Mitomycin C Research Articles

Effect of mitomycin C on the corneal endothelial cells of Saudi patients with myopia after transepithelial photorefractive keratectomy: a two-armed cohort study

AIM: 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. METHODS: 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/mm2), average (μm2), standard deviation (μm2), coefficient of variation (CV%), ECmax, ECmin, 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. RESULTS: 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 (P=0.644), change in CV (P=0.374), and change in the percentage of hexagonality of EC (P=0.164) at W1. However, the use of MMC was a significant predictor of changes in CV (P=0.014) and the change in the percentage of hexagonality of EC (P=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. CONCLUSION: 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.

Pigtail with self-retaining bicanalicular intubation combined with Mitomycin C for the treatment of acquired lower punctal stenosis.

The pigtail was used to create an opening at the lower punctal site in grade 0 stenosis with insertion of self-retaining tube and Mitomycin C (MMC). The patients with acquired lower punctal stenosis (grade 0) were divided randomly into equal groups, Group A: were treated with pigtail and MMC 0.02% and Group B: were treated with pigtail alone. The pigtail was inserted through the upper punctum until its tip reached the occluded punctum, this site was incised with a scalpel (No. 11). A self-retaining bicanalicular tube was then placed. Results of 36 eyes from 26 patients were included. No differences were observed between both groups regarding epiphora score, FDD test and punctal size preoperatively. The postoperative epiphora score, there were significant differences at 1month (P = 0.035), 3months (P = 0.005), and 6months after removal (P < 0.001). The FDD test, there were significant differences at 6months (P = 0.045), 1month (P = 0.021), 3months (P = 0.012), and 6months post tube removal (P = 0.005). The punctal size, both groups differed at 1month (P = 0.045), 3months (P = 0.03), and 6months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube. The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.

Enhancing the Efficacy of HIPEC Through Bromelain: A Preclinical Investigation in Appendiceal Cancer.

Appendiceal cancer (AC) excessive mucin production is a barrier to heated intraperitoneal chemotherapy (HIPEC) drug delivery. Bromelain is a pineapple stem extract with mucolytic properties. We explored bromelain treatment effects against mucinous AC in a patient-derived tumor organoid (PTO) model and an AC cell line. PTOs were fabricated from tumor specimens obtained from patients with AC undergoing cytoreductive surgery with HIPEC. PTOs underwent HIPEC treatment with bromelain, cisplatin, and mitomycin C (MMC) at 37°C and 42°C with and without bromelain pretreatment. From October 2020 to May 2023, 16 specimens were collected from 13 patients with low-grade (12/16, 75%) and high-grade AC (4/16, 25%). The mucin-depleting effects of bromelain were most significant in combination with N-acetylcysteine (NAC) compared with bromelain (47% versus 10%, p = 0.0009) or NAC alone (47% versus 12.8%, p = 0.0027). Bromelain demonstrated > 31% organoid viability reduction at 60 min (p < 0.001) and > 66% in 48 h (p < 0.0001). Pretreatment with bromelain increased cytotoxicity of both cisplatin and MMC HIPEC conditions by 31.6% (p = 0.0001) and 35.5% (p = 0.0001), respectively. Ki67, CK20, and MUC2 expression decreased after bromelain treatment; while increased caspase 3/7 activity and decreased Bcl-2 (p = 0.009) and Bcl-xL (p = 0.01) suggest induction of apoptosis pathways. Furthermore, autophagy proteins LC3A/B I (p < 0.03) and II (p < 0.031) were increased; while ATG7 (p < 0.01), ATG 12 (p < 0.04), and Becline 1(p < 0.03), expression decreased in bromelain-treated PTOs. Bromelain demonstrates cytotoxicity and mucolytic activity against appendiceal cancer organoids. As a pretreatment agent, it potentiates the cytotoxicity of multiple HIPEC regimens, potentially mediated through programmed cell death and autophagy.

The effect of adjuvant Mitomycin C during vitrectomy on functional and anatomical outcomes in patients with severe diabetic tractional retinal detachment.

