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Fibrosis of the filtering bleb is one of the main causes of failure after bleb-forming glaucoma surgery. Intraoperative application of mitomycin C (MMC) is the current gold standard to reduce the fibrotic response. However, MMC is cytotoxic and one-time application is often insufficient. A sustained-release drug delivery system (DDS), loaded with MMC, may be less cytotoxic and equally or more effective. Two degradable (polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA)) MMC-loaded DDSs are developed. Release kinetics are first assessed in vitro followed by rabbit implants in conjunction with the PRESERFLO MicroShunt. As a control, the MicroShunt is implanted with adjunctive use of a MMC solution. Rabbits are euthanized at postoperative day (POD) 28 and 90. The PLGA and PCL DDSs release (on average) 99% and 75% of MMC, respectively. All groups show functioning blebs until POD 90. Rabbits implanted with a DDS show more inflammation with avascular thin-walled blebs when compared to the control. However, collagen is more loosely arranged. The PLGA DDS shows less inflammation, less foreign body response (FBR), and more complete degradation at POD 90 when compared to the PCL DDS. Further optimization with regard to dosage is required to reduce side effects to the conjunctiva.

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.

AimTo evaluate the safety and efficacy of posterior scleral application (a modified technique) of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.MethodsThis retrospective study included 101 patients (115 eyes) with glaucoma (aged 12-83y) who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method. A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus. The mitomycin C concentration and exposure time were 0.2-0.5 mg/mL and 1-5min, respectively. Intraocular pressure, best-corrected visual acuity, and hypotensive medications were recorded at baseline and at the final visit. Complications, interventions required, and bleb morphology were recorded postoperatively. The primary outcome was trabeculectomy safety, including complications and bleb morphology; the secondary outcome was the trabeculectomy success rate.ResultsAt the final follow-up [median 28mo, range 7-67mo and interquartile range (IQR) 13mo], the qualified (cumulative) success rate was 93.0% and the complete success rate was 60.0%. No bleb-related complications were observed. The mean height, extent, and vascularity grades were 0.6±0.9, 1.1±0.4, and 2.4±0.9, respectively. All Seidel tests were negative. The mean posteriority grade was 0.8±0.4.ConclusionTrabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.

For moderate-to-severe glaucoma, trabeculectomy remains the “gold standard” intraocular pressure (IOP)-lowering treatment; nonetheless, this method requires extensive post-operative maintenance. Microinvasive glaucoma surgery (MIGS) treatments are designed to lessen intra-and post-operative care burden while offering an acceptable IOP decrease for individuals with mild to moderate glaucoma. The PreserFlo® MicroShunt (previously InnFocus MicroShunt) is an 8.5 mm glaucoma drainage device manufactured from poly(styrene-block-isobutylene-block-styrene) (SIBS), an extremely biocompatible and bioinert material. The lumen is narrow enough to prevent hypotony, but big enough to avoid being obstructed by sloughed cells or pigment. The device is implanted ab externo, as a stand-alone procedure or in conjunction with cataract surgery, with intraoperative mitomycin C, and a bleb is produced under the conjunctiva and Tenon’s capsule. The MicroShunt was CE-marked in 2012 and designed for primary open-angle glaucoma, the IOP of which remains uncontrolled after maximally tolerated topical treatment. Several clinical trials evaluating the MicroShunt’s long-term safety and effectiveness have been conducted, highlighting the effectiveness of the device over time, along with a tolerable safety profile. The present review aims to gather evidence of PreserFlo’s effectiveness and safety results almost 10 years after its introduction, and furthermore, to compare it with other MIGS and with the gold-standard trabeculectomy for glaucoma management.

Background: The purpose of this study is to compare the morphology of six-month follow-up blebs created by a subconjunctival glaucoma surgical device (XEN45) to those created by a PreserFlo MicroShunt with a sub-Tenon insertion, utilizing AS-OCT. Methods: A retrospective study of 29 eyes who underwent XEN45 implantation and 29 eyes who underwent PreserFlo MicroShunt implantation. The patients were analyzed at 24 h, 1 week, 1 month, 3 months and 6 months. At each visit, the maturation and morphological alterations of the blebs were observed, as well as connections with the IOP. Results: In both groups, IOP showed significant reduction at all follow ups (p < 0.0001). In XEN group, the most common bleb morphology in the immediate postoperative was the subconjuntival separation type (42%) followed by the uniform type (34%), with a trend inversion at 6 month follow up (51% of uniform type). On the contrary, the most common morphology after PreserFlo was the multiple internal layer (55%), which showed a tendency to reduce over time and was substituted by the microcystic multiform, whose percentage increased over time (17% at day 1 vs. 44% at month 6). Uniform appearance was associated by the posterior episcleral fluid (PEF) lake presence. Both horizontal and vertical diameters significantly increased over time. Conclusion: XEN and PreserFlo implantation resulted in the production of diffuse blebs with different characteristics, which may influence IOP lowering capacity and bleb revisions necessity over time.

Purpose: Since there is a lack of clear information regarding the benefit to combine supportive therapies (such as artificial tears) to mitomycin C (MMC) in the treatment of ocular surface neoplasia, the primary purpose of the study was to evaluate hyaluronic acid eye drops and hyaluronic acid-conjugated lactobionic acid (LACTOyal FREE) eye drops as supportive therapy. Methods: Retrospective evaluation of patients with ocular surface squamous neoplasia or conjunctival melanocytic tumor treated with MMC, who had used also artificial tears as supportive treatment. A 6-month follow-up with evaluation of subjective and objective tests for ocular surface integrity was conducted. Results: A total of 35 patients were analyzed, most of them with squamous disease (71.4%). The break-up time (BUT), Ocular Surface Disease Index (OSDI) and Schirmer test values showed a significant difference at any time point with overall population. No statistical difference was found among subgroups (Lactoyal vs No Lactoyal). Conclusion: The use of an ancillary therapy based on hyaluronic acid allows to improve both subjective and objective ocular parameters, reducing MMC induced adverse effects. Meantime, hyaluronic acid-conjugated lactobionic acid eye drops highlighted the same advantages with a more positive trend in OSDI results.

