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Journal of Surgical Oncology May 2024The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic...
BACKGROUND AND OBJECTIVES
The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). These two treatments are combined in the operating room. A crucial requirement for benefit long-term is proper patient selection. Clinical and histopathologic prognostic indicators are used, along with the patient's fitness for surgery, to select patients to receive CRS and HIPEC.
METHODS
This study seeks to identify the reliable prognostic indicators for four different groups of patients. They are (1) the low-grade appendiceal mucinous neoplasms (LAMN) with a complete CRS, (2) the mucinous appendiceal adenocarcinomas (MACA) with complete CRS, (3) MACA with lymph node metastases (MACA-LN) with complete CRS, and (4) all histologic subtypes with incomplete cytoreduction. The prognostic indicators were evaluated for their impact on overall survival in these four groups of patients.
RESULTS
The completeness of cytoreduction (CC) score statistically significantly showed survival differences in all three histologic subtypes. The peritoneal cancer index (PCI) showed significance with LAMN and MACA-LN but not with MACA and not with incomplete CRS. The prior surgical score (PSS) was a prognostic indicator that predicted the outcome with LAMN, MACA-LN, and incomplete CRS patients but not with the MACA group. Patients who were symptomatic or who had extensive systemic chemotherapy before CRS had a significantly reduced survival.
CONCLUSION
The utility of prognostic indicators varied greatly within our four different groups of appendiceal mucinous neoplasms. CC score was always a reliable prognosticator. Surprisingly, PCI was not.
PubMed: 38752445
DOI: 10.1002/jso.27682 -
Journal of Hepatocellular Carcinoma 2024The progression of hepatocellular carcinoma (HCC) is related to macrophage polarization (MP). Our aim was to identify genes associated with MP in HCC patients and...
BACKGROUND
The progression of hepatocellular carcinoma (HCC) is related to macrophage polarization (MP). Our aim was to identify genes associated with MP in HCC patients and develop a prognostic model based on these genes.
RESULTS
We successfully developed a prognostic model consisting of six MP-related genes (SCN4A, EBF3, ADGRB2, HOXD9, CLEC1B, and MSC) to calculate the risk score for each patient. Patients were then classified into high- and low-risk groups based on their median risk score. The performance of the MP-related prognostic model was evaluated using Kaplan-Meier and ROC curves, which yielded favorable results. Additionally, the nomogram demonstrated good clinical effectiveness and displayed consistent survival predictions with actual observations. Gene Set Enrichment Analysis (GSEA) revealed enrichment of pathways related to KRAS signaling downregulation, the G2M checkpoint, and E2F targets in the high-risk group. Conversely, pathways associated with fatty acid metabolism, xenobiotic metabolism, bile acid metabolism, and adipogenesis were enriched in the low-risk group. The risk score positively correlated with the number of invasion-related genes. Immune checkpoint expression differed significantly between the two groups. Patients in the high-risk group exhibited increased sensitivity to mitomycin C, cisplatin, gemcitabine, rapamycin, and paclitaxel, while those in the low-risk group showed heightened sensitivity to doxorubicin. These findings suggest that the high-risk group may have more invasive HCC with greater susceptibility to specific drugs. IHC staining revealed higher expression levels of SCN4A in HCC tissues. Furthermore, experiments conducted on HepG2 cells demonstrated that supernatants from cells with reduced SCN4A expression promoted M2 macrophage polarization marker, CD163 in THP-1 cells. Reduced SCN4A expression induced HCC-related genes, while increased SCN4A expression reduced their expression in HepG2 cells.
CONCLUSION
The MP-related prognostic model comprising six MPRGs can effectively predict HCC prognosis, infer invasiveness, and guide drug therapy. SCN4A is identified as a suppressor gene in HCC.
PubMed: 38751862
DOI: 10.2147/JHC.S453080 -
International Ophthalmology May 2024The 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). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
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).
METHODS
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
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 1 month (P = 0.035), 3 months (P = 0.005), and 6 months after removal (P < 0.001). The FDD test, there were significant differences at 6 months (P = 0.045), 1 month (P = 0.021), 3 months (P = 0.012), and 6 months post tube removal (P = 0.005). The punctal size, both groups differed at 1 month (P = 0.045), 3 months (P = 0.03), and 6 months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube.
CONCLUSION
The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.
Topics: Humans; Mitomycin; Male; Female; Lacrimal Duct Obstruction; Middle Aged; Intubation; Aged; Treatment Outcome; Dacryocystorhinostomy; Lacrimal Apparatus; Adult; Follow-Up Studies; Stents; Prospective Studies; Alkylating Agents
PubMed: 38744721
DOI: 10.1007/s10792-024-03146-1 -
The ISME Journal Jan 2024Temperate phages can interact with bacterial hosts through lytic and lysogenic cycles via different mechanisms. Lysogeny has been identified as the major form of...
