Adjuvant Therapy Research Articles

Biphenotypic Sinonasal Sarcoma: Literature Review of a Peculiar Pathological Entity—The Neurosurgical Point of View

Background: Biphenotypic sinonasal sarcoma (BSNS) is a low-grade tumor of the sinonasal tract with frequent extension to the orbit and skull base. Due to its rare incidence and recent histopathological and molecular characterization, little data are available in regard to its natural history, treatment and surveillance protocol. Methods: A comprehensive literature review in Embase online electronic databases on BSNS was made. The analyzed factors included the patients’ sex and age, presenting symptoms and signs, anatomical origin and pattern of growth of the tumor, immunohistochemical and molecular features, time to treatment, type of treatment, surgical approach, extent of resection, peri- and post-operative complications, adjuvant therapies, clinical outcome, recurrence and overall survival rates. Results: This literature review involved 34 studies for an overall series of 149 cases of BSNS. The female (66.9%) and middle-aged populations (median 54.88 years old) were mainly affected. The most frequent clinical onset was nasal obstruction (81%), followed by facial discomfort (44%), epistaxis (15.5%) and ocular impairment (14.3%). Ethmoid sinus (67.8%) and nasal cavity (45.4%) were the most common anatomical site of tumor origin, while an extension to the orbit and skull base was registered in 28.7% and 24.5% of cases. Surgery was the main treatment, especially in the form of endoscopic endonasal approach (56.9%), and allowed for gross total resection in 79% of cases. The recurrence rate was 26.2%; three cases of tumor-related death were reported. Median follow-up was 4.6 years. Conclusions: Biphenotypic sinonasal sarcoma is a rare and unique tumoral entity in terms of biological and clinical behavior. Based on the current knowledge, surgery plays the leading role in treatment, accounting for gross total tumor resection in most cases, allowing for clinical symptom and sign resolution and presenting a low rate of perioperative complications. The type of approach and the aim of surgery should be assessed case by case according to patient and pathology features and the surgeon’s experience, as well as the aim of the treatment. Further studies including large surgical series and with long follow-up are required to define prognostic factors and guidelines of treatment for this peculiar pathological entity.

Systemic hormone therapy after breast and gynecological cancers: an Italian expert group consensus opinion.

The specific Italian Group of Study of the Menopause formulated a consensus opinion on the use of estrogen therapy (ET) or combined estro-progestin hormone therapy (HT) after breast and gynecological cancers. This consensus is based on the risk of recurrence of the specific cancer during ET/HT, the presence of steroid receptors in cancer cells, the use of adjuvant hormone therapies and data on the use of ET/HT after cancer. The following positions were reached. ET/HT can be used after vulvar cancers and melanoma, but with great caution after the rare adenocarcinomas. ET/HT can be used after cervical cancer, but ET should be used with caution after adenocarcinomas. ET/HT can be used after International Federation of Obstetrics and Gynecology (FIGO) stage I-II estrogen-dependent endometrial cancers, except in Black women, and can probably be used after estrogen-independent endometrial cancers. ET/HT cannot be administered or should be used with great caution after most uterine sarcomas. ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

Efficacy and Safety Profile of Different Schedules of Adjuvant Trastuzumab Therapy among Patients with HER2-Positive Breast Cancer: Real-World Experience from a Tertiary Cancer Center in South India

One year of adjuvant trastuzumab is the standard of care for HER2-positive breast cancer. In low–middle income countries, delivery of 1-year trastuzumab is challenging due to significant financial burden. Evidence for shorter durations of adjuvant trastuzumab is gaining popularity in this regard. In this study, we compared the effectiveness and safety of 1 year versus shorter durations of adjuvant trastuzumab practiced in our center. In total, 312 patients were included in this analysis. The median age was 52 years. More than two-thirds of patients (67.6%) had stage 2 disease and majority were hormone-receptor-positive (62.5%). The median follow-up duration was 50 months. The 4-year disease-free survival was 97.3%. The 4-year disease-free survival for shorter durations of adjuvant trastuzumab was 98% compared with 96.7% in 1-year trastuzumab therapy group. In univariate analysis, stage at diagnosis was the only factor which had statistically significant association with disease-free survival. In multivariate analysis, none of the variables were found to be predictive of survival. Two patients (0.6%) had significant left ventricular ejection fraction decline.Shorter durations of adjuvant trastuzumab have comparable 4-year disease-free survival to standard 1-year therapy and is an alternative adjuvant treatment option for HER2-positive breast cancer patients in resource-limited settings.