Purpose: To assess the safety, aberrometric and keratometric changes, and stability of transepithelial topography-guided phototherapeutic keratectomy (TE-TG-PTK) with mitomycin C (MMC) using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. Methods: This is a retrospective case series including 57 eyes that underwent TE-TG-PTK + MMC using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. CDVA, manifest refraction (MR), keratometry readings, and aberrometry readings were analyzed at 1, 3, 6, and 12 months. Results: Causes of corneal irregularity included non-infectious leucoma (n=23), infectious leucoma (n=7), adenoviral keratitis (n=20), corneal haze (n=2), post-penetrant keratoplasty (PKP) (n=1), and others (n=4). Overall, 76% of the eyes (n=40) gained lines of vision; patients gained 1, and 2 or more lines of vision in 76%, and 38% of cases, respectively. Only 1 patient (2%) lost 5 lines of vision. Mean preoperative CDVA (LogMAR) was 0.37 ±0.31 and improved to 0.14 ±0.18 (p<0.001) at final follow-up (12 months). CDVA remained unchanged in 10 eyes (21%). No significant changes were observed in mean keratometry (Kmean) and keratometric astigmatism readings. Regarding aberrometry, only changes in coma proved to be significant 6 months after surgery (P<0.01). No intraoperative/postoperative complications were reported. Conclusion: At final follow-up, significant improvements were observed in CDVA and coma. TE-TG-PTK + MMC proved to be an effective and safe procedure for the treatment of corneal irregular astigmatism due to several causes.

Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.

Purpose: To assess the safety, aberrometric and keratometric changes, and stability of transepithelial topography-guided phototherapeutic keratectomy (TE-TG-PTK) with mitomycin C (MMC) using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. Methods: This is a retrospective case series including 57 eyes that underwent TE-TG-PTK + MMC using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. CDVA, manifest refraction (MR), keratometry readings, and aberrometry readings were analyzed at 1, 3, 6, and 12 months. Results: Causes of corneal irregularity included non-infectious leucoma (n=23), infectious leucoma (n=7), adenoviral keratitis (n=20), corneal haze (n=2), post-penetrant keratoplasty (PKP) (n=1), and others (n=4). Overall, 76% of the eyes (n=40) gained lines of vision; patients gained 1, and 2 or more lines of vision in 76%, and 38% of cases, respectively. Only 1 patient (2%) lost 5 lines of vision. Mean preoperative CDVA (LogMAR) was 0.37 ±0.31 and improved to 0.14 ±0.18 (p<0.001) at final follow-up (12 months). CDVA remained unchanged in 10 eyes (21%). No significant changes were observed in mean keratometry (Kmean) and keratometric astigmatism readings. Regarding aberrometry, only changes in coma proved to be significant 6 months after surgery (P<0.01). No intraoperative/postoperative complications were reported. Conclusion: At final follow-up, significant improvements were observed in CDVA and coma. TE-TG-PTK + MMC proved to be an effective and safe procedure for the treatment of corneal irregular astigmatism due to several causes.

Purpose: To assess the safety, aberrometric and keratometric changes, and stability of transepithelial topography-guided phototherapeutic keratectomy (TE-TG-PTK) with mitomycin C (MMC) using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. Methods: This is a retrospective case series including 57 eyes that underwent TE-TG-PTK + MMC using the ALLEGRO Topolyzer platform for the treatment of irregular astigmatism. CDVA, manifest refraction (MR), keratometry readings, and aberrometry readings were analyzed at 1, 3, 6, and 12 months. Results: Causes of corneal irregularity included non-infectious leucoma (n=23), infectious leucoma (n=7), adenoviral keratitis (n=20), corneal haze (n=2), post-penetrant keratoplasty (PKP) (n=1), and others (n=4). Overall, 76% of the eyes (n=40) gained lines of vision; patients gained 1, and 2 or more lines of vision in 76%, and 38% of cases, respectively. Only 1 patient (2%) lost 5 lines of vision. Mean preoperative CDVA (LogMAR) was 0.37 ±0.31 and improved to 0.14 ±0.18 (p<0.001) at final follow-up (12 months). CDVA remained unchanged in 10 eyes (21%). No significant changes were observed in mean keratometry (Kmean) and keratometric astigmatism readings. Regarding aberrometry, only changes in coma proved to be significant 6 months after surgery (P<0.01). No intraoperative/postoperative complications were reported. Conclusion: At final follow-up, significant improvements were observed in CDVA and coma. TE-TG-PTK + MMC proved to be an effective and safe procedure for the treatment of corneal irregular astigmatism due to several causes.

Background: Bladder recurrence after radical treatment of upper urinary tract urothelial cancer (UTUC) is frequent, and patients are required to undergo surveillance cystoscopies following surgery. The use of intravesical adjuvant chemotherapy is an accepted method to prevent bladder recurrence, but the timing of this method is not standardized and the concept of intraoperative use is unexplored. Objective: The objective of the study is to examine the feasibility and safety of intraoperative intravesical mitomycin C (MMC) instillation using a closed-circuit system following bladder cuff excision and bladder closure. Design, setting, and participants: All patients who underwent radical nephroureterectomy (RNU) for UTUC at the Department of Urology of Zealand University Hospital, Roskilde, Denmark from 2017 to 2020 were identified. Patient complications within 30 d and data regarding oncological outcome were registered. Outcome measurements and statistical ana lysis: Clavien-Dindo grade for complications and descriptive statistics were used. Results: During the study period, 64 patients underwent RNU. Of these patients, 49 received bladder instillation of MMC during RNU. Complications were observed in 11 patients (21.4%), where four patients (8.2%) had Clavien-Dindo complication grade (CD) I, four patients (8.2%) had CD II, one patient (2%) had CD III, and one patient (2%) had CD IIIa. None of the complications were suspected to be related to MMC. Five of the 15 patients (33%) who did not receive MMC experienced complications. There were no significant differences in complication rates between patients who received MMC and those who did not. Study limitations include a small sample size and a single-center study. Conclusions: Intraoperative vesical instillation of MMC is feasible and was, in the present study, not associated with an increased complication rate. Patient summary: Bladder recurrence after radical treatment of upper urinary tract cancer is frequent. Th

Trabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.

