scholarly journals Elevated Serum Interleukin-8 Level Correlates with Cancer-Related Cachexia and Sarcopenia: An Indicator for Pancreatic Cancer Outcomes

2018 ◽  
Vol 7 (12) ◽  
pp. 502 ◽  
Author(s):  
Ya-Chin Hou ◽  
Chih-Jung Wang ◽  
Ying-Jui Chao ◽  
Hao-Yun Chen ◽  
Hao-Chen Wang ◽  
...  

Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was negatively correlated with total psoas area (TPA). IL-8 expression in tissue samples was also positively associated with weight loss. Furthermore, serum IL-8 level was an independent predictor of survival. In conclusion, elevated serum IL-8 level significantly correlates with CC and sarcopenia and can be used as a prognostic indicator in PC.

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenyu Li ◽  
Hongxia Wang ◽  
Jian Liu ◽  
Bing Chen ◽  
Guangping Li

Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.Methods. A total of 102 patients with sepsis were divided into survival group (n=60) and nonsurvival group (n=42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05).Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16267-e16267
Author(s):  
Elena Serrano ◽  
Elizabeth Inga Saavedra ◽  
Maria Padilla Vico ◽  
Eduardo Perdomo ◽  
Maria Teresa Cano Osuna ◽  
...  

e16267 Background: Venous thromboembolism (VTE) is a common complication in oncology patients. It has been reported that VTE increases morbidity and mortality in these patients. It’s prevalence in metastatic pancreatic cancer (mPC) ranges around 4-7.5% Preclinic studies suggest that the mutation of the KRAS oncogene (KRASm) is associated with a higher risk of VTE among patients with colorectal cancer. KRASm appears to increase the expression of tissue factor, a physiological trigger of coagulation that is found on the surface of tumor cells. This association has not been studied in mPC, where this mutation can be found in 90% of the cases. Our aim is to determine the prevalence and risk factors associated with VTE taking into consideration the status of KRAS. Methods: We conducted a retrospective study within a cohort of patients with mPC that had a determination of the KRAS status. These patients were treated at Medical Oncology between January 2017 and December 2020. We performed a descriptive and survival analysis of our sample. We also studied the prevalence of VTE among the. Results: Our study cohort was 88 patients (pts), 63 (61, 2%) men and 40 (38, 8%) women. The median age was 63 years (32-84). 19 pts (18, 4%) were KRAS wild type (KRASwt), 69 pts (67%) KRASm. There was no statistically significant difference in gender, age, performance status, comorbidities, primary tumor/metastases location, disease control rate and toxicity between KRASwt and KRASm. Median serum levels of Ca 19.9 were higher in KRASm (39.847 U/ml vs 2026 U/ml). At the time of diagnosis, 78 pts (88, 6%) were metastatic and 10 pts (11, 4%) were localized/locally-advanced. Most of metastatic pts (62/78) were KRASm (p = 0, 015). Most common histology (86, 4%) was adenocarcinoma. This histology was more frequent in KRASm, 61, 8% (p = 0, 02). At time of analysis, 72 pts (69, 9%) were dead, most of them (54, 4%) were KRASm (p = 0, 001). 31 pts developed VTE: 4 were KRASwt and 27 KRASm. The prevalence of VTE was 36, 3%. It was greater in KRASm (39, 1%) than in KRASwt (26, 3%). There were 7 cases of rethrombosis instead of anticoagulant treatment (1 KRASwt and 6 KRASm). KRASwt seems to be a protective factor in the development of VTE (OR 0, 55; CI 95% 0, 18-1, 71). The most common entity were VTE of splenoportomensenteric axis (16 pts), followed by pulmonary embolism, EP, (7 pts), deep venous thrombosis, DVT, (4 pts) EP + DVP (3 pts), thrombosis associated with central venous catheter (3 pts) and other locations (2 pts). There were no differences in VTE location between KRASwt and KRASm. The median overall survival (OS) was 12, 82 months (CI 95%: 7, 87-17, 78). It was higher in KRASwt (26 months; CI 95%: 12, 21-40, 48) than in KRASm (9, 8 months; CI 95%: 6, 07-13, 65). This difference was statistically significant (p = 0, 001). Conclusions: In our cohort, the prevalence of VTE is higher than de prevalence described in the literature and was greater in KRASm population. OS was significantly larger in KRASwt.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 709 ◽  
Author(s):  
Patrick Naumann ◽  
Jonathan Eberlein ◽  
Benjamin Farnia ◽  
Thilo Hackert ◽  
Jürgen Debus ◽  
...  

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 288-288 ◽  
Author(s):  
Hyunkyung Park ◽  
Ju-Hee Bang ◽  
Ah-Rong Nam ◽  
Ji Eun Park ◽  
Mei Hua Kim ◽  
...  

288 Background: Transforming growth factor-beta (TGF-β) is a multifunctional regulatory factor. Here, we measured serum soluble TGF-β (sTGF-β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. Methods: Sixty patients treated with FOLFIRINOX as the first-line palliative chemotherapy were prospectively enrolled. We prospectively collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF-β using an enzyme-linked immunosorbent assay. Results: The patients’ median overall survival (OS) and progression free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5–12.1) and 6.5 (95% CI, 4.9–8.1) months, respectively. Patients with low sTGF-β at diagnosis ( < 31.2ng/mL) had better OS and PFS than patients with high sTGF-β, respectively (OS, 13.7 vs. 9.2 months; hazard ratio [HR], 2.602; P =0.004; PFS, 9.0 vs. 5.8 months; HR, 2.010; P =0.034). At the time of disease progression, sTGF-β was increased compared with that of diagnosis (mean 26.4 vs. 23.9ng/mL). Especially, in patients with a partial response, sTGF-β was significantly increased at disease progression (mean 25.7 vs. 31.0ng/mL; P =0.049). Conclusions: Pre-treatment sTGF-β levels serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. Likewise, the dynamics of sTGF-β during chemotherapy have prognostic value.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16731-e16731
Author(s):  
Mariacristina Di Marco ◽  
Claudio Ricci ◽  
Riccardo Carloni ◽  
Elisa Grassi ◽  
Stefania De Lorenzo ◽  
...  

e16731 Background: Locally advanced pancreatic cancer (LAPC) is usually treated with chemoradiotherapy with poor results, thus additional therapies have been proposed. Of the latter, electrochemotherapy (ECT) represents a non-thermal ablation method, which combines the administration of chemotherapeutic drugs with permeabilizing electric pulses for cell membrane electroporation. The present study is the first to assess the short and long-term results, and the quality of life of the patients who underwent ECT for LAPC. Methods: Observational study of patients affected by LAPC who underwent intraoperative ECT after chemoradiotherapy. The inclusion criteria were: 1- patients with LAPC (defined according to the National Comprehensive Cancer Network 2019), 2- previous chemoradiotherapy and 3- absence of disease progression at restaging. Data at diagnosis and at restaging were collected for each patient. The Quality of life was evaluated using the Euro Quality of Life Group Association Questionnaire (EQ-5D-5L). The questionnaire was administered to all patients before and after ECT. Results: From May 25, 2018 to November 26, 2019 five patients underwent ECT: in 4 cases, the tumors were located in the head and, in one, in the body of the pancreas. Preoperative chemotherapy consisted mainly of 6 cycles of modified folfirinox, while the radiotherapy consisted of 54 Gy (27 fractions). At restaging, the serum value of CA 19-9 and tumor size were reduced; however, the vascular involvement did not change. No downstaging was recorded. Intravenous bleomycin 15,000IU/m2 was given as a bolus, the ECT procedure was performed using at least 4 needles with a mean duration time of 27 minutes, (range 15-40). No postoperative mortality or major complications were reported. The mean length of stay was 8 days (range 5-14). Four patients were alive and well at the end of the study while one patient died from disease progression. The mean follow-up was 20.8 months (range 9-34) from diagnosis and 9.4 months (range 2-19) from ECT. The quality of life was good (EQ-5D-5L scale > 50 in all cases) and there was improvement in pain/discomfort with respect to the pre-treatment period in 3 out of 5 patients. Conclusions: Electrochemotherapy can be considered a simple, feasible and safe palliative additional treatment in LAPC without progression after chemoradiotherapy, and it seems to allow a good quality of life and pain improvement.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 483-483 ◽  
Author(s):  
Ana Fernandez Montes ◽  
Paula Gonzalez Villarroel ◽  
Manuel Valladares Ayerbes ◽  
Juan Cruz De la Cámara Gómez ◽  
Guillermo Quintero ◽  
...  