Multi-task Bayesian model combining FDG-PET/CT imaging and clinical data for interpretable high-grade prostate cancer prognosis.

We propose a fully automatic multi-task Bayesian model, named Bayesian Sequential Network(BSN), for predicting high-grade(Gleason 8) prostate cancer(PCa) prognosis using pre-prostatectomy FDG-PET/CT images and clinical data. BSN performs one classification task and five survival tasks: predicting lymph node invasion (LNI), biochemical recurrence-free survival (BCR-FS), metastasis-free survival, definitive androgen deprivation therapy-free survival, castration-resistant PCa-free survival, and PCa-specific survival(PCSS). Experiments are conducted using a dataset of 295patients. BSN outperforms widely used nomograms on all tasks except PCSS, leveraging multi-task learning and imaging data. BSN also provides automated prostate segmentation, uncertainty quantification, personalized feature-based explanations, and introduces dynamic predictions, a novel approach that relies on short-term outcomes to refine long-term prognosis. Overall, BSN shows great promise in its ability to exploit imaging and clinicopathological data to predict poor outcome patients that need treatment intensification with loco-regional or systemic adjuvant therapy for high-risk PCa.

Balancing Fertility Preservation and Treatment Efficacy in (Neo)adjuvant Therapy for Adolescent and Young Adult Breast Cancer Patients: a Narrative Review.

Adolescent and young adult (AYA) breast cancer survivors face a significant risk of infertility due to the gonadotoxic effects of (neo)adjuvant therapy, which complicates their ability to conceive post-treatment. While (neo)adjuvant therapy primarily aims to improve recurrence-free and overall survival, fertility preservation strategies should also be considered for young patients. This narrative review explores recent advancements in fertility preservation techniques, such as oocyte, embryo, and ovarian tissue cryopreservation, and evaluates the feasibility of modifying breast cancer (neo)adjuvant therapy to preserve fertility without compromising survival outcomes. Our review highlights that clinical trials with co-primary endpoints of oncological safety and fertility preservation are limited, and substituting standard treatment regimens solely for fertility preservation is currently not recommended. Nevertheless, new clinical studies have emerged that either exclude highly ovarian-toxic agents, such as cyclophosphamide, or omit adjuvant therapy altogether, even if fertility preservation is not their primary endpoint. Unfortunately, many of these trials have not evaluated ovarian toxicity. Notably, since 2020, major oncology organizations, including the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO) have advocated for the routine assessment of ovarian toxicity in all clinical trials. The review underscores the importance of incorporating ovarian toxicity as a standard endpoint in future trials involving premenopausal breast cancer patients to identify treatment regimens that can effectively balance fertility preservation with treatment efficacy.

The Effect of Adjuvant Therapy on Metabolic Syndrome in Schizophrenia Patients at Madani Hospital

Background: Schizophrenia is a mental disorder that impacts behavior, emotions, and communication. In recent years, atypical antipsychotics have been increasingly prescribed because they significantly reduce both positive and negative symptoms. However, the long-term effects of atypical can cause metabolic syndrome. Additional therapy is provided to maximize the primary therapy and reduce the side effects. Method: This study used a quasi-experimental design with a single-blind, pretest-posttest approach. Patients who had been using atypical antipsychotics, either monotherapy or combination therapy, for more than 3 were examined pretest to determine metabolic syndrome levels. Group A received adjuvant therapy, while Group B did not receive adjuvant therapy. Based on this data, an analysis of the reduction in metabolic syndrome categories was conducted. Result: The percentage of schizophrenia patients by gender was dominated by males (60%). By age, the majority were adults (87%). In Group A, the incidence of metabolic syndrome decreased from 53% in the pretest to 40% in the posttest after being given vitamin A, B, and folic acid therapy. The most commonly used other medication was THP (38%). Conclusion: The administration of adjuvant therapy with vitamins A, B, E, and folic acid can reduce the value of one or two of the five metabolic syndrome criteria for schizophrenia patients (p = 0.052) compared to the group of patients who did not receive vitamins A, B, E, and folic acid adjuvant therapy. Future research should use a longer duration to observe the effects of vitamins A, B, E, and folic acid and evaluate their therapeutic doses. Additionally, it should narrow down the criteria for medication use, focusing solely on the atypical antipsychotic’s clozapine or olanzapine.

Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.

Bladder cancer (BC) is a common malignancy and its most prevalent type is urothelial carcinoma, which accounts for ~90% of all cases of BC. The current treatment options for BC are limited, which necessitates the development of alternative treatment strategies. Hyperthermia (HT), as an adjuvant cancer therapy, is known to improve the efficacy of chemotherapy or radiotherapy. The present study aimed to investigate the anti‑tumor effects of HT on cell survival, invasiveness, chemoresistance and immune evasion in human BC cell lines (5637, T24 and UMUC3). Calcein AM staining was performed to analyze the cytotoxicity of natural killer (NK) cells against human BC cells following HT treatment. Cell migration and invasion affected by HT were analyzed using Transwell migration and invasion assays. It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B. Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11. It was further demonstrated that HT inhibited the migration and invasion of BC cells and enhanced the cytotoxic effects of NK cells. In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells. Thus, HT appears to be a promising adjunctive therapy for human BC.

Definition and Predictors of Early Recurrence in Neoadjuvantly Treated Esophageal and Gastroesophageal Adenocarcinoma: a Dual-Center Retrospective Cohort Study.

BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC). This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS)protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence. Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence. Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.

A nanoencapsulated oral formulation of fenretinide promotes local and metastatic breast cancer dormancy in HER2/neu transgenic mice

BackgroundPrevention and treatment of metastatic breast cancer (BC) is an unmet clinical need. The retinoic acid derivative fenretinide (FeR) was previously evaluated in Phase I-III clinical trials but, despite its excellent tolerability and antitumor activity in preclinical models, showed limited therapeutic efficacy due to poor bioavailability. We recently generated a new micellar formulation of FeR, Bionanofenretinide (Bio-nFeR) showing enhanced bioavailability, low toxicity, and strong antitumor efficacy on human lung cancer, colorectal cancer, and melanoma xenografts. In the present study, we tested the effect of Bio-nFeR on a preclinical model of metastatic BC.MethodsWe used BC cell lines for in vitro analyses of cell viability, cell cycle and migratory capacity. For in vivo studies, we used HER2/neu transgenic mice (neuT) as a model of spontaneously metastatic BC. Mice were treated orally with Bio-nFeR and at sacrifice primary and metastatic breast tumors were analyzed by histology and immunohistochemistry. Molecular pathways activated in primary tumors were analyzed by immunoblotting. Stem cell content was assessed by flow cytometry, immunoblotting and functional assays such as colony formation ex vivo and second transplantation assay in immunocompromised mice.ResultsBio-nFeR inhibited the proliferation and migration of neuT BC cells in vitro and showed significant efficacy against BC onset in neuT mice. Importantly, Bio-nFeR showed the highest effectiveness against metastatic progression, counteracting both metastasis initiation and expansion. The main mechanism of Bio-nFeR action consists of promoting tumor dormancy through a combined induction of antiproliferative signals and inhibition of the mTOR pathway.ConclusionThe high effectiveness of Bio-nFeR in the neuT model of mammary carcinogenesis, coupled with its low toxicity, indicates this formulation as a potential candidate for the treatment of metastatic BC and for the adjuvant therapy of BC patients at high risk of developing metastasis.

Telitacicept add-on therapy in refractory idiopathic inflammatory myopathy: insights from a pilot study.

