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Cancers Oct 2023Upper tract urothelial carcinoma (UTUC) poses unique challenges in diagnosis and treatment. This comprehensive review focuses on prophylactic intravesical therapy for... (Review)
Review
Upper tract urothelial carcinoma (UTUC) poses unique challenges in diagnosis and treatment. This comprehensive review focuses on prophylactic intravesical therapy for UTUC, summarizing key aspects of intravesical therapy in various clinical scenarios, including concurrent with or following radical nephroureterectomy, kidney-sparing surgery, ureteroscopy-guided biopsy. The incidence of intravesical recurrence in UTUC after surgical treatment is significant, necessitating effective preventive measures. Intravesical therapy plays a vital role in reducing the risk of bladder recurrence following UTUC surgery. Tailoring timing, drug selection, dosage, and frequency is vital in optimizing treatment outcomes and reducing intravesical recurrence risk in UTUC. This review provides a comprehensive summary of the history, clinical trials, guideline recommendations, and clinical applications of intravesical therapy for UTUC. It also discusses the future directions based on current clinical needs and ongoing trials. Future directions entail optimizing dosage, treatment duration, and drug selection, as well as exploring novel agents and combination therapies. Intravesical therapy holds tremendous potential in improving outcomes for UTUC patients and reducing the risk of bladder recurrence. Although advancements have been made in UTUC treatment research, further refinements are necessary to enhance efficacy and safety.
PubMed: 37894387
DOI: 10.3390/cancers15205020 -
Frontiers in Oncology 2023HPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV-) disease. We report a planned interim analysis...
BACKGROUND AND PURPOSE
HPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV-) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status.
MATERIALS AND METHODS
HPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV- received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category.
RESULTS
In the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV- patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients.
CONCLUSION
De-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.
PubMed: 37456246
DOI: 10.3389/fonc.2023.1183854 -
Investigative Ophthalmology & Visual... Dec 2023Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is...
PURPOSE
Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is necessary for experimental research to explore the etiology and pathogenesis of eyelid SeC. This study established and characterized an eyelid SeC cell line with a TP53 mutation that might be useful for analyzing potential treatment options for eyelid SeC.
METHODS
The eyelid SeC cell line SHNPH-SeC was obtained from a patient with eyelid SeC at Shanghai Ninth People's Hospital (SHNPH), Shanghai JiaoTong University School of Medicine. Immunofluorescence staining was employed to detect the origination and proliferation activity. Short tandem repeat (STR) profiling was performed for verification. Chromosome analysis was implemented to investigate chromosome aberrations. Whole exome sequencing (WES) was used to discover genomic mutations. Cell proliferation assays were performed to identify sensitivity to mitomycin-C (MMC) and 5-fluorouracil (5-FU).
RESULTS
SHNPH-SeC cells were successively subcultured for more than 100 passages and demonstrated rapid proliferation and migration. Karyotype analysis revealed abundant chromosome aberrations, and WES revealed SeC-related mutations in TP53, KMT2C, and ERBB2. An in vivo tumor model was successfully established in NOD/SCID mice. Biomarkers of eyelid SeC, including cytokeratin 5 (CK5), epithelial membrane antigen (EMA), adipophilin, p53, and Ki-67, were detected in SHNPH-SeC cells, original tumors, and xenografts. MMC and 5-FU inhibited the proliferation and migration of SHNPH-SeC cells, and SHNPH-SeC cells presented a greater drug response than non-TP53-mutated SeC cells.
CONCLUSIONS
The newly established eyelid SeC cell line SHNPH-SeC demonstrates mutation in TP53, the most commonly mutated gene in SeC. It presents SeC properties and malignant characteristics that may facilitate the investigation of cellular behaviors and molecular mechanisms of SeC to explore promising therapeutic strategies.
Topics: Animals; Mice; Humans; Tumor Suppressor Protein p53; Biomarkers, Tumor; Mice, SCID; Mice, Inbred NOD; China; Adenocarcinoma, Sebaceous; Carcinoma; Chromosome Aberrations; Cell Line, Tumor; Eyelids; Eyelid Neoplasms; Skin Neoplasms; Sebaceous Gland Neoplasms; Fluorouracil
PubMed: 38095907
DOI: 10.1167/iovs.64.15.16 -
Journal of Clinical Medicine Oct 2023Intranasal adhesions (synechiae) develop as a result of improper healing of the nasal mucosa. Their incidence ranges from 6.8% to 36% of rhinosurgical procedures. The... (Review)
Review
Intranasal adhesions (synechiae) develop as a result of improper healing of the nasal mucosa. Their incidence ranges from 6.8% to 36% of rhinosurgical procedures. The aim of this study was to review the available publications and monographs dealing with intranasal adhesions-both in the context of formation and risk factors. The study used a review of the literature to determine the articles and studies available in the following medical databases: MEDLINE (National Library of Medicine's), PubMed, and Google Scholar. The following search terms were used: synechiae nasal + synechial nasal + intranasal adhesions + nasal adhesions. The time criterion of available materials was not applied. Available filters in the search engines were used to narrow down the search results. Artificial intelligence was not applied. The review indicated that the risk of intranasal adhesions correlates with the type of surgery, the surgical technique, the dressing materials, and wound care in the postoperative period. Every case requires an individualized approach. Nasal septum separators, (self-)dissolving dressings and (in selected cases) Mitomycin C were investigated thoroughly. Further studies are required which may result in a universal classification system for intranasal adhesions.
