Local Therapy Research Articles

Development of Chlorhexidine-loaded Lipid Nanoparticles Incorporated in a Bioceramic Endodontic Sealer

IntroductionThis study aimed to assess BioRoot RCS (BR) incorporating liposomal chlorhexidine digluconate (CHX) for its antibacterial activity, drug release capacity, and physicochemical properties. MethodsDrug release of CHX liposomal formulations in combination with BR was evaluated spectrophotometrically and through mathematical release models for 30 days. A selected combination was evaluated for antimicrobial properties against Enterococcus faecalis biofilm growth on human dentin. Cytotoxicity was assessed following the ISO 10993-5:2019 standard on days 1, 3, and 7. Physicochemical properties were evaluated through setting time, Fourier transform infrared spectroscopy, solubility, contact angle, and film thickness. ResultsFrom BR, liposomal CHX released up to 7-fold higher CHX than CHX solution (P < .05), following a triphasic drug release pattern compared to the CHX solution, which followed a quasi-Fickian diffusion. BR combined with a selected liposomal CHX completely inhibited E. faecalis biofilm growth compared to the combination of BR with CHX solution and the control group (P < .05). Liposomal CHX decreased the contact angle (P < .05) and solubility but increased cytotoxicity (P < .05) of BR, staying above the ISO threshold. None of the other physicochemical characteristics tested differed from BR (P > .05). ConclusionThis liposomal formulation improved CHX release from BR, enhancing the antibacterial effectiveness. It presents a promising approach for local antibiofilm therapy in endodontics without substantially altering the physicochemical characteristics of BR.

Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Evolution of hormonal therapy for prostate cancer.

Prostate cancer (PCa) is the most common malignancy after skin cancer in men in Australia. Its management varies according to tumour stage. Due to the significant dependence on androgen receptor signalling, agents that interfere with this pathway (most commonly medical castration in the form of androgen deprivation therapy [ADT]) are the mainstay treatment of advanced disease. This review provides a contemporary update on ADT, withfurther discussion of emerging novel therapies for primary care. ADT is currently indicated for the treatment of metastatic prostate cancer, disease recurrence following attempted local curative therapy, as well as combined use with radiotherapy for intermediate/high-risk disease. There has been rapid development of new pharmaceuticals targeting the androgen receptor. These are reviewed historically with an emphasis placed on emerging therapies, their common side effects, and how to managethem in the general practice setting.

Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial

A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. For the French translation of the abstract see Supplementary Materials section.

First-line osimertinib for lung cancer with uncommon EGFR exon 19 mutations and EGFR compound mutations

IntroductionUp to 20% of EGFR-mutated non-small cell lung cancer (NSCLC) cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. MethodsPatients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using RECIST 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). ResultsThirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% CI 10-15), 22 months (95% CI 17-32) and 36 months (95% CI 29-48) respectively. Among atypical exon 19 mutations (n=25), ORR was 80%, median PFS was 12 months (95% CI 10-15), median TTD was 19 months (95% CI 17-38), and median OS was 48 months (95% CI 25-not reached). Compound mutations (n=12) had an ORR of 67%, median PFS of 14 months (95% CI 5-22), median TTD of 26 months (95% CI 5-36), and median OS of 36 months (95% CI 20-46). Twelve patients (32%) continued first-line osimertinib following local therapy for oligoprogression. ConclusionsOsimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.

The use of minimally invasive surgical procedures in complications of combat thoracic trauma