Background: Bladder recurrence after radical treatment of upper urinary tract urothelial cancer (UTUC) is frequent, and patients are required to undergo surveillance cystoscopies following surgery. The use of intravesical adjuvant chemotherapy is an accepted method to prevent bladder recurrence, but the timing of this method is not standardized and the concept of intraoperative use is unexplored. Objective: The objective of the study is to examine the feasibility and safety of intraoperative intravesical mitomycin C (MMC) instillation using a closed-circuit system following bladder cuff excision and bladder closure. Design, setting, and participants: All patients who underwent radical nephroureterectomy (RNU) for UTUC at the Department of Urology of Zealand University Hospital, Roskilde, Denmark from 2017 to 2020 were identified. Patient complications within 30 d and data regarding oncological outcome were registered. Outcome measurements and statistical ana lysis: Clavien-Dindo grade for complications and descriptive statistics were used. Results: During the study period, 64 patients underwent RNU. Of these patients, 49 received bladder instillation of MMC during RNU. Complications were observed in 11 patients (21.4%), where four patients (8.2%) had Clavien-Dindo complication grade (CD) I, four patients (8.2%) had CD II, one patient (2%) had CD III, and one patient (2%) had CD IIIa. None of the complications were suspected to be related to MMC. Five of the 15 patients (33%) who did not receive MMC experienced complications. There were no significant differences in complication rates between patients who received MMC and those who did not. Study limitations include a small sample size and a single-center study. Conclusions: Intraoperative vesical instillation of MMC is feasible and was, in the present study, not associated with an increased complication rate. Patient summary: Bladder recurrence after radical treatment of upper urinary tract cancer is frequent. Th

Purpose: Favourable outcome after glaucoma surgery depends on proper control of the inflammatory response. Failing filtration bleb and consequently increased intraocular pressure is an important cause of continuous visual field deterioration after uncomplicated glaucoma surgery. The present systematic review and meta-analysis aimed to compare the effects of employing either Mitomycin C (MMC), 5-Fluoruracil (5-FU) or no anti-metabolite in needling revision of trabeculectomies. Methods: We performed a systematic literature search in PubMed, Cochrane and EMBASE to identify randomized and non-randomized trials published between year 2000 and March 2019 comparing the efficacy of needling filtering blebs when using no anti-fibrotic agent, MMC or 5-FU in patients with glaucoma. Efficacy was defined as intraocular pressure at 12 months or latest follow-up, rate of complications, rates of success and the number of re-needling cases. Comparisons were made using network meta-analyses. Results: We identified one randomized trial and five retrospective trials. Twelve months after needling revision of trabeculectomy, no significant difference was observed when comparing the effect of the use of MMC with 5-FU or without any use of anti-metabolite on intraocular pressure, complication rates, qualified success, complete success or number of re-needling cases. Conclusion: We found no significant difference in the efficacy of using either MMC, 5-FU or no anti-metabolite in needling revision of trabeculectomies. The number of studies meeting our inclusion criteria was limited. Considering the design of studies, only one was randomized leading to an overall low quality of evidence on the subject matter. Further research is warranted.

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.

Purpose: Compare (a) nonmitomycin C (MMC) trabeculectomy and 1.5% dexamethasone nanoparticle (DexNP) eye drops postoperatively with (b) trabeculectomy with MMC and Maxidex® eye drops postoperatively. Methods: Randomized prospective single masked clinical trial with 20 patients with primary open‐angle glaucoma undergoing primary trabeculectomy. The study group consisted of 10 patients without MMC intraoperatively and postoperative DexNP eye drops, and the control group consisted of 10 patients treated with MMC intraoperatively and postoperative Maxidex®. The drops were tapered out over 8 weeks. The main outcome measures were as follows: rates of complete success, that is intraocular pressure (IOP) within target pressures at different time‐points without IOP‐lowering medication, or reoperation. Secondary outcome measures included the following: relative success rate (with IOP‐lowering medications), number of glaucoma medications and reoperations. Patients were followed for 36 months. Results: Both groups showed similar postoperative course and IOP reduction. Intraocular pressures (IOPs) in the DexNP group and in the control group were 25.6 and 24.4 mmHg, respectively, at baseline. Intraocular pressures (IOPs) were reduced to 13.2 and 14.5 mmHg at 12 months, 11.7 and 12.6 mmHg at 24 months and 11.7 and 12.1 mmHg at 36 months, respectively. There were no statistically significant differences between the groups in absolute (p = 0.36) or relative (p = 1.0) success rates, number of medications (p = 0.71) or reoperations (p = 1.0) between the groups at any time‐point. Conclusions: DexNP eye drops are effective postoperative treatment following trabeculectomy. The potent anti‐inflammatory and antifibrotic effect of DexNP may offer an alternative to mitomycin C in glaucoma surgery.

Treatment of cancer in the peritoneal cavity may be improved with macroscale drug delivery systems that offer control over intraperitoneal concentration of chemotherapeutic agents. Currently, suitable drug carriers to facilitate a sustained release of small hydrophilic drugs such as mitomycin C are lacking. For this purpose, a pH-responsive supramolecular hydrogel based on ureido-pyrimidinone (UPy) chemistry is utilized here. In order to provide a sustained release profile, a lipophilicity-increasing cholesterol conjugation strategy is proposed that enhances affinity between the modified drug (mitomycin-PEG24-cholesterol, MPC) and the hydrophobic compartments in the UPy gel. Additional advantages of cholesterol conjugation include improved chemical stability and potency of mitomycin C. In vitro the tunability of the system to obtain optimal effective concentrations over time is demonstrated with a combinatorial treatment of mitomycin C and MPC in one UPy hydrogel delivery system.