PubMed: 37959296
DOI: 10.3390/jcm12216831 -
Indian Journal of Ophthalmology Mar 2024Filtration surgery is one of the most frequently performed surgeries in the management of glaucoma, and trabeculectomy is considered the gold standard surgical technique... (Review)
Review
Filtration surgery is one of the most frequently performed surgeries in the management of glaucoma, and trabeculectomy is considered the gold standard surgical technique for the same. Though trabeculectomy has been reported to have an excellent initial success rate, about 30% of them fail in 3 years, and nearly 50% of them fail in 5 years. The most significant risk of failure still seems to be wound scarring, especially episcleral fibrosis, leading to bleb failure. As a result, it is essential to explore the role of anti-scarring agents, including mitomycin C, and 5-fluorouracil in wound modulation and improving the bleb survival rate. Since these agents are widely used in trabeculectomy, it is crucial to understand the various modes of application, advantages, and adverse effects of these agents. On an evidence-based approach, all these points have been highlighted in this review article. In addition, the newer agents available for wound modulation and their scope for practical application are discussed.
Topics: Humans; Cicatrix; Intraocular Pressure; Glaucoma; Trabeculectomy; Fluorouracil; Mitomycin
PubMed: 38153968
DOI: 10.4103/IJO.IJO_2013_23 -
Cells Sep 2023Karyomegalic interstitial nephritis (KIN) is a genetic kidney disease caused by mutations in the FANCD2/FANCI-Associated Nuclease 1 () gene on 15q13.3, which results in...
Karyomegalic interstitial nephritis (KIN) is a genetic kidney disease caused by mutations in the FANCD2/FANCI-Associated Nuclease 1 () gene on 15q13.3, which results in karyomegaly and fibrosis of kidney cells through the incomplete repair of DNA damage. The aim of this study was to explore the possibility of using a human induced pluripotent stem cell (hiPSC)-derived kidney organoid system for modeling -deficient kidney disease, also known as KIN. We generated kidney organoids using WTC-11 (wild-type) hiPSCs and -mutant hiPSCs which include KIN patient-derived hiPSCs and -edited hiPSCs (WTC-11 ), created using the CRISPR/Cas9 system in WTC-11-hiPSCs. Kidney organoids from each group were treated with 20 nM of mitomycin C (MMC) for 24 or 48 h, and the expression levels of Ki67 and H2A histone family member X (H2A.X) were analyzed to detect DNA damage and assess the viability of cells within the kidney organoids. Both WTC-11-hiPSCs and -mutant hiPSCs were successfully differentiated into kidney organoids without structural deformities. MMC treatment for 48 h significantly increased the expression of DNA damage markers, while cell viability in both -mutant kidney organoids was decreased. However, these findings were observed in WTC-11-kidney organoids. These results suggest that -mutant kidney organoids can recapitulate the phenotype of -deficient kidney disease.
Topics: Humans; Induced Pluripotent Stem Cells; Endodeoxyribonucleases; Exodeoxyribonucleases; Kidney; Endonucleases; Nephritis, Interstitial; Organoids; Multifunctional Enzymes
PubMed: 37759541
DOI: 10.3390/cells12182319 -
World Journal of Gastrointestinal... Nov 2023In recent years survival of patients with metastatic colorectal cancer (mCRC), though still limited, has improved significantly; clearly, when the disease becomes...
BACKGROUND
In recent years survival of patients with metastatic colorectal cancer (mCRC), though still limited, has improved significantly; clearly, when the disease becomes refractory to standard regimens, additional treatment options are needed. Studies have shown that mitomycin C (MMC), an antitumor antibiotic, and capecitabine, a precursor of 5-fluorouracil, may act synergistically in combination. The efficacy of MMC/capecitabine has been demonstrated in the first-line setting, but only a few small studies have tested it in the advanced-line setting, with contradictory results.
AIM
To summarize our experience using MMC/capecitabine as an advanced line treatment for mCRC.
METHODS
A retrospective study was conducted at a tertiary medical center including all patients with histologically proven mCRC who were treated with MMC/capecitabine after at least two previous lines of standard chemotherapy in 2006-2020. Data on patient demographics and past medical history, laboratory, pathological, and radiological factors, and treatment and survival were collected from the files. Survival analyses were performed using the Kaplan-Meier method. The association of patient and tumor characteristics with treatment effectiveness and toxicity was evaluated with univariate and multivariate proportional hazard Cox regression analyses. ≤ 0.05 was considered statistically significant.
