World Journal of Oncology最新文献

Background: This study aimed to compare surgical outcomes between Stratafix barbed sutures and conventional sutures in patients undergoing total mastectomy for breast cancer.

Methods: This retrospective study analyzed patients who underwent total mastectomy and/or axillary lymph node dissection at our hospital.

Results: A total of 29 patients were included. No significant differences were observed in clinicopathological features between the two groups. However, the percentage of suturing time within the total operative time was significantly lower in the Stratafix group compared to conventional group (10% vs. 8%). In addition, the suturing time per centimeter was also significantly shorter with Stratafix group (P < 0.001). No wound-related complications were observed in either group during at least 3 months of follow-up.

Conclusions: The use of barbed sutures for wound closure in mastectomy procedures effectively reduces suturing time without increasing the incidence of wound complications. Bidirectional Stratafix barbed sutures offer an improved and efficient alternative to conventional sutures for breast surgeons.

Background: Factors influencing in-hospital mortality in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remain understudied, highlighting gaps in optimizing acute clinical outcomes. This study aimed to identify sociodemographic and clinical predictors of all-cause in-hospital mortality in this population.

Methods: Using 2016 - 2020 data from the National Inpatient Sample (NIS), patients with malignant well-differentiated GEP-NETs were identified via the International Classification of Diseases, 10th Revision (ICD-10) codes. The primary outcome was in-hospital mortality. Sociodemographic and clinical variables (heart failure (HF), malnutrition, Charlson Comorbidity Index (CCI), and tumor site) were analyzed using multivariable logistic regression.

Results: Among 5,642 patients (mean age 64, standard deviation (SD) 12.9), multivariable analysis identified HF (adjusted odds ratio (aOR) 2.09, 95% confidence interval (CI): 1.10 - 3.95), malnutrition (aOR 1.84, 95% CI: 1.29 - 2.62), pancreatic (aOR 1.52, 95% CI: 1.01 - 2.30) or colon tumors (aOR 2.31, 95% CI: 1.51 - 3.53), CCI ≥ 5 (aOR 1.49, 95% CI: 1.06 - 2.10), hypertension (aOR 0.65, 95% CI: 0.47 - 0.91) and elective admissions (aOR 0.40, 95% CI: 0.25 - 0.63) as clinically relevant factors associated with in-hospital mortality.

Conclusions: Advanced age, tumor location, malnutrition, and HF may be critical mortality predictors among patients with GEP-NETs. These findings advocate for integrated care models prioritizing nutritional support, cardiovascular monitoring, and early elective interventions to improve outcomes.

Background: The genetic characteristics of surgically removed cancerous tissues are examined using cancer gene panel testing in cancer genome medicine to detect the pathogenic variants involved in the proliferation and progression of cancer cells. An antitumor drug is prescribed if it directly acts on the detected pathogenic variant; however, some aspects require careful consideration by medical professionals in such cases. The genetic mutations involved in the progression or onset of malignant tumors differ with race. Furthermore, genetic mutations that are variants of unknown significance (VUS) may be involved in the progression or onset of malignant tumors in some races according to the ClinVar results from the National Center for Biotechnology Information. Single nucleotide variations can result in silent mutations or splice sites.

Methods: We therefore reexamined the CGP results (VUS) of patients suspected of developing hereditary tumors based on their family background using IGV and RT-PCR.

Results: KRAS Q61K, which is found in many gastrointestinal cancers, was identified as a VUS by ClinVar, but this gene mutation was found to cause splicing. The cancer gene panel test of a 41-year-old male patient with paraganglioma identified succinate dehydrogenase complex, iron-sulfur subunit B (SDHB) G642T as a VUS. However, this mutation was later discovered to cause the splicing site to shift, preventing SDHB from translating from the correct mRNA. In addition, a cancer gene panel test of a 47-year-old patient with right breast cancer determined that breast cancer susceptibility gene 2 (BRCA2) 631 3A>T was a VUS. However, this mutation may create a splicing site, which means that the correct BRCA2 mRNA for BRCA2 is not produced.

Conclusions: The diagnosis of gene mutations based on the results of cancer gene panel testing may not always be correct, and a detailed examination of gene mutations is necessary. Our medical staff has performed cancer gene panel testing on approximately 5,500 cases of intractable malignant tumors to date and are investigating new treatments for these tumors. In this article, we discuss our experience with cancer gene panel testing as well as the problems encountered and new findings.

Background: Several types of regulated cell deaths are known, including apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Among these types of cell deaths, apoptosis is induced by many cancer therapeutic agents. In the case of resistance, however, induction of other regulated cell death, such as necroptosis, are required. Liquid plasma, which is prepared by treatment of non-thermal plasma to solution, induces various types of regulated cell death via reactive oxygen and nitrogen species.