Background: In case of high grade non-muscle invasive bladder cancer (HG-NMIBC), intravesical BCG represents the first-line treatment; despite the "gold" standard therapy, up to 50% of patients relapse, needing radical cystectomy. Hence, alternative therapeutic strategies have been developed. The aim of the study was to evaluate a first-line salvage treatment with EMDA®-MMC in patients with HGNMIBC unresponsive to BCG. Methods: We carried out a prospective, single-center, single-arm Phase II study in order to evaluate the efficacy (in terms of recurrence and progression) and the safety of the EMDA®-MMC treatment in 26 (21 male, 5 female) consecutive patients with "BCG refractory" HGNMIBC on a 3 years follow-up. EMDA®-MMC treatment consisted of 40 mg of MMC diluted in 100 ml of sterile water retained in the bladder for 30 min with 20 mA pulsed electric current. EMDA®-MMC regimen consisted of an induction course of 6 weekly instillations followed by a maintenance course of 6 monthly instillations. Follow-up was performed with systematic mapping biopsies of the bladder (with sampling in the prostatic urethra for men), voiding and washing urinary cytology, radiological study of the upper urinary tract. We performed Survival Kaplan-Meier curves and Log-rank test in order to analyze high grade disease-free survival. Results: At the end of follow-up, 16 patients (61.5%) preserved their native bladder; 10 patients (38.4%) underwent radical cystectomy, in 6 patients (23.1%) for recurrent HGNMIBC and in 4 patients (15.4%) for progression to muscle-invasive disease. At the end of follow-up, stratifying patients based on TNM classification (TaG3, T1G3, Cis, TaT1G3 + Cis), disease-free rates were 75, 71.4, 50 and 25%, respectively; survival curves showed statistically significant differences (p value < 0.05). Regarding toxicity, we reported severe adverse systemic event of hypersensitivity to the MMC in 3 patients (11.5%), and local side effects in 6 patients (26.1%). Conclus

Treatment of cancer in the peritoneal cavity may be improved with macroscale drug delivery systems that offer control over intraperitoneal concentration of chemotherapeutic agents. Currently, suitable drug carriers to facilitate a sustained release of small hydrophilic drugs such as mitomycin C are lacking. For this purpose, a pH-responsive supramolecular hydrogel based on ureido-pyrimidinone (UPy) chemistry is utilized here. In order to provide a sustained release profile, a lipophilicity-increasing cholesterol conjugation strategy is proposed that enhances affinity between the modified drug (mitomycin-PEG24-cholesterol, MPC) and the hydrophobic compartments in the UPy gel. Additional advantages of cholesterol conjugation include improved chemical stability and potency of mitomycin C. In vitro the tunability of the system to obtain optimal effective concentrations over time is demonstrated with a combinatorial treatment of mitomycin C and MPC in one UPy hydrogel delivery system.

Objective. Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Material and Methods. Electromotive Drug Administration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body. Results. Results indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m2. Conclusions. The present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.

Objective: Chronic tympanic membrane perforation (TMP) in a clinical setting may attract surgical intervention. With the advent of modern biomaterials, new options are available for myringoplasty but safety and efficacy need evaluation in a chronic TMP animal model. The aim of this study was to evaluate the efficacy of ventilation tube (VT) insertion in conjunction with topical application of mitomycin Cl dexamethasone (M/D) for the creation of chronic TMP in rats. Methods: Thirty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were divided into three experimental groups: spontaneous healing (myringotomy control), VT insertion for 2 weeks and VT insertion for 2 weeks in conjunction with topical application of M/D (VT-M/D). All TMs were regularly assessed by otoscopy for 10 weeks and then animals were sacrificed for histological evaluation. Results: In the VT-M/D group, seven out of ten (70%) perforations were patent at 10 weeks (mean patency, 57.9 days; P < 0.01). The VT group had two out of ten (20%) perforations patent at 10 weeks (mean patency, 26.5 days; P < 0.01), while all TMPs from the myringotomy control group were closed by day 9 (mean patency, 7.2 days). Histologically, the TMPs patent at week 10 had a stratified squamous epithelialized rim, keratinocyte layer thickening around the perforation edge as well as increased collagen deposition and macrophage infiltration. Conclusion: Chronic TMP in a rat model was successfully created by VT insertion and the efficacy was increased in combination with topical application of M/D.

Introduction: A pterygium is a triangular wedge of fibro-vascular conjunctival tissue that appears on the epibulbar conjunctiva, which can be removed by various methods. Recurrence of Pterygium after exicision is a very common problem encountered by ophthalmologist. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after application of intraoperative mitomycin C (0.04%). Method: This is a prospective study of fifty eyes in fifty patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C(25 patients) and without using mitomycin c(25 patients) during September 20014—September 2015 in the ophthalmology department at Jhalawar medical college, Jhalawar( raj.). 0.04% Mitomycin applied to bare sclera after excision for two minutes by swab sticks. Postoperative follow up period was 6 months. Outcomes measured in the form of recurrence and complications were analyzed. Results: In Group A with use of mitomycin C there was no recurrence after 6 months follow-up while in Group B recurrence was seen in 5 patients within 3-6 months, however in group A, 1 patient had scleral thinning. Conclusion: Intraoperative administration of mitomycin C 0.04% is safe and effective to prevent pterygium recurrences.

Introduction: A pterygium is a triangular wedge of fibro-vascular conjunctival tissue that appears on the epibulbar conjunctiva, which can be removed by various methods. Recurrence of Pterygium after exicision is a very common problem encountered by ophthalmologist. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after application of intraoperative mitomycin C (0.04%). Method: This is a prospective study of fifty eyes in fifty patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C(25 patients) and without using mitomycin c(25 patients) during September 20014—September 2015 in the ophthalmology department at Jhalawar medical college, Jhalawar( raj.). 0.04% Mitomycin applied to bare sclera after excision for two minutes by swab sticks. Postoperative follow up period was 6 months. Outcomes measured in the form of recurrence and complications were analyzed. Results: In Group A with use of mitomycin C there was no recurrence after 6 months follow-up while in Group B recurrence was seen in 5 patients within 3-6 months, however in group A, 1 patient had scleral thinning. Conclusion: Intraoperative administration of mitomycin C 0.04% is safe and effective to prevent pterygium recurrences.

