The multifaceted mechanisms of Dihydrotanshinone I in the treatment of tumors.

The morbidity and mortality of malignant tumors are progressively rising on an annual basis. Traditional Chinese Medicine (TCM) holds promise as a possible therapeutic agent for the avoidance or therapy of malignant tumors. Salvia miltiorrhiza Bunge (Danshen), a traditional Asian functional food, has therapeutic characteristics in application for the treatment of malignant tumors. Dihydrotanshinone I (DHTS) is the principal lipophilic phenanthraquinone compound found in Salvia miltiorrhiza Bunge, whose anti-tumor effect has attracted widespread attention. The anti-tumor effects include inhibiting cancer cell proliferation, triggering apoptosis of tumor cells, inducing ferroptosis in tumor cells, inhibiting tumor cell invasion and metastasis, and improving drug resistance of tumor cells. In this paper, we summarized and analyzed the mechanisms and targets of anti-tumor effect of DHTS, providing new ideas and establishing a solid theoretical basis for the future advancement and clinical treatment of DHTS.

A Systematic Review on Artificial Intelligence Evaluating Metastatic Prostatic Cancer and Lymph Nodes on PSMA PET Scans.

Early detection of metastatic prostate cancer (mPCa) is crucial. Whilst the prostate-specific membrane antigen (PSMA) PET scan has high diagnostic accuracy, it suffers from inter-reader variability, and the time-consuming reporting process. This systematic review was registered on PROSPERO (ID CRD42023456044) and aims to evaluate AI's ability to enhance reporting, diagnostics, and predictive capabilities for mPCa on PSMA PET scans. Inclusion criteria covered studies using AI to evaluate mPCa on PSMA PET, excluding non-PSMA tracers. A search was conducted on Medline, Embase, and Scopus from inception to July 2023. After screening 249 studies, 11 remained eligible for inclusion. Due to the heterogeneity of studies, meta-analysis was precluded. The prediction model risk of bias assessment tool (PROBAST) indicated a low overall risk of bias in ten studies, though only one incorporated clinical parameters (such as age, and Gleason score). AI demonstrated a high accuracy (98%) in identifying lymph node involvement and metastatic disease, albeit with sensitivity variation (62-97%). Advantages included distinguishing bone lesions, estimating tumour burden, predicting treatment response, and automating tasks accurately. In conclusion, AI showcases promising capabilities in enhancing the diagnostic potential of PSMA PET scans for mPCa, addressing current limitations in efficiency and variability.

A Systematic Review on Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET) Evaluating Localized Low- to Intermediate-Risk Prostate Cancer: A Tool to Improve Risk Stratification for Active Surveillance?

Active surveillance remains a treatment option for low- to intermediate-risk prostate cancer (PCa) patients. Prostate-specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT) has emerged as a useful modality to assess intraprostatic lesions. This systematic review aims to evaluate PSMA PET/CT in localized low- to intermediate-risk PCa to determine its role in active surveillance. Following PRISMA guidelines, a search was performed on Medline, Embase, and Scopus. Only studies evaluating PSMA PET/CT in localized low- to intermediate-risk PCa were included. Studies were excluded if patients received previous treatment, or if they included high-risk PCa. The search yielded 335 articles, of which only four publications were suitable for inclusion. One prospective study demonstrated that PSMA PET/CT-targeted biopsy has superior diagnostic accuracy when compared to mpMRI. One prospective and one retrospective study demonstrated MRI occult lesions in 12.3-29% of patients, of which up to 10% may harbor underlying unfavorable pathology. The last retrospective study demonstrated the ability of PSMA PET/CT to predict the volume of Gleason pattern 4 disease. Early evidence demonstrated the utility of PSMA PET/CT as a tool in making AS safer by detecting MRI occult lesions and patients at risk of upgrading of disease.

Reoperation for post hepatectomy complications.

