Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review.

Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.

EM-transcriptomic signature predicts drug response in advanced stages of high-grade serous ovarian carcinoma based on ascites-derived primary cultures.

Introduction: High-grade serous ovarian carcinoma (HGSOC) remains a medical challenge despite considerable improvements in the treatment. Unfortunately, over 75% of patients have already metastasized at the time of diagnosis. Advances in understanding the mechanisms underlying how ascites cause chemoresistance are urgently needed to derive novel therapeutic strategies. This study aimed to identify the molecular markers involved in drug sensitivity and highlight the use of ascites as a potential model to investigate HGSOC treatment options. Methods: After conducting an in silico analysis, eight epithelial-mesenchymal (EM)-associated genes related to chemoresistance were identified. To evaluate differences in EM-associated genes in HGSOC samples, we analyzed ascites-derived HGSOC primary cell culture (AS), tumor (T), and peritoneal nodule (NP) samples. Moreover, in vitro experiments were employed to measure tumor cell proliferation and cell migration in AS, following treatment with doxorubicin (DOX) and cisplatin (CIS) and expression of these markers. Results: Our results showed that AS exhibits a mesenchymal phenotype compared to tumor and peritoneal nodule samples. Moreover, DOX and CIS treatment leads to an invasive-intermediate epithelial-to-mesenchymal transition (EMT) state of the AS by different EM-associated marker expression. For instance, the treatment of AS showed that CDH1 and GATA6 decreased after CIS exposure and increased after DOX treatment. On the contrary, the expression of KRT18 has an opposite pattern. Conclusion: Taken together, our study reports a comprehensive investigation of the EM-associated genes after drug exposure of AS. Exploring ascites and their associated cellular and soluble components is promising for understanding the HGSOC progression and treatment response at a personalized level.

Dynamics of RAS Mutations in Liquid Biopsies in Metastatic Colorectal Cancer Patients-Case Series and Literature Review.

Liquid biopsies can accurately identify molecular alterations in patients with colorectal cancer with high concordance with tissue analysis and shorter turnaround times. Circulating tumor (ct) DNA analysis can be used for diagnosing and monitoring tumor evolution in patients with metastatic colorectal cancer who are treated with EGFR inhibitors. In this article, we reported three clinical cases to illustrate the relevance of RAS mutations identified in ctDNA samples of patients with wild-type metastatic colorectal cancer who received an EGFR inhibitor plus chemotherapy as first-line treatment. The identification of RAS mutations in these patients is one of the most frequently identified mechanisms of acquired resistance. However, detecting a KRAS mutation via liquid biopsy can be caused by inter-tumor heterogeneity or it can be a false positive due to clonal hematopoiesis. More research is needed to determine whether ctDNA monitoring may help guide therapy options in metastatic colorectal cancer patients. We performed a literature review to assess the technologies that are used for analysis of RAS mutations on ctDNA, the degree of agreement between tissue and plasma and the importance of tissue/plasma discordant cases.

The impact of SARS-CoV-2 infection on renal function in patients with biopsy-proven kidney diseases.

BACKGROUND: We sought to evaluate the long-term effects of COVID-19 on renal function in patients with biopsy-proven kidney diseases. METHODS: A total of 451 patients with biopsy-proven kidney disease and at least 12 months of follow-up subsequent to COVID-19 pandemic onset were included in the study. The primary study endpoint was a composite of a persistent decline of more than 30% in eGFR or ESRD. RESULTS: 23.1% of patients had COVID-19 during a follow-up period of 2.5 y (0.8-2.6), while 17.6% of patients reached the composite endpoint. Those with COVID-19 were more likely to reach the composite endpoint [26.7% vs. 14.8%; OR, 2.1 (95%CI, 1.23-3.58), p = 0.006). There was a significant eGFR change in the first year of follow-up between the two study groups [-2.24 (95%CI,-4.86; 0.37) vs. +2.31 (95%CI, 0.78; 3.85) ml/min, p = 0.004], with an adjusted mean difference of -4.68 ml/min (95%CI,-7.7; -1.59)(p = 0.03). The trend for worse renal outcomes remained consistent in patients with IgAN, MN and FSGS, but not in those with LN. After multivariate adjustment, the independent predictors of the composite endpoint were baseline eGFR (HR, 0.94; 95%CI, 0.92-0.95), COVID-19 (HR, 1.91; 1.16-3.12) and male gender (HR, 1.64; 95%CI, 1.01-2.66). In multivariate linear regression analysis, COVID-19 independently determined a reduction of eGFR at 12 months by 4.62 ml/min/1.73m2 (ß coefficient, -4.62; 95%CI, -7.74 to -1.5, p = 0.004). CONCLUSIONS: There is a significant impact of COVID-19 on long-term renal function in patients with biopsy-proven kidney diseases, leading to a greater decline of eGFR and a worse renal survival.