Purpose: The purpose of this study was to compare inflammatory events and graft characteristics 1 month and 6 months after conjunctival limbal autograft (CLAU) with and without intraoperative mitomycin C (MMC). Methods: This study included 69 eyes of 69 patient’s eyes with pterygium. Clinical data concerning patient demography, preoperative examination including pterygium morphology, recurrence clinical assessment, and complications after CLAU with (MMC+) and without (MMC-) intraoperative MMC were all registered at 1 month and 6 months after surgery. Results: Thirty-five eyes were included in MMC+ and 34 in MMC-. Preoperative data were similar in both groups (Student’s t test and Fisher’s exact test; p > 0.05). Thirty-four (49.6%) eyes in the whole sample showed at least one inflammatory complication at 1 month after surgery. MMC- group showed a significantly higher number of cases with complications (p < 0.001; Chi2 test) (MMC+ 28.5%; MMC- 70.5%). No patients presented clinical recurrence at 1 month after surgery. The examination revealed a higher incidence of clinical hyperemia surrounding the surgical site and graft contraction on the host site on the MMC- group, both with statistical signification (p < 0.001; Chi2 test). Although the hemorrhages were less frequent in the MMC- group, there were no significant differences between the two groups (p > 0.05; Chi2 test). Pyogenic granuloma developed at the surgical site in three eyes (4.37%), two of those granulomas were at the MMC- group (p > 0.05). Tendency for recurrences was significantly different between both groups (p = 0.0001; Fisher’s exact test) at the end of 6 months. Thirteen (38%) eyes showed recurrence in MMC- and no cases were displayed in MMC+. Presence of at least 1 inflammatory event was only seen in 16 (23%) cases, all of them in MMC-. Specifically, 15 (44%) eyes showed hyperemia and one (3%) eye presented conjunctival hemorrhages. No new cases of pyogenic granuloma or graft contraction were seen at, Postprint (author's final draft)

Objectives: Surgical intervention such as myringoplasty or tympanoplasty is an option in the current clinical management of chronic tympanic membrane perforation (TMP). Animal models of chronic TMP are needed for pre-clinical testing of new materials and to improve existing techniques. We evaluated several reported animal model techniques from the literature for the creation of chronic TMPs. The aim of this study was to evaluate production of chronic TMPs in a rat model using topical mitomycin C/dexamethasone, paper insertion into middle ear cavity (MEC) or re-myringotomy. Methods: Forty male Sprague-Dawley rats underwent myringotomy of the right tympanic membrane (TM) and were randomly divided into 3 experimental groups: application of topical mitomycin C/dexamethasone, paper insertion into middle ear cavity, or re-myringotomy. Control perforations were allowed to close spontaneously. TMs were assessed regularly with otoscopy for 8 weeks. At the end of 8 weeks, animals were sacrificed for histology. Results: The closure of TMPs was significantly delayed by mitomycin C/dexamethasone (mean patency, 18.9 days; P <= 0.01) compared with the control (mean patency, 7 days), but was not significantly delayed in the paper insertion group (mean patency, 9.4 days; P = 0.74). Repeated myringotomy of closed perforations (mean number of myringotomies, 8.9 per ear) stimulated acceleration of closure rather than delay. Histologically, the mitomycin C/dexamethasone group had almost normal TM morphology, while the paper insertion group revealed inflammatory and granulomatous responses. The re-myringotomy group had a thickened TM fibrous layer with collagen deposition. Conclusions: Mitomycin C/dexamethasone delayed TMP closure in rats but the effect was not sufficiently long-lasting to be defined as a chronic TMP. Neither paper insertion into middle ear cavity nor re-myringotomy created chronic TMP in rats. (C) 2015 Elsevier Ireland Ltd. All rights reserved., This study has been funded by The University of Western Australia Scholarship and The Garnett Passe & Rodney Williams Memorial Foundation to AYW, and the National Health and Medical Research Council of Australia (1056589). MvU was supported by a Raine Medical Research Foundation Visiting Professorship.

Background: 5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination. Methods and materials: Patients with locally advanced anal cancer, T2 (> 4 cm) -4N0-3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule. Results: Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46-70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3-4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%. Conclusion: The MTDs were determined as 5FU 800 mg/m(2) on RT days 1-4 and 29-32 and MMC 8 mg/m(2) on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.

Purpose To analyze conjunctival cytological features 1 month after pterygium excision using limbo-conjunctival autograft (LCA) with and without intraoperative mitomycin C and to assess tissue short-term evolution in both situations.; Methods Fifty-nine primary nasal pterygia from 59 patients were excised with LCA. Twenty-nine were treated with intraoperative mitomycin C 0.02% (MMC+) and 30 were treated without it (MMC-). Impression cytology was performed in nasal and temporal conjunctiva before and 1 month after the excision. Goblet cell density (GCD) and nucleus-to-cytoplasm nongoblet epithelial cell ratio were quantified.; Results Surgical strategy comparisons (intergroup comparisons): All the preoperative data were, in mean, within the reference range, except for a slight goblet cell hyperplasia in the area of the lesion in MMC+ but no significant differences were found between the groups (p = 0.079 for GCD and p = 0.245 for nucleus-to-cytoplasm ratio; analysis of variance). Clinically relevant differences after surgery were only shown in nasal GCD that was significantly lower in MMC+ than in MMC- (p = 0.000; analysis of variance), with the mean value in MMC+ slightly below normal values whereas that in MMC- remained normal. Tissue evolution (intragroup comparisons): No clinically relevant changes were found in MMC-. Data from MMC+ displayed no changes 1 month after surgery, except for nasal GCD that showed a significant reduction (p = 0.000; paired t test). Nevertheless, this GCD decrease was more modest than that previously described using mitomycin C without autograft, because in the present study, nasal GCD was not lower but similar to postoperative temporal data of the same eye (p = 0.164; paired t test).; Conclusions Limbo-conjunctival autograft is a good technique for conjunctiva early recovery. When mitomycin C was added, the GCD reduction was lower than described using other surgical techniques. Mitomycin C, in optimal concentration and exposure, associa, Postprint (author's final draft)