BACKGROUND: Reoperation for post hepatectomy complications is associated with high rates of morbidity and mortality. We aim to describe the frequency, indications, and risk factors for reoperation after liver resection in a single centre. METHODS: Perioperative data of 464 patients, who underwent elective hepatectomy from 2001 to 2020 at The Queen Elizabeth Hospital in South Australia, were retrospectively analysed. The frequency and indications for reoperation for post hepatectomy complications were recorded. Binary logistic regression analysis was performed to determine variables associated with reoperation. RESULTS: A total of seven patients (1.5%) underwent reoperation post hepatectomy. The most common indications for reoperation were intra-abdominal abscess, post-operative haemorrhage, bile leak, and ischaemic bowel. Three out of the seven patients died. Patients were more likely to require reoperation if an additional major non-hepatic procedure was performed. CONCLUSION: Reoperation post hepatectomy is associated with morbidity and mortality and is more likely to occur in patients who have undergone a non-hepatic procedure at the same time as the primary hepatic resection. Surgeons should ensure these patients are appropriately monitored and be selective about performing complex, multiple procedures. When possible, procedures should be staged.

Implementing routine use of self-removed ureteric stents on extraction strings: prospective patient-reported outcome measures and complications.

PURPOSE: Ureteric stents placed after ureteroscopy typically require cystoscopy for removal. Stent extraction strings allow the option of patient self-removal. This facilitates shorter stent dwell time, and cost-savings. Concerns regarding safety and limited evidence regarding patient acceptability are speculated reasons for infrequent clinical use of extraction strings. This study investigates our recent experience using routine self-removal of stents on extraction strings to provide evidence to address these concerns. METHODS: In February 2020, our hospital adopted a policy for self-removal of stents on extraction strings to be routine following ureteroscopy. This was influenced by motivation to improve service capacity for diagnostic flexible cystoscopy, hospital avoidance during the pandemic, perceived improvement for the patient experience, and cost-saving. Prospective clinical and patient-reported outcome data were collected and evaluated. RESULTS: There were 168 patients who had stents on extraction strings. Mean stent dwell time was 5.2 ± 1.8 days. Primary ureteroscopy was performed in 40.5%, and 59.5% had procedures using an access sheath. Self-removal at home was successful for 79% of patients. Stent dislodgement rate was 3.0% (5/168) and retained stents due to string detachment occurred in 1.8% (3/168). Almost all indicated they "would remove the stent on string again" (90%, 128/142) and the majority reported stent removal as "very easy" (61%, 87/142). Cost modelling estimates a total saving of AUD $148,869 per annum for routine use of extraction strings at our hospital. CONCLUSION: Our experience reflects that stent extraction strings may be used routinely with acceptable low complication rates, favourable patient experiences and associated cost savings.

Clinical predictors of rectal cancer response after neo-adjuvant (Chemo)Radiotherapy in Australia and New Zealand: Analysis of the Bi-National Colorectal Cancer Audit (BCCA).

Pathological complete response (pCR) is observed in 11-26% of locally advanced rectal cancers undergoing neoadjuvant chemoradiotherapy (nCRT). This study aims to determine pCR rates and clinicopathological predictors in the Australian and New Zealand (ANZ) cohort. The Bi-National Colorectal Cancer Audit (BCCA) was interrogated for all rectal cancer patients who underwent nCRT prior to surgical resection between 2007 and 2020. Patients were divided in two groups: pCR (AJCC tumour regression grade 0) and partial/no response (pPR, regression grade 1,2 or 3). In total, 3230 patients were included. Rates of pCR and pPR were 704 (21.8%) and 2526 (78.2%), respectively. Long-course nCRT (p < 0.0001), lower clinical tumour stage (cT; p < 0.0001), and nodal stage (cN; p = 0.003) were associated with pCR on univariate analysis. On multivariable analysis, cN0 stage and long-course nCRT remained independent factors for a pCR. Awareness of these predictors provides valuable information when counseling patients regarding prognosis and treatment options.

Ionic liquids with reversible photo-induced conductivity regulation in aqueous solution.

