Predicting survival in locally advanced rectal cancer with effective chemoradiotherapy response.

BACKGROUND: Locally advanced rectal cancer patients often display favorable responses and favorable oncologic outcomes. Due to the low recurrence rate, there is scarcity of studies investigating the prognostic factors influencing their survival. Therefore, our study sought to assess the prognostic factors associated with survival in rectal cancer patients who achieved either a pathologic complete response or a pathologic stage I after neoadjuvant chemoradiotherapy combined with radical resection. METHODS: In this retrospective study, we analyzed data from cohort of 1394 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy combined with total mesorectal excision from January 2008 to April 2017. Finally, we selected 474 (34.2 %) who exhibited either a pathologic complete response or attained pathologic stage I following the treatment. Subsequently, we analyzed the prognostic factors influencing disease-free and overall survival. RESULTS: A total of 161 (34 %) achieved a pathologic complete response. Our analysis revealed that circumferential resection margin and the administration of adjuvant chemotherapy were prognostic factors for disease-free survival (p = 0.011, p = 0.022). Furthermore, factors influencing overall survival included the clinical N stage and administration of adjuvant chemotherapy (p = 0.035, p = 0.015). CONCLUSION: In conclusion, the circumferential resection margin, clinical N stage, and administration of adjuvant chemotherapy were prognostic factors for survival in patients showing good response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. For patients with a positive circumferential resection margin and clinical N (+) stage, intensive follow-up might be needed to achieve favorable oncologic outcomes. Also, we recommend considering adjuvant chemotherapy as a beneficial treatment approach for these patients.

Vascularized tissue on mesh-assisted platform (VT-MAP): a novel approach for diverse organoid size culture and tailored cancer drug response analysis.

This study presents the vascularized tissue on mesh-assisted platform (VT-MAP), a novel microfluidic in vitro model that uses an open microfluidic principle for cultivating vascularized organoids. Addressing the gap in 3D high-throughput platforms for drug response analysis, the VT-MAP can host tumor clusters of various sizes, allowing for precise, size-dependent drug interaction assessments. Key features include capability for forming versatile co-culture conditions (EC, fibroblasts and colon cancer organoids) that enhance tumor organoid viability and a perfusable vessel network that ensures efficient drug delivery and maintenance of organoid health. The VT-MAP enables the culture and analysis of organoids across a diverse size spectrum, from tens of microns to several millimeters. The VT-MAP addresses the inconsistencies in traditional organoid testing related to organoid size, which significantly impacts drug response and viability. Its ability to handle various organoid sizes leads to results that more accurately reflect patient-derived xenograft (PDX) models and differ markedly from traditional in vitro well plate-based methods. We introduce a novel image analysis algorithm that allows for quantitative analysis of organoid size-dependent drug responses, marking a significant step forward in replicating PDX models. The PDX sample from a positive responder exhibited a significant reduction in cell viability across all organoid sizes when exposed to chemotherapeutic agents (5-FU, oxaliplatin, and irinotecan), as expected for cytotoxic drugs. In sharp contrast, PDX samples of a negative responder showed little to no change in viability in smaller clusters and only a slight reduction in larger clusters. This differential response, accurately replicated in the VT-MAP, underscores its ability to generate data that align with PDX models and in vivo findings. Its capacity to handle various organoid sizes leads to results that more accurately reflect PDX models and differ markedly from traditional in vitro methods. The platform's distinct advantage lies in demonstrating how organoid size can critically influence drug response, revealing insights into cancer biology previously unattainable with conventional techniques.

Is Robotic Surgery Beneficial for Rectal Cancer Patients with Unfavorable Characteristic After Neoadjuvant Chemoradiotherapy?

