45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Patterns of treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients among Arab urologists.

PURPOSE: To understand the treatment plans suggested for BCG-unresponsive non-muscle invasive disease (NMIBC) patients in the Arab countries and therapeutic decisions applied for BCG-naive patients during BCG shortage time. METHODS: A 10-minute online survey was distributed through the Arab Association of Urology (AAU) office to urologists in the Arab countries who treat patients with NMIBC. RESULTS: One hundred six urologists responded to the survey. The majority of urologists had treated, in the past 6 months, > 10 patients with NMIBC who were considered BCG-unresponsive (55% of respondents). Radical cystectomy (RC) was the most popular treatment option (recommended by 50%) for these patients. This was followed by intravesical chemotherapy (30%), repeat BCG therapy (12%), resection with ongoing surveillance (8%). Clinical trials and intravenous checkpoint inhibitors were never selected. The most preferred intravesical chemotherapy was by ranking: 60% gemcitabine, 19% mitomycin C, 8% docetaxel, 8% gemcitabine/docetaxel, 4% sequential gemcitabine/mitomycin C, and 1% valrubicin. The use of intravesical chemotherapy appears limited by Arab urologists due to concerns regarding clinical efficacy (fear of progression) and the lack of clear recommendations by urology societies. Given the BCG shortage, which may vary per Arab country, Arab urologists have adjusted by prioritizing BCG for T1 and carcinoma in situ (CIS) patients over Ta, adapting intravesical chemotherapy, and reducing the dose/strength of BCG administered. Most physicians report an eagerness to utilize novel therapies to address the BCG deficit, especially to try intravesical chemotherapy. CONCLUSIONS: Even though Arab urologists are in the majority of cases selecting RC for BCG-unresponsive cases, one-third of them are most recently initiating intravesical chemotherapy as an alternative option. To further assist Arab urologists in the appropriate selection of BCG unresponsive high risk NMIBC patient treatments, enhanced education and pathway protocols are needed.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma

Purpose To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). Method and materials All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. Results ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. Conclusion The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC (AU)

Use of In Vivo Corneal Confocal Microscopy to Guide Excimer Laser With Adjunctive Mitomycin C for Treatment of Recalcitrant Acanthamoeba Keratitis.

PURPOSE: The aim of this study was to describe 3 cases of recalcitrant Acanthamoeba keratitis (AK) that were successfully treated using in vivo corneal confocal microscopy (IVCM) to guide excimer laser ablation depth with adjunctive mitomycin C 0.02%. METHODS: Three patients diagnosed with AK did not respond to several weeks of intensive topical therapy with antiamoebic agents. The patient underwent phototherapeutic keratectomy with topical mitomycin C 0.02% application. The maximum stromal depth of cysts measured by IVCM was 80 µm, 100 µm, and 240 µm, and the stromal ablation depths were 80 µm, 100 µm, and 100 µm, respectively. RESULTS: In all 3 eyes, AK resolved after a single excimer laser application, and topical treatment was gradually discontinued within 6 weeks afterward. In 1 eye, penetrating corneal transplantation was performed 6 weeks after phototherapeutic keratectomy because of ongoing severe corneal pain. IVCM and histology of the corneal transplant did not reveal any Acanthamoeba cysts within the excised corneal button. No recurrence was observed during the follow-up period of 19 to 34 months. CONCLUSIONS: IVCM-guided phototherapeutic keratectomy with mitomycin C 0.02% seems to be a safe and successful approach for the treatment of AK, especially in cases of resistance to topical treatment. Corneal IVCM should be performed before laser application to measure cyst depth, determine ablation depth, and assess postoperative treatment success.

Combination intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) as first-line or rescue therapy: where do we stand now?

