•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.
Proliferative vitreoretinopathy (PVR) is an abnormal and prolonged healing response to retinal injury (retinal detachment, post retinal detachment surgery) characterised by: pre/subretinal membrane ...formation; retinal gliosis and retinal shortening, retinal pigment epithelium cell proliferation; and increased glial (mainly Mu¨ller cells), fibroblast and inflammatory cell (macrophage, lymphocyte) activity, leading to tractional retinal holes/breaks and multiple costly eye operations suffered by patients. PVR can cause retinal re-detachment following primary surgical intervention for rhegmatogenous retinal detachment. Vitrectomy and scleral buckling surgery are the main approaches for treating PVR complications of retinal detachment. Patients require many operations to remove the scar tissue but vision results are suboptimal, and do not meet patient expectations. Over the past 40 years, this has been one of the greatest challenges for vitreoretinal surgeons and patients. Despite previous large clinical trials of multiple candidate drug therapeutics, no proven adjunctive treatment currently exists to either prevent, reduce, or treat PVR formation in retinal detachment. Both cellular proliferation and the intraocular inflammatory response are realistic targets for adjunctive treatments in PVR. The cellular components of PVR periretinal membranes (retinal pigment epithelial, glial, inflammatory and fibroblastic cells) proliferate and are thus targets for antiproliferative agents. In recent years, several new therapeutics have been tested, and we present an updated review of the clinical therapeutics for PVR in retinal detachment.
To study the effect of mitomycin C (MMC) applied during transepithelial photorefractive keratectomy (TPRK) on the corneal endothelium one week (W1) and three months (M3) after surgery and its ...determinants.
In this two-armed cohort study conducted in 2022, eyes treated with MMC during TPRK (group 1) were compared with eyes not treated with MMC (group 2). The corneal endothelial cell (EC) count, EC density (ECD; cells/mm
), average (µm
), standard deviation (µm
), coefficient of variation (CV%), EC
, EC
, and EC percentage of hexagonality were estimated at W1 and M3. The postoperative changes in the EC count in the two groups were compared and correlated with the other independent variables.
Group 1 had 26 eyes, and group 2 had 78 eyes. All TPRK indices were significantly higher for the eyes in group 1 than for those in group 2. The MMC usage was not a significant predictor of the change in ECD (
=0.644), change in CV (
=0.374), and change in the percentage of hexagonality of EC (
=0.164) at W1. However, the use of MMC was a significant predictor of changes in CV (
=0.014) and the change in the percentage of hexagonality of EC (
=0.039) at M3. The duration of laser exposure and the size of the optical zone influenced the correlation of MMC use with the changes in EC indices, postoperatively.
The use of MMC doesn't affect ECD, CV, and percentage of hexagonality at W1 if other surgical indices are considered. At M3 after operating myopic eyes by TPRK, MMC significantly influence the CV and percentage of hexagonality. The duration of the laser application and the size of the optical zone should be considered when determining the effect of MMC on the EC indices.
Study Type – Therapy (RCT) Level of Evidence 1b
What’s known on the subject? and What does the study add?
Microwave‐induced hyperthermia and mitomycin C is a device‐assisted approach used to treat ...non‐muscle invasive bladder cancer (NMIBC) either in the adjuvant (prophylactic) set‐up or in an ablative regimen. Until recently, around 20 different studies have been published with data on the short term results of treatment. Previous prospective randomized studies showed the superiority of the chemo‐hyperthermia regimen when compared to intravesical chemotherapy alone in terms of recurrence‐free survival in intermediate and high‐risk NMIBC patients at minimum 24‐month follow‐up. The current study confirmed the result also in long‐term (minimum 10 years) follow‐up. It also represents one of a few to show such extended follow‐up periods for any intravesical therapy for NMIBC.
OBJECTIVE
• To present long‐term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin‐C (MMC) randomly administered to patients with non‐muscle‐invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection.
PATIENTS AND METHODS
• In all, 83 patients with intermediate‐/high‐risk NMIBC, following complete transurethral resection, were randomly assigned to receive either intravesical thermochemotherapy by means of Synergo® (Medical Enterprises, Amsterdam, The Netherlands) or intravesical chemotherapy alone, for prophylaxis of tumour recurrence.
• Two doses of MMC (20 mg dissolved in 50 mL distilled water administered throughout two consecutive sessions) was used as the chemotherapeutic agent in both arms.
• In all, 75 patients completed the original study (35 of 42 in the treatment arm, 40 of 41 in the control arm), whose results at minimum 2‐year follow‐up have already been published.
• Recently, the files of these patients have been updated for long‐term outcome definition. Data on general health, follow‐up examinations, tumour relapse or progression, and cause of death were collected and analysed.