Stimulus-responsive ionic liquids have gained significant attention for their applications in various areas. Herein, three kinds of azobenzimidazole ionic liquids with reversible photo-induced conductivity regulation were designed and synthesized. The change of electrical conductivity under UV/visible light irradiation in aqueous solution was studied, and the effect of chemical structure and concentration of ionic liquids containing azobenzene to the regulation of photoresponse conductivity were discussed. The results showed that exposing the ionic liquid aqueous solution to ultraviolet light significantly increased its conductivity. Ionic liquids with longer alkyl chains exhibited an even greater increase in conductivity, up to 75.5%. Then under the irradiation of visible light, the electrical conductivity of the solution returned to its initial value. Further exploration of the mechanism of the reversible photo-induced conductivity regulation of azobenzene ionic liquids aqueous solution indicated that this may attributed to the formation/dissociation of ionic liquids aggregates in aqueous solution induced by the isomerization of azobenzene under UV/visible light irradiation and resulted the reversible conductivity regulation. This work provides a way for the molecular designing and performance regulation of photo-responsive ionic liquid and were expected to be applied in devices with photoconductive switching and micro photocontrol properties.

Treatment outcomes of mucosal melanoma of the head and neck: Analysis of 190 cases from a single institution.

Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.

Nitrogen addition increases topsoil carbon stock in an alpine meadow of the Qinghai-Tibet Plateau.

Soil carbon (C) sequestration plays a critical role in mitigating climate change. Nitrogen (N) deposition greatly affects soil C dynamics by altering C input and output. However, how soil C stocks respond to various forms of N input is not well clear. This study aimed to explore the impact of N addition on soil C stock and to elucidate the underlying mechanisms in an alpine meadow on the eastern Qinghai-Tibet Plateau. The field experiment involved three N application rates and three N forms, using a non-N treatment as a control. After six years of N addition, the total C (TC) stocks in the topsoil (0-15 cm) were markedly increased by an average of 12.1 %, with a mean annual rate of 20.1 ‰, and no difference was found between the N forms. Irrespective of rate or form, N addition significantly increased the topsoil microbial biomass C (MBC) content, which was positively correlated with mineral-associated and particulate organic C content and was identified as the most important factor that affecting the topsoil TC. Meanwhile, N addition significantly increased the aboveground biomass in the years with moderate precipitation and relatively high temperature, which leads to higher C input into soils. Owing to decreased pH and/or activities of ß-1,4-glucosidase (ßG) and cellobiohydrolase (CBH) in the topsoil, organic matter decomposition was most likely inhibited by N addition, and this inhibiting effect varied under different N forms. Additionally, TC content in the topsoil and subsoil (15-30 cm) exhibited parabolic and positive linear relationship with the topsoil dissolved organic C (DOC) content, respectively, indicating that DOC leaching might be an important influencing factor for soil C accumulation. These findings improve our understanding of how N enrichment affects C cycles in alpine grassland ecosystems and suggest that soil C sequestration in alpine meadows probably increases with N deposition.

Understanding unplanned return to theatre in rural South Australia general surgery: review of four major hospitals over a six-year period.

BACKGROUND: Unplanned return to theatre (URTT) is associated with longer hospital stay and higher mortality rates, placing extra burden on hospital resources. There is a lack of literature analysing causes of URTT in a rural general surgery department. This knowledge may be important to help identify patients at risk of URTT. This study aims to identify causes of URTT in rural general surgical patients. METHODS: This is a retrospective multicenter cohort involving four rural South Australian (SA) hospitals: Mount Gambier (MGH), Whyalla (WH), Port Augusta (PAH), and Port Lincoln (PLH). All general surgical inpatients admitted from February 2014 to March 2020 were analysed to identify all-cause of URTT. RESULTS: Of the 44 191 surgical procedures performed, there were 67 (0.15%) URTT. The most common surgical subspecialty cases that resulted in URTT were Colorectal (47.1%), General surgery (33.2%) Plastics (9.8%), and Hepatopancreatico-biliary (3.9%). The three commonest operations during URTT were washouts 22 (32.8%), interventions for haemostasis 11 (16.4%) and bowel resections 9 (13.4%). Sixteen (24%) of URTT followed emergency surgery. When comparing between elective and emergency admissions needing URTT, there were no statistical difference in age, gender, speciality type, types of surgery performed, and median number of days until URTT. CONCLUSION: Rates of URTT are low in South Australian rural hospitals when compared to our overseas counterpart. A wide range of surgery is being performed in rural centres, further supporting the need for rural surgical trainees to have a tailored curriculum encompassing subspecialities and being competent in managing any potential complications.

