High Recurrence Research Articles

The Safety and Efficacy of Left Atrial BOX Ablation in Persistent Atrial Fibrillation: A Meta-Analysis.

Circumferential pulmonary vein isolation (CPVI) has a high recurrence rate in managing persistent atrial fibrillation (AF). While some studies suggest that augmenting CPVI with additional left atrial BOX ablation can diminish this recurrence rate among patients with persistent AF, this approach remains controversial. This meta-analysis assesses the safety and efficacy of adjunctive left atrial BOX ablation in treating persistent atrial fibrillation. We conducted a comprehensive literature search across China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Cochrane Library, focusing on randomized controlled trials. The primary outcome was the recurrence rate of any atrial arrhythmias (AAs) within one-year post-treatment, with the secondary outcome being the frequency of adverse events related to the surgery. The combination of CPVI and left atrial BOX ablation did not lead to a significant reduction in the overall recurrence rate of atrial arrhythmias (risk ratios (RR) = 0.86, 95% confidence interval (CI) = 0.73-1.02, I2 = 35%). However, subgroup analyses revealed that this therapeutic approach significantly decreased the recurrence rates of all atrial arrhythmias (RR = 0.67, 95% CI = 0.49-0.92, I2 = 15%) and specifically atrial fibrillation (RR = 0.53, 95% CI = 0.37-0.77, I2 = 0%) in patients with a left atrial diameter ≤44 mm. Notably, there was no significant increase in the incidence of procedure-related adverse events (RR = 1.04, 95% CI = 0.56-1.94, I2 = 0%). However, the durations of both the ablation (mean difference (MD) = 19.77, 95% CI = 15.84-23.70, I2 = 0%) and the overall procedure (MD = 15.64, 95% CI = 6.99-24.29, I2 = 0%) were longer due to the additional ablation steps. In patients with smaller left atrial diameters, augmenting CPVI with left atrial BOX ablation significantly lowers the recurrence rates of atrial arrhythmias and atrial fibrillation without elevating surgical risk levels.

Diagnostic value of expressions of cancer stem cell markers for adverse outcomes of hepatocellular carcinoma and their associations with prognosis: A Bayesian network meta‑analysis.

The expression of cancer stem cell (CSC) markers adversely affect the survival prognosis of patients with hepatocellular carcinoma (HCC), but it is not clear which cancer stem cell marker has the best predictive effect on the survival prognosis and diagnostic value indicators of patients with HCC. Therefore, the present study performed a network meta-analysis to compare the prognostic and diagnostic value of the expressions of several CSC markers for patients with HCC and to identify the most efficient CSC marker. Studies on the associations of positive CSC markers with the overall survival (OS) rate, disease-free survival (DFS) rate, recurrence-free survival (RFS) rate, recurrence rate, differentiation, microvascular invasion and metastasis in patients with HCC were included in the network meta-analysis following searches on the PubMed, Embase, Elsevier and The Cochrane Library databases from January 1, 2013 to November 17, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality assessment of studies, and R (version 4.3.1), Stata (version 15.0) and Review Manager (version 5.3) were used for analysis. A total of 37 studies involving 3,980 participants were included. For patients with HCC, simultaneous positivity of cytokeratin 19 (CK19) and epithelial cell adhesion molecule (EpCAM) was the strongest predictor of the OS rate [surface under the cumulative ranking curve (SUCRA), 78.65%], positive keratin 19 (K19) was the strongest predictor of the RFS and DFS rates (SUCRA, 98.93 and 84.95%, respectively), and simultaneous positivity of EpCAM and cluster of differentiation (CD)90 was the strongest predictor of the recurrence rate (SUCRA, 5.61%). In addition, positivity of CD56, K19 and CD133 had the best diagnostic efficacy for poor differentiation [superiority index, 7.4498; 95% confidence interval (CI): 0.3333, 13.0000], microvascular invasion (superiority index, 8.4777; 95% CI: 0.2308, 17.0000), and metastasis (superiority index, 5.6097; 95% CI: 0.3333, 11.0000), respectively. In conclusion, no single CSC marker possessed the best predictive effect on all indexes of survival prognosis and diagnosis of patients with HCC. In terms of survival prognosis, simultaneous positivity of CK19 and EpCAM demonstrated the strongest predictive effect on the OS rate, suggesting an association with a low OS rate in patients with HCC; positive K19 revealed the strongest predictive effect on the RFS rate and DFS rate, suggesting an association with low RFS and DFS rates in patients with HCC; and simultaneous positivity of EpCAM and CD90 had the strongest predictive effect on the recurrence rate, suggesting a high recurrence rate in patients with HCC patients. In terms of diagnostic value, CD56, K19 and CD133 were the strongest predictors of poor differentiation, microvascular invasion and metastasis, respectively. In the future, well-designed randomized controlled trials are required to further confirm these findings.