483 Background: Placement of a biliary stent is a standard measure for patients (pts) with pancreatic cancer. We evaluated prognostic/predictive factors that could predict the benefit of gemcitabine/nabpaclitaxel in pts with locally advanced unresectable and metastatic pancreatic adenocarcinoma and whether the presence of a biliary stent reduced the treatment efficacy Methods: We retrospectively analyzed 39 pts with locally advanced and metastatic pancreatic cancer treated with gemcitabine/nabpaclitaxel. Data included lactate dehydrogenase (LDH) level, alkaline phosphatase, neutrophil/lymphocyte ratio (NLR), performance status (PS), weight loss, presence of stent, analgesics use and CA 19.9 level. The correlation with response rate, progression-free survival (PFS) and overall survival (OS) was analyzed. Objective toxicities were assessed. Results: 30 pts (77%) had metastatic disease and 9 (23%) locally advanced pancreatic cancer. 46% had liver metastases and 41% lung metastases. Mean age of pts: 62 years (62% male). 20% had PS:0, 67% PS:1 and 13% PS:2. Stents were placed in 30% of pts, 69% had weight loss and 64% used analgesics at diagnosis. At the time of analysis 14 pts had died (25 alive). 56% had progressed, 3% were lost to follow-up and 41% had not progressed. A total of 54% disease stabilizations, 21% partial responses and 18% progressions were achieved (deaths: 7%). 43% required dose reduction. The main toxicity was hematologic (grade 1 anemia). Median PFS: 6 months (95%CI 4.4-7.6). Median OS: 15 months (95%CI 10.4-19.6). There was a statistically significant relationship between LDH level, NLR and PS and OS: LDH level higher than 363 increased the risk of death, NLR above 3.1 increased 1.8 times the risk of death and mean OS of pts with ECOG:0,1 was greater than that of pts with ECOG:2. No relationship between the presence of stent and PFS or OS was found, as well as with any of the other variables. Conclusions: The presence of stent did not reduce the efficacy of gemcitabine/nabpaclitaxel. Univariate analysis showed PS as a prognostic factor while multivariate showed LDH and NLR.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 346-346 ◽  
Author(s):  
Suayib Yalcin ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
Nuriye Yildirim ◽  
Abdurrahman Isikdogan ◽  
...  

346 Background: Although clinical efficacy of gemcitabine in combination with nabpaclitaxel has been shown to be superior to single agent gemcitabine in a randomize phase 3 trial, data are lacking on the quality of life of this combination regimen as first-line therapy in patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma. Methods: We randomly assigned 125 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 to receive gemcitabine, 1000 mg/m2 plus nabpaclitaxel 125 mg/m2 or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Treatment continued until disease progression or unacceptable toxicity. The primary end point was 3-months deterioration-free rate (percentage of patients free from definitive deterioration) and quality of life of patients. Results: The median overall survival was 9.92 months in the gemcitabine plus nabpaclitaxel group as compared with 5.95 months in the gemcitabine group (hazard ratio for death, 0.642, 95% confidence interval, 0.422 to 0.866; p < 0.038). Median progression-free survival was 6.28 months in the combination group and 3.22 months in the gemcitabine group (hazard ratio for disease progression, 0.582; 95% CI, 0.391 to 0.866; p < 0.008). The objective response rate was 37.1% in the combination group versus 23.7% in the gemcitabine group (p < 0.009). Median time to deterioration was 3.68 months in the gemcitabine arm versus 5.36 months in the combination arm. More data on quality of life will be presented. Conclusions: As compared with gemcitabine, gemcitabine plus nabpaclitaxel was associated with an overall and progressive free survival advantage, with increased response rate, without increasing toxicity and deterioration of quality of life. Gemcitabine and nabpaclitaxel combination regimen with this form is a preferable option for the treatment of patients with advanced pancreatic cancer Clinical trial information: EudraCT: 2013-004180-32.


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