BACKGROUND: The objective of this study was to compare long-term oncologic outcomes of robot and laparoscopic surgeries for patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT) followed by radical resection. METHODS: This study analyzed 3240 rectal cancer patients who underwent radical surgery from 2008 to 2019. Among them, 1204 patients who received nCRT (robotic, n = 316; laparoscopic, n = 888) were analyzed. The oncological outcome according to the number of unfavorable factors (male, body mass index ≥ 25, receiving CCRT) present in patients also was analyzed. We used 1:1 propensity score matching (PSM) to adjust for potential baseline confounders between groups. RESULTS: After PSM, two groups showed similar demographics and pathological results. After PSM analysis, the robotic group showed higher 5-year disease-free survival (DFS) and local recurrence-free survival rates than the laparoscopic group, whereas 5-year overall survival and distant recurrence-free survival rates were similar between the two groups. In addition, by comparing survival rates for each yp stage, it was found 5-year DFS and local recurrence-free survival of the robotic group in yp stage III were significantly higher than those of the laparoscopic group. Five-year DFS was conducted according to the number of unfavorable factors (male, body mass index ≥ 25 kg/m2, and undergoing nCRT) as a subgroup analysis. In patients with all three unfavorable factors, the robotic group showed significantly higher DFS than the laparoscopic group. CONCLUSIONS: Robotic approach for rectal cancer after nCRT, especially for patients with yp stage III and unfavorable factors, have the advantage of improving oncologic outcomes even for surgeons specializing in colorectal cancer.

Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer.

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the thylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC. [BMB Reports 2024; 57(2): 110-115].

Pulmonary Metastasis as the First Site of Metastasis After Curative Surgery for Colon Cancer: Incidence and Risk Factors According to the TNM Stage.

BACKGROUND: The lungs are one of the most common sites for colon cancer metastasis. A few studies reported that approximately 2% to 10% of patients with colon cancer developed pulmonary metastasis. However, among these studies, patient characteristics were heterogeneous, and information on pulmonary metastasis incidence by the TNM stage was scarce. OBJECTIVE: This study evaluated the incidence of pulmonary metastasis in colon cancer without synchronous metastasis treated with radical surgery and identified risk factors for pulmonary metastasis according to the TNM stage. DESIGN AND SETTINGS: This retrospective study included all patients with colon cancer without metastasis who underwent radical surgery for primary tumor at Samsung Medical Center between January 2007 and December 2016. PATIENTS: A total of 4889 patients who underwent radical surgery for stage I and III colon cancer were included. MAIN OUTCOME MEASURES: The main outcome measures were the incidence of pulmonary metastasis and overall survival. RESULTS: A total of 156 patients (3.2%) were diagnosed with pulmonary metastasis after a median of 16 months from the time of radical surgery for colon cancer to detection of pulmonary metastasis. The pulmonary metastasis incidence rate by the TNM stage was 0.5% in stage I, 1.6% in stage II, and 6% in stage III. Risk factors for pulmonary metastasis were preoperative CEA >5 ng/mL, cancer obstruction, N stage, vascular invasion, perineural invasion, and adjuvant chemotherapy for primary colon cancer in multivariable analysis. LIMITATION: This was a retrospective single-center study. CONCLUSIONS: Preoperative CEA >5 ng/mL, cancer obstruction, pN stage, vascular invasion, perineural invasion, and receiving adjuvant chemotherapy for primary colon cancer were risk factors for pulmonary metastasis in colon cancer. Therefore, patients with risk factors for pulmonary metastasis should be recommended for intensive follow-up to detect lung metastases. See Video Abstract . METSTASIS PULMONAR EN EL PRIMER SITIO TRAS CIRUGA CURATIVA DEL CNCER DE COLON INCIDENCIA Y FACTORES DE RIESGO SEGN ESTADIO TNM: ANTECEDENTES:Los pulmones son uno de los sitios más comunes de metástasis del cáncer de colon. Algunos estudios informaron que aproximadamente entre el 2% y el 10% de los pacientes con cáncer de colon desarrollaron metástasis pulmonar. Sin embargo, entre estos estudios, las características de los pacientes fueron heterogéneas y la información sobre la incidencia de metástasis pulmonares según el estadio TNM fue escasa.OBJETIVO:Este estudio evaluó la incidencia de metástasis pulmonar en cáncer de colon sin metástasis sincrónica tratada con cirugía radical e identificó factores de riesgo para metástasis pulmonar según el estadio TNM.DISEÑO Y AJUSTES:Este estudio retrospectivo incluyó a todos los pacientes con cáncer de colon sin metástasis que se sometieron a cirugía radical por tumor primario en el Samsung Medical Center entre enero de 2007 y diciembre de 2016.PACIENTES:Se incluyó un total de 4.889 pacientes sometidos a cirugía radical por cáncer de colon en estadio I-III.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la incidencia de metástasis pulmonar y la supervivencia general.RESULTADOS:Un total de 156 pacientes (3,2%) fueron diagnosticados con metástasis pulmonar con una duración media de 16 meses desde el momento de la cirugía radical por cáncer de colon hasta la detección de la metástasis pulmonar. La tasa de incidencia de metástasis pulmonares por estadio TNM fue del 0,5% en el estadio I, del 1,6% en el estadio II y del 6% en el estadio III. Los factores de riesgo de metástasis pulmonar fueron CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio N, invasión vascular, invasión perineural y quimioterapia adyuvante para el cáncer de colon primario en un análisis multivariable.LIMITACIÓN:Este fue un estudio retrospectivo de un solo centro.CONCLUSIÓN:CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio pN, invasión vascular, invasión perineural y recibir quimioterapia adyuvante para el cáncer de colon primario fueron factores de riesgo de metástasis pulmonar en el cáncer de colon. Por lo tanto, se debe recomendar un seguimiento intensivo a los pacientes con factores de riesgo de metástasis pulmonares para detectar metástasis pulmonares. (Traducción-Dr Yolanda Colorado ).

