Nomogram incorporating prognostic immune-inflammatory-nutritional score for survival prediction in pancreatic cancer: a retrospective study.

BACKGROUND: Prognosis prediction for pancreatic cancer has always been difficult in clinical practice because of its high heterogeneity and mortality. The aim of the study was to assess the value of prognostic immune-inflammatory-nutritional (PIIN) score on overall survival (OS) in postoperative patients with pancreatic cancer and to develop a nomogram incorporating PIIN score. METHODS: This study retrospectively analyzed the clinic pathological data of 155 patients with pancreatic cancer who underwent radical surgery. PIIN score was calculated by measuring the fibrinogen (FIB), neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), albumin-bilirubin (ALBI) score, and prognostic nutritional index (PNI). Patients were divided into two groups by PIIN score levels over a threshold of 37.2. Univariate and multivariate analysis were performed using the Cox regression analysis model. The time-dependent receiver operating characteristic (ROC) curve was plotted to compare the prognostic values of the scoring systems. Finally, a nomogram based on PIIN score was constructed and validated. RESULTS: Multivariate regression analysis showed that PIIN score (hazard ratio (HR) = 2.171, 95% confidence interval (CI) = 1.207-3.906, P = 0.010), lymphovascular invasion (HR = 1.663, 95% CI = 1.081-2.557, P = 0.021), poor tumor grade (HR = 2.577, 95% CI = 1.668-3.982, P < 0.001), bad TNM stage (I vs. II: HR = 1.791, 95% CI = 1.103-2.906, P = 0.018; I vs. III: HR = 4.313, 95% CI = 2.365-7.865, P < 0.001) and without adjuvant chemotherapy (HR = 0.552, 95% CI = 0.368-0.829, P = 0.004) were independent risk factors for OS. The time-dependent ROC curves revealed that PIIN score was better than the other scoring systems in predicting survival prognosis. And last, the nomogram established from independent factors such as PIIN score had good predictive power for OS. The ROC curve results showed that the AUC values for 1, 3 and 5 years were 0.826, 0.798 and 0.846, respectively. The calibration plots showed the superior clinical applicability of the nomogram. CONCLUSION: The nomogram model based on PIIN score can be utilized as one of the prognosis stratifications as well as postoperative follow-up for the development of individual treatment for pancreatic cancer.

Machine learning-based nomogram for 30-day mortality prediction for patients with unresectable malignant biliary obstruction after ERCP with metal stent: a retrospective observational cohort study.

BACKGROUND: This study aimed to investigate the risk factors for 30-day mortality in patients with malignant biliary obstruction (MBO) after endoscopic retrograde cholangiopancreatography (ERCP) with endobiliary metal stent placement. Furthermore, we aimed to construct and visualize a prediction model based on LASSO-logistic regression. METHODS: Data were collected from 245 patients who underwent their first ERCP with endobiliary metal stent placement for unresectable MBO between June 1, 2013, and August 31, 2021. Univariable and multivariable logistic regression analyses were conducted to identify the risk factors for 30-day mortality. We subsequently developed a logistic regression model that incorporated multiple parameters identified by LASSO regression. The model was visualized and the nomogram was plotted. Risk stratification was performed based on nomogram-derived scores. RESULTS: The 30-day mortality rate was 10.7% (23/245 patients). Distant metastasis, total bilirubin, post-ERCP complications, and successful drainage were independent risk factors of 30-day mortality. The variables screened by LASSO regression, including distant metastasis, total bilirubin, post-ERCP complications, and successful drainage, were incorporated into the logistic model. The results were visualized through a nomogram based on the model. To assess the model's performance, discrimination was evaluated using the area-under-the-curve values obtained from receiver operating characteristic analyses with 10-fold cross-validation in the training group and validated in the testing group. The calibration curve showed the good predictive ability of the model. Decision curve analysis is used to evaluate the clinical application of nomogram. Finally, we performed risk stratification based on the risk calculated using the nomogram. Patients were assigned to the low-, moderate-, and high-risk groups based on their probability scores. The Kaplan-Meier survival curves for the different nomogram-based groups were significantly different (p < 0.001). CONCLUSIONS: We developed a nomogram using the LASSO-logistic regression model to forecast the 30-day mortality rate in patients who had undergone ERCP with endobiliary metal stent placement due to MBO. This nomogram can assist in identifying individuals at high-risk of 30-day mortality following ERCP.

Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats.

Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC. Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats. Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (>360 µmol/L, n = 80) and 176.0 days in the normal serum uric acid group (<360 µmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher's ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group. Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.