Purpose. To compare corneal astigmatism after pterygium excision, using limbal-conjunctival autograft (LCA) with and without mitomycin C (MMC) and to establish a threshold for postoperative astigmatism reduction.; Methods. Sixty-eight eyes with primary pterygium were consecutively sampled and assigned to LCA with MMC (MMC+) or LCA without MMC (MMC-). Corneal lesion length, corneal lesion area, preoperative corneal astigmatism (PRCA), and postoperative corneal astigmatism (POCA) at 1, 3, and 6 months were assessed.; Results. Thirty-six men and 24 women (60 eyes), aged between 24 and 65 years (mean +/- SD, 41 +/- 8.2 years), completed the study. Thirty-one eyes were included in the MMC+ group and 29 were in the MMC- group. Both groups showed astigmatism reduction (p < 0.05; paired, two-tailed t test) 1 month after the surgery and remained stable. No differences were found between groups in corneal lesion length, corneal lesion area, or astigmatism results at the four time points (p 9 0.05, independent t test). Preoperative corneal astigmatism showed a significant correlation with POCA at 6 months (r = 0.529; p < 0.01). According to receiver operating characteristic curve analysis, the better threshold for astigmatism reduction with the surgery was 1.05 diopters of PRCA, with 82.5% sensitivity and 80.5% specificity.; Conclusions. Both surgical procedures could have similar astigmatism results. Pterygium patients with more than 1.05 diopters of PRCA could reduce it after the surgery. Direct relationship between PRCA and POCA revealed that postoperative astigmatism reduction was partial. Therefore, for minimizing final astigmatism, preoperative values should be slightly above the threshold., Postprint (published version)

Ureaplasma parvum and Ureaplasma urealyticum are sexually transmitted, opportunistic pathogens of the human urogenital tract. There are 14 known serovars of the two species. For decades, it has been postulated that virulence is related to serotype specificity. Understanding of the role of ureaplasmas in human diseases has been thwarted due to two major barriers: (1) lack of suitable diagnostic tests and (2) lack of genetic manipulation tools for the creation of mutants to study the role of potential pathogenicity factors. To address the first barrier we developed real-time quantitative PCRs (RT-qPCR) for the reliable differentiation of the two species and 14 serovars. We typed 1,061 ureaplasma clinical isolates and observed about 40% of isolates to be genetic mosaics, arising from the recombination of multiple serovars. Furthermore, comparative genome analysis of the 14 serovars and 5 clinical isolates showed that the mba gene, used for serotyping ureaplasmas was part of a large, phase variable gene system, and some serovars shown to express different MBA proteins also encode mba genes associated with other serovars. Together these data suggests that differential pathogenicity and clinical outcome of an ureaplasmal infection is most likely due to the presence or absence of potential pathogenicity factors in individual ureaplasma clinical isolates and/or patient to patient differences in terms of autoimmunity and microbiome. To address the second barrier we are adapting the traditional molecular biology and novel synthetic biology tools to Ureaplasma, such as creation of oriC plasmids, use of transposons, and most prominently the engineering bacterial genomes cloned as yeast centromeric plasmids followed by genome transplantation to make ureaplasma mutants programmed by the genomes manipulated in yeast. This will allow for the creation of targeted single or multiple mutants that will greatly increase the understandin

This work tested the hypothesis that the conserved archaeal Nre protein functions as a PCNA-dependent DNA repair factor. By exploiting the genetic tools available in the halophilic euryarchaeal organism Haloferax volcanii, it was shown that [1] Nre does indeed have a role in DNA damage repair (cells lacking Nre are supersensitive to specific DNA damaging agents and show delayed repair of DNA double strand breaks evidenced by DNA pulsed field gel electrophoresis) and [2] that the function of Nre in DNA damage repair in dependent on its ability to interact through its C-terminal PIP motif with PCNA (cells expressing an Nre protein lacking the PIP motif display similar phenotypes to cells lacking Nre altogether). Thus, the original hypothesis was validated. Further genetic analysis indicates that Nre performs its function, at least in part, in cooperation with the UvrABC excinuclease complex. This work contributes significant to our understanding of the diversity of DNA repair functions in archaea., The original document contains color images.

ObjectivesIdentification of the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. To develop D. melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high-throughput toxicity assays and prove that the interindividual variation in toxicity as measured by such assays is highly heritable.MethodsWe developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose-dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed by a decrease in female fecundity. The chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride.ResultsWe found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose-dependent and a highly heritable manner. The following heritability estimates were found: carboplatin, 0.72; floxuridine, 0.52; gemcitabine hydrochloride, 0.72; methotrexate, 0.99; mitomycin C, 0.64; and topotecan hydrochloride, 0.63.ConclusionThe high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component.