Sacrococcygeal Chordoma: A Clinical and Imaging Review

Sacrococcygeal chordoma is a rare, locally aggressive malignant tumor originating from remnants of the notochord, and it represents the most common primary malignancy of the sacrum. This review provides an in-depth discussion of the clinical presentation, pathological features, imaging characteristics, and management of sacrococcygeal chordomas. These tumors typically present with local pain, neurological deficits, and a palpable mass, and they are known for their high recurrence rate and challenging surgical management. Imaging, especially MRI, is crucial for accurate diagnosis and surgical planning, given its ability to delineate the extent of the tumor and its relationship with surrounding structures. Complete surgical excision remains the cornerstone of treatment, with prognosis largely depending on the ability to achieve negative surgical margins. We present a case of a 45-year-old male who presented with bowel and bladder dysfunction and a painful, progressively enlarging mass over the sacrum. MRI revealed a large, well-defined soft tissue mass involving the distal sacrum and coccyx, extending into the retrorectal space. The patient underwent successful en bloc surgical resection, and histopathological examination confirmed the diagnosis of chondroid chordoma.

Higher rates of recurrence and worse quality of life in obese patients undergoing inguinal hernia repair.

Prior investigations regarding the effect of obesity on inguinal hernia repair have been mixed. The aim of our study was to retrospectively compare perioperative outcomes, recurrence rate, and quality of life between obese and non-obese patients undergoing inguinal hernia repair. Patients who underwent inguinal hernia repair by any approach at a single institution were identified from a prospectively maintained quality database. Patients with a body mass index (BMI) greater than or equal to 30kg/m2 were considered obese. Quality of life was measured with the Surgical Outcomes Measurement System (SOMS) and Carolinas Comfort Scale (CSS) surveys. Differences between obese and non-obese patients were assessed using independent samples t-tests, Wilcoxon rank-sum, and chi-square tests. Between 2010 and 2021, a total of 5575 patients underwent inguinal hernia repair. Fifteen percent of patients were identified as obese (835 patients, mean BMI 33.2 ± 3.3kg/m2). A significantly higher percentage of obese patients were diabetic, and operative time and estimated blood loss were higher in the obese group (all p < 0.001). Rates of hernia recurrence in obese patients was significantly more likely than in non-obese patients (4.2% vs 2.0%, p < 0.001). Up to 2 years postoperatively, a greater percentage of obese patients reported worse quality of life on the SOMS and more bothersome symptoms on the CCS. Inguinal hernia repair in obese patients is a more technically challenging operation. Long-term follow-up revealed a greater risk of hernia recurrence and worse quality of life up to 2 years postoperatively in this patient population.

Bacteria-responsive drug release platform for the local treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a common vaginal infection affecting millions of women. Vaginal anaerobic dysbiosis occurs whenLactobacillusspp., the dominant flora in healthy vagina is replaced by certain overgrown anaerobes, resulting in unpleasant symptoms such as vaginal discharge and odor. With a high recurrence rate, BV also severely impacts the overall quality of life of childbearing women by inducing preterm delivery and increasing the risks of pelvic inflammatory disease and sexually transmitted infections. Among various BV-associated bacteria,Gardnerella vaginalis(G. vaginalis) has been identified as a primary pathogen since it has been isolated from almost all women carrying BV and exhibits higher virulence potential over other bacteria. When dealing with BV relapse, intravaginal drug delivery systems are superior to conventional oral antibiotic therapies in improving therapeutic efficacy owing to more effective drug dose, reduced drug resistance and minimized side effects such as stomach irritation. Traditional intravaginal drug administration generally involves solids, semi-solids and delivery devices inserted into the vaginal lumen to achieve sustained drug release. However, they are mostly designed for continuous drug release and are not preventative therapies, resulting in severe side effects caused by excess dosing. Stimuli-responsive systems that can release drug only when needed ('on-demand') can help diminish these negative side effects. Hence, we developed a bacteria-responsive liposomal platform for the prevention and treatment of BV. This platform demonstrated sustained drug release in the presence of vaginolysin, a toxin secreted specifically byG. vaginalis. We prepared four liposome formulations and evaluated their responsiveness toG. vaginalis. The results demonstrated that the liposome formulations could achieve cumulative drug release ranging from 46.7% to 51.8% over a 3-5 d period in response toG. vaginalisand hardly any drug release in the presence ofLactobacillus crispatus(L. crispatus), indicating the high specificity of the system. Overall, the bacteria-responsive drug release platform has great potential, since it will be the first time to realize sustained drug release stimulated by a specific pathogen for BV prevention and treatment. This on-demand therapy can potentially provide relief to the millions of women affected by BV.

