scholarly journals External validation of three nomograms predicting survival using an international cohort of patients with resected pancreatic head ductal adenocarcinoma

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
M Schneider ◽  
I Labgaa ◽  
D Vrochides ◽  
A Zerbi ◽  
G Nappo ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Sensitivity And Specificity ◽  
Goodness Of Fit ◽  
Neoadjuvant Treatment ◽  
Pancreatic Head ◽  
Tumor Grade ◽  
Ductal Adenocarcinoma ◽  
Youden Index ◽  
Predictive Values ◽  
Kaplan Meier

Abstract Objective Lymph node ratio (LNR, positive lymph nodes/collected lymph nodes during surgery) was identified as an important prognostic factor of survival in resected pancreatic cancer. Several nomograms based on LNR were recently proposed to predict survival after pancreatoduodenectomy (PD). The present study aimed to externally validate 3 published nomograms using an international cohort. Methods Consecutive patients with ductal adenocarcinoma of the pancreatic head who underwent PD without neoadjuvant treatment from 6 tertiary centers in Europe and the USA were retrospectively collected from 2000 to 2017. Patients with metastases at diagnosis, R2 resection, missing data regarding LNR, and who died within 90 postoperative days were excluded. The 3 selected nomograms were the updated Amsterdam nomogram (including LNR, adjuvant therapy, margin status, and tumor grade), the nomogram by Pu et al. (including LNR, age, tumor grade, and T stage) and the nomogram by Li et al. (including LNR, age, tumor location, grade, size, and TNM stage). Overall survivals (OS) were calculated using Kaplan-Meier method. For the validation, calibration (Hosmer-Lemeshow test), discrimination capacity (ROC curves for 3-year OS), and clinical utility (sensitivity and specificity at the value of Youden index) were assessed. Results After exclusion of 95 patients with metastases, R2 resection, and who died within 90 postoperative days, 1167 patients were included. Median OS of the entire cohort was 23 months (95% confidence interval: 21-24). For the 3 nomograms, Kaplan-Meier curves showed significant diminution of OS with increasing scores (p < 0.01 for the 3 nomograms). All nomograms showed good calibration (non significant Hosmer-Lemeshow goodness-of-fit tests). For the updated Amsterdam nomogram, the area under the ROC curve (AUROC) for 3-year OS was 0.66. Sensitivity and specificity were 73% and 50%. Regarding the nomogram by Pu et al., the AUROC was 0.67. Sensitivity and specificity were 65% and 60%. For the nomogram by Li et al., the AUROC was 0.67, while sensitivity and specificity were 56% and 71%. Conclusion The 3 selected nomograms were validated using an external international cohort and displayed interesting and comparable predictive values. Those nomograms may be used in clinical practice to estimate survival after PD for ductal adenocarcinoma.

scholarly journals Molecular targets for diagnostic and intraoperative imaging of pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX treatment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
F. A. Vuijk ◽  
L. D. A. N. de Muynck ◽  
L. C. Franken ◽  
O. R. Busch ◽  
J. W. Wilmink ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Lymph Nodes ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Metastatic Lymph Node ◽  
Imaging Techniques ◽  
Intraoperative Imaging ◽  
Neoadjuvant Treatment ◽  
Radical Resection ◽  
Ductal Adenocarcinoma ◽  
Primary Tumors

