Adjuvant Approach Research Articles

Platelets up-Regulate Tumor Cell Programmed Death-Ligand 1 through Epidermal Growth Factor Receptor Signal Transduction

Introduction: Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) are important immune checkpoint proteins in cancer immunotherapy and targeted therapies against PD-L1 have significantly prolonged many patients' lives. Recently, high baseline platelet to lymphocyte ratio was reported to be associated with decreased patient response rate to immune checkpoint inhibition (ICI) therapies, including anti-PD-L1 therapy, suggesting the potential role of platelets in tumor immunity. Platelets express PD-L1 on their surface, and platelets binding to PD-L1 negative tumor cells can “decorate” tumor cells with PD-L1 and protect against T cell-mediated cytotoxicity. However, whether platelet can affect PD-L1 expression on tumor cells is still unknown.Methods: In this study, we designed platelet-tumor cell co-culture systems to investigate whether direct or indirect exposure to platelets affects tumor cell PD-L1 surface expression. Considering platelets can be artificially activated by commonly used cell culture medium, the co-culture was performed in platelet resuspension buffer (HEPES, NaCl, KCl, MgCl2, NaHCO3, Glucose, pH7.4) supplied with fetal bovine serum and L-glutamine. After 24 hours of co-culture, platelets were washed out and fresh culturing medium was added to tumor cells and cultured for another 24 hours. At the end of the experiments, tumor cells were harvested and the PD-L1 expression analyzed by flow cytometry and RT-qPCR.Results and discussion: Here we report that direct co-culture of platelets with either breast cancer cell line MDA-MB-468 or lung cancer cell line A549 increased tumor cell PD-L1 surface expression by up-regulating PD-L1 transcription. This platelet-induced tumor cell PD-L1 up-regulation can be partly reduced by pre-treating platelets with antiplatelet agents such as aspirin and ticagrelor, suggesting platelet activation contributes to platelet induced tumor cell PD-L1 up-regulation. The up-regulation of tumor cell PD-L1 by platelets was not due to abundant platelet cytokines such as C-C Motif Chemokine Ligand 5 (CCL5) and C-X-C motif chemokine 5 (CXCL5). However, both an epidermal growth factor (EGF) neutralizing antibody and cetuximab (EGFR neutralizing monoclonal antibody) decreased the platelet-induced increase in tumor cell PD-L1, suggesting that platelets initiate tumor cell PD-L1 transcription through the EGF signaling pathway. Our data indicate a novel function of platelets in tumor immunity and warrant further investigation to determine if targeting platelets offers a novel adjuvant approach to improve ICI therapy. DisclosuresItaliano: Sierra Oncology: Consultancy; PlateletBio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Carrick Therapeutics: Consultancy.

Novel intestinal dialysis interventions and microbiome modulation to control uremia.

In patients with chronic kidney disease (CKD), the gut plays a key role in the homeostasis of fluid and electrolyte balance and the production and disposal of uremic toxins. This review summarizes the current evidence on the gut-targeted interventions to control uremia, fluid overload, hyperkalemia and hyperphosphatemia in CKD. Studies have emerged that support the concept of intestinal dialysis, such as colonic perfusion with a Malone antegrade continence enema stoma or colonic irrigation with a rectal catheter, as a promising adjuvant approach to control uremia in CKD, although most findings are preliminary. The use of AST-120, an oral adsorbent, has been shown to reduce circulating levels of indoxyl sulfate and p-cresol sulfate and have potential renoprotective benefits in patients with advanced CKD. Diarrhea or inducing watery stools may modulate fluid retention and potassium and phosphorus load. Accumulating evidence indicates that plant-based diets, low-protein diets, and pre-, pro-, and synbiotic supplementation may lead to favorable alterations of the gut microbiota, contributing to reduce uremic toxin generation. The effects of these gut-targeted interventions on kidney and cardiovascular outcomes are still limited and need to be tested in future studies including clinical trials. Interventions aimed at enhancing bowel elimination of uremic toxins, fluid and electrolytes and at modulating gut microbiota may represent novel therapeutic strategies for the management of uremia in patients with CKD.

Senescent cells in cancer therapy: why and how to remove them.