Background. The incidence of chest injuries in the overall structure of combat surgical trauma is approximately 4 % in present-day military conflicts, and according to the data from Anti-Terrorist Operation/Joint Forces Operation in the Eastern Ukraine, it varies from 7.5 to 11.7 %. In case of penetrating chest injuries, the overall mortality reaches 10 %. Objective: to improve the treatment outcomes in chest injuries through the application of endovideosurgical technologies and local fibrinolytic therapy during the quaternary care in complications of combat thoracic trauma. Materials and methods. A clinical statistical analysis of the surgical outcomes was conducted in 103 victims with combat chest trauma, who received specialized thoracic surgical treatment for complications such as clotted hemothorax at the quaternary care level. The control group included 54 (52.4 %) casualties, and the experimental group included 49 (47.6 %). Results. According to the research findings, among the total number of chest injuries and traumas, lung injuries were the most common, accounting for 61.2 %. In the experimental group, lung injuries were identified in 27 cases. When analyzing the treatment of thoracic injuries and traumas in the control group, it was found that 21 (38.9 %) patients did not have sufficient pleural cavity drainage during the provision of primary medical and qualified care to eliminate hemo- and pneumothorax, and 33 (61.1 %) required various surgical procedures through thoracotomy accesses. Videothoracoscopy was performed in casualties with gunshot penetrating chest injuries, when metal fragments were located in the anterior mediastinum (between the sternum and ascending aorta) and posterior mediastinum (between the right main bronchus and esophagus, without damage to them). The removal of metal fragments from the mediastinum, sanitation, and drainage of the pleural cavity were performed. Among 26 casualties, who underwent pleural drainage, 4 patients have had unstable vacuum in the pleural cavity for three days. Conclusions. The implementation of the developed differentiated surgical approaches in the patients with chest injuries and clotted hemothorax contributed to a reduction in specific injury complications from 24.1 to 8.2 % and allowed for a decrease in the duration of hospital stay from 24 to 16 bed-days.

Dual nanoparticle immunostimulant hydrogel for synergistic combating “Cold” tumor

The immunosuppressive tumor microenvironment (TME) in “cold” triple-negative breast cancer (TNBC) leads to resistance to current immunotherapies. Here, we designed an in-situ hydrogel reservoir to deliver two types of nanoparticles (NPs) targeting 4T1 tumor cells and tumor-associated macrophages (TAMs) for cancer cell elimination and reversal of the immunosuppressive TME. The 4T1 tumor cell-targeted NPs could specifically deliver the mitochondria-targeted photosensitizer and catalase into 4T1 tumor cells to execute an enhanced photodynamic therapy and induce immunogenic cell death. The TAMs-targeted NPs delivered the stimulator of interferon genes (STING) agonist into macrophages to activate the STING pathway, triggering a type I interferon-driven innate immune response that induces a shift to a “hot” T cell-inflamed TME. This local synergistic therapy could effectively stimulate dendritic cell activation and the continuous T-cell infiltration, thereby reprograming the immunosuppressive TME, reinvigorating a powerful anti-tumor immune response and inhibiting tumor growth and metastasis in TNBC tumor model. In addition, this study combined with immune checkpoint blockade further achieves reinforced therapeutic outcome against “cold” tumor, providing a promising hydrogel-mediated platform for treatment of TNBC.

Successful Management of Opioid-refractory Pelvic Cancer Pain Using Continuous Local Anesthetic Infusion via a Tunneled Epidural

Opioid refractory pelvic cancer pain is common and difficult to manage, which often results in analgesic polypharmacy and escalating opioid doses, alongside the use of interventional techniques. However, up-titration of opioids often results in systemic side effects, and interventional procedures have limitations in their duration of action, efficacy, and risk of nerve damage. Therefore, intrathecal pumps have been utilized as a more permanent option for pain management. Their ability to deliver localized therapy using a variety of pharmacological agents makes it an attractive option for cancer pain management. However, they are limited by a need for careful titration, pump volume constraints, and risks of severe side effects. These limitations can be mitigated by targeting the epidural space instead, and we propose the use of a tunneled epidural catheter technique for continuous local anesthetic infusion in opioid-refractory pelvic and abdominal cancer pain. In this case report, we describe a patient with pelvic and abdominal cancer pain due to stage IV sigmoid adenocarcinoma with widespread metastases, who received adequate pain management from a continuous local anesthetic infusion through a tunneled lumbar epidural catheter. Throughout this patient’s hospital admission, their opioid requirements remained the same, and their pain remained well controlled on review in the community one month after discharge. This case demonstrated that epidural catheters with local anesthetic as the sole neuraxial analgesic agent over a short duration could potentially provide preventive analgesia. This case highlights that a local anesthetic tunneled epidural, without addition of neuraxial opioids, is an effective alternative to intrathecal pumps in managing complex cancer pain and has potential for preventive analgesia.

