Changes in CRP and CA19-9 during Preoperative Oncological Therapy Predict Postoperative Survival in Pancreatic Ductal Adenocarcinoma

Oncology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Anna Maria Nurmi ◽  
Harri Mustonen ◽  
Caj Haglund ◽  
Hanna Seppänen
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Median Survival ◽  
Postoperative Outcome ◽  
University Hospital ◽  
Postoperative Survival ◽  
Ductal Adenocarcinoma ◽  
Preoperative Treatment ◽  
Borderline Resectable ◽  
Oncological Therapy ◽  
The Impact

<b><i>Introduction:</i></b> Tumor and systemic inflammatory markers predict survival. This retrospective study aimed to explore the changes in CRP, CA19-9, and other routine laboratory tests during preoperative oncological therapy as prognostic factors in pancreatic ductal adenocarcinoma (PDAC). <b><i>Methods:</i></b> Between 2000 and 2016, 68 borderline resectable PDAC patients received preoperative oncological therapy and underwent subsequent surgery at Helsinki University Hospital, Finland. We investigated changes in CRP, CA19-9, CEA, albumin, leukocytes, bilirubin, and platelets and examined the impact on survival. <b><i>Results:</i></b> In the multivariate analysis, CRP remaining at ≥3 mg/L after preoperative oncological therapy predicted a poorer postoperative outcome when compared to CRP decreasing to or remaining at &#x3c;3 mg/L (hazard ratio [HR] 2.766, 95% confidence interval [CI]: 1.300–5.885, <i>p</i> = 0.008). Furthermore, a CA19-9 decrease &#x3e;90% during preoperative treatment predicted a favorable postoperative outcome (HR 0.297, 95% CI: 0.124–0.708, <i>p</i> = 0.006). In the Kaplan-Meier analysis, the median survival for patients with CRP remaining at &#x3c;3 mg/L was longer than among patients with an increased CRP level at ≥3 mg/L (42 months vs. 24 months, <i>p</i> = 0.001). Patients with a CA19-9 decrease &#x3e;90% or level normalization (to ≤37 kU/L) during preoperative treatment exhibited a median survival of 47 months; those with a 50–90% decrease, 15 months; and those with a &#x3c;50% decrease, 17 months (<i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> Changes in CRP and CA19-9 during preoperative oncological therapy predict postoperative survival.

scholarly journals Neoadjuvant Treatment for Borderline Resectable Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 36 (6) ◽  
pp. 455-461 ◽  
Author(s):  
Benedikt Kaufmann ◽  
Daniel Hartmann ◽  
Jan G. D’Haese ◽  
Pavel Stupakov ◽  
Dejan Radenkovic ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Neoadjuvant Treatment ◽  
Ductal Adenocarcinoma ◽  
Preoperative Treatment ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Treatment Regimens ◽  
Dismal Prognosis ◽  
First Choice

One of the main reasons for the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is its late diagnosis. At the time of presentation, only approximately 15–20% of all patients with PDAC are considered resectable and around 30% are considered borderline resectable. A surgical approach, which is the only curative option, is limited in borderline resectable patients by local involvement of surrounding structures. In borderline resectable pancreatic cancer (BRPC), neoadjuvant treatment regimens have been introduced with the rationale to downstage and downsize the tumor in order to enable resection and eliminate ­microscopic distant metastases. However, there are no official guidelines for the preoperative treatment of BRPC. In the majority of cases, patients are administered ­Gemcitabine-based or FOLFIRINOX-based chemotherapy regimens with or without radiation. Radiologic restaging after neoadjuvant therapy has to be judged with caution when it comes to predict tumor response and resectability, since inflammation induced by neoadjuvant therapy may mimic solid tumor. Patients who do not show any disease progression during neoadjuvant therapy should be offered surgical exploration, since a high percentage is likely to undergo resection with negative margins (R0) and, thus, achieve improved overall survival although imaging judged it unlikely. Despite the promising new approaches of neoadjuvant treatment regimens during the last 2 decades, surgery remains the first choice if the tumor appears to be primary resectable at the time of diagnosis. At present, there are no international guidelines regarding the preoperative treatment of BRPC. Therefore, in order to standardize and adjust neoadjuvant treatment in the future, new guidelines have to be determined on the basis of upcoming prospective randomized studies.