INTRODUCTION: The combination of intravesical gemcitabine (Gem) with docetaxel (Doce) or with mitomycin C (MMC) has been used in the primary setting as an alternative to Bacillus Calmette-Guerin (BCG) to treat high-risk (HR) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC), as well in the rescue setting for patients in whom BCG has failed. AREA COVERED: Efficacy and safety of Gem/Doce and Gem/MMC to treat NMIBC in BCG-naive and failure settings. EXPERT OPINION: In the BCG-naive setting, Gem/Doce was the primary alternative combination therapy reported, with a weighted mean of 12- and 24-month recurrence-free survival (RFS) of 79% and 77% for HR disease and 84% and 76% for IR disease, respectively. In the HR BCG-failure setting, the weighted mean of 12- and 24-month RFS was 60% and 42% for Gem/Doce and 63% and 40% for Gem/MMC. While patients without BCG exposure and papillary disease only benefit the most from Gem/Doce, there is also reasonable efficacy in BCG refractory disease and CIS. Combination therapy is well tolerated, with grade III toxicity reported in less than 1% of patients. Unlike single-agent chemotherapy, intravesical Gem/Doce is considered effective and safe regardless of risk-stratification.

Periocular and ocular surface nonmelanoma skin cancer.

Periocular and ocular surface nonmelanoma malignancies, including basal cell carcinoma (BCC), squamous cell carcinomas (SCC), and ocular surface squamous neoplasia (OSSN), are rare, but their management requires special considerations. The most common periocular malignancy is BCC, which constitutes 80% to 96% of tumors, followed by SCC, which represents 5% to 10% of tumors. OSSN represents a spectrum of diseases that encompass dysplastic alteration to the squamous epithelium of the eye. OSSN ranges from squamous dysplasia to conjunctival intraepithelial neoplasia/carcinoma in situ to invasive SCC, which is the most common ocular malignancy. These tumors can be staged using the eighth edition of the American Joint Committee on Cancer categorization system. The standard of care for periocular malignancies is Mohs micrographic surgery, while medical management with 5-fluorouracil (5-FU), interferon alfa-2b (INF), and mitomycin C (MMC) or "no touch" surgical excision are options for OSSN. Systemic therapies, including sonic hedgehog inhibitors for BCC and epidermal growth factor inhibitors and immune-checkpoint inhibitors for SCC, can be utilized for advanced disease. Recurrence rates are higher for periorbital and ocular malignancies than their respective cutaneous counterparts. These carcinomas and their respective treatments have unique side effects and considerations in an effort to preserve visual function.

US Clinical Practice Patterns of Intravesical Chemotherapy for Bacillus Calmette-Guérin-Unresponsive and Bacillus Calmette-Guérin-Exposed Nonmuscle-Invasive Bladder Cancer.

INTRODUCTION: The goal of this survey was to evaluate the treatment and practice pattern of patients with high-grade papillary Ta, T1 nonmuscle-invasive bladder cancer (NMIBC), and carcinoma in situ (CIS) in bacillus Calmette-Guérin (BCG)-unresponsive (with adequate BCG exposure = adequate BCG) and those with less than adequate BCG exposure (BCG-exposed). METHODS: An internet-based survey with a target duration of 5 minutes was sent to US urologists who manage patients with NMIBC. Respondents were recruited from the Sesen Bio target list based upon BCG utilization. RESULTS: In 2022, 100 urologists who manage patients with papillary tumors and 159 urologists who manage patients with CIS tumors filled out the survey. Most (78%) were community-based urologists. Study respondents managed an average of 33 (range: 6-158) CIS patients and 44 (range: 10-200) high-grade patients with papillary disease (without CIS) over the past 6 months. Approximately 70% of physicians identified either gemcitabine (∼40%) or mitomycin C (∼30%) as the most often used intravesical chemotherapies for BCG unresponsive and BCG exposed groups. Most physicians reported the use of gemcitabine 2 g or mitomycin C 40 mg in a specific regimen for induction (once a week × 6 weeks) and maintenance (once a month × 12 months). Responses were consistent across groups of BCG therapy (adequate vs BCG-exposed). Physicians were slightly more likely to use a maintenance regimen for the adequate BCG patient. CONCLUSIONS: The most common treatments received by patients with BCG-unresponsive and BCG-exposed NMIBC were intravesical chemotherapy (single-agent gemcitabine or mitomycin C), regardless of whether CIS or papillary disease was present.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

PURPOSE: To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). METHOD AND MATERIALS: All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. RESULTS: ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. CONCLUSION: The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

2022 Peritoneal Surface Oncology Group International Consensus on HIPEC Regimens for Peritoneal Malignancies: Colorectal Cancer.