Prognostic Significance of Microvascular Invasion in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND The incidence, pathogenesis, and prognostic effect of microvascular invasion on pancreatic ductal adenocarcinoma (PDAC) remain controversial. This study aimed to summarize the incidence, pathogenesis, role in clinical management, recurrence, and prognostic significance of microvascular invasion in PDAC. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Systematic literature searches were conducted using PubMed and Google Scholar up to February 2021. RESULTS Seventeen studies were included in the meta-analysis. The incidence of microvascular invasion was 49.0% (95% confidence interval [CI], 43.8-54.5%) among PDAC patients who underwent surgery. The weighted multivariate Cox proportional hazards model hazard ratio for disease-free survival of 8 studies was 1.78 (95% CI 1.53-2.08, P<0.001), and there was no statistically significant difference between the subgroups (P=0.477). The hazard ratio for overall survival of 14 studies was 1.49 (95% CI 1.27-1.74, P<0.001), and there was no statistically significant difference between the subgroups (P=0.676). CONCLUSIONS Microvascular invasion occurred in nearly half of PDAC patients after surgery and was closely related to disease-free and overall survival. Understanding the role of microvascular invasion in PDAC will help provide more personalized and effective preoperative or postoperative strategies to achieve better survival outcomes.

Prognostic Impact of DHRS9 Overexpression in Pancreatic Cancer.

PURPOSE: Pancreatic cancer (PC) has poor prognosis despite systemic treatment. Dehydrogenase/reductase member 9 (DHRS9) has been reported to be involved in many events of tumorigenesis, but its prognostic impact in PC remains undetermined. Thus, this study aimed to explore the association between DHRS9 expression and the prognosis of PC and investigate the possible mechanism by which DHRS9 is involved in PC progression. PATIENTS AND METHODS: The study used data: from Gene Expression Omnibus (GEO) and our institution to compare the DHRS9 expression between PC and adjacent normal tissues; from The Cancer Genome Atlas (TCGA) and our institution to assess the clinicopathological characteristics and prognosis of PC patients in high and low DHRS9 expression groups; and from TCGA to predict the potential mechanism of DHRS9 in PC. Western blot assay was used to identify DHRS9 expression in specimens collected from five patients who underwent surgery in our institute. Furthermore, immunohistochemistry (IHC) was then used to identify DHRS9 expression in the specimens of 109 patients who underwent surgery at our institute. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of DHRS9 expression among PC patients. RESULTS: All the IHC, Western blot, and GEO datasets indicated that compared to normal tissues, DHRS9 was significantly overexpressed in PC tissues. IHC results demonstrated that the strong intensity of DHRS9 expression was significantly correlated with vascular infiltration (P < 0.05). Further, high DHRS9 expression was identified as a prognostic risk factor for overall survival. Functional analysis of DHRS9 co-expressed genes indicated that DHRS9 was involved in mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. CONCLUSION: DHRS9 is upregulated in PC tissue, and high DHRS9 expression is correlated with poor prognosis in PC. DHRS9 may affect the oncological process of PC through MAPK/ERK pathway.

Clinical characteristics and disease-specific prognostic nomogram for primary gliosarcoma: a SEER population-based analysis.

Because the study population with gliosarcoma (GSM) is limited, the understanding of this disease is insufficient. In this study, the authors aimed to determine the clinical characteristics and independent prognostic factors influencing the prognosis of GSM patients and to develop a nomogram to predict the prognosis of GSM patients after craniotomy. A total of 498 patients diagnosed with primary GSM between 2004 and 2015 were extracted from the 18 Registries Research Data of the Surveillance, Epidemiology, and End Results (SEER) database. The median disease-specific survival (DSS) was 12.0 months, and the postoperative 0.5-, 1-, and 3-year DSS rates were 71.4%, 46.4% and 9.8%, respectively. We applied both the Cox proportional hazards model and the decision tree model to determine the prognostic factors of primary GSM. The Cox proportional hazards model demonstrated that age at presentation, tumour size, metastasis state and adjuvant chemotherapy (CT) were independent prognostic factors for DSS. The decision tree model suggested that age <71 years and adjuvant CT were associated with a better prognosis for GSM patients. The nomogram generated via the Cox proportional hazards model was developed by applying the rms package in R version 3.5.0. The C-index of internal validation for DSS prediction was 0.67 (95% confidence interval (CI), 0.63 to 0.70). The calibration curve at one year suggested that there was good consistency between the predicted DSS and the actual DSS probability. This study was the first to develop a disease-specific nomogram for predicting the prognosis of primary GSM patients after craniotomy, which can help clinicians immediately and accurately predict patient prognosis and conduct further treatment.

Genetic Profiles Related to Pathogenesis in Sporadic Intracranial Aneurysm Patients.

