Excision combined with ocular surface reconstruction followed by topical chemotherapy for ocular surface squamous neoplasia.

PURPOSE: To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence. RESULTS: Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence. CONCLUSION: Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA.

Safety and Efficacy of Mitomycin C: Augmented Trabeculectomy: Subtenon's Injection versus Sponge Application.

Objective: The objective of the study was to study the safety and efficacy of subtenon injection of mitomycin C (MMC) versus sponge application of MMC during trabeculectomy. Materials and Methods: Thirty-seven patients having primary glaucoma warranting trabeculectomy were enrolled in the study and their forty eyes were alternately allocated into either of the two groups: subtenon injection (ST) of 0.1 mL of 0.01% of MMC or sponge application (SP) of 0.02% of MMC and were operated by a single surgeon and followed for 3 months. The outcome was analyzed primarily based on reduction in intraocular pressure (IOP) and bleb morphology. Results: Similar outcome in terms of complete success (ST - 90% and SP - 85%), qualified success (ST - 5% and SP - 5%), and failure rate (ST - 5% and SP - 10%) was seen at the end of 3 months. The absolute reduction in IOP from the baseline was -10.00 ± 3.67 mmHg (-41.2% ± 12.30) in ST versus -8.90 ± 5.56 mmHg (-35.9% ± 16.1) in the SP group at the end of 3 months. At the end of 3 months, blebs in the ST group had low-to-medium height and in the SP group had low height. Blebs in both the groups were diffuse with mild vascularity. Antiglaucoma medications required postoperatively were 0.20 ± 0.62 versus 0.40 ± 1.10 in the ST and SP group, respectively. The duration of surgery was 19.85 ± 0.75 min in the ST group versus 22.50 ± 0.51 min in the SP group. Conclusion: Subtenon injection of MMC is as efficacious and safe as the conventional sponge application technique.

Increased Expression Level of Human Blood Clotting Factor VIII Using NS0 Cell Line as a Host Cells.

Background: Coagulation factor VIII (FVIII) is applied for spontaneous hemorrhaging inhibition and excessive bleeding after trauma in patients with hemophilia A. High-quality human recombinant factor VIII (rFVIII) has been produced relatively in large quantities in cultured mammalian cells. NS0 is one of the most common mammalian cell lines for therapeutic protein production. Production of rFVIII has increased due to low FVIII expression levels and rising demand for hemophilia A prophylactic treatment. Several methods have been developed to prevent cell cycle progression in mammalian cells for increased recombinant protein yields. Objective: The aim of the study was to investigate the level of recombinant BDD-FVIII expression in NS0 mouse myeloma cells. Additionally, the study aimed to determine the effects of chemical drugs, Mitomycin C, Lovastatin, and Metformin on the secretion of FVIII through cell cycle arrest. Materials and Methods: We cultured NS0 cells and transfected them with the 2 µg pcDNA3-hBDDFVIII plasmid by Lipofectamine 3000. The cells were treated with 10 µg.mL-1 Mitomycin C, 20 µM Lovastatin, and 20 mM Metformin separately. After 24 and 48 hours, the samples were collected and, protein expression was analyzed using RT-PCR, Dot blot, and ELISA. Results: A higher protein expression level was observed in treated cells 24h and 48h after treatment with all three drugs. According to real-time PCR, Metformin treatment resulted in the highest expression level within 24 h (P=0.0026), followed by Mitomycin C treatment within 48 h (P=0.0030). Conclusion: The NS0 cell line can be regarded as a suitable host for FVIII production. FVIII protein expression level was increased by using Lovastatin, Metformin, and Mitomycin C drugs. Further investigations are suggested, and the potential application of these drugs to increase recombinant protein yield can be used to produce therapeutic proteins in the industry.

Secondary corneal keloid: a report of two cases.