BACKGROUND: Selected patients with peritoneal metastases of colorectal cancer (PM-CRC) can benefit from potentially curative cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC), with a median overall survival (OS) of more than 40 months. OBJECTIVE: The aims of this evidence-based consensus were to define the indications for HIPEC, to select the preferred HIPEC regimens, and to define research priorities regarding the use of HIPEC for PM-CRC. METHODS: The consensus steering committee elaborated and formulated pertinent clinical questions according to the PICO (patient, intervention, comparator, outcome) method and assessed the evidence according to the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Standardized evidence tables were presented to an international expert panel to reach a consensus (4-point, weak and strong positive/negative) on HIPEC regimens and research priorities through a two-round Delphi process. The consensus was defined as ≥ 50% agreement for the 4-point consensus grading or ≥ 70% for either of the two combinations. RESULTS: Evidence was weak or very weak for 9/10 clinical questions. In total, 70/90 eligible panelists replied to both Delphi rounds (78%), with a consensus for 10/10 questions on HIPEC regimens. There was strong negative consensus concerning the short duration, high-dose oxaliplatin (OX) protocol (55.7%), and a weak positive vote (53.8-64.3%) in favor of mitomycin-C (MMC)-based HIPEC (preferred choice: Dutch protocol: 35 mg/m2, 90 min, three fractions), both for primary cytoreduction and recurrence. Determining the role of HIPEC after CRS was considered the most important research question, regarded as essential by 85.7% of the panelists. Furthermore, over 90% of experts suggest performing HIPEC after primary and secondary CRS for recurrence > 1 year after the index surgery. CONCLUSIONS: Based on the available evidence, despite the negative results of PRODIGE 7, HIPEC could be conditionally recommended to patients with PM-CRC after CRS. While more preclinical and clinical data are eagerly awaited to harmonize the procedure further, the MMC-based Dutch protocol remains the preferred regimen after primary and secondary CRS.

Surgical outcomes of trabeculectomy augmented with sub-Tenon injected mitomycin C.

BACKGROUND: Recently, trabeculectomy with mitomycin C (MMC) where MMC is applied by injection into the Tenon layer has attracted close attention. However, the data on efficacy and safety of this technique is still limited and more clinical studies are needed. Therefore, the work is aimed at comprehensive evaluation of the effectiveness of trabeculectomy using MMC applied by intra-Tenon injection. METHODS: A set of 50 eyes in 50 patients underwent trabeculectomy using MMC at concentration of 0.4 mg/ml in a total volume of 0.05 ml. The primary end point was to control intraocular pressure (IOP) on postoperative days 1, 8, 30 and 90 and subsequently at 6 and 12 months after surgery. The secondary end point was to evaluate the changes in various corneal parameters prior to and 90 days after surgical procedure. RESULTS: The mean preoperative IOP was 32.34 ± 9.45 mmHg. After surgery, the mean IOP significantly decreased to 17.52 ± 4.58 mmHg at the 90-day follow-up, and to 18.14 ± 3.74 and 19.30 ± 3.82 mmHg at 6 and 12 months after the procedure, respectively. The mean BCVA values remained unchanged compared to baseline (0.77 ± 0.23) to the 90-day follow-up (0.80 ± 0.23).  The mean number of anti-glaucoma medications significantly reduced from 3.50 ± 0.74 to 0.58 ± 1.03 postoperatively. Similarly, the mean corneal hysteresis and ACD of the eye as well as CECD were significantly changed postoperatively. CONCLUSIONS: Trabeculectomy using MMC applied by injection is a safe and effective surgical method for the treatment of primary and secondary forms of open-angle glaucoma. It has a significant hypotonising effect and allows a complete discontinuation of antiglaucoma drugs (Tab. 3, Fig. 3, Ref. 58).

