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Erschienen in: Surgery Today 2/2020

30.08.2019 | Original Article

Prognostic significance of platelet × C-reactive protein multiplier in patients with esophageal squamous cell carcinoma

verfasst von: Yuji Shishido, Hiroaki Saito, Shota Shimizu, Yusuke Kono, Yuki Murakami, Kozo Miyatani, Tomoyuki Matsunaga, Manabu Yamamoto, Yoji Fukumoto, Soichiro Honjo, Yoshiyuki Fujiwara

Erschienen in: Surgery Today | Ausgabe 2/2020

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Abstract

Purpose

The prognostic significance of the peripheral platelet count × serum C-reactive protein level multiplier (P-CRP) has not been widely studied in patients with esophageal squamous cell carcinoma (ESCC).

Methods

We retrospectively analyzed data from 116 thoracic ESCC patients who underwent curative esophagectomy.

Results

The patients were divided into the P-CRPHigh ( > 1.674) and P-CRPLow ( ≤ 1.674) groups, according to a cut-off value determined by a receiver operator curve. The 5-year overall survival (OS) rates significantly differed between the groups (P-CRPHigh: 46.4% and P-CRPLow: 77.3%; P = 0.0056). In the multivariate analysis, the P-CRP was an independent prognostic factor. We also evaluated the survival in the subgroup of patients who received neoadjuvant chemotherapy (NAC; n = 49). Among 28 patients who were P-CRPHigh before NAC, 20 remained. P-CRPHigh after NAC, while eight became post-P-CRPLow. Among 21 patients who were P-CRPLow before NAC, 16 remained post-P-CRPLow after NAC, while five became post-P-CRPHigh. The 5-year OS rate for patients who were P-CRPLow both before and after NAC was 92.9%, compared with 30.2% in other patients (P = 0.0034). In the multivariate analysis, the combination of P-CRP + post-P-CRP was an independent prognostic factor in ESCC patients who underwent NAC.