We conducted clinical and histological evaluations on two male patients who presented with corneal keloid. One patient had a history of corneal trauma due to contact with boiling sunflower oil, while the other had undergone pterygium removal. Upon slit lamp examination, the corneal lesions were identified as single, well-circumscribed, pearly white nodules with a smooth surface. We successfully removed these nodules using a combination of superficial keratectomy and the application of mitomycin C. Light microscopy analysis of the excised nodules revealed hyperplastic epithelium, disrupted Bowman's layer, and irregularly arranged abundant collagen fibers within the stroma. Notably, there was no recurrence of the lesions in either case within six months following the surgical excision. Secondary corneal keloids should be considered as a potential diagnosis in patients with elevated corneal nodules, especially when there is a history of ocular surface trauma or surgery.

Pterygium recurrence following preoperative topical Mitomycin C and 5-Fluorouracil eyedrops.

INTRODUCTION: Various adjuvant therapies have been used to prevent recurrence after pterygium excision. However, no single agent has been proven to be a gold standard for completely preventing recurrence with no associated complications. PURPOSE: This study aims to compare the recurrence rate following preoperative topical mitomycin C (MMC) and 5-fluorouracil (5-FU) eye drops in pterygium excision surgery. METHODS: In this interventional longitudinal comparative study, 90 patients with primary pterygium attending the Ophthalmology Clinic were enrolled and randomized into three equal groups of 30 each. Groups A, B, and C received preoperative 0.02% MMC eye drops, 1% 5-FU eyedrops, and placebo treatment respectively for one week before surgery followed by pterygium excision with conjunctival autograft and histopathological analysis. Patients were followed for 6months to identify recurrence. RESULTS: At the end of the 6months, the recurrence rate in the preoperative MMC group (6.7%) was less than the 5-FU (13.3%) and placebo (20%) groups. The histopathological findings were consistent with pterygium tissues. There were high grades of inflammation, degeneration, and vascularization in both the MMC and 5-FU groups in the specimens which recurred within a period of 6months. Five patients had a novel finding of smooth muscle choristoma tissue with bundles of smooth muscle cells and fat cells clustered among the conjunctival tissue. CONCLUSION: Based on our study results, we demonstrate that preoperative topical MMC and 5-FU eyedrops have efficacy in reducing recurrence in pterygium surgeries. The eyedrop route of administration has been proven to be an effective and easier alternative, enabling us to monitor for adverse effects of adjuvant drugs. Histopathological evaluation provides indices to predict features of future recurrence in pterygium specimens. This is the first study in which the efficacy of preoperative MMC and 5-FU is studied in eyedrop formulation along with histopathological correlation with recurrence.

Conjunctival melanoma with pronounced central corneal invasion: One-year relapse free follow-up.

Purpose: Conjunctival melanoma with large corneal involvement is a rarity. We here present a case of conjunctival melanoma with pronounced central corneal involvement. Observation: A 69-year-old fair white male presented with a visual axis impeding corneal nodular lesion with associated conjunctival melanosis. Tumor excision with intraoperative mitomycin c (0.02 %) application for 180 seconds and amniotic membrane transplantation for defect coverage was performed in retrobulbar anesthesia. Histopathological evaluation revealed the nodular lesion to be a conjunctival melanoma (pT1a) with associated conjunctival melanocytic intraepithelial lesion (C-MIL). Conclusion and importance: Most conjunctival melanomas with corneal affection reach a radial corneal involvement of 1 mm. The here reported case accounted for 4 mm, which is seldom and therefore an important report. Surgical excision followed by intraoperative and postoperative mitomycin c exposure was a successful primary treatment. Currently there are no signs of tumor relapse in any part of the eye or the organism 12 months after excision. However, the long-term follow-up needs to be awaited.

Mitomycin C as an Anti-Persister Strategy against Klebsiella pneumoniae: Toxicity and Synergy Studies.

The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.

Establishment and Characterization of Three Human Ocular Adnexal Sebaceous Carcinoma Cell Lines.

