Instillation In Patients Research Articles

Effectiveness of 0.3% Hyaluronic Acid Eye Drops for Benign Essential Blepharospasm and Hemifacial Spasm with Botulinum Toxin-induced Dry Eye.

This study evaluates the effectiveness of 0.3% hyaluronic acid (HA) eye drops in patients receiving concurrent botulinum toxin (BoNT) injections for benign essential blepharospasm (BEB) or hemifacial spasm (HFS). This randomized controlled cross-over trial study involved 14 patients with BEB and 33 patients with HFS randomized into two groups (early treatment and deferred treatment) for 3 months of treatment with 0.3% HA eye drops. Data collected at baseline, 3 months, and 6 months included Blepharospasm Severity Scale (BSS) score in patients with BEB; Samsung Medical Class Grading Scale score in patients with HFS; and dry eye symptoms, lower eyelid tear meniscus height (TMH), tear breakup time (TBUT), and corneal fluorescein staining in both groups. After 3 months of 0.3% HA instillation, patients with BEB in both groups showed significant improvement in BSS, TMH, TBUT, and the amelioration of subjective dry eye symptoms and corneal staining (P < 0.05). However, discontinuation of 0.3% HA eye drops worsened BSS, TMH, and TBUT. Patients with HFS also experienced significant improvement in Samsung Medical Class score, subjective dry eye symptoms, and objective corneal findings (P < 0.05). Treatment with 0.3% HA eye drops led to significant improvement in spasm severity, and dry eye parameters, after 3 months of instillation in patients with BEB or HFS during concurrent treatment with BoNT injections. The 0.3% HA eye drops were safe and might serve as an add-on treatment for symptom improvement.

Safety and oncological outcome of early intraoperative intravesicle mitomycin C vs. deferred instillation in patients receiving robot-assisted radical nephroureterectomy.

Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE. This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes. A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, p < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, p = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group. IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune responses that correlate with safety and may be associated to therapy potential

BackgroundStandard of care treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette Guérin (BCG) is associated with side effects, disease recurrence/progression and supply shortages. We recently showed in...

Usability of an Eye Drop Delivery Aid for Single-Dose Instillation: Results from a Market Research Study.

One of the challenges of treating chronic ocular diseases like vernal keratoconjunctivitis (VKC), glaucoma, and ocular surface disease is patient adherence to topical medication. To support correct eye drop instillation, a variety of delivery aids have been developed for both single-dose and conventional multi-dose containers. To evaluate Dropaid™ Single-dose, an eye drop delivery aid designed for single-dose containers, a usability study was conducted on 30 parents and caregivers of patients with VKC. After assessing the ability to squeeze a single eye drop from the single-dose container onto the eye of a pediatric medical dummy, the delivery aid was evaluated using an 11-point Likert scale on a variety of characteristics: from "very difficult" (-5) to "very easy" (+5). The majority of participants rated the task of opening the single-dose units (SDUs), preparing, and positioning the Dropaid™ Single-dose device as "very easy". When providing a single eye drop from the container, 87% of participants rated the Dropaid™ Single-dose device as either "very easy" or "easy", with a median rating score of +5.0 (interquartile range [IQR], 4.0-5.0). For general ease of use, 84% considered the delivery aid as either "very easy" or "easy", with a median score of +4.0 (IQR, 3.0-5.0). Most participants (93%) rated Dropaid™ Single-dose as either "very comfortable" or "comfortable" to hold, with a median score of +5.0 (IQR, 4.0-5.0). The Dropaid™ Single-dose delivery aid demonstrated rapid learning and ease of use across all stages of application, including opening the container, eye drop administration, and handling comfort. Although designed for use with single-dose containers to help eye drop instillation in patients with VKC, Dropaid™ Single-dose may provide a wider utility across a range of other ocular diseases such as glaucoma and dry eye.