Conclusions

The P-CRP is useful for predicting the prognosis in ESCC patients.
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA. 2011;61:69–90.PubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA. 2011;61:69–90.PubMed
2.
Zurück zum Zitat Tachimori Y, Ozawa S, Numasaki H, Ishihara R, Matsubara H, Muro K, et al. Comprehensive registry of esophageal cancer in Japan, 2010. Esophagus. 2017;14:189–21414.PubMedPubMedCentral Tachimori Y, Ozawa S, Numasaki H, Ishihara R, Matsubara H, Muro K, et al. Comprehensive registry of esophageal cancer in Japan, 2010. Esophagus. 2017;14:189–21414.PubMedPubMedCentral
3.
Zurück zum Zitat Akiyama H, Tsurumaru M, Udagawa H, Kajiyama Y. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 1994;220:364–72.PubMedPubMedCentral Akiyama H, Tsurumaru M, Udagawa H, Kajiyama Y. Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 1994;220:364–72.PubMedPubMedCentral
4.
Zurück zum Zitat Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.PubMed Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Gunji Y, et al. Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma. Surgery. 2003;133:486–94.PubMed
5.
Zurück zum Zitat Kosugi S, Nishimaki T, Kanda T, Nakagawa S, Ohashi M, Hatakeyama K. Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19–9, and squamous cell carcinoma antigen levels in esophageal cancer patients. World J Surg. 2004;28:680–5.PubMed Kosugi S, Nishimaki T, Kanda T, Nakagawa S, Ohashi M, Hatakeyama K. Clinical significance of serum carcinoembryonic antigen, carbohydrate antigen 19–9, and squamous cell carcinoma antigen levels in esophageal cancer patients. World J Surg. 2004;28:680–5.PubMed
7.
Zurück zum Zitat Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Fushiya N, et al. Comparison of the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma. Br J Cancer. 2012;107:988–93.PubMedPubMedCentral Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Fushiya N, et al. Comparison of the prognostic value of inflammation-based prognostic scores in patients with hepatocellular carcinoma. Br J Cancer. 2012;107:988–93.PubMedPubMedCentral
8.
Zurück zum Zitat Inoue D, Ozaka M, Matsuyama M, Yamada I, Takano K, Saiura A, et al. Prognostic value of neutrophil-lymphocyte ratio and level of C-reactive protein in a large cohort of pancreatic cancer patients: a retrospective study in a single institute in Japan. Jpn J Clin Oncol. 2015;45:61–6.PubMed Inoue D, Ozaka M, Matsuyama M, Yamada I, Takano K, Saiura A, et al. Prognostic value of neutrophil-lymphocyte ratio and level of C-reactive protein in a large cohort of pancreatic cancer patients: a retrospective study in a single institute in Japan. Jpn J Clin Oncol. 2015;45:61–6.PubMed
9.
Zurück zum Zitat Miyamoto R, Oda T, Hashimoto S, Kurokawa T, Kohno K, Akashi Y, et al. Platelet x CRP multiplier value as an indicator of poor prognosis in patients with resectable pancreatic cancer. Pancreas. 2017;46:35–41.PubMed Miyamoto R, Oda T, Hashimoto S, Kurokawa T, Kohno K, Akashi Y, et al. Platelet x CRP multiplier value as an indicator of poor prognosis in patients with resectable pancreatic cancer. Pancreas. 2017;46:35–41.PubMed
10.
Zurück zum Zitat Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Prognostic significance of platelet-based inflammatory indicators in patients with gastric cancer. World J Surg. 2018;42:2542–50.PubMed Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Prognostic significance of platelet-based inflammatory indicators in patients with gastric cancer. World J Surg. 2018;42:2542–50.PubMed
11.
Zurück zum Zitat Japanese Classification of Esophageal Cancer. 11th Edition: part I. Esophagus. 2017;14:1–36. Japanese Classification of Esophageal Cancer. 11th Edition: part I. Esophagus. 2017;14:1–36.
12.
Zurück zum Zitat Japanese Classification of Esophageal Cancer. 11th Edition: part II and III. Esophagus. 2017;14:37–65. Japanese Classification of Esophageal Cancer. 11th Edition: part II and III. Esophagus. 2017;14:37–65.
13.
Zurück zum Zitat Perkins NJ, Schisterman EF. The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163:670–5.PubMedPubMedCentral Perkins NJ, Schisterman EF. The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol. 2006;163:670–5.PubMedPubMedCentral
14.
Zurück zum Zitat Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its associated cutoff point. Biometrical J Biometrische Zeitschrift. 2005;47:458–72. Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its associated cutoff point. Biometrical J Biometrische Zeitschrift. 2005;47:458–72.
16.
Zurück zum Zitat Yang PW, Huang PM, Yong LS, Chang YH, Wu CW, Hua KT, et al. Circulating interleukin-6 is associated with prognosis and genetic polymorphisms of MIR608 in patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 2018;25:2449–566.PubMed Yang PW, Huang PM, Yong LS, Chang YH, Wu CW, Hua KT, et al. Circulating interleukin-6 is associated with prognosis and genetic polymorphisms of MIR608 in patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 2018;25:2449–566.PubMed