Ocular adnexal sebaceous carcinoma (SebCA) represents one of the most clinically problematic periocular tumors, often requiring aggressive surgical resection. The pathobiology of this tumor remains poorly understood, and few models exist that are suitable for preclinical testing. The aim of this study was to establish new cell lines to serve as models for pathobiological and drug testing. With patient consent, freshly resected tumor tissue was cultured using conditional reprogramming cell conditions. Standard techniques were used to characterize the cell lines in terms of overall growth, clonogenicity, apoptosis, and differentiation in vitro. Additional analyses including Western blotting, short tandem repeat (STR) profiling, and next-generation sequencing (NGS) were performed. Drug screening using mitomycin-C (MMC), 5-fluorouricil (5-FU), and 6-Diazo-5-oxo-L-norleucine (DON) were performed. JHH-SebCA01, JHH-SebCA02, and JHH-SebCA03 cell lines were established from two women and one man undergoing surgical resection of eyelid tumors. At passage 15, they each showed a doubling time of two to three days, and all could form colonies in anchorage-dependent conditions, but not in soft agar. The cells contained cytoplasmic vacuoles consistent with sebaceous differentiation, and adipophilin protein was present in all three lines. STR profiling confirmed that all lines were derived from their respective patients. NGS of the primary tumors and their matched cell lines identified numerous shared mutations, including alterations similar to those previously described in SebCA. Treatment with MMC or 5-FU resulted in dose-dependent growth inhibition and the induction of both apoptosis and differentiation. MYC protein was abundant in all three lines, and the glutamine metabolism inhibitor DON, previously shown to target high MYC tumors, slowed the growth of all our SebCA models. Ocular adnexal SebCA cell lines can be established using conditional reprogramming cell conditions, and our three new models are useful for testing therapies and interrogating the functional role of MYC and other possible molecular drivers. Current topical chemotherapies promote both apoptosis and differentiation in SebCA cells, and these tumors appear sensitive to inhibition or MYC-associated metabolic changes.

"Long-term safety and efficacy of injection mitomycin C(MMC) versus sponge application in trabeculectomies".

AIMS: To compare the long-term safety and efficacy of subconjunctival injection mitomycin C(MMC) with conventional sponge applied MMC during trabeculectomy. METHODS AND MATERIAL: Retrospective analysis of 98 eyes of 90 patients who underwent trabeculectomy with Mitomycin C were divided into two groups, group 1- sponge (n = 52) and group 2- Injection(n = 46). Follow-up data were collected on day one, day 15, one month, three months, six months, one year, two years and three years. Data from baseline and follow-up visits were analyzed and compared to study the significant difference in intraocular pressure (IOP), number of antiglaucoma medications (AGM) and best corrected visual acuity (BCVA) . P-value of <0.05 was considered statistically significant. RESULTS: Mean preop IOP was 34.61 ± 13.3 mmHg in group one and 33.07 ± 9.6 mmHg in group two, which reduced to 11.43 ± 3.2 and 11.59 ± 3.2 mmHg at three years (p < 0.001 in both groups) with no significant difference between the groups. Mean number of preoperative AGM was 2.28 ± 0.8 and 2.42 ± 0.7 in group one and two respectively which reduced to 1.19 ± 1.1(p = 0.405) and 0.88 ± 0.9(p = 0.001) at three years. Complete and overall success rates (complete + qualified) were 59.3% and 78.9% in group one and 60.9% and 80.4% in group two at three years. No statistically significant difference was found in complication rates, post-operative interventions, and final visual outcome in both groups. CONCLUSIONS: Subconjunctival Injection MMC was a safe and effective alternative to sponge application with comparable long term surgical outcomes.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

PURPOSE: To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). METHODS: We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. RESULTS: We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CONCLUSIONS: CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Regulatory Effects of Senescent Mesenchymal Stem Cells: Endotheliocyte Reaction.

Currently, there is a growing focus on aging and age-related diseases. The processes of aging are based on cell senescence, which results in changes in intercellular communications and pathological alterations in tissues. In the present study, we investigate the influence of senescent mesenchymal stem cells (MSCs) on endothelial cells (ECs). In order to induce senescence in MSCs, we employed a method of stress-induced senescence utilizing mitomycin C (MmC). Subsequent experiments involved the interaction of ECs with MSCs in a coculture or the treatment of ECs with the secretome of senescent MSCs. After 48 h, we assessed the EC state. Our findings revealed that direct interaction led to a decrease in EC proliferation and migratory activity of the coculture. Furthermore, there was an increase in the activity of the lysosomal compartment, as well as an upregulation of the genes P21, IL6, IL8, ITGA1, and ITGB1. Treatment of ECs with the "senescent" secretome resulted in less pronounced effects, although a decrease in proliferation and an increase in ICAM-1 expression were observed. The maintenance of high levels of typical "senescent" cytokines and growth factors after 48 h suggests that the addition of the "senescent" secretome may have a prolonged effect on the cells. It is noteworthy that in samples treated with the "senescent" secretome, the level of PDGF-AA was higher, which may explain some of the pro-regenerative effects of senescent cells. Therefore, the detected changes may underlie both the negative and positive effects of senescence. The findings provide insight into the effects of cell senescence in vitro, where many of the organism's regulatory mechanisms are absent.