Temperate phages can interact with bacterial hosts through lytic and lysogenic cycles via different mechanisms. Lysogeny has been identified as the major form of bacteria-phage interaction in the coral-associated microbiome. However, the lysogenic-to-lytic switch of temperate phages in ecologically important coral-associated bacteria and its ecological impact have not been extensively investigated. By studying the prophages in coral-associated Halomonas meridiana, we found that two prophages, Phm1 and Phm3, are inducible by the DNA-damaging agent mitomycin C and that Phm3 is spontaneously activated under normal cultivation conditions. Furthermore, Phm3 undergoes an atypical lytic pathway that can amplify and package adjacent host DNA, potentially resulting in lateral transduction. The induction of Phm3 triggered a process of cell lysis accompanied by the formation of outer membrane vesicles (OMVs) and Phm3 attached to OMVs. This unique cell-lysis process was controlled by a four-gene lytic module within Phm3. Further analysis of the Tara Ocean dataset revealed that Phm3 represents a new group of temperate phages that are widely distributed and transcriptionally active in the ocean. Therefore, the combination of lateral transduction mediated by temperate phages and OMV transmission offers a versatile strategy for host-phage coevolution in marine ecosystems.
Topics: Halomonas; Anthozoa; Prophages; Animals; Lysogeny; Transduction, Genetic; Mitomycin
PubMed: 38739683
DOI: 10.1093/ismejo/wrae085 -
Vestnik Oftalmologii 2024Chronic inflammatory process in the lacrimal drainage system is the main etiological factor leading to dacryostenosis and consequent obliteration - partial and total... (Review)
Review
Chronic inflammatory process in the lacrimal drainage system is the main etiological factor leading to dacryostenosis and consequent obliteration - partial and total nasolacrimal duct obstruction. Prevention of this process is an urgent problem in dacryology. Currently, there is very little research on the development and use of conservative methods for treating dacryostenosis using anti-inflammatory, as well as anti-fibrotic drugs. In this regard, the main method of treating lacrimal drainage obstruction is dacryocystorhinostomy. However, the problem of recurrence after this operation has not been resolved. The causes of recurrence can be cicatricial healing of dacryocystorhinostomy ostium, canalicular obstruction, formation of granulations and synechiae in its area. Surgical methods of recurrence prevention are associated with possible complications, and there is conflicting data on the feasibility of their use. Based on this, the development of pharmacological methods for the prevention of fibrosis in dacryology is promising, among which the antitumor antibiotic Mitomycin C is the most studied. However, there are no specific scientifically substantiated recommendations for the use of this drug, and the data on its effectiveness vary. This has prompted researchers to look for and study alternative anti-fibrotic agents, such as antitumor drugs, glucocorticoids, hyaluronic acid, small molecule, biological, immunological and genetically engineered drugs, as well as nanoparticles. This review presents the current data on the efficacy and prospects of the use of these drugs in dacryology.
Topics: Humans; Dacryocystorhinostomy; Fibrosis; Lacrimal Duct Obstruction; Postoperative Complications; Antifibrotic Agents
PubMed: 38739149
DOI: 10.17116/oftalma2024140022180 -
International Journal of Molecular... Apr 2024Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label...
Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.
Topics: Humans; Riboflavin; Urinary Bladder Neoplasms; Gemcitabine; Deoxycytidine; Cell Line, Tumor; Light; Photosensitizing Agents; Oxidative Stress; Cell Survival; Lipid Peroxidation; Adenosine Triphosphate; Mitochondria; Blue Light
PubMed: 38732087
DOI: 10.3390/ijms25094868 -
Frontiers in Surgery 2024Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma...
INTRODUCTION
Radical nephroureterectomy with concurrent bladder cuff excision (RNUBCE) is the gold standard surgical approach for high-risk primary upper tract urothelial carcinoma (UTUC). Given the notably high incidence of bladder tumor recurrence following this procedure, this study aimed to evaluate the effect and safety of intraoperative mitomycin-C (MMC) instillation vs. deferred instillation on overall oncological outcomes following robot-assisted RNUBCE.
METHODS
This is a retrospective chart review study. Patients with non-invasive (N0, not T3/T4) UTUC who underwent robotic RNUBCE combined an intraoperative MMC instillation or a deferred MMC instillation after surgery at a medical center in Taiwan between November 2013 and June 2020 were eligible for inclusion. Patients with prior bladder UC, carcinomas of other origins, received neoadjuvant chemotherapy, and had undergone kidney transplantation were excluded. All surgeries were executed by a single surgical team under the guidance of the same surgeon. The primary outcomes was the risk of bladder tumor recurrence between patients received intraoperative (IO) vs. deferred MMC instillation postoperatively (PO) during one-year follow-up. The secondary outcome was postoperative adverse events assessed by the Clavien-Dindo classification. Univariate and multivariable Cox regression analyses were performed to determine the associations between study variables and the outcomes.
