Molecular and clinical oncology最新文献

Angiomatous meningioma (AM) is a relatively rare subtype of WHO grade I meningioma. A relatively rare case of AM was recently encountered in a 45-year-old woman. The present case not only observed the typical AM histological pattern but also a large number of cells with bizarre, large, deeply staining and unevenly distributed nuclei. These cells with bizarre nuclei showed a similar pattern of immunoreactivity as meningeal epithelial cells. Although the presence of a large number of cells with bizarre nuclei in this case increased tumour cell atypia, the cells did not differ with regard to proliferative activity and mitotic imaging. Therefore, the patient was ultimately diagnosed as having AM with bizarre nuclei, WHO grade I. This manifestation of nuclear atypia and pleomorphism may be due to 'degenerative changes' in pre-existing, long-established vascular lesions, similar to those seen in degenerative schwannomas and symplastic haemangioma, rather than being considered an indicator of malignancy.

Patients with non-small cell lung cancer (NSCLC) are often positive for oncogenic driver mutations, such as EGFR, ALK, BRAF, RET and MET exon 14 skipping mutations (METex14 skipping). Recently, METex14 skipping has become a functional biomarker for NSCLC with the approval of MET kinase inhibitors. Tepotinib is an oral MET kinase inhibitor. Its overall response rate is 46%, and the median duration of the response is 11.1 months. In Japan, companion diagnostics for tepotinib are limited with the ArcherMET and AmoyDx test, but not with Oncomine Dx target test. The present study reports the case of a 60-year-old male patient with lung adenocarcinoma harboring METex14 skipping, which was positive on Oncomine DxTT, but not on ArcherMET. In his sample used for Oncomine DxTT, the read count of MET(13)-MET(15) products was only 46. He was treated with various chemotherapeutic agents, but developed cardiac tamponade due to the progression of the disease of mediastinal lymph node metastases. Tepotinib was administered following pericardial drainage, resulting in an immediate response in all lesions. The majority of the discordant samples between Oncomine DxTT and ArcherMET had read counts <800, and the patient described herein had only 46. Therefore, the results of the present study indicate that the use of tepotinib should be considered even in patients whose METex14 skipping results were negative with ArcherMET, yet positive on Oncomine DxTT, particularly relatively with low lead counts.

Hip rotationplasty is a surgical method used to treat malignant tumors of the proximal femur. A 52-year-old woman, who underwent hip rotationplasty for Ewing sarcoma of the proximal left femur at the age of 24, fell and hit the left buttock. The patient was then admitted to the Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus. Radiography and computed tomography (CT) revealed a comminuted fracture of the reconstructed bone distally. The patient underwent open reduction and internal fixation (ORIF) and external fixator. External fixation was removed 1 month after the surgery. At two years after surgery, at the latest follow-up, bone union was confirmed by 3-dimensional CT. The combination of ORIF and temporal external fixation was effective for the reconstructed bone fractures after hip rotationplasty.

Lymph node dissection is used to treat early-stage lung cancer. The present study aimed to investigate if resecting the subcarinal lymph nodes affects prognosis of patients with stage IB non-small cell lung cancer (NSCLC). A total of 597 patients with stage IB NSCLC who underwent lung cancer surgery at Sun Yat-Sen University Cancer Center from January 1999 to December 2009 were included in the present study. The potential prognostic factors were evaluated using the Cox proportional hazard regression model. A total of 252 cases were obtained following propensity score matching (PSM). To compare overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier method and log-rank test were used. Among the 597 cases included, 185 did not undergo subcarinal lymph node resection, whereas 412 did. There were statistically significant differences between the two groups in terms of bronchial invasion, number of resected lymph node stations and resected lymph node numbers (P<0.05). Age, family history of cancer and the number of resected lymph nodes were prognostic factors for OS, whereas age and the number of resected lymph nodes were prognostic factors for RFS (P<0.05). Resection of subcarinal lymph nodes was not associated with OS and RFS. After PSM, survival analysis was recalculated using the Kaplan-Meier method and log-rank test; subcarinal lymph node resection was not statistically associated with OS and RFS. (P>0.05). For stage IB NSCLC, there was no statistically significant association between subcarinal lymph node resection and OS and RFS. Subcarinal lymph node resection in surgery of stage IB NSCLC may be considered optional.

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization strategies for the next generation of drugs. Subsequently, experts have improved the first-generation ADCs and have developed second-generation ADCs such as ado-trastuzumab emtansine. Second-generation ADCs have higher specific antigen levels, more stable linkers and longer half-lives and show great potential to transform cancer treatment models. Since the first two generations of ADCs have served as a good foundation, the development of ADCs is accelerating, and third-generation ADCs, represented by trastuzumab deruxtecan, are ready for wide application. Third-generation ADCs are characterized by strong pharmacokinetics and high pharmaceutical activity, and their drug-to-antibody ratio mainly ranges from 2 to 4. In the past decade, the research prospects of ADCs have broadened, and an increasing number of specific antigen targets and mechanisms of cytotoxic drug release have been discovered and studied. To date, seven ADCs have been approved by the FDA for lymphoma, and three have been approved to treat breast cancer. The present review explores the function and development of ADCs and their clinical use in cancer treatment.

Nuclear medicine is an essential part of prostate cancer management concerning initial staging, patient follow-up and even therapy. Prostate-specific membrane antigen (PSMA) is a glutamate carboxypeptidase II transmembrane glycoprotein expressed by 80% of prostatic cells. The interest in this protein is due to its specificity for prostatic tissue. The use of 68GaPSMA PET/CT in the context of disease staging is thus well-established and recommended, especially for high-risk disease with metastases and lymph node involvement. However, the risk of false positives raises questions regarding its place in the management of patients with prostate cancer. The present study aimed to determine the use of PET-PSMA in the care of patients with prostate cancer but also to assess its limits of use.

