Axillary Tumor Research Articles

Multiparametric Magnetic Resonance Imaging Assessment of Primary Tumors for Predicting Axillary Tumor Burden in Women with Invasive Breast Cancer.

To assess the association between multiparametric MRI features of primary tumors and axillary lymph node tumor burden in women with invasive breast cancer. In this retrospective study, women diagnosed with invasive breast cancer who underwent 3T multiparametric MRI, including diffusion-weighted imaging (DWI) from 2019-2020, were evaluated. Two radiologists reviewed T2-weighted images (T2WI) for peritumoral edema and intratumoral necrosis, and measured apparent diffusion coefficient (ADC) values by manually placing regions of interest within breast tumors. We also analyzed quantitative kinetic features of breast cancer using computer-aided diagnosis (CAD) and clinical-pathologic characteristics. Uni- and multivariable logistic regression analyses were conducted to identify predictors of a high axillary nodal burden (≥3 positive nodes). In total, 301 women (mean age, 54.13 years) were evaluated. Forty-three (14.3%) had a high axillary nodal burden by surgical pathology. Multivariate analysis revealed that factors significantly associated with high axillary nodal burden included peritumoral edema (OR:7.970; p<0.001), lower tumor ADCmax (≤ 1.098 × 10-3 mm2/s) (OR:6.978; p<0.001), larger tumor size (>2cm) (OR:2.986; p=0.046), lobular histology (OR:12.620; p<0.001), and the presence of lymphovascular invasion (OR:3.622; p=0.003). CAD-derived kinetic features did not show an association with axillary nodal burden. In subgroup analysis of 238 patients with early clinically node-negative breast cancer, both peritumoral edema (OR:7.831; p=0.002) and lower tumor ADCmax (≤ 1.098 × 10-3 mm2/s) (OR:8.002; p=0.002) remained significant predictors. Our results suggest that peritumoral edema as viewed in T2WI and the ADCmax value of breast cancer in DWI are valuable for predicting axillary nodal burden in women with invasive breast cancer. Multiparametric MRI features of a primary tumor are useful for predicting axillary nodal burden in patients with invasive breast cancer.

The Efficacy of MRI-Based ADC Measurements in Detecting Axillary Lymph Node Metastasis: Evaluation of a Prospective Study.

Objective: This study aimed to evaluate the efficacy of MRI-based Apparent Diffusion Coefficient (ADC) measurements in detecting axillary lymph node metastasis in breast cancer patients. By comparing preoperative MRI findings with intraoperative sentinel lymph node biopsy (SLNB) and postoperative pathological results, we sought to explore the potential of ADC values as a non-invasive alternative to axillary interventions. Methods: A total of 104 female patients diagnosed with breast cancer between 2019 and 2021 were included in this prospective study. ADC values of axillary lymph nodes, tumors, and muscle tissues were measured using a 3T MRI system. The correlation between these measurements and pathological outcomes was analyzed. Statistical analyses, including t-tests, ANOVA, and ROC curve analysis, were employed to assess the diagnostic performance of ADC values. Results: The results indicated that, while the mean ADC values of metastatic lymph nodes were lower than those of benign nodes, the sensitivity and specificity of MRI-based ADC measurements were inferior to the expected standards. The tumor ADC value and the tumor-to-lymph node ADC ratio were found to be more reliable indicators of metastasis than the lymph node ADC value alone. The diagnostic power of the tumor ADC value was significant, with a sensitivity of 75% and a specificity of 73%. Conclusions: MRI-based ADC measurements, particularly the tumor ADC value and the tumor-to-lymph node ADC ratio, show promise as potential non-invasive markers for axillary lymph node metastasis in breast cancer patients. However, the current results suggest that ADC measurements cannot yet replace SLNB in clinical practice.

Spontaneously Draining Axillary Tumors in a Young Woman.

Spontaneously Draining Axillary Tumors in a Young Woman.

Distant recurrence of non-muscle invasive bladder cancer 8 years after initial treatment.

Distant recurrence of non-muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow-up protocols. A 73-year-old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression. Non-muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.