RESULTS
A total of 54 patients were included in the analysis. 12 (22.2%) patients experienced a bladder tumor recurrence during follow-up (IO: 7.7%, PO: 35.7%, < 0.021). After adjustment in the multivariable, intraoperative MMC instillation was significantly associated with lower risk of bladder recurrence [adjusted hazard ratio (aHR) = 0.15, 95% CI: 0.03-0.81, = 0.028]. No MMC-related Clavien-Dindo Grade III-IV adverse events were found in either group.
CONCLUSION
IIntraoperative MMC instillation is safe and associated with a lower bladder tumor recurrence risk in patients undergoing robotic RNUBCE for UTUC than deferred instillation. Future large, prospective studies are still warranted to confirm the findings.
PubMed: 38726470
DOI: 10.3389/fsurg.2024.1366982 -
BJS Open May 2024This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international...
BACKGROUND
This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients.
PATIENTS AND METHODS
Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed.
RESULTS
Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period.
CONCLUSIONS
Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.
Topics: Humans; Colorectal Neoplasms; Male; Female; Hyperthermic Intraperitoneal Chemotherapy; Middle Aged; Peritoneal Neoplasms; Mitomycin; Aged; Oxaliplatin; Cytoreduction Surgical Procedures; Retrospective Studies; Adult; Antineoplastic Combined Chemotherapy Protocols; Propensity Score; Disease-Free Survival; Treatment Outcome; Proportional Hazards Models
PubMed: 38722737
DOI: 10.1093/bjsopen/zrae017 -
Journal of Glaucoma May 2024After failure of a glaucoma drainage device in children, implantation of a second Ahmed glaucoma valve with mitomycin-C allows a significant reduction of intraocular...
PRECIS
After failure of a glaucoma drainage device in children, implantation of a second Ahmed glaucoma valve with mitomycin-C allows a significant reduction of intraocular pressure and number of medications with good medium- and long-term survival.
INTRODUCTION
The effectiveness of glaucoma drainage devices (GDD) is limited in time. There is little literature regarding the optimal management strategy after failure of a GDD in pediatric glaucoma.
PURPOSE
To report the outcomes of Ahmed glaucoma valve implantation (AGV) with mitomycin-C (MMC) after failure of a GDD in children.
METHODS
Retrospective chart review of patients with a history of at least one GDD receiving an AGV implantation with MMC between 2000 and 2019. We defined complete success as an IOP of 5 to 21 mmHg without glaucoma medication and qualified success as a final IOP of 5 to 21 mmHg with one or more glaucoma medication, without loss of vision.
RESULTS
Twenty-one patients (22 eyes) met the inclusion criteria. The intraocular pressure and number of medications were significantly reduced. The probability of complete success was 47% [95%CI: 29% - 75%] at 2 years and 34% [95%CI: 18% - 65%] at 4 years. The probability of qualified success was 74% [95%CI: 56% - 97%] at 2 years, and 54% [95%CI: 34% - 84%] at 5 years. Failure happened in 10 eyes after a mean time of 4.3 years ±3.6 [6 mo - 15 y], 5 of which (23%) for severe complication or loss of vision.
DISCUSSION
This study of implantation of a second valve with MMC reports a significant decrease of IOP and medications with medium- and long-term success rates close to those reported for a first valve implantation, although with a high risk of complications.
PubMed: 38722198
DOI: 10.1097/IJG.0000000000002422 -
International Journal of Ophthalmology 2024To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone-impregnated biodegradable nasal packing (TABP) in endoscopic...
AIM
To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone-impregnated biodegradable nasal packing (TABP) in endoscopic dacryocystorhinostomy (DCR). And to evaluate the efficacy of combining intraoperative mitomycin C and TABP for endoscopic DCR.
METHODS
A total of 198 eyes of 148 patients who underwent endoscopic DCR for acquired nasolacrimal duct obstruction were retrospectively analysed. The patients were randomly divided into three groups: Group A included patients treated without intraoperative mitomycin C but with TABP, Group B included patients treated without triamcinolone but with intraoperative mitomycin C and normal saline-impregnated nasal packing, and Group C included patients treated with intraoperative mitomycin C and TABP.
RESULTS
The results revealed no significant difference in the overall success rates between Groups A (86.8%) and B (89.2%; =0.377). However, Group C (97.5%) showed a significantly higher overall success rate than Groups A and B. The incidence of granulomas was significantly lower in group C (5%) than in Groups A (20.8%) and B (15.2%; =0.009). Other complications, such as crust, synechiae, and revision surgery, did not differ significantly among the three groups.
CONCLUSION
The combination of intraoperative mitomycin C and TABP effectively prevents granulomas and enhances surgical success rate. Additionally, there is no statistically significant difference observed between the use of mitomycin C or TABP alone.
PubMed: 38721511
DOI: 10.18240/ijo.2024.03.09