Abstract Neoadjuvant systemic treatment is increasingly being integrated in the standard treatment of pancreatic ductal adenocarcinoma (PDAC) patients to improve oncological outcomes. Current available imaging techniques remain unreliable in assessing response to therapies, as they cannot distinguish between (vital) tumor tissue and therapy induced fibrosis (TIF). Consequently, resections with tumor positive margins and subsequent early post-operative recurrences occur and patients eligible for potential radical resection could be missed. To optimize patient selection and monitor results of neoadjuvant treatment, PDAC-specific diagnostic and intraoperative molecular imaging methods are required. This study aims to evaluate molecular imaging targets for PDAC after neoadjuvant FOLFIRINOX treatment. Expression of integrin αvβ6, carcinoembryonic antigen cell adhesion molecule 5 (CEACAM5), mesothelin, prostate-specific membrane antigen (PSMA), urokinase-type plasminogen activator receptor, fibroblast activating receptor, integrin α5 subunit and epidermal growth factor receptor was evaluated using immunohistochemistry. Immunoreactivity was determined using the semiquantitative H-score. Resection specimens from patients after neoadjuvant FOLFIRINOX treatment containing PDAC (n = 32), tumor associated pancreatitis (TAP) and TIF (n = 15), normal pancreas parenchyma (NPP) (n = 32) and tumor positive (n = 24) and negative (n = 56) lymph nodes were included. Integrin αvβ6, CEACAM5, mesothelin and PSMA stainings showed significantly higher expression in PDAC compared to TAP and NPP. No expression of αvβ6, CEACAM5 and mesothelin was observed in TIF. Integrin αvβ6 and CEACAM5 allow for accurate metastatic lymph node detection. Targeting integrin αvβ6, CEA, mesothelin and PSMA has the potential to distinguish vital PDAC from fibrotic tissue after neoadjuvant FOLFIRINOX treatment. Integrin αvβ6 and CEACAM5 detect primary tumors and tumor positive lymph nodes.

scholarly journals Expression of p53, p16 and Ki67 proteins in ductal adenocarcinoma of the pancreatic head and their relation with survival and cell differentiation

2010 ◽  
Vol 8 (4) ◽  
pp. 444-448
Author(s):  
Mário Benjamin Goitia-Durán ◽  
Marcelo Moura Linhares ◽  
Ricardo Artigiani Neto ◽  
Franz Robert Apodaca-Torrez ◽  
Edson José Lobo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Median Survival ◽  
Pancreatic Head ◽  
Tumor Grade ◽  
Labeling Index ◽  
Ductal Adenocarcinoma ◽  
Tumor Type ◽  
Immunohistochemical Expression ◽  
Ki 67 ◽  
Focal Expression

ABSTRACT Objective: To determine the expression of p53, p16 and Ki-67 and its relevance in survival and cell differentiation. Methods: Fifteen duodenopancreatectomized patients were included. Immunohistochemical expression of p53, p16 and Ki-67 was determined in paraffin embedded tumor blocks. The relation of these expressions with different variables was studied. Results: Ninety-three per cent of tumors showed expression of p53 and p16. Ki-67 was expressed in 86.66% of tumors (labeling index – LI 11.91 ± 9.47). The presence of combined alterations was not related to significant differences in tumor type, stage or survival; similar results were obtained analyzing isolated expressions. When groups of p16 and Ki-67 expressions where created, the median survival was not significant. However, there was a slightly better survival in patients with focal expression of p16 (median survival 20.75 versus 14.34), when compared to patients with diffuse expression. Conclusion: The overexpression of p53, p16 and Ki-67 was not related to survival or tumor grade, when comparing isolated or combined expressions.

scholarly journals Development and Validation of a Nomogram to Predict Survival in Pancreatic Head Ductal Adenocarcinoma After Pancreaticoduodenectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Feng Peng ◽  
Tingting Qin ◽  
Min Wang ◽  
Hebin Wang ◽  
Chao Dang ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Cox Regression ◽  
External Validation ◽  
Pancreatic Head ◽  
Tnm Stage ◽  
University Hospital ◽  
Ductal Adenocarcinoma ◽  
Kaplan Meier ◽  
Staging Systems ◽  
Differentiation Degree