Improved Drug-Response Prediction Model of APC Mutant Colon Cancer Patient-Derived Organoids for Precision Medicine.

Colorectal cancer is the third most common cancer in the world, with an annual incidence of 2 million cases. The success of first-line chemotherapy plays a crucial role in determining the disease outcome. Therefore, there is an increasing demand for precision medicine to predict drug responses and optimize chemotherapy in order to increase patient survival and reduce the related side effects. Patient-derived organoids have become a popular in vitro screening model for drug-response prediction for precision medicine. However, there is no established correlation between oxaliplatin and drug-response prediction. Here, we suggest that organoid culture conditions can increase resistance to oxaliplatin during drug screening, and we developed a modified medium condition to address this issue. Notably, while previous studies have shown that survivin is a mechanism for drug resistance, our study observed consistent survivin expression irrespective of the culture conditions and oxaliplatin treatment. However, clusterin induced apoptosis inhibition and cell survival, demonstrating a significant correlation with drug resistance. This study's findings are expected to contribute to increasing the accuracy of drug-response prediction in patient-derived APC mutant colorectal cancer organoids, thereby providing reliable precision medicine and improving patient survival rates.

Targeted Isolation of N-Acetylcysteine-Containing Angucycline Derivatives from Streptomyces sp. MC16 and Their Antiproliferative Effects.

Liquid chromatography-mass spectrometry (LC-MS/MS)-based molecular networking analysis was applied to Streptomyces sp. MC16. The automatic classification of the MolNetEnhancer module revealed that its major constituent was an angucycline derivative. By targeted isolation of unique clusters in the molecular network, which showed different patterns from typical angucycline compounds, two new N-acetylcysteine-attached angucycline derivatives (1 and 2) were isolated. The structures were elucidated based on intensive NMR analysis and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). All isolated compounds (1-4) were tested for their inhibitory effects on the proliferation of A431, A549, and HeLa cell lines. Antibiotics 100-1 (3) and vineomycinone B2 (4) showed moderate inhibitory effects on these three cell lines with IC50 values ranging from 18.5 to 59.0 µM, while compounds 1 and 2 with an additional N-acetylcysteine residue showed weak inhibitory effects only on the HeLa cell line with IC50 values of 54.7 and 65.2 µM, respectively.