Extended scope of practice needed for Australian rural general surgeons: a review of South Australia's rural general surgical caseload and case mix.

BACKGROUND: There is a shortage of surgeons caring for the 33% of Australians residing in rural and regional areas. In order to help appreciate what rural general surgery entails and optimize training for aspiring rural surgeons, the aim of this study was to analyse the general surgical departments' procedural caseload and casemix in four rural South Australian hospitals. METHODS: This is a retrospective multi-centre study involving four rural surgical centres in South Australia (Mt Gambier, Whyalla, Port Augusta, and Port Lincoln). Surgical procedures performed from 2014-2020 were extracted from departmental audits. To identify trends of surgical procedure over time, the data was divided into three time periods (Period 1: February 2014-December 2015, Period 2: January 2016-December 2017, Period 3: January 2018-March 2020). RESULTS: A total of 44 191 surgical procedures were performed, 70.2% being day procedures. 54% were endoscopic procedures, 46% were operative procedures. 60.6% of the operative procedures were general surgery procedures. 28.5% were general surgery-based subspecialty (colorectal, hepato-pancreato-biliary, upper gastrointestinal, and breast). 10.9% were non-general surgery-based subspecialty (urology, plastics, vascular, orthopaedics, head and neck, and obstetrics and gynaecology). There were no statistically significant fluctuations in procedure caseload in all aspects (endoscopic and operative procedures) over the three time periods. CONCLUSION: The majority of a rural Australian general surgeon's procedures are endoscopic. Operative procedures are mainly general surgery based. It may be beneficial to equip aspiring rural general surgeons to manage basic non-general surgery procedures (urological, vascular, and orthopaedic).

Pyrite Dissolution in the Cretaceous Yogou Formation of the Niger (Chad) Basin: Implications for Basin Evolution under a Rift Tectonic Setting.

This is the first study of pyrite minerals in the entire West and Central African Rift System (WCARS). Several polished organic-rich core samples from the Cretaceous Yogou Formation of the Niger (Chad) Basin located in the WCARS were investigated for their pyrite content using FE-SEM and SEM-EDS imaging techniques. An attempt was made to classify the types and provenance of the pyrites and to highlight the control of rift fractures on the oxidation and dissolution of pyrites in the region. Three major types of pyrites are present in the studied formation, including euhedral pyrite (EPy) crystals, pyrite framboids (FPy), and sunflower pyrites (SPy). A statistical analysis of 307 FPy shows that the framboids are diagenetically formed with an average diameter of 6.61 µm. SPy is present in a relatively low amount compared to framboids. The pyrites underwent a variety of diagenetic modifications, from mechanical compaction to oxidation, dissolution, and recrystallization. Unoxidized pyrites primarily contain Fe, S, and C, but oxidized pyrites also contain O, Al, and Si. There is a strong correlation between the fractures and the spatial distribution of the physicochemical alteration of the pyrite in the study. Dissolution in relatively deep-buried samples occurs mainly along fracture planes. The fractures provide a pathway for oxidants and other metal elements to reach the pyrites. The pattern of pyrite dissolution reflects the timing of fracture formation and fracture activities as a purveyor or drainage for fluids in the organic-rich samples investigated. The pyrites are associated intimately with organic matter (OM); thus, the relationship between the fracture and the pyrites' transformation is significant in the assessment of organic matter preservation at deep-burial depth.

Functional Porous Ionic Polymers as Efficient Heterogeneous Catalysts for the Chemical Fixation of CO2 under Mild Conditions.