BackgroundPancreatic head ductal adenocarcinoma (PHDAC) patients with the same tumor-node-metastasis (TNM) stage may share different outcomes after pancreaticoduodenectomy (PD). Therefore, a novel method to identify patients with poor prognosis after PD is urgently needed. We aimed to develop a nomogram to estimate survival in PHDAC after PD.MethodsTo estimate survival after PD, a nomogram was developed using the Tongji Pancreatic cancer cohort comprising 355 PHDAC patients who underwent PD. The nomogram was validated under the same conditions in another cohort (N = 161) from the National Taiwan University Hospital. Prognostic factors were assessed using LASSO and multivariate Cox regression models. The nomogram was internally validated using bootstrap resampling and then externally validated. Performance was assessed using concordance index (c-index) and calibration curve. Clinical utility was evaluated using decision curve analysis (DCA), X-tile program, and Kaplan–Meier curve in both training and validation cohorts.ResultsOverall, the median follow-up duration was 32.17 months, with 199 deaths (64.82%) in the training cohort. Variables included in the nomogram were age, preoperative CA 19-9 levels, adjuvant chemotherapy, Tongji classification, T stage, N stage, and differentiation degree. Harrell’s c-indices in the internal and external validation cohorts were 0.79 (95% confidence interval [CI], 0.76–0.82) and 0.83 (95% CI, 0.78–0.87), respectively, which were higher than those in other staging systems. DCA showed better clinical utility.ConclusionThe nomogram was better than TNM stage and Tongji classification in predicting PHDAC patients’ prognosis and may improve prognosis-based selection of patients who would benefit from PD.

scholarly journals Prognostic Estimator of Survival for Patients with Localized and Extended Pancreatic Ductal Adenocarcinoma

2013 ◽  
Vol 12 ◽  
pp. CIN.S11496 ◽  
Author(s):  
Michael X. Gleason ◽  
Tengiz Mdzinarishvili ◽  
Chandrakanth Are ◽  
Aaron Sasson ◽  
Alexander Sherman ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Tumor Grade ◽  
Ductal Adenocarcinoma ◽  
Model Parameters ◽  
Web Based ◽  
T Stage ◽  
Kaplan Meier ◽  
Group A

The 18,352 pancreatic ductal adenocarcinoma (PDAC) cases from the Surveillance Epidemiology and End Results (SEER) database were analyzed using the Kaplan-Meier method for the following variables: race, gender, marital status, year of diagnosis, age at diagnosis, pancreatic subsite, T-stage, N-stage, M-stage, tumor size, tumor grade, performed surgery, and radiation therapy. Because the T-stage variable did not satisfy the proportional hazards assumption, the cases were divided into cases with T1- and T2-stages (localized tumor) and cases with T3- and T4-stages (extended tumor). For estimating survival and conditional survival probabilities in each group, a multivariate Cox regression model adjusted for the remaining covariates was developed. Testing the reproducibility of model parameters and generalizability of these models showed that the models are well calibrated and have concordance indexes equal to 0.702 and 0.712, respectively. Based on these models, a prognostic estimator of survival for patients diagnosed with PDAC was developed and implemented as a computerized web-based tool.

scholarly journals Pre-Operative MDCT Staging Predicts Mesopancreatic Fat Infiltration—A Novel Marker for Neoadjuvant Treatment?

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4361
Author(s):  
Sami-Alexander Safi ◽  
Lena Haeberle ◽  
Sophie Heuveldop ◽  
Patric Kroepil ◽  
Stephen Fung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Neoadjuvant Treatment ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
Tumor Diameter ◽  
Radiographic Findings ◽  
Fat Infiltration ◽  
Extent Of Surgery ◽  
Fat Stranding