Delayed presentation of surgically induced scleral necrosis after I-BRITE procedure treated with immunosuppressive therapy.

Surgically induced scleral necrosis (SISN) is an uncommon complication of ocular procedures. Cosmetic eye-whitening surgery involves conjunctival and Tenon's capsule dissection, cautery, and mitomycin C application. We report the case of a 36-year-old white woman referred to our clinic for severe pain, scleral inflammation, and necrosis in both eyes 9 years after I-BRITE, an elective eye-whitening procedure. An extensive workup yielded negative results. The patient improved with aggressive lubrication and topical and high-dose systemic prednisone (60 mg), with recurrence upon steroid tapering. Concomitant weekly methotrexate was added, resulting in inflammatory control and allowing discontinuance of topical and oral steroids.

Comparison between primary Ahmed valve implantation and primary trabeculectomy with mitomycin C in pseudophakic patients with exfoliative glaucoma.

PURPOSE: To compare the efficacy and safety of primary Ahmed valve implantation (AVI) and primary trabeculectomy with mitomycin C (MMC) in patients with pseudophakic exfoliative glaucoma (XFG). METHODS: All enrolled patients were divided into two groups: the TRAB group, comprising patients who underwent trabeculectomy with MMC, and the AVI group, comprising patients who underwent AVI. Intraocular pressure (IOP), mean deviation (MD), endothelial cell density of cornea (ECD), and the number of topical anti-glaucoma agents used during study period were retrospectively analyzed. Surgical success rates were compared between two groups using Kaplan-Meier survival analysis. Three levels of surgical success were defined as follows: (1) IOP ≤ 18 mmHg and an IOP reduction of 20% without medication; (2) IOP ≤ 15 mmHg and an IOP reduction of 25% without medication; and (3) IOP ≤ 18 mmHg and an IOP reduction of 20%, irrespective of medication. RESULTS: The TRAB and AVI groups comprised 40 and 36 patients, respectively. At 36 months postoperatively, IOP was 15.7 ± 2.8 mmHg in the TRAB group and 16.9 ± 3.3 mmHg in the AVI group (p = 0.140). Surgical success rates in the TRAB group were 47.5, 37.5, and 77.5% and those in the AVI group were 41.6, 33.3, and 75.0% at 36 months for surgical criteria 1, 2, and 3, respectively. There were no statistically significant differences in the success rates between the two groups. However, regarding surgical criteria 2, the success rate of the AVI group at 1 year was significantly better than that of the TRAB group (p = 0.030). CONCLUSIONS: Primary AVI was not inferior to primary trabeculectomy with MMC in medically uncontrolled patients with XFG.

Drug repurposing of mito-atovaquone for cancer treatment.

Repurposing of approved drugs in a new strategy to combat cancer that leads to savings in time and investment. Atovaquone is a US FDA-approved drug for treatment of Pneumocystis carinii pneumonia and malaria. Patent US2023017373 describe the use of mito-atovaquone for the treatment of several types of cancer. Mito-atovaquone demonstrated antiproliferative activity in cell lines of pancreatic cancer, lung cancer and brain cancer and inhibited tumor growth in syngeneic mouse models and in animals genetically prone to breast cancer. Mito-atovaquone has the potential to be used successfully in the treatment of various types of tumors.

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

Capecitabine/Mitomycin versus 5-Fluorouracil/Mitomycin in Combination with Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy for Anal Cancer.

