Prognostic value of dynamic changes of pre- and post-operative tumor markers in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) prognosis assessment is vital for personalized treatment plans. This study investigates the prognostic value of dynamic changes of tumor markers CEA, CA19-9, CA125, and AFP before and after surgery and constructs prediction models based on these indicators. METHODS: A retrospective clinical study of 2599 CRC patients who underwent radical surgery was conducted. Patients were randomly divided into training (70%) and validation (30%) datasets. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and nomograms were constructed. RESULTS: A total of 2599 CRC patients were included in the study. Patients were divided into training (70%, n = 1819) and validation (30%, n = 780) sets. Univariate and multivariate Cox regression analyses identified age, total number of resected lymph nodes, T stage, N stage, the preoperative and postoperative changes in the levels of CEA, CA19-9, and CA125 as independent prognostic factors. When their postoperative levels are normal, patients with elevated preoperative levels have significantly worse overall survival. However, when the postoperative levels of CEA/CA19-9/CA125 are elevated, whether their preoperative levels are elevated or not has no significance for prognosis. Two nomogram models were developed, and Model I, which included CEA, CA19-9, and CA125 groups, demonstrated the best performance in both training and validation sets. CONCLUSION: This study highlights the significant predictive value of dynamic changes in tumor markers CEA, CA19-9, and CA125 before and after CRC surgery. Incorporating these markers into a nomogram prediction model improves prognostic accuracy, enabling clinicians to better assess patients' conditions and develop personalized treatment plans.

Activation of RhoA/ROCK2 signaling by hypoxia-inducible factor 1α in promoting tumor growth and metastasis in human colon cancer.

Background: Recent evidence strongly suggests the profound role of the tumor microenvironment in cancer development and progression. A hypoxic microenvironment is widely acknowledged to be a typical feature of solid tumors, and altered hypoxia-inducible factor 1α (HIF-1α) expression has been associated with the formation and the progression of many solid tumors; however, the underlying mechanism of this relationship remains obscure. Methods: Clinical colorectal cancer tissue samples were collected to detect the differential expression of HIF-1α, Ras homolog family member A (RhoA), and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2). With hypoxic stress, small interfering RNA (siRNA) targeting HIF-1α, lentivirus transfection of RhoA was used to study the mechanism of HIF-1α and RhoA/ROCK2 signaling pathways in the growth and metastasis of colon cancer. Results: According to Cell Counting Kit 8, wound-healing, and Transwell assays, HIF-1α expression activated the RhoA/ROCK2 pathway within colon cancer cell lines, accelerating their growth and expansion. In cells transfected with LV-RhoA, inactivating the RhoA/ROCK2 pathway with the specific inhibitor Y-27632 decreased tumor growth and metastasis under hypoxic conditions, while activating the RhoA/ROCK2 pathway restored these biological properties. The Western blot results showed that the expression levels of pMYPT1, cyclin D1, and MMP2 in the siRNA + LV-RhoA group were also significantly increased compared with those in the siRNA group. Conclusions: For the first time, this study demonstrated that HIF-1α can promote the growth and metastasis of colon cancer via directly affecting RhoA/ROCK2 signaling and thus represents a novel therapeutic target for colon cancer.

Small extracellular vesicles-mediated cellular interactions between tumor cells and tumor-associated macrophages: Implication for immunotherapy.

The tumor microenvironment consists of cancer cells and various stromal cells, including macrophages, which exhibit diverse phenotypes with either pro-inflammatory (M1) or anti-inflammatory (M2) effects. The interaction between cancer cells and macrophages plays a crucial role in tumor progression. Small extracellular vesicles (sEVs), which facilitate intercellular communication, are known to play a vital role in this process. This review provides a comprehensive summary of how sEVs derived from cancer cells, containing miRNAs, lncRNAs, proteins, and lipids, can influence macrophage polarization. Additionally, we discuss the impact of macrophage-secreted sEVs on tumor malignant transformation, including effects on proliferation, metastasis, angiogenesis, chemoresistance, and immune escape. Furthermore, we address the therapeutic advancements and current challenges associated with macrophage-associated sEVs, along with potential solutions.

Prognostic value of normal levels of preoperative tumor markers in colorectal cancer.

Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment.

The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1high resting cells to activated TPSAB1high, CPA3high, and KIThigh cells. The elevated KITLG expression in the tumor microenvironment's fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.