Two antisense RNAs-AFAP1-AS1 and MLK7-AS1-promote colorectal cancer progression by sponging miR-149-5p and miR-485-5p.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Antisense RNAs (asRNAs) are closely associated with cancer malignancy. This study aimed to identify the action mechanism of asRNAs in controlling CRC malignancy. Analysis of the RNA sequencing data revealed that AFAP1-AS1 and MLK7-AS1 were upregulated in CRC patients and cell lines. High levels of both asRNAs were associated with poor prognosis in patients with CRC. Both in vitro and in vivo experiments revealed that the knockdown of the two asRNAs decreased the proliferative and metastatic abilities of CRC cells. Mechanistically, AFAP1-AS1 and MLK7-AS1 decreased the levels of miR-149-5p and miR-485-5p by functioning as ceRNAs. Overexpression of miRNAs by introducing miRNA mimics suppressed the expression of SHMT2 and IGFBP5 by directly binding to the 3' UTR of their mRNA. Knockdown of both asRNAs decreased the expression of SHMT2 and IGFBP5, which was reversed by inhibition of both miRNAs by miRNA inhibitors. In vivo pharmacological targeting of both asRNAs by small interfering RNA-loaded nanoparticles showed that knockdown of asRNAs significantly reduced tumor growth and metastasis. Our findings demonstrate that AFAP1-AS1 and MLK7-AS1 promote CRC progression by sponging the tumor-suppressing miRNAs miR-149-5p and miR-485-5p, thus upregulating SHMT2 and IGFBP5.

Molecular networking-assisted isolation of chlorophenolic glycosides from the rhizomes of Curculigo orchioides and their inhibitory effect on α-glucosidase.

Molecular networking analysis and in silico tools, such as Network Annotation Propagation (NAP) and MolNetEnhancer, were applied to explore bioactive constituents present in the ethyl acetate-soluble fraction of the rhizomes of Curculigo orchioides. Among the molecular networks, the most abundant cluster was classified as a phenolic glycoside using the ClassyFire module of MolNetEnhancer. Further, the major node in this cluster was accurately predicted as curculigine A using the in silico fragment analysis tool, NAP. Six undescribed chlorophenolic glycosides (1-6) and 11 known phenolic glycosides were isolated, using molecular networking-assisted isolation methods, and their structures were elucidated using 1D, 2D-NMR and HRESIMS. In particular, the structures of the isolated chlorophenolic glycosides, which have non-protonated aromatic rings, were determined using various NMR experiments, such as 1D-selective NOE, ROESY, and LR-HMBC, and acid hydrolysis. All isolated compounds were examined to determine their inhibitory effects on α-glucosidase and compounds 3, 8, 10, 11, 13, 14, and 16 revealed the IC50 values ranging from 19.6 to 35.5 µM. Their structure-activity relationships were also evaluated based on the analysis of their inhibitory effects and performance of molecular docking simulations.

Information about immune cell proportions and tumor stage improves the prediction of recurrence in patients with colorectal cancer.

Predicting cancer recurrence is essential to improving the clinical outcomes of patients with colorectal cancer (CRC). Although tumor stage information has been used as a guideline to predict CRC recurrence, patients with the same stage show different clinical outcomes. Therefore, there is a need to develop a method to identify additional features for CRC recurrence prediction. Here, we developed a network-integrated multiomics (NIMO) approach to select appropriate transcriptome signatures for better CRC recurrence prediction by comparing the methylation signatures of immune cells. We validated the performance of the CRC recurrence prediction based on two independent retrospective cohorts of 114 and 110 patients. Moreover, to confirm that the prediction was improved, we used both NIMO-based immune cell proportions and TNM (tumor, node, metastasis) stage data. This work demonstrates the importance of (1) using both immune cell composition and TNM stage data and (2) identifying robust immune cell marker genes to improve CRC recurrence prediction.

Prognostic Impact of Mucinous Adenocarcinoma in Stage II and III Colon Cancer.