Combination of IVIM with DCE-MRI for diagnostic and prognostic evaluation of breast cancer

PurposeTo identify the most effective combination of DCE-MRI (Ktrans,Kep) and IVIM (D,f) and analyze the correlations of these parameters with prognostic indicators (ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size) to improve the diagnostic and prognostic efficiency in breast cancer. MethodsThis is a prospective study. We performed T1WI, T2WI, IVIM, DCE-MRI at 3 T MRI examinations on benign and malignant breast lesions that met the inclusion criteria. We also collected pathological results of corresponding lesions, including ER, PR, and HER2, Ki-67 index, axillary lymph node (ALN) and tumor size. The diagnostic efficacy of DCE-MRI, IVIM imaging, and their combination for benign and malignant breast lesions was assessed. Correlations between the DCE-MRI and IVIM parameters and prognostic indicators were assessed. ResultsOverall,59 female patients with 62 lesions (22 benign lesions and 40 malignant lesions) were included in this study. The malignant group showed significantly lower D values (p < 0.05) and significantly higher Ktrans, Kep, and f values (p < 0.05). The AUC values of DCE, IVIM, DCE + IVIM were 0.828, 0.882, 0.901. Ktrans, Kep, D and f values were correlated with the pathological grade (p < 0.05); Ktrans was negatively correlated with ER expression (r = −0.519, p < 0.05); Kep was correlated with PR expression and the Ki-67 index (r = −0.489, 0.330, p < 0.05); the DCE and IVIM parameters showed no significant correlations with the HER2 and ALN (p > 0.05). Tumor diameter was correlated with the Kep, D and f values (r = 0.246, −0.278, 0.293; p < 0.05). ConclusionIVIM and DCE-MRI allowed differential diagnosis of benign and malignant breast lesions, and their combination showed significantly better diagnostic efficiency. DCE- and IVIM-derived parameters showed correlations with some prognostic factors for breast cancer.

Establishment of a logistic regression model nomogram for clinicopathological characteristics and risk factors with axillary lymph node metastasis in T1 locally advanced breast cancer: a retrospective study.

Although the research reports on locally advanced breast cancer (LABC) are increasing year by year, there are few reports on T1 LABC axillary lymph node metastasis (ALNM). By establishing a prediction model for T1 LABC ALNM, this study provides a reference value for the probability of ALNM of related patients, which helps clinicians to develop a more effective and individualized treatment plan for LABC. Cases with pathologically confirmed T1 breast cancer (BC) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were identified. Logistic regression was used to analyze the correlation between LABC lymph node metastasis and every factor, and the odds ratio (OR) and 95% confidence interval (CI) were used to identify any influencing factors. A nomogram was drawn after incorporating meaningful factors identified in multivariate logistic regression into the model. The receiver operating characteristic (ROC) curve of the model was drawn, and the area under the curve (AUC) and its 95% CI were calculated. Hosmer-Lemeshow goodness-of-fit test and clinical decision curve analysis (DCA) were performed. The results were validated in the validation group. A total of 200,933 female T1 BC patients were included in this study. Univariate and multivariate logistic regression analysis of T1 BC showed that progesterone receptor (PR)-negative, race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and larger tumor diameter increased the probability of ALNM in T1 LABC. A predictive nomogram was established using the above predictors, the AUC of the modeling group was 0.739 (95% CI: 0.732-0.747), and when the AUC cut-off value was 0.026, the specificity and sensitivity of the model were 65.78% and 69.99%, respectively. Validation of the model showed that the AUC of the validation group (n=60,280) was 0.741. When all the risk factors were met, the predicted probability of N2-N3 was 50.40%. In this study, it was found that PR-negative, Black race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and tumor diameter increased the probability of large lymph node metastasis in T1 LABC small tumors.

Tumor-infiltrating lymphocytes as a predictor of axillary and primary tumor pathological response after neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study

PurposeTumor-infiltrating lymphocytes (TILs) can predict complete pathological response (pCR) of tumor in the breast but not so well-defined in the axilla after neoadjuvant chemotherapy. Since axillary surgery is being increasingly de-escalated after NACT, we aimed to investigate the relationship between TILs and pCR in the axilla and breast, as well as survival amongst NACT patients.MethodsClinicopathological data on patients who underwent NACT between 2013 and 2020 were retrospectively examined. Specifically, pre-TILs (before NACT), post-TILs (after NACT) and ΔTIL (changes in TILs) were assessed. Primary endpoint was pCR and secondary endpoints were breast cancer-free interval (BCFI) and overall survival (OS).ResultsTwo hundred and twenty patients with nodal metastases were included. Overall axillary and breast pCR rates were 42.7% (94/220) and 39.1% (86/220), respectively, whereas the combined pCR rate was 32.7% (72/220). High pre-TILs (OR 2.03, 95% CI 1.02–4.05; p = 0.04) predicted axillary pCR whereas, high post-TILs (OR 0.33, 95% CI 0.14–0.76; p = 0.009) and increased ΔTILs (OR 0.25, 95% CI 0.08–0.79; p = 0.02) predicted non-axillary pCR. TILs were not a significant predictor for BCFI and OS.ConclusionsThis study supports the potential use of pre-TILs to select initially node-positive patients for axillary surgical de-escalation after NACT.