Cellular senescence is a stress response that imposes a growth arrest on cancer and nonmalignant cells during cancer therapy. By secreting a plethora of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP), therapy-induced senescent cells can promote tumorigenesis. Moreover, the SASP from senescent cells is also able to drive therapy resistance and mediate many adverse effects of cancer therapy. Because senescent cell production often occurs during cancer therapy, it is important to carefully consider these potential detrimental effects. Senotherapy, which refers to selective removal of senescent cells, has been proposed as a promising adjuvant approach to eliminate the adverse effects of senescent cells. Thus, in this review we summarize in detail the mechanisms by which senescent cells contribute to tumorigenesis and therapeutic resistance. Also, we thoroughly discuss the potential strategies regarding how to effectively circumvent the undesirable effects of therapy-induced senescent cells.

Efficacy and Safety of Adjuvant Breast Radiation Therapy for Patients With Early-Stage Breast Cancer: A Systematic Review and Network Meta-Analysis

<h3>Purpose/Objective(s)</h3> To compare the efficacy and safety of various adjuvant breast radiation therapy treatment approaches for patients with early-stage breast cancer treated with breast conservation surgery. <h3>Materials/Methods</h3> We searched PubMed, EMBASE, CENTRAL for randomized trials comparing two or more adjuvant breast RT treatment approaches for patients with early-stage breast cancer treated with breast conservation surgery. Eligible trials reported at least one of the outcomes including time to ipsilateral breast recurrence, overall survival and breast tissue related adverse events. We performed frequentist and Bayesian meta-analyses for time to ipsilateral breast recurrence and overall survival outcomes. We used the synthesis without meta-analysis (SWiM) approach to evaluate the breast tissue related adverse events outcome. <h3>Results</h3> We identified nine eligible trials involving 14799 patients and five treatments: conventional or moderately hypofractionated whole breast irradiation (CF/MFWBI), ultra hypofractionated whole breast irradiation (UFWBI), accelerated ultra hypofractionated whole breast irradiation (AUFWBI), moderately hypofractionated partial breast irradiation (MFPBI) and accelerated partial breast irradiation (APBI). MFPBI was ranked the most favorable for delay in time to ipsilateral breast recurrence (<i>P</i> score: 78%) and overall survival (<i>P</i> score: 70%) compared to other treatment approaches, although there were no statistically significant differences. APBI was ranked the least favorable for both time to ipsilateral breast recurrence (<i>P</i> score: 17%) and overall survival (<i>P</i> score 35%) and was associated with statistically significant higher hazards for ipsilateral breast recurrence compared to CF/MFWBI (Hazard ratio 1.28, 95% confidence interval 1.01 - 1.63). Sensitivity analysis using Bayesian analyses showed similar results. SWiM approach demonstrated that the overall direction of effect favors MFPBI when compared to MFWBI for breast tissue related adverse events. The overall direction of effect favors CF/MFWBI when compared to UFWBI, AUFWBI and APBI for breast tissue related adverse events. <h3>Conclusion</h3> Amongst the alternatives to CF/MFWBI, adjuvant MFPBI was associated with the best time to ipsilateral breast recurrence and overall survival benefits. MFPBI also reduced breast tissue related adverse events for patients with early-stage breast cancer treated with breast conservation surgery, compared with CF/MFWBI.

A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

1435TiP Adjuvant immunotherapy for resected esophageal squamous cell carcinoma with high risk of recurrence (AIRES): A multicenter, open-label, randomized, controlled phase III trial

Esophageal squamous cell carcinoma (ESCC) patients with nodal disease (ypN+) after conventional trimodality are at high risk of recurrence. Furthermore, chemoradiotherapy is not the standard of care for localized ESCC patients in many parts of the world, where neoadjuvant chemotherapy is preferred. Immunotherapy, as an adjuvant approach, has been demonstrated effective and changed the standard of care. Adjuvant immunotherapy following perioperative chemotherapy has not been investigated as a treatment option in the Asian population.

The upregulation of oncogenic miRNAs in swabbed samples obtained from oral premalignant and malignant lesions.