To evaluate the effect of adjuvant Mitomycin C (MMC) use on the anatomical and functional success of vitreoretinal surgery (VRS) in severe diabetic tractional retinal detachment (dTRD) patients. A retrospective analysis of consecutive patients undergoing VRS due to severe dTRD was conducted. Patients were categorized into those who received 20µg/0.1mL MMC via MMC sandwich method (Group 1) and those who did not (Group 2). Demographics, surgical characteristics, visual outcomes, and complications that may related to MMC were analyzed. A total of 25 eyes were included, 13 in Group 1 and 12 in Group 2. No statistical difference was observed in baseline characteristics between the groups. The mean best-corrected visual acuity was 1.90 ± 0.43 logMAR and 1.93 ± 0.41 logMAR preoperatively and 1.60 ± 0.78 logMAR and 1.56 ± 0.78 logMAR postoperatively in Groups 1 and 2, respectively (p = 0.154). The postoperative mean intraocular pressure was 16.23 ± 2.55mmHg and 13.08 ± 4.94mmHg in Groups 1 and 2, respectively (p = 0.225). The rate of re-surgery was significantly lower in Group 1 (0% vs. 41.7% in Group 2, p = 0.015). Retina was attached in all patients at the last visit. No MMC-related complication was recorded. Intraoperative adjuvant MMC application for severe dTRD significantly reduces re-surgery rates with good anatomical and functional outcomes safely.

A Comparison of Deep sclerectomy Outcomes in Eyes with Pseudoexfoliation versus Primary Open Angle Glaucoma

PurposeTo compare outcomes of augmented deep sclerectomy surgery (DS) with mitomycin C.(MMC) between pseudoexfoliative glaucoma (PEXG) and primary open angle.glaucoma (POAG) patients.. DesignRetrospective cohort study MethodsRetrospective review of patients undergoing DS surgery at the University Eye Hospital Bonn, Germany, from 04/2021 to 09/2022. We performed a matched-pair analysis.between eyes with PEXG (group 1, n=45) and eyes with POAG (group 2, n=45). Results90 eyes of 85 patients were included. Complete and qualified success rates for Groups.1 and 2 at one year were 55.6% and 86.7% (p=0.002) and 91.1% and 93.3% (p=0.78).for ≤21mmHg, and 55.6% and 86.7% (p=0.002) and 88.9% and 93.3% (p=0.53) for.≤18mmHg respectively..Mean preoperative IOP decreased from 21.11 mmHg in group 1 and 19.64 mmHg in.group 2 (p=0.31) to 13.64 mmHg and 11.42 mmHg after surgery, respectively, whilst it.was significantly lower in eyes with POAG (p=0.01). The number of pressure-lowering.drops was also significantly lower in eyes with POAG after 12 months (PEXG: 0.58;.POAG: 0.18; p=0.01). Eyes with PEXG had a significantly higher rate of Nd:YAG laser.goniopuncture (PEXG: 64.4%, POAG: 40%, p=0.02)..Postoperative complications occurred in 6 eyes (6.7%) with no vision-threatening.sequelae in either group.There were no significant differences between complication.rates in the two groups (p=0.18) ConclusionsDS is a safe and effective procedure for lowering IOP in eyes with both POAG and PEXG, with lower overall IOP levels being achieved in eyes with POAG. Significantly more postoperative laser goniopunctures were needed in eyes with PEXG.

Wound Modulations in Glaucoma Surgery: A Systematic Review

Excessive fibrosis and resultant poor control of intraocular pressure (IOP) reduce the efficacy of glaucoma surgeries. Historically, corticosteroids and anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5-FU), have been used to mitigate post-surgical fibrosis, but these have unpredictable outcomes. Therefore, there is a need to develop novel treatments which provide increased effectiveness and specificity. This review aims to provide insight into the pathophysiology behind wound healing in glaucoma surgery, as well as the current and promising future wound healing agents that are less toxic and may provide better IOP control.

Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB.