COMPARATIVE STUDY TO ASSES ANALGESIC EFFICACY AND OPIOID SPARING EFFECT OF USG GUIDED SUBCOSTAL TRANSVERSUS ABDOMINIS PLANE BLOCK WITH INTRAPERITONEAL INSTILLATION OF BUPIVACAINE IN PATIENT UNDERGOING LAPAROSCOPIC CHOLECYSTECTOMY FOR POSTOPERATIVE PAIN RELIEF.

Background- Intensity of pain in early post-operative period after laparoscopic cholecystectomy is signicant. There are several methods employed in the management of postoperative pain after laparoscopic cholecystectomy such as conventional systemic analgesics, including paracetamol, non-steroidal anti-inammatory drugs, systemic opioids, and thoracic epidural analgesia with all having its limitations and side effects. Objective- The present study aims to compare ultrasound-guided subcostal transversus abdominis (STA) block with intraperitoneal instillation of bupivacaine in reducing postoperative pain, total analgesic consumptions after elective laparoscopic cholecystectomy. Materials and methods: 60 adult patients were randomly divided into 2 groups of 30 in each. The selected patients were randomly divided into two groups Group 1, patients received USG guided tap block before surgery. Group 2 patients received 40 ml of 0.25 % bupivacaine after surgery, instillation done by surgeon intraperitoneally at gall blabber bed and under the domes of diaphragm. Statistical analysis: In all Quantitative data were expressed in mean and standard deviation. Qualitative data were expressed in proportion and percentages. To nd the signicant difference between the bivariate samples in independent groups the Unpaired sample t-test and the Mann-Whitney U test was used. Above statistical tools the probability value &gt; .05 was considered as signicant level. Results: The mean Numerical Rating Scale scores were less in Group 1 than in Group 2 from 1 hours to 24 hours and it was statistically signicant. Demand of rescue analgesia was higher in group 2 when compared to group 1 and it was statistically signicant. Conclusion: TAP block is a better modality for analgesia compared to intraperitoneal instillation in patients undergoing elective laparoscopic cholecystectomy

Abstract LB246: Enfortumab vedotin, a nectin-4-directed antibody-drug conjugate, demonstrates compelling antitumor activity in non-muscle invasive bladder cancer models which predicts minimal systemic exposure when administered by intravesical instillation in patients

Abstract Enfortumab vedotin (EV) is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate directed to Nectin-4, which is highly expressed in bladder cancers. Preclinically, EV has demonstrated tumor cell killing by direct cytotoxicity and bystander effect and can induce the hallmarks of immunogenic cell death. EV improves survival in adults with previously treated locally advanced or metastatic urothelial carcinoma (la/mUC) and is approved in the US, Europe, Japan, and others. Most newly diagnosed bladder cancer cases are non-muscle invasive (NMIBC). Standard treatment of high-risk NMIBC involves transurethral resection followed by intravesical Bacillus Calmette-Guerin (BCG) or chemotherapy. Although response to BCG is high, recurrence is common, and treatment options for patients with BCG-unresponsive tumors are limited, underscoring the significant unmet need. Previously, we demonstrated compelling preclinical antitumor activity of EV in NMIBC models with a favorable safety profile and minimal systemic exposure. EV-mediated antitumor activity was confirmed in a mouse model of NMIBC by both bioluminescence imaging and IHC for hNectin-4-expressing cancer cells. Following intravesical administration of EV, tumor growth inhibition ranged 46-96% across the dose range tested. Colocalization of EV to Nectin-4-positive tumor tissues was confirmed by IHC in the engrafted tumor cells. Systemic EV exposure in tumor-bearing mice was low, consistent with previous nonclinical studies, supporting that the antitumor activity is driven by local exposure within the bladder. In a repeat-dose GLP toxicology study in rats, no systemic toxicities were observed at intravesical doses up to 6-fold higher than the maximum tolerated IV dose. This lack of systemic toxicities that can occur with IV administration in rats was likely due to minimal systemic exposure of both EV and unconjugated MMAE. Currently, the safety, tolerability, and antitumor activity of intravesical EV are being evaluated in a Phase 1 study in adults with high-risk, BCG-unresponsive NMIBC (EV-104, NCT05014139). The initial dose level for EV-104 was selected to be active and predicted to have minimal systemic absorption based on preclinical and known clinical IV data. Here, we present confirmatory clinical data demonstrating that EV and unconjugated MMAE are undetectable in the bloodstream at the starting dose. These findings confirm the translatability of our nonclinical models and provide evidence that intravesical administration of EV in NMIBC is a promising approach that limits systemic exposure. These data support the potential for a favorable safety and activity profile and warrant continued investigation of intravesical EV in patients with NMIBC. Citation Format: Devra Olson, Yen Lin Chia, Enaharo Iboi, Lauren Farr, Maddy Burcher, Anthony Lee, Kelly Hensley, Sean Allred, Abbie Wong, Masashi Shimazaki, Masamichi Mori, Sharsti Sandall, Christopher Carosino. Enfortumab vedotin, a nectin-4-directed antibody-drug conjugate, demonstrates compelling antitumor activity in non-muscle invasive bladder cancer models which predicts minimal systemic exposure when administered by intravesical instillation in patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB246.

Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter.

You have accessJournal of UrologyLetters to the Editor1 Apr 2023Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study. Letter. Ashish Ranjan, Ankit Misra, Sanjoy Kumar Sureka, and Uday Pratap Singh Ashish RanjanAshish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Ankit MisraAnkit Misra * E-mail Address: [email protected] Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , Sanjoy Kumar SurekaSanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author , and Uday Pratap SinghUday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003363AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail J Urol. 2023;209(1):131-139. To the Editor: We read with great interest the study investigating the novel role of intravesical mitomycin-C (MMC) in nonmuscle-invasive bladder cancer (NMIBC) in a neoadjuvant setting.1 Single, immediate, post-transurethral resection of bladder tumor (TURBT) instillation of MMC is the standard protocol in NMIBC.2 It primarily reduces the recurrence risk by eliminating viable residual tumors and preventing reseeding of the free-floating cancer cells.3 However, fear of extravasation and its associated serious complications has led to its low practical compliance worldwide.4 This study has demonstrated the use of neoadjuvant intravesical MMC for NMIBC with promising therapeutic efficacy, better tolerability, and low significant adverse effects. Although the dose and schedule of neoadjuvant MCC followed in the study were convenient for the patient, we would like to know the scientific basis for using 2 doses at a specific interval. The writers mention a preliminary study for deciding on 2 doses of neoadjuvant MMC, but no reference has been given. Do the authors feel that the control group should have received a single immediate post-TURBT MMC per the standard? Were any morphological or radiological criteria considered before administering the neoadjuvant therapy? The rationale of giving MMC post-TURBT is only to give it to patients with superficial disease on resection. Would it not be an overtreatment and waste of resources on those that eventually come out as muscle invasive? MMC concentration in tumor and normal tissue was measured to know about uptake, but is there any standard concentration in the postoperative instillation setting to which it was matched? Moreover, it would be interesting to know the method used to detect the concentration of MMC in the tissue. Would continuous saline irrigation used during the TURBT have diluted the effect of MMC on the tissue? Multifocal tumors were more in the control arm (24, 63%) than in the intervention arm (15, 46%). Was this difference statistically significant? This could have a bearing on better recurrence-free survival in the intervention arm and more progression in control. Lastly, we appreciate the authors' focus on an important area in NMIBC treatment. REFERENCES 1. . Clinical efficacy of neoadjuvant intravesical mitomycin-C therapy immediately before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer: preliminary results of a prospective, randomized phase II study. J Urol. 2023; 209(1):131-139. Link, Google Scholar 2. . Trial-based cost-effectiveness analysis of an immediate postoperative mitomycin C instillation in patients with non–muscle-invasive bladder cancer. Eur Urol Open Sci. 2022; 37:7-13. Crossref, Medline, Google Scholar 3. . Continuous saline bladder irrigation in reducing recurrence and progression when compared to immediate mitomycin-C instillation post-resection of bladder tumor: a short communication. Asian Pac J Cancer Prev. 2022; 23(1):171-175. Crossref, Medline, Google Scholar 4. . Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa-pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation?Eur Urol. 2016; 69(2):231-244. Crossref, Medline, Google Scholar Submitted December 19, 2022; accepted February 2, 2023; published 000. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue 4April 2023Page: 677-678 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashish Ranjan Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Ankit Misra Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India * E-mail Address: [email protected] More articles by this author Sanjoy Kumar Sureka Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Uday Pratap Singh Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India More articles by this author Expand All Submitted December 19, 2022; accepted February 2, 2023; published 000. 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Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer

To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.