RESULTS
The cohort consisted of 119 patients of median age 64 years (range 37-85). Patients received a median of 2 MMC/capecitabine cycles (range 0.5-9.0). Thirty-four patients (28.6%) experienced grade ≥ 3 toxicity, including 2 (1.7%) with grade 4; there was no drug-related mortality. The objective response rate was 0.8%, and the disease control rate, 24.4%. Median progression-free survival (PFS) was 2.1 mo (range 0.2-20.3), and median overall survival, 4.8 mo (range 0.2-27.5). The 6-month overall survival rate was 44%; 8.7% of patients remained progression-free. Factors associated with longer PFS were lower gamma-glutamyl transferase level ( = 0.030) and primary tumor location in the left colon ( = 0.017). Factors associated with longer overall survival were lower gamma-glutamyl transferase level ( = 0.022), left-colon tumor location ( = 0.044), low-to-moderate histological grade ( = 0.012), Eastern Cooperative Oncology Group performance status 0-1 ( = 0.036), and normal bilirubin level ( = 0.047).
CONCLUSION
MMC/capecitabine is an active, available, and relatively safe regimen for use beyond standard lines of therapy in mCRC. Several clinical and laboratory parameters can identify patients more likely to benefit.
PubMed: 38077638
DOI: 10.4251/wjgo.v15.i11.1913 -
Scientific Reports Jul 2023Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor...
Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.
Topics: Humans; Mitomycin; Cisplatin; Hyperthermic Intraperitoneal Chemotherapy; Combined Modality Therapy; Hyperthermia, Induced; Mesothelioma; Mesothelioma, Malignant; Peritoneal Neoplasms; Perfusion; Organoids; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies
PubMed: 37468581
DOI: 10.1038/s41598-023-38545-4 -
Current Oncology (Toronto, Ont.) Feb 2024Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with... (Review)
Review
Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.
Topics: Humans; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Mitomycin; Complementary Therapies
PubMed: 38392073
DOI: 10.3390/curroncol31020079 -
Oncology 2024The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer...
INTRODUCTION
The aim was to investigate the risk factors for recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to provide a basis for clinical prevention of recurrence of NMIBC.
METHODS
From January 2012 to December 2020, 592 patients with NMIBC who underwent TURBT attending the Second Affiliated Hospital of Xi'an Jiaotong University were retrospectively included in this study. Patients were divided into relapse and relapse-free groups according to whether relapse occurred within 2 years. Ultimately, 72 patients were included in the relapse group and 350 patients were included in the relapse-free group. Observation indicators included age, sex, smoking, underlying disease (hypertension, diabetes, coronary heart disease), two or more lesions, tumor size, hematuria, pathology grading (low, medium, high), staging (Ta, T1), muscular invasion in initial pathology, tumor base (sessile, pedunculated), use of intravesical drug (pirarubicin, bacillus Calmette-Guerin [BCG], mitomycin, hydroxycamptothecin, gemcitabine).
RESULTS
In this study, the 2-year recurrence rate of NMIBC patients after TURBT was 17.06%. There were significant differences in comparison of pirarubicin, BCG, and mitomycin treatment between the two groups (p < 0.05). To avoid missing risk factors for recurrence, factors with p < 0.1 were analyzed. The results of univariate logistic regression analysis showed that NMIBC patients with BCG treatment (OR = 5.088, 95% CI = 1.444-17.73, p = 0.012), high pathology grading (OR = 0.415, 95% CI = 0.197-0.880, p = 0.023), T1 stage (OR = 2.097, 95% CI = 0.996-4.618, p = 0.059), mitomycin treatment (OR = 5.029, 95% CI = 1.149-21.77, p = 0.031), and pirarubicin treatment (OR = 1.794, 95% CI = 1.079-3.030, p = 0.024) had significantly higher risk of recurrence within 2 years after TURBT. The results of multivariate logistic regression analysis showed that NMIBC patients with high pathology grading (OR = 0.4030, 95% CI = 0.1702-0.8426, p = 0.0241), pirarubicin treatment (OR = 1.961, 95% CI = 1.159-3.348, p = 0.0125), and BCG treatment (OR = 6.201, 95% CI = 1.275-29.73, p = 0.0190) had significantly higher risk of recurrence within 2 years after TURBT.
CONCLUSION
Our study highlights the importance of postoperative surveillance and individualized treatment for patients with NMIBC. Our findings show that high pathology grading, pirarubicin treatment, and BCG treatment are independent risk factors for recurrence after TURBT in patients with NMIBC. However, caution is warranted when interpreting our findings due to the small sample size and the need for further research to confirm the negative impact of mitomycin and BCG on recurrence rates.
Topics: Humans; Non-Muscle Invasive Bladder Neoplasms; Follow-Up Studies; Retrospective Studies; BCG Vaccine; Transurethral Resection of Bladder; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Mitomycin; Risk Factors; Recurrence; Neoplasm Invasiveness; Doxorubicin
PubMed: 37647883
DOI: 10.1159/000533410