Mitomycin C (MMC) repair factor A (mrfA) and factor B (mrfB), encode a conserved helicase and exonuclease that repair DNA damage in the soil-dwelling bacterium Bacillus subtilis. Here we have focused on the characterization of MrfB, a DEDDh exonuclease in the DnaQ superfamily. We solved the structure of the exonuclease core of MrfB to a resolution of 2.1 Å, in what appears to be an inactive state. In this conformation, a predicted α-helix containing the catalytic DEDDh residue Asp172 adopts a random coil, which moves Asp172 away from the active site and results in the occupancy of only one of the two catalytic Mg2+ ions. We propose that MrfB resides in this inactive state until it interacts with DNA to become activated. By comparing our structure to an AlphaFold prediction as well as other DnaQ-family structures, we located residues hypothesized to be important for exonuclease function. Using exonuclease assays we show that MrfB is a Mg2+-dependent 3'-5' DNA exonuclease. We show that Leu113 aids in coordinating the 3' end of the DNA substrate, and that a basic loop is important for substrate binding. This work provides insight into the function of a recently discovered bacterial exonuclease important for the repair of MMC-induced DNA adducts.

The efficacy of adjunctive mitomycin C and/or anti-VEGF agents on glaucoma tube shunt drainage device surgeries: a systematic review.

The effectiveness of mitomycin C (MMC) in trabeculectomy has long been established. The aim of this review is to evaluate the efficacy and safety of adjunctive agents in tube shunt drainage device surgery for glaucoma or ocular hypertension, since controversy still exists regarding their benefit. We searched CENTRAL, PubMed, Embase, Web of Science, Scopus, and BASE for RCTs, which have used adjuvant antimetabolites-either MMC or 5-Fluorouracil (5-FU)-and/or anti-vascular endothelial growth factors (anti-VEGF) agents. The main outcome was IOP reduction at 12 months. Ten studies met our inclusion criteria. Nine used the Ahmed Glaucoma Valve (AGV) implant, while the double-plate Molteno implant was used in one study. Four studies used MMC. The remaining six studies used an anti-VEGF drug - either bevacizumab, ranibizumab or conbercept. Only one MMC-study reported a significant difference in the IOP reduction between groups at 12 months, favouring the MMC group (55% and 51%; p < 0.01). A significant difference was also reported by two out of five bevacizumab-studies, both favouring the bevacizumab group (55% and 51%, p < 0.05; 58% and 27%, p < 0.05), with the highest benefit seen in neovascular glaucoma cases, especially when panretinal photocoagulation (PRP) was also used. Neither ranibizumab nor conbercept were found to produce significant differences between groups regarding IOP reduction. There is no high-quality evidence to support the use of MMC in tube shunt surgery. As for anti-VEGF agents, specifically bevacizumab, significant benefit seems to exist in neovascular glaucoma patients, especially if combined with PRP.

Mitomycin C and its analog trigger cytotoxicity in MCF-7 and K562 cancer cells through the regulation of RAS and MAPK/ERK pathways

Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks (ICLs) between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer cells with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 deficient) cells in a TP53-independent mode. We also found that MC/DMC regulate AKT activation in a TP53-dependent manner and that AKT deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment. RAS proteins are known players in the upstream mediated signaling of p21WAF1/CIP1 activation that leads to control of cell proliferation and cell death. Thus, this prompted us to investigate the effect of both drugs on the expression of RAS proteins and regulation of the MAPK/ERK signaling pathways in MCF-7 and K562 cancer cells. To accomplish this goal, we performed comparative label free proteomics profiling coupled to bioinformatics/complementary phosphoprotein arrays and Western blot validations of key signaling molecules. The MAPK/ERK pathway exhibited an overall downregulation upon MC/DMC treatment in MCF-7 cells but only DMC exhibited a mild downregulation of that same pathway in TP53 mutant K562 cells. Furthermore, treatment of MCF-7 and K562 cell lines with oligonucleotides containing the interstrand crosslinks (ICLs) formed by MC or DMC shows that both ICLs had a stronger effect on the downregulation of RAS protein expression in mutant TP53 K562 cells. We discuss the implication of this regulation of the MAPK/ERK pathway in relation to cellular TP53 status.

Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction.