Introduction: Endolaryngeal microsurgical management of bilateral glottic lesions such as webs or scars is devastating and challenging for the surgeon to treat, with poor functional results. These lesions require a variety of multiple procedures with postoperative scarring, synechiae, more web formation and subsequent dysphonia. Mitomycin C (MMC) is an antineoplastic antibiotic that acts an alkylating agent by inhibiting DNA and protein synthesis. Materials and methods: A retrospective chart review of all patients treated with glottic lesions involving the anterior commissure during five years. Details such as age, sex, diagnosis, history of past laryngeal surgery, follow up duration, complications among others were analyzed. The lesions were removed by transoral microsurgery using a CO2 laser, and immediately treated with a cottonoid pledget soaked in MMC with 0.4 mg/ml for 5 minutes at the end of surgery. Outcome was assessed at one year using a visual scale. Results: A total of 26 patients were included in the analysis with ages ranging from 50 to 81 years old. Most of the topical applications were on the bilateral anterior aspect of the glottis (98.5%), after the resection of malignant lesions. We performed 2 types of surgery, for the prevention of synechiae (45%), or to treat secondary scars or restenosis (55%). The success (no synechiae) was statistically insignificant (p = .6). Conclusions: MMC is not statistically effective in treating or preventing any of these lesions after long term control and, only prevents scars and webs in acute wound healed, but after some time it reappeared. In previous damaged mucosa with a static process of healing no benefit was neither observed., Introducción: El manejo microquirúrgico de las bridas y sinequias que se forman tras la exéresis de lesiones glóticas bilaterales, es devastador y desafiante para el cirujano que las trata, con pobres resultados funcionales. Estas lesiones requieren una amplia variedad de múltiples procedimientos con la consiguiente formación de aún más bridas, sinequias, cicatrices y disfonía persistente. La Mitomicina C (MMC) es una antibiótico antineoplásico que actúa como agente alquilante al inhibir la síntesis de ADN y de proteínas. Materiales y métodos: Revisión de las historias clínicas de pacientes con lesiones glóticas anteriores malignas incluyendo la comisura anterior durante cinco años. Detalles como edad, sexo, diagnóstico, historia de cirugías laríngeas previas, duración del seguimiento, complicaciones entre otros fueron analizados. Las lesiones fueron resecadas mediante microcirugía transoral con láser CO2, para inmediatamente ser tratadas con algodón embebido en MMC a 0.4 mg/ml durante 5 minutos al final de la cirugía. Los resultados fueron evaluados al año usando una escala visual. Resultados: Un total de 26 pacientes se incluyeron en el análisis con edades comprendidas entre 50 y 81 años. La mayoría de las aplicaciones tópicas fueron en la parte anterior bilateral del la glotis (98.5%), luego de resección de lesiones malignas. Se realizaron 2 tipos de cirugía, para prevenir sinequias (45%), y para tratar las cicatrices o restenosis (55%). El éxito (ausencia de sinequias) en ambos grupos fue estadísticamente no significativo (p=.6). Conclusiones: La MMC no es estadísticamente efectiva en tratar ni prevenir cualquiera de estas lesiones y, sólo previene cicatrización y por consiguiente sinequias, en heridas recientes (agudas); sin embargo, luego de un tiempo reaparecen. En mucosa previamente dañada con un proceso de cicatrización estable, tampoco se obtuvo beneficio significativo.

Introduction: Endolaryngeal microsurgical management of bilateral glottic lesions such as webs or scars is devastating and challenging for the surgeon to treat, with poor functional results. These lesions require a variety of multiple procedures with postoperative scarring, synechiae, more web formation and subsequent dysphonia. Mitomycin C (MMC) is an antineoplastic antibiotic that acts an alkylating agent by inhibiting DNA and protein synthesis. Materials and methods: A retrospective chart review of all patients treated with glottic lesions involving the anterior commissure during five years. Details such as age, sex, diagnosis, history of past laryngeal surgery, follow up duration, complications among others were analyzed. The lesions were removed by transoral microsurgery using a CO2 laser, and immediately treated with a cottonoid pledget soaked in MMC with 0.4 mg/ml for 5 minutes at the end of surgery. Outcome was assessed at one year using a visual scale. Results: A total of 26 patients were included in the analysis with ages ranging from 50 to 81 years old. Most of the topical applications were on the bilateral anterior aspect of the glottis (98.5%), after the resection of malignant lesions. We performed 2 types of surgery, for the prevention of synechiae (45%), or to treat secondary scars or restenosis (55%). The success (no synechiae) was statistically insignificant (p = .6). Conclusions: MMC is not statistically effective in treating or preventing any of these lesions after long term control and, only prevents scars and webs in acute wound healed, but after some time it reappeared. In previous damaged mucosa with a static process of healing no benefit was neither observed., Introducción: El manejo microquirúrgico de las bridas y sinequias que se forman tras la exéresis de lesiones glóticas bilaterales, es devastador y desafiante para el cirujano que las trata, con pobres resultados funcionales. Estas lesiones requieren una amplia variedad de múltiples procedimientos con la consiguiente formación de aún más bridas, sinequias, cicatrices y disfonía persistente. La Mitomicina C (MMC) es una antibiótico antineoplásico que actúa como agente alquilante al inhibir la síntesis de ADN y de proteínas. Materiales y métodos: Revisión de las historias clínicas de pacientes con lesiones glóticas anteriores malignas incluyendo la comisura anterior durante cinco años. Detalles como edad, sexo, diagnóstico, historia de cirugías laríngeas previas, duración del seguimiento, complicaciones entre otros fueron analizados. Las lesiones fueron resecadas mediante microcirugía transoral con láser CO2, para inmediatamente ser tratadas con algodón embebido en MMC a 0.4 mg/ml durante 5 minutos al final de la cirugía. Los resultados fueron evaluados al año usando una escala visual. Resultados: Un total de 26 pacientes se incluyeron en el análisis con edades comprendidas entre 50 y 81 años. La mayoría de las aplicaciones tópicas fueron en la parte anterior bilateral del la glotis (98.5%), luego de resección de lesiones malignas. Se realizaron 2 tipos de cirugía, para prevenir sinequias (45%), y para tratar las cicatrices o restenosis (55%). El éxito (ausencia de sinequias) en ambos grupos fue estadísticamente no significativo (p=.6). Conclusiones: La MMC no es estadísticamente efectiva en tratar ni prevenir cualquiera de estas lesiones y, sólo previene cicatrización y por consiguiente sinequias, en heridas recientes (agudas); sin embargo, luego de un tiempo reaparecen. En mucosa previamente dañada con un proceso de cicatrización estable, tampoco se obtuvo beneficio significativo.

