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Prognostic Significance of Serum Inflammatory Markers in Gastric Cancer
Mo1225 THE EFFECT OF DIFFERENT TREATMENT MODALITIES ON THE SURVIVAL OF PATIENTS WITH LINITIS PLASTICA Omidreza Tabatabaie, Gyulnara G. Kasumova, Meir Mizrahi, Tyler M. Berzin, Ayotunde B. Fadayomi, Promise O. Ukandu, Sing Chau Ng, Mark P. Callery, Mandeep Sawhney, Jennifer F. Tseng Background: Linitis plastica (LP) is an uncommon but aggressive form of gastric adenocarcinoma that usually presents at advanced stages and has a dismal prognosis. The aim of this study was to analyze the effects of different treatment modalities on LP. Methods: National Cancer Database (NCDB) 2004-2014 was queried for patients with histologic diagnosis of gastric adenocarcinoma and divided into LP and non-LP gastric adenocarcinoma (GAC) based on defined variables. Patients with unknown stage and/or treatment modality were excluded. Treatment groups were defined as chemo and/or radiotherapy, surgery plus chemotherapy and/or radiotherapy, surgery alone and no treatment. Chi square and Kaplan-Meier methods were used to compare patient and tumor characteristics and to calculate median overall survivals, respectively. Results: Of the 118,468 included patients with gastric cancer, 893 (0.8%) had LP. Median age was 66.0 [IQR=58.0-78.0] and 69.0 [IQR=55.0-76.0] for patients with LP and GAC, respectively. There was a female predominance in patients with LP as compared to those with GAC (52.9% vs 35.4%, p-value<0.0001). Compared to those with GAC, patients with LP were more likely to have high grade/undifferentiated tumors (91.1% vs 67.4%; p-value<0.0001) and metastatic disease (63.1% vs 49.1%; pvalue<0.0001). Moreover, LP patients were less often treated at academic centers compared to those with GAC (30.1% vs 38.56% p-value<0.0001). The proportion of patients that received surgical resection or chemotherapy did not differ between LP and GAC (41% vs 43% for surgery and 52.6% vs 51.3% for chemotherapy in LP and GAC, respectively); however, fewer patients with LP received radiotherapy (17.5% vs 28.6% p-value<0.0001). Overall median survival in patients with LP and GAC was 6.8 months (95%CI=6.4-7.4) and 12.4 months (95%CI=12.3-12.6), respectively (Figure 1). Median survivals by reported stage for patients with LP and GAC (in months) were 11.3 (95%CI=8.7-16.7) and 39.4(95%CI=37.9-41.2) for stage I, 12.2(95%CI=8.8-14.8) and 24.4(95%CI=23.4-25.2) for stage II, 8.2(95%CI=7.2-11.0) and 16.6 (95%CI=16.3-17.1) for stage III, and 4.8(95%CI= 4.1-5.4) and 5.2(95%CI=5.3-5.6) for stage IV (all P<0.05). Median survivals for each treatment group and by stage are given in Table 1. Across both cohorts, resection plus chemotherapy/radiotherapy conferred the best survival results as compared to surgery only or nonsurgical intervention. However, across all stages and treatment groups, patients with LP had inferior survival than those with non-LP GAC. Conclusion: Prognosis for patients with LP remains poor. However, despite worse prognosis compared with non-LP patients, linitus plastica patients who are reasonable candidates should be offered resection and systemic treatment, which prolong survival. Table 1. Median survival of patients with Linitis plastica (LP) and other gastric adenocarcinomas (GAC) by different treatment modalities.
LP= Linitis plastica, GAC=non-linitis plastica gastric adenocarcinoma
Mo1226 PROGNOSTIC SIGNIFICANCE OF SERUM INFLAMMATORY MARKERS IN GASTRIC CANCER Arfon G. Powell, Tarig Abdelrahman, Chris Brown, Neil Patel, Tim Havard, Xavier Escofet, Wyn G. Lewis
SSAT Abstracts
Introduction Cancer related inflammation plays a significant role in cancer progression and is an important determinant of survival, yet it remains unknown which inflammatoryserum markers offer the greatest prognostic information for patients undergoing potentially curative gastric cancer surgery. Methods Consecutive 388 patients undergoing surgery in a tertiary referral centre were identified from a prospectively maintained database. Serum C-reactive Protein (CRP), Albumin and Full Blood Count differential were recorded prior to surgery, and the Modified Glasgow Prognostic Score (MGPS, based on CRP and Albumin), NeutrophilLympocyte Ratio (NLR) and Platellet-Lymphocyte Ratio (PLR) were calculated. NLR and PLR were dichotomised based on a threshold of 5.5 and 150 respectively. The primary measures of outcome were overall (OS) and disease free survival (DFS). Results During the 5-year follow-up period, 101 (26.0%) patients developed recurrent cancer and 171 (44.1%) died. On univariable OS analysis, pTNM (p<0.001), vascular invasion (p<0.001), poor differentiation (p=0.007), CRP (p<0.001) and MGPS (p<0.001) were associated with poor survival but not Albumin (p=0.358), NLR (p=0.701) or PLR (p=0.259). On multivariable OS analysis, MGPS (Hazard Ratio (HR) 1.70, 95% CI 1.27-2.72, p<0.001) was the only inflammatory marker to retain independent significance. On univariable DFS analysis, pTNM (p<0.001), vascular invasion (p<0.001), poor differentiation (p=0.001), CRP (p=0.003) and MGPS (p=0.006) were associated with poor survival but not Albumin (p=0.450), NLR (p= 0.695) or PLR (p=0.114). On multivariable DFS analysis, MGPS (HR 1.76, 95% CI 1.012.10, p=0.043) was again the only inflammatory marker to retain independent significance. Conclusion MGPS is an important prognostic indicator and delineating the physiological reasons may offer the potential for novel therapeutic targets in gastric cancer.
Mo1227 REGULATION OF TRIGGER RECEPTOR EXPRESSED ON MYELOID CELLS1 (TREM-1) IN HEPATOCYTES (IN-VIVO) AND HEPG2 CELL LINE (INVITRO) DURING INSULIN RESISTANCE Kalyana Nandipati, Poona Sharma, Saravanan Subramnian, Devendra K. Agrawal Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) has been recently recognized as a potent amplifier of pro-inflammatory innate immune response. However, the significant role of TREM-1 remains unclear in non-infectious diseases such as obesity, insulin resistance etc. We examined the expression of TREM-1 and TREM-2 in hepatocytes using dualimmunofluorescence staining in liver biopsy samples from human study populations [nonobese (NO; N=6), obese non-diabteics (OND; N=11) and obese diabetics (OD; N=11)] and Yucatan micro-swine model [normal diet (ND; N=3) and high fructose and high cholesterol diet (HFHCD; N=7)]. We also examined the mRNA and protein expression of TREM-1 and TREM-2 in in-vitro HepG2 cell line with or without stimulation of palmitic acid (PA: 100, 250, 500, 750 and 1000µM) and glucose (GL: 5, 10, 15, 20, 25mM). The dual immunofluorescence study revealed that the mean fluorescence identity (MFI) of TREM-1 was significantly up-regulated and co-localized with albumin hepatocyte marker in OD patients compared to OND (16.61±5.45 vs 4.44±2.37; p<0.0001) and NO (16.61±5.45 vs 2.26±0.32; p<0.0001) groups; however, the levels of TREM-2 co-localized with albumin hepatocyte marker were significantly (p<0.05) down regulated. The OD population had shown increased TREM-1 expression [11/11 (100%) vs 5/11 (45.4%); p<0.0001) in hepatocytes compared to OND. The expression of TREM-1 in hepatocytes was highly correlated with FFA levels and HOMA-IR in OD patients. In in-vivo model, increased expression of TREM-1 (MFI: 6.96±3.77 vs 1.17±0.52; p<0.05) co-localized with albumin marker in HFHCD group compared to ND group was observed. We also found significantly increased mRNA [PA: (4.57±0.42 vs 1.05±0.04; p<0.001); GLU: (3.98±0.13 vs 1.06±0.09; p<0.0001)], protein [PA: (3.70±0.14 vs 1.12±0.17; p<0.0001); GLU: (3.89±0.09 vs 1.06±0.080; p<0.0001] and soluble TREM-1 expression [PA: Elisa (15.09±1.48 vs 82.93±1.68 pg/ml; p<0.0001); GLU: Elisa (15.79±0.41 vs 63.19±2.86 pg/ml; p<0.0001)] in HepG2 cell line with palmitic acid (1000µM) or glucose (25mM) stimulation compared to non-stimulated cells. Thus TREM-1 in hepatocytes may play a significant role in the pathophysiology of obesity and associated co-morbidities. Hence, TREM-1 may serve as a prognostic marker for insulin resistance.
LP: Linitis plastica; GAC: gastric adenocarcinoma, LCL: lower 95% confidence limit; UCL: upper 95% confidence limit *Not reportable according to the National Cancer Database guidelines.
SSAT Abstracts
S-1268
LP= Linitis plastica, GAC=non-linitis plastica gastric adenocarcinoma
Mo1226 PROGNOSTIC SIGNIFICANCE OF SERUM INFLAMMATORY MARKERS IN GASTRIC CANCER Arfon G. Powell, Tarig Abdelrahman, Chris Brown, Neil Patel, Tim Havard, Xavier Escofet, Wyn G. Lewis
SSAT Abstracts
Introduction Cancer related inflammation plays a significant role in cancer progression and is an important determinant of survival, yet it remains unknown which inflammatoryserum markers offer the greatest prognostic information for patients undergoing potentially curative gastric cancer surgery. Methods Consecutive 388 patients undergoing surgery in a tertiary referral centre were identified from a prospectively maintained database. Serum C-reactive Protein (CRP), Albumin and Full Blood Count differential were recorded prior to surgery, and the Modified Glasgow Prognostic Score (MGPS, based on CRP and Albumin), NeutrophilLympocyte Ratio (NLR) and Platellet-Lymphocyte Ratio (PLR) were calculated. NLR and PLR were dichotomised based on a threshold of 5.5 and 150 respectively. The primary measures of outcome were overall (OS) and disease free survival (DFS). Results During the 5-year follow-up period, 101 (26.0%) patients developed recurrent cancer and 171 (44.1%) died. On univariable OS analysis, pTNM (p<0.001), vascular invasion (p<0.001), poor differentiation (p=0.007), CRP (p<0.001) and MGPS (p<0.001) were associated with poor survival but not Albumin (p=0.358), NLR (p=0.701) or PLR (p=0.259). On multivariable OS analysis, MGPS (Hazard Ratio (HR) 1.70, 95% CI 1.27-2.72, p<0.001) was the only inflammatory marker to retain independent significance. On univariable DFS analysis, pTNM (p<0.001), vascular invasion (p<0.001), poor differentiation (p=0.001), CRP (p=0.003) and MGPS (p=0.006) were associated with poor survival but not Albumin (p=0.450), NLR (p= 0.695) or PLR (p=0.114). On multivariable DFS analysis, MGPS (HR 1.76, 95% CI 1.012.10, p=0.043) was again the only inflammatory marker to retain independent significance. Conclusion MGPS is an important prognostic indicator and delineating the physiological reasons may offer the potential for novel therapeutic targets in gastric cancer.
Mo1227 REGULATION OF TRIGGER RECEPTOR EXPRESSED ON MYELOID CELLS1 (TREM-1) IN HEPATOCYTES (IN-VIVO) AND HEPG2 CELL LINE (INVITRO) DURING INSULIN RESISTANCE Kalyana Nandipati, Poona Sharma, Saravanan Subramnian, Devendra K. Agrawal Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) has been recently recognized as a potent amplifier of pro-inflammatory innate immune response. However, the significant role of TREM-1 remains unclear in non-infectious diseases such as obesity, insulin resistance etc. We examined the expression of TREM-1 and TREM-2 in hepatocytes using dualimmunofluorescence staining in liver biopsy samples from human study populations [nonobese (NO; N=6), obese non-diabteics (OND; N=11) and obese diabetics (OD; N=11)] and Yucatan micro-swine model [normal diet (ND; N=3) and high fructose and high cholesterol diet (HFHCD; N=7)]. We also examined the mRNA and protein expression of TREM-1 and TREM-2 in in-vitro HepG2 cell line with or without stimulation of palmitic acid (PA: 100, 250, 500, 750 and 1000µM) and glucose (GL: 5, 10, 15, 20, 25mM). The dual immunofluorescence study revealed that the mean fluorescence identity (MFI) of TREM-1 was significantly up-regulated and co-localized with albumin hepatocyte marker in OD patients compared to OND (16.61±5.45 vs 4.44±2.37; p<0.0001) and NO (16.61±5.45 vs 2.26±0.32; p<0.0001) groups; however, the levels of TREM-2 co-localized with albumin hepatocyte marker were significantly (p<0.05) down regulated. The OD population had shown increased TREM-1 expression [11/11 (100%) vs 5/11 (45.4%); p<0.0001) in hepatocytes compared to OND. The expression of TREM-1 in hepatocytes was highly correlated with FFA levels and HOMA-IR in OD patients. In in-vivo model, increased expression of TREM-1 (MFI: 6.96±3.77 vs 1.17±0.52; p<0.05) co-localized with albumin marker in HFHCD group compared to ND group was observed. We also found significantly increased mRNA [PA: (4.57±0.42 vs 1.05±0.04; p<0.001); GLU: (3.98±0.13 vs 1.06±0.09; p<0.0001)], protein [PA: (3.70±0.14 vs 1.12±0.17; p<0.0001); GLU: (3.89±0.09 vs 1.06±0.080; p<0.0001] and soluble TREM-1 expression [PA: Elisa (15.09±1.48 vs 82.93±1.68 pg/ml; p<0.0001); GLU: Elisa (15.79±0.41 vs 63.19±2.86 pg/ml; p<0.0001)] in HepG2 cell line with palmitic acid (1000µM) or glucose (25mM) stimulation compared to non-stimulated cells. Thus TREM-1 in hepatocytes may play a significant role in the pathophysiology of obesity and associated co-morbidities. Hence, TREM-1 may serve as a prognostic marker for insulin resistance.
LP: Linitis plastica; GAC: gastric adenocarcinoma, LCL: lower 95% confidence limit; UCL: upper 95% confidence limit *Not reportable according to the National Cancer Database guidelines.
SSAT Abstracts
S-1268