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction. We denoted 198 and 71 unique, differentially expressed proteins (DEPs) in the MMC-treated HCAECs and HITAECs, respectively; only 4 DEPs were identified in both the HCAECs and HITAECs. In the MMC-treated HCAECs, 44.5% of the DEPs were upregulated and 55.5% of the DEPs were downregulated, while in HITAECs, these percentages were 72% and 28%, respectively. The denoted DEPs are involved in the processes of nucleotides and RNA metabolism, vesicle-mediated transport, post-translation protein modification, cell cycle control, the transport of small molecules, transcription and signal transduction. The obtained results could improve our understanding of the fundamental basis of atherogenesis and help in the justification of genotoxic stress as a risk factor for atherosclerosis.

Collaborative Study of Thresholds for Mutagens: Adaptive Responses in the Micronucleus Test and Gene Induction by Mutagenic Treatments.

We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45A and P21, were induced in a dose- and time-dependent manner. Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.

PRESERFLO MicroShunt in Severe Myopia: A Case Report and Review of the Literature.

The PRESERFLO™ MicroShunt (MP; Santen Inc., Osaka, Japan) is a minimally invasive bleb surgery (MIBS) manufactured to treat primary open-angle glaucoma (POAG), with lower postoperative adverse effects than with conventional filtering surgeries. We describe here the case study of a 58-year-old woman who presented with bilateral severe myopia with bilateral advanced POAG and unreached target pressure under quadritherapy, who was successfully managed by PM surgery. A review of the literature completes our observation. At presentation, the patient had a spherical equivalent of - 7.50 RE and - 7.75 LE with an IOP of 22 mmHg right and left eye (RLE) under quadritherapy, and with severe bilateral visual field loss, including scotomas within the central 5°. The patient presented with systemic hypertension treated with an antihypertensive drug. Two selective laser trabeculoplasties (SLT), performed 3 months apart, were first tried on the LE, without any change in IOP at 2 months. After considering the high risk of postoperative complications, a PM operation was proposed, with a targeted IOP in the mid-fifteens RLE. The patient's eyes underwent PM surgery with mitomycin C (MMC) MMC0.2 mg/mL for 3 minutes without any complications. The LE required 2 consecutive needlings with 1 mL MMC0.2 mg/mL. At 24 months after surgery, the two eyes gave successful results without the need for any additional medical therapy, and with well-functioning conjunctival blebs. The PM was an effective alternative to the gold standard trabeculectomy in our severely myopic patient. A comparative study between conventional filtering operations and this MIBS in highly myopic patients would confirm our observation.

Abstract 7130: Dysregulated DNA repaired elicited by type 1 PRMT inhibitor in clear cell renal cell carcinoma enables development of novel combination therapies

Abstract Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer, notorious for its resistance to treatment and dismal prognosis. Advanced or metastatic cases on average display an 8% 5-year survival rate. Given the considerable number of diagnoses in advanced stages, it is evident that we require innovative therapeutic approaches. Our lab has developed a methodology to establish cell lines from tumors and adjacent normal tissues sourced from patients. Consequently, we've amassed a collection of cell lines, including those from patient-derived ccRCC and normal kidney cells. Using these ccRCC models, we demonstrated that the type I protein arginine methyltransferase inhibitor, MS023, elicits a dysregulated DNA repair phenotype. RNA-Seq analysis of ccRCC cells treated with MS023 unveiled a marked downregulation of genes associated with the homologous recombination (HR) pathway for double-strand break repair and the Fanconi Anemia (FA) pathway for interstrand crosslink (ICL) repair. In a follow-up investigation using paired normal and cancerous cell lines from the same patient, we identified resistance to MS023 in normal kidney cells that is not mirrored in the corresponding ccRCC cell line. This hints at a potential therapeutic window and provides a strong rationale for clinical pursuit. Poly-ADP ribose polymerase (PARP) inhibitors are known to yield a synergistic effect when employed in HR-deficient diseases, such as BRCA-deficient breast cancers. Since MS023 induces an HR-deficient phenotype, we hypothesize that combining it with Talazoparib, a PARP inhibitor, will produce a similar synergistic effect. Additionally, mitomycin C (MMC) is a clinically approved compound that induces ICLs. As MS023 impedes ICL repair by downregulating crucial ICL-repairing genes, combining these two drugs should likewise generate a synergistic effect. Through a drug screen across two of our ccRCC cell lines, we discovered that the cells exhibit sensitivity to various PARP inhibitors. Employing synergy checkerboard assays and the highest single-agent model of synergy, we have found that the combination of MS023 and Talazoparib, as well as the combination of MS023 and MMC, demonstrate synergy, significantly reducing cellular viability at lower doses of the combination treatments compared to mono-treatment conditions at their respective doses. Preliminary in vivo studies using patient-derived xenograft models have revealed that both MS023 and Talazoparib are well-tolerated in mice, both when administered individually and in combination. Our current knowledge base indicates that MS023 holds promise for clinical investigation, both as a standalone treatment and in combination with Talazoparib or MMC. These results present an exciting opportunity to shed new light on the challenging therapeutic landscape faced by ccRCC patients today. Citation Format: Karen Arevalo, Joseph Walton, Jalna Meens, Angel Sau Ni Ng, Laurie Ailles. Dysregulated DNA repaired elicited by type 1 PRMT inhibitor in clear cell renal cell carcinoma enables development of novel combination therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7130.

