Objective:To explore the effect of tumor deposit (TD) on the prognosis of patients with stage Ⅲ colon cancer after radical resection.Methods:The clinicopathological data of patients with stage Ⅲ colon cancer after radical surgery at the Department of Gastrointestinal Surgery, Peking University People's Hospital from Jan to Dec 2015 were analyzed collected. Clinicopathological characteristics such as tumor location, degree of differentiation, mismatch repair status, lymphatic and venous invasion, and preoperative CEA and CA19-9 levels were used to study the effect of TD on the postoperative survival of patients.Results:Among the 155 patients with stage Ⅲ colon cancer, 37 (23.9%) had tumor deposits. The incidence of tumor deposits was higher in patients with intravascular tumor thrombus and preoperative serum CA19-9 elevation ( χ2=9.567, P=0.002; χ2=11.561, P=0.003); Patients with tumor deposits had worse overall survival and disease-free survival than those without cancer nodules (OS: P=0.029, DFS: P=0.025). Multivariate COX analysis found that tumor deposit was an independent risk factor for postoperative overall survival and disease-free survival ( HR=1.990, 95% CI: 1.032-3.835, P=0.040; HR=2.416, 95% CI : 1.205-3.820, P=0.009). Conclusions:Tumor deposit is an independent risk factor affecting postoperative overall survival and disease-free survival in patients with stage Ⅲ colon cancer. For patients with lymph node metastasis, incorporating TD into TNM staging can more accurately predict the postoperative prognosis.
The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid (PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z' factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore, the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.
Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Intestinal organoids (IOs) are crypt–villus structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) and have the potential to serve as a platform for individualized medicine and research. However, this emerging field has not been bibliometric summarized to date. Here, we performed a bibliometric analysis of the Web of Science Core Collection (WoSCC) database to evaluate 5,379 publications concerning the use of organoids; the studies were divided into four clusters associated with the current situation and future directions for the application of IOs. Based on the results of our bibliometric analysis of IO applications, we systematically summarized the latest advances and analyzed the limitations and prospects.
Objective:To observe the clinical characteristics of esophageal reflux after total gastrectomy (ERATG), and to explore the mechanism of occurrence.Methods:Fourteen gastric cancer patients who underwent total gastrectomy were prospectively enrolled in this study. The postoperative symptoms were observed and recorded and 24 h MII-pH with pH monitoring was performed to investigate the characteristics of postoperative reflux.Results:After total gastrectomy patients were with different degrees of ERATG as heartburn, appetite loss, chest tightness and belching. The overall nature of ERATG is mainly weak acid, with a pH between 4 and 7. ERATG involved esophageal-jejunal anastomosis and a length of esophagus 7 cm above the anastomosis. Patients with typical reflux symptoms had a lower pH minimum in the upright position than those without typical symptoms[(4.76±0.71) vs.(5.68±0.37), t=2.866, P<0.05]. Patients with typical reflux symptoms had a higher frequency of reflux of mixed liquid and liquid-air reflux than those without typical symptoms[liquid(31.25±29.76) vs.(4.50±9.14), t=0.011, P<0.05; liquid-air(19.50±12.99) vs.(2.00±2.61), t=0.004, P<0.05]. Conclusion:ERATG is mainly a upward reflux of weakly acidic gas, with typical symptoms of heartburn, appetite loss, chest tightness and belching. Patients with typical symptoms usually have lower pH in the upright position.
: Hemophagocytic lymphohistiocytosis (HLH) comprises a group of severe immune function disorders that can lead to immune-mediated organ damage. There are two subtypes of HLH: primary and secondary. Secondary HLH is associated with infectious, oncologic, chemotherapeutic, and other underlying causes, and studies on HLH triggered by tumors have mainly focused on hematological malignancies. Secondary HLH in patients with solid tumors is rare. Here, we present two cases of gastric cancer complicated with HLH. The patient 1 was diagnosed as gastric cancer at stage I and got intractable fever after a distal subtotal gastrectomy without any evidence of infections or other complications. The patient 2 suffered from unresectable gastric adenocarcinoma and got fever, hemorrhagic rashes, and petechiae in mouth after six cycles of neoadjuvant chemotherapy. After detailed and comprehensive examinations, HLH was diagnosed in the two patients according to 2004 HLH diagnostic criteria, and the patients received treatment including immunosuppressive agents immediately. After therapy, the two patients showed partial remission, but both eventually died due to HLH relapse or progression of the primary tumor. The treatment regimen for HLH is intricate, and only a few relevant studies have focused on the treatment of cancer patients with HLH. The high mortality associated with this disease calls for more attention and additional research to improve the prognosis for these patients.