BACKGROUND: Mucinous adenocarcinoma is a rare histologic feature of colorectal cancer and is characterized by oncologic features that are different from those of adenocarcinoma. However, there are conflicting views regarding the prognostic impact of mucinous adenocarcinoma on colon cancer. OBJECTIVE: This study aimed to evaluate the prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted between January 2010 and December 2015. Patients were divided into the mucinous adenocarcinoma and nonmucinous adenocarcinoma groups. Disease-free survival and overall survival were assessed using propensity score matching. PATIENTS: Overall, 2532 patients who underwent radical surgery for stage II and III colon cancer were included in the study. MAIN OUTCOME MEASURES: The main outcome measures were disease-free survival and overall survival. RESULTS: The median follow-up duration was 86 months. The disease-free survival and overall survival were significantly lower in the mucinous adenocarcinoma group than in the nonmucinous adenocarcinoma group. In subgroup analysis, there was no significant difference in the disease-free survival and overall survival between patients with and without mucinous adenocarcinoma with stage II colon cancer. In stage III colon cancer, the disease-free survival and overall survival were significantly lower in patients with mucinous adenocarcinoma than in those without mucinous adenocarcinoma. Multivariable analysis showed that mucinous adenocarcinoma was a poor prognostic factor for disease-free survival and overall survival. LIMITATION: The study's limitations include those that are inherently associated with retrospective single-center studies. CONCLUSIONS: Mucinous adenocarcinoma is a poor prognostic factor in stage III but not in stage II colon cancer. Therefore, mucinous adenocarcinoma might not be regarded as an independent risk factor requiring chemotherapy for favorable oncologic outcomes. However, for stage III colon cancer, patients with mucinous adenocarcinoma require close observation. IMPACTO PRONSTICO DEL ADENOCARCINOMA MUCINOSO EN LAS ETAPAS II Y III DE CNCER DE CLON: ANTECEDENTES:El adenocarcinoma mucinoso es una característica histológica rara del cáncer colorrectal, se caracteriza por propiedades oncológicas que son diferentes a las del adenocarcinoma. Sin embargo, existen puntos de vista contradictorios con respecto al impacto pronóstico del adenocarcinoma mucinoso en el cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar el impacto pronóstico del adenocarcinoma mucinoso en las etapas II y III de cáncer de cólon.DISEÑO Y CONFIGURACIONES:Este estudio de cohorte retrospectivo se realizó entre enero de 2010 y diciembre de 2015. Los pacientes se dividieron entre grupos de adenocarcinoma mucinoso y adenocarcinoma no mucinoso. La supervivencia libre de enfermedad y la supervivencia global se evaluaron utilizando emparejamiento por puntuación de propensión.PACIENTES:En general, 2,532 pacientes que se sometieron a cirugía radical para etapa II y III de cáncer de colon se incluyeron en el estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana de duración del seguimiento fue de 86 meses. La supervivencia libre de enfermedad y la supervivencia global fueron significativamente menores en el grupo de adenocarcinoma mucinoso que en el grupo de adenocarcinoma no mucinoso. En el análisis de subgrupos, no hubo diferencias significativas en la supervivencia libre de enfermedad y la supervivencia global entre los pacientes con o sin adenocarcinoma mucinoso con cáncer de cólon etapa II. En el cáncer de colon etapa III, la supervivencia libre de enfermedad y la supervivencia global fueron significativamente más bajas en pacientes con adenocarcinoma mucinoso que en aquellos sin adenocarcinoma mucinoso. El análisis multivariable mostró que el adenocarcinoma mucinoso era un factor de mal pronóstico para la supervivencia libre de enfermedad y la supervivencia global.LIMITACIONES:Las limitaciones del estudio incluyen aquellas que están inherentemente asociadas con estudios retrospectivos de un solo centro.CONCLUSIONES:El adenocarcinoma mucinoso es un factor de mal pronóstico en el cáncer de colon etapa III pero no en etapa II. Por lo tanto, el adenocarcinoma mucinoso podría no considerarse un factor de riesgo independiente que requiera quimioterapia para obtener resultados oncológicos favorables. Sin embargo, para el cáncer de colon etapa III, los pacientes con adenocarcinoma mucinoso requieren observación cercana. (Traducción-Dr. Aurian Garcia Gonzalez ).

The Prognostic Value of Micropapillary Pattern in Colon Cancer and Its Role as a High-Risk Feature in Patients With Stage II Disease.

BACKGROUND: The association of a micropapillary pattern with oncologic outcomes has not been fully studied in patients with colon cancer. OBJECTIVE: We evaluated the prognostic value of a micropapillary pattern, especially for patients with stage II colon cancer. DESIGN: A retrospective comparative cohort study using propensity score matching. SETTING: This study was conducted at a single tertiary center. PATIENTS: Patients with primary colon cancer undergoing curative resection from October 2013 to December 2017 were enrolled. Patients were grouped into micropapillary pattern positive or micropapillary pattern negative. MAIN OUTCOME MEASUREMENTS: Disease-free survival and overall survival. RESULTS: Of the eligible 2192 patients, 334 (15.2%) were with micropapillary pattern (+). After 1:2 propensity score matching, 668 patients with micropapillary pattern-negative status were selected. The micropapillary pattern-positive group showed significantly worse 3-year disease-free survival (77.6% vs 85.1%, p = 0.007). Three-year overall survival of micropapillary pattern-positive and micropapillary pattern-negative patients did not show a statistically significant difference (88.9% vs 90.4%, p = 0.480). In multivariable analysis, micropapillary pattern-positive was an independent risk factor for poor disease-free survival (HR 1.547, p = 0.008). In the subgroup analysis for 828 patients with stage II disease, 3-year disease-free survival deteriorated significantly in micropapillary pattern-positive patients (82.6% vs 93.0, p < 0.001). Three-year overall survival was 90.1% and 93.9% in patients positive and negative for micropapillary pattern, respectively ( p = 0.082). In the multivariable analysis for patients with stage II disease, micropapillary pattern-positive status was an independent risk factor for poor disease-free survival (HR 2.003, p = 0.031). LIMITATIONS: Selection bias due to the retrospective nature of the study. CONCLUSIONS: Micropapillary pattern-positive status may serve as an independent prognostic factor for colon cancer, especially for patients with stage II disease. VALOR PRONSTICO DEL PATRN MICROPAPILAR Y SU PAPEL COMO CARACTERSTICA DE ALTO RIESGO EN PACIENTES CON CNCER DE COLON EN ESTADO II: ANTECEDENTES:La asociación del patrón micropapilar con los resultados oncológicos no ha sido completamente estudiada en pacientes con cáncer de colon.OBJETIVO:Evaluamos el valor pronóstico del patrón micropapilar, especialmente en pacientes con cáncer de colon en estadio II.DISEÑO:Estudio de cohortes comparativo y retrospectivo que utilize el emparejamiento por puntuación de propensiones.AJUSTE:Estudio realizado en un solo centro terciario.PACIENTES:Se incluyeron los pacientes con cáncer de colon primario sometidos a resección curativa desde octubre de 2013 hasta diciembre de 2017. Los pacientes se agruparon en patrón micropapilar positivo ( + ) o patrón micropapilar negativo ( - ).PRINCIPALES MEDIDAS DE RESULTADO:Sobrevida libre de enfermedad y la sobrevida global.RESULTADOS:De los 2192 pacientes elegibles, 334 (15,2%) tenían patrón micropapilar (+). Después de emparejar el puntaje de propensión 1:2, se seleccionaron 668 pacientes con patrón micropapilar (-). El grupo con patrón micropapilar (+) mostró una sobrevida libre de enfermedad significativamente inferior a los tres años (77,6% frente a 85,1%, p = 0,007). La sobrevida global a los tres años del patrón micropapilar (+) y del patrón micropapilar (-) no mostró una diferencia estadísticamente significativa (88,9 % frente a 90,4%, p = 0,480). En el análisis multivariable, el patrón micropapilar (+) fue un factor de riesgo independiente para una deficiente sobrevida libre de enfermedad (índice de riesgo 1,547, p = 0,008). En el análisis de subgrupos de 828 pacientes con enfermedad en estadio II, la sobrevida libre de enfermedad a los tres años se deterioró significativamente en los pacientes con patrón micropapilar (+) (82,6% frente a 93,0, p < 0,001). La sobrevida global a los tres años fué del 90,1% y del 93,9% en el patrón micropapilar (+) y el patrón micropapilar (-), respectivamente ( p = 0,082). En el análisis multivariable de los pacientes con enfermedad en estadio II, el patrón micropapilar (+) fue un factor de riesgo independiente para una sobrevida libre de enfermedad deficiente (índice de riesgo 2,003, p = 0,031).LIMITACIONES:Sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:El patrón micropapilar (+) sirve como factor pronóstico independiente para el cáncer de colon, especialmente para pacientes con enfermedad en estadio II. (Traducción-Dr. Xavier Delgadillo ).

Multi-Inlet Spheroid Generator for High-Throughput Combinatorial Drug Screening Based on the Tumor Microenvironment.

Tumor spheroids are powerful tools for drug screening and understanding tumor physiology. Among spheroid formation methods, the hanging drop method is considered most suitable for high-throughput screening (HTS) of anticancer drugs because it does not require surface treatment. However, it still needs to increase the liquid-holding capacity because hanging drops often fall due to the increased pressure caused by the addition of drugs, cells, etc. Here, we report a multi-inlet spheroid generator (MSG) enabling the stable addition of liquid-containing drugs or cells into a spheroid through its side inlet. The MSG was able to load additional solutions through the side inlet without increasing the force applied to the hanging drop. The volume of the additional liquid was easily controlled by varying the diameter of the side inlet. Furthermore, the sequences of the solution injections were manipulated using multiple side inlets. The feasibility of the MSG in clinical application was demonstrated by testing the efficacy of drugs in patient-derived cancer (PDC) cells and controlling the stromal cell ratio in the tumor microenvironment (TME) containing spheroids. Our results suggest that the MSG is a versatile platform for HTS of anticancer drugs and recapitulating the TME.

Public effect of the 2022 Colorectal Cancer Awareness Campaign delivered through a metaverse platform.

Purpose: The Korean Society of Coloproctology has been conducting Colorectal Cancer Awareness Campaign, also known as the Gold Ribbon Campaign, every September since 2007. The 2022 campaign was held through a metaverse platform targeting the younger age group under the slogan of raising awareness of early-onset colorectal cancer (CRC). This study aimed to analyze the impact of the 2022 campaign on a metaverse platform. Methods: Anonymized survey data were collected from participants in the metaverse campaign from September 1 to 15, 2022. The satisfaction score of the participants was evaluated by sex, age group, and previous campaign participation status. Results: During the campaign, 2,770 people visited the metaverse. Among them, 455 people participated in the survey (response rate, 16.4%). Approximately 95% of the participants reported being satisfied with the information provided by the campaign, understood the necessity of undergoing screening for and prevention of early-onset CRC, and were familiar with the structure of the metaverse. The satisfaction score for campaign information tended to decrease as the participants' age increased. When the participants' overall level of satisfaction with the metaverse platform was assessed, teenagers scored particularly lower than the other age groups. The satisfaction scores for CRC information provided in the metaverse, as well as the scores for recognizing the seriousness and necessity of screening for early-onset CRC, indicated a high positive tendency (P<0.001). Conclusion: Most of the 2022 Gold Ribbon Campaign participants were satisfied with the metaverse platform. Medical society should pay attention to increasing participation in and satisfaction with future public campaigns.

Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients.

BACKGROUND: Previous investigations of transcriptomic signatures of cancer patient survival and post-therapy relapse have focused on tumor tissue. In contrast, here we show that in colorectal cancer (CRC) transcriptomes derived from normal tissues adjacent to tumors (NATs) are better predictors of relapse. RESULTS: Using the transcriptomes of paired tumor and NAT specimens from 80 Korean CRC patients retrospectively determined to be in recurrence or nonrecurrence states, we found that, when comparing recurrent with nonrecurrent samples, NATs exhibit a greater number of differentially expressed genes (DEGs) than tumors. Training two prognostic elastic net-based machine learning models-NAT-based and tumor-based in our Samsung Medical Center (SMC) cohort, we found that NAT-based model performed better in predicting the survival when the model was applied to the tumor-derived transcriptomes of an independent cohort of 450 COAD patients in TCGA. Furthermore, compositions of tumor-infiltrating immune cells in NATs were found to have better prognostic capability than in tumors. We also confirmed through Cox regression analysis that in both SMC-CRC as well as in TCGA-COAD cohorts, a greater proportion of genes exhibited significant hazard ratio when NAT-derived transcriptome was used compared to when tumor-derived transcriptome was used. CONCLUSIONS: Taken together, our results strongly suggest that NAT-derived transcriptomes and immune cell composition of CRC are better predictors of patient survival and tumor recurrence than the primary tumor.

Single-port laparoscopic versus single-port robotic right hemicolectomy: Postoperative short-term outcomes.