Next-generation skin cancer treatment: A quality by design perspective on artificial neural network-optimized cationic ethosomes with bleomycin sulphate

Skin cancer, exacerbated by environmental factors like ozone layer depletion, poses a global health concern. Topical administration of chemotherapy, a promising approach, minimizes systemic toxicity. Bleomycin Sulphate (BLM), effective intravenously, faces challenges due to limited skin penetration. Cationic ethosomes, known for superior skin penetration, address this by enhancing electrostatic interactions with cancer cells. This ensures localized drug delivery, preventing systemic circulation. Employing thin film hydration, we prepared cationic ethosomes with BLM, optimizing through Artificial Neural Network (ANN) and Response Surface Methodology (RSM). Characterization included entrapment efficiency, vesicle size, morphology, and zeta potential. In-vitro drug release and various kinetic models were analyzed. Ex-vivo evaluations, like dermatokinetic studies and fluorescence microscopy, and in-vivo skin sensitivity testing were conducted. Results showed the optimized formulation with 27.1 % entrapment efficiency, 144.3 nm vesicle size, smooth surface morphology, and positive zeta potential. Ex-vivo assessments indicated favorable skin retention and in-vivo tests suggested suitability for topical administration, highlighting its potential in skin cancer treatment. This research offers a promising strategy for localized and effective skin cancer therapy, addressing challenges associated with systemic toxicity and limited drug penetration.

Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

Brain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential strategy for improving radiation resistance. We used databases to detect the expression of MIF in NSCLC and its relationship with prognosis. We analyzed the effects of targeted blockade of the MIF/CD74 axis on the polarization and function of microglia during radiotherapy using flow cytometry. The mouse model of brain metastasis was used to assess the effect of targeted blockade of MIF/CD74 axis on the growth of brain metastasis. Our findings reveals that the macrophage migration inhibitory factor (MIF) was highly expressed in NSCLC and is associated with the prognosis of NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation in microglia and promoted the M1 polarization in combination of radiation. Additionally, blocking the MIF-CD74 interaction between NSCLC and microglia promoted microglia M1 polarization. Furthermore, radiation improved tumor hypoxia to decrease HIF-1α dependent MIF secretion by NSCLC. MIF inhibition enhanced radiosensitivity for brain metastasis via synergistically promoting microglia M1 polarization in vivo. Our study revealed that targeting the MIF-CD74 axis promoted microglia M1 polarization and synergized with radiotherapy for brain metastasis in NSCLC.

Clinico-pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis.

Patients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico-pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB). The NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan-Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival. Out of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson-Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy. The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy. This analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti-HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup.

Microbial landscape of periodontal pockets against local antibacterial therapy of chronic generalized periodontitis: a multicenter clinical trial