Since EXTRA, a non-randomized phase II trial with 31 patients, explored the use of capecitabine, mitomycin and radiation therapy (RT) in the treatment of localized squamous cell carcinoma of the anal canal (SCCAC), this treatment has been considered as an acceptable alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in chemoradiation therapy (CRT) with simultaneous integrated boost (SIB) radiation therapy (SIB-IMRT) for local SCCAC are not well documented. Patients included in this prospective monocentric cohort study were treated with SIB-RapidArc (a unique RT method treatment for all patients: identical technique, volume and constraints for at-risk organs), mitomycin C and 5-FU each day of RT for 7 weeks (group 1) or capecitabine each day of RT (group 2). Patients treated between July 2009 and August 2017 (group 1) and between November 2012 and April 2018 (group 2) for local SCCAC T2-4 classified as N, M0 or T, N1-3, M0 were included. Primary endpoints were progression-free survival (PFS) and acute toxicities. Results: One hundred forty-seven patients were included, 91 in group 1 and 56 in group 2. The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM. With a median duration of follow-up of 53.5 months, the PFS rate at 3 years was 80% for group 1 and 75% for group 2 (p = 0.32). The 3-year colostomy-free survival rate was 92% for group 1 and 85% for group 2 (p = 0.11). The rate of patients with at least one grade 3 or higher acute toxicity was 35.5% in group 1 and 21.4% in group 2 (p = 0.10), with a trend of fewer acute toxicities with capecitabine. Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well tolerated with minimal toxicity.

Treatment Outcomes for Juvenile Open Angle Glaucoma in Thailand.

PRCIS: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years. PURPOSE: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand. PATIENTS AND METHODS: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand. RESULTS: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0±10.1 years (range: 5-40 y), with male predominance (60.5%). Over 90% of patients had bilateral JOAG and 25% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10 µm adjusted odds ratio=1.29, P =0.01). Over 70% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5%) with a cumulative probability of complete success of 71.0%, 57.8%, 39.2%, and 26.9% and qualified success of 86.3%, 73.6%, 64.8%, and 45.7% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 ± 69.8 months (range: 13-153 mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure. CONCLUSIONS: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications.

Mytomicin-C, Metronomic Capecitabine, and Bevacizumab in Patients With Unresectable or Relapsed Pseudomyxoma Peritonei of Appendiceal Origin.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens. PATIENTS AND METHODS: We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m2 every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety. RESULTS: Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events. CONCLUSION: Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series.

Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events. RESULTS: Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria. CONCLUSIONS: Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.

Sequential intravesical gemcitabine and docetaxel for treatment-naïve and previously treated intermediate-risk nonmuscle invasive bladder cancer.

INTRODUCTION: Adjuvant intravesical therapy is recommended for patients with intermediate-risk NMIBC. While intravesical gemcitabine-docetaxel (Gem/Doce) has demonstrated favorable outcomes for high-risk NMIBC, its utility in the intermediate-risk setting is not well described. We report outcomes of Gem/Doce as an adjuvant treatment for intermediate-risk NMIBC. METHODS: We retrospectively identified patients with intermediate-risk NMIBC by AUA criteria treated with Gem/Doce following TURBT between 2012 and 2022. Patients received weekly sequential intravesical instillations of 1 g gemcitabine and 37.5 mg docetaxel for 6 weeks. Monthly maintenance of 2 years was initiated if disease-free at first surveillance. The primary outcome was recurrence-free survival (RFS), assessed using the Kaplan-Meier method. RESULTS: The cohort included 77 patients with median follow-up of 26 (IQR 14-50) months. Prior to induction, 67 (87%) patients presented with Ta low-grade (LG) lesions, 3 (3.9%) with Ta high-grade (HG), 5 (6.5%) with TaLG plus focal TaHG, and 2 (2.6%) with T1LG. Thirty-three (43%) patients received previous intravesical therapy including BCG (23), mitomycin (13), and docetaxel monotherapy (12). The 2-year RFS was 71% among all patients. Treatment-naïve patients had superior RFS compared to previously treated patients (P = 0.04); 2-year estimates were 79% and 64%, respectively. Twenty-nine (38%) patients experienced adverse events; all were Grade 1 to 2 except 1 (1.3%) Grade 3 (acute oxygen desaturation). Three (3.9%) patients did not tolerate a full induction course. CONCLUSIONS: In this retrospective review of a heterogenous population of patients with intermediate-risk NMIBC, Gem/Doce was an effective and well-tolerated adjuvant therapy. Further prospective evaluation in this setting is needed.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform.

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.