PAX3/7 fusion-negative rhabdomyosarcoma (FN-RMS) is a childhood mesodermal lineage malignancy with a poor prognosis for metastatic or relapsed cases. Limited understanding of advanced FN-RMS is partially attributed to the absence of sequential invasion and dissemination events and the challenge in studying cell behavior, using, for example, non-invasive intravital microscopy (IVM), in currently used xenograft models. Here, we developed an orthotopic tongue xenograft model of FN-RMS to study cell behavior and the molecular basis of invasion and metastasis using IVM. FN-RMS cells are retained in the tongue and invade locally into muscle mysial spaces and vascular lumen, with evidence of hematogenous dissemination to the lungs and lymphatic dissemination to lymph nodes. Using IVM of tongue xenografts reveals shifts in cellular phenotype, migration to blood and lymphatic vessels, and lymphatic intravasation. Insight from this model into tumor invasion and metastasis at the tissue, cellular, and subcellular level can guide new therapeutic avenues for advanced FN-RMS.

BACKGROUND: Extrauterine malignancies in cervical samples are rarely seen. It is important to differentiate these cells from those of primary uterine malignancies to determine appropriate line of further investigations and management. Literature on these lesions is limited largely restricted to case reports. The aim of the present study was to study the spectrum and cytomorphological features of extrauterine malignancies in cervical Pap smears.
METHODS: It is a retrospective and descriptive study conducted in Department of Cytopathology from January 2019 to July 2023. All cases of extrauterine malignancies with available cytology material were included in this study. All cases of primary uterine malignancies, i.e., uterine corpus or cervix confirmed by clinical, radiological, and histopathological examination were excluded.
RESULTS: 104 out of 11,674 cytology Pap smears were those of extrauterine malignancy. Diagnosis of extrauterine malignancy was given in 47.1% cases, 30.9% were reported as positive for malignancy without giving the possibility of an extrauterine origin, and 22.0% were reported as atypical glandular cells only. In 56 cases where Pap smear was the first investigation which led to the diagnosis. Most common extrauterine malignancy was adenocarcinoma principally from ovarian, colorectal, and vaginal origin. Other epithelial malignancies noted were urothelial carcinoma and invasive breast carcinoma. Among non-epithelial malignancies, we reported vaginal mucosal melanoma, cutaneous melanoma, acute leukaemia, and anaplastic large cell lymphoma.
CONCLUSIONS: High index of suspicion, presence of squamous and glandular elements with no atypical features, and occasional clusters of cells with marked atypia and usually no necrosis in the background are helpful cytomorphological clues to raise suspicion for extrauterine malignancy. Correlation with serology, radiology, and immunocytochemistry can help in reaching final diagnosis.

BACKGROUND: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC.
METHODS: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes.
RESULTS: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation.
CONCLUSIONS: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification.

Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady\'s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.

暂无摘要。

OBJECTIVE: To develop and validate a predictive combined model for metastasis in patients with clear cell renal cell carcinoma (ccRCC) by integrating multimodal data.
METHODS: In this retrospective study, the clinical and imaging data (CT and ultrasound) of patients with ccRCC confirmed by pathology from three tertiary hospitals in different regions were collected from January 2013 to January 2023. We developed three models, including a clinical model, a radiomics model, and a combined model. The performance of the model was determined based on its discriminative power and clinical utility. The evaluation indicators included area under the receiver operating characteristic curve (AUC) value, accuracy, sensitivity, specificity, negative predictive value, positive predictive value and decision curve analysis (DCA) curve.
RESULTS: A total of 251 patients were evaluated. Patients (n = 166) from Shandong University Qilu Hospital (Jinan) were divided into the training cohort, of which 50 patients developed metastases; patients (n = 37) from Shandong University Qilu Hospital (Qingdao) were used as internal testing, of which 15 patients developed metastases; patients (n = 48) from Changzhou Second People\'s Hospital were used as external testing, of which 13 patients developed metastases. In the training set, the combined model showed the highest performance (AUC, 0.924) in predicting lymph node metastasis (LNM), while the clinical and radiomics models both had AUCs of 0.845 and 0.870, respectively. In the internal testing, the combined model had the highest performance (AUC, 0.877) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.726 and 0.836, respectively. In the external testing, the combined model had the highest performance (AUC, 0.849) for predicting LNM, while the AUCs of the clinical and radiomics models were 0.708 and 0.804, respectively. The DCA curve showed that the combined model had a significant prediction probability in predicting the risk of LNM in ccRCC patients compared with the clinical model or the radiomics model.
CONCLUSIONS: The combined model was superior to the clinical and radiomics models in predicting LNM in ccRCC patients.

OBJECTIVE: Status epilepticus (SE) represents a neurological emergency with significant morbidity and mortality. SE in patients with primary brain tumors received only limited attention to date; detailed analysis of treatment flow is lacking, especially as compared to other SE causes. This study aims to describe the frequency and treatment flow of tumor-related SE and compare it to other SE etiologies.
METHODS: Retrospective cohort study based on an institutional SE registry (SERCH) comprising adult SE (excluding post-anoxic causes), treated between January 2013 and December 2022, comparing SE management, frequency of refractory SE, and clinical outcome, among four patients\' groups stratified by SE etiology: Non-neoplastic, Gliomas, Brain metastases, Other brain tumors.
RESULTS: We analyzed 961 episodes in 831 patients (Non-neoplastic: 649, Gliomas: 85, Metastases: 77, Other brain tumors: 20). Although tumor-patients presented more often with focal episodes and less consciousness impairment than non-neoplastic patients, administration of benzodiazepines as first-line treatment (>75% across all groups), and utilization of second-line ASM were similar across groups. Treatment adequacy was marginally higher in glioma patients compared to the non-neoplastic population (p: 0.049), while refractory SE was comparable in all groups (p: 0.269). No significant differences in clinical outcomes were observed (mortality: non-neoplastic (89/649, 13.7%), glioma (8/85, 9.4%), metastases (14/77, 18.2%), other tumors (5/20, 25.0%), p: 0.198; non-neoplastic vs. glioma, p: 0.271) CONCLUSION: Tumor-associated SE represents 1/5 of all SE episodes, and is managed similarly to other SE causes. Treatment responsiveness and short-term clinical outcomes also exhibit comparable results.

UNASSIGNED: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma.
UNASSIGNED: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted.
UNASSIGNED: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases.
UNASSIGNED: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

暂无摘要。

BACKGROUND: This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab.
METHODS: This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model.
RESULTS: During the median follow-up period of 7.3 months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2 g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42 mg/L was a significant prognostic factor for OS (p = 0.001).
CONCLUSIONS: The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.