RESULTS
• Updated complete data collection was available for 65/75 (87%) of the original patients.
• The median follow‐up for tumour‐free patients was 91 months. The 10‐year disease‐free survival rate for thermochemotherapy and chemotherapy alone were 53% and 15%, respectively (P < 0.001).
• An intent‐to‐treat analysis performed to overcome the potential bias introduced by the asymmetrical discontinuation rate still showed a significant advantage of the active treatment over the control treatment. Bladder preservation rates for thermochemotherapy and chemotherapy alone were 86% and 79%, respectively.
CONCLUSION
• This is the first analysis of long‐term follow‐up of patients treated with intravesical thermochemotherapy. The high rate (53%) of patients who were tumour‐free 10 years after treatment completion, as well as the high rate (86%) of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long‐term follow‐up, even in patients with multiple tumours.
Purpose
Myopic glaucoma patients display a considerable risk of complications following antiglaucomatous filtering surgery, e.g., trabeculectomy. Canaloplasty with mitomycin C may reduce this risk by ...avoiding massive overfiltration.
Methods
We performed retrospective analysis of 31 eyes with myopia that underwent canaloplasty modified with mitomycin C in a consecutive single-surgeon case series. Annual data and success rates were analysed. Twenty-three myopic eyes that had received conventional trabeculectomy with mitomycin C were recorded as a comparison.
Results
The 31 eyes with a follow-up of 40 ± 26 months after canaloplasty had a mean spherical equivalent of − 8.4 ± 4.5 dioptres. Intraocular pressure decreased from 32.3 ± 9.6 mmHg (range: 17 to 58) to 16.8 ± 8.1 mmHg (range: 5 to 44) 1 year after surgery (− 46%;
p
< 0.001) with a medication score reduction from 5 to 1.2 (
p
< 0.001). Qualified success rates (Criterion B: no revision surgery, IOP < 21 mmHg, IOP reduction > 20%) were 83% after 1 year and 61% at the 2nd and 3rd years. In 5 eyes (16%), early ocular hypotony (≤ 5 mmHg) was observed. Two eyes (7%) showed transient choroidal detachment and swelling. The 23 eyes that had received trabeculectomy had success rates (Criterion B) of 91% at the 1st and 86% at the 2nd and 3rd years. Hypotony occurred in 10 eyes (44%), and 4 eyes (17%) showed choroidal detachment or macular folds.
Conclusions
Postoperative complications related to overfiltration were less frequent after canaloplasty with mitomycin C. Midterm data proved good efficacy. Pressure reduction, success rates and rates of medication free patients were significantly higher in trabeculectomy compared to modified canaloplasty with mitomycin C.
•46 studies on CRS/HIPEC for PMCRC using MMC- or OX-based regimens were included.•OX based CRS/HIPEC showed a higher proportion of severe complications.•No meaningful comparison could be made ...regarding DFS and OS.•Induction systemic therapy was mostly given in OX studies.•The published literature on MMC- or OX-based CRS/HIPEC regimens is very heterogeneous.
The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal metastases of colorectal cancer. Whether this applies to all published CRS/HIPEC regimens is unclear.
A systematic literature search identified 46 studies on CRS/HIPEC using either oxaliplatin of mitomycin C with at least one oncological outcome parameter
Oxaliplatin and mitomycin C studies were comparable regarding extent of disease, but differed substantially regarding synchronous versus metachronous presentation, application of neo-adjuvant systemic chemotherapy, duration of HIPEC, and completeness of cytoreduction for at least one of the oncological endpoints. Severe postoperative complication rate seemed significantly higher after oxaliplatin-based CRS/HIPEC.
Published cohorts on oxaliplatin-based CRS/HIPEC differed essentially from MMC-based procedures, especially considering the application of oxaliplatin-containing neo-adjuvant systemic therapy and shorter exposure time to intraperitoneal chemotherapy in oxaliplatin studies. No meaningful comparison could be made regarding DFS and OS.
Trabeculectomy has been performed since the mid-1960s and remains the gold standard for glaucoma surgery. Newer surgical options have evolved, collectively referred to as minimally invasive glaucoma ...surgeries. Despite producing large intraocular pressure decreases, full-thickness procedures into the subconjunctival space may be limited by fibrosis. Mitomycin C (MMC) and 5-fluorouracil have been in use with trabeculectomy with good evidence of significantly increased success at the cost, however, of an increased risk of complications. Off-label MMC application can be found in almost all clinical trials, including in combination with minimally invasive glaucoma surgeries. We explore current evidence for MMC use in trabeculectomy and how this may differ for minimally invasive glaucoma surgery devices and analyze the range of agents and doses that are used. Although we found that most studies could not show any correlation between MMC dosage and the surgical outcome, the success rates with the Xen® microshunt seemed to be higher when using 20 mcg of MMC than when using 10 mcg. Certain important methodological considerations make this hard to confirm definitively, and other factors such as placement of the device may play a more substantial role. For the PreserFlo® microshunt, preliminary data suggest higher success rates with higher MMC dosage at the cost of higher device-related adverse events and reoperations. Although the ideal dose still needs to be established, it seems very likely that MMC provides significant improvement in outcomes in bleb-forming minimally invasive glaucoma procedures.