Unusual odontogenic keratocyst with impacted maxillary central incisor: A diagnosis challenge

Background: Odontogenic keratocyst (OKC) is considered an odontogenic cyst, with the unique clinical characteristics of this entity being local destruction, aggressive behavior, a high recurrence rate, specific histopathologic features, and the tendency for multiple lesions when associated with syndromes. Odontogenic keratocyst accounts for 12–14% of all cysts in the jaws. Purpose: The aim of this case report is to present an unusual odontogenic keratocyst associated with impacted maxillary central incisor, case management of anterior maxilla odontogenic keratocyst involving an adjacent tooth, and its postoperative six-month follow-up. Case: A 13-year-old female patient was referred to the Universitas Airlangga Hospital with a complaint that her upper front teeth had not erupted. The parents revealed that the patient had suffered trauma from falling down the stairs at the age of four, i.e., eight years ago. Case Management: The cyst was enucleated together with the associated permanent upper right central incisor, retained deciduous upper right central incisor, the permanent upper right lateral incisor, and upper right canine. Post surgical treatment, the patient used a partial denture to increase her self-confidence. Conclusion: Enucleation of the cyst with extraction of the permanent teeth should be performed to avoid recurrence of the OKC. Periodic radiographic evaluation is required with long-term follow-up.

Primary Open Latarjet Procedure Versus Revision to Open Latarjet Procedure for Anterior Shoulder Instability.

Although the Latarjet operation may be performed as a revision surgery for anterior shoulder instability, the high recurrence rate of anterior shoulder instability after arthroscopic Bankart repair (ABR) has led some to advocate for performing the Latarjet procedure as a primary stabilization surgery. The purpose of this study was to compare the intermediate-term outcomes after primary open Latarjet (PLJ) and revision to open Latarjet (RLJ). This was a single-institution retrospective analysis of patients who underwent either PLJ or RLJ procedures for anterior shoulder instability between 2014 and 2023. Patients with less than 1 year of follow-up, seizure history, multidirectional instability, concurrent rotator cuff repair, or the absence of preoperative imaging were excluded. Glenoid bone loss (GBL), the width of Hill-Sachs lesions, recurrent dislocations, and reoperations were assessed. The study included 29 patients, with 12 undergoing PLJ procedures and 17 undergoing RLJ procedures. The mean duration of follow-up was similar for the two groups (4.7 vs 4.6 years, P=.854). Patients undergoing PLJ procedures demonstrated a higher mean GBL (18.4%) compared with patients undergoing revision (10.5%; P=.035); however, there was no significant difference in Hill-Sachs lesion size (14.2 vs 10.4 mm, P=.374). After stratifying according to GBL, the groups undergoing PLJ and RLJ procedures had similar recurrent dislocation rates (8.3% and 11.8%, respectively; P=1.0) and reoperation frequency (25.0% and 23.5%, respectively; P=1.0). The PLJ and RLJ groups had comparable rates of recurrent dislocations, complications, and reoperations, emphasizing the value of considering Latarjet procedures as revision surgery after unsuccessful primary arthroscopic stabilization. [Orthopedics. 202x;4x(X):xx-xx.].

Eating for Optimization: Unraveling the Dietary Patterns and Nutritional Strategies in Endometriosis Management.