ObjectivesIdentification of the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. To develop D. melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high-throughput toxicity assays and prove that the interindividual variation in toxicity as measured by such assays is highly heritable.MethodsWe developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose-dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed by a decrease in female fecundity. The chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride.ResultsWe found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose-dependent and a highly heritable manner. The following heritability estimates were found: carboplatin, 0.72; floxuridine, 0.52; gemcitabine hydrochloride, 0.72; methotrexate, 0.99; mitomycin C, 0.64; and topotecan hydrochloride, 0.63.ConclusionThe high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component.

Anterior glottic webs are most frequently acquired and result in a major vocal handicap. Many treatment modalities have been reported in the literature. None of them achieves perfect morphological or functional results. We present our series treated by an endoscopic technique based on CO 2 laser section of the web, mitomycin application and placement of a temporary silastic stent. We retrospectively reviewed the charts of 18 consecutive patients with anterior webs treated at our university hospital between 2003 and 2010. The endoscopic technique consisted of the section of the web with the CO 2 Acublade system, immediate application of mitomycin C and placement of a silastic stent. No tracheostomy was required. The stent was removed 3 weeks later. Patients had a vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic examination, the global score of the Voice Handicap Index, the global and roughness scores of the perceptive voice evaluation according to Hirano, acoustic and aerodynamic parameters. Eighteen patients were included in the study with a mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All patients had postoperative speech therapy. The mean follow-up is 48.4 months (3-87 months). At the last follow-up, none of the patients had recurrence of the laryngeal web. The grade G of dysphonia signiWcantly decreased from 2 to 1 (p = 0.035). CO 2 laser resection of anterior webs with mitomycin C application and placement of a silastic stent for 3 weeks induces a good morphological result with absence of web reformation but without substantial voice improvement observed in our series. © Springer-Verlag 2012.

Anterior glottic webs are most frequently acquired and result in a major vocal handicap. Many treatment modalities have been reported in the literature. None of them achieves perfect morphological or functional results. We present our series treated by an endoscopic technique based on CO 2 laser section of the web, mitomycin application and placement of a temporary silastic stent. We retrospectively reviewed the charts of 18 consecutive patients with anterior webs treated at our university hospital between 2003 and 2010. The endoscopic technique consisted of the section of the web with the CO 2 Acublade system, immediate application of mitomycin C and placement of a silastic stent. No tracheostomy was required. The stent was removed 3 weeks later. Patients had a vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic examination, the global score of the Voice Handicap Index, the global and roughness scores of the perceptive voice evaluation according to Hirano, acoustic and aerodynamic parameters. Eighteen patients were included in the study with a mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All patients had postoperative speech therapy. The mean follow-up is 48.4 months (3-87 months). At the last follow-up, none of the patients had recurrence of the laryngeal web. The grade G of dysphonia signiWcantly decreased from 2 to 1 (p = 0.035). CO 2 laser resection of anterior webs with mitomycin C application and placement of a silastic stent for 3 weeks induces a good morphological result with absence of web reformation but without substantial voice improvement observed in our series. © Springer-Verlag 2012.

Purpose: Mucoepidermoid carcinoma is a rare variant of squamous cell carcinoma of the conjunctiva. It appears more frequently in the elderly, it is more aggressive than squamous cell carcinoma, and it has a higher recurrence rate and higher incidence of intraocular and orbital invasion. Methods: We report a case of a 74-year-old man who presented to the Emergency Department with a one month history of painful red left eye. Results: The patient presented with visual acuity was 10/10 in both eyes and a conjunctiva tumor on the bulbar conjunctiva of left eye. The UBM revealed a thickening of the conjunctiva-sclera complex with no signs of intraocular invasion. A biopsy was performed and the diagnosis was of mucoepidermoid carcinoma. Two local excisions with adjuvant cryotherapy and mitomycin C aplication were carried out in a period of 6 months. After 9 months of follow-up there has not been any sign of recurrence.Conclusions: The early diagnosis and treatment of carcinoma is essential not only to prevent the intraocular spread and preserve visual function but also to prevent local or systemic recurrence and dissemination.

Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. Design, setting, and participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. Intervention: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. Measurements: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. Results and limitations: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all random-ized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). Conclusions: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA.

Strategic planning for the Radiation Therapy Committee of the Southwest Oncology Group (SWOG) is comprehensively evaluated every six years in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2008 Strategic Planning Workshop included clinical trial experts from multiple specialties, industry representatives from both pharmaceuticals and equipment manufacturers, and basic scientists. High-priority research areas such as image-guided radiation therapy for control of limited metastatic disease, analysis of biomarkers for treatment response and late toxicity, assessment of novel agents in combination with radiation, standardization of radiation target delineation, and the assessment of new imaging techniques to individualize cancer therapy, were discussed. Research priorities included clinical study designs featuring translational end points that identify patients most likely to benefit from combined modality therapy; intervention including combination radiation with standard chemotherapy; radiation with radiosensitizing molecular-targeted therapies; and stereotactic radiation for treatment of patients with regard to asymptomatic metastasis and radiation-induced tumor autoimmunity. The Committee concluded that the future research opportunities are among the most exciting to have developed in the last decade, and work is in progress to embark on these plans.

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Purpose: To assess the feasibility and activity of radio-chemotherapy with mitomycin C (MMC) and cisplatin (CDDP) in locally advanced squamous cell anal carcinoma with reference to radiotherapy (RT) combined with MMC and fluorouracil (5-FU). Patients and methods: Patients with measurable disease >4 cm N0 or N+ received RT (36 Gy + 2 week gap + 23.4 Gy) with either MMC/CDDP or MMC/5-FU (MMC 10 mg/m2 d1 of each sequence; 5-FU 200 mg/m2/day c.i.v. daily; CDDP 25 mg/m2 weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, α = 10%, β = 10%). Results: The ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/ 37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p = 0.005). Conclusions: Radio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile. © 2009 Elsevier Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published