Adverse drug reactions of intravesical instillation therapy for bladder cancer: based on FDA adverse event reporting system.

BACKGROUND: Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment. STUDY DESIGN AND METHODS: Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events. RESULTS: The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity. CONCLUSION: This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Combining Mitomycin C with inhibition of BAD phosphorylation enhances apoptotic cell death in advanced cervical cancer.

OBJECTIVE: Mitomycin C (MMC), a DNA-damaging chemotherapeutic, is commonly used clinically for recurrent cervical carcinoma (CC), either alone or in combination. MMC generates DNA damage resulting in CC cell death yet also induces increased AKT-BAD phosphorylation associated with drug resistance and reduced clinical benefit. The present study evaluates the efficacy of combined MMC and a BAD phosphorylation inhibitor in CC. METHODS: The association and function of phosphorylation of BAD on serine 99 (pBADS99) for cell survival of both MMC-resistant or sensitive-CC cells was explored. BAD was mutated to BADS99A to examine the requirement of BADS99 for CC cell survival and a novel small-molecule inhibitor of pBADS99 was utilized. Cell proliferation, survival, foci formation, and patient-derived organoids (PDOs) assays were utilized to determine efficacy, synergy and related mechanisms. RESULTS: MMC IC50 was positively correlated to the cell line pBADS99/BAD ratio. Increased BADS99 phosphorylation was observed in both MMC-sensitive or -resistant CC cells after MMC treatment. Inhibition of pBADS99 in CC cell lines produced synergistic apoptosis through BAD-mediated apoptotic pathways and enhanced DNA damage in response to MMC. The concurrent use of pharmacological inhibition of pBADS99 and MMC was synergistic, resulting in diminished cell viability and inducing apoptotic cell death in MMC-sensitive and -resistant CC cell lines or patient-derived organoids. CONCLUSION: A combination of MMC with inhibition of BAD phosphorylation potentiated efficacy compared to single agent treatment. The potential further development of such strategies may provide outcome benefits to patients with CC.

Case report: Clinical features and management outcomes of isolated corneal intraepithelial neoplasia.

Purpose: To report clinical features and treatment outcome of three cases with isolated corneal intraepithelial neoplasia (CIN). Methods: This case series presents 3 patients with isolated CIN. Data collected included, presenting signs and symptoms including vision, anterior segment examination, medical and surgical outcomes and signs and symptoms at lost post-treatment visit. Results: Case 1 was a 45-year-old male who presented with an isolated grayish amoeboid corneal lesion which was excised with alcohol assisted epitheliectomy, he also received 6 cycles of topical mitomycin C (MMC) 0.02% and one injection of interferon alfa-2b with no recurrence during the 10-year follow-up period. Case 2 was 78-year-old male referred for a suspicious white corneal lesion which was completely excised, the patient also received 6 subconjunctival injections of interferon alpha-2b. However, the lesion recurred at 2.5-years post-treatment. Case 3 was a 63-year-old male patient who presented with an isolated corneal lesion that was excised using alcohol-assisted epitheliectomy, patient received four cycles of topical 5-fluorouracil with no recurrence at last follow-up visit at 6 months. Conclusion: Isolated corneal intraepithelial neoplasia (CIN) is a rare entity with few reported cases in the literature. In this case series, we report long and short-term management outcomes of combined surgical and medical therapy for isolated CIN.

Diagnosing Fanconi Anemia: A Rare Case Report From Rural India.