Summary: The rates of microscopic incomplete resections (R1/R0CRM+) in patients receiving standard pancreaticoduodenectomy for PDAC remain very high. One reason may be the reported high rates of mesopancreatic fat infiltration. In this large cohort study, we used available histopathological specimens of the retropancreatic fat and correlated high resolution CT-scans with the microscopic tumor infiltration of this area. We found that preoperative MDCT scans are suitable to detect cancerous infiltration of this mesopancreatic tissue and this, in turn, was a significant indicator for both incomplete surgical resection (R1/R0CRM+) and worse overall survival. These findings indicate that a neoadjuvant treatment in PDAC patients with CT-morphologically positive infiltration of the mesopancreas may result in better local control and thus improved resection rates. Mesopancreatic fat stranding should thus be considered in the decision for neoadjuvant therapy. Background: Due to the persistently high rates of R1 resections, neoadjuvant treatment and mesopancreatic excision (MPE) for ductal adenocarcinoma of the pancreatic head (hPDAC) have recently become a topic of interest. While radiographic cut-off for borderline resectability has been described, the necessary extent of surgery has not been established. It has not yet been elucidated whether pre-operative multi-detector computed tomography (MDCT) staging reliably predicts local mesopancreatic (MP) fat infiltration and tumor extension. Methods: Two hundred and forty two hPDAC patients that underwent MPE were analyzed. Radiographic re-evaluation was performed on (1) mesopancreatic fat stranding (MPS) and stranding to peripancreatic vessels, as well as (2) tumor diameter and anatomy, including contact to peripancreatic vessels (SMA, GDA, CHA, PV, SMV). Routinely resected mesopancreatic and perivascular (SMA and PV/SMV) tissue was histopathologically re-analyzed and histopathology correlated with radiographic findings. A logistic regression of survival was performed. Results: MDCT-predicted tumor diameter correlated with pathological T-stage, whereas presumed tumor contact and fat stranding to SMA and PV/SMV predicted and correlated with histological cancerous infiltration. Importantly, mesopancreatic fat stranding predicted MP cancerous infiltration. Positive MP infiltration was evident in over 78%. MPS and higher CT-predicted tumor diameter correlated with higher R1 resection rates. Patients with positive MP stranding had a significantly worse overall survival (p = 0.023). Conclusions: A detailed preoperative radiographic assessment can predict mesopancreatic infiltration and tumor morphology and should influence the decision for primary surgery, as well as the extent of surgery. To increase the rate of R0CRM− resections, MPS should be considered in the decision for neoadjuvant therapy.

scholarly journals The value of serum progesterone level on day of human chorionic gonadotrophin administration / metaphase II oocyte ratio in predicting IVF/ICSI outcome in patients with normal ovarian reserve

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ahmad Mahran ◽  
Mohammed Khairy ◽  
Reham Elkhateeb ◽  
Abdel Rahman Hegazy ◽  
Ayman Abdelmeged ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Ovarian Response ◽  
Pregnancy Rates ◽  
Clinical Pregnancy ◽  
Progesterone Level ◽  
Receiver Operating Curve ◽  
Serum Progesterone ◽  
Predictive Values ◽  
Significant Difference ◽  
Assisted Reproduction Treatment

Abstract Background The clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART. Material & methods Two hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured. Results P/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn’t whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5). Conclusions In patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

scholarly journals Predictors of Central Compartment Involvement in Patients with Positive Lateral Cervical Lymph Nodes according to Clinical and/or Ultrasound Evaluation

2021 ◽  
Vol 10 (15) ◽  
pp. 3407
Author(s):  
Giuseppa Graceffa ◽  
Giuseppina Orlando ◽  
Gianfranco Cocorullo ◽  
Sergio Mazzola ◽  
Irene Vitale ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Univariate Analysis ◽  
Roc Curves ◽  
Central Compartment ◽  
Central Neck Dissection ◽  
Level Of Evidence ◽  
Cervical Lymph Nodes ◽  
Kaplan Meier ◽  
Ultrasound Evaluation ◽  
Central Lymph

Lymph node neck metastases are frequent in papillary thyroid carcinoma (PTC). Current guidelines state, on a weak level of evidence, that level VI dissection is mandatory in the presence of latero-cervical metastases. The aim of our study is to evaluate predictive factors for the absence of level VI involvement despite the presence of metastases to the lateral cervical stations in PTC. Eighty-eight patients operated for PTC with level II–V metastases were retrospectively enrolled in the study. Demographics, thyroid function, autoimmunity, nodule size and site, cancer variant, multifocality, Bethesda and EU-TIRADS, number of central and lateral lymph nodes removed, number of positive lymph nodes and outcome were recorded. At univariate analysis, PTC location and number of positive lateral lymph nodes were risk criteria for failure to cure. ROC curves demonstrated the association of the number of positive lateral lymph nodes and failure to cure. On multivariate analysis, the protective factors were PTC located in lobe center and number of positive lateral lymph nodes < 4. Kaplan–Meier curves confirmed the absence of central lymph nodes as a positive prognostic factor. In the selected cases, Central Neck Dissection (CND) could be avoided even in the presence of positive Lateralcervical Lymph Nodes (LLN+).

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

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