Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer

Background Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC. Methods Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method. Results At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001). Conclusions The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.

Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses

Background Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. Main body CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. Conclusion Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.

Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature

Background This study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients. Methods Ten LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed. Results (1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4–168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27–228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years. Conclusion As a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

Sarcomas of the extremities and the pelvis: comparing local recurrence after incisional and after core-needle biopsy

Background The degree of contamination of healthy tissue with tumor cells during a biopsy in bone or soft tissue sarcomas is clearly dependant on the type of biopsy. Some studies have confirmed a clinically relevant contamination of the biopsy tract after incisional biopsies, as opposed to core-needle biopsies. The aim of our prospective study was to evaluate the risk of local recurrence depending on the biopsy type in extremity and pelvis sarcomas. Methods We included 162 patients with a minimum follow-up of 6 months after wide resection of extremity sarcomas. All diagnostic and therapeutic procedures were performed at a single, dedicated sarcoma center. The excision of the biopsy tract after an incisional biopsy was performed as a standard with all tumor resections. All patients received their follow-up after the conclusion of therapy at our center by means of regional MRI studies and, at a minimum, CT of the thorax to rule out pulmonary metastatic disease. The aim of the study was the evaluation of the influence of the biopsy type and of several other clinical factors on the rate of local recurrence and on the time of local recurrence-free survival. Results One hundred sixty-two patients with bone or soft tissue tumors of the extremities and the pelvis underwent either an incisional or a core-needle biopsy of their tumor, with 70 sarcomas (43.2%) being located in the bone. 84.6% of all biopsies were performed as core-needle biopsies. The median follow-up time was 55.6 months, and 22 patients (13.6%) developed a local recurrence after a median time of 22.4 months. There were no significant differences between incisional and core-needle biopsy regarding the risk of local recurrence in our subgroup analysis with differentiation by kind of tissue, grading of the sarcoma, and perioperative multimodal therapy. Conclusions In a large and homogenous cohort of extremity and pelvic sarcomas, we did not find significant differences between the groups of incisional and core-needle biopsy regarding the risk of local recurrence. The excision of the biopsy tract after incisional biopsy in the context of the definitive tumor resection seems to be the decisive factor for this result.

Significant co-expression of putative cancer stem cell markers, EpCAM and CD166, correlates with tumor stage and invasive behavior in colorectal cancer

Background The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients. Methods This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides. Results Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P = 0.02), tumor stage (P = 0.007), tumor differentiate (P = 0.005), vascular (P = 0.01), neural (P = 0.01), and lymph node (P = 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P = 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P = 0.03), tumor differentiation (P = 0.05), neural, and lymph node invasion (P =0.01). Conclusions The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.

Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis

Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.

The role of vascular invasion and lymphatic invasion in predicting recurrent thoracic oesophageal squamous cell carcinoma

Background Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. Methods This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. Results Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P<0.001) and pTNM stage (P<0.001), and similar results were found in VI. Moreover, survival analysis showed that pT stage (P<0.001), pN stage (P=0.001), pTNM stage (p<0.001), VI (P=0.001) and LI (P<0.001) were associated with DFS in ESCC. Furthermore, multivariate analysis suggested that pT stage (RR=1.4, P =0.032), pN stage (RR=1.9, P<0.001) and LI (RR=1.5, P=0.008) were independent predictive factors for DFS. Finally, relapse was observed in 110 patients (lymph node metastasis, 78 and distant, 32) and 147 patients with cancer-related deaths. Subanalysis showed that LI-positive patients had higher lymph node metastasis, although there was no significant difference (32.1% vs. 15.6%, P=0.100). Conclusions LI and VI were common in ESCC; they were all survival predictors for patients with ESCC, and LI was independent. Patients with positive LI were more likely to suffer lymph node metastasis.

Gasless, endoscopic trans-axillary thyroid surgery: our series of the first 51 human cases

Background The safety of gasless endoscopic trans-axillary thyroid surgery is still undetermined. Methods Clinical findings and postoperative complications of patients who had undergone trans-axillary thyroid surgery due to thyroid cancer and thyroid nodules were retrospectively studied. The sensory change and paralysis results from this technique and patients’ satisfaction with the cosmesis were also studied. Results Fifty-one patients (49 females and 2 males) received operations by gasless, endoscopic trans-axillary approaches with one patient whose operation was converted to open surgery because of internal jugular vein injury. Only two patients developed temporary vocal cord paralysis and no patients developed other severe complications. The alleviation of the discomfort in the anterior neck area and sternocleidomastoid, and the cosmetic effect of gasless endoscopic trans-axillary thyroid surgery were acceptable. No evidence of recurrence was found during the follow-up period. Conclusions Gasless, endoscopic trans-axillary thyroid surgery is a feasible procedure with acceptable safety and better cosmetic results in strictly selected patients.

Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution

Background The overall survival of patients with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer. Methods The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected. Results Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup. Conclusions Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.

Recurrent malignant peripheral nerve sheath tumor presenting as an asymptomatic intravenous thrombus extending to the heart: a case report

Background Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart. Case presentation A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation. Conclusions In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.