Safety and Efficacy of Intravesical Epinephrine Instillation in Patients with Intractable Lower Urinary Tract Hematuria – A Novel Approach

To treat intractable hematuria with intravesical instillation of epinephrine. Sixty patients were treated with intravesical instillation of epinephrine at Mackay Memorial Hospital. The control group was composed of 60 patients who were treated with standard-of-care cystoscopic electrocautery fulguration. Under general anesthesia, epinephrine-treated group were injected with 150 mL of diluted epinephrine (1:10,000) through cystoscopy, followed by bladder irrigation with 1:100,000-diluted epinephrine at the ward. Successful hemostasis was defined as hematuria resolution within 1 month post-treatment without additional invasive procedures. In the 60 patients who underwent intravesical instillation of epinephrine, radiation cystitis was the most common etiology (65.0%). Fifty-two patients (86.7%) required no additional therapy within 1 month after one course of intravesical epinephrine instillation treatment compared with 28 patients (46.7%) in the electrocautery fulguration-control group (P <.001). We observed a significant decrease in both the median length of hospitalization (P=.049) and the need for additional invasive procedures (P <.001) in the epinephrine group. In addition, cardiopulmonary monitoring of mean blood pressure, mean heart rate, and mean respiratory rate demonstrated no significant differences after epinephrine treatment. In this study, intravesical instillation of epinephrine was an innovative method of hemostasis for intractable lower urinary tract hematuria with a success rate of 86.7%, compared to 46.7% in the control group, and significantly reduced the number of additional procedures required and the length of hospitalization. It was well-tolerated by all patients, and was a safe and effective treatment modality for intractable hematuria or bladder hemorrhage.

Preoperative sarcopenia and systemic immune-inflammation index can predict response to intravesical Bacillus Calmette-Guerin instillation in patients with non-muscle invasive bladder cancer.

BackgroundTo explore the prognostic significance of sarcopenia and systemic immune-inflammation index (SII) for response to intravesical Bacillus Calmette-Guerin (BCG) in patients with intermediate-, and high-risk non-muscle invasive bladder cancer (NMIBC).MethodsWe retrospectively analyzed 183 consecutive patients treated in Qilu hospital of Shandong University for a first diagnosis of intermediate and high risk NMIBC. Using computed tomography scans at the third lumbar vertebra level, we calculated skeletal muscle index (SMI). Sarcopenia was defined as SMI <43 cm2/m2 for males with BMI < 25 kg/m2, <53 cm2/m2 for males with BMI ≥ 25 kg/m2, and <41 cm2/m2 for females. The response to intravesical BCG immunotherapy and relapse-free survival (RFS) were analyzed.ResultsCompared with BCG responders, BCG non-responders were associated with sarcopenia (P < 0.001), carcinoma in situ (P < 0.001), T1 stage (P < 0.001), multiple tumor (P < 0.001), tumor diameter >=3cm (P < 0.001), and have a significant increase of neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), platelet to lymphocyte ratio (PLR) (P = 0.004), SII (P < 0.001). The area under the ROC curve (AUC) of the BMI, NLR, PLR, and SII for response to intravesical BCG immunotherapy were 0.425, 0.693, 0.631, and 0.702 respectively. Logistic regression analysis demonstrated that sarcopenia and SII were predictors of response to intravesical BCG immunotherapy. The Kaplan-Meier survival analysis showed that the RFS of patients with BCG response, lower SII and no sarcopenia was significantly increased compared with that of patients with BCG non-response, higher SII and sarcopenia, respectively. Subgroup analysis demonstrated that the RFS of patients with high SII and sarcopenia was significantly decreased compared with those with low SII and no sarcopenia in Ta stage subgroup, T1 stage subgroup, non-Cis subgroup, multiple tumor subgroup, single tumor subgroup, tumor diameter≥3cm subgroup and tumor diameter<3cm subgroup, respectively (P < 0.05). However, there was no significant difference in RFS for patients in CIS subgroup (P > 0.05). Multivariate Cox analysis shown that sarcopenia (p=0.005) and high SII (p = 0.003) were significantly associated with poor RFS.ConclusionsBoth sarcopenia and high SII are useful predictors of response to intravesical BCG in intermediate- and high-risk NMIBC patients. Patients with intermediate- and high-risk NMIBC that had sarcopenia or high SII at diagnosis were associated with poor RFS, and the combination of sarcopenia and SII may be a better predictor of RFS.

