BackgroundNeoadjuvant chemotherapy (NAC) has become the standard of care for resectable esophageal squamous cell carcinoma (ESCC) which is one of the most lethal cancers, to improve resectability and prognosis. On this basis, to provide individually optimized therapy for ESCC, a minimally-invasive biomarker for response to NAC is strongly desired. This study aimed to identify the miRNA signature in serum specimens taken from ESCC patients undergoing NAC through genome-wide microarray technology.MethodsComprehensive miRNA-expression profiles of serum specimens from ESCC patients before initial treatment were analyzed using microarray. A qPCR assay was performed to test the robustness of identified serum-based miRNA signature for discriminating response to NAC with serum specimens taken from 100 ESCC cases undergoing NAC.ResultsWe prioritized 62 miRNAs differentially expressed between responders and non-responders (absolute log2 fold change > 1.0, corresponding P < 0.05) and from the 62 miRNAs, we selected the miR-23a-5p, miR-193b-5p, and miR-873-3p, which were highly expressed in non-responders. Following qPCR analysis indicated the expression of miR-193b-5p and miR-873-3p in serum specimens were significantly higher in non-responders among three selected miRNAs (P = 0.004 and 0.001, respectively). Subsequently, we developed 2-miR-model (miR-193b-5p and miR-873-3p), 3-miR-model, and 2-miR + lymphatic invasion (ly) model based on logistic regression analysis, which achieved the better area under the receiver operating characteristic curves than those of single miRNAs as 2-miR-model, 0.70 (95% CI 0.57 to 0.82); 3-miR-model, 0.70 (95% CI 0.57 to 0.83); and 2-miR + ly, 0.73 (95% CI 0.60–0.86), respectively. Furthermore, we compared the detective power of the combined model: 2-miR + ly for discriminating non-responders to NAC, to other pretreatment clinical features. Consequently, 2-miR + ly model was superior to serum SCC antigen with great significance (P = 0.01) and to ly, and clinical T stage with marginal significance (P = 0.18, 0.07, respectively).ConclusionsCollectively, we demonstrated that the potential of a multi-miRNA biomarker for identifying NAC response in ESCC is realistic, and can be used in the clinic with the further validation.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1762-6) contains supplementary material, which is available to authorized users.
Background: This study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines.Methods: 369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified.Results: Based on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status 2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 500 U/ml was not (HR: 1.23, P = 0.190). Conclusion:The IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria.
In a naturally deposited soil foundation subject to embankment loading, a delayed settlement can often be observed after the embankment's completion, sometimes also showing acceleration over time. Frequently in such cases the soil exhibits an increase rather than a dissipation of excess pore pressure in some of its parts, a phenomenon which cannot be explained by conventional elasto-plastic consolidation theory. In this paper the possible mechanism for this kind of delayed settlement is investigated numerically using a soil-water coupled elasto-plastic computation under plane strain conditions. It is assumed that the soil section contains a medium dense sand layer and highly structured clay layers. A Super /subloading Yield Surface Cam-clay model is used to describe the elasto-plastic behavior of both the sand and the clay with respect to soil structure, overconsolidation and anisotropy. It is found that the delayed settlement behavior occurs under a certain constant embankment load, and persists over a period of 40 years, with increases in the settlement rate accompanied by both dissipation and a rise in excess pore pressure. The cause of this is the softening that co-occurs with the plastic compression of the soil skeleton. In other words, consolidation settlement can be considered as an example of "progressive consolidation with decay of structure". Some typical characteristics of this delayed settlement behavior are also numerically examined with reference to the height and weight of the embankment, and to soil improvements using sand drains. When the embankment is much lower, the foundation does not undergo delayed consolidation, and when it is higher, the foundation becomes subject to circular slip failure. Soil improvement with sand drains can effectively shorten the length of time up to final settlement.
NAT for PC could aggravate nutritional status and hamper its postoperative recovery. Furthermore, malnutrition might decrease tolerance of NAT. These findings suggest the importance of nutritional support for patients with NAT in PC.
Aim This study aimed to assess the clinical utility of preoperative evaluation of liver fibrosis using platelet–albumin–bilirubin (PALBI) grade, Fibrosis‐4 index (FIB‐4), and aspartate transaminase‐to‐platelet ratio index (APRI) for hepatocellular carcinoma (HCC) patients and explore the clinical impact of these models with regard to perioperative risks and HCC prognosis. Methods Between January 2003 and December 2018, 305 consecutive patients who underwent hepatectomy for HCC were enrolled. Results The APRI showed the most robust diagnostic performance through each fibrosis stage among three models (PALBI, FIB‐4, and APRI): fibrosis stage 3 (f3), area under the curve [AUC] = 0.55, 0.72, and 0.76; and f4, AUC = 0.51, 0.71, and 0.76, respectively). In addition, survival analysis revealed that all three models were significantly associated with HCC prognosis. PALBI (grade 1 vs. 2, 3): recurrence‐free survival (RFS): median survival time (MST), 34 vs. 17 months, 0.007; overall survival (OS): MST, 115 vs. 68, 0.02. FIB‐4 (grade 1, 2 vs. 3): RFS: MST, 34 vs. 22, 0.004, OS: MST, 120 vs. 63, 0.0001. APRI (grade 1, 2 vs. 3), RFS: MST, 30 vs. 20, 0.0005; OS: MST, 107 vs. 55, 0.0003. Among three scoring systems, only PALBI grade was significantly associated with both operative time (median, 303 vs. 340 min, 0.01) and intraoperative blood loss (median, 581 vs. 859 mL, 0.03). Conclusions This study showed robust performances of selected liver reserve and fibrosis models to predict HCC prognosis. Of them, PALBI might be used for assessing perioperative risks for hepatectomy for HCC.
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