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Abstract Extracellular vesicle-derived DNA (evDNA) encapsulates the complete genome and mutational status of cells; however, whether cancer cell-derived evDNA mirrors the epigenetic features of parental genomic DNA remains uncertain. This study aimed to assess and compare the DNA methylation patterns of evDNA from cancer cell lines and primary cancer tissues with those of the nuclear genomic DNA. We isolated evDNA secreted by two cancer cell lines (HCT116 and MDA-MB-231) from various subcellular compartments, including the nucleus and cytoplasm. Additionally, we obtained evDNA and nuclear DNA (nDNA) from the primary cancer tissues of colon cancer patients. We conducted a comprehensive genome-wide DNA methylation analysis using the Infinium Methylation EPIC BeadChip, examining > 850,000 CpG sites. Remarkable similarities were observed between evDNA and nDNA methylation patterns in cancer cell lines and patients. This concordance extended to clinical cancer tissue samples, showcasing the potential utility of evDNA methylation patterns in deducing cellular origin within heterogeneous populations through methylation-based deconvolution. The observed concordance underscores the potential of evDNA as a noninvasive surrogate marker for discerning tissue origin, particularly in cancer tissues, offering a promising future for cancer diagnostics. This finding enhances our understanding of cellular origins and would help develop innovative diagnostic and therapeutic strategies for cancer.

Abstract We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7–10.4). The common treatment-related adverse events of grades 3–4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10−4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

Purpose: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. Materials and Methods: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. Results: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140--6.649, p=0.024; OR=2.986, 95% CI=1.451--6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064--4.617, p=0.034). Conclusion: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD. [ABSTRACT FROM AUTHOR]

Background: The modified complete mesocolic excision (mCME) procedure for right-sided colon cancer is a tailored approach based on the original complete mesocolic excision (CME) methodology. Limited studies evaluated the safety and feasibility of laparoscopic mCME using objective surgical quality assessments in patients with right colon cancer. The objectives of the PIONEER study were to evaluate oncologic outcomes after laparoscopic mCME and to identify optimal clinically relevant endpoints and values for standardizing laparoscopic right colon cancer surgery based on short-term outcomes of procedures performed by expert laparoscopic surgeons. Materials and methods: This is an ongoing prospective, multi-institutional, single-arm study conducted at five tertiary colorectal cancer centers in South Korea. Study registrants included 250 patients scheduled for laparoscopic mCME with right-sided colon adenocarcinoma (from the appendix to the proximal half of the transverse colon). The primary endpoint was 3-year disease-free survival. Secondary outcomes included 3-year overall survival, incidence of morbidity in the first 4 weeks postoperatively, completeness of mCME, central radicality, and distribution of metastatic lymph nodes. Survival data will be available after the final follow-up date (June 2024). Results: The postoperative complication rate was 12.9%, with a major complication rate of 2.7%. In 87% of patients, central radicality was achieved with dissection at or beyond the level of complete exposure of the superior mesenteric vein. Mesocolic plane resection with an intact mesocolon was achieved in 75.9% of patients, as assessed through photographs. Metastatic lymph node distribution varied by tumor location and extent. Seven optimal clinically relevant endpoints and values were identified based on the analysis of complications in low-risk patients. Conclusions: Laparoscopic mCME for right-sided colon cancer produced favorable short-term postoperative outcomes. The identified optimal clinically relevant endpoints and values can serve as a reference for evaluating surgical performance of this procedure. [ABSTRACT FROM AUTHOR]