Aqueous Humour Ofloxacin Concentration after Topical Instillation in Patients with Dry Eye Disease.

Background and Objectives: A prospective, randomized clinical trial was conducted to evaluate the concentration of ofloxacin in the aqueous humour (AqH) of patients suffering from dry eye disease (DED) after topical instillation. Materials and Methods: Ninety-one (91) cataract patients scheduled for phacoemulsification were categorized into three groups according to DED severity. Group I (n = 17) was comprised of subjects without DED, patients in group II (n = 37) were evaluated as having non-severe DED, while group III (n = 37) consisted of patients suffering from severe DED. Preoperatively, patients received 4 drops of 0.3% of ofloxacin at 15 min intervals. One hour after the last instillation, aqueous samples were collected intraoperatively. Results: The median AqH concentration of ofloxacin in group I was 199.9 ng/mL (range 92.2–442.8 ng/mL), while in group II it was 530.5 ng/mL (range 283.7–1004.9 ng/mL), and 719.2 ng/mL (range 358.0–1512.4 ng/mL) in Group III, p < 0.001 (Kruskal-Wallis tests). Pairwise tests (two-tailed with Bonferroni corrections) between groups resulted in a p-value of 0.001 when group II was compared to group I and group III was compared to group I, and a p-value of 0.020 when group II was compared to group III. The severity of DED, across groups I, II, and III, and the levels of ofloxacin revealed a strong positive correlation (r = 0.639, p < 0.001). Conclusions: Ofloxacin concentration in the AqH after topical drop instillation may be affected by the degree of ocular surface inflammation in patients suffering from DED.

Frequency of Complications Post-Intravesical BCG Instillation in Patients with Superficial Urinary Bladder Carcinoma

Objectives: To analyze patients who underwent intravesical BCG instillation for non-muscle invasive bladder tumor and to determine the frequency of complications after intravesical BCG instillation. Study Design: Cross-sectional study. Place and Duration of Study: Departments of Urology and General Surgery, Pakistan Ordinance Factories Hospital Wah Cantt from 1st January 2019 till 31st December 2020. Methodology: Fifty patients; Results: The mean age was 57.06±7.93 years. Forty two patients (84%) were male and 8 patients (16%) were female. Four patients (8%) were Ta stage, 34 patients (68%) were Tis stage and 12 patients (24%) were T1 stage. Mean time interval between TURBT and BCG instillation was 28.68±5.07 days, mean number of BCG instillation cycles was 6.80±2.06 days. Ten (20%) patients had urinary tract infection, 19 (38%) patients had bladder TB, 9 (18%) patients had BCG sepsis, 5 (10%) patients had miliary TB, 2 (4%) patients had epidimo-orchitis, 2 (4%) patients developed ophthalmic complications, 1 (2%) patient had polyarthralgia, 1 (2%) patient had septic arthritis and 1 (2%) patient developed spinal Conclusion: Bacillus Calmette-Guérin is most commonly used drug as chemotherapeutic agent for superficial bladder tumors after TURBT. Repeated cycles of BCG i.e. 6-12 cycles have been administered to patients. Previously most of symptoms i.e. LUTS, dysuria, hematuria were being associated with presence of tumor but now many case reports and few studies have associated these symptoms with BCG administration. Keywords: Superficial bladder carcinoma, Intravesical BCG, Lower urinary tract symptoms

Efficacy of Pretreatment with Preservative-Free Topical Bromfenac in Improving Post-Intravitreal-Injection Pain: A Prospective Pilot Study.

