AIM To evaluate the clinical properties of three subpopulations of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS We identified CTCs for expression of the epithelial cell marker cytokeratin or epithelial cell adhesion molecule (EpCAM) (E-CTC), the mesenchymal cell markers vimentin and twist (M-CTC), or both (E/M-CTC) using the. CanPatrol system. Between July 2014 and July 2016, 107 patients with PDAC were enrolled for CTC evaluation. CTC enumeration and dassification were correlated with patient clinicopathological features and outcomes. RESULTS CTCs were detected in 78.5% of PDAC patients. The number of total CTCs ranged from 0 to 26 across all 107 patients, with a median value of six. CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with >= 6 total CTCs had significantly decreased overall survival and progression-free survival compared with patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage (P < 0.01) and distant metastasis (P < 0.01). Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation (P < 0.01). CONCLUSION Classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.
BACKGROUND In recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients. AIM To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC. METHODS Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability. RESULTS Four hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypTO-2N0M0 (ypTNM 0-D. The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation. CONCLUSION We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.
AIM To assess the efficiency of endoscopic trans-esophageal submucosal tunneling surgery (EESTS) technique for diseases located around the aorta ventralis. METHODS Nine pigs were assigned to EESTs. The procedures were as follows: First, a long esophageal submucosal tunnel was established. Second, full-thickness myotomy was created. Third, an endoscope was entered into the abdominal cavity through a muscle incision and the endoscope was around the aorta ventralis. Eventually, celiac trunk ganglion neurolysis, partial hepatectomy and splenectomy, partial tissue resection in the area of the posterior peritoneum, and endoscopic submucosal dissection (ESD) combined with lymph node dissection were performed. The animals were given antibiotics for 5 d and necropsied 7 d after surgery. RESULTS In all surgeries, one pig died from intraperitoneal hemorrhage after doing partial splenectomy, while the other pigs were alive after successfully operating other surgeries. For surgery of celiac trunk ganglion damage, at necropsy, there was no exudation in the abdominal cavity. Regarding surgery of partial hepatectomy, the wound with part healing was observed in the left hepatic lobe, and no bleeding or obvious exudation was seen. In surgery of partial splenectomy, massive hemorrhage was observed on the splenic wound surface, and the metal clips could not stop bleeding. After surgery of retroperitoneal tissue resection, mild tissue adhesion was observed in the abdominal cavity of one animal, and another one suffered from severe infection. For surgery of ESD and lymph node dissection, a moderate tissue adhesion was observed. CONCLUSION EESTS is a feasible and safe technique for diseases located around the aorta ventralis.
BACKGROUND Anastomotic leakage (AL) is a severe complication associated with high morbidity and mortality after radical gastrectomy (RG) for gastric cancer (GC). We hypothesized that a novel abdominal negative pressure lavage-drainage system (ANPLDS) can effectively reduce the failure-to-rescue (FTR) and the risk of reoperation, and it is a feasible management for AL. AIM To report our institution's experience with a novel ANPLDS for AL after RG for GC. METHODS The study enrolled 4173 patients who underwent R0 resection for GC at our institution between June 2009 and December 2016. ANPLDS was routinely used for patients with AL after January 2014. Characterization of patients who underwent R0 resection was compared between different study periods. AL rates and postoperative outcome among patients with AL were compared before and after the ANPLDS therapy. We used multivariate analyses to evaluate clinicopathological and perioperative factors for associations with AL and FTR after AL. RESULTS AL occurred in 83 (83/4173, 2%) patients, leading to 7 deaths. The mean time of occurrence of AL was 5.6 days. The AL rate was similar before (2009-2013, period 1) and after (2014-2016, period 2) the implementation of the ANPLDS therapy (1.7% vs 2.3%, P = 0.121). Age and malnourishment were independently associated with AL. The FTR rate and abdominal bleeding rate after AL occurred were respectively 8.4% and 9.6% for the entire period; however, compared with period 1, this significantly decreased during period 2 (16.2% vs 2.2%, P = 0.041; 18.9% vs 2.2%, P = 0.020, respectively). Moreover, the reoperation rate was also reduced in period 2, although this result was not statistically significant (13.5% vs 2.2%, P = 0.084). Additionally, only ANPLDS therapy was an independent protective factor for FTR after AL (P = 0.04). CONCLUSION Our experience demonstrates that ANPLDS is a feasible management for AL after RG for GC.