Purpose
To compare the long‐term outcomes of trabeculectomy using mitomycin C (MMC) alone versus MMC plus intracameral bevacizumab.
Methods
Retrospective, comparative study (#ISRCTN93098069). ...Patients’ charts from two centers were reviewed for data between October 2015 and March 2019. Minimum follow‐up of 12 months was required. The main efficacy outcome was intraocular pressure (IOP) lowering at 12 and 24 months, with surgical success defined as IOP ≤18 mmHg and >5 mmHg with at least 30% reduction from baseline. Absolute success was achieved if no IOP‐lowering medication was needed and a qualified success considered otherwise. Safety outcomes were also analyzed.
Results
A total of 111eyes underwent trabeculectomy with MMC, 52 of them combined with intracameral bevacizumab. 78% were followed for at least two years. Baseline IOP was 24.5 ± 8.9 mmHg and 23.8 ± 8.3 mmHg for the MMC and the MMC+bevacizumab groups, respectively (p = 0.97). During the early post‐operative period (at 3 months), mean IOP was lower in the MMC+bevacizumab group (9.3 ± 2.3 mmHg versus 11.1 ± 5.5 mmHg, p = 0.03). At 24‐month visit, IOP was significantly reduced (MMC group: 10.6 ± 3.4 mmHg; MMC+bevacizumab group: 10.9 ± 4.1 mmHg, p < 0.01) with no difference between groups (p = 0.61). Absolute success was higher in the MMC+bevacizumab group at 12 months (86% versus 75%, p = 0.16) and at 24 months (83% versus 67%, p = 0.14), with the need for IOP‐lowering re‐interventions (needlings) being lower in this group (2% versus 17%, p = 0.01). Almost all patients (98%) of the MMC+bevacizumab group were drop‐free at 12 months and nearly half (44%) had an IOP in the single‐digit range (≤ 9 mmHg) at 24 months. Complication rates were low and similar between groups, with no systemic adverse events.
Conclusions
Adding perioperative intracameral bevacizumab to the standard of care use of MMC in trabeculectomy seems to allow for sustained low IOP outcomes. Furthermore, it seems to decrease the need for additional interventions during the early post‐operative period.
Instillation therapy for non–muscle-invasive bladder cancer (NMIBC) reduces recurrences but is associated with side effects. Preoperative instillation of chemotherapy could potentially be associated ...with fewer side effects compared with adjuvant instillations and in some patients make tumour resection (transurethral resection of the bladder tumour TURBT) superfluous.
To investigate tumour response and adverse events related to short-term, intensive chemoresection with mitomycin C compared with adjuvant instillations in patients with recurrent NMIBC.
A randomised, controlled trial was conducted in two urological departments in Denmark from January 2018 to June 2019. In total, 120 participants with a history of Ta bladder tumours, low grade or high grade, were included upon recurrence.
Intravesical mitomycin C (40 mg/40 ml) three times a week for 2 wk in the intervention group (59 patients) was compared with TURBT and six weekly adjuvant instillations in the control group (61 patients).
Tumour response was evaluated in the intervention group by flexible cystoscopy after 4 wk. Side effects were prospectively registered in both groups using the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Groups were compared using χ2 or Fisher's exact test.
Complete tumour response was seen in 33 participants (57%) in the intervention group. Fewer adverse events were reported in the intervention group than in the control group. Two patients in each group ceased instillation treatment due to adverse events. The main limitation is the current lack of long-term follow-up.
Short-term, intensive chemoresection yields a tumour response of 57%. Hence, only half of those treated with chemoresection needed TURBT. The treatment was furthermore associated with fewer clinically significant side effects. Owing to small numbers, further investigations on Ta high-grade tumours are needed.
We compared a nonsurgical treatment with standard treatment in patients with superficial bladder tumours. We found it to be safe and able to avoid surgery in more than half of the patients.
Short-term, intensive chemoresection for recurrent intermediate- or high-risk Ta non–muscle-invasive bladder cancer is feasible with a complete tumour response in 57% of patients. Hence, only half of the patients treated with chemoresection needed transurethral resection of the bladder tumour. The treatment was furthermore associated with fewer clinically significant side effects. Long-term follow-up will demonstrate whether chemoresection may serve as a standard nonsurgical treatment option.
PDF