(1) Background: To determine the analgesic effect of pretreatment topical bromfenac instillation in patients undergoing intravitreal anti-VEGF treatment. (2) Methods: A prospective, non-randomized pilot study was conducted in patients scheduled to receive repeated intravitreal anti-VEGF injections at a single tertiary hospital. Before the planned second injection, the patients received topical bromfenac eye drops twice a day for 3 days. At 1, 6, and 24 h after the first and second injections, the post-injection pain scores were determined using the numerical rating scale (NRS) telephonically. (3) Results: A total of 28 patients were enrolled in this study. After the first intravitreal injection, the NRS pain scores were 4.04 ± 1.90 at 1 h, 1.57 ± 1.75 at 6 h, and 0.93 ± 1.27 at 24 h. The pain scores after the second intravitreal injection significantly decreased at each measurement time point (p = 0.002, 0.055, and 0.004, respectively) compared to the first injection. (4) Conclusions: The use of topical bromfenac eye drops before intravitreal injection can lead to a significant improvement in injection-related pain scores, which is the basis for a future large-scale randomized comparative study.

Association of Increased Age With Decreased Response to Intravesical Instillation of Bacille Calmette-Guérin in Patients With High-Risk Non-Muscle Invasive Bladder Cancer: Retrospective Multi-Institute Results From the Japanese Urological Oncology Research Group JUOG-UC-1901-BCG

ObjectiveTo compare the therapeutic effect of Bacille Calmette-Guérin (BCG) intravesical instillation in older and younger patients with high-risk non-muscle-invasive bladder cancer. The comparison was performed with propensity score matching (PSM) without terminating the death of the older patients using relatively large-scale retrospective data from multiple institutes in Japan. Materials and MethodsOverall, 3283 patients diagnosed with non-muscle-invasive bladder cancer treated with intravesical BCG instillation during 2000-2018 in 31 institutes were examined; 1437 and 602 patients with high-grade T1 and Tis tumors were divided into those aged ≥75 and <75 years. Multivariate analysis using the Fine–Gray competing risks regression model before PSM and survival analysis using the cumulative incidence method after PSM were performed. ResultsIn the pre-PSM series of high-grade T1 tumors, age ≥75 years was an independent prognostic factor for both recurrence and progression in multivariate analysis (P = .015 and P = .013). In the pre-PSM series with Tis tumor, no variables to predict recurrence and progression was found. In the post-PSM series of 870 high-grade T1 tumors, cumulative probability of recurrence after BCG intravesical instillation were significantly higher in patients aged ≥75 years than in those aged <75 years (P = .008). The frequency of discontinuation of BCG instillation in patients aged ≥75 years with high-grade T1 and Tis was not significantly different from those in patients aged <75 years (P = .564 and P = .869). ConclusionThe cumulative probability of recurrence after intravesical BCG instillation was significantly higher in older than in younger patients with high-grade T1 bladder cancer.

Antegrade Instillation of UGN-101 (Mitomycin for Pyelocalyceal Solution) for Low-Grade Upper Tract Urothelial Carcinoma: Initial Clinical Experience.

UGN-101 (mitomycin for pyelocalyceal solution) is a recently approved chemoablative treatment for low-grade (LG) upper tract urothelial carcinoma (UTUC). While approved for retrograde or antegrade administration, previous reports discuss only patients treated by retrograde approach. We report our techniques for antegrade administration along with early outcomes from our cohort of patients who have undergone UGN-101 administration via nephrostomy. UGN-101 is administered as 6 weekly instillations in patients who have undergone endoscopic ablation of LG UTUC. We outline our approach in patients thought to have LG UTUC from initial ureteroscopy to nephrostomy placement, UGN-101 administration and eventual nephrostomy removal. We discuss early durability of response along with adverse events with special attention to ureteral strictures. Eight patients underwent antegrade UGN-101 administration during the study period, all of whom underwent followup ureteroscopy with complete response in 4 patients. Three patients reported 5 adverse events-3 grade 1, 1 grade 2 requiring 1 week delay of treatment and 1 asymptomatic ureteral stricture. Median followup was 7 months. We outline our approach for antegrade administration of UGN-101 and discuss early results along with adverse events. Future studies should evaluate our method's potential to increase patient comfort, improve logistics and decrease risk of adverse events.