BACKGROUND: This study aimed to compare the short-term postoperative outcomes of single-port robotic (SPR) using da Vinci SP® system and single port laparoscopic (SPL) right hemicolectomy and determine whether the novel SPR system is safe and feasible. METHODS: From January 2019 to December 2020, a total of 141 patients (41 patients for SPR and 100 patients for SPL) who electively underwent right hemicolectomy for colon cancer performed by a single surgeon were included in the study. RESULTS: The time to the first bowel movement was 3 (range, 1-4) days after surgery in the SPR group and 3 (2-9, range) days in the SPL group (p = 0.017). However, there were no differences in pathologic outcomes or postoperative complications. CONCLUSIONS: SPR is a safe and feasible surgical technique and has an advantage in the time to first postoperative bowel movement over SPL with no other complications.

Association Between Distress at Diagnosis and Disease-free Survival Among Patients With Resectable Colon Cancer: A Large Cohort Study.

OBJECTIVE: This study aimed to evaluate the association between distress at initial diagnosis and disease-free survival in patients with resectable colon cancer. SUMMARY BACKGROUND DATA: Considerable research has examined the psychological impact of having a confirmed diagnosis of cancer, but relatively limited research has examined the impact of distress during the diagnostic phase on oncological outcomes. METHODS: This is a retrospective cohort study. We included newly diagnosed colon cancer patients who had resectable surgery and underwent distress screening between July 2014 and July 2021 (N=1,362). The Korean versions of the Distress Thermometer were used to assess distress and related problems. Patients were categorized into 3 groups based on distress score: low (<4), moderate (4-7), and severe (≥8). The primary outcome was disease-free survival. RESULTS: The mean distress was 5.1 (SD=2.4) and 61%, and 15% of patients had moderate and severe distress at diagnosis, respectively. The severe distress group was more likely to report fear, sadness, and concerns regarding insurance/finance, work, and childcare than the low distress group. Compared with the low distress group, the severe distress group had worse disease-free survival (Hazard Ratio=1.84, 95% CI=1.03, 3.29). The association was more evident in patients with stage IV disease (Hazard Ratio=2.53, 95% CI=1.02, 6.25). CONCLUSIONS: A substantial number of patients with colon cancer experience distress at diagnosis, and severe distress has a negative impact on oncologic outcomes. Active monitoring and appropriate management of distress at diagnosis should be adopted at clinical settings.

Targeted isolation of sesquiterpene lactone dimers from Aucklandia lappa guided by LC-HRMS/MS-based molecular networking.

An LC-HRMS/MS-based molecular networking strategy was applied to investigate the potential sesquiterpene dimers of Aucklandia lappa, leading to the isolation of three undescribed guaiane-guaiane dimers and one guaiane-eudesmane dimer together with six known sesquiterpenes. The structures were determined by analyzing their 1D, 2D NMR, and HRESIMS data as well as ECD calculations. The biogenetic pathway of the sesquiterpene dimers was postulated to involve the Diels-Alder cycloaddition as the key step. All compounds exhibited their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values ranging from 0.3 to 25.1 µM.

A Phase II Study of Preoperative Chemoradiotherapy with Capecitabine Plus Simvastatin in Patients with Locally Advanced Rectal Cancer.

PURPOSE: The purpose of this phase II trial was to evaluate whether the addition of simvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, to preoperative chemoradiotherapy (CRT) with capecitabine confers a clinical benefit to patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Patients with LARC (defined by clinical stage T3/4 and/or lymph node positivity) received preoperative radiation (45-50.4 Gy in 25-28 daily fractions) with concomitant capecitabine (825 mg/m2 twice per day) and simvastatin (80 mg, daily). Curative surgery was planned 4-8 weeks after completion of the CRT regimen. The primary endpoint was pathologic complete response (pCR). The secondary endpoints included sphincter-sparing surgery, R0 resection, disease-free survival, overall survival, the pattern of failure, and toxicity. RESULTS: Between October 2014 and July 2017, 61 patients were enrolled; 53 patients completed CRT regimen and underwent total mesorectal excision. The pCR rate was 18.9% (n=10) by per-protocol analysis. Sphincter-sparing surgery was performed in 51 patients (96.2%). R0 resection was achieved in 51 patients (96.2%). One patient experienced grade 3 liver enzyme elevation. No patient experienced additional toxicity caused by simvastatin. CONCLUSION: The combination of 80 mg simvastatin with CRT and capecitabine did not improve pCR in patients with LARC, although it did not increase toxicity.