Abstract PO1-23-02: Magnetic seeds used for the detection of target lymph nodes after neoadjuvant therapy for early breast cancer – a subgroup analysis of the prospective AXSANA (EUBREAST-03) trial

Abstract Background: Surgical strategies for axillary staging in patients with early breast cancer who convert from clinical lymph node positivity (cN+) to a clinically negative lymph node status (ycN0) after neoadjuvant therapy (NAT) vary between breast cancer centers and countries. The international prospective multicenter-cohort study AXSANA (EUBREAST-03) aims to comparatively evaluate long-term outcomes of different surgical staging procedures such as axillary lymph node dissection, sentinel lymph node biopsy (SLNB), target lymph node biopsy (TLNB) and targeted axillary dissection (TAD). A secondary study aim is the comparison of different localization techniques for the target lymph node (TLN), one of which is the use of magnetic seeds. Here we report on the largest so far studied prospective cohort using this technique. Methods: We prospectively examined the retrieval rate of magnetic seeds and the identification rate of a TLN in cN+ patients who underwent NAT and were scheduled for TAD. Magnetic seeds were inserted under ultrasound guidance before the start of NAT. The detection rate of TLN and its associations with residual axillary tumor burden as well as with techniques used for detection of SLN were analyzed. Results: Of the 169 patients with magnetic seed marking of the TLN prior to NAT who were included in the AXSANA study, 135 (79.9%) had undergone final surgery at the time of analysis. 13 patients had 2 magnetic seeds implanted, 122 only 1 seed. In 133 (98.5%) patients the magnetic seeds were successfully identified and removed. No additional procedures or imaging were performed in the two cases with seeds still in situ. In 131 out of 135 patients (97.0%) the TLN was identified and resected, in 4 cases no TLN could be identified although in two of those a dislocated magnetic seed was removed. 85 patients converted from cN+ to ycN0 and a TAD was planned. In 84 of these cases (98.8%) the TLN could be detected during TAD. Eight patients (9.4%) had residual tumor only in the TLN, 15 (17.6%) had residual tumor in TLN and SLN and seven (8.2%) only in the SLN. In 71 (84.2%) cases the TLN was also a SLN. Techniques used for the detection of SLN were Tc99 alone (41.2%), blue dye alone (3.5%), both tracers combined (7.1%), indocyanine green (1.2%) and magnetic tracers (36.5%). Because of the high detection rate of 98.5% for all TLN and 98.8% during TAD a formal analysis of confounding parameters was not performed. Conclusion: To our knowledge this is the largest prospective series of patients using magnetic seeds for the marking of involved lymph nodes prior to NAT. The retrieval rate of the seed and the detection rate for the TLN after NAT is excellent. Magnetic seeds are a reliable tool for the marking of involved lymph nodes before NAT. Citation Format: Hans-Christian Kolberg, Steffi Hartmann, Maggie Banys-Paluchowski, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Marc Thill, Michael P. Lux, Guldeniz Karadeniz Cakmak, Isabel Rubio, Michalis Kontos, Rosa Di Micco, Dawid Murawa, Thorsten Kühn. Magnetic seeds used for the detection of target lymph nodes after neoadjuvant therapy for early breast cancer – a subgroup analysis of the prospective AXSANA (EUBREAST-03) trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-23-02.

Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer

ObjectivesTo develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs).Materials and methodsWomen with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis.ResultsOne hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs.ConclusionPatients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making.Trial registrationThis trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020.Critical relevance statementA nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer.Key points• CEUS can help identify and diagnose SLN in early breast cancer preoperatively.• Combining lymphatic and grayscale US findings can predict axillary tumor burden.• The nomogram showed a high diagnostic value in validation cohorts.Graphical

Clinicopathological features, psychological status, and prognosis of 33 patients with occult breast cancer.

Occult breast cancer (OBC) has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer. Due to the small number of cases and limited clinical ex-perience, treatments vary greatly around the world and no standardized treat-ment has yet been established. To investigate the clinicopathological features, psychological status and prog-nostic features of patients with OBC. The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed. The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale. Patients' emotions, stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule, the Chinese Perceived Stress Scale, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Patient survival was calculated using the Kaplan-Meier method, and survival curves were plotted for analysis with the log-rank test. Univariate and multivariate survival analyses were performed using the Cox regression model. The 33 OBC patients included 32 females and 1 male. Of the 33 patients, 30 (91%) had axillary tumors, 3 (9%) had a neck mass as the primary symptom; 18 (54.5%) had estrogen receptor-positive tumors, 17 (51.5%) had progesterone receptor-positive tumors, and 18 (54.5%) had Her-2-positive tumors; 24 (72.7%) received surgical treatment, including 18 patients who underwent modified radical mastectomy, 1 patient who underwent breast-conserving surgery plus axillary lymph node dissection (ALND), and 5 patients who underwent ALND alone; 12 patients received preoperative neoadjuvant therapy. All 30 patients developed anxiety and depression, with low positive affect scores and high negative affect scores, accompanied by a high stress level and poor psychological resilience. There were no differences in the psychological status of patients according to age, body mass index, or menopausal status. The overall survival and disease-free survival (DFS) of all the patients were 83.3% and 55.7%, respectively. Univariate analysis demonstrated that the initial tumor site (P = 0.021) and node stage (P = 0.020) were factors that may affect patient prognosis. The 5-year DFS rate of OBC patients who received radiotherapy was greater (P < 0.001), while the use of different surgical methods (P = 0.687) had no statistically significant effect on patient outcomes. Multivariate analysis revealed that radiotherapy (P = 0.031) was an independent prognostic factor. Receiving radiotherapy had a significant effect on the CD-RISC score (P = 0.02). OBC is a rare breast disease whose diagnosis and treatment are currently controversial. There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy. In addition, radiotherapy can significantly improve patient outcomes. We should pay attention to the psychological state of patients while they receive antitumor therapy.

The Clinical and Pathological Characteristics That Differentiate Cases With "Low Estrogen Receptor Expression" From Triple-Negative Breast Cancer.

Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

P53 expression correlates with low axillary tumor burden in breast cancer.

The p53 mutation in breast cancer confers a worse prognosis and is usually associated with p53 overexpression (p53+) on immunohistochemistry. Previous studies have shown that p53+ tumors could be associated with low axillary tumor burden (ATB). We aimed to evaluate the association between p53+ and ATB in a large series of breast cancers as an aid to personalizing axillary surgical treatment. We retrieved 1762 infiltrating breast carcinomas from our database that were treated with upfront surgery in Hospital del Mar from 2004 to 2018. We compared p53+ and p53-negative (p53-) tumors in terms of the percentage of cases with high ATB and overall survival. This comparison was made overall and for each immunophenotype. Overall, 18.7% of breast tumors were p53+. High ATB was less common in p53+ tumors than in p53- tumors in the luminal B-Her2-negative immunophenotype (6.2% versus 16.9%, respectively, P =0.025), but not in the other immunophenotypes or overall. Overall survival was worse in patients with p53+ breast cancer (P =0.002). p53+ breast cancers were associated with worse overall survival. However, low ATB was more common in these tumors than in p53- tumors in the luminal B-Her2-negative subtype. Information on p53 expression could be of use to predict ATB in some breast cancer tumors.

Receptor Positive Breast Lesions and Status of Axillary Lymph Node.