BACKGROUND: Intracranial aneurysm (IA) represents a cerebrovascular disorder that featured by dilation or bulging of the weakened blood vessel wall. When it ruptures, an IA leads to subarachnoid hemorrhage with high disability and mortality rates. Despite the numerous studies focusing on IA ruptures, little research on IA pathogenesis has been reported. In this study, we aimed to reveal key genes related to IA formation. METHODS: Four datasets from Gene Expression Omnibus data were downloaded, normalized, and separated into the IA group and the normal vessel control group for analyses. We screened for differentially expressed genes (DEGs) between groups and conducted functional enrichment, pathway enrichment, and gene set enrichment analysis analyses among significant DEGs. RESULTS: according to our analyses, significant DEGs majorly associate with smooth muscle system and the complement system. Among all DEGs, 5 down-regulated genes (MYH11, CNN1, MYOCD, ACTA1, and LMOD1) and 3 up-regulated genes (C1QB, C3AR1, and VSIG4) are most relevant in IA formation. CONCLUSIONS: Key DEGs identified in this study are related to IA pathogenesis. Among identified DEGs, LMOD1 is the most significant and merits more attention.

Prognostic Nomogram for Disease-Specific Survival in Patients with Non-metastatic Ampullary Carcinoma After Surgery.

OBJECTIVE: The aim of this study was to establish and validate an individualized nomogram for predicting disease-specific survival (DSS) in patients with non-metastatic ampullary carcinoma after surgery. METHODS: The nomogram was prepared using retrospective data from the Surveillance, Epidemiology, and End Results database, and included 2022 patients (training dataset: 1276; validation dataset: 746 patients) with non-metastatic ampullary carcinoma who were surgically treated between 2004 and 2014. Cox multivariate regression was performed to identify independent risk factors. The predictive accuracy was determined using the concordance index (C-index) and calibration curves. Results were validated internally using bootstrap resampling, and externally against the validation dataset. RESULTS: The median follow-up for the training dataset was 25.5 months (range 1-143), the median survival time was 52 months [95% confidence interval (CI) 41.67-62.33], and the postoperative 1-, 3-, and 5-year DSS rates were 86.7%, 57.3%, and 47.2%, respectively. Univariate and multivariate regression analysis demonstrated that age, grade, tumor size, lymph node ratio, extension range, and histology were independent risk factors for DSS. The C-index of the internal validation dataset for predicting DSS was 0.70 (95% CI 0.68-0.72), which was superior to that of the American Joint Committee on Cancer staging, i.e. 0.64 (95% CI 0.62-0.66; p < 0.001). The 5-year DSS and median DSS time for the low-risk group were significantly greater than those for the high-risk group (p < 0.001). CONCLUSION: Our nomogram reliably and accurately predicted DSS in patients with non-metastatic ampullary carcinoma after surgery. This model may help clinicians in their decision making.

A Prognostic Nomogram for Disease-Specific Survival in Patients with Pancreatic Ductal Adenocarcinoma of the Head of the Pancreas Following Pancreaticoduodenectomy.

BACKGROUND This study developed and validated a nomogram to predict patient prognosis for pancreatic ductal adenocarcinoma (PDAC) of the head of the pancreas following pancreaticoduodenectomy. MATERIAL AND METHODS Retrospective data were obtained from 4,383 patients with PDAC of the head of the pancreas who underwent pancreaticoduodenectomy between 2004-2013 from 11 Registries Research Data of the Surveillance, Epidemiology,and End Results (SEER) database. Cox proportional hazards model was used to identify independent risk factors. The predictive accuracy of the nomogram was determined by the concordance index (C-index) and calibration curve. The results were externally validated by comparison with data from 1,743 patients from 7 other Registries Research Data. RESULTS Of the 4,383 patients in the training dataset, median disease-specific survival (DSS) was 17.0 months (range, 1.0-131 months), and postoperative 1-year, 3-year, and 5-year DSS rates were 70.3%, 26.1%, and 16.8%, respectively. Multivariate analysis showed that patient sex, age, tumor grade, regional lymph nodes examined, positive regional lymph nodes, tumor size, extent of local invasion, and tumor metastases were independent risk factors for DSS. The C-index of the internal validation dataset for prediction of DSS was 0.64 (95% CI, 0.63-0.65), which was superior to the American Joint Committee on Cancer (AJCC) staging, 0.57 (95% CI, 0.56-0.58) (P<0.001). The 5-year DSS rates and median DSS time for patients in the low-risk group were significantly greater compared with high-risk group (P<0.001). CONCLUSIONS A validated prognostic disease-specific nomogram for patient survival in PDAC of the head of the pancreas following pancreaticoduodenectomy was developed.