This study aimed to evaluate the therapeutic efficacy of telitacicept based on the conventional treatment in adults with idiopathic inflammatory myopathy (IIM), focusing on its impact on clinical manifestations. IIM patients who had been treated with telitacicept for at least 3 months based on the conventional treatment from January 2023 to January 2024 were included in this study. The clinical response to telitacicept was determined based on the ACR/EULAR criteria for minimal, moderate, and major improvement in the total improvement score (TIS). Disease activity was monitored using Core Set Measures (CSMs), while myositis damage was assessed with established assessment tools. The Manual Muscle Test assessed the muscle performance for 8 muscle groups (MMT-8). A total of 11 patients administered with telitacicept (160 mg per week) were included in this study. Post-treatment assessments revealed improvements in all patients according to ACR/EULAR criteria. Notably, there was a significant reduction in the prednisone dosage from baseline to last visit (27.05 ± 12.47 mg to 12.05 ± 7.32 mg; p< 0.005). Enhancements were observed in MMT-8 scores improved (from 109.18 ± 14.18-137.64 ± 15.28; p< 0.005) and in the reduction of creatine kinase (CK) levels (from 2670.27 ± 2675.00 U/l to 561.09 ± 754.09; p< 0.05). Telitacicept demonstrated effectiveness in treating refractory inflammatory myopathy, contributing to a significant reduction in steroid dosage among the patients. These findings highlight the potential of telitacicept as a valuable therapeutic option in the management of IIM.

Surgical management of conventional ameloblastoma: a retrospective cohort study over the past 21 years.

Conventional ameloblastoma presents infiltrative behavior and its treatment ranges from enucleation combined with adjuvant therapies to marginal/segmental resection. The purpose of this study is to present a cohort of twenty-four patients with ameloblastoma treated in the same institution after marginal/segmental resection for the past 21 years. All cases had diagnosis confirmation by incisional biopsy. Patients with an unconfirmed diagnosis and missing follow-up information were excluded. Data were categorized into clinicopathological, surgical and recurrence aspects. Thirteen patients were females (54%). The mean age was 40.2 years. Mandible was the most affected site (91%). The mean length of the lesions was 4.10cm (± 2.06) and the multilocular aspect was predominant (83%). Root resorption (37.5%), tooth displacement (45.8%) and cortical perforation (45.8%) were noticed. Histologically, most of the cases were follicular (n = 19,79%). Microscopic analysis showed positive margins in four cases. Patients were treated by marginal (n = 19) and segmental (n = 5) resections. Recurrence occurred in two cases (8.33%). Both primary and recurrent ameloblastomas were treated through marginal resections and no recurrence was observed during the past 9 and 5 years after the last intervention, respectively. The overall mean follow-up was 79.25 months and patients are still monitored over these years. Marginal/segmental resection of conventional ameloblastoma is associated with a low recurrence rate.

Ultrashort Cell-Free DNA Fragments and Vimentin-Positive Circulating Tumor Cells for Predicting Early Recurrence in Patients with Biliary Tract Cancer.

Background/Objectives: Biliary tract cancer (BTC) is a rare but aggressive malignancy that requires surgical treatment. However, postoperative recurrence rates are high, and reliable predictors of recurrence are limited. This study aimed to investigate the effectiveness of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) in predicting early recurrence after curative surgery and complete adjuvant therapy in patients with BTC. Methods: Twenty-four patients who underwent R0 and R1 resections and completed adjuvant therapy for BTC between September 2019 and March 2022 were followed up until March 2024. Patients were categorized into early recurrence (ER) and non-ER groups, using one year as the cutoff for recurrence. Results: The combination score derived from ultrashort fragments of cfDNA, vimentin-positive CTCs, and carbohydrate antigen (CA) 19-9 levels showed a statistically significant difference between the ER and non-ER groups (p-value < 0.001). The receiver operating characteristic curve from the combination score and CA 19-9 levels yielded areas under the curve of 0.891 and 0.750, respectively. Conclusions: Although further research is required, these findings suggest that cfDNA and CTCs may increase the accuracy of predicting postoperative recurrence in patients with BTC.

Fear of the Cancer Coming Back: A Metasynthesis of Fear of Recurrence in Breast Cancer.