PURPOSE: The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. METHODS: The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. RESULTS: Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. CONCLUSION: This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

Cuproptosis-Mediated Patterns Characterized by Distinct Tumor Microenvironment and Predicted the Immunotherapy Response for Gastric Cancer.

Cuproptosis is a newly discovered programmed cell death process, and several cuproptosis-related genes have been reported to regulate cancer cell proliferation and progression. The association between cuproptosis and tumor microenvironment in gastric cancer (GC) remains unclear. This study aimed to explore multiomics characteristics of cuproptosis-related genes regulating tumor microenvironment and provide strategies for prognosis and prediction of immunotherapy response in GC patients. We collected 1401 GC patients from the TCGA and 5 GEO data sets and identified three different cuproptosis-mediated patterns, each of which shared a distinct tumor microenvironment and different overall survival. The GC patients with high cuproptosis levels were enriched in CD8+ T cells and had a better prognosis. Whereas, the low cuproptosis level patients were associated with inhibitory immune cell infiltration and had the worst prognosis. In addition, we constructed a 3-gene (AHCYL2, ANKRD6 and FDGFRB) cuproptosis-related prognosis signature (CuPS) via Lasso-Cox and multivariate Cox regression analysis. The GC patients in the low-CuPS subgroup had higher TMB levels, MSI-H fractions, and PD-L1 expression, which suggests a better immunotherapy response. Therefore, the CuPS might have the potential value for predicting prognosis and immunotherapy sensitivity in GC patients.

Variation of the ileocolic artery and superior mesenteric artery in a patient with right-sided colon cancer with Lynch syndrome: a case report.

Background: Complete mesangectomy and central vascular detachment are the core elements of laparoscopic right hemicolectomy. Failure to identify vascular variations in patients undergoing laparoscopic right hemicolectomy can result in unwanted bleeding, a prolonged surgical time, transfer to open surgery, and an elevated risk of postoperative complications. In this case report, we describe a new vascular variation that has not yet been reported in the literature. Parallelly vascular variation and the management of vessels in key areas are essential for successful surgery. Case Description: The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like "X"-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient's family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS). Conclusions: This report describes the first case of simultaneous variation of the ileocolic artery (ICA) and SMA in a female patient with colon cancer. This type of vascular variation should be fully recognized by surgeons in order to avoid unnecessary intraoperative bleeding.

Analysis of Prognostic Factors of Rectal Cancer and Construction of a Prognostic Prediction Model Based on Bayesian Network.

Background: The existing prognostic models of rectal cancer after radical resection ignored the relationships among prognostic factors and their mutual effects on prognosis. Thus, a new modeling method is required to remedy this defect. The present study aimed to construct a new prognostic prediction model based on the Bayesian network (BN), a machine learning tool for data mining, clinical decision-making, and prognostic prediction. Methods: From January 2015 to December 2017, the clinical data of 705 patients with rectal cancer who underwent radical resection were analyzed. The entire cohort was divided into training and testing datasets. A new prognostic prediction model based on BN was constructed and compared with a nomogram. Results: A univariate analysis showed that age, Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), Carbohydrate antigen 125 (CA125), preoperative chemotherapy, macropathology type, tumor size, differentiation status, T stage, N stage, vascular invasion, KRAS mutation, and postoperative chemotherapy were associated with overall survival (OS) of the training dataset. Based on the above-mentioned variables, a 3-year OS prognostic prediction BN model of the training dataset was constructed using the Tree Augmented Naïve Bayes method. In addition, age, CEA, CA19-9, CA125, differentiation status, T stage, N stage, KRAS mutation, and postoperative chemotherapy were identified as independent prognostic factors of the training dataset through multivariate Cox regression and were used to construct a nomogram. Then, based on the testing dataset, the two models were evaluated using the receiver operating characteristic (ROC) curve. The results showed that the area under the curve (AUC) of ROC of the BN model and nomogram was 80.11 and 74.23%, respectively. Conclusion: The present study established a BN model for prognostic prediction of rectal cancer for the first time, which was demonstrated to be more accurate than a nomogram.

Clinicopathological and prognostic values of PD-L1 expression in oesophageal squamous cell carcinoma: a meta-analysis of 31 studies with 5368 patients.

Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC.A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model.A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p<0.010) but not disease-free survival (DFS) (HR 1.180, 95% CI 0.937 to 1.487, p=0.160). Heterogeneity decreased significantly in subgroup analyses. The overexpression of PD-L1 was associated with poor DFS at the cut-off point of ≥1% (HR 1.642, 95% CI 1.367 to 1.973, p<0.010; I2=0%) and worse OS at the cut-off point of ≥10% (HR 1.575, 95% CI 1.175 to 2.111, p<0.010; I2=0%).The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.

Prognostic Value of Fibrinogen and Lymphocyte Count in Intermediate and High Risk Gastrointestinal Stromal Tumors.

PURPOSE: Data about the prognostic value of fibrinogen concentration and absolute lymphocyte count for the prognosis of gastrointestinal stromal tumors (GISTs) were limited. Thus, the aim of the present study was to investigate the predictive value of preoperative fibrinogen concentration and absolute lymphocyte count in GISTs. PATIENTS AND METHODS: From March 2002 to December 2017, 143 intermediate and high risk GIST patients treated with R0 resection were enrolled in the present study. Clinicopathological characteristics were recorded. The optimal cut-off values of patients were calculated by X-tile software. Categorical variables were analyzed using Chi-square test or Fisher's exact test. Disease-free survival was analyzed by the Kaplan-Meier method and compared by a Log rank test. RESULTS: There were 71 males (49.65%) and 72 females. The median age was 56 years (range 19-86). The optimal cut-off value was 4.5 g/L for fibrinogen concentration (P=0.000) and 1.0×109/L for lymphocyte count (P=0.002). No significant association was found between lymphocyte level and clinicopathological features. However, elevated fibrinogen level was correlated with tumor location, tumor size and NIH risk category. Tumor size, fibrinogen concentration and lymphocyte count were independent risk factors for the prognosis of patients according to the multivariate analysis. The prognosis of patients with high fibrinogen concentration or low lymphocyte count was significantly worse than that with low fibrinogen concentration or high lymphocyte count. Further, combination of fibrinogen concentration and lymphocyte count could increase the prognostic value for GIST patients. CONCLUSION: Fibrinogen concentration and absolute lymphocyte count were independent prognostic factors for intermediate and high risk GIST patients. The combination of fibrinogen concentration and absolute lymphocyte count could further increase the predictive value for the prognosis of GIST patients.

Necessity of prophylactic splenic hilum lymph node clearance for middle and upper third gastric cancer: a network meta-analysis.

BACKGROUND: It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer. METHODS: A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G + S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G + SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. RESULTS: Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G + S. Similarly, the 5-year overall survival rate between G + SPSHD and G + S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G + SPSHD was lower than that of G + S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G + SPSHD. CONCLUSIONS: Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer.

The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis.

Background The benefit of surgical resection for advanced gastrointestinal stromal tumors (GISTs) following tyrosine kinase inhibitors (TKIs) treatment was still under debate. The present meta-analysis was designed to assess the value of surgical resection for the prognosis of patients with metastatic, recurrence and unresectable GISTs. Methods A systematic search of PubMed Central, PubMed, EMBASE and the Cochrane Library database was performed. Relevant studies of the role of surgery in advanced GISTs published before 1 May 2019 were identified. The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. The progression-free survival (PFS) and overall survival (OS) were assessed through software Stata 15.0. Results A total of 6 retrospective studies including 655 patients were analyzed. The pooled result revealed that surgical resection group was associated with better PFS (HR = 2.08; 95% CI: 1.58 to 2.76; P<0.001) and better OS (HR = 2.13; 95% CI: 1.59 to 2.85; P<0.001) compared with TKIs treatment alone group. Conclusions Surgical resection following TKIs treatment could significantly improve the prognosis of patients with advanced GISTs.

SP promotes cell proliferation in esophageal squamous cell carcinoma through the NK1R/Hes1 axis.