Trial-based Cost-effectiveness Analysis of an Immediate Postoperative Mitomycin C Instillation in Patients with Non–muscle-invasive Bladder Cancer

BackgroundBladder cancer imposes a significant public health burden on the European Union. There is a need for cost-effective treatment and follow-up regimens. ObjectiveTo assess the cost-effectiveness of immediate mitomycin C (MMC) instillation within 1 d after surgery compared to delayed MMC instillation within 2 wk after surgery with further adjuvant treatment, depending on the patient’s risk group. Design, setting, and participantsThis economic evaluation was based on a randomized controlled trial among 2243 Dutch patients with non-muscle-invasive bladder cancer (NMIBC) patients from a health care perspective over a 3-yr time period. Outcome measurements and statistical analysisThe treatment effect was measured as time to recurrence and recurrence-free survival. Missing effect data were imputed with multiple imputation. Health care utilization and related costs were estimated on the basis of treatment protocols for NMIBC patients in the Netherlands. Statistical uncertainty was estimated using bootstrapping and is graphically presented using cost-effectiveness planes and cost-effectiveness acceptability curves. Results and limitationsTime to recurrence was significantly longer for immediate MMC instillation (27.31 mo) than for delayed MMC instillation (24.97 mo), with an adjusted mean difference of 2.21 mo (95% confidence interval [CI] 1.58–2.84). The proportion of patients with recurrence-free survival was significantly higher after immediate MMC instillation (0.65) than after delayed MMC instillation (0.56), with an adjusted mean difference of 0.08 (95% CI 0.06–0.11). Total mean health care costs per patient were significantly lower for immediate MMC instillation (€22959) than for delayed MMC instillation (€24624), with an adjusted mean difference of −€1350 (95% CI −€1799 to −€900). The study is limited by the retrospective estimation of costs. ConclusionsThis trial-based cost-effectiveness analysis shows that from a health care perspective, immediate MMC instillation is more effective and less expensive compared to delayed MMC instillation. Patient summaryWe assessed the cost-effectiveness of immediate bladder instillation of mitomycin C after surgery to reduce the risk of recurrence after removal of the bladder tumor as compared to delayed instillation in a large Dutch population of patients with non–muscle-invasive bladder cancer. We found that immediate instillation was more effective and less expensive than delayed instillation. We conclude that immediate mitomycin C instillation is a cost-effective treatment for non–muscle-invasive bladder cancer.

Low-dose versus standard-dose bacille Calmette-Guérin for non-muscle-invasive bladder cancer: Systematic review and meta-analysis of randomized controlled trials.