AIM To evaluate the effectiveness and safety of submucosal tunneling endoscopic resection (STER) and compare its outcomes in esophageal and cardial submucosal tumors (SMTs) of the muscularis propria (MP) layer. METHODS From May 2012 to November 2017, 173 consecutive patients with upper gastrointestinal (GI) SMTs of the MP layer underwent STER. Overall, 165 patients were included, and 8 were excluded. The baseline characteristics of the patients and SMTs were recorded. The en bloc resection rate, complete resection rate, residual rate, and recurrence rate were calculated to evaluate the effectiveness of STER, and the complication rate was recorded to evaluate its safety. Effectiveness and safety outcomes were compared between esophageal and cardial SMTs. RESULTS One hundred and twelve men and 53 women with a mean age of 46.9 +/- 10.8 years were included. The mean tumor size was 22.6 +/- 13.6 mm. Eleven SMTs were located in the upper esophagus (6.7%), 49 in the middle esophagus (29.7%), 46 in the lower esophagus (27.9%), and 59 in the cardia (35.7%). Irregular lesions accounted for 48.5% of all lesions. STER achieved an en bloc resection rate of 78.7% (128/165) for GI SMTs with an overall complication rate of 21.2% (35/165). All complications resolved without intervention or were treated conservatively without the need for surgery. The en bloc resection rates of esophageal and cardial SMTs were 81.1% (86/106) and 72.1% (42/59), respectively (P = 0.142), and the complication rates were 19.8% (21/106) and 23.7% (14/59), respectively, (P = 0.555). The most common complications for esophageal SMTs were gas-related complications and fever, while mucosal injury was the most common for cardial SMTs. CONCLUSION STER is an effective and safe therapy for GI SMTs of the MP layer. Its effectiveness and safety are comparable between SMTs of the esophagus and cardia.
BACKGROUND Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.
BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome (IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor (BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D). AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology. METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 age- and sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined. RESULTS The patients had a higher anxiety score [median (interquartile range), 6.0 (2.0-10.0) vs 3.0 (1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0 (44.0-61.0) vs 21.0 (17.3-30.0), P < 0.001] than controls. The defecating sensation threshold [60.0 (44.0-80.0) vs 80.0 (61.0-100.0), P = 0.009], maximum tolerable threshold [103.0 (90.0-128.0) vs 182.0 (142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0 (20.0-30.0) vs 30.0 (30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46E-2 (3.06E-2-4.44E-2) vs 3.07E-2 (2.91E-2-3.48E-2), P = 0.031] and mRNA [1.57 (1.31-2.61) vs 1.09 (0.74-1.42), P = 0.001] expression and nerve fiber density [4.12E-2 (3.07E-2-7.46E-2) vs 1.98E-2 (1.21E-2-4.25E-2), P = 0.002] were significantly elevated in the patients. Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters. CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.
BACKGROUND Recent evidence shows that long non-coding RNAs (lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma (HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival (OS) of HCC, but the results varied. Thus, more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC. AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC. METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival (RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator (LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas (TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed. RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2J4, EIF3J-AS1, SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio (HR) being 1.807 (95% CI [confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples (P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-beta signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification. CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses, alcoholism, and metabolic disorders, such as Wilson disease (WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features. AIM To delineate the liver features between WD-associated cirrhosis and hepatitis B- associated cirrhosis in the Chinese population. METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma, severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group (60 patients) and hepatitis B-associated cirrhosis group (56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups. RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers, however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients (16-29 years) had lower levels of alanine transaminase, aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter (P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients (45-62 years). Importantly, they had decreased risks of progression from Child-Pugh grade. A to B (odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites (odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WD-associated cirrhosis patients had a higher risk of splenomegaly (odds ratio = 4.15, 95% confidence interval: 1.38-12.45, P = 0.011). CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.