Oncogenic miRNAs upregulated in OSCC play a range of versatile roles in oral carcinogenesis. Oral potentially malignant disorders (OPMDs) are the antecedent lesions to oral squamous carcinoma (OSCC) and they require a definitive diagnosis and early intervention. This study hypothesizes the presence of aberrant oncogenic miRNA expression in swabbed oral lesions. The expression of miR-21, miR-31, miR-134, miR-146a, and miR-211 in swabbed samples from 36 dysplastic or hyperplastic OPMDs and 10 OSCCs, relative to respective normal mucosa within the same patient, is analyzed with qRT-PCR to develop a diagnosis. Upregulation of all tested miRNAs in OPMD and OSCC samples comparing to controls is found to have occurred. Receiver operating characteristics curve analysis shows that miR-31 gives the best diagnostic accuracy of 0.91 when differentiating OPMD/OSCC from controls. An analysis of miR-134 and miR-211 expression allows the discrimination of the dysplastic state associated with OPMD, while the use of expression of the combined miRNAs further improves the analytical performances when identifying the dysplastic state. The concordant upregulation of miR-21, miR-31, and miR-146a is found to occur during an early stage of OSCC carcinogenesis. This study demonstrates the upregulation of multiple oncogenic miRNAs in swabbed OPMD and OSCC samples. miRNA expression in swabbed collectives enables the differentiation between normal mucosa and OPMD/OSCC, independent of their histopathological severity. This conventional and convenient sampling tool, when coupled with an assessment of miR-31 expression, would seem to be an adjuvant approach to the diagnosis of OPMD and OSCC.

Advances and Perspectives in the Use of Carbon Nanotubes in Vaccine Development.

Advances in nanobiotechnology have allowed the utilization of nanotechnology through nanovaccines. Nanovaccines are powerful tools for enhancing the immunogenicity of a specific antigen and exhibit advantages over other adjuvant approaches, with features such as expanded stability, prolonged release, decreased immunotoxicity, and immunogenic selectivity. We introduce recent advances in carbon nanotubes (CNTs) to induce either a carrier effect as a nanoplatform or an immunostimulatory effect. Several studies of CNT-based nanovaccines revealed that due to the ability of CNTs to carry immunogenic molecules, they can act as nonclassical vaccines, a quality not possessed by vaccines with traditional formulations. Therefore, adapting and modifying the physicochemical properties of CNTs for use in vaccines may additionally enhance their efficacy in inducing a T cell-based immune response. Accordingly, the purpose of this study is to renew and awaken interest in and knowledge of the safe use of CNTs as adjuvants and carriers in vaccines.

Electroacupuncture as an Adjuvant Approach to Rehabilitation during Postacute Phase after Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Increasing attention has been paid to electroacupuncture (EA) for promoting postoperative rehabilitation, but the effectiveness of EA for rehabilitation after total knee arthroplasty (TKA) remains obscure. Objective To examine the effect of EA on rehabilitation after TKA. Methods Database searches on PubMed, CINAHL, Embase, and China National Knowledge Infrastructure (CNKI) were carried out to obtain articles, from inception to 15 October 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was conducted to assess the effects of acupuncture on pain, range of knee motion, and postoperative vomiting after TKA. Results In the current study, a total of ten randomized clinical trials were included according to the inclusion and exclusion criteria. Compared to basic treatment, EA combined with basic treatment showed a significantly greater pain reduction on 3, 7, and 14 days postoperatively after TKA. However, we found that EA had no significant improvement in enhancing the range of knee motion and decreasing the percentage of vomiting. Subgroup analysis suggested that a combination of EA and rehabilitation training was superior to rehabilitation training in pain relief, while EA combined with celecoxib capsules showed no significant difference in improving pain compared to celecoxib capsules alone. Conclusions In the postacute phase after TKA, EA, as a supplementary treatment, could reduce postoperative pain, but no evidence supported the benefits of EA for improving ROM of knee and decreasing the ratio of vomiting. Additional high-quality and large-scale RCTs are warranted.

Moving beyond PARP Inhibition: Current State and Future Perspectives in Breast Cancer.