Retrospective determination of the correlation between the distance of tumor manifestation to peripancreatic arteries and overall survival in primary resected pancreatic ductal adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15745-e15745
Author(s):  
Uwe A Wittel ◽  
Michael Uhl ◽  
Frank Makowiec ◽  
Ulrich Theodor Hopt ◽  
Stefan Fichtner-Feigl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Survival ◽  
Average Distance ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Resection Margins ◽  
R0 Resection ◽  
Borderline Resectable ◽  
R1 Resection

e15745 Background: Current guidelines determine the resectability of PDAC by evaluating the contact of the tumor to peripancreatic vasculature. We wanted to evaluate the influence of this distance of the tumor to peripancreatic arteries on the overall survival of patients with primary resection of pancreatic ductal adenocarcinoma. Methods: Preoperative radiographs of 208 consecutive patients after distal pancreatectomy and/or pancreatoduodenectomy operated between 2007 and 2014 were included in the analysis. In reconstructions of CT and MRI data 90° planes to the centerline of the celiac trunc (CT), hepatic artery(HA) and superior mesenteric artery(SMA) were computed with Aquarius Intuition Viewer (V4.4.11, Terarecon). The closest distance between the tumor and the CT /HA and SMA was determined by an experienced pancreatic surgeon and radiologist independently and upon a deviation greater than 3 mm consent was reached by additional review in 33,2% (69/208) of the cases. Results: 176 CT and 32 MRI scans of 208 patients were evaluated. 2.4 % (5/208) of the radiographs were excluded due to insufficient quality. Average distance of the tumor to the CT/HA and SMA was 16.3 and 6.5 mm for PD and 12.7 and 11.0 mm for DP. Distance between the artery and the tumor did not influence the R0 resection rates (overall R0 > 1mm resection margin 64%) and median overall survival was 24.0 months after R0 resection and 13.5 months after R1 resection (log-rank test P < 0.05). Borderline resectable patients (n = 57) showed a median survival of 13.4 months, patients with their tumor 1-5mm distant to the closest artery (n = 65) and greater than 5 mm distance (n = 81) showed a median survival of 20.3 and 32.9 months respectively. Patients with 0-5 and greater than 5 mm distance between arteries and tumor showed a survival benefit from R0 resection (R0/R1 0-5mm 20.3/13.5 months; > 5mm 37.3/12.8 months) while R0 resected borderline resectable patients showed a similar survival than R1 resected patients (R0 12.7months, R1 15.1 months). Conclusions: The negative resection margins in borderline resectable patients not increase the survival when compared to R1 resected patients. Patients with primary R0 resection and initially large distance of the tumor to peripancreatic vasculature show a prolonged survival.

scholarly journals Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Taija Korpela ◽  
Ari Ristimäki ◽  
Marianne Udd ◽  
Tiina Vuorela ◽  
Harri Mustonen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Chronic Inflammation ◽  
Tumor Size ◽  
Combined Effect ◽  
University Hospital ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Curative Intent ◽  
Node Metastases ◽  
The Impact

Abstract Background Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). Methods Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. Results DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0–57.6 vs. 20.6 months, 95% CI 10.3–30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19–9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02–2.16], lymph node metastases N1–2 (HR 1.71, 95% CI 1.16–2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04–2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27–2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03–2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). Conclusions Our results indicate that the pancreatic stroma is associated with PDAC patients’ DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 40 (12) ◽  
pp. 7017-7023
Author(s):  
KOICHI TOMITA ◽  
SHIGETO OCHIAI ◽  
TAKAHIRO GUNJI ◽  
KOSUKE HIKITA ◽  
TOSHIMICHI KOBAYASHI ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Prognostic Significance ◽  
Postoperative Outcome ◽  
Plasma Fibrinogen ◽  
Ductal Adenocarcinoma ◽  
Albumin Ratio

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

2021 ◽  
pp. 000313482110111
Author(s):  
Weizheng Ren ◽  
Dimitrios Xourafas ◽  
Stanley W. Ashley ◽  
Thomas E. Clancy
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
Borderline Resectable ◽  
Stepwise Selection ◽  
R1 Resection ◽  
Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