Abstract 5052: Novel drug resistance mechanisms and drug targets in BRAF mutated peritoneal metastasis from colorectal cancer

Abstract Objective: Patients with peritoneal metastasis (PM) from colorectal cancer (CRC) have inferior prognosis and respond poorly to chemotherapy compared to other metastatic locations. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC. Design: Tumor samples from a Norwegian national cohort of 230 patients undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations between molecular findings and clinical data were analyzed. mRNA sequencing was conducted on a subset of thirty samples to compare gene expression in tumors harboring mutations in the BRAF or KRAS oncogenes and wild-type tumors. Results: Almost one-third of the patients had mutations in the BRAF oncogene, which were associated with RNF43/R-Spondin aberrations and low expression of negative Wnt regulators (ligand dependent Wnt activation). This molecular profile, with high abundance in PM, could be an underlying mechanism promoting aggressive tumor biology that facilitates metastasis to the peritoneal cavity, and could contribute to the observed poor overall survival of this patient subgroup. BRAF mutations were also associated with gene expression changes in transport solute carrier proteins and drug metabolism enzymes that could influence the efficacy of MMC and irinotecan, commonly used in PM-CRC treatment. BRAF-mutated tumors exhibited increased expression of BTN immune checkpoint molecules, and targeting these checkpoints in addition to ligand dependent Wnt activation could be two novel targeted therapy approaches. Conclusion: BRAF mutations were associated with particularly poor survival in this cohort, possibly related to altered drug transport and metabolism conferring resistance to MMC and irinotecan. Two potential novel therapeutic approaches were identified, suggesting specific targeting of BTN immune checkpoint molecules and the use of inhibitors to target ligand-dependent Wnt activation. Citation Format: Christin Lund-Andersen, Annette Torgunrud, Chakravarthi Kanduri, Vegar J. Dagenborg, Ida S. Frøysnes, Mette M. Larsen, Ben Davidson, Stein Larsen, Kjersti Flatmark. Novel drug resistance mechanisms and drug targets in BRAF mutated peritoneal metastasis from colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5052.

Reassessing Trabeculectomy: A Long-Term Study with Stringent Success Criteria.