The development of efficient and metal-free heterogeneous catalysts for the chemical fixation of CO2 into value-added products is still a challenge. Herein, we reported two kinds of polar group (-COOH, -OH)-functionalized porous ionic polymers (PIPs) that were constructed from the corresponding phosphonium salt monomers (v-PBC and v-PBH) using a solvothermal radical polymerization method. The resulting PIPs (POP-PBC and POP-PBH) can be used as efficient bifunctional heterogeneous catalysts in the cycloaddition reaction of CO2 with epoxides under relatively low temperature, ambient pressure, and metal-free conditions without any additives. It was found that the catalytic activities of the POP-PBC and POP-PBH were comparable with the homogeneous catalysts of Me-PBC and PBH and were higher than that of the POP-PPh3-COOH that was synthesized through a post-modification method, indicating the importance of the high concentration catalytic active sites in the heterogeneous catalysts. Reaction under low CO2 concentration conditions showed that the activity of the POP-PBC (with a conversion of 53.8% and a selectivity of 99.0%) was higher than that of the POP-PBH (with a conversion of 32.3% and a selectivity of 99.0%), verifying the promoting effect of the polar group (-COOH group) in the porous framework. The POP-PBC can also be recycled at least five times without a significant loss of catalytic activity, indicating the high stability and robustness of the PIPs-based heterogeneous catalysts.

Carbon stock stability in drained peatland after simulated plant carbon addition: Strong dependence on deeper soil.

Peatlands are vital soil carbon sinks, yet this function is jeopardized by plant carbon which could change the decomposition rate of soil organic carbon, knowing as "priming effect". How the priming effect depends on depth is a critical question in drained peatland given the heterogeneity of soil layers defined by the water table, which include the surface acrotelm, inter-mesotelm and deep catotelm. Here, through incubation, we quantified the response of these three soil layers to addition of 13C-labeled oxalate, glucose, cellulose, or cinnamic acid under anoxic or oxic conditions on the Zoige Plateau in Tibet. Soil carbon in the inter-mesotelm showed the greatest decomposition, with the highest humification index and lowest microbial biomass carbon, while the soil carbon at the surface acrotelm was least decomposed. Under anoxic conditions, exogenous carbon addition reduced CO2 emission by 12.2% at the surface acrotelm but increased by 59.8% in the inter-mesotelm and 23.5% in the deep catotelm. In the inter-mesotelm, oxalate addition significantly increased CO2 emission by 63.9%, while cinnamic acid significantly increased it by 92.9%. In the deep catotelm, cinnamic acid significantly increased CO2 emission by 55.3%. These results suggested that deeper soil organic carbon was more sensitive to plant carbon, particularly complex or recalcitrant carbon, than surface acrotelm soil. Under oxic conditions, carbon addition increased surface soil CO2 emission by 18.9%, and triggered even greater increase at inter-mesotelm and deep catotelm soil, with proportions of 48.3% and 32.0%, respectively. Under both conditions, peat profile CO2 release increased by 17.2-31.4% after exogenous carbon addition, and more than 77.8% of the increase came from the deeper two layers. These findings highlighted the need to take full account of priming effect of deeper soil in order to assess and predict the stability of carbon stocks in drained peatland.

Analysis of surgical mortality in rural South Australia: a review of four major rural hospital in South Australia.