scholarly journals MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma

Stresses ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 30-47
Author(s):  
Maria Mortoglou ◽  
David Wallace ◽  
Aleksandra Buha Buha Djordjevic ◽  
Vladimir Djordjevic ◽  
E. Damla Arisan ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Metabolic Stress ◽  
Resistance Mechanisms ◽  
Current Data ◽  
Cellular Damage ◽  
Ductal Adenocarcinoma ◽  
Aberrant Expression ◽  
Metabolic Alterations ◽  
Limited Effectiveness ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer (PCa) and is expected to be the second most common cause of cancer-associated deaths. The high mortality rate is due to the asymptomatic progression of the clinical features until the advanced stages of the disease and the limited effectiveness of the current therapeutics. Aberrant expression of several microRNAs (miRs/miRNAs) has been related to PDAC progression and thus they could be potential early diagnostic, prognostic, and/or therapeutic predictors for PDAC. miRs are small (18 to 24 nucleotides long) non-coding RNAs, which regulate the expression of key genes by targeting their 3′-untranslated mRNA region. Increased evidence has also suggested that the chemoresistance of PDAC cells is associated with metabolic alterations. Metabolic stress and the dysfunctionality of systems to compensate for the altered metabolic status of PDAC cells is the foundation for cellular damage. Current data have implicated multiple systems as hallmarks of PDAC development, such as glutamine redox imbalance, oxidative stress, and mitochondrial dysfunction. Hence, both the aberrant expression of miRs and dysregulation in metabolism can have unfavorable effects in several biological processes, such as apoptosis, cell proliferation, growth, survival, stress response, angiogenesis, chemoresistance, invasion, and migration. Therefore, due to these dismal statistics, it is crucial to develop beneficial therapeutic strategies based on an improved understanding of the biology of both miRs and metabolic mediators. This review focuses on miR-mediated pathways and therapeutic resistance mechanisms in PDAC and evaluates the impact of metabolic alterations in the progression of PDAC.

scholarly journals Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models

2020 ◽  
Author(s):  
S. Mahnaz ◽  
L. Das Roy ◽  
M. Bose ◽  
C. De ◽  
S. Nath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathways ◽  
Suppressor Cells ◽  
Ductal Adenocarcinoma ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Transmembrane Glycoprotein ◽  
The Impact

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.

P-P13 Long-term outcome after portal vein resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matched analysis

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
James Russell ◽  
Claire Stevens ◽  
Rahul Bhome ◽  
Dimitrios Karavias ◽  
Ali Arshad ◽  
...  
Keyword(s):  
Propensity Score ◽  
Portal Vein ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Perineural Invasion ◽  
Nodal Metastasis ◽  
Ductal Adenocarcinoma ◽  
Safe Procedure ◽  
Portal Vein Resection ◽  
Vein Resection ◽  
The Impact

Abstract Background Portal vein resection (PVR) with pancreaticoduodenectomy (PD) is often performed to achieve clear margins for patients with vascular involvement in pancreatic ductal adenocarcinoma (PDAC). However, there is evidence to suggest that patients undergoing PVR often have more advanced cancers, therefore the impact of PVR on survival and recurrence remains unclear. The aim of this study is to assess overall (OS) and recurrence free (RFS) survival in patients who underwent PVR during PD, with particular attention to margin positivity. Methods A retrospective analysis was performed on 638 patients who underwent PD during a 12-year period. Exclusion criteria included PD for non-PDAC tumours, neoadjuvant chemotherapy or intra-operative radiotherapy. 374 patients were included in the study (90 PVR and 284 non-PVR). Patient characteristics and histopathological factors associated with OS and RFS were then evaluated using univariate and multivariate Cox regression analyses. 270 patients (90 PVR and 180 non-PVR), were matched by propensity score based on perineural invasion, pT and pN staging. The Kaplan-Meier method was used to calculate survival and log-rank tests. Results Resection margin positivity was associated with shorter OS and RFS (p &lt; 0.0001), and the superior mesenteric vein (SMV) margin was the most significant risk factor for survival on competing risks analysis. Absent adjuvant chemotherapy, nodal metastasis and margin positivity were independent risk factors for OS and RFS on multivariate analysis. PVR was associated with higher intra-operative blood loss (p = 0.009), but was not associated with increased length of stay, complications or readmissions. PVR patients had increased pT staging, nodal metastasis and perineural invasion, however, there was no difference in OS (p = 0.551) or RFS (p = 0.256) between PVR and non-PVR after propensity matching. Conclusions Positive resection margins are associated with shorter survival times, and the SMV margin is the most significant prognostic indicator for overall survival and recurrence compared to other margins. PVR is a relatively safe procedure, however, it does not achieve the intended survival benefits of complete margin clearance. The impact on survival for margin positivity, particularly the SMV margin, and nodal metastasis should be considered when making decisions with regards to vein resection and adjuvant treatments.

Sign in / Sign up

Export Citation Format

Share Document