Metaplastic breast carcinoma (MBC) is a heterogeneous group of invasive breast carcinomas (IBCs) characterized by the differentiation of the neoplastic epithelium toward squamous cells and/or mesenchymal-appearing elements. The present study describes the case of a 42-year-old woman who underwent a mastectomy and sentinel lymph node biopsy for two tumors in their left breast. One of the resected tumors was diagnosed as MBC with neuroendocrine (NE) differentiation and the other was diagnosed as IBC of no special type. The MBC tumor contained a matrix composed of basal lamina with a focal area of myxoid matrix and squamoid differentiation. To the best of our knowledge, the present study is the first report of MBC producing prominent basal lamina. The patient has remained alive and well for >10 years without recurrence, and has been treated with oral and injected anticancer drugs.

Immune checkpoint inhibitor (ICI) therapy has been less effective in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations than in patients with EGFR wild-type NSCLC. This retrospective study was conducted to investigate the associations of clinical parameters with the efficacy of ICI therapy in patients with EGFR-mutant NSCLC. Clinical information was retrieved from the medical charts, and immunohistochemical analysis was performed in some cases to determine the tumor-infiltrating CD68-positive cell count. Data from 46 patients were included in the analysis. The median (95% confidence interval) progression-free survival and overall survival from the initiation of ICI therapy was 1.4 months (1.0-1.7 months) and 6.4 months (3.9-19.0 months), respectively. Analysis using a Cox proportional hazards model revealed that tumor programmed death-ligand 1 expression was associated with the overall survival of patients with EGFR-mutant NSCLC after ICI treatment. The tumor-infiltrating CD68-positive cell count was evaluated in 11 patients. Comparison using the log-rank test revealed that the progression-free survival time after ICI treatment was longer in the patients with lower tumor-infiltrating CD68-positive cell counts than those with higher tumor-infiltrating CD68-positive cell counts. The present analysis demonstrated that PD-L1 expression and the tumor-infiltrating CD68-positive cell count may be associated with the efficacy of ICI therapy in patients with NSCLC harboring EGFR mutations.

Systemic oncological treatment may cause drug-induced liver injury (DILI). Therefore, there is a pressing need for an active drug able to accelerate liver regeneration. Silymarin mitigates oxidative stress, and inhibits pro-inflammatory and pro-apoptotic cytokines and the fibrotic transformation of liver tissue. Currently, there are a lack of data regarding the optimal dosage of silymarin and its efficacy. Thus, the present retrospective study aimed to determine the optimal dose of silymarin for use in oncological DILI treatment. For this purpose, 180 patients with solid malignancies treated with systemic oncological therapy and silymarin between January, 2015 and November, 2021 were enrolled in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (Bil) levels, as well as the dose of silymarin were assessed at the initiation of silymarin treatment, after 3-6 weeks and after 6-12 weeks. Pearson's correlation analysis was performed to evaluate the correlation between the initial dose of silymarin (IDoS), and the ALT, AST and Bil levels. The effects of four independent variables, namely IDoS, the initial dose reduction of systemic treatment, the systemic treatment dose reduction at first assessment (DR1M) and the elevation of the silymarin dose at first control on the ALT, AST and Bil levels were evaluated using regression analysis. The median IDoS was 450 mg. A decrease in or the stabilization of the ALT, AST and Bil levels after 6-12 weeks were observed in 68.63, 65.85 and 53.25% of patients, respectively. There was a weak correlation between IDoS and the decrease in ALT and AST levels after 6-12 weeks (correlation coefficient, R=0.361 and 0.277 respectively, P<0.001). No significant correlation between the IDoS and a decrease in Bil levels was observed. DR1M was a negative predictor for a decrease in Bil levels in patients with liver tumors. On the whole, the present study demonstrates that silymarin appears to be efficient in alleviating DILI at a dose of 300-450 mg. A further increase in the dose of silymarin may not lead to an adequate increase in its efficacy.

The present study aimed to evaluate the rate of positive surgical margins for magnetic resonance imaging (MRI) performed in the supine position prior to breast-conserving surgery (BCS). The rate of positive surgical margins and the clinicopathological factors were examined in consecutive patients with BCS who underwent preoperative MRI performed in the supine position at Sapporo Medical University Hospital (Sapporo, Japan) and related hospitals and clinics between January 2012 and December 2013. Of 1,175 eligible patients, 1,150 were included after excluding 25 patients with either bilateral breast cancer or stage IV disease. Positive margin was defined as no cancer seen on the resected margin. The primary endpoint was the rate of positive surgical margins when preoperative MRI was performed in the supine position and the secondary endpoint was identification of the factors that predict positive margins. Of the 1,150 female patients (median age, 55 years; range, 29-97 years) who underwent BCS for breast cancer following MRI performed in the supine position, 215 (18.8%) had positive margins, which is similar to the rate with MRI in the prone position, and 930 (81.2%) had negative margins. The rate of positive surgical margins in patients of the human epidermal growth factor receptor 2 (HER2) type was significantly higher than that in the non-HER2 type group (6.5 and 2.9%; χ² P=0.0103). There was no increase in the rate of positive margins in breast cancers with a diameter of >T2. The rate of positive surgical margins following MRI performed in the supine position was 18.8%. Supine MRI appears to be suitable for informing on the extent of resection of breast cancer.