Breast cancer is the most frequent and lethal tumor in women and finding the best therapeutic strategy for each patient is an important challenge. PARP inhibitors (PARPis) are the first, clinically approved drugs designed to exploit synthetic lethality in tumors harboring BRCA1/2 mutations. Recent evidence indicates that PARPis have the potential to be used both in monotherapy and combination strategies in breast cancer treatment. In this review, we show the mechanism of action of PARPis and discuss the latest clinical applications in different breast cancer treatment settings, including the use as neoadjuvant and adjuvant approaches. Furthermore, as a class, PARPis show many similarities but also certain critical differences which can have essential clinical implications. Finally, we report the current knowledge about the resistance mechanisms to PARPis. A systematic PubMed search, using the entry terms “PARP inhibitors” and “breast cancer”, was performed to identify all published clinical trials (Phase I-II-III) and ongoing trials (ClinicalTrials.gov), that have been reported and discussed in this review.

Moderate-intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats.

What is the central question of this study? The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well-established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known. What is the main finding and its importance? Moderate-intensity aerobic training had benefits in a rodent model of iron-overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non-pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron-overloaded patients. Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100mg/kg, 5days/week for 4weeks); thereafter, the rats were kept sedentary or exercised (60min/day, progressive aerobic training, 60-70% of maximal speed, 5days/week on a treadmill) for 8weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen typeI and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for iron-overload cardiomyopathy.

Evaluation effectiveness analysis of adjuvant antibiotic therapy in the process of complex periodontal patients treatment

Annotation. Received the large set of factors influencing the success of the results and duration of patients treatment with periodontal disease, as well as different levels of correlation of these factors it is advisable to study the use of adjuvant antibiotic therapy in the patients treatment with periodontal disease, which became the purpose of our work. To test the effectiveness of adjuvant antibiotic therapy in the complex treatment of periodontal pathology from the primary study category of patients, four groups were formed a total numbering of 240 people: the group of antibiotics without determining antibiotic sensitivity, the group of antibiotics according to rapid diagnosis, the group of antibiotics according to detailed analysis group of amoxiclav and ciprofloxacin. Mathematical and statistical data processing was performed using the application software STATISTICA 6.0. According to a meta-analysis of the effectiveness of antimicrobial and subantimicrobial antibiotic therapy as an adjuvant approach to the treatment of periodontal disease, it was found that the use of broad-spectrum agents and targeted antianaerobic drugs contributed to a more pronounced improvement in clinical attachment and reduced depth levels. Thus, antibacterial support of the active phase of the periodontal therapy protocol contributes to the clinically significant reduction of the main symptoms associated with the influence of relevant associations of periodontal pathogens, reducing the actual number of such and imbalance of their quantitative ratios in the biofilm structure as a specific factor. Reducing the volume of repeated iatrogenic surgical and conservative interventions due to the early use of antibacterial agents also contributes to the increase in cost-effectiveness, as fewer total manipulations contribute to achieving the appropriate target effect.

Spiky Gold Nanoparticles for the Photothermal Eradication of Colon Cancer Cells.

Colorectal cancer (CRC) is a widespread and lethal disease. Relapses of the disease and metastasis are very common in instances of CRC, so adjuvant therapies have a crucial role in its treatment. Systemic toxic effects and the development of resistance during therapy limit the long-term efficacy of existing adjuvant therapeutic approaches. Consequently, the search for alternative strategies is necessary. Photothermal therapy (PTT) represents an innovative treatment for cancer with great potential. Here, we synthesize branched gold nanoparticles (BGNPs) as attractive agents for the photothermal eradication of colon cancer cells. By controlling the NP growth process, large absorption in the first NIR biological window was obtained. The FBS dispersed BGNPs are stable in physiological-like environments and show an extremely efficient light-to-heat conversion capability when irradiated with an 808-nm laser. Sequential cycles of heating and cooling do not affect the BGNP stability. The uptake of BGNPs in colon cancer cells was confirmed using flow cytometry and confocal microscopy, exploiting their intrinsic optical properties. In dark conditions, BGNPs are fully biocompatible and do not compromise cell viability, while an almost complete eradication of colon cancer cells was observed upon incubation with BGNPs and irradiation with an 808-nm laser source. The PTT treatment is characterized by an extremely rapid onset of action that leads to cell membrane rupture by induced hyperthermia, which is the trigger that promotes cancer cell death.