BACKGROUND: Substance P (SP) plays an important role in several types of cancer promotion and progression by binding to its preferential neurokinin 1 receptor (NK1R). However, the clinical significance and downstream mechanism of NK1R in esophageal squamous cell carcinoma (ESCC) have not been elucidated. The aim of this study was to investigate the role of SP/NK1R in the proliferation of ESCC and to screen related downstream molecules. METHODS: In the current investigation, the expression of NK1R was detected via immunohistochemistry (IHC), western blot (WB) analysis and real-time reverse transcription-polymerase chain reaction (RT-qPCR) in ESCC tissues and cell lines. Thereafter, the optimal concentration of SP was determined in vitro. The proliferation ability of SP/NK1R was assessed by cell counting kit-8 (CCK-8) and colony formation assays and subcutaneous tumour formation in nude mice with EC109 cells. Moreover, the related downstream molecules were screened by performing isobaric tags for relative and absolute quantitation (iTRAQ) protein spectrum analysis. RESULTS: NK1R was upregulated in ESCC, and its overexpression correlated with larger tumour size, deeper tumour invasion, more perineural invasion and eventually caused poorer overall survival (OS). Both intrinsic and SP-activated NK1R upregulation could promote the proliferation and clonogenic capacity of ESCC cells. In nude mice, tumour growth was suppressed by EC109 cells of NK1R downregulation. Further experiments demonstrated that Hairy and Enhancer of Split 1 (Hes1) was markedly reduced upon NK1R downregulation in EC109 cell lines and could regulate cell proliferation in the downstream of SP/NK1R. CONCLUSIONS: The significant role of NK1R in mediating ESCC cell proliferation depended on the activation of SP and might be related to the downstream regulation of Hes1.

Clinicopathological Features and Prognosis of Gastrointestinal Stromal Tumor Located in the Jejunum and Ileum.

BACKGROUND: Data about the clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) located in jejunum and ileum are lacking. The present study aims to investigate the features and prognosis of jejunal and ileal GISTs based on the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: Cases of jejunal and ileal GISTs were extracted from SEER database. Clinicopathological characteristics and survival data of patients were recorded. The clinicopathological features and prognosis of patients were analyzed. RESULTS: There were 399 male (56.8%) and 303 female (43.2%). The median age was 60 years (17-96). Four hundred and seventy-two tumors were located in the jejunum (67.2%) and 230 tumors in the ileum (32.8%). The median tumor size was 7.0 cm (0.5-90). The 5-, 10-, and 20-year disease specific survival (DSS) was 84.4, 71.2, and 54.2% respectively. Clinicopathological features were comparable between tumors located in the jejunum and ileum (all p > 0.05) except gender and tumor size (both p < 0.05). Jejunal GISTs, rather than ileal GISTs (p = 0.043), were commonly found in the males. The tumor size of jejunal GISTs was smaller than that of ileal GISTs (p = 0.010). The DSS of jejunal GISTs was comparable to that of ileal GISTs (p = 0.269). CONCLUSIONS: Jejunal GISTs were more common than ileal GISTs. The prognosis was comparable between jejunal and ileal GISTs.

Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer.

BACKGROUND: Existing data about the prognostic value of absolute count of blood cells in gastric cancer was limited. Thus, the present study aims to investigate the prognostic value of absolute count of white blood cell (WBC), neutrophil, lymphocyte, monocyte and platelet in gastric cancer patients. METHODS: From September 2008 to March 2015, 3243 patients treated with radical gastrectomy were enrolled in the present study. Clinicopathological characteristics were recorded. The prognostic value of blood test in gastric cancer patients were analyzed. RESULTS: There were 2538 male and 705 female. The median age was 58 years (range 20-90). The median follow-up time was 24.9 months (range 1-75). The 1-, 3- and 5-year overall survival rate was 88.9%, 65.8% and 57.2%, respectively. The optimal cut off value was 6.19 × 109/L for WBC (P = 0.146), 4.19 × 109/L for neutrophil (P = 0.004), 1.72 × 109/L for lymphocyte (P = 0.000), 0.51 × 109/L for monocyte (P = 0.019) and 260.0 × 109/L for platelet (P = 0.002), respectively. Neutrophil, lymphocyte, monocyte and platelet were risk factors for the prognosis of gastric cancer (all P < 0.05). However, only lymphocyte and monocyte were independent risk factors (both P < 0.05). Combination of lymphocyte and monocyte could increase the prognostic value for gastric cancer patients, especially in stage II/III gastric cancer patients. CONCLUSIONS: High absolute count of neutrophil, monocyte and platelet, and low absolute count of lymphocyte were associated with poor prognosis of gastric cancer. However, only lymphocyte and monocyte count were independent prognostic predictors. Combination of lymphocyte and monocyte count could further increase the predictive value for gastric cancer.

Prognostic value of differentiation status in gastric cancer.

