•1 vs. 2 cycles of MMC along with 5FU and radiotherapy is associated with comparable treatment outcomes in general.•Stage IIIb and IIIc patients are at a higher risk for locoregional and distant ...failure.•2 doses of MMC improves anal cancer specific survival and distant disease free survival in stage IIIb and IIIc.
We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM).
In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS).
451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc.
Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS.
Purpose: Preserflo Microshunt surgery is a new surgical procedure in the management of glaucoma. We evaluated the effectiveness and safety of Preserflo Microshunt surgery throughout the first ...6 months postoperatively, by comparing intraocular pressure (IOP), number of drop agents pre and post operatively and any registered complications.
Methods: A case series of 30 patients with primary open angle glaucoma underwent Preserflo Microshunt surgery at a District General Hospital in the UK. Surgical technique included scleral application of Mitomycin C 0.4 mg/mL for 3 minutes prior to microshunt insertion. Patients had their intra ocular pressure recorded pre operatively, day 1, week 2, month 2 and after 6 months. The number of therapeutic agents in their glaucoma drops was also compared pre‐operatively and after 6 months.
Results: Mean IOP was reduced form 17.4 mmHg at baseline to 8.9 mmHg at 2 months and 11.6 mmHg at 6 months. The mean number of drug agents reduced from 2.25 to 0.07, and a total of 28 out of 30 (93.3%) remained drop free at 6 months. There were three cases where patients required needling of the bleb, two subsequently required repositioning of the shunt, and an IOP spike at day one post operatively in one case.
Conclusions: Early results for Preserflo Microshunt surgery show sustained reduction in IOP at 6 months, with the majority of patients requiring no glaucoma drops postoperatively. The surgery has been well tolerated by patients with less intense follow up compared to a traditional trabeculectomy and low complication rates.
Objectives
To evaluate the activity of intravesical mitomycin‐C (MMC) to ablate recurrent low‐risk non‐muscle‐invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid ...surgical intervention for treatment of recurrence.
Patients and Methods
CALIBER is a phase II feasibility study. Participants were randomized (2:1) to treatment with four once‐weekly MMC 40‐mg intravesical instillations (chemoablation arm) or to surgical management. The surgical group was included to assess the feasibility of randomization. The primary endpoint was complete response to intravesical MMC in the chemoablation arm at 3 months, reported with exact 95% confidence intervals (CIs). Secondary endpoints included time to subsequent recurrence, summarized by Kaplan–Meier methods.
Results
Between February 2015 and August 2017, 82 patients with visual diagnosis of recurrent low‐risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28). The median follow‐up was 24 months. Complete response at 3 months was 37.0% (20/54; 95% CI 24.3–51.3) with chemoablation and 80.8% (21/26; 95% CI 60.6–93.4) with surgical management. Amongst patients with complete response at 3 months, a similar proportion was recurrence‐free by 12 months in both groups (84%). Amongst those with residual disease at 3 months, the 12‐month recurrence‐free proportion was lower in the surgical management group (40.0%) than in the chemoablation group (84%). Recruitment stopped early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months.
Conclusion
Intravesical chemoablation in low‐risk NMIBC is feasible and safe, but did not demonstrate sufficient response in the present trial. After chemoablation there may be a reduction in recurrence rate, even in non‐responders, that is greater than with surgery alone. Further research is required to investigate the role and optimal schedule of neoadjuvant intravesical chemotherapy prior to surgery for NMIBC.
Background: The introduction of mitomycin C (MMC) as an adjunct to trabeculectomy was a major advance in the ability to improve the Intra ocular pressure lowering efficiency of the procedure. The ...time tested traditional way of administration of MMC is via a sponges soaked in it, duration and concentration varies depending on risk of failure. A subconjunctival injection of MMC instead of these sponges is recently being used as a promising alternative. Purpose: Here is the video demonstrating the 2 possible ways to prepare and apply MMC during a trabeculectomy surgery. Synopsis: Intraoperative injection of MMC in trabeculectomy has several advantages over conventional method ofsponge application. A large MMC treatment area produces more diffuse and elevated blebs. Large-area MMC application also seems to increase long-term success without increasing the complication rates in trabeculectomies. Direct and diffuse application of MMC by injection may promote less scarring and vascularization of the bleb. To achieve the same surface area of exposure with sponges, i.e.achieved with injection, the surgeon must use multiple sponges, all of which must be carefully collected thereafter. The injection method,therefore,eliminates the risk of retained sponges. Highlights: injection of MMC may be as safe and as effective as conventional sponge application of MMC with comparable estimated complete treatment success with relatively lower complication rates.
Video link: https://youtu.be/RLEbK4IeRtU
This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, Cora N. Sternberg, MD, has led groundbreaking research ...in understanding cancer's genetic makeup and shared her knowledge with fellow physicians to help give patients with cancer hope of better outcomes. In addition, a new study shows that young adult Black patients with acute myeloid leukemia have significantly lower survival rates than White patients despite similar intensive treatment, and MatchMiner software is helping match patients with cancer to precision trials through genomic eligibility.
Objective: Toxic anterior segment (TASS) is a rare acute sterile anterior segment inflammation that typically develops within 12 to 24 hours after an anterior segment surgery. The purpose of this ...case report is to alert surgeons to the possibility of this complication following any anterior segment surgery, including trabeculectomy, and to highlight the possible etiologies and measures to prevent it.Patient and method: A 58-year-old male glaucoma patient was initially managed medically for primary open angle glaucoma with antiglaucoma medications. There was rapidly progressive glaucomatous optic nerve damage in his left eye within the following year, despite the use of antiglaucoma medications, hence the need for trabeculectomy.Result: The post-operative condition of the patient’s eye was stormy with diffuse limbus-to-limbus corneal edema and profound Descemet’s membrane folds, among other features of TASS, with associated deteriorating visual acuity. Conclusion: Although there is no documented report of TASS following trabeculectomy with mitomycin C, surgeons should be alerted to this possibility. Preventive measures include extreme care to avoid errors while preparing and administering diluted solutions, especially medications that are administered into the intracameral space.
Objectives
To assess the safety and feasibility of early single‐dose mitomycin C (MMC) bladder instillation after robot‐assisted radical nephroureterectomy (RARNU) at a tertiary kidney cancer centre. ...RARNU with bladder cuff excision and subsequent MMC bladder instillation to reduce recurrence risk is the ‘gold standard’ for high‐risk upper urinary tract urothelial carcinoma (UUTUC). We adapted a RARNU technique with precise distal ureteric dissection, bladder cuff excision and watertight bladder closure.
Patients and Methods
We retrospectively reviewed all patients undergoing RARNU for UUTUC at our centre performed as a standardised transperitoneal procedure comprising of: bladder cuff excision, two‐layer watertight closure and intraoperative bladder leak test; without re‐docking/re‐positioning of the robotic surgical system. Patient demographics, the timing of MMC instillation, adverse events (surgical and potentially MMC‐related) and length of stay (LOS) were assessed according to the Clavien–Dindo classification.
Results
A total of 69 patients underwent a RARNU with instillation of MMC. The median (interquartile range IQR) age was 70 (62–78) years. The median (IQR) day of MMC instillation was 2 (1–3) days and the median (IQR) LOS was 2 (2–4) days, with urethral catheter removal on day of discharge in all cases. Only Grade I Clavien–Dindo complications occurred in seven patients (10%); five had ileus, one a wound infection and one a self‐limiting delirium, all managed conservatively. No adverse events potentially related to MMC instillation were noted within 30 days postoperatively.
Conclusion
The use of intravesical MMC instillation given in the immediate postoperative period appears feasible and safe in patients undergoing RARNU with intraoperative confirmation of a water‐tight closure ensuring early catheter‐free discharge, with no significant adverse events. The potential reduction in intravesical recurrence in patients receiving early MMC needs to be assessed with longitudinal follow‐up studies.
Purpose
To study the long‐term outcome of deep sclerectomy with and without mitomycin‐C (MMC) in patients with normal‐tension glaucoma (NTG).
Methods
We prospectively analysed consecutive patients ...randomized to surgery performed either with (MMC group) or without (non‐MMC) MMC. Surgery was considered totally successful if, after surgery, the preoperative intra‐ocular pressure (IOP) level was reduced by 25% without medication, and a qualified success if medication was required to achieve the same limits.
Results
A total of 37 patients were enrolled, 15 in the MMC and 22 in the non‐MMC group. The median (range) follow‐up was 7.9 (1.0–9.0) years, with a drop‐out of three (8%) patients. The preoperative IOP was 15 (11–21) mmHg in the MMC and 15 (10–19) mmHg in the non‐MMC group. At the last 6‐ to 9‐year follow‐up, IOP was significantly reduced to 9 (2–13) mmHg (p = 0.002) and 10 (5–13) mmHg (p < 0.001). The overall (groups combined) complete and qualified success rates were 50% and 71%, with no significant difference between groups (p = 0.48 and p = 0.25). Goniopuncture was performed in 87% and 100% of eyes in the MMC and non‐MMC groups (p = 0.14). Needling with MMC injection was performed 0 (0–1) times in the MMC group and 0.5 (0–4) times in the non‐MMC group (p = 0.056). We encountered no cases of hyphema, shallow anterior chamber, hypotony maculopathy, choroidal effusion, late bleb leakage, blebitis, endophthalmitis or malignant glaucoma.
Conclusion
In NTG, long‐term significant IOP reduction can be achieved with deep sclerectomy with a low incidence of sight‐threatening complications.
Mitomycin C, (MC), an antitumor drug, is a DNA alkylating agent currently used in the clinics. Inert in its native form, MC is reduced to reactive mitosenes, which undergo nucleophilic attack by ...guanine or adenine bases in DNA to form monoadducts as well as interstrand crosslinks (ICLs). Although ICLs are considered the most cytotoxic lesions, the role of each individual adduct in the drug's cytotoxicity is still not fully understood. Synthetic routes have been developed to access modified oligonucleotides containing dG MC‐monoadducts and dG‐MC‐dG ICL at a single position of their base sequences to investigate the biological effects of these adducts. However, until now, oligonucleotides containing monoadducts formed by MC at the adenine base had not been available, thus preventing the examination of the role played by these lesions in the toxicity of MC. Here, we present a route to access these substrates. Structural proof of the adducted oligonucleotides were provided by enzymatic digestion to nucleosides and high‐resolution mass spectral analysis. Additionally, parent oligonucleotides containing a dG monoadduct and a dG‐MC‐dG ICL were also produced. The stability and physical properties of all substrates were compared via CD spectroscopy and UV melting temperature studies. Finally, virtual models were created to explore the conformational space and structural features of these MC‐DNA complexes.
A route to access modified oligonucleotides containing trans dA monoadducts produced from the reaction between mitomycin C and DNA is presented. Parent oligonucleotides containing a trans dG monoadduct and a trans dG‐MC‐dG ICL were also produced. The stability and spectral properties of all substrates were compared and virtual models were created to explore the conformational space and structural features of these MC‐DNA complexes.
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