This review aimed to consolidate existing knowledge on this phenomenon by incorporating direct testimonies from individuals who have experienced breast cancer. A thorough metasynthesis of qualitative studies was conducted. English articles published prior to September 18 2023 were searched from eight databases, including PubMed, Cochrane Library, Web of Science, Embase, the Chinese biomedical literature service system, the China National Knowledge Infrastructure, the Wanfang Database, and the Wipu Database. After screening the titles, abstracts, and full texts, six articles were finally included in the quality appraisal and metaaggregation. A total of 30 research findings were distilled and integrated into three themes: causes of fear of cancer recurrence (FCR); feelings of FCR; coping with FCR; and six subthemes: disease treatment factors; psychological factors; FCR is worry and fear; overcoming; negative response; positive response. FCR is a subjective feeling; it is influenced by the interplay between the external environment (adjuvant therapy) and internal environment (psychological factors). Therefore, future care measures should be designed comprehensively, considering the individual characteristics of breast cancer survivors and the external environment. This could be the primary focus for addressing FCR in cancer patients in the future.

The optimal timing of breast cancer surgery after COVID-19 infection: an observational study

PurposeIt is controversial for the optimal time of breast cancer surgery after COVID-19 infection. Purpose was to assess the risk of postoperative complication in breast cancer patients with COVID-19 infection, in order to select optimal surgery timing after COVID-19 infection.MethodsBreast cancer patients infected with COVID-19 and performed surgery between December 20th, 2022 to March 20th, 2023 were included in this prospective study (n = 577). Patients performed surgery between May 1, 2019 to October 1, 2019 were listed as control group (n = 329). They had not been infected with COVID-19 before surgery. Patients were grouped by time of surgery relative to COVID-19 infection. Database was evaluated using logistic regression.ResultsPatients infected with COVID-19 had a higher incidence of complications after surgery compared to that not-COVID-19 infection (6.59% vs. 3.04%). Multivariable logistic analysis demonstrated that timing of surgery was associated with complications (OR = 4.253; 95% CI: 0.855–21.153, P = 0.044). Patients performed surgery within 2 weeks after COVID-19 infection had the highest rates of complication (17.65%) when compared with other groups, while the incidence was decreased into 5.51% when surgery 2 weeks or more after COVID-19 infection. With a median follow-up was 10 months, all patients with complications were recovered without serious complications or death, which had no adverse effect on subsequent anti-tumor therapy.ConclusionsIt needs to be cautious when breast cancer surgery was performed within 2 weeks after COVID-19 infection. Although the incidence of complications in patients undergoing surgery 2 weeks after COVID-19 infection is still slightly high, surgery might be recommended considering urgency of treatment, good prognosis of complications and the lack of influence on subsequent adjuvant therapy.

A preliminary study of developing an MRI-based model for postoperative recurrence prediction and treatment direction of intrahepatic cholangiocarcinoma.

To establish an MRI-based predictive model for postoperative recurrence in intrahepatic cholangiocarcinoma (iCCA) and further to evaluate the model utility in treatment direction for neoadjuvant and adjuvant therapies. Totally 114 iCCA patients with curative surgery were retrospectively included, including 38 patients in the neoadjuvant treatment, traditional surgery, and adjuvant treatment groups for each. Predictive variables associated with postoperative recurrence were identified using univariate and multivariate Cox regression analyses, and a prognostic model was formulated. Recurrence-free survival (RFS) curves were compared using log-rank test between MRI-predicted high-risk and low-risk iCCAs stratified by the optimal threshold. Tumor multiplicity (hazard ratio (HR) = 1.671 [95%CI 1.036, 2.695], P = 0.035), hemorrhage (HR = 2.391 [95%CI 1.189, 4.810], P = 0.015), peri-tumor diffusion-weighted hyperintensity (HR = 1.723 [95%CI 1.085, 2.734], P = 0.021), and positive regional lymph node (HR = 2.175 [95%CI 1.295, 3.653], P = 0.003) were independently associated with postoperative recurrence; treatment group was not significantly related to recurrence (P > 0.05). Independent variables above were incorporated for the recurrence prediction model, the 1-year and 2-year time-dependent area under the curve values were 0.723 (95%CI 0.631, 0.815) and 0.725 (95%CI 0.634, 0.816), respectively. After risk stratification, the MRI-predicted high-risk iCCA patients had higher cumulative incidences of recurrence and worse RFS than the low-risk patients (P < 0.001 for both). In the MRI-predicted high-risk patients, neoadjuvant therapy was associated with improved all-stage RFS (P = 0.034), and adjuvant therapy was associated with improved RFS after 4months (P = 0.014). The MRI-based iCCA recurrence predictive model may serve as a decision-making tool for both personalized prognostication and therapy selection.

Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

Effect of ethyl acetate extract from Usnea longissima on chemotherapy-associated multiple organ dysfunction in rats

BackgroundThe toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity. MethodsAlbino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction. ResultsULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy. ConclusionULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.

Kidney-Sparing Surgery for Upper Tract Urothelial Carcinoma-Modalities, Outcomes, and Limitations.

Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of urothelial cancers and is associated with high morbidity and mortality. Increasing incidence of UTUC has been observed since the 1970's, alongside the evolution of advance imaging techniques, precision biopsy equipment, and risk stratification models. The high morbidity of radical nephroureterectomy (RNU) which is still the gold-standard treatment for high-risk UTUC, has driven the development of kidney-sparing surgery alternatives for low-risk UTUC. Now, several treatment approaches have outcomes comparable to RNU for low-risk UTUC and guidelines are recommending kidney-sparing surgery for favorable low-risk disease. The main categories of kidney-sparing surgery include segmental ureterectomy, endoscopic ablation, chemoablation, and vascular-targeted phototherapy. These treatments are highly nuanced making them difficult to compare, but for most cases of favorable low-grade disease, we recommend endoscopic laser ablation with optional adjuvant intracavitary therapy. Adverse events associated with kidney-sparing surgery include ureteral stricture, bleeding requiring transfusion, and bladder recurrence of UTUC. Limitations of kidney-sparing surgery include appropriate tissue sampling (contributing to under-grading and under-staging), higher rates of ipsilateral recurrence, and potential for grade and stage progression. Collectively, these may subsequently necessitate RNU. Here, we review the technical variations and evidence behind kidney-sparing therapies as well as their practicality in the real world.

The Role of Epigallocatechin-3-gallate (EGCG) In Inhibiting MMP3 Expression and Human Pterygium Fibroblast Migration: A Review

Background: Pterygium is characterized by the overgrowth of fibroblasts and the remodeling of the extracellular matrix (ECM), driven by MMPs. The review outlines the pathophysiology of pterygium, emphasizing the role of MMP-3 in cell motility, proteolysis, and angiogenesis. The recurrence rate of pterygium following surgical excision remains a significant challenge, with current adjuvant therapies like mitomycin-C presenting serious side effects. Methods: The review synthesizes findings from various studies on the effects of EGCG on MMP-3 expression and fibroblast migration. It discusses the mechanisms by which EGCG inhibits MMP-3 activity and its potential impact on pterygium progression. Findings: EGCG has been shown to inhibit MMP-3 expression and activity in several models, including mouse Lewis lung carcinoma-derived cells and photoaged hairless mouse models. It also suppresses the migration of human pterygium fibroblast cells, potentially preventing pterygium formation. EGCG's ability to reduce oxidative stress and modulate inflammatory pathways further supports its therapeutic potential. Conclusion: EGCG emerges as a promising agent for inhibiting MMP-3 expression and human pterygium fibroblast migration, offering a safer alternative to current adjuvant therapies. Its anti-inflammatory, antioxidant, and anti-angiogenic properties make it a potential therapeutic option for managing pterygium, warranting further clinical investigation.

Margin-to-depth ratio as an independent prognostic factor in resected oral cavity squamous cell carcinoma: A nationwide cohort study

BackgroundThe prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort. MethodsA total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures. ResultsAfter excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes. ConclusionsAn MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins.