Abstract Pseudomyxoma peritonei (PMP), a rare condition characterized by mucinous ascites in the peritoneal cavity, often leads to a poor prognosis. However, omics profiling of this disease remains significantly underexplored. Here, we present single-cell transcriptomic profiling of five PMP cases to identify cell type-specific gene features associated with PMP pathogenesis. Additionally, we provide bulk RNA-seq datasets from two independent cohorts: 19 fresh frozen tissue samples (12 PMPs) and 34 formalin-fixed paraffin-embedded (FFPE) samples (25 PMPs). We also offer protein expression data from a tissue microarray (TMA) analysis of 90 samples (45 PMPs). Our single-cell and bulk transcriptomic profiles, along with TMA verifications, reveal the cellular diversity of PMP, highlighting the coexistence of epithelial and mesenchymal characteristics within PMP cells. These datasets enhance our understanding of PMP pathogenesis and provide a valuable resource for uncovering the intricate molecular landscape of PMP, with the potential to improve clinical utility through further research.
Purpose Colorectal cancer (CRC) is generally considered a disease of old age. Most CRCs are diagnosed at age 50 and over. CRC rarely occurs in teenagers, and the clinical features and prognosis of CRC are not clear in this population. The aim of this study was to uncover the clinicopathologic characteristics of teenage sporadic CRC. Methods Of the 21,042 patients who underwent operation for primary CRC at Asan Medical Center between July 1989 and December 2014, 19 cases (0.09%) without a familial history of CRC before 20 years of age at diagnosis were enrolled in this study. The clinicopathologic features of the teenage sporadic CRC patients were retrospectively reviewed. Results Of the 19 patients, 16 patients (84.2%) were male. The most common primary site was the left colon (descending colon & sigmoid colon) in nine patients. With respect to histologic type, adenocarcinoma represented 57.8% of cases, mucinous adenocarcinoma, 31.5%, and signet ring cell carcinoma, 10.5%. Six (31.5%) patients showed peritoneal seeding at presentation. In survival analysis, the 5-year overall survival rate of the patients who underwent curative surgery was 71.3%. Conclusion Teenage sporadic CRC is a very rare disease and the proportion of patients with a poor histologic subtype is high, but early detection and radical treatment can lead to favorable survival rates. Keywords: Colorectal cancer, Teenage, Sporadic Cancer
We aimed to evaluate oncological outcomes after repeat metastasectomies in patients having undergone previous resections for colorectal cancer metastases.We examined 248 patients who underwent metastasectomies for lung and/or liver metastases at our center during a 7-year period, from January 2005 to December 2011. Recurrence-free survival 1 (RFS1) after the metastasectomy for the initial recurrence, recurrence-free survival 2 (RFS2) after the second, and recurrence-free survival 3 (RFS3) after the third repeated resections for recurrence were assessed. The overall survival (OS) rate after the first metastasectomy for the first recurrence (OS) was also assessed.Sites of recurrence of the first metastasectomy were the liver, lung, and liver and lung in 115, 117, and 16 cases, respectively, and 133 patients had a second recurrence (133/248, 53.6%). Twenty-seven patients had a third recurrence (27/52, 51.9%), of whom 14 underwent a third metastasectomy. The 5-year and 10-year OS rates were 74.8% and 57.9%, respectively. The 1-year RFS1, RFS2, and RFS3 rates were 76%, 75%, and 39%, respectively. The hazard ratios for RFS were 1.142 and 2.590 for the first and second repeat surgeries, when compared to the first metastasectomy. The third metastasectomy showed significantly lower RFS than did the second metastasectomy.A second metastasectomy should be considered the optimal treatment for a second recurrence. However, careful considerations should be made before performing a third metastasectomy.
Diverting ileostomy during resection of rectal cancer is frequently performed in patients at risk of anastomotic failure. Clostridium difficile infection (CDI) is reported to be frequent in patients who receive ileostomy closure with a questionable association to postoperative anastomosis leak. The primary aim of this study was to determine the incidence of CDI following ileostomy closure in patients who underwent rectal cancer surgery; the secondary aim was to assess the rate of postileostomy closure CDI in patients who presented with leakage at the original colorectal anastomosis site.Medical records of patients with rectal cancer who underwent ileostomy closure between January 2015 and December 2019 were retrospectively reviewed. All patients had previously received resection and anastomosis for primary rectal cancer with diverting ileostomy. Data regarding CDI incidence, preoperative status, perioperative management, and clinical outcomes were collected. CDI positivity was determined by direct real-time PCR and enzyme-linked fluorescent assays for detecting toxin A and B.Statistical analyses were computed for CDI risk factors.A total of 1270 patients were included and 208 patients were tested for CDI owing to colitis-related symptoms. The incidence of CDI was 3.6 per cent (46 patients). Multivariable analysis for CDI risk factors identified adjuvant chemotherapy (hazard ratio (HR) 2.28; P = 0.034) and colorectal anastomosis leakage prior to CDI (HR 3.75; P = 0.008). Finally, patients with CDI showed higher colorectal anastomosis leakage risk in multivariable analysis after ileostomy closure (HR 6.922; P = 0.001).Patients with CDI presented with a significantly higher rate of colorectal anastomosis leakage prior to ileostomy closure.
Abstract Background and Aim We aimed to assess the gene expression profiles of nonlesional small bowels in patients with Crohn's disease (CD) to identify its accompanying molecular alterations. Methods We performed RNA sequencing of the uninflamed small bowel tissues obtained from 70 patients with ileal CD and 9 patients with colon cancer (non‐CD controls) during bowel resection. Differentially expressed gene (DEG) analyses were performed using DESeq2. Gene set enrichment, correlation, and cell deconvolution analyses were applied to identify modules and functionally enriched transcriptional signatures of CD. Results A comparison of CD patients and non‐CD controls revealed that of the 372 DEGs, 49 protein‐coding genes and 5 long non‐coding RNAs overlapped with the inflammatory bowel disease susceptibility loci. The pathways related to immune and inflammatory reactions were upregulated in CD, while metabolic pathways were downregulated in CD. Compared with non‐CD controls, CD patients had significantly higher proportions of immune cells, including plasma cells ( P = 1.15 × 10 −4 ), and a lower proportion of epithelial cells ( P = 1.12 × 10 −4 ). Co‐upregulated genes (M14 module) and co‐downregulated genes (M9 module) were identified in CD patients. The M14 module was enriched in immune‐related genes and significantly associated with the responses to anti‐tumor necrosis factor (TNF) therapy. The core signature of the M14 module was comprised of six genes and was upregulated in nonresponders to anti‐TNF therapy of five independent cohorts ( n = 163), indicating acceptable discrimination ability (area under the receiver operating characteristic curve of 75–86%). Conclusions The differences in gene expression and cellular composition between CD patients and non‐CD controls imply significant molecular alterations, which are associated with the response to anti‐TNF treatment.
The present study aimed to evaluate the clinicopathologic characteristics of patients with extranodal extension (ENE) and the prognostic implications of ENE in stage III colorectal cancer (CRC).ENE was more frequent in younger patients and those with rectal cancer, higher T stage, higher N stage, lymphovascular invasion (LVI), and perineural invasion (PNI). Five-year disease-free survival (DFS) and overall survival (OS) were lower in patients with ENE-positive than in those with ENE-negative tumors (DFS, 66.4% vs. 80.1%; and OS, 74.8% vs. 85.6%, respectively; P < 0.001 both). In multivariate analysis, pathologic stage, the presence of ENE, LVI, PNI, and no adjuvant chemotherapy were significant independent prognostic factors for DFS and OS. There were no statistically significant differences in DFS and OS between ENE-positive stage IIIB tumors and ENE-negative stage IIIC tumors.The records of 1,948 stage III CRC patients who underwent curative surgery between January 2003 and December 2010 were retrospectively reviewed.The presence of ENE is independently and significantly associated with lower DFS and OS rates after curative resection for stage III CRC. ENE status should be considered in both the pathologic report and CRC staging system.
Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.
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