Endometriosis is a chronic gynecological disorder affecting millions of women worldwide, causing chronic pelvic pain, dyspareunia, dysmenorrhea, and infertility, and severely impacting their quality of life. Treatment primarily involves hormonal therapies and surgical excision, but high recurrence rates and the economic burden are substantial. With these challenges, significant discussion surrounds the potential role of dietary patterns in managing endometriosis, making it necessary to bridge this critical gap. This review investigates the current scientific evidence on the dietary patterns (eg, Mediterranean, vegetarian, anti-inflammatory, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [low-FODMAP], and Western-style diets) associated with endometriosis and provides a concise, yet thorough, overview on the subject. In addition, antioxidants, microbiota, and artificial intelligence (AI) and their potential roles were also evaluated as future directions. An electronic-based search was performed in MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, Scopus, and Web of Science. The current data on the topic indicate that a diet based on the Mediterranean and anti-inflammatory diet pattern, rich in dietary fiber, omega-3 fatty acids, plant-based protein, and vitamins and minerals, has a positive influence on endometriosis, yielding a promising improvement in patient symptoms. Preclinical investigations and clinical trials indicate that dietary antioxidants and gut microbiota modulation present potential new approaches in managing endometriosis. Also, AI may offer a promising avenue to explore how dietary components interact with endometriosis. Ultimately, considering genetic and lifestyle factors, a healthy, balanced, personalized approach to diet may offer valuable insights on the role of diet as a means of symptom improvement, facilitating the utilization of nutrition for the management of endometriosis.

Consensus of Chinese expert on neoadjuvant and conversion therapies for hepatocellular carcinoma: 2023 update

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multi-disciplinary team (MDT) and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.

Outcomes and complications of percutaneous nephrolithotomy as primary versus secondary procedure for kidney stones: A prospective cohort study

Introduction: Currently, percutaneous nephrolithotomy (PCNL) is the gold standard of treatment for large renal stones. The high prevalence of urolithiasis is associated with a high recurrence rate increasing the risk of re-intervention. This study aimed to compare the effectiveness and complications of PCNL among patients with previous therapeutic interventions for renal stones. Methods: Between August 2018 and September 2023, 245 patients were prospectively enrolled in this study and who underwent PCNL for renal stones at our institution. We compared patients who had no previous renal surgery (group1: n=171) with those who had a history of open renal surgery (group2: n=45) or previous PCNL on the ipsilateral kidney (group 3: n=31). All patients underwent surgery in the Galdakaomodified Valdivia position. Data on stone characteristics and perioperative and postoperative parameters were collected. Technical features, the success rates and morbidity were analysed and compared between the groups. Results: The fluoroscopy time was significantly longer in the group of patients with previous open surgery than in groups 1 and 3 (161.47±52.44, 223.05±33.29, 172.27±30.51sec, P&lt;0.001). Similarly, the operative time was longer in group 2 (138.20±38.86 min, P&lt;0.001). The immediate stone-free rates in groups 1, 2, and 3 were 74.8%, 72.1%, and 77.4%, respectively(P=0.945). At 1- month, these rates increased to 98.8%, 96.2% and 96.8%, respectively (P=0.857). No difference was detected between the groups in terms of complication rate. The average Hb variation was 1.08±0.82, 1.34±1.01 and 0.94±0.69 g/dL for groups 1, 2 and 3, respectively(P=0.082). Hospital stay was longer in group 2 than in groups 1 and 3 (2.17±1.03, 2.53±1.22, 1.88±1.00 d, P=0.07), respectively. Conclusion: PCNL in patients with a history of renal surgery was associated with longer fluoroscopy and operative time. However, the success and morbidity rates as a secondary procedure were similar to those of PCNL in patients with no previous intervention.

Clinical and Prognostic Characteristics in Childhood Osteosarcoma: A Single-Center Experience in Türkiye.

In our study, we aimed to share the clinical experiences of our center regarding osteosarcoma cases, the most common primary malignant bone tumor in children and adolescents. With approval from the Clinical Research Ethics Committee of our center, the data of 59 pediatric patients who were followed up in our center with the diagnosis of osteosarcoma between 2007 and 2021 were evaluated retrospectively. The mean time between the onset of symptoms and diagnosis was 3 months. Although not statistically significant, patients with a diagnostic delay of 3 months or less had a higher rate of recurrence and mortality. 59.3% of patients had metastatic disease, and the presence of metastases was associated with higher rates of recurrence and mortality. Significant number of patients had multiple surgical operations. Amputation as the first operation and the need for multiple surgeries were associated with higher mortality. Pathologically poor response to chemotherapy is associated with mortality. 42.4% of patients died, and the 5-year overall and disease-free survival rates were 47.5% and 30.5%, respectively. Survival rates were highest in non-metastatic and non-relapsed patients, and lowest in metastatic patients and patients with poor response to chemotherapy. Renal problems and cardiotoxicity were most frequently treatment-related complications. Significant improvements have been achieved in the survival and quality of life in osteosarcoma cases compared to previous years; however, there is still a long way to go, and more multicenter and multidisciplinary studies are needed on osteosarcoma.