Efficacy of inferior turbinate reduction in pediatric patients: a prospective analysis.

Chronic nasal congestion is a common presentation in the pediatric setting. For patients who fail to respond to maximal medical therapy and adenoidectomy, inferior turbinate reduction (ITR) may be a reasonable adjuvant surgical approach. Our objective was to prospectively evaluate nasal congestion symptoms and daily medication use in the year following ITR in children with and without allergic rhinitis (AR). Patients younger than 18 years undergoing ITR alone or in combination with nonsinonasal procedures were enrolled. Scores from the Nasal Obstruction Symptom Evaluation (NOSE) survey were collected preoperatively and at 3, 6, and 12 months postoperatively from 96 patients. Number and type of pertinent daily medications utilized were also analyzed using Wilcoxon signed-rank and McNemar's tests. Patients with and without comorbid AR were then compared using Wilcoxon rank-sum tests. Median (range) NOSE sum scores significantly improved from preoperative median of 65 out of 100 points (0-100) to 20 (0-100), (z=7.12, p<0.001) at 12 months postoperatively. The median number of daily medications was significantly reduced from 1 (range, 0-4) preoperatively to 0 (range, 0-5) postoperatively (z=2.38, p=0.017). Fifty-six (58.3%) patients had AR. AR patients received more medications preoperatively and postoperatively compared with those without AR (z=-2.96, p=0.003; z=-2.23, p=0.024). At 12 months, NOSE scores remained significantly greater in patients with AR compared with those without AR (β=11.6; 95% confidence interval [CI], 0.676-22.5; p=0.038). Our data highlight the need for a multimodal approach to chronic nasal congestion, particularly in children with AR.

An In vitro System to Gauge the Thrombolytic Efficacy of Histotripsy and a Lytic Drug.

Deep vein thrombosis (DVT) is a global health concern. The primary approach to achieve vessel recanalization for critical obstructions is catheter-directed thrombolytics (CDT). To mitigate caustic side effects and the long treatment time associated with CDT, adjuvant and alternative approaches are under development. One such approach is histotripsy, a focused ultrasound therapy to ablate tissue via bubble cloud nucleation. Pre-clinical studies have demonstrated strong synergy between histotripsy and thrombolytics for clot degradation. This report outlines a benchtop method to assess the efficacy of histotripsy-aided thrombolytic therapy, or lysotripsy. Clots manufactured from fresh human venous blood were introduced into a flow channel whose dimensions and acousto-mechanical properties mimic an iliofemoral vein. The channel was perfused with plasma and the lyticrecombinant tissue-type plasminogen activator. Bubble clouds were generated in the clot with a focused ultrasound source designed for the treatment of femoral venous clots. Motorized positioners were used to translate the source focus along the clot length. At each insonation location, acoustic emissions from the bubble cloud were passively recorded, and beamformed to generate passive cavitation images. Metrics to gauge treatment efficacy included clot mass loss (overall treatment efficacy), and the concentrations of D-dimer (fibrinolysis) and hemoglobin (hemolysis) in the perfusate. There are limitations to this in vitro design, including lack of means to assess in vivo side effects or dynamic changes in flow rate as the clot lyses. Overall, the setup provides an effective method to assess the efficacy of histotripsy-based strategies to treat DVT.

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot.

Immune checkpoint blockade (ICB) is transforming treatment for many cancers. While ICB alone initially demonstrated efficacy in patients with metastatic melanoma, it has expanded to other types and to earlier-stage cancers. We describe ICB history, mechanisms underlying variation in response, and how ICB is being integrated into adjuvant and neoadjuvant treatment approaches.

Diaphragm Pacing and a Model for Respiratory Rehabilitation After Spinal Cord Injury.