BACKGROUND Exposure to high sustained +Gz. (head-to-foot inertial load) is known to have harmful effects on pilots body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined. AIM To investigate rat liver function changes in response to repeated +Gz. exposure. METHODS Ninety male. Wistar rats were randomly divided into a blank control group (BC group, n = 30), a +6 Gz/5 min stress group (6GS group, n = 30), and a +10 Gz/5min stress group (10GS group, n = 30). The 6GS and 10GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure (for 5 exposures, and 5-nun intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury by measuring the portal venous flow volume, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AK), liver tissue malondialdehyde (MDA), Na - K'-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures. RESULTS After repeated +Gz exposures in the 6GS and the 10GS groups, the velocity and flow signal in the portal vein (PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6GS group had a much higher portal venous flow volume than the 1.0GS group at 0 h after exposure. The 6GS group had significantly lower ALT, AST, and MDA values than the 1.0GS group 0 h and 6 h post exposure. The Na+-K+-ATPase activity in the 6GS group was significantly higher than that in the 10GS group 0 h and 6 h post exposure. Hepatocyte injury, determined pathologically, was significantly lower in the 6GS group than in the lOGS group. CONCLUSION Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.
The Na+/Ca2+ exchanger (NCX) protein family is a part of the cation/Ca2+ exchanger superfamily and participates in the regulation of cellular Ca2+ homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption. This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.
Long-term nucleos(t)ide analogue therapy in chronic hepatitis B virus (HBV) infection is effective in suppressing viral replication and reducing liver-related complications. However, HBV-related liver events can still occur in different patient sub-groups. There is emerging evidence that, similar to chronic hepatitis C virus infection, metabolic risk factors may play a role in the disease process of chronic HBV. While the mechanistic nature of metabolic-HBV interactions remains uncertain, studies in different HBV-infected populations have demonstrated that hepatic steatosis, increased body-mass index, diabetes, or a combination of different metabolic risk factors are associated with an increased risk of hepatocellular carcinoma and cirrhosis. The impact of metabolic risk factors is especially prominent in patients with quiescent virological activity, including on-treatment patients with effective viral suppression. As the proportion of on-treatment chronic HBV patients increases worldwide, longitudinal studies determining the relative risks of different metabolic parameters with respect to clinical outcomes are needed. Future studies should also determine if metabolic-directed interventions can improve disease outcomes in chronic HBV.
BACKGROUND Increasing evidence demonstrates that by acting as microRNA sponges modulating gene expression at the transcriptional or post-transcriptional level, circular RNAs (circRNAs) participate in the pathogenesis of a variety of diseases and are considered ideal biomarkers of human disease. AIM To examine the expression of circRNA_103516 in inflammatory bowel disease (IBD) and its associations with clinical phenotypes and inflammatory cytokines. METHODS Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IBD, healthy controls (HCs), and patient controls (PCs). Expression of circRNA_103516 and hsa-miR-19b-1-5p was assessed by quantitative reverse transcription-polymerase chain reaction. Crohn's disease activity index (CDAI), Mayo score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) were measured. To assess the inflammatory cytokines tumour necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10), blood samples were analysed by flow cytometry. RESULTS Ninety Crohn's disease (CD) and 90 ulcerative colitis (UC) patients, 80 HCs, and 35 PCs were included in the study. CircRNA_103516 was upregulated in CD and UC patients compared with HCs and PCs (P < 0.05). The area under the curve of circRNA_103516 for diagnosing CD and UC was 0.790 and 0.687, respectively. In addition, circRNA_103516 levels were increased in active CD and UC compared with remittent groups (P = 0.027, P = 0.045). Furthermore, in CD, circRNA_103516 correlated positively with CDAI (P < 0.001), CRP (P < 0.001), ESR (P < 0.001), TNF alpha (P < 0.001), and IFN-gamma (P < 0.001) and negatively correlated with IL-10 (P = 0.006). In UC patients, circRNA_103516 correlated with Mayo score (P < 0.001), CRP (P < 0.001), ESR (P < 0.001), TNF alpha (P < 0.001), IFN-gamma (P =0.011), and IL-10 (P = 0.002). Additionally, circRNA_103516 correlated positively with stricturing (P = 0.018) and penetrating (P = 0.031) behaviour. Moreover, hsa-miR-19b-1-5p correlated negatively with circRNA_103516 in CD. CONCLUSION CircRNA_103516 levels in PBMCs can be considered an ideal candidate biomarker for diagnosing IBD. Dysregulation of circRNA_103516 may participate in the molecular mechanism of IBD through hsa-miR-19b-1-5p sponging.