Methods: Liquid plasma was generated by N₂/Ar plasma treatment in culture medium (minimum essential medium (MEM), Dulbecco's modified Eagle medium (DMEM), or Roswell Park Memorial Institute (RPMI)-1640) for 120 s per milliliter of medium (2 cm). Cell viability was determined using Cell Counting Kit-8 (CCK8), and apoptosis was determined by terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assay. Tumor necrosis factor alpha (TNF-α), cycloheximide (CHX), and zVAD-fmk were used to induce necroptosis in head and neck squamous cell carcinoma (HNSCC) cells, and necroptosis inhibitors, such as necrostatin-1 (Nec-1, 50 µM), GSK872 (10 µM), and necrosulfonamide (NSA, 2 µM) were used to inhibit necroptosis. Statistical comparisons between groups were carried out using the Student's t-test.

Results: Here, we determined the type of cell death induced by liquid plasma in head and neck cancer (HNC) cells. Our results show that liquid plasma caused necroptosis in HNC cells, and peroxynitrite in the liquid plasma might be involved in the cell death. The expression of inflammation-related molecules, including nuclear factor kappa B (NF-κB), interleukin (IL)-6, and mitochondrial antiviral signaling proteins, were detected in HNC cells, and treatment of HNC cells with liquid plasma decreased their expression.

Conclusions: These results suggest that liquid plasma could be used to treat HNC by inducing necroptosis without inflammatory responses. In this study, we demonstrated that liquid plasma treatment may kill HNC cells without causing necroptosis-induced inflammation and inflammation-mediated diseases.

Background: Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide, often characterized by the aberrant activation of multiple signaling pathways. Y-box binding protein 1 (YBX1), a multifunctional regulator of transcription and translation, has been identified as an oncogenic factor in various solid tumors. However, its expression profile and mechanistic role in CRC remain largely unclear.

Methods: In this study, integrative bioinformatic analyses were conducted on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets to assess YBX1 expression and its correlation with CRC progression. Functional assays, including cell proliferation and migration assays, were performed to investigate the role of YBX1 in CRC cells. The impact of YBX1 on the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was evaluated, and the effects of the PI3K inhibitor buparlisib (BKM120) on YBX1-driven cellular phenotypes were also tested.

Results: YBX1 was found to be significantly upregulated in CRC tissues and was closely associated with the activation of the PI3K/AKT signaling pathway. YBX1 overexpression promoted CRC cell proliferation and migration, whereas knockdown of YBX1 inhibited these processes. Mechanistically, YBX1 was shown to enhance PI3K/AKT signaling activity, promoting malignant phenotypes in CRC. Treatment with BKM120 partially reversed these effects. Additionally, Gene Set Enrichment Analysis (GSEA) identified enrichment of reactive oxygen species (ROS)-related pathways in YBX1-high CRC samples.

Conclusions: This study highlights the oncogenic role of YBX1 in CRC and reveals a potential YBX1-PI3K/AKT regulatory axis that may serve as a promising therapeutic target. The findings suggest that targeting this axis could provide a novel strategy for CRC treatment, especially under hypoxic or microenvironmental stress conditions.

Background: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are two major pathological diagnoses of breast cancer, but few studies have described their differences within luminal (estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative) subtypes at the molecular level.

Methods: Using The Cancer Genome Atlas (TCGA) (n = 584) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,355) cohorts, we analyzed luminal ILC and IDC, excluding mixed type, in patients with stage I-III breast cancer.

Results: ILC was associated with Nottingham histological grade 2, larger tumor size and more stage III disease than IDC (all P < 0.01) but no difference in lymph node nor distant metastasis in both cohorts. There was no survival difference between ILC and IDC. ILC had less aggressive genomic features compared to IDC, and the cell proliferation score and Ki67 gene expression were significantly lower in ILC in TCGA (P < 0.001); however, these findings were not validated in METABRIC. Hallmark cell proliferation-related gene sets (E2F targets, G2M checkpoint, MYC targets V1, and MTORC1 signaling) were significantly less enriched in ILC in both cohorts (all normalized enrichment score (NES) > 1.4, false discovery rate (FDR) < 0.12). While ILC appeared to have a lower trend of pathological complete response (pCR) in the GSE20194 and GSE1140494 cohorts, ILC was infiltrated with significantly more CD4⁺ cells and dendritic cells and significantly less T helper type I (Th1) cells, regulatory T cells and M1 and M2 macrophages in both cohorts (all P < 0.05). Stromal cells, adipocytes and lymphatic endothelial cells were highly infiltrated in ILC, and cytolytic activity that represented the global anti-tumor immunity was significantly elevated in ILC in TCGA and subsequently validated in METABRIC.

Conclusions: ILC has higher immune response and immune cell infiltration than IDC in the luminal subtype.