Fanconi anemia is a rare but most prevalent form of inherited aplastic anemia, predominantly transmitted in an autosomal recessive manner, except for one X-linked variant. It arises from mutations in the genes across 16 different complementation groups that are crucial for DNA stability. It is marked by a wide range of congenital malformations, progressive pancytopenia, and an increased risk of both hematological malignancies and solid tumors. The congenital abnormalities associated with it can affect various organ systems, including the skeletal system, with significant variability among patients. One similar case has been reported here, which had the typical clinical features of FA. Due to varied phenotypic presentation, diagnosing FA can be challenging. A Chromosomal Breakage Study using mitomycin C (MMC) or diepoxybutane (DEB) is a distinctive cellular marker that aids in the diagnosis.

Determination of mitomycin C in rat plasma by liquid chromatography-tandem mass spectrometry and its application for determining pharmacokinetics in rat.

To develop the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring mitomycin C in rat plasma, samples were processed using solid-phase extraction, with the internal standard being carbamazepine. A reversed phased C18 column was utilized for the LC-MS/MS study, and mobile phases consisting of 0.1 % formic acid in acetonitrile and water were injected into it at a rate of 0.3 mL/min. Multiple reaction monitoring in positive-ion mode with precursor-product ion pairs 335.3 â†’ 242.3 (mitomycin C) and 237.1 â†’ 194.1 (carbamazepine) was employed to quantify the compounds. The linear range in plasma was found to be 10-4000 ng/mL (r2 = 0.992). The inter-batch and intra-batch precision were <14.3 % (LLOQ: 14.7 %) and 13.4 % (LLOQ: 16.1 %), respectively. The recovery and the matrix effect of mitomycin C in plasma were 113 % and 111 %, respectively. Mitomycin C was stable under the conditions of this assay method. In the end, this approach proved effective in a pharmacokinetic investigation with the intravenous and oral administration of mitomycin C to rats.

The effect of intravesical chemohyperthermia with mitomycin in non-muscle-invasive bladder tumour patients who cannot tolerate BCG treatment or recur after treatment and refuse cystectomy.

PURPOSE: Many patients receiving intravesical BCG treatment for non-muscle-invasive bladder cancer experience high recurrence rates despite initial adequate response. In this study, the effectiveness of intravesical chemohyperthermia (CHT) with mitomycin C (MMC) was evaluated in patients who developed relapse after intravesical BCG treatment or could not tolerate the treatment and could not undergo radical cystectomy for any reason. MATERIALS AND METHODS: 59 patients who underwent complete bladder tumour resection, who had a T1 high-grade tumour and no variant histology was observed in the pathology, and who had previously received intravesical BCG treatment were included in the study. Adjuvant treatment with intravesical CHT-MMC was applied. As a treatment protocol, induction was applied once a week for 6 weeks, followed by maintenance treatment 6 times at 4-week intervals. Each treatment session, it involved bladder wall hyperthermia with a temperature of up to 42 â„ƒ ± 2 and intravesical administration of 20 mg/50 ml MMC solution twice at 30-min intervals. RESULTS: Recurrence-free survival after warm mitomycin was 58.7 and 48%, respectively, at 24 months and 44 months, and progression-free survival was 72.6 and 66.2%, respectively. In the subgroup analysis performed according to the number of tumours at diagnosis (single, 2-5, more than 5), recurrence-free survival rates were 81.8%, 48.2% and 11%, respectively, during the median follow-up period of 44 months. CONCLUSIONS: Intravesical CHT-MMC can be considered as an alternative treatment in selected well-informed patients with non-muscle-invasive papillary urothelial carcinoma who are unresponsive to BCG or intolerant to BCG. Prospectively designed studies with larger number of patients are needed.

Mitomycin C vs. Bacillus Calmette-Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients-A comparative analysis from a single center.

BACKGROUND: Induction followed by 1 year maintenance instillation of intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. METHODS: We retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan-Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. RESULTS: Optimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. CONCLUSIONS: Optimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Critical appraisal of total gastrectomy plus total colectomy with hyperthermic intraperitoneal chemotherapy as a treatment for advanced pseudomyxoma peritonei.

BACKGROUND: The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy. METHODS: We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival. RESULTS: Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014). CONCLUSIONS: A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.

The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.