Background: The aim was to evaluate the long-term outcome and efficacy of primary trabeculectomy with adjunctive mitomycin c (MMC) for treating glaucoma. Methods: We examined the medical records of 286 eyes that underwent trabeculectomy between 2008 and 2009 at the University Eye Hospital in Freiburg, Germany. Preoperative and follow-up data were collected, including intraocular pressure (IOP) measurements, surgical glaucoma interventions, and prescribed glaucoma medication. The first success criterion was defined as IOP ≤ 15 mmHg with no use of pressure-lowering medication by the patient, the second criterion was defined as the absence of surgical revision, and the third criterion as no further IOP-lowering surgery excluding early revisions following trabeculectomy. Statistical analyses comprised Cox regression and Kaplan-Meier survival estimations. Results: The mean follow-up duration was 1841 days (5 years). The mean preoperative IOP was 26.1 mmHg. Evaluating the success criteria at the time of average follow-up yielded a success rate of only 25% for the first criterion but 80% for both the second and third success criteria. Conclusions: The findings suggest that trabeculectomy with adjunctive MMC can be an effective procedure for permanently lowering IOP. However, surgical revisions and/or further glaucoma surgeries might still be needed. The long-term success rate is lower in comparison to previous research, which may be explained by the stricter success criteria in our study.

Machine learning-assisted prediction of trabeculectomy outcomes among patients of juvenile glaucoma by using 5-year follow-up data.

To develop machine learning (ML) models, using pre and intraoperative surgical parameters, for predicting trabeculectomy outcomes in the eyes of patients with juvenile-onset primary open-angle glaucoma (JOAG) undergoing primary surgery. The study included 207 JOAG patients from a single center who met the following criteria: diagnosed between 10 and 40 years of age, with an IOP of >22 mmHg in the eyes on two or more occasions, open angle on gonioscopy in both eyes, with glaucomatous optic neuropathy, and requiring a trabeculectomy for IOP control. Only the patients with a minimum 5-year follow-up after surgery were included in the study. A successful surgical outcome was defined as IOP ≤18 mmHg (criterion A) or 50% reduction in IOP from baseline (criterion B) 5 years after trabeculectomy. Feature selection techniques were used to select the most important contributory parameters, and tenfold cross-validation was used to evaluate model performance. The ML models were evaluated, compared, and prioritized based on their accuracy, sensitivity, specificity, Matthew correlation coefficient (MCC) index, and mean area under the receiver operating characteristic curve (AUROC). The prioritized models were further optimized by tuning the hyperparameters, and feature contributions were evaluated. In addition, an unbiased relationship analysis among the parameters was performed for clinical utility. Age at diagnosis, preoperative baseline IOP, duration of preoperative medical treatment, Tenon's thickness, scleral fistulation technique, and intraoperative mitomycin C (MMC) use, were identified as the main contributing parameters for developing efficient models. The three models developed for a consensus-based outcome to predict trabeculectomy success showed an accuracy of >86%, sensitivity of >90%, and specificity of >74%, using tenfold cross-validation. The use of intraoperative MMC and a punch for scleral fistulation compared to the traditional excision with scissors were significantly associated with long-term success of trabeculectomy. Optimizing surgical parameters by using these ML models might reduce surgical failures associated with trabeculectomy and provide more realistic expectations regarding surgical outcomes in young patients.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.

Topical 5-fluorouracil 1% for moderate to extensive ocular surface squamous neoplasia in 73 consecutive patients: Primary versus secondary treatment

ImportanceOcular surface squamous neoplasia (OSSN) is a spectrum of malignancies that generally includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). OSSN can be treated with topical therapies including interferon α-2b (IFN), mitomycin C (MMC), or 5-fluorouracil 1% (5FU). Recently, due to unavailability of IFN and toxicity associated with MMC, therapy has shifted towards 5FU. ObjectiveHerein, we compare the use of 5FU 1% as a primary versus (vs) secondary treatment regimen in eyes with moderate to extensive OSSN. Design Setting and ParticipantsRetrospective cohort study of 73 consecutive patients with unilateral moderate to extensive OSSN treated at a single tertiary ocular oncology center from 2016 to 2023. Mean follow up time was 478.2 days overall, with 283.0 days for primary 5FU group and 860.3 days for secondary 5FU group. InterventionTopical 5FU 1% 4 times daily for 2 weeks with option for 2-weekly extension until tumor control, either as primary treatment or as secondary treatment to surgical resection, topical IFN or topical MMC, or cryotherapy. Main OutcomesOutcome measures included tumor response, need for additional surgery, complications, and visual outcomes. ResultsA comparison (primary vs secondary treatment) revealed no difference in mean tumor basal dimension (19.6 vs 17.2 mm, P = 0.46), thickness (3.7 vs 3.4 mm, P = 0.64), or tumor extent (4.4 vs 4.5 clock hours, P = 0.92). The primary treatment group showed greater complete tumor control (77% vs 38%, P = 0.04). Multivariable analysis comparison (primary vs secondary treatment) showed primary treatment more likely to achieve complete tumor control (P = 0.01). There was no difference in the complication rate from 5FU treatment between the groups. There was no difference in visual outcome, and no tumor-related metastasis (0%) or death (0%). Conclusion and RelevanceTopical 5FU 1% is efficacious and safe as a primary or secondary treatment for moderate to extensive OSSN. Tumors treated with primary 5FU 1% demonstrated more complete resolution. In patients with moderate to extensive OSSN, primary treatment with topical 5FU 1% may be warranted.