The number of episodes of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity.

We investigate whether number of episodes (NoEs) meaningfully reflect genetic risk and genetic heterogeneity for five primary disorders-Drug Use Disorder (DUD), Alcohol Use Disorder (AUD), Major Depression (MD), Bipolar Disorder (BD), and Schizophrenia (SZ) ascertained from Swedish population registries. We utilize Genetic Risk Ratios (GRR)-defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder-derived from Family Genetic Risk Scores (FGRS). For all five primary disorders, genetic risk rose robustly with increasing NoEs. For both AUD and DUD, the GRR for all six secondary disorders-selected to have a likely genetic relationship with the particular primary disorder-declined with increasing NoEs so that cases of AUD and DUD with high versus low NoEs had both a higher genetic risk and a purer genetic signal. With MD, genetic risk maximized at an intermediate NoEs. While the GRRs for AUD and DUD in MD cases dropped sharply with increasing NoEs, GRR for BD increased. For BD, genetic risk rose sharply with increasing NoEs while for all secondary disorders the GRRs showed a mixture of modest increases and decreases. Like AUD and DUD, but even more markedly, selecting BD cases with high rates of recurrence would produce a sample with a high overall genetic risk and a relatively homogeneous genetic signal. For SZ, genetic risk rose moderately with increases in NoEs. GRRs for other non-affective psychoses (ONAP) and autism spectrum disorder (ASD) fell quite slowly with increasing NoEs, and more rapidly for other secondary disorders. Cases of SZ with high recurrence rates had a high genetic risk and a relatively pure signal, albeit with contributions from ONAP and ASD. In summary, NOEs are a robust index of genetic risk and genetic heterogeneity across our primary disorders with important inter-disorder differences.

Abdomen Malignant Myxoid Leiomyosarcoma with PDGFRA and TP53 Missense Mutation: A Case Report

Background: Malignant myxoid leiomyosarcoma (MMLS) is most commonly found in the uterus but can also occur in other areas, such as the extremities, vulva, chest wall, and abdominal cavity. This cancer is more prevalent in women and has a poor prognosis with a high rate of recurrence and a significant percentage of metastasis. Case Representation: Herein, we report the case of a 64-year-old female patient who presented with 3-month history of left lower abdominal mass. The patient underwent abdominal malignancy resection and was subsequently diagnosed with myxoid leiomyosarcoma. The patient experienced a recurrence and metastasis with significant ascites after the initial surgery and did not respond to treatment with oral Anrotinib in combination with Tislelizumab immunotherapy. Further genetic testing using next-generation sequencing (NGS) identified missense mutations in the PDGFRA and TP53 genes in the patient's plasma, but no mutations in the KIT gene were detected. Immunohistochemical analysis of the tumor tissue also revealed a negative expression of PD-L1. As a result, we altered her targeted therapy to Avapritinib, which resulted in significant improvement in her symptoms, including abdominal distension and pain, a decrease in ascites, and the KPS score increased from 60 points before treatment to 90 points after treatment SD (stable disease) was achieved for three months after treatment. Conclusion: In this case report, we present the instance of a patient with malignant myxoid leiomyosarcoma with a missense mutation in both the PDGFRA and TP53 genes. We found that targeted therapy with Avapritinib was effective in achieving a positive outcome in this patient. Our findings suggest that genetic detection is possible to better understand the biological behavior, genetic characteristics, and patient's response and tolerance to certain drugs, thus selecting the best treatment plan for the patient. Avapritinib may be a promising new treatment option for leiomyosarcoma patients with similar genetic mutations.

