Displaying publications 1 - 20 of 32 in total

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  1. Gakis G, Fahmy O
    Bladder cancer (Amsterdam, Netherlands), 2016 Jul 27;2(3):293-300.
    PMID: 27500197
    Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression. Material and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non-muscle invasive bladder cancer between 2000 and 2016. A two-stage selection process was utilized to determine eligible studies. Of a total of 294 studies, 5 (4 randomized and one retrospective) were considered for final analysis. The primary objective was the rate of progression. Results: The median follow-up for patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months, respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of 657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10-2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in a single study with a trend towards improved survival for patients treated with HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression was significantly lower in patients treated with HAL- vs. WL-based TURBT. These results support the initiation of randomized trials on HAL with progression as primary endpoint.
  2. Patel V, Collazo Lorduy A, Stern A, Fahmy O, Pinotti R, Galsky MD, et al.
    Bladder cancer (Amsterdam, Netherlands), 2017 Apr 27;3(2):121-132.
    PMID: 28516157 DOI: 10.3233/BLC-170108
    Background: Cisplatin-based combination chemotherapy is standard treatment for metastatic urothelial carcinoma; however, the vast majority of patients experience disease progression. As systemic therapy alone is rarely curative for the treatment of metastatic urothelial cancer, not only are new therapies needed but also refinement of general treatment principles. Herein, we conducted a systematic review and meta-analysis to explore the role of metastasectomy in metastatic urothelial carcinoma. Methods: We conducted a systematic review of the literature regarding local treatment for metastatic urothelial carcinoma. An online electronic search of the PubMed/MEDLINE and EMBASE databases was performed to identify peer-reviewed articles. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information was then extracted including number of patients, gender, the site of the primary urothelial tumor, site of metastasis, chemotherapy before or after metastasectomy, overall survival (OS), and disease specific survival (DSS) after metastasectomy. A meta-analysis was performed with those studies with sufficient survival data to obtain pooled overall survival. The article quality was assessed using the Cochrane Handbook "risk of bias" tool. Results: Seventeen out of 3963 articles were eligible for review between 1990-2015, including a total of 412 patients. The mean time to recurrence after metastasectomy was 14.25 months. The overall survival from time of metastasectomy ranged from 2 to 60 months. Pooled analyses of studies reported survival data revealed an improved overall survival for patients treated with metastasectomy compared with non-surgical treatment of metastatic lesions (HR 0.63; 95% CI, 0.49-0.81). All, except for three studies, were retrospective and non-randomized, leading to a high risk of bias associated with patient selection, patient attrition, and reporting. Such high potential of selection bias may lead to higher OS than expected. Additionally, treatment and outcome details reported across studies was highly variable. Conclusions: Limited conclusions can be drawn from the available literature exploring the role of metastasectomy in the management of metastatic urothelial cancer due to lack of uniform reporting elements and multiple sources of bias particularly related to a lack of prospective randomized trials. As a subset of patients treated with metastasectomy achieve durable disease control, this approach may be considered for select patients.
  3. Fahmy O, El-Fayoumi AR, Gakis G, Amend B, Khairul-Asri MG, Stenzl A, et al.
    Cent European J Urol, 2015;68(4):466-70.
    PMID: 26855804 DOI: 10.5173/ceju.2015.627
    Laparoscopic pyeloplasty is considered a standard treatment for ureteropelvic junction obstruction (UPJO). However, the presence of another pathology makes it a more challenging operation and guides the surgeon towards open conversion. In this study, we present our experience in difficult pyeloplasty cases managed by laparoscopy.
  4. Khor V, Fahmy O, Lee CKS, Khairul-Asri MG
    Cent European J Urol, 2023;76(4):311-314.
    PMID: 38230320 DOI: 10.5173/ceju.2023.91
    Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer.
  5. Zahran MH, Fahmy O, El-Hefnawy AS, Ali-El-Dein B
    Climacteric, 2016 Dec;19(6):546-550.
    PMID: 27649461
    OBJECTIVES: To evaluate the impact of radical cystectomy and urinary diversion on female sexual function.

    MATERIALS AND METHODS: A Medline search was conducted according to the PRISMA statement for all English full-text articles published between 1980 and 2016 and assessing female sexual function post radical cystectomy and urinary diversion. Eligible studies were subjected to critical analysis and revision. The primary outcomes were the reporting methods for female sexual dysfunction (FSD), manifestations of FSD, and factors associated with FSD, postoperative recoverability of FSD, and awareness level regarding FSD.

    RESULTS: From the resulting 117 articles, 11 studies were finally included in our systematic review, with a total of 361 women. Loss of sexual desire and orgasm disorders were the most frequently reported (49% and 39%). Dyspareunia and vaginal lubrication disorders were reported in 25% and 9.5%, respectively. The incidence of sexual dysfunction was 10% in 30 patients receiving genital- or nerve-sparing cystectomy vs. 59% receiving conventional cystectomy.

    CONCLUSION: Although female sexual function is an important predictor of health-related quality of life post radical cystectomy and urinary diversion, the available literature is not enough to provide proper information for surgeons and patients.

  6. Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G
    Clin. Exp. Metastasis, 2016 10;33(7):629-35.
    PMID: 27380916 DOI: 10.1007/s10585-016-9807-9
    For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.
  7. Kochergin M, Fahmy O, Asimakopoulos AD, Gakis G
    Curr Opin Urol, 2023 Jul 01;33(4):288-293.
    PMID: 37158221 DOI: 10.1097/MOU.0000000000001101
    PURPOSE OF REVIEW: Primary urethral carcinoma (PUC) is a rare urologic tumor. There is limited evidence on this entity. This review summarizes the existing evidence on lymph node dissection (LND) in patients with PUC.

    RECENT FINDINGS: We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure.

    RESULTS: Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1-2 N0 and 37% in cT3-4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes.

    SUMMARY: The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.

  8. Altyar AE, Fahmy O
    Dose Response, 2022 01 12;20(1):15593258211063983.
    PMID: 35069050 DOI: 10.1177/15593258211063983
    Background: In current years, researchers have shown their prime interest in developing multifunctional drug delivery systems, especially against cancers, for effective anticancer outcomes.

    Methodology: Raloxifene (RLX) loaded liposomal-graphene nanosheet (GNS) was developed. The novelty of this work was to enhance the solubilization of RLX and improvement of its bioavailability in the disease area. So, the selection of optimized formula design of experiment was implemented which produced the desired formula with the particle size of 156.333 nm. Further, encapsulation efficiency, in vitro release, and thermodynamic stability of optimized formulation were evaluated. The optimized formulation exhibited prolonged release of RLX for a longer period of 24 h, which can minimize the dose-related toxicity of the drug. Furthermore, optimized formulation demonstrated remarkable thermodynamic stability in terms of phase separation, creaming, and cracking.

    Results: The cytotoxicity study on the A549 cell line exhibited significant (P < .05) results in favor of optimized formulation than the free drug. The apoptotic activity was carried out by Annexin V staining and Caspase 3 analysis, which demonstrated remarkable promising results for optimized liposomal formulation.

    Conclusion: From the findings of the study, it can be concluded that the novel optimized liposomal formulation could be pondered as a novel approach for the treatment of lung cancer.

  9. Fahmy O, Khairul-Asri MG, Schwentner C, Schubert T, Stenzl A, Zahran MH, et al.
    Eur Urol, 2016 08;70(2):293-8.
    PMID: 26776935 DOI: 10.1016/j.eururo.2015.12.047
    CONTEXT: Although urethral covering during hypospadias repair minimizes the incidence of fistula, wide variation in results among surgeons has been reported.

    OBJECTIVE: To investigate what type of flap used during Snodgrass or fistula repair reduces the incidence of fistula occurrence.

    EVIDENCE ACQUISITION: We systematically reviewed published results for urethral covering during Snodgrass and fistula repair procedures. An initial online search detected 1740 reports. After exclusion of ineligible studies at two stages, we included all patients with clear data on the covering technique used (dartos fascia [DF] vs tunica vaginalis flap [TVF]) and the incidence of postoperative fistula.

    EVIDENCE SYNTHESIS: A total of 51 reports were identified involving 4550 patients, including 33 series on DF use, 11 series on TVF use, and seven retrospective comparative studies. For distal hypospadias, double-layer DF had the lowest rate of fistula incidence when compared to single-layer DF (5/855 [0.6%] vs 156/3077 [5.1%]; p=0.004) and TVF (5/244, 2.0%), while the incidence was highest for single-layer DF among proximal hypospadias cases (9/102, 8.8%). Among repeat cases, fistula incidence was significantly lower for TVF (3/47, 6.4%) than for DF (26/140, 18.6%; p=0.020). Among patients with fistula after primary repair, the incidence of recurrence was 12.2% (11/90) after DF and 5.1% (5/97) after TVF (p=0.39). The absence of a minimum follow-up time and the lack of information regarding skin complications and rates of urethral stricture are limitations of this study.

    CONCLUSION: A double DF during tubularized incised plate urethroplasty should be considered for all patients with distal hypospadias. In proximal, repeat, and fistula repair cases, TVF should be the first choice. On the basis of these findings, we propose an evidence-based algorithm for surgeons who are still in their learning phase or want to improve their results.

    PATIENT SUMMARY: We systematically reviewed the impact of urethral covering in reducing fistula formation after hypospadias repair. We propose an algorithm that might help to maximize success rates for tubularized incised plate urethroplasty.

  10. Fahmy O, Schubert T, Khairul-Asri MG, Stenzl A, Gakis G
    Int J Urol, 2017 04;24(4):320-323.
    PMID: 28208217 DOI: 10.1111/iju.13307
    The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.
  11. Fahmy O, Fahmy UA, Alhakamy NA, Khairul-Asri MG
    J Clin Med, 2021 Dec 07;10(24).
    PMID: 34945018 DOI: 10.3390/jcm10245723
    BACKGROUND: Single-port robotic-assisted radical prostatectomy has been reported as a safe and feasible technique. However, recent studies comparing single-port versus multiple-port robotic radical prostatectomy have displayed conflicting results.

    OBJECTIVES: To investigate the benefit of single-port robotic radical prostatectomy and the impact on outcome compared to multiple-port robotic radical prostatectomy.

    METHODS: Based on PRISMA and AMSTAR criteria, a systematic review and meta-analysis were carried out. Finally, we considered the controlled studies with two cohorts (one cohort for single-port RARP and the other cohort for multiple-port RARP). For statistical analysis, Review Manager (RevMan) software version 5.4 was used. The Newcastle-Ottawa Scale was employed to assess the risk of bias.

    RESULTS: Five non-randomized controlled studies with 666 patients were included. Single-port robotic radical prostatectomy was associated with shorter hospital stays. Only 60.6% of single-port patients (109/180) required analgesia compared to 90% (224/249) of multiple-port patients (Z = 3.50; p = 0.0005; 95% CI 0.07:0.47). Opioid administration was also significantly lower in single-port patients, 26.2% (34/130) vs. 56.6% (77/136) (Z = 4.90; p < 0.00001; 95% CI 0.15:-0.44) There was no significant difference in operative time, blood loss, complication rate, positive surgical margin rate, or continence at day 90.

    CONCLUSION: The available data on single-port robotic radical prostatectomy is very limited. However, it seems comparable to the multiple-port platform in terms of short-term outcomes when performed with expert surgeons. Single-port prostatectomies might provide a shorter hospital stay and a lower requirement for opioids; however, randomized trials with long-term follow-up are mandatory for valid comparisons.

  12. Fahmy O, Alhakamy NA, Rizg WY, Bagalagel A, Alamoudi AJ, Aldawsari HM, et al.
    J Clin Med, 2021 Oct 31;10(21).
    PMID: 34768647 DOI: 10.3390/jcm10215127
    Prostate cancer (PCa) represents the most commonly non-cutaneous diagnosed cancer in men worldwide and occupies a very wide area of preclinical and clinical research. Targeted therapy for any cancer depends on the understanding of the molecular bases and natural behaviour of the diseases. Despite the well-known effect of androgen deprivation on PCa, many patients develop resistance either for antiandrogen therapy or other new treatment modalities such as checkpoint inhibitors and chemotherapy. Comprehensive understanding of the development of PCa as well as of the mechanisms underlying its progression is mandatory to maximise the benefit of the current approved medications or to guide the future research for targeted therapy of PCa. The aim of this review was to provide updates on the most recent mechanisms regarding the development and the progression of PCa. According to the current understanding, future treatment strategies should include more predictive genetic and biomarker analysis to assign different patients to the expected most appropriate and effective treatment.
  13. Shsm H, Fahmy UA, Alhakamy NA, Khairul-Asri MG, Fahmy O
    J Pers Med, 2021 Nov 13;11(11).
    PMID: 34834547 DOI: 10.3390/jpm11111195
    BACKGROUND: Neoadjuvant chemotherapy is the standard of care before radical cystectomy for muscle invasive bladder cancer. Recently, checkpoint inhibitors have been investigated as a neoadjuvant treatment after the reported efficacy of checkpoint inhibitors in metastatic urothelial carcinoma.

    OBJECTIVES: The aim of this systematic review is to investigate the role of checkpoint inhibitors as a neoadjuvant treatment for muscle invasive bladder cancer before radical cystectomy.

    METHODS: Based on the PRISMA statement, a systematic review of the literature was conducted through online databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Suitable publications were subjected to full-text assessment. The primary outcome of this review was to identify the impact of neoadjuvant immunotherapy on the oncological outcomes and survival benefits.

    RESULTS: From the retrieved 254 results, 8 studies including 404 patients were included. Complete response varied between 30% and 50%. Downstaging varied between 50% and 74%. ≥Grade 3 AEs were recorded in 8.6% of patients who received monotherapy with either Atezolizumab or Pembrolizumab. In patients who received combination treatment, the incidence of ≥Grade 3 AEs was 16.3% for chemoimmunotherapy and 36.5% for combined immunotherapy. A total of 373 patients (92%) underwent radical cystectomy. ≥Grade 3 Clavien-Dindo surgical complications were reported in 21.7% of the patients. One-year overall survival (OS) and relapse-free survival (RFS) varied between 81% and 92%, and 70% and 88%, respectively.

    CONCLUSION: The evidence on the use of immune checkpoint inhibitors in the setting of pre-radical cystectomy is quite limited, with noted variability within published trials. Combination with chemotherapy or another checkpoint inhibitor may boost response, although prospective studies with extended follow-up are needed to report on the survival advantages.

  14. Fahmy O, Alhakamy NA, Khairul-Asri MG, Ahmed OAA, Fahmy UA, Fresta CG, et al.
    J Pers Med, 2021 Dec 23;12(1).
    PMID: 35055323 DOI: 10.3390/jpm12010008
    Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated.

    OBJECTIVES: The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors.

    METHODS: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle-Ottawa Scale for the randomized and non-randomized trials, respectively.

    RESULTS: From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; p = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; p < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; p = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; p = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; p = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; p = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; p = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; p = 0.003).

    CONCLUSIONS: Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.

  15. Fahmy O, Asri K, Schwentner C, Stenzl A, Gakis G
    J Surg Oncol, 2015 Sep;112(4):427-9.
    PMID: 26265262 DOI: 10.1002/jso.24007
    To investigate the current status and feasibility of robotic neobladder diversion after robotic assisted radical cystectomy. A Medline search was conducted resulting in identification of 423 articles. After exclusion of ineligible studies, 3 case series and 5 case reports were considered with a total number of reported cases of 203. Although robotic intracorporeal neobladder reconstruction is in its starting phase, initial perioperative results seem to be comparable to open series. However, randomized studies are needed to confirm non-inferiority.
  16. Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G
    Med Hypotheses, 2016 Jul;92:57-8.
    PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037
    Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.
  17. Fahmy UA, Fahmy O
    Photodiagnosis Photodyn Ther, 2020 Jun;30:101714.
    PMID: 32165337 DOI: 10.1016/j.pdpdt.2020.101714
    INTRODUCTION: 5-Aminolevulinic (5-ALA) may be used as a photo diagnostic agent in bladder cancer. The aim of this study was to investigate the cytotoxic effect of 5-ALA on bladder cancer cells.

    MATERIALS AND METHODS: T24 cells treated with various concentrations of mitomycin (MC), 5-ALA and an MC/5-ALA mixture were evaluated to determine the role of 5-ALA on MC cytotoxicity. Cell cycle analysis was conducted, and apoptosis was analyzed by flow cytometry. Caspase 3 enzyme and reactive oxygen species were measured.

    RESULTS: Our initial studies exploring the impact of combination therapy on cell viability demonstrated improved cytotoxic effects on T24 and RT cells with relatively low doses of 5-ALA/MC in conjunction with MC alone. Indicated no significant difference between the IC50 of MC and MC/5-ALA in T24 cells, while IC50 value was decreased by 25 % in RT4 cells in 5-ALA/MC in comparing with MC alone. However, examination of cell cycle phase arrests by flow cytometry revealed significant PreG1 apoptosis and cell growth arrest in G2/M in T24 cells treated with the MC/5-ALA mixture compared with MC treatment. In addition, caspase 3 enzyme was increased by 1.15-fold in T24 cells treated with MC/5-ALA in comparison with MC alone.

    CONCLUSION: These results suggest that 5-ALA might possess anti-cancer properties and is not only a photo diagnostic element.

  18. Alfaleh MA, Fahmy O, Al-Rabia MW, Abourehab MAS, Ahmed OAA, Fahmy UA, et al.
    Sci Rep, 2022 Nov 14;12(1):19446.
    PMID: 36376469 DOI: 10.1038/s41598-022-24151-3
    As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.
  19. Fahmy O, Kochergin M, Asimakopoulos AD, Gakis G
    Semin Oncol, 2023;50(3-5):102-104.
    PMID: 37718162 DOI: 10.1053/j.seminoncol.2023.09.001
    For many decades, extended pelvic lymph node dissection has been an integral part during radical cystectomy for patients with muscle invasive bladder cancer. This practice was based on large retrospective meta-analyses suggesting an oncologic benefit to an extended dissection. This mini review and meta-analysis includes the two available randomized trials in the current literature. Therefore, it can be considered as the strongest level of evidence regarding the prognostic benefit of an extended pelvic lymphadenectomy. Based on current randomized data, standard pelvic lymph node dissection up to the level of iliac bifurcation is sufficient, and extension of the dissection above this level does not provide any additional oncologic benefit.
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