Objective:To determine the diagnostic value of tumor markers in peritoneal lavage fluid from colorectal cancer patients for tumor peritoneal metastasis.Methods:A total of 227 colorectal cancer patients who undergoing surgical treatment were included. 300 ml of peritoneal lavage fluid was irrigated immediately upon laparotomy for traditional cytology (PLC) testing, 134 patients were tested for tumor marker of peritoneal lavage fluid (pTM). Univariate analysis was performed to determine the risk factors for peritoneal metastasis; pTM ROC curve was used to determine the best cutoff value; paired chi-square test was used to compare the difference between PLC and pTM detection.Results:The positive rate of PLC was 12.3% (28/227). Age>65, stage T3 + , lymph node metastasis, mucinous adenocarcinoma and increased serum CA125, CA19-9 are related to peritoneal metastasis; The best cutoff value of pTM for peritoneal metastasis : pCEA 17.095 ng/dl, sensitivity 58.3%, specificity 93.9%; pCA19-9 4.515 U/ml, sensitivity 83.3%, specificity 80.0%; pCA125 303.2 U/ml, sensitivity 58.3%, specificity 95.7%; pCA-724 3.01 U/ml, sensitivity 66.7%, specificity 95.7%; The best cutoff value of pTM for peritoneal micrometastasis: pCA19-9 3.43 U/ml, sensitivity 100%, specificity 72.2%. The positive rate of pCA19-9 was 29.85%, which was higher than that of PLC (χ 2=2.00, P<0.05). Conclusion:Peritoneal metastasis of colorectal cancer is related to tumor T stage, lymph node metastasis, tumor pathological type, and increased serum CA125 and CA19-9; pTM has diagnostic value for peritoneal metastasis of colorectal cancer.
Background MicroRNAs (miRNAs), such as miR-654-3p, regulate gene expression at the post-transcriptional level affecting malignant tumor behavior. However, the expression levels, function, and mechanism of miR-654-3p in colorectal cancer (CRC) are unknown. Methods The expression levels of miR-654-3p and SRC in 103 CRC tissues and matched normal colorectal tissues were detected by a quantitative real-time polymerase chain reaction (qRT-PCR). miR-654-3p was overexpressed by RNA mimics and SRC knockdown by siRNA. Function-based experiments were carried out to detect the proliferation and migration abilities in CRC cell lines. Flow cytometry assay was performed to evaluate the effect of miR-654-3p on cell apoptosis and cycle distribution. Xenograft tumor models in nude mice were utilized to evaluate miR-654-3p functions in vivo. Dual-fluorescence reporter assay was used to verify the direct binding between miR-654-3p and SRC. Results miR-654-3p was downregulated in CRC tissues as compared to matched normal colorectal tissues. The expression levels of miR-654-3p were closely associated with distant metastasis. In addition, elevated expression of miR-654-3p in CRC patients prolonged the overall survival. Upregulated miR-654-3p significantly suppressed the proliferation and migration capacity of CRC cells by enhancing apoptosis and promoting G0/G1 phase arrest. The direct binding between miR-654-3p and SRC was verified by the dual-luciferase reporter gene. Furthermore, the suppression of proliferation and migration capacity by elevated miR-654-3p level could be reversed by overexpressing SRC. Conclusion miR-654-3p acts as a tumor suppressor through regulating SRC. It might also serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy.
Objective To evaluate different methods in detecting intraperitontal free cancer cells (IFCCs) in patients with gastric cancer and to clarify the relationship between positive IFCCs and short-term prognosis.Methods A total of 119 gastric cancer patients who underwent surgical treatment were enrolled.Peritoneal lavage was performed with 300-400 ml saline respectively at three points of time:immediately after abdominal cavity entry;when surgical operation was completed;when extensive intraoperative peritoneal lavage was done.The IFCCs were detected with methods of traditional centrifugal cytology,membrane cytology,ICC and RT-PCR.The survival curve of patients with gastric cancer was drawn using Kaplan-Meier method.Results The positive rate of PLC was 16.8%,20.7% and 11.2% respectively at 3 timepoints (P < 0.05).The positive rates of ICC were 28.6%,38.8% and 20.7% respectively at 3 timepoints.The positive rates of RT-PCR were 39.3%,69.5% and 50.8% respectively at 3 time points.The positive rate of IFCCs detected through RT-PCR was higher than that of PLC and ICC (P < 0.05).The short-term prognosis of patients with positive IFCCs was worse than those with negative results detected with any three method at the timg point immediately after opening the abdomen (P < 0.05).At the timg point immediately after removing the tumors,the short-term prognosis of patients with positive IFCCs detected with PLC was worse (P < 0.05).Conclusion The short-term prognosis was poor in patients with positive IFCCs.It is the best time to detect IFCCs before radical resection.Surgical procedures increase the risk of shedding of IFCCs.