Subcutaneous Onlay Laparoscopic Approach for small ventral hernias associated with divarication of rectus abdominis muscle

BackgroundVentral hernias when associated with divarication of rectus abdominis if repaired without concomitant repair of the divarication is plagued by higher rates of recurrences. Out of the many options available for the repair, Subcutaneous Onlay Laparoscopic Approach (SCOLA) with concurrent plication of the divarication is gaining popularity. MethodsAll patients with a ventral hernia associated with divarication of recti were included in this prospective study. The calculated sample size was 34 with a confidence level of 95% and a margin of error of 5%. The patient demographics, operative time, intraoperative and postoperative complications, need for post-operative blood transfusion, and the recurrence were recorded. Categorical data were compared using Student's t-test, whereas chi-square test was used to compare the nominal variables between the two groups. A P-value of <0.05 was considered to be statistically significant. ResultsThirty-six patients were analysed for the study with a mean age of 43.40 years. A total of 55.55% patients were female. Twelve patients had co-morbidities. Umbilical hernia was the most common hernia. The mean size of the hernial defect was 3.67 cm, and the mean operative time was 156.66 min (±31.02 min). The first 15 cases took longer time for the surgery (mean operative time 183.53 min [±19.73 min]). No intraoperative complications were recorded, except for one patient in whom we encountered an excessive bleeding but was tackled with harmonic scalpel. Eight patients (22.2%) had complications with Seroma formation being the commonest. ConclusionSCOLA is feasible and advantageous because of faster recovery and minimal complication and recurrence rates.

Vulvar Paget's disease: A population-based cancer registry descriptive study

BackgroundAlthough vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. ObjectivesOur objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). MethodsThis retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. ResultsAmong the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0–110 months], with a median age of 72 years [38–88 years]. An associated cancer was present in 6 patients (29 %). At 5 years of follow-up, the recurrence rate was 26 %, but then increased to 42 % after a median follow-up of 145 months [31–503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100 %), associated with a postoperative recurrence rate of 86 % which was much higher than the rate observed in patients first topically treated (20 %). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). ConclusionsPostoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

Narrative review of research progress of RNA m5C methylation in head and neck malignancies.

Head and neck malignancies encompass a spectrum of malignant tumors occurring in the head and neck region, characterized by rapid progression, high recurrence rates, and dismal prognoses. Despite significant advancements in comprehensive surgery-based therapies, the 5-year survival rate for patients has not shown substantial improvement. There is an urgent need to investigate novel targeted therapies. With the advancements in epigenetics, RNA 5-methylcytosine (m5C) methylation, a prevalent form of RNA modification, has been identified by numerous studies as playing a pivotal role in the pathological processes of tumorigenesis and development. However, a comprehensive review within the realm of head and neck malignancies is currently lacking. This study aims to comprehensively review the biological implications of RNA m5C methylation regulators in the pathogenesis and progression of various systemic malignant tumors, with a specific focus on exploring the potential impact of RNA m5C methylation on head and neck malignancies. A literature search on RNA m5C methylation and head and neck malignancies was conducted using PubMed, resulting in the inclusion of 46 relevant articles. The Cancer Genome Atlas (TCGA) database was utilized to analyze the correlation between m5C regulatory factors and clinicopathological features in patients with head and neck squamous cell carcinoma (HNSCC). Aberrant expression of RNA m5C methylation regulators is observed in head and neck malignancies, displaying a correlation with the clinicopathological grading of tumors. RNA m5C methylation may contribute to the progression of head and neck malignancies and could be associated with an unfavorable prognosis for patients. These findings offer valuable insights for the development of targeted treatments for head and neck malignancies.

Myxoid pleomorphic liposarcoma.

Myxoid pleomorphic liposarcoma (MPL) is an extremely rare adipocytic tumor, recently recognized as a distinct entity in the 5th edition of the World Health Organization (WHO) Classification of Soft Tissue and Bone Tumors. Predominantly found in the mediastinum of young women, MPLs exhibit a combination of histological features characteristic of myxoid liposarcoma and pleomorphic (lipo)sarcoma. Their unique molecular features distinguish MPLs from other liposarcomas. Unlike myxoid liposarcomas and well-differentiated/dedifferentiated liposarcomas, MPLs lack specific FUS/EWSR1::DDIT3 gene fusions and MDM2/CDK4 gene amplifications, respectively. MPLs are associated with complex karyotypes, further highlighting their distinct genetic profile. They demonstrate aggressive growth patterns, high recurrence rates, and a high tendency to metastasize. These factors contribute to a poor prognosis, with a median survival of approximately 22.6 months. The aim of this review article is to provide a comprehensive summary of previously documented case reports and studies related to MPLs. By shedding light on the intricate details of MPLs, researchers and clinicians can gain valuable insights that may pave the way for improvements in diagnosis, treatment, and patient outcomes in the future.