BACKGROUND: One-third of Australia's population reside in rural and remote areas. This audit aims to describe all-causes of mortality in rural general surgical patients, and identify areas of improvement. METHODS: This is a retrospective multi-centre study involving four South Australian hospitals (Mt Gambier, Whyalla, Port Augusta, and Port Lincoln). All general surgical inpatients admitted from June 2014 to September 2019 were analysed to identify all-cause of mortality. RESULTS: A total of 80 mortalities were recorded out of 26 996 admissions. The overall mortality rate of 0.3% was the same as the 2020 Victorian state-wide Audit of Surgical Mortality. No mortality was secondary to trauma. Mean age was 79 ± 11 years and ASA was 3.9 ± 1. Malignancy was associated in over a third of cases (41.2%), mostly colorectal and pancreatic. Most cases were related to general surgical subspecialties: colorectal (51.3%), upper gastrointestinal (21.3%), hepatopancreaticobiliary (13.8%); however, there were also vascular (6.3%) and urology (3.8%) cases. The most common causes of mortality were large bowel obstruction (13.4%), ischemic bowel (10.4%), and small bowel obstruction (7.5%). Majority of mortality were beyond the surgeon's control (73.8%). Of the 21 potentially preventable mortalities, 42.9% were attributed to aspiration pneumonia and decompensated heart failure. Only one (1.3%) mortality case was due to pulmonary embolism. CONCLUSION: Rural general surgical mortalities occur in older, comorbid patients. Rural surgeons should be equipped to manage basic subspeciality conditions. To further reduce mortalities, clear protocols to prevent aspiration pneumonia and resuscitation associated fluid overload are needed.

Antibacterial mechanism of the Asp-Asp-Asp-Tyr peptide.

Previously, we found that ASP-ASP-ASP-TYR (DDDY) from Dendrobium aphyllum has a minimum inhibitory concentration of 36.15 mg/mL against Pseudomonas aeruginosa. Here, we explored the antibacterial mechanism of DDDY and its potential preservation applications. Metabolomic and transcriptomic analyses revealed that DDDY mainly affects genes involved in P. aeruginosa membrane transport and amino acid metabolism pathways. Molecular dynamics simulation revealed that DDDY had a stronger effect on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine phospholipid membranes than on 1-palmitoyl-2-oleoyl-lecithin or 1-palmitoyl-2-oleoyl phosphatidylglycerol membranes, with high DDDY concentrations displaying stronger efficacy on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine. Mechanistically, the N-terminal of DDDY first bound to the phospholipid head group, while its C-terminal amino acid residue bound the hydrophobic tail, thereby creating a gap in the membrane when the phospholipids were clustered by hydrogen bonding. Finally, DDDY inhibited the growth of food microorganisms inoculated onto chestnut kernels, suggesting that DDDY is a promising antibacterial agent against multidrug-resistant gram-negative bacteria.

Malignant Features in Pretreatment Metastatic Lateral Lymph Nodes in Locally Advanced Low Rectal Cancer Predict Distant Metastases.

INTRODUCTION: Pretreatment enlarged lateral lymph nodes (LLN) in patients with locally advanced low rectal cancer are predictive for local recurrences after neoadjuvant (chemo)radiotherapy (n(C)RT) followed by total mesorectal excision (TME). Not much is known of the impact on oncological outcomes when in addition malignant features are present in enlarged LLN. PATIENTS AND METHODS: A multicenter retrospective cohort study was conducted at five tertiary referral centers in the Netherlands and Australia. All patients were diagnosed with locally advanced low rectal cancer with LLN on pretreatment magnetic resonance imaging (MRI) and underwent n(C)RT followed by TME. LLN were considered enlarged with a short axis of ≥ 5 mm. Malignant features were defined as nodes with internal heterogeneity and/or border irregularity. Outcomes of interest were local recurrence-free survival (LRFS), distant metastatic-free survival (DMFS), and overall survival (OS). RESULTS: Out of 115 patients, the majority was male (75%) and the median age was 64 years (range 26-85 years). Median pretreatment LLN short axis was 7 mm (range 5-28 mm), and 60 patients (52%) had malignant features. After a median follow-up of 47 months, patients with larger LLN (7 + mm) had a worse LRFS (p = 0.01) but no difference in DMFS (p = 0.37) and OS (p = 0.54) compared with patients with smaller LLN (5-6 mm). LLN patients with malignant features had no difference in LRFS (p = 0.20) but worse DMFS (p = 0.004) and OS (p = 0.006) compared with patients without malignant features in the LLN. Cox regression analysis identified LLN short axis as an independent factor for LR. Malignant features in LLN were an independent factor for DMFS. CONCLUSION: The current study suggests that pretreatment enlarged LLN that also harbor malignant features are predictive of a worse DMFS. More studies will be required to further explore the role of malignant features in LLN.