IgM myeloma is a rare subtype of multiple myeloma (MM) comprising 0.5% of all of its cases. It is characterized by the unregulated proliferation of IgM-secreting plasma cells in the bone marrow. The underlying pathogenesis involves dysregulation of isotype switch recombination, leading to various translocations involving chromosomes such as 11q13 and 4p16. Patients usually present with symptoms of hyperviscosity syndrome, bone marrow infiltration, and organomegaly. Diagnostic workup includes clinical evaluation, laboratory tests (electrophoresis, bone marrow biopsy, cytogenetics, immunohistochemistry), and imaging. Treatment options for IgM myeloma include proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and autologous stem cell transplantation. However, no clear management guidelines are established for this rare subtype of MM. This article provides an up-to-date detailed overview of the pathogenesis, clinical features, and diagnostics of IgM myeloma.

Background: Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in cancer therapy, but the resultant immune activation also precipitates autoimmune toxicities termed immune-related adverse events (irAEs). However, system-specific analyses of irAEs remain limited, particularly their variation with body mass index (BMI), race, sex, age, and type of ICI.

Methods: A retrospective analysis was conducted on 244 patients who developed irAEs after receiving ICI. Among the study population, 58% were female; the racial and ethnic distribution was 84% White, 13% Hispanic, 2% African American, and 1% Asian; and the age breakdown was 23% under 65 years, 38% between 65 and 79 years, and 39% over 80 years. Univariate analysis was performed employing the Chi-square test. Multivariable logistic regression and cluster analyses revealed distinct irAE predictors.

Results: Univariate analysis (Chi-square) showed significant associations between BMI and pneumonitis (P = 0.02) and between race and hepatitis (P = 0.04), but these did not persist in multivariate regression. No significant correlations were found between thyroiditis or colitis and sex, race, BMI, age, or immunotherapy type. Increasing age was protective against neutropenia, with significantly lower risk in patients aged 65 - 79 (odds ratio (OR) 0.38, P = 0.007) and ≥ 80 years (OR 0.18, P < 0.001); African Americans were at higher risk (OR 10.29, P = 0.02), and male sex was protective (OR 0.51, P = 0.03). Anemia was less frequent in those ≥ 80 years (OR 0.48, P = 0.03) and Hispanics (OR 0.4, P = 0.03). Thrombocytopenia risk was reduced in patients aged 65 - 79 (OR 0.41, P = 0.03) and ≥ 80 (OR 0.36, P < 0.001). Cluster analysis showed higher irAE rates in patients treated with nivolumab (alone or with ipilimumab) compared to pembrolizumab.

Conclusion: Advanced age showed a protective effect on cytopenias. Hispanics had reduced anemia and dermatitis risk; African Americans and females had higher neutropenia, and obesity was linked to dermatitis. These findings may aid clinicians in personalizing ICI counseling and recognizing at-risk groups.

Background: High mRNA expression levels of receptor activator of nuclear factor-kB (RANK) were linked with several adverse prognostic factors in breast cancer. The present study aims to assess the activity of neoadjuvant chemotherapy combined with denosumab compared to chemotherapy alone in premenopausal patients with hormonal receptors (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Methods: In this single-center randomized phase II study, we enrolled patients with ER Allred score 4 - 8 at diagnostic biopsy with locally advanced either inoperable tumors or tumors that need downsizing to allow for breast conservative surgery (BCS). Enrolled patients were randomized to receive either neoadjuvant chemotherapy (four cycles of epirubicin/doxorubicin with cyclophosphamide and four cycles of docetaxel) with denosumab or the same chemotherapy alone. Patients in the experimental arm received subcutaneous denosumab 120 mg starting with the first chemotherapy cycle and then with every other cycle (total of four doses). Residual cancer burden (RCB) was the primary endpoint.

Results: We recruited 50 patients (26 in control arm, 24 in experimental arm) for the study. Baseline characteristics were balanced between the two arms including age at diagnosis, ER Allred score (≤ 6 vs. > 6), progesterone receptor (PR) status, Ki67 level, clinical T, clinical N, and clinical stage (stage II vs. III). Noteworthy, 86% of patients were node-positive, 44% had cT4 tumors and 80% had ER Allred score > 6. Two patients in the control arm did not undergo breast surgery (one lost to follow-up, the other had local progression). There was no difference in the rates of BCS (58.3% in both arms) between the two arms. No difference in RCB between control and experimental arms (RCB 0-1: 25% vs. 20.8%, respectively, P = 0.73) was found. Similarly, there were no differences in pathological T stage (pT0-1: 87.5% vs. 70.8%, P = 0.29), pathological N stage (N0: 41.7% vs. 29.2%, P = 0.55) or pathological stage (41.6% vs. 33.3%, P = 0.75). No significant difference in adverse events profiles between the two arms was observed.

Conclusions: Adding denosumab to neoadjuvant chemotherapy was not associated with lower RCB or improved pathological stage in premenopausal HR+/HER2-negative breast cancer patients with comparable rate of BCS. No new safety signals were observed with the addition of denosumab.