Lysosome-Associated Membrane Protein-3 (LAMP3) Expression in Oral Squamous Cell Carcinoma and Its Relationship With Clinicopathological Parameters: A Cross-Sectional Study.

Background Oral squamous cell carcinoma (OSCC) accounts for the majority of oral cancers globally. It is characterized by metastasis, poor prognosis, high recurrence rate, and poor five-year survival rate due to late detection or diagnosis at an advanced stage. Novel biomarkers that can predict the prognosis of patients with OSCC are needed to improve survival. Lysosome-associated membrane protein-3 (LAMP3) glycoprotein, a member of the LAMP protein family, is a molecular marker for mature dendritic cells. LAMP3 expression has been correlated with unfavorable prognosis in patients with various cancers. Few studies have examined the relationship between LAMP3 and clinicopathological parameters in OSCC. This study aims to analyze the immunohistochemical expression of LAMP3 in OSCC and its relationship with clinicopathological characteristics. Methodology In this study, 75 formalin-fixed, paraffin-embedded samples of cases diagnosed with primary OSCC were obtained and immunostained with LAMP3 antibody. Its expression was compared with clinicopathological parameters such as age, sex, tobacco and alcohol consumption habits, differentiation, TNM staging, tumor location, lymph node metastasis, lymphovascular invasion, perineural invasion, and pattern of invasion. Results Higher LAMP3 expression was highly significantly associated with the TNM stage (p = 0.001). High expression of LAMP3 was significantly associated with T stage (p = 0.002) and lymph node metastasis (p = 0.002). All poorly differentiated OSCC cases (n = 2, 100%) showed a high expression of LAMP3. Conclusions High LAMP3 expression and its significant association with TNM stage, T stage, and lymph node metastasis suggest a potential role for LAMP3 in OSCC carcinogenesis. High LAMP3 expression in poorly differentiated OSCC might indicate that it plays a pivotal role in oncogenic cell transformation. Our results indicate that LAMP3 may be a predictive marker for poor prognosis in OSCC.

The Influence of Dietary Isothiocyanates on the Effectiveness of Mitomycin C and Bacillus Calmette-Guérin in Treating Nonmuscle-Invasive Bladder Cancer.

Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment. Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences. Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; P for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; P for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified. For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.

Melatonin increases Olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC

Triple-negative breast cancer (TNBC) is the most malignant breast cancer subtype, characterized with high aggressiveness and a high recurrence rate. Olaparib is the first US Food and Drug Administration-approved poly(ADP ribose) polymerase (PARP) inhibitor (PARPi) to treat breast cancer patients with a germline BRCA1 or BRCA2 mutation. However, resistance to Olaparib treatment restricts the therapeutic effects, and thus novel therapeutics are urgently required. In the present study, we identified that the combination of melatonin and Olaparib synergistically enhanced the sensitivity of TNBC cells. Moreover, melatonin exerted promising antitumor activities in Olaparib-resistant cells, implying the potential for its clinical application. An RNA-sequencing analysis revealed that melatonin treatment downregulated laminin subunit beta 3 (LAMB3) expression. Genetic ablation of LAMB3 significantly increased Olaparib sensitivity, and subsequently suppressed proliferation, epithelial-to-mesenchymal transition (EMT)-related gene expressions, and aggressiveness of breast cancer cells. Accordingly, LAMB3 expression was positively correlated with C-X-C motif chemokine ligand 2 (CXCL2), and they collaboratively promoted cancer-associated fibroblast (CAF) infiltration. An in vivo study demonstrated that combined treatment with melatonin and Olaparib showed enhanced inhibitory efficacy against tumor growth, LAMB3 expression, CXCL2 levels, and CAF infiltration compared to single treatment groups, and combined treatment with melatonin and Olaparib significantly ameliorated the immunosuppressive tumor microenvironment. These findings illustrate a promising therapeutic strategy using melatonin to overcome Olaparib resistance and activate antitumor immunity via attenuating the LAMB3-CXCL2 axis in breast cancer patients.