17.
Zurück zum Zitat Morris-Stiff G, Gomez D, Prasad KR. C-reactive protein in liver cancer surgery. Eur J Surg Oncol. 2008;34:727–9.PubMed Morris-Stiff G, Gomez D, Prasad KR. C-reactive protein in liver cancer surgery. Eur J Surg Oncol. 2008;34:727–9.PubMed
18.
Zurück zum Zitat Chen MF, Chen PT, Lu MS, Lin PY, Chen WC, Lee KD. IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. Mol Cancer. 2013;12:26.PubMedPubMedCentral Chen MF, Chen PT, Lu MS, Lin PY, Chen WC, Lee KD. IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. Mol Cancer. 2013;12:26.PubMedPubMedCentral
19.
Zurück zum Zitat Zheng T-L, Cao K, Liang C, Zhang K, Guo H-Z, Li D-P, et al. Prognostic value of C-reactive protein in esophageal cancer: a meta-analysis. Asian Pacific J Cancer Prevention. 2014;15:8075–81. Zheng T-L, Cao K, Liang C, Zhang K, Guo H-Z, Li D-P, et al. Prognostic value of C-reactive protein in esophageal cancer: a meta-analysis. Asian Pacific J Cancer Prevention. 2014;15:8075–81.
20.
Zurück zum Zitat Huang Y, Feng JF, Liu JS, Chen QX. Prognostic role of serum C-reactive protein in esophageal cancer: a systematic review and meta-analysis. Ther Clin Risk Manag. 2015;11:89–94.PubMedPubMedCentral Huang Y, Feng JF, Liu JS, Chen QX. Prognostic role of serum C-reactive protein in esophageal cancer: a systematic review and meta-analysis. Ther Clin Risk Manag. 2015;11:89–94.PubMedPubMedCentral
21.
Zurück zum Zitat Nielsen HJ, Christensen IJ, Sorensen S, Moesgaard F, Brunner N. Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer The RANX05 colorectal cancer study group. Ann Surg Oncol. 2000;7:617–23.PubMed Nielsen HJ, Christensen IJ, Sorensen S, Moesgaard F, Brunner N. Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer The RANX05 colorectal cancer study group. Ann Surg Oncol. 2000;7:617–23.PubMed
22.
Zurück zum Zitat Gockel I, Dirksen K, Messow CM, Junginger T. Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus. World J Gastroenterol. 2006;12:3746–50.PubMedPubMedCentral Gockel I, Dirksen K, Messow CM, Junginger T. Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus. World J Gastroenterol. 2006;12:3746–50.PubMedPubMedCentral
23.
Zurück zum Zitat Polterauer S, Grimm C, Tempfer C, Sliutz G, Speiser P, Reinthaller A, et al. C-reactive protein is a prognostic parameter in patients with cervical cancer. Gynecol Oncol. 2007;107:114–7.PubMed Polterauer S, Grimm C, Tempfer C, Sliutz G, Speiser P, Reinthaller A, et al. C-reactive protein is a prognostic parameter in patients with cervical cancer. Gynecol Oncol. 2007;107:114–7.PubMed
24.
Zurück zum Zitat Lindenmann J, Fink-Neuboeck N, Avian A, Pichler M, Habitzruther M, Maier A, et al. Preoperative glasgow prognostic score as additional independent prognostic parameter for patients with esophageal cancer after curative esophagectomy. Eur J Surg Oncol. 2017;43:445–53.PubMed Lindenmann J, Fink-Neuboeck N, Avian A, Pichler M, Habitzruther M, Maier A, et al. Preoperative glasgow prognostic score as additional independent prognostic parameter for patients with esophageal cancer after curative esophagectomy. Eur J Surg Oncol. 2017;43:445–53.PubMed
25.
Zurück zum Zitat Imai T, Koike K, Kubo T, Kikuchi T, Amano Y, Takagi M, et al. Interleukin-6 supports human megakaryocytic proliferation and differentiation in vitro. Blood. 1991;78:1969–74.PubMed Imai T, Koike K, Kubo T, Kikuchi T, Amano Y, Takagi M, et al. Interleukin-6 supports human megakaryocytic proliferation and differentiation in vitro. Blood. 1991;78:1969–74.PubMed
26.
Zurück zum Zitat Ruscetti FW. Hematologic effects of interleukin-1 and interleukin-6. Curr Opinion Hematol. 1994;1:210–5. Ruscetti FW. Hematologic effects of interleukin-1 and interleukin-6. Curr Opinion Hematol. 1994;1:210–5.
27.
Zurück zum Zitat Troxler M, Dickinson K, Homer-Vanniasinkam S. Platelet function and antiplatelet therapy. B J Surg. 2007;94:674–82. Troxler M, Dickinson K, Homer-Vanniasinkam S. Platelet function and antiplatelet therapy. B J Surg. 2007;94:674–82.
28.
Zurück zum Zitat Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 2002;9:287–91.PubMed Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 2002;9:287–91.PubMed
29.
Zurück zum Zitat Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Preoperative leukocytosis, anemia and thrombocytosis are associated with poor survival in non-small cell lung cancer. Anticancer Res. 2009;29:2687–90.PubMed Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Preoperative leukocytosis, anemia and thrombocytosis are associated with poor survival in non-small cell lung cancer. Anticancer Res. 2009;29:2687–90.PubMed
30.
Zurück zum Zitat Gislason T, Nou E. Sedimentation rate, leucocytes, platelet count and haemoglobin in bronