Clinical­imaging­radiomic nomogram based on unenhanced CT effectively predicts adrenal metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas.

The aim of the present study was to develop and evaluate a clinical-imaging-radiomic nomogram based on pre-enhanced computed tomography (CT) for pre-operative differentiation lipid-poor adenomas (LPAs) from metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas (AIs). A total of 196 consecutive patients with lung cancer, who underwent initial chest or abdominal pre-enhanced CT scan with small hyperattenuating AIs, were included. The patients were randomly divided into a training cohort with 71 cases of LPAs and 66 cases of metastases, and a testing cohort with 31 cases of LPAs and 28 cases of metastases. Plain CT radiological and clinical features were evaluated, including sex, age, size, pre-enhanced CT value (CTpre), shape, homogeneity and border. A total of 1,316 radiomic features were extracted from the plain CT images of the AIs, and the significant features selected by the least absolute shrinkage and selection operator were used to establish a Radscore. Subsequently, a clinical-imaging-radiomic model was developed by multivariable logistic regression incorporating the Radscore with significant clinical and imaging features. This model was then presented as a nomogram. The performance of the nomogram was assessed by calibration curves and decision curve analysis (DCA). A total of 4 significant radiomic features were incorporated in the Radscore, which yielded notable area under the receiver operating characteristic curves (AUCs) of 0.920 in the training dataset and 0.888 in the testing dataset. The clinical-imaging-radiomic nomogram incorporating the Radscore, CTpre, sex and age revealed favourable differential diagnostic performance (AUC: Training, 0.968; testing, 0.915) and favourable calibration curves. The nomogram was revealed to be more useful than the Radscore and the clinical-imaging model in clinical practice by DCA. The clinical-imaging-radiomics nomogram based on initial plain CT images by integrating the Radscore and clinical-imaging factors provided a potential tool to effectively differentiate LPAs from metastases in patients with lung cancer with small hyperattenuating AIs.

Efficacy and safety of intercostal nerve anastomosis in immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy: a randomized, controlled, open-label clinical study.

Purpose: This aims to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Methods: From 2022 to 2023, female patients between the ages of 20 and 60 diagnosed with stage I-IIIA breast cancer, who required and were willing to undergo immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (the nerves with appropriate length and thickness were selected from the 2nd-4th intercostal nerves, which were then dissociated and anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. The patients' breast local sensation was assessed using Semmes-Weinstein monofilaments before the operation as well as at 10 days, 3 months, and 6 months postoperatively. Furthermore, the patients' quality of life was evaluated 6 months postoperatively using the EORTC QLQ-C30 questionnaire. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded. Results: Compared to the pre-operative period, a significant decrease in local sensation was observed 10 days after surgery in both groups. However, the control group showed a significant reduction in sensation at 3 and 6 months postoperatively, while the treatment group showed noticeable recovery. A statistically significant difference (P < 0.001) in local sensation between the pre-operative and post-operative periods was observed at the final follow-up in the two groups. By the time of 3 and 6 months postoperatively, a significant difference was seen in the local sensation between the two groups. Intercostal nerve anastomosis was found to significantly improve the patients' quality of life, including emotional (P = 0.01), physical (P = 0.04), and social functioning (P = 0.02) and pain (P = 0.04). There were no significant differences in general characteristics (such as age, BMI, and subtypes). Although intercostal nerve anastomosis increased the duration of operation by around 20 min (P < 0.001), it did not affect the volume or duration of postoperative drainage tube usage between the two groups. Conclusion: This study indicated that intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate subpectoral prosthetic breast reconstruction after nipple-areola-sparing mastectomy. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=42487, identifier ChiCTR1900026340.

Serum cell division cycle 42 in advanced hepatocellular carcinoma patients: Linkage with clinical characteristics and immune checkpoint inhibitor-related treatment outcomes.