BACKGROUND Increasing numbers of laboratory blood parameters (BPM) have been reported to greatly affect the long-term outcomes of gastric cancer (GC) patients. However, the existing prognostic models do not comprehensively analyze these predictors. AIM To construct a new prognostic tool, based on all the prognostic BPM, to achieve more accurate prognosis prediction for GC. METHODS We retrospectively assessed 850 consecutive patients who underwent curative resection for stage II-III GC from January 2010 to April 2013. The patients were classified into developing (n = 567) and validation (n = 283) cohorts using computer-generated random numbers. A scoring system, namely BPM score, was then constructed using least absolute shrinkage and selection operator (LASSO) Cox regression model in the developing cohort, and validated in the validation cohort. A nomogram consisting of BPM score and tumor-lymph node-metastasis (TNM) stage was further created. The discrimination and calibration of the nomogram were evaluated via Harrell's C-statistic and the Hosmer-Lemeshow test. RESULTS Using the LASSO model, we established the BPM score based on five BPM: Albumin, lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, carcinoembryonic antigen, and carbohydrate antigen 19-9. The BPM scores were divided into high- and low-BPM groups based on a cut-off value of -0.93. High-BPM patients were significantly older and had more advanced, larger tumors. In the developing cohort, significant differences were found in 5-year overall survival (OS) and 5-year disease-specific survival between the high-BPM and low-BPM patients. Similar results were found in the validation group. Multivariable analysis showed that the BPM score was an independent predictor of OS. High-BPM patients had a poorer 5-year OS for each subgroup. Furthermore, a nomogram that combined the BPM score and TNM stage had significantly better prognostic value compared with TNM stage alone. CONCLUSION The BPM score provides more accurate prognosis prediction in stage II-III GC patients and is an effective complement to the TNM staging system.
BACKGROUND Platelets have been reported to participate in tumor cell growth, extravasation, epithelial-mesenchymal transition, metastasis, and drug resistance. However, the importance of platelets in pancreatic neuroendocrine tumor (pNET) lacks adequate literature support. The predictive value of tumor-infiltrating platelets (TIPs) in pNET remains unclear. AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection. METHODS In total, 113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study. Immunohistochemical analysis of cluster of differentiation 42b (CD42b) expression in the tumor specimens was performed to determine the presence of TIPs. Univariate and multivariate analyses were used to analyze the prognostic value of TIPs. RESULTS TIPs were observed in intratumoral areas in 54 patients. Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs (all P > 0.05). Patients with positive intratumoral CD42b expression had worse overall survival (P = 0.005) and recurrence-free survival (P < 0.001) than those with negative intratumoral CD42b expression. Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival (P = 0.049) and recurrence-free survival (P = 0.003). Nevertheless, platelet count, mean platelet volume, and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients (all P > 0.05). CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET, and their detection represents a promising tool for pNET treatment strategy decisions.