Objective This study aimed to examine the axillary pathological condition through the development of an assessment framework for hormone receptor-positive breast cancer subsequent to neoadjuvant chemotherapy (NAC). Furthermore, the primary objective of this study was to examine the association between axillary status and breast tumors that are positive for hormone receptors following neoadjuvant chemotherapy. Methodology The present retrospective investigation encompassed a cohort including 300 individuals who were administered neoadjuvant chemotherapy before receiving surgical intervention. The data collection period for this study was from September 2021 to December 2022. All patients received neoadjuvant chemotherapy, per the guidelines established by the National Comprehensive Cancer Network (NCCN). We divided patients into two distinct groups: a test set of 250 patients and a validity set of 50 patients. Patients with no evidence of lymphoid involvement underwent a biopsy of sentinel lymph nodes (SLNB) and would have undergone axillary dissection if the biopsy results had indicated positive findings. A logistic regression analysis was employed to investigate the variables linked to the presence of residual positive axillary lymph nodes in the test set. Subsequently, a multivariate analysis was conducted on the variables that exhibited a p-value below 0.2 in the univariate study. In addition, a value of 1 was assigned to all risk factors to construct a comprehensive correlation prediction model. Results The participants included in this study had a mean age and body mass index (BMI) of 46.24 ± 9.1 years and 25.8 ± 2.5 kg, respectively. The present investigation examined the presence of pathological axillary metastases in a cohort of 188 patients, which accounted for 62.55% of the total sample, by utilizing core-needle biopsy. Furthermore, the incidence rates of individuals presenting with clinical T1 were reported as 14.6%, while 55.2% cases of T2, 17.8% cases of T3, and 13% cases of T4 tumors were reported, respectively. Of the overall occurrences, the prevailing histological subtype was invasive ductal carcinoma, accounting for 91.4% (222 out of 243) of the cases. Multiple criteria were identified as independent predictors of the presence of residual positive axillary lymph nodes. The factors under consideration encompass lymphovascular invasion (odds ratio= 7.108; 95% breast cancer stage (odd ratio = 5.025; 95%, HER2 negativity (odd ratio= 2.997), low Ki-67 expression (odd ratio = 4.231), and suspected positive axillary lymph nodes before surgical intervention. Conclusion The present study presents a novel prediction model that integrates imaging and pathology data, aiming to assist patients and healthcare practitioners in evaluating the efficacy of NACfor hormone-receptor-positive breast tumors. The model holds particular significance for individuals who exhibit clinical positivity in their lymph nodes (LNs). Consequently, the model has the potential to provide guidance for the management of axillary lymph nodes and prevent unnecessary dissection.

A case of Castlemans disease presenting as left axillary tumor

No abstract available

Cinobufacini injection delays hepatocellular carcinoma progression by regulating lipid metabolism via SREBP1 signaling pathway and affecting macrophage polarization

Ethnopharmacological relevanceCinobufacini injection, an aqueous extract of the toad, is a commonly used anti-tumor animal herbal medicine in clinical practice. It has the effects of detoxifying, reducing swelling, and relieving pain. Aims of the studyTo investigate the effects of Cinobufacini injection on hepatocellular carcinoma progression by regulating lipid metabolism and macrophage polarization in the tumor microenvironment and to identify the potential molecular mechanisms. Materials and methodsTo establish the axillary transplantation tumor model of hepatocellular carcinoma Hepa1-6 in C57BL/6 mice, and to evaluate the inhibitory effect of Cinobufacini injection on hepatocellular carcinoma in vivo as well as drug delivery security. Combined metabolomics and transcriptomics analysis of the effect of Cinobufagin Injection on tumor microenvironment. An in vitro mouse co-culture model of peritoneal macrophages and Hepa1-6 cells was established to research the effects of Cinobufacini injection on macrophage polarization, hepatocellular carcinoma cell growth, migration, and changes in lipid metabolism. Cinobufacini injection inhibition of the AMPK/SREBP1/FASN signaling pathway regulating cholesterol metabolism and affecting macrophage polarization was examined using qRT-PCR, lentiviral transfection, immunofluorescence, and Western blot. ResultIn vivo experiments demonstrated that Cinobufacini injection treatment significantly inhibited the growth of Hepa1-6 hepatomas, along with a reduction in cholesterol content and a decrease in the percentage of M2 macrophages in tumor tissue. In vitro, we found that Cinobufacini injection inhibits IL-4-induced M2 macrophage polarization, reduces the cholesterol content of Hepa1-6 cells in a co-culture system, and inhibits the promotion of hepatocellular carcinoma cells by M2 macrophages. In addition, successful overexpression of SREBP1 in Hepa1-6 cells showed more pronounced cellular activity whereas Cinobufacini injection inhibited this change and reduced intracellular lipid levels. ConclusionCinobufacini injection inhibits cholesterol synthesis within the tumor microenvironment via the AMPK/SERBP1/FASN signaling pathway, which in turn blocks the M2 polarization of macrophages, leading to the weakening of hepatocellular carcinoma growth and migration, and the promotion of its apoptosis. Our findings provide an important Introduction to understanding the molecular mechanism of Cinobufacini injection's anticancer activity and provide reliable theoretical and experimental support for its clinical application.