Cervical spinal cord injury (CSCI) can cause severe respiratory impairment. Although mechanical ventilation (MV) is a lifesaving standard of care for these patients, it is associated with diaphragm atrophy and dysfunction. Diaphragm pacing (DP) is a strategy now used acutely to promote MV weaning and to combat the associated negative effects. Initial reports indicate that DP also may promote neuromuscular plasticity and lead to improvements in spontaneous diaphragm activation and respiratory function. These outcomes suggest the need for reevaluation of respiratory rehabilitation for patients with CSCI using DP and consideration of new rehabilitation models for these patients and their unique care needs. This article discusses the rationale for consideration of DP as a rehabilitative strategy, particularly when used in combination with established respiratory interventions. In addition, a model of respiratory rehabilitation and recovery (RRR) is presented, providing a framework for rehabilitation and consideration of DP as an adjuvant rehabilitation approach. The model promotes goals such as respiratory recovery and independence, and lifelong respiratory health, via interdisciplinary care, respiratory training, quantitative measurement, and use of adjuvant strategies such as DP. Application of the model is demonstrated through a description of an inpatient rehabilitation program that applies model components to patients with CSCI who require DP. As DP use increases for patients with acute CSCI, so does the need and opportunity to advance rehabilitation approaches for these patients. This perspective article is a critical step in addressing this need and motivating the advancement of rehabilitation strategies for CSCI patients. (See Video Abstract, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A348).

The clinicopathological and survival analysis of urological mucosal melanoma: A single-center retrospective observational study.

e21588 Background: Primary mucosal melanoma arising in the urinary tract is rare and poorly characterized. Methods: The records of patients with urological mucosal melanoma who presented to the department of Renal Cancer and Melanoma of Peking University Cancer Hospital between September, 2004 and April, 2019 were reviewed. Available clinicopathological and molecular characteristics were summarized, including pathological parameters, gene mutation, primary surgical intervention, systemic treatment and clinical course. The rates of local recurrence rate, loco-regional lymph node metastasis and distant metastasis were assessed. American Joint Committee on Cancer (AJCC) TNM Staging System for bladder cancer/renal pelvis and ureter cancer/urethral carcinoma (8th ed., 2017) were adopted for staging. Results: Fifty-eight patients were involved in the study with a median age of 62.5 years (range: 32-82). The anatomic sites of the primary urological mucosal melanomas were from the urethra (89.7%), bladder (6.9%), ureter (0%) and kidney (0%), and the left (4.4%) were from multiple loci. At initial diagnosis, 75.9% (n=44) were stage I/II disease, 1.7% (n=1) stage III, and 22.4% (n=13) stage IV. There was 3.4% incidence of CKIT mutation and 1.7% of BRAF mutation. After median follow-up of 22.6 mo, 31.4% (16/51) relapsed locally after organ-preserved surgery. 21.6% (11/51) and 39.2% (20/51) developed metastases to reginal lymph nodes and distance, respectively. The median relapse free survival and median overall survival were 12.2 (95%CI: 7.9-16.4) mo and 33.9 (95%CI: 19.2-48.6) mo, respectively. Univariate Cox analysis showed that TNM stage and systemic adjuvant therapy were the prognostic factors of OS, while no association was found with Breslow thickness, miotic rate, ulceration and gender. Conclusions: Urological mucosal melanoma predominantly arises from lower urinary tract with rare BRAF and CKIT mutation. AJCC TNM Staging System for urothelial carcinoma is proved practical for urothelial melanoma, which should be validated in larger population. Future research is required to identify adjuvant treatment approaches to improve disease outcomes.

Chemoradiotherapy or chemotherapy as adjuvant treatment for resected gastric cancer: should we use selection criteria?

The management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches. This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapy. We retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT. After a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2-N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy. There is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI.

Platelet Rich Fibrin( PRF )-A Novel Generation of Regeneration in Endodontics: A Review

In the field of regenerative medicine, PRP/PRF whichwas will be is used as a surgical adjuvant becamethe new glorified approach. For the Regenerative endodontic treatment based on the tissue engineeringconcept, creating a favourable environment free of pathogens, for preservation and migration of stem cells,pathogen eradication, stem cell preservation, presence of scaffold facilitating spatial orientation and signalmolecules released by cells is of utmost importance. In tooth revascularisation and revitalization, successfulapplication of platelet concentrates as scaffolds have been reported. Being autologous, comprising of highgrowth factor concentrates and relatively hassle-free preparation in dental setup, platelet concentrates arepreferred. The advancement in the regenerative endodontics field, with the introduction of the differentgeneration of platelet concentrates, is a breakthrough.