Background. A microbial nature of periodontitis requires an accurate analysis of the pathogenic potential of the periodontal pocket microflora thereby enabling correct diagnosis to be made and the most effective pharmacological agent to be selected for treating chronic periodontitis. Metronidazole demonstrates excellent results for anaerobic microorganisms in the periodontal pocket, whereas minocycline hydrochloride, moxifloxacin and amoxicillin/clavulanate are efficient for aerobic microorganisms. However, specialists find considerably relevant to analyze the correlations between specific bacterial associations in the periodontal pocket against local antibacterial therapy, as well as to track the contents of periodontal pockets long after antibacterial therapy. Therefore, a microbiological analysis of periodontal pocket contents is considered necessary in order to select and monitor the effectiveness of local antibacterial therapy.Objective. To evaluate the effectiveness of local antibacterial therapy for chronic generalized periodontitis by means of analysis of changes in the microbiological composition of periodontal pockets.Methods. The clinical trial involved 144 patients with chronic generalized periodontitis. The study included examination of patients and analysis of clinical data bases of the Department for General Practice Dentistry, Kuban State Medical University and the Dentistry Department, Stavropol State Medical University of the Ministry of Health of the Russian Federation. The trial included patients aged 30 to 60 with a diagnosis of chronic generalized periodontitis of different severity. All periodontitis patients were divided into 2 groups depending on the therapy: main and control groups. Each group had three subgroups depending on the severity of the pathologic process. The first subgroup of the control group (chronic generalized periodontitis of mild degree) consisted of 16 people (11.1%), the second subgroup (chronic generalized periodontitis of moderate degree) — 31 people (21.5%), the third subgroup (chronic generalized periodontitis of severe degree) — 7 people (4.9%). The first, second and third subgroups of the main group consisted of 28 (19.4%), 48 (33.3%) and 14 persons (9.7%) respectively. The severity of periodontitis was determined by the depth of the periodontal pocket, degree of bone resorption (according to x-ray examination), and pathologic tooth mobility. A local anti-inflammatory therapy for the patients of the control group included oral baths with propolis (15–20 drops of 10% propolis tincture diluted in 100 ml of warm water) 3 times a day for 7 days starting from the first visit. At the final stage of treatment after preliminary scaling and rootplaning, patients of the control group received antiseptic gel with 10% metronidazole and 2% chlorhexidine bigluconate to be injected into periodontal pockets with over 4 mm depth. Additionally, applications of adhesive dental films Diplene Denta L (with lincomycin) and Diplene Denta M (with metronidazole) were prescribed to be done in the home. In addition to the above-mentioned comprehensive therapy, patients of the main group received a single insufflation of minocycline hydrochloride microspheres into each periodontal pocket. The tools for the patients of the main group included plastic cannulas with minocycline hydrochloride microspheres in the form of powder in the tip of the cartridge, and a special syringe-insufflator. The technique of antibiotic insufflation into the periodontal pocket was preliminary trained on the model of jaws with the studied pathology. Statistical analysis of the results was performed using variance analysis in the Excel Microsoft Office 2016 (Microsoft, USA).Results. According to the systematic observation of the patients from the control group, periodic fluctuations in microbial population in the majority of pathologic pockets obtained a specific regularity: a decrease in the number of microorganisms on day 21 was followed by its increase in the subsequent period of observation after 30 and especially 60 days. According to the ongoing follow-up of the patients of the main group, fluctuations of microbial population in the majority of pathologic pockets obtained a certain regularity: a significant reduction in the number of microorganisms on day 21 was followed by its slight rise in the subsequent period of observation after 30 and a slight increase again in 60 days. Fluctuations in the number of microorganisms of periodontal pockets in the main group reveal their specific character: their number remained invariably lower than that of the control group throughout the observation period, while the total number of detected periodontopathogens decreased.Conclusion. The established correlations between the main indicators of microbiological status of periodontal pockets and the severity of chronic generalized periodontitis within different periods after the local therapy confirm the positive dynamics of treatment in the main group, where patients were insufflated with minocycline hydrochloride microspheres, proved by a change in the typology of microbial status of periodontal pockets and a number of periodontopathogenic microorganisms.

S1-Guideline Sebaceous Carcinoma.

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

The Role of Vibrators in Women's Pelvic Health: An Alluring Tool to Improve Physical, Sexual, and Mental Health.

In limited studies vibrators have been shown to improve sexual function and pelvic floor health; however, there are even fewer studies on the effect of vibrator use on overall genitourinary and mental health. To investigate the effect of regular vibrator use on sexual, genitourinary, and mental health in addition to quality of life. We performed a prospective pilot study of women aged 18 to 80years recruited from a urogynecology clinic. Study participants were instructed to use a vibrator according to the protocol. Sexual function, pelvic floor function, mental health, and pelvic examination were assessed at the initial visit and at 3 months' follow-up using validated questionnaires. Of the 79 participants enrolled in the study, 53 women (66%) completed the study. The mean age of the participants was 54.7years (range 19-80years), and the majority of participants were white (n = 59, 74.7%), post-menopausal (n = 48, 60.8%), and not receiving systemic (n = 63, 79.7%) or local (n = 63, 79.7%) hormone therapy. Sexual function significantly improved over time (p = 0.002), whereas the rate of bothersome pelvic organ prolapse symptoms and pain scores significantly decreased (p = 0.034 and 0.0008 respectively). Rates of urge urinary incontinence decreased although this was not statistically significant (p = 0.059). There was a significant improvement in the gross appearance of lichen sclerosus lesions (p = 0.025) and in the severity of vaginal atrophy (p = 0.018). Rates of depression were significantly decreased (p = 0.011). Vibrator use was associated with improved sexual, genitourinary, and mental health.