BACKGROUND: Up to date, investigation of the prognostic value of differentiation status mainly focused on signet ring cell and mucinous gastric cancer. Thus, the present study aims to investigate the clinicopathological features and prognosis of gastric cancer patients with well, moderately and poorly differentiation status. METHODS: From September 2008 to March 2015, a total of 3090 gastric cancer patients treated with radical D2 gastrectomy were enrolled in the present study. Clinicopathological characteristics and prognosis of gastric cancer patients with well, moderately and poorly differentiation status were analyzed. RESULTS: There were 2422 male (78.4%) and 668 female (21.6%). The median age was 58 (20-90) years. There were 370 (12.0%) well differentiated tumors, 836 (27.0%) moderately differentiated tumors and 1884 (61.0%) poorly differentiated tumors. Well and moderately differentiation status were associated with older age, male gender, smaller tumor, shallower invasion, less lymph node involvement and earlier tumor stage (all p < 0.001). Inversely, poorly differentiation status was associated with younger age, female gender, larger tumor, deeper invasion, more lymph node involvement and later tumor stage (all p < 0.001). With respect to prognosis, well differentiation status was associated with favorable overall survival and poorly differentiation status was associated with unfavorable overall survival (p < 0.001). However, after matching with age, tumor size, T and N stage, there was no significant difference among the overall survival of the three groups (p = 0.415). CONCLUSIONS: Well, moderately and poorly differentiation status was significantly associated with clinicopathological features of gastric cancer patients. However, it was not associated with the prognosis of gastric cancer patients.

PD-L1 Expression On tumor Cells Was Associated With Unfavorable Prognosis In Esophageal Squamous Cell Carcinoma.

Background: Evidence about the association between programmed cell death ligand 1 (PD-L1) expression and prognosis of esophageal squamous cell carcinoma (ESCC) were limited and controversial. Thus, the present study aims to investigate the prognostic value of tumor immune microenvironment (TIM) based on PD-L1 expression and CD8+ T cell infiltration in ESCC tissues. Methods: From September 2008 to March 2010, a total of 146 ESCC patients received radical esophagectomy were retrospectively analyzed in our present study. PD-L1 expression and CD8+ T cell infiltration were evaluated through immunohistochemistry. The clinicopathological characteristics and survival were analyzed. Results: There were 111 male and 35 female. The median age was 59.1 years (37-78 years). The positive rate of PD-L1 expression was 61.7%. The rate of high CD8+ T cell infiltration was 33%. No significant differences were found between clinicopathological features and PD-L1 expression or CD8+ T cell infiltration. PD-L1 expression was significantly associated with poor overall survival (P=0.010). However, CD8+ T cell infiltration was not a prognostic risk factor. Type of TIM was significantly associated with the prognosis of ESCC patients (P=0.021). Conclusions: PD-L1 expression was an independent risk factor for the prognosis of ESCC patients. Immunotherapy may achieve promising outcomes in ESCC patients with type I TIM.

Clinicopathological features, surgical strategy and prognosis of duodenal gastrointestinal stromal tumors: a series of 300 patients.

BACKGROUND: The relatively low incidence of duodenal gastrointestinal stromal tumors (GISTs) and the unique anatomy make the surgical management and outcomes of this kind of tumor still under debate. Thus, this study aimed to explore the optimal surgical strategy and prognosis of duodenal GISTs. METHODS: A total of 300 cases of duodenal GISTs were obtained from our center (37 cases) and from case reports or series (263 cases) extracted from MEDLINE. Clinicopathological features, type of resections and survivals of duodenal GISTs were analyzed. RESULTS: The most common location of duodenal GISTs was descending portion (137/266, 51.5%). The median tumor size was 4 cm (0.1-28). Most patients (66.3%) received limited resection (LR). Pancreaticoduodenectomy (PD) was mainly performed for GISTs with larger tumor size or arose from descending portion (both P < 0.05). For both the entire cohort and tumors located in the descending portion, PD was not an independent risk factor for disease-free survival (DFS) and disease-specific survival (DSS) (both P > 0.05). Duodenal GISTs were significantly different from gastric GISTs with respect to tumor size, mitotic index and NIH risk category (all P < 0.05). The DFS and DSS of duodenal GISTs was significantly worse than that of gastric GISTs (both P < 0.05). CONCLUSIONS: LR was a more prevalent surgical procedure and PD was mainly performed for tumors with larger diameter or located in descending portion. Type of resection was not an independent risk factor for the prognosis of duodenal GISTs. Prognosis of duodenal GISTs was significantly worse than that of gastric GISTs.