Subscleral trabeculectomy with Ologen implant versus mitomycin C in primary infantile glaucoma

Abstract: PURPOSE: The purpose of this study is to compare the effect of subscleral trabeculectomy (SST) augmented with mitomycin C (MMC) versus Ologen implant as secondary procedures for treatment of primary congenital glaucoma. METHODS: This is a retrospective study evaluating records of 38 eyes that had undergone SST with MMC (Group M, 17 eyes) versus Ologen (Group O, 21 eyes) by the authors of the study. The study primary endpoint was set at 5–9 months postoperatively, and the secondary endpoint was the last follow-up. A successful outcome was an intraocular pressure (IOP) ≤18 mmHg for infants &lt;1 year and ≤20 mmHg for older ones. RESULTS: The follow-up duration was 1.25–51 (26.79 ± 27.583) months in Group M and 0.25–103 (22.86 ± 28.991) months in Group O (P = 0.673). The mean preoperative IOP was 28.06 ± 3.929 in Group M and 26.95 ± 6.095 in Group O (P = 0.522). A reduction of IOP was significant in Group M at all follow-up visits but starting at the 4th postoperative month in Group O. Recorded IOP in Groups M and O, respectively, was 14.9 ± 6.437 and 12.1 ± 5.043 at the primary endpoint and 22.35 ± 8.536 and 22.52 ± 10.152 (P &gt; 0.05) at the secondary endpoint. A successful outcome was achieved in Groups M and O, respectively, in 47.1% and 47.6% at the primary endpoint and in 47.1% and 52.4% at the secondary endpoint (P &gt; 0.05). Cataract, posterior synechiae, and pupillary abnormalities were insignificantly different in both the groups (P = 0.623). CONCLUSION: Ologen implant was comparable to MMC in terms of efficacy and safety. Reoperations are inadvisable before 4 months of Ologen implants.

Interferon alpha 2b or Mitomycin-C as Adjuvant Therapy of Pigmented Conjunctival Malignancy : A Literature Review

Abstract&#x0D; Introduction &amp; Objectives : To compare the efficacy and safety between Mitomycin C (MMC) and Interferon alpha-2b (IFN-α2b) eye drops as adjuvant therapy for conjunctival melanoma.&#x0D; Methods : Literature searching was conducted using PubMed, ScienceDirect, and Google Scholar. All studies that met the inclusion and exclusion criteria were categorized based on the level of evidence. The data of patients demographics, staging of disease, type of treatments, and outcomes of this review including local control rate, side effect, and recurrence and/or metastases were also reported.&#x0D; Results : From twelve articles, topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable complete remission rate. Local control (complete remission) of IFN α-2b group is 46%, while in MMC group is 57%. The most side effect of MMC group were severe corneal-conjunctival irritation and corneal defect, while the IFN α-2b group showed mild side effect. Recurrency rate of IFN α-2b group and MMC group both is 35%. Metastases case of IFN α-2b group is 3.8%, while none of cases from MMC group metastases.&#x0D; Conclusion : Topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable local control rate even though the recurrency rate also relatively high. Both medications showed promising results to reduce residual tumor size after wide excision surgery, preserving eye so reduce the chance of exenteration in various stages. It is important to consider adjuvant therapy following wide excision surgery as the first line treatment.