Yize Mao

Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma

We investigated whether elevated neutrophil-to-lymphocyte ratio (NLR) was associated with poor anti-tumor immunity and prognosis in patients with intrahepatic cholangiocarcinoma (ICC). Clinicopathologic data of 102 patients with ICC who underwent hepatectomy was retrospectively analyzed. The Kaplan-Meier method and Cox regression model were used to analyze the survival and prognosis. The percentage of overall lymphocytes, T cells and CD8+ T cells in the high NLR group was lower than that in the low NLR group. The percentage of PD-1+CD4+ and PD-1+CD8+ T cells was higher and the percentage of IFN-γ+CD4+ and IFN-γ+CD8+ T cells was lower in the high NLR group than that in the low NLR group (p = 0.045, p = 0.008; p = 0.012, p = 0.006). Density of tumor-infiltrating CD3+ T cells in the high NLR group was lower than that in the low NLR group (p < 0.001). Elevated NLR was an independent predictor for poor overall survival (OS; p = 0.035) and recurrence-free survival (RFS; p = 0.008). These results indicate that elevated NLR is associated with poor anti-tumor immunity and could be a poor biomarker for prognosis in patients with ICC.

Imaging features predict prognosis of patients with combined hepatocellular-cholangiocarcinoma

AIM To evaluate the prognostic value of imaging patterns in combined hepatocellular-cholangiocarcinoma. MATERIALS AND METHODS A total of 36 patients with histopathologically confirmed combined hepatocellular-cholangiocarcinoma were enrolled. Pretreatment imaging was conducted to evaluate the tumour enhancement patterns, based on which the disease was classified as two subtypes: radiographic hepatocellular carcinoma-dominant (n=26) and radiographic cholangiocarcinoma-dominant (n=10). Moreover, based on the proportion of components, all combined hepatocellular-cholangiocarcinoma cases were divided into histopathological hepatocellular carcinoma-dominant (n=26) or histopathological cholangiocarcinoma-dominant (n=10). The Kaplan-Meier method was used to compare patient outcome between the two subtypes of each classification. Univariate Cox regression analysis were employed to evaluate the prognostic relevance of the imaging and histopathological classification. RESULTS Consistency between histopathological and imaging classification was not high. Only 66.7% of patients had consistent classification. Moreover, the median overall survival of the radiographic cholangiocarcinoma-dominant and radiographic hepatocellular carcinoma-dominant population was 15.03 and 40.4 months, respectively (p=0.012); however, no significant difference was observed between histopathological type, with median overall survival being 32.07 and 40.4 months in the histopathological cholangiocarcinoma-dominant group and histopathological hepatocellular carcinoma-dominant group, respectively (p=0.784). CONCLUSION There was an association between imaging patterns and overall survival in combined hepatocellular-cholangiocarcinoma. Postoperative re-evaluation of imaging patterns could help to assess patient outcome.

Intravoxel incoherent motion magnetic resonance imaging for differentiating metastatic and non-metastatic lymph nodes in pancreatic ductal adenocarcinoma

ObjectivesTo evaluate the diagnostic potential of intravoxel incoherent motion (IVIM) DWI for differentiating metastatic and non-metastatic lymph node stations (LNS) in pancreatic ductal adenocarcinoma (PDAC).Methods59 LNS histologically diagnosed following surgical resection from 15 patients were included. IVIM DWI with 12 b values was added to the standard MRI protocol. Evaluation of parameters was performed pre-operatively and included the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f). Diagnostic performance of ADC, D, D* and f for differentiating between metastatic and non-metastatic LNS was evaluated using ROC analysis.ResultsMetastatic LNS had significantly lower D, D*, f and ADC values than the non-metastatic LNS (p< 0.01). The best diagnostic performance was found in D, with an area under the ROC curve of 0.979, while the area under the ROC curve values of D*, f and ADC were 0.867, 0.855 and 0.940, respectively. The optimal cut-off values for distinguishing metastatic and non-metastatic lymph nodes were D = 1.180 × 10−3 mm2/s; D* = 14.750 × 10−3 mm2/s, f = 20.65 %, and ADC = 1.390 × 10−3 mm2/s.ConclusionIVIM DWI is useful for differentiating between metastatic and non-metastatic LNS in PDAC.Key Points• IVIM DWI is feasible for diagnosing LN metastasis in PDAC.• Metastatic LNS has lower D, D*, f, ADC values than non-metastatic LNS.• D-value from IVIM model has best diagnostic performance, followed by ADC value.• D* has the lowest AUC value.

PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation

Cholangiocarcinoma (CCA) is a highly malignant tumor with resistance to radiotherapy alone. Olaparib, a highly potent poly(ADP‐ribose) polymerase (PARP) inhibitor, has been shown to sensitize many types of tumor to radiotherapy. However, the effect of olaparib, either as monotherapy or as combination therapy with radiotherapy, on CCA is not known, and our study aimed to explore this. To assess radiosensitization in three CCA cell lines (QBC939, HuH28 and TFK‐1), viability and clonogenic assays were conducted. The absorbed radiation doses were 0 Gy, 2 Gy, 4 Gy, and 6 Gy; olaparib concentrations were 0 nmol/L, 1 nmol/L, 10 nmol/L, 100 nmol/L, 1000 nmol/L, 2500 nmol/L, 5000 nmol/L and 10 000 nmol/L. The mechanism of olaparib radiosensitization was explored by Western blotting. Immunofluorescence staining and flow cytometry were conducted to explore DNA damage and apoptosis. The radiosensitivity of CCA cells was enhanced by olaparib, which alone had little effect on the CCA cell lines without BRCA mutations. The degree of radiosensitization increased with increasing doses of olaparib by viability and clonogenic assays in vitro. Olaparib was able to enhance the effect of radiation by inhibiting PARP1, inducing DNA lesions and apoptosis. These findings emphasize the role of olaparib in the radiosensitization of CCA cells.

Nomograms predict long-term survival for patients with periampullary adenocarcinoma after pancreatoduodenectomy

BackgroundThe prognosis of patients with periampullary adenocarcinoma after pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this study was to develop a nomogram to predict individual risk of overall survival (OS) and progression-free survival (PFS) in patients with periampullary adenocarcinoma after pancreatoduodenectomy.MethodsA total of 205 patients with periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for predicting OS and PFS were established, and the predictive accuracy was measured by the concordance index (Cindex) and calibration plots.ResultsLymph node ratio (LNR), carbohydrate antigen 19–9 (CA19–9) and anatomical location were incorporated into the nomogram for OS prediction and LNR, CA19–9; anatomical location and tumor differentiation were incorporated into the nomogram for PFS prediction. All calibration plots for the probability of OS and PFS fit well. The Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68, respectively. The OS and PFS survival times were stratified significantly using the nomogram-predicted survival probabilities.ConclusionsThe present nomograms for OS and PFS prediction can provide valuable information for tailored decision-making for patients with periampullary adenocarcinoma after pancreatoduodenectomy.

Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma

The neutrophil-to-lymphocyte ratio (NLR) has been regarded as a prognostic factor in various types of cancer. The present study aimed to identify the association between NLR and combined hepatocellular cholangiocarcinoma (cHCC-CC) in patients who underwent surgical resection. The present study retrospectively reviewed 59 patients who were diagnosed with cHCC-CC and treated with surgical resection between January 2000 and October 2014 at the Department of Hepatobiliary and Pancreatic Surgery at Sun Yat-sen University Cancer Center (Guangzhou, China). The patients were divided into two groups: NLR≤2.75 and NLR>2.75. Patients with stage I and II or stage III and IV disease were classified into early- and advanced-stage groups, respectively, according to the Tumor-Node-Metastasis (TNM) staging system. Overall survival time (OS) was estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to evaluate the prognostic value of NLR. The NLR value was significantly higher in the HCC advanced-stage group compared with that in the HCC early-stage group according to the TNM staging system (3.19 vs. 2.00; P=0.001). The median survival time was 83.6 months in the NLR≤2.75 group and 15 months in the NLR>2.75 group (P=0.004). Upon multivariate analysis, NLR>2.75 was an independent prognostic factor for poor cHCC-CC outcomes. Overall, the easily evaluated pre-treatment NLR may be an independent prognostic factor for patients with cHCC-CC treated by surgical resection.