Axillary cutaneous metastasis of colon cancer with microsatellite instability-high and BRAF V600E mutation treated with curative-intent surgery: a case report

BackgroundColorectal cancer (CRC) metastasizes to various organs, while cutaneous metastases are rare. Although there have been several previous reports of axillary cutaneous metastases with other metastases of CRC, there has never been a report of axillary cutaneous metastasis of CRC that could be treated with curative-intent surgery.Case presentationA 68-year-old female was diagnosed with an axillary cutaneous tumor and ascending colon cancer with invasion to the duodenum. Histopathological and immunohistochemical analysis revealed that the axillary cutaneous tumor showed adenocarcinoma and the same expression pattern for cytokeratin 7, cytokeratin 20, and CDX2 as the ascending colon cancer, and that proved to be KRAS–NRAS wild type, MSI-H, and with a BRAF V600E mutation. The patient underwent a two-stage resection with curative intent after receiving neoadjuvant chemotherapy which consisted of one cycle of modified FOLFOX6 followed by two cycles of FOLFOXIRI. During and after the two operations, the patient received a total of nine cycles of modified FOLFOX6 as adjuvant chemotherapy. Two years after the initial surgery, and 1 year and 8 months after the second surgery, the patient is alive without recurrence.ConclusionsTo the best of our knowledge, this is the first report of axillary cutaneous metastasis of CRC with microsatellite instability-high and BRAF V600E mutation that could be treated with curative-intent surgery. It is important to recognize the presence of such cases for the accurate diagnosis and treatment of CRC with cutaneous metastasis.

Prognostic impact of HER2-low positivity in patients with HR-positive, HER2-negative, node-positive early breast cancer

Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1–3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1–3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 ≥ 20%. Cohort 3 comprised patients with 1–3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 < 20%. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) between HER2-low (IHC1+ or IHC2+/FISH−) and HER2-zero (IHC0) groups in each cohort. In cohort 1, HER2-low patients exhibited significantly better 5-year IDFS (84.2% vs. 73.6%, p = 0.0213) and DRFS (88.2% vs. 79.8%, p = 0.0154). However, no significant differences were observed in cohorts 2 and 3. Our findings suggest HER2-low positivity as a prognostic factor in HR-positive, HER2-negative, and node-positive EBC.

Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer.

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.

Isolated axillary tumor deposit consistent with primary breast carcinoma: A case report

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.

A Comparative Study of Antitumor Immunity Induced by Radiofrequency Microwave and Cryoablation in Hepatocellular Carcinoma.

This study aimed to compare the immune responses induced by microwave ablation (MWA), radiofrequency ablation (RFA), and cryoablation (CRYO) in hepatocellular carcinoma (HCC) and identify differences in immune responses and the timing of immune changes. A bilateral subcutaneous model was established in C57 mice, and the successfully modeled mice were divided into the microwave (n = 15), radiofrequency (n = 15), CRYO (n = 15), control (n = 9), and blank groups (n = 3). Mice in the control group were dissected before ablation, whereas mice in the three ablation groups underwent ultrasound-guided ablation of one axillary tumor. Three mice were sacrificed and dissected at 1-4 weeks after ablation. After tissue processing, flow cytometry was used to detect the levels of CD8 + T and regulatory T (Treg) cells in the tissue, and western blotting was used to assess the level of programmed cell death ligand 1 (PD-L1) protein in the tumor tissue. The pattern of immune changes after the three types of ablation was consistent, with immune changes occurring at 3-4 weeks. CRYO induced the most significant increase in the percentage of CD8 + T cells. There were no significant differences in the levels of Treg cells and the level of PD-L1 protein among the three types of ablation (p > 0.05), but the decline in Treg cells and PD-L1 protein level caused by CRYO was the most pronounced. In the HCC mouse model, the immune changes following the three types of ablation were consistent, with immune changes occurring at 3-4 weeks. Among them, CRYO elicited the strongest adaptive immune response, and RFA outperformed MWA.