Status of mental and social activities of young and middle-aged patients after papillary thyroid cancer surgery.

Background: Papillary thyroid cancer (PTC) is prevalent among younger populations and has a favorable survival rate. However, a significant number of patients experience psychosocial stress and a reduced quality of life (QoL) after surgical treatment. Therefore, comprehensive evaluations of the patients are essential to improve their recovery. Methods: The present study enrolled 512 young and middle-aged patients diagnosed with PTC who underwent surgery at our institution between September 2020 and August 2021. Each participant completed a series of questionnaires: Generalized Anxiety Disorder 7 (GAD-7), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Thyroid Cancer-Specific Quality of Life Questionnaire (THYCA-QoL), and Readiness to Return-to-Work Scale (RRTW). Results: GAD-7 data showed that almost half of the study subjects were experiencing anxiety. Regarding health-related quality of life (HRQoL), participants reported the highest levels of fatigue, insomnia, voice problems, and scarring, with patients in anxious states reporting worse symptoms. Based on RRTW, more than half of the subjects had returned to work and had better HRQoL compared to the others who were evaluating a possible return to work. Age, gender, BMI, education, diet, residence, health insurance, months since surgery, monthly income, and caregiver status were significantly correlated with return to work. Additionally, having a caregiver, higher monthly income, more time since surgery, and living in a city or village were positively associated with return to work. Conclusion: Young and middle-aged patients with PTC commonly experience a range of health-related issues and disease-specific symptoms following surgery, accompanied by inferior psychological well-being, HRQoL, and work readiness. It is crucial to prioritize timely interventions targeting postoperative psychological support, HRQoL improvement, and the restoration of working ability in PTC patients.

Effects of COVID-19 vaccination on cervical lymph nodes in patients with thyroid cancer.

Background: Cervical lymph node enlargement caused by coronavirus disease 2019 (COVID-19) vaccination has been reported, but little is known on whether the vaccination would influence preoperative cervical lymph node evaluation and its risk of lymph node metastasis in thyroid cancer. Methods: We retrospectively analyzed data of patients who underwent thyroid cancer surgery in Tangdu Hospital, China, from 1 March 2021 to 30 June 2021. A total of 182 patients were included in the cohort study. All patients with suspected malignant tumors underwent ultrasound (US)-guided fine needle aspiration (FNA) of thyroid lesions before surgery to confirm the diagnosis. Cervical lymph nodes were evaluated by preoperative physical examination and imaging. Wilcoxon rank-sum test and Fisher's exact test were used to evaluate the effect of vaccination on cervical lymph nodes in patients with thyroid cancer. Statistical significance was defined at P<0.05. Results: The patients were divided into two groups according to whether they had been vaccinated or not. Our results showed that there were no significant differences between the two groups in the brand of the vaccine, operation method, and the extent of surgery. Moreover, there was no significant difference in the evaluation of US characteristics of cervical lymph nodes between the two groups regardless of having the vaccination or not. Interestingly, US evaluation found that the experimental group's proportion of cervical lymph node enlargement increased significantly within 14 days after vaccination, which was statistically significant. Conclusions: This study found that vaccination against COVID-19 did not increase the number of cervical lymph node metastases, but inaccurate assessment of cervical lymph nodes in thyroid cancer patients within 14 days of vaccination (due to temporary lymph node enlargement) may lead to more extensive surgery.

Full-sized realistic 3D printed models of liver and tumour anatomy: a useful tool for the clinical medicine education of beginning trainees.

BACKGROUND: Simulation-based medical education (SBME) and three-dimensional printed (3DP) models are increasingly used in continuing medical education and clinical training. However, our understanding of their role and value in improving trainees' understanding of the anatomical and surgical procedures associated with liver surgery remains limited. Furthermore, gender bias is also a potential factor in the evaluation of medical education. Therefore, the aim of this study was to evaluate the educational benefits trainees receive from the use of novel 3DP liver models while considering trainees' experience and gender. METHODS: Full-sized 3DP liver models were developed and printed using transparent material based on anonymous CT scans. We used printed 3D models and conventional 2D CT scans of the liver to investigate thirty trainees with various levels of experience and different genders in the context of both small group teaching and formative assessment. We adopted a mixed methods approach involving both questionnaires and focus groups to collect the views of different trainees and monitors to assess trainees' educational benefits and perceptions after progressing through different training programs. We used Objective Structured Clinical Examination (OSCE) and Likert scales to support thematic analysis of the responses to the questionnaires by trainees and monitors, respectively. Descriptive analyses were conducted using SPSS statistical software version 21.0. RESULTS: Overall, a 3DP model of the liver is of great significance for improving trainees' understanding of surgical procedures and cooperation during operation. After viewing the personalized full-sized 3DP liver model, all trainees at the various levels exhibited significant improvements in their understanding of the key points of surgery (p < 0.05), especially regarding the planned surgical procedure and key details of the surgical procedures. More importantly, the trainees exhibited higher levels of satisfaction and self-confidence during the operation regardless of gender. However, with regard to gender, the results showed that the improvement of male trainees after training with the 3DP liver model was more significant than that of female trainees in understanding and cooperation during the surgical procedure, while no such trend was found with regard to their understanding of the base knowledge. CONCLUSION: Trainees and monitors agreed that the use of 3DP liver models was acceptable. The improvement of the learning effect for practical skills and theoretical understanding after training with the 3DP liver models was significant. This study also indicated that training with personalized 3DP liver models can improve all trainees' presurgical understanding of liver tumours and surgery and males show more advantage in understanding and cooperation during the surgical procedure as compared to females. Full-sized realistic 3DP models of the liver are an effective auxiliary teaching tool for SBME teaching in Chinese continuing medical education.

Enhancing vulnerability of Afatinib using Erastin via xCT-mediated ROS/P38MAPK signaling feedback loop in gastric cancer cells.

Ferroptosis, being classified as a form of regulated cell death, was driven by the oxidative injury induced by lipid peroxidation (LPO). Recently, ferroptosis has been confirmed to exert a critical effect in the pathogenesis and treatment of various tumors, including gastric cancer (GC). Erastin, as a frequently used ferroptosis inducer, caused ferroptosis by downregulating the xCT expression resulting in increasing reactive oxygen species (ROS) and aggravating the LPO. However, the mechanisms of Erastin in ferroptosis regulation, especially in GC, remain largely elusive. This work firstly demonstrated that Erastin inhibited cell growth and promoted apoptosis and ferroptosis in AGS and BGC823 cells. Then, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of Erastin-related targets screened by using PharmMapper Web, the P38MAPK signaling was explored and validated in AGS and BGC-823 cells. Besides, the Fer-1 and P38 inhibitor were performed to investigate the mechanisms of ferroptosis induced by Erastin in depth. This work revealed a feedback mode among xCT, ROS and the P38MAPK pathway, which affected each other. It meant that Erastin regulated ferroptosis through the xCT-mediated ROS/P38MAPK signaling feedback loop. In addition, it was noticed that in co-operation with Erastin, the cytotoxic effects of Afatinib on cells were aggravated by further strengthening ferroptosis with activation of the P38MAPK pathway. In summary, those works provided evidence that Erastin plays an important role in increasing the cytotoxic effect on GC cells treated with Afitinib. Furthermore, the Erastin-induced ferroptosis via the xCT-mediated ROS/P38MAPK pathway feedback loop provides new strategies for GC comprehensive treatment.

Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low.

BACKGROUND: HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear. METHODS: We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2low) and 94 HER2-negtive (HER2neg) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2neg vs. HER2low, 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples. RESULTS: Compared with HER2neg TNBC, HER2low TNBC patients exhibited malignant clinical features with larger tumor size (P = 0.04), more lymph nodes involvement (P = 0.02), higher histological grade of lesions (P < 0.001), higher Ki67 status (P < 0.01), and a worse prognosis (P < 0.001; HR [CI 95%] = 3.44 [2.10-5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2low TNBC but not in HER2neg TNBC patients. ScRNA-seq revealed that HER2low TNBC which showed more metabolically active and aggressive hallmarks, while HER2neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglobulin-related genes (IGHG1, IGHG4, IGKC, IGLC2); this was further confirmed by immunofluorescence in clinical TNBC samples. Furthermore, HER2low and HER2neg TNBC exhibited distinct tumor evolutionary characteristics. Moreover, HER2neg TNBC revealed a potentially more active immune microenvironment than HER2low TNBC, as evidenced by positively active regulation of macrophage polarization, abundant CD8+ effector T cells, enriched diversity of T-cell receptors and higher levels of immunotherapy-targeted markers, which contributed to achieve immunotherapeutic response. CONCLUSIONS: This study suggests that HER2low TNBC patients harbor more malignant clinical behavior and aggressive tumor biological properties than the HER2neg phenotype. The heterogeneity of HER2 may be a non-negligible factor in the clinical management of TNBC patients. Our data provide new insights into the development of a more refined classification and tailored therapeutic strategies for TNBC patients.

Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment.

Background: It has been established that clusterin is involved in the invasion of immune cells in the tumor microenvironment, but it remains unknown how it promotes immune invasion in breast cancer. Methods: We used Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to assess the relation between expression of clusterin and immunoinfiltration-related marker genes. TIMER database was used to evaluate the expression of clusterin, and its relation to tumor immune invasion was examined. Based on Kaplan-Meier plotter database, we investigated the association between clusterin expression and prognosis in patients with cancer, and the impact of clinicopathological factors and cancer-related outcomes. Results: Clusterin expression was markedly associated with prognosis of a variety of tumors, specifically breast cancer. Enhanced clusterin expression was markedly associated with molecular typing of breast cancer and expression of multiple markers related to specific immune cell subsets. Conclusions: These results indicate that clusterin is connected to prognosis of breast cancer patients and tumor immune cell infiltration. This demonstrates that clusterin may be a biomarker of immune cell recruitment into breast tumors and an important biomarker for immune cell infiltration; consequently being a valuable prognostic factor in breast cancer patients.

Impact of intraoperative frozen section pathology on the treatment outcome of unilateral papillary thyroid microcarcinoma and its influencing factors-a retrospective cohort study.

Background: Most patients with papillary thyroid carcinoma have a good prognosis. Excessive resection of thyroid and cervical lymph nodes is an important reason for affecting the quality of life of patients after surgery. Intraoperative rapid frozen pathological examination is an important step in the development of a surgical plan for thyroid cancer (especially micropapillary carcinoma); however, whether it affects the treatment outcome remains unclear. Methods: The clinicopathological data of papillary thyroid microcarcinoma (PTMC) patients who underwent surgery in our center from 1 January 2021 to 31 December 2021 were retrospectively analyzed. Patients with unilateral low-risk PTMC who underwent radical surgery were selected as the main research subjects. The negative results of intraoperative frozen section of the central lymph node (CLN) of the affected side were the experimental group, and the positive results were the control group. Subjects with lesions larger than 10 mm and those who did not undergo intraoperative frozen section pathological examination were excluded. After excluding other risk factors for recurrence, we calculated the proportion of patients requiring radioactive iodine (RAI) treatment among those with metastases detected by intraoperative rapid frozen section pathology and its influencing factors. Patient data were analysed using SPSS version 20. Continuous variables were presented as means when symmetrical or as medians and ranges when asymmetrical. Categorical variables were presented as proportions. A P value <0.05 was considered significant. Results: A total of 564 PTMC patients were included, among whom 122 patients (21.6%) underwent total thyroidectomy due to the presence of metastases in the ipsilateral CLNs. Compared with the experimental group, the patients with male, young age and tumor located in the middle and lower pole in the control group had higher lymph node metastasis (P<0.05). Conclusions: The proportion of patients requiring postoperative RAI treatment for unilateral low-risk PTMC is relatively low, and the possibility that an intraoperative frozen pathological finding will change the treatment outcome is low. However, the need for postoperative RAI therapy notably increases when the intraoperative frozen pathological analysis reveals ipsilateral CLN metastases, especially in males, younger patients, and/or patients with lesions located in the middle and lower poles.

EccDNA-oriented ITGB7 expression in breast cancer.

Background: Extrachromosomal circular DNA (eccDNA) is omnipresent in cancers and related to the progression of tumors and oncogene amplification. However, its function in breast cancer (BC) is unclear. Methods: After constructing the DNA library, CLeavage Effects by Circularization for In vitro Reporting of sequencing was performed for eccDNA detection using 1 BC tissue sample. Fastqc was used to evaluate the quality of the original data. Burrows-Wheeler-Alignment Tool was used to compare the original data to the reference genome. A Circle-MAP was subsequently performed to detect eccDNA, and Bedtools was used to annotate the eccDNA genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted by ClusterProfiler. The Genotype-Tissue Expression and the Cancer Genome Atlas databases were used to collect the ribonucleic acid-sequencing data of the BC and normal samples. A Gene Expression Profiling Interactive Analysis, the University of Alabama at Birmingham CANcer data analysis Portal, and Kaplan-Meier survival curves were used to analyze the Cancer Genome Atlas data. Results: A total of 200 eccDNA genes, including IGTB7, were obtained. About the biological processes (BPs), these 200 genes were mainly enriched in actin cytoskeleton reorganization and axon guidance. Concerning the molecular functions (MFs), these 200 genes were mainly enriched in sodium ion transmembrane transporter activity and metal ion transmembrane transporter activity. As for cellular components (CCs), these 200 genes were mainly enriched in the transcription regulator complex and focal adhesion. ITGB7 was significantly enriched in cell-matrix adhesion and localization within the membrane in the BPs, integrin binding in the MFs, and cell-substrate junction and focal adhesion in the CCs. The 200 eccDNA genes were mainly enriched in the PI3K-Akt signaling pathway and focal adhesion. Notably, ITGB7 was enriched in focal adhesion, ECM-receptor interaction, the PI3K-Akt signaling pathway, and human papillomavirus infection. Besides, ITGB7 was significantly upregulated in BC patients and was associated with the menopause status of the BC patients. Conclusions: ITGB7 might serve as a prognostic marker for BC patients. ITGB7 has important implications for the individualized clinical treatment of BC patients.

PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role.

BACKGROUND: Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC. MATERIALS AND METHODS: A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations. RESULTS: Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1-1.63), P < 0.01; HR (95% CI) = 1.4 (1.07-1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC. CONCLUSION: Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.

GJA1 rs2071165 A > G Variant Increased Gastric Cancer Risk in Females of Northwest China: A Case-Control Study.

Gastric cancer (GC) is one of the most common malignancies, and its incidence rates vary widely between men and women. Previous studies have suggested that connexin 43 (Cx43, encoded by gap junction protein alpha 1 (GJA1)) and secretory carrier membrane protein 1 (SCAMP1) are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated. A total of three single-nucleotide polymorphisms among 681GC patients and 756 controls were tested using the Agena MassARRAY RS1000 system, including GJA1 rs2071165, SCAMP1 rs4530741, and SCAMP1 rs6874309. The strength of the association with GC risk was assessed by the odds ratios (ORs) and 95% confidence intervals (CIs) generated from the logistic regression model. Kaplan-Meier curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry. The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (OR = 1.55, 95% CI = 1.03-2.32, p=0.034). Furthermore, the risk effect of GJA1 rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between SCAMP1 rs4530741 and rs6874309 polymorphisms and GC risk or prognosis was observed. In conclusion, this study suggests for the first time that the GJA1 rs2071165 polymorphism is associated with increased GC risk in females, revealing a potential new clinical marker for assessing GC risk in females.

Side effects of CDK4/6 inhibitors in the treatment of HR+/HER2- advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although combination of cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors with endocrine therapy for advanced breast cancer (ABC) prolongs PFS in patients, but also has associated toxic side effects. However, few previous studies have summarized the toxic and side effects of CDK4/6 inhibitors. Therefore, this study summarized the corresponding toxic and side effects of CDK/6 inhibitors, which is of great importance for doctors and patients to understand how to balance the high survival rate brought by drugs with the decreased quality of life and improve the management of BC. METHODS: PubMed, Embase, The Cochrane Library, and VIP databases were systematically searched to collect randomized controlled trials (RCTs) of CDK4/6 inhibitors combined with endocrine therapy for advanced breast cancer from January 2010 to December 2019.Two investigators independently reviewed the literatures. Before using the RevMan 5.3 software for a meta-analysis, date were extracted and the risk of bias with the include studies were assessed. RESULTS: A total of 64 RCTs involving 3685 patients were included. Compared with placebo combined with endocrine therapy, CDK4/6 inhibitors combined with endocrine therapy could improve the median progression free survival rate (hazard ratio 0.54, 95% confidence interval (CI):0.50-0.60, P<0.00001). In terms of adverse reactions, CDK4/6 inhibitors combined with endocrine therapy had higher rates of neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased alanine aminotransferase (ALT). DISCUSSION: CDK4/6 inhibitors have strong specification in the treatment of ABC because of their role in regulating the cell cycle. Although CDK4/6I combined with endocrine therapy can improve the effective rate and median PFS of patients with HR+/HER2-ABC, this treatment regimen increases the incidence of adverse reactions such as neutropenia, leukopenia, thrombocytopenia, anemia, fatigue, diarrhea, febrile neutropenia, nausea and increased ALT. Further research into improving the survival rate while reducing or even avoiding the side effects of CDK4/6Isis needed for better clinical management of BC. TRIAL REGISTRATION: PROSPERO (CRD42020171112).

Exosomal long noncoding RNA AGAP2-AS1 regulates trastuzumab resistance via inducing autophagy in breast cancer.

Trastuzumab has been widely used for treatment of HER-2-positive breast cancer patients, however, the clinical response has been restricted due to emergence of resistance. Recent studies indicate that long noncoding RNA AGAP2-AS1 (lncRNA AGAP2-AS1) plays an important role in cancer resistance. However, the precise regulatory function and therapeutic potential of AGAP2-AS1 in trastuzumab resistance is still not defined. In this study, we sought to reveal the essential role of AGAP2-AS1 in trastuzumab resistance. Our results suggest that AGAP2-AS1 disseminates trastuzumab resistance via packaging into exosomes. Exosomal AGAP2-AS1 induces trastuzumab resistance via modulating ATG10 expression and autophagy activity. Mechanically, AGAP2-AS1 is associated with ELAVL1 protein, and the AGAP2-AS1-ELAVL1 complex could directly bind to the promoter region of ATG10, inducing H3K27ac and H3K4me3 enrichment, which finally activates ATG10 transcription. AGAP2-AS1-targeting antisense oligonucleotides (ASO) substantially increased trastuzumab-induced cytotoxicity. Clinically, increased expression of serum exosomal AGAP2-AS1 was associate with poor response to trastuzumab treatment. In conclusion, exosomal AGAP2-AS1 increased trastuzumab resistance via promoting ATG10 expression and inducing autophagy. Therefore, AGAP2-AS1 may serve as predictive biomarker and therapeutic target for HER-2+ breast cancer patients.

Near-infrared laparoscopy with indocyanine green for axillary sentinel lymph node biopsy in early breast cancer: preliminary experience of a single unit.

BACKGROUND: A sentinel lymph node biopsy (SLNB) is a routine procedure for axillary staging in cN0 breast cancer (BC) patients. Indocyanine green (ICG) fluorescence can detect sentinel lymph nodes with higher sensitivity than carbon nanoparticle suspension (CNS). The present study investigated the availability and benefits of a near-infrared (NIR) laparoscopy-assisted SLNB using ICG and carbon nanoparticle suspension as tracers. METHODS: Forty patients with invasive BC, who had clinically negative axillary lymph nodes, participated in this observational study. ICG and CNS tracers were injected into the periareolar region simultaneously or sequentially. In the endoscopy-assisted group (n=20), the patients were given NIR laparoscopic SLNB based on ICG fluorescence and CNS staining. In the open-surgery group, the patients were given traditional SLNB using an open incision, and CNS tracers were injected into the same region as that in the endoscopy-assisted group. RESULTS: In the endoscopy-assisted group, lymphatic vessels and sentinel lymph nodes (SLNs) were successfully identified using ICG fluorescence imaging in most patients (19/20). The average number of SLNs removed was 2.85 (range, 1-4) in the endoscopy-assisted group, and 3.40 (range, 1-7) in the open-surgery group. There was no significant difference between the number of detected nodes (P=0.30). The patients who underwent endoscopy-assisted SLNBs had similar operating times, blood loss and hospital-stay lengths, but lower postoperative drainage volumes and higher satisfaction scores, as they did not have axillary incisions. CONCLUSIONS: The NIR laparoscopy-assisted ICG-guided technique is a feasible and surgeon-friendly method for SLNB with good efficacy and acceptable safety. When combined with CNS, more SLNs can be detected and dissected.

Preoperative Nomogram for Predicting Sentinel Lymph Node Metastasis Risk in Breast Cancer: A Potential Application on Omitting Sentinel Lymph Node Biopsy.

BACKGROUND: Sentinel lymph node (SLN) biopsy is feasible for breast cancer (BC) patients with clinically negative axillary lymph nodes; however, complications develop in some patients after surgery, although SLN metastasis is rarely found. Previous predictive models contained parameters that relied on postoperative data, thus limiting their application in the preoperative setting. Therefore, it is necessary to find a new model for preoperative risk prediction for SLN metastasis to help clinicians facilitate individualized clinical decisions. MATERIALS AND METHODS: BC patients who underwent SLN biopsy in two different institutions were included in the training and validation cohorts. Demographic characteristics, preoperative tumor pathological features, and ultrasound findings were evaluated. Multivariate logistic regression was used to develop the nomogram. The discrimination, accuracy, and clinical usefulness of the nomogram were assessed using Harrell's C-statistic and ROC analysis, the calibration curve, and the decision curve analysis, respectively. RESULTS: A total of 624 patients who met the inclusion criteria were enrolled, including 444 in the training cohort and 180 in the validation cohort. Young age, high BMI, high Ki67, large tumor size, indistinct tumor margins, calcifications, and an aspect ratio ≥1 were independent predictive factors for SLN metastasis of BC. Incorporating these parameters, the nomogram achieved a robust predictive performance with a C-index and accuracy of 0.92 and 0.85, and 0.82 and 0.80 in the training and validation cohorts, respectively. The calibration curves also fit well, and the decision curve analysis revealed that the nomogram was clinically useful. CONCLUSIONS: We established a nomogram to preoperatively predict the risk of SLN metastasis in BC patients, providing a non-invasive approach in clinical practice and serving as a potential tool to identify BC patients who may omit unnecessary SLN biopsy.

Association study between KCNQ1 and KCNQ1OT1 genetic polymorphisms and gastric cancer susceptibility and survival in a Chinese Han population: a case-control study.

BACKGROUND: The present study analyzed gene polymorphisms in the potassium voltage-gated channel KQT-like subfamily member 1 (KCNQ1) and the long noncoding RNA, KCNQ1OT1, and their impacts on genetic susceptibility and survival in a Chinese Han population with gastric cancer (GC). METHODS: We designed a case-control study that included 681 patients with GC and 756 healthy controls. Three single-nucleotide polymorphisms (SNPs) in the KCNQ1 gene region and eight SNPs in the KCNQ1OT1 gene region were selected for further research. RESULTS: Among the 11 SNPs, we found no significant differences in the genotype and allele frequencies between GC patients and the healthy population. Hierarchical analysis by the log-additive model indicated that the KCNQ1 rs231348 CT genotype was significantly associated with an increased GC risk in individuals aged ≥55 years, regardless of gender. The KCNQ1OT1 rs231352 CC and rs7128926 AA genotypes increased the risk of GC in individuals with stage III/IV tumors larger than 5 cm in diameter. On evaluating the genotype polymorphism and survival analysis, we detected that the AA genotypes of the KCNQ1OT1 rs7128926 and rs7939976 polymorphisms presented a significant survival advantage over the GA/GG genotypes, especially in patients with the following characteristics: age >55, Helicobacter pylori infection, BMI >24, tumor in the non-cardia region with a diameter greater than 5 cm, clinical stage II, and postoperative adjuvant chemotherapy. CONCLUSIONS: Our results suggest that the KCNQ1 rs231348 and KCNQ1OT1 rs231352 polymorphisms might be independent predictors of the risk of GC susceptibility depending on certain factors, such as the age of the individual and the tumor stage and diameter. Simultaneously, genotype polymorphism of the rs7128926 and rs7939976 loci of the KCNQ1OT1 gene independently predicted the recurrence-free survival (RFS) and overall survival (OS) of GC patients.