The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study

BackgroundCombined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection.MethodsThe data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)—dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)—dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves.ResultsThe 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores.ConclusionsHCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice.

Surgical management of periampullary adenocarcinoma: Defining an optimal prognostic lymph node stratification schema

Background: Lymph node (LN) metastasis is a strong predictor of unfavorable prognosis for patients with periampullary adenocarcinoma after surgical resection. We sought to assess the prognostic performance of several LN staging systems, including American Joint Committee on Cancer (AJCC)/ International Union Against Cancer (7th edition) N stage, the total number of LN (TLN), the number of metastatic LN (MLN), the lymph node ratio (LNR) and the log odds of MLNs (LODDS), in patients with periampullary adenocarcinoma after surgical resection and identify the optional LN staging system to accurately stratify patients with different prognoses. Methods: We retrospectively analyzed 205 patients with periampullary adenocarcinoma after surgical resection. The predictive effects of several LN staging systems on overall survival (OS) and progression free survival (PFS) for all included patients and patients with more than 12 TLNs examined were evaluated and compared using the time-dependent receive operating characteristic (ROC) curve and decision curve analysis (DCA), respectively. Results: Eighty-nine patients (43.4%) had LN metastasis and their survival was not significantly decreased compared with patients without LN metastasis. LODDS and LNR were able to stratify patients into various subgroups with significant differences of both OS and PFS. When assessed using ROC curve and DCA, LODDS outperformed LNR and other LN staging systems in predicting OS and PFS. In addition, when analyzed in patients with more than 12 TLNs examined, LODDS had a higher value of area under ROC curve (AUC) and showed better performance of DCA. Conclusion: LODDS performs better than other LN staging systems in predicting OS and PFS for patients with periampullary adenocarcinoma after surgical resection. Adequate LN dissection is necessary for curative surgery, as well as to achieve a more accurate staging of the disease and a more precise prediction of survival for these patients.

Early osteosclerotic changes predict chemotherapy response in non-small-cell lung cancer patients with bone metastases

ObjectivesTo explore the relationship between osteosclerotic changes and chemotherapy response in non-small-cell lung cancer (NSCLC) patients with bone metastases (BM).MethodsFifty-two NSCLC patients with BM were enrolled from 1 January 2010–31 June 2015 and divided into two groups based on their CT features: an osteosclerotic change (OC) group and a no-osteosclerotic change (NOC) group. The disease control rate (DCR) was evaluated, and progression-free survival (PFS) was analysed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were performed to analyse the factors that could affect PFS.ResultsOsteosclerotic changes were observed in 35/52 patients. The median interval when osteosclerotic changes occurred was 2 months (range 1–3 months) after chemotherapy. The OC group had a significantly higher 3-month DCR than the NOC group (p < 0.001). The OC group had a higher 1-year PFS rate than the NOC group (1-year PFS: 74.9% vs. 30.2%, p < 0.001). Univariate Cox regression analysis indicated that pathological subtype (HR = 4.419; 95% CI = 1.635–11.941, p = 0.003) and osteosclerotic changes (HR = 0.199; 95% CI = 0.083–0.477, p < 0.001) were significant predictors of PFS.ConclusionEarly osteosclerotic changes predict chemotherapy response in NSCLC patients with BM.Key Points• Osteosclerotic changes were prevalent CT features after chemotherapy in NSCLC patients.• Osteosclerotic changes were positively related to increased 3-month DCR.• Osteosclerotic changes were positively related to increased 1-year PFS rate.