PurposeIntravesical BCG (bacille Calmette–Guérin) instillation in patients with non-muscle-invasive bladder cancer decreases the risk for tumor recurrence and progression. After one BCG product was discontinued, a chronic global BCG shortage occurred. We focused on identifying a reduced dose of BCG that could maintain efficacy and reduce adverse effects.Materials and MethodsWe conducted a comprehensive literature search of PubMed, Embase, the Cochrane Library, CINAHL, Web of Science, and Scopus to identify randomized controlled trials through April 2021. The odds ratios (ORs) and 95% confidence intervals (CIs) for the low and standard doses in nine studies were compared. A low dose was defined as a low volume of BCG compared with the standard BCG dose (Armand Frappier, 120 mg; Connaught, 81 mg; Danish 1331, 120 mg; modified Danish 1331, 120 mg; Tokyo 172, 80 mg).ResultsThe low-dose group experienced aggravated recurrence (OR, 1.45; 95% CI, 1.09–1.94; p=0.01) but similar progression (OR, 1.11; 95% CI, 0.76–1.62; p=0.59), similar cancer-specific survival (OR, 1.02; 95% CI, 0.60–1.75; p=0.93), similar overall survival (OR, 1.09; 95% CI, 0.76–1.56; p=0.65), favorable adverse effects (OR, 0.41; 95% CI, 0.28–0.62; p<0.0001), and favorable withdrawal (OR, 0.42; 95% CI, 0.25–0.71; p=0.001).ConclusionsLow-dose BCG had more unfavorable outcomes than did standard-dose BCG in terms of recurrence. Tumor progression, cancer-specific survival, and overall survival were similar between the doses. Low-dose BCG improved adverse effects and withdrawal. In the setting of BCG shortage, low-dose BCG may have strong potential as an alternative.

Bladder instillation for urinary tract infection prevention in neurogenic bladder patients practicing clean intermittent catheterization: A systematic review.

To assess the efficacy and safety of different modalities of bladder instillation in patients with neurogenic bladder practicing intermittent catheterization. A systematic review of the literature were conducted using two databases: Medline via PubMed and Scopus. Articles evaluating bladder instillation in patients with neurogenic bladder, who are practicing intermittent catheterization, were collected and assessed for the efficacy and safety of the studied agent by two different reviewers. Among the 1896 studies, eight involving 346 patients with neurogenic bladder, were included in this systematic review according to the PRISMA protocols. Gentamicin, Hyaluronic acid, and Lactobacillus rhamnosus was found to decrease the incidence of urinary tract infections, the former reduced multidrug-resistant organisms. Kanamycin-colistin, showed a drop in the mean incidence of bacteriuria in males only. Trisdine, the only studied antiseptic, significantly reduced bacteriuria. Neomycin, however, showed no efficacy in term of bacteriuria. Regarding safety, when evaluated, no major adverse events were reported with any of the studied modalities. Bladder instillations of either antibiotics, antiseptics, hyaluronic acid, or Lactobacillus rhamnosus GG are efficient and safe in patients having neurogenic bladder, with recurrent urinary tract infections and practicing clean intermittent catheterization, with gentamicin being the most recommended product among the different studied agents.

Efficacy and safety of intravesical fibrin glue instillation for management of patients with refractory hemorrhagic cystitis: 12-months results. A promising therapy for hemorrhagic cystitis.

Fibrin glue (FG) endo-vesical application seems to be a promising therapy for hemorrhagic cystitis (HC). We aimed to evaluate efficacy and safety of FG instillation in patients with HC. Patients with HC not responsive to conventional treatments (bladder irrigation, catheterization, blood transfusions, hyperhydration and endoscopic coagulation) were treated with FG endo-vesical instillation (April 2017- December 2018). FG was prepared from 120 mL of patient blood with the Vivostat® system. After standard cystoscopy, bladder was insufflated with carbon dioxide (CO2) according to bladder compliance and autologous FG was applied to bladder wall and bleeding sites. Ten patients included with grade 2 or higher HC secondary to bone marrow graft for hematological diseases (30%) or to actinic cystitis caused by prostate cancer radiotherapy (RT) (70%). The median HC onset time after RT was 4.8 (IQR 3.9- 6.3) years and 35 (IQR 27.5-62.5) days after hematopoietic stem cell transplantation (HSCT). Five patients had a complete response after one treatment, three patients had clinical response (grade < 2 hematuria, amelioration of symptoms), one of them required catheterization and bladder irrigation. One patient required a second instillation of FG achieving a clinical response. No adverse events related to the procedure were recorded, however one patient died for causes not related to the procedure. Median Interstitial Cystitis Symptoms Index was 13.0 (IQR 11.0-15.0) pre-operatively and 4.0 (IQR 2.0-5.0) post-operatively. Our study showed that, even in hematological patients, autologous FG instillation maybe a safe, repeatable and effective treatment modality in patients with refractory HC.