OBJECTIVE: Cell division cycle 42 (CDC42) facilitates immune escape and drug resistance towards immunotherapy in several malignancies. This prospective study aimed to explore the predictive value of serum CDC42 for immune checkpoint inhibitor (ICI)-treatment response and survival in advanced hepatocellular carcinoma (HCC) patients. METHODS: Thirty advanced HCC patients scheduled for ICI or ICI-based treatment were enrolled in this prospective study, whose serum CDC42 was determined via enzyme-linked immunosorbent assay before therapy initiation. RESULTS: The median (interquartile range) of serum CDC42 level was 766.5 (605.0-1329.5) pg/mL. Serum CDC42 was related to increased tumor size but decreased programmed death-ligand 1 combined positive score (PD-L1 CPS). With respect to ICI or ICI-based treatment outcomes, elevated serum CDC42 was associated with decreased disease control rate, but did not link with objective response rate. Patients with high serum CDC42 (vs. low, cut by its median level) had shortened progression-free survival (PFS), while overall survival (OS) only disclosed a reduced trend (lacked statistical significance) in patients with high serum CDC42 (vs. low). In detail, the median (95%CI) PFS and OS were 3.0 (0.0-6.0) months and 11.7 (2.7-20.7) months in patients with high serum CDC42, while they were 11.1 (6.6-15.6) months and 19.3 (14.5-24.1) months in patients with low CDC42. After adjusted by multivariate cox regression analysis, high serum CDC42 (vs. low) was independently associated with shortened PFS, but not OS. CONCLUSIONS: Elevated serum CDC42 possesses a potential value in predicting worse ICI or ICI-based treatment outcomes in advanced HCC.

The efficacy and safety of using pyrotinib combined with capecitabine as neoadjuvant therapy in elderly patients with HER2-positive breast cancer: a single-arm prospective clinical trial.

Background: Pyrotinib combined with capecitabine has been approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in China. To date, the management of early-stage or locally advanced HER2-positive breast cancer in the clinic remains challenging. We conducted this trial to investigate the efficacy and safety of pyrotinib combined with capecitabine as neoadjuvant therapy (NAT) in elderly patients with HER2-positive breast cancer. Due to the stimulation of blood vessels by chemotherapy drugs, the elasticity of blood vessels in the elderly decreases, and then chemotherapy infusion is more likely to lead to phlebitis. Both pyrotinib and capecitabine can be taken to facilitate home treatment for elderly patients with HER2-positive breast cancer (BC). Methods: From January 2020 to March 2021, patients aged between 70 and 81 years old with stage IIA-IIIB HER2-positive breast cancer were screened, enrolled, and assigned to receive six cycles of pyrotinib (320-400 mg, orally, once daily) plus capecitabine (1,250 mg/m2, orally, twice daily) on days 1-14 in every 21-day cycle. The primary endpoint was the objective response rate (ORR). Adverse events (AEs) were assessed in every neoadjuvant cycle. Surgery was performed after the last cycle, and the total pathological complete response (tpCR) was evaluated postoperatively. Results: Of the 23 patients enrolled, the ORR was 100% (23/23; 95% confidence intervals: 85 to 100). All patients underwent surgery with a tpCR rate of 43.5% (10/23; 95% confidence intervals: 23 to 66). The most common AE was diarrhea, occurring in 19 of 23 patients (82.6%); most of these patients sustained mild diarrhea (Grade 1 or Grade 2) and only three had moderate diarrhea (Grade 3). The incidences of other AEs, including weakness, loss of appetite, leukopenia, nausea, vomiting, hand-foot syndrome, etc., were low and the symptoms were mild. No severe AEs (Grade 4 or 5) were observed throughout the treatment. Conclusion: In our study, pyrotinib combined with capecitabine as neoadjuvant therapy in elderly women with HER2-positive breast cancer is safe and showed efficacy in this population, which may be widely used as a protocol for clinical neoadjuvant therapy.

MiRNA-145-5p Restrains Malignant Behaviors of Breast Cancer Cells Via Downregulating H2AFX Expression.

Breast cancer is a prevalent tumor with high aggressiveness among female populations. MiRNA-145-5p plays an important role in multiple cancers. Materials and Methods: qRT-PCR detected miRNA-145-5p and histone protein family member X (H2AFX) mRNA expression in breast cancer cells, and western blot determined the protein expression of H2AFX. After predicting the target genes via the bioinformatics methods, the targeting relationship between miRNA-145-5p and H2AFX was verified by dual-luciferase, RIP, and RNA pull-down assays. The relationship between H2AFX and clinical indexes was also analyzed. Furthermore, the effects of miRNA-145-5p/H2AFX regulatory axis on breast cancer cell progression were determined by colony formation, wound healing, CCK-8, and Transwell assays. Results: The results suggested that miRNA-145-5p was markedly lowly-expressed in breast cancer tissue and cells, while H2AFX was upregulated, which had a positive correlation with T stages of breast cancer. Besides, overexpressed miRNA-145-5p was found to remarkably suppress progression of breast cancer cells. As bioinformatic analysis predicted that H2AFX was the potential target of miRNA-145-5p, the dual-luciferase assay was conducted, which demonstrated that miRNA-145-5p negatively regulated the expression of H2AFX by targeting its 3'-UTR. The rescue experiment demonstrated that overexpression of miRNA-145-5p could offset the promotion effects of oe-H2AFX on malignant progression. Objective: Our study is aimed at exploring how miRNA-145-5p functions in breast cancer cells. Conclusion: Our findings confirmed that miRNA-145-5p hindered malignant progression of breast cancer by negatively regulating H2AFX. MiRNA-145-5p/H2AFX axis may be a novel therapeutic target for breast cancer.

Neoadjuvant pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide for HER2-positive locally advanced breast cancer: a retrospective case-series study.

BACKGROUND: The anti-tumor activity of pyrotinib has been confirmed in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study investigated the effect of pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with HER2-positive locally advanced breast cancer. METHODS: In this single-center retrospective study, female patients with HER2-positive locally advanced breast cancer received pyrotinib 320 mg orally once a day and the TAC regimen (nab-paclitaxel 260 mg/m2, liposomal doxorubicin 20 mg/m2, and cyclophosphamide 600 mg/m2) on day 1 of each 21-day cycle. Surgery was performed after 4-6 cycles of neoadjuvant therapy. The outcomes included total pathological complete response (tpCR, ypT0/Tis ypN0) rate, objective response rate (ORR) after neoadjuvant therapy, progression-free survival, overall survival, and the incidence of adverse events (AEs). RESULTS: Between March 2019 and January 2020, a total of 22 patients were included. The median age was 48 years (range, 32-60). The ORR was 100% after the completion of neoadjuvant therapy. Ten (45.5%) patients achieved tpCR, including four of ten (40.0%) patients with positive hormone receptor, and six of 12 (50.0%) patients with negative hormone receptor. As at December 2020, no disease recurrence, progression, or death occurred. All patients suffered AEs after neoadjuvant therapy, most of which were grade 1-2. Grade ≥3 AEs included diarrhea [4 (18.2%)], rash [2 (9.1%)], and hand-foot syndrome [1 (4.5%)]. CONCLUSIONS: Neoadjuvant pyrotinib combined with the TAC regimen showed promising clinical benefit in patients with HER2-positive locally advanced breast cancer, with an acceptable safety profile.

Relationship between red cell distribution width and prognosis in patients with breast cancer after operation: a retrospective cohort study.

We retrospectively enrolled 825 breast cancer patients, who was primarily diagnosed in our hospital between January 2009 and December 2014 and explored the relationship between red blood cell distribution width (RDW) and long-term prognosis in patients with breast cancer. There were 412 patients with high RDW (RDW > 13.82) and 413 patients with low RDW (RDW ≤ 13.82). Compared with low RDW group, the high w group has large tumor size (the rate of tumor size >2 cm: 60.7 vs 44.8%, P=0.013). The rate of lymph node metastases was higher in the high RDW group thaten that in the low RDW group (62.1 vs 45.8%, P=0.000). RDW was positively associated with tumor stage. The high RDW tended to be advanced stage (P=0.000). Compared with low RDW group, the high RDW group tended to be higher lymphocyte count (P=0.004), elevated fibrinogen (P=0.043), and elevated high-sensitivity C-reactive protein (P=0.000). The Kaplan-Meier analysis indicated elevated RDW was positively associated with disease-free survival (DFS) (P=0.004) and overall survival (OS) (P=0.011). The multivariate Cox regression analysis indicated that the high RDW group had poorer OS (Hazard risk [HR] = 2.43; 95% CI: 1.62-3.21; P=0.024) and DFS (HR = 1.89; 95% CI: 1.28-3.62; P=0.000) compared with low RDW group. The present study found that high pretreatment RDW levels in breast cancer patients were associated with poor OS and DFS. RDW could be a potential predictive factor in differential diagnosis of poor prognosis from all patients.