The application of the three-dimensional high-definition laparoscope in thyroid microcarcinoma.

BACKGROUND: This study aimed to evaluate the feasibility and safety of the three-dimensional (3D) high-definition (HD) laparoscope via a chest-breast approach in thyroid microcarcinoma. METHODS: In this retrospective study, ten patients with thyroid microcarcinoma who underwent laparoscopic thyroidectomy in the Department of General Surgery of Tangdu Hospital from May 2016 to October 2016 were included. Preoperative thyroid and neck ultrasound in these patients showed a thyroid nodule ≤1 cm, and no significantly enlarged cervical lymph nodes were observed. The patients' thyroid function showed no subclinical hyperthyroidism. Three trocars were used via the chest and breast during the surgery. The main outcome measures included the operation time, intraoperative blood loss, postoperative hospital stay time, postoperative drainage volume, and the incidence of complications. RESULTS: The ten patients were successfully treated using a 3D HD laparoscope. The mean operation time was 70-160 minutes, the average intraoperative blood loss was 10-30 mL, the mean postoperative hospital stay was 4.5 days, and the mean postoperative drainage volume was 10-20 mL. None of the patients needed to receive a traditional open thyroidectomy during the operation. No patient experienced hoarseness, numbness of limbs, or choking or coughing while drinking water. CONCLUSIONS: The 3D endoscopic thyroidectomy operation via the chest-breast approach is a feasible and safe therapeutic method for the treatment of thyroid microcarcinoma.

Development and external validation of a prognostic nomogram for patients with gastric cancer after radical gastrectomy.

BACKGROUND: Gastric cancer (GC) is one of the most malignant diseases and threatens the health of individuals across the globe. Hitherto, the identification of prognosis risk stratification on GC has mainly depended on the TNM staging, but owing to its inaccuracy and incompleteness, the prognostic value it offers remains controversial in the current clinical setting. Thus, an effective prognostic model for GC after radical gastrectomy is still needed. METHODS: Patients with pathologically confirmed GC who underwent radical gastrectomy from 2 different centers were retrospectively enrolled into a training and the validation cohort, respectively. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select variables among multiple factors, including clinical characteristics, pathological parameters, and surgery- and treatment-related indicators. The multivariate Cox regression method was used to establish the model to predict 1-, 2-, and 3-year survival. Both internal and external validations of the nomogram were then completed in terms of discrimination, calibration, and clinical utility. Finally, prognostic risk stratification of GC was conducted with X-tile software. RESULTS: A total of 1,424 patients with GC were eligible in this study, including 1,010 in the training cohort and 414 in the validation cohort. Seven indicators were selected by LASSO to develop the nomogram, including the number of positive lymph nodes, tumor size, adjacent organ invasion, vascular invasion, the level of carbohydrate antigen 125 (CA 125), depth of invasion, and human epidermal growth factor receptor 2 (HER2) status. The nomogram demonstrated a robust predictive capacity with favorable accuracy, discrimination, and clinical utility both in the internal and external validations. Moreover, we divided the population into 3 risk groups of survival according to the cutoff points generated by X-tile, and in this way, the nomogram was further improved into a risk-stratified prognosis model. CONCLUSIONS: We have developed a prognostic risk stratification nomogram for GC patients after radical gastrectomy with 7 available indicators that may guide clinical practice and help facilitate tailored decision-making, thus avoiding overtreatment or undertreatment and improving communication between clinicians and patients.

Neoadjuvant targeted therapy for apocrine carcinoma of the breast: A case report.

BACKGROUND: Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice. Neoadjuvant therapy, especially neoadjuvant targeted therapy, has rarely been reported for apocrine carcinoma of the breast. CASE SUMMARY: A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy. The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status (estrogen receptor and progesterone receptor) but showed overexpression of human epidermal factor receptor 2 (HER-2). Moreover, positive expression of androgen receptor (approximately 60%) and gross cystic disease fluid protein 15 was observed. The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen (docetaxel, carboplatin area under curve 6 and trastuzumab) every 21 d. The mass in the left breast was significantly reduced, and pain in the breast and left upper arm also improved. CONCLUSION: HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.

Potential protection of indocyanine green on parathyroid gland function during near-infrared laparoscopic-assisted thyroidectomy: A case report and literature review.

BACKGROUND: In recent decades, significant advances have been made in protecting the parathyroid glands and recurrent laryngeal nerves during thyro-idectomy. However, reliable and convenient technical means are still lacking. In this study, the reliability, safety and feasibility of near-infrared (NIR) laparoscopy-assisted thyroid lobectomy with isthmectomy and prophylactic central lymph node dissection (CLND) were reported. CASE SUMMARY: A 63-year-old female patient with a free previous medical history, was admitted to our department due to multiple thyroid nodules. Ultrasonic examination suggested diffuse thyroid changes and one thyroid nodule in the right upper lobe with the largest diameter of 1.5 cm adjacent to the trachea and Breast Imaging Reporting and Data System grade 4B. Imaging examination of the neck showed no obvious enlarged lymph nodes. Fine needle aspiration biopsy suggested a papillary thyroid carcinoma. Combined with thyroid function examination, the patient was diagnosed with papillary thyroid carcinoma and Hashimoto's thyroiditis. Considering the risk of invading the capsule and the patient's extreme anxiety, a right thyroid lobectomy with isthmectomy and prophylactic CLND was planned. No significant abnormalities were found during preoperative examinations, except for an increased thyroid stimulating hormone level. The patient underwent NIR laparoscopy-assisted thyroid lobectomy with isthmectomy and prophylactic CLND. During the operation, two right parathyroid glands (PGs) adjacent to the thyroid gland capsule and the right recurrent laryngeal nerve (RLN) were examined by indocyanine green (ICG) fluorescence using a NIR fluorescence camera, and the PGs and RLN were reliably preserved. Considering the ICG-positive PG, prophylactic CLND was performed. The postoperative parathyroid hormone level was in the normal range and no significant hypocalcemia symptoms were observed. CONCLUSION: During NIR laparoscopy-assisted thyroidectomy, ICG fluorescence may aid PG identification and protection.

Growth factor receptor bound protein-7 regulates proliferation, cell cycle, and mitochondrial apoptosis of thyroid cancer cells via MAPK/ERK signaling.

It is of great significance to explore the molecular mechanism of thyroid cancer (TC) pathogenesis for its improvement and therapy. Growth factor receptor bound protein-7 (GRB7) has been regarded as an important regulatory gene in the developments of various malignant tumors. Our study aimed to illustrate the role of GRB7 in the TC pathology mechanism. Firstly, GRB7 was found to be significantly upregulated in 49 cases of TC tissues and 5 TC cell lines by using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Silencing GRB7 with siRNA dramatically inhibited proliferation and induced cell cycle arrest in TC cells. Besides, GRB7 silence resulted in the decrease of adenosine triphosphate content, glucose uptake, and lactose production in TC cells and attenuated the activity and expression of mitochondrial respiratory complex. We also demonstrated that GRB7 downregulation increased the levels of Bax and caspase 3, and inhibited the expression of Bcl-2, suggesting the induced mitochondrial apoptosis. More importantly, our study proved that mitogen-activated protein kinase/extracellular-regulated protein kinases (MAPK/ERK) signaling played a crucial role in the regulation of GRB7 on TC cell functions. In general, the present research verified that GRB7 was upregulated during TC development and modulated the proliferation, cell cycle, and mitochondrial apoptosis of TC cells by activating MAPK/ERK pathway. This may provide a novel target for the therapeutic strategy of TC.