Navigating Breast Cancer Oligometastasis and Oligoprogression: Current Landscape and Future Directions.

We examine the potential for curative approaches among metastatic breast cancer (MBC) patients by exploring the recent literature on local ablative therapies like surgery and stereotactic body radiation therapy (SBRT) in patients with oligometastatic (OM) breast cancer. We also cover therapies for MBC patients with oligoprogressive (OP) disease. Surgery and SBRT have been studied for OM and OP breast cancer, mainly in retrospective or non-randomized trials. While many studies demonstrated favorable results, a cooperative study and single-institution trial found no support for surgery/SBRT in OM and OP cases, respectively. While there is interest in applying local therapies to OM and OP breast cancer, the current randomized data does not back the routine use of surgery or SBRT, particularly when considering the potential for treatment-related toxicities. Future research should refine patient selection through advanced imaging and possibly explore these therapies specifically in patients with hormone receptor-positive or HER2-positive disease.

Racial disparities in outcomes of patients with stage I-III triple-negative breast cancer after adjuvant chemotherapy: a post-hoc analysis of the E5103 randomized trial.

Breast cancer mortality is higher in Black women than other racial groups. This difference has been partially attributed to a higher proportion of triple-negative breast cancer (TNBC). However, it is uncertain if survival disparities exist in racially diverse TNBC patients receiving similar treatments. Here, we examine racial differences in disease-related outcomes in TNBC patients treated on the E5103 clinical trial. From 2007 to 2011, 4,994 patients with stage I-III HER2-negative breast cancer were randomized to adjuvant chemotherapy with or without bevacizumab. This analysis was limited to the subset of 1,742 TNBC patients with known self-reported race. Unadjusted Kaplan-Meier curves and adjusted Cox-Proportional Hazards models were used to determine breast cancer events and survival outcomes. Of the analysis population, 51 (2.9%) were Asian, 269 (15.4%) Black, and 1422 (81.6%) White. Median age was 51 years. Patient characteristics, treatment arm, and local therapies were similar across racial groups. White women were more commonly node-negative (56% vs. 49% and 44% in Asian and Black women, respectively; p < 0.01). At a median follow-up of 46 months, unadjusted Kaplan-Meier locoregional and distant recurrence, and disease-free and overall survival, did not differ significantly by race. In Cox models adjusted for patient and tumor characteristics and treatment arm, race was not associated with any disease event. Larger tumor size and nodal involvement were consistently associated with breast cancer events. This clinical trial population of similarly treated TNBC patients showed no racial differences in breast cancer outcomes. Disease extent, rather than race, was associated with disease events.

Cetuximab for the treatment of cutaneous squamous-cell carcinoma in kidney transplant recipients – A retrospective cohort study

Background: Kidney transplant recipients are at high risk of developing cutaneous squamous cell carcinoma (cSCC) due to prolonged immunosuppression. While most lesions can be managed with local therapy, a subset of patients develop advanced cSCC that is unresectable, recurrent or metastatic. Immune check point inhibitors (ICI) and chemotherapy may jeopardize the transplanted kidney. Cetuximab, an anti-epidermal growth factor receptor antibody, has demonstrated efficacy in advanced cSCC, but data regarding efficacy and safety in solid organ transplant recipients is lacking. Methods: This retrospective cohort study analyzed kidney transplant recipients diagnosed with locally advanced or metastatic cSCC who were treated with cetuximab. Results: Seventeen patients were included in the analysis. The median age was 57 years at the time of kidney transplantation and 62 years at diagnosis of index lesion. Cetuximab was administered with radiation therapy as a radiosensitizer in 58.8% of patients, as monotherapy in 17.6% of patients, and with chemotherapy in 23.5% of patients. Importantly, no detrimental impacts on kidney graft function were observed. The main toxicites were grade 1–2 skin reactions and electrolyte imbalance. Of the 10 patients receiving cetuximab with chemoradiotherapy as a radiosesnitizer, 2 were treated with definitive intent, 7 of them in the adjuvantsetting, and 1 for palliative pourpose. Over half of these patients achieved a complete response (37.29%) or no recurrence after resection (23.5%). Median time to disease progression was 10 months. Conclusions: This novel study suggests cetuximab has a reasonable safety profile and potential efficacy in kidney transplant recipients with advanced cSCC, without impairing allograft function. Further prospective research with larger sample sizes is warranted to confirm these findings. Cetuximab should be investigated as a systemic treatment option for this high-risk population of solid organ transplant recipientss with recurrent, metastatic, or unresectable cSCC.

Biodegradable Microspheres for Transarterial Chemoembolization in Malignant Liver Disease.

Transarterial chemoembolization (TACE) has revolutionized the treatment landscape for malignant liver disease, offering localized therapy with reduced systemic toxicity. This manuscript delves into the use of degradable microspheres (DMS) in TACE, exploring its potential advantages and clinical applications. DMS-TACE emerges as a promising strategy, offering temporary vessel occlusion and optimized drug delivery. The manuscript reviews the existing literature on DMS-TACE, emphasizing its tolerability, toxicity, and efficacy. Notably, DMS-TACE demonstrates versatility in patient selection, being suitable for both intermediate and advanced stages. The unique properties of DMS provide advantages over traditional embolic agents. The manuscript discusses the DMS-TACE procedure, adverse events, and tumor response rates in HCC, ICC, and metastases.

Visceral Leishmaniasis (Kala-azar) in Merti Sub-County, Isiolo County: A Case of Socio-Cultural Challenges

Introduction: Visceral Leishmaniasis (VL) also known as Kala-azar is a fatal neglected tropical disease (NTD) with a 95% fatality rate among untreated cases. Although there is little information available about the disease's prevalence in Isiolo County, it is extremely endemic in a number of villages in Merti Sub-County. Case Presentation: In this case presentation, a family of three children resulted to traditional therapy when the children contracted Kala-azar. All the three children exhibited signs of fever, loss of appetite, swollen abdomen, vomiting, and general weakness. Discussion: Low levels of Visceral Leishmaniasis knowledge, ignorance characterized by cultural beliefs, and the use of local therapies are among socio-cultural challenges impeding implementation of effective Kala-azar control strategies in Isiolo County. Conclusion: This case highlights the importance of focused community awareness for prompt and efficient diagnosis and treatment to lower Kala-azar prevalence, monitoring the burden and spread of the disease as well as lowering transmission.

Ankle arthrodesis through minimally-invasive transfibular approach: a new surgical technique.

The purpose of our work was to demonstrate the surgical technique of ankle arthrodesis using the minimally-invasive transfibular (MITF) approach, which minimizes soft tissue damage and is advantageous for high-risk patients. In this prospective study, a total of 12 patients with end-stage varus ankle osteoarthritis, including high-risk individuals, underwent ankle arthrodesis using the MITF approach. The technique involves a unique osteotomy at the joint space level, minimizing soft tissue detachment from the fibula. The primary outcomes assessed included bony union, time to weight-bearing, correction of varus deformity, and functional outcomes measured by the American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scale. However, the study's limitations encompass a small sample size and the absence of a control group. At 6months post-operation, all patients achieved bony union, with a mean time to union of 13.7 ± 5.2weeks. The average time to initiate weight-bearing without additional support was 11.2 ± 3.8weeks. Preoperative varus deformity (17.08 ± 8.36 degrees) and talar tilt (8.75 ± 4.33 degrees) were successfully corrected, with postoperative alignment within 0-5 degrees of valgus. Functional outcomes showed a significant improvement in AOFAS scores from 37.83 ± 7.79 points preoperatively to 77.42 ± 5.63 points one year after surgery (p = 0.002). Minor complications occurred in two patients, both effectively treated with local therapy and antibiotics. The MITF approach for ankle arthrodesis demonstrates promising results in addressing end-stage varus ankle osteoarthritis, even in high-risk patients. However, the study's limitations highlight the need for a prospective comparative clinical trial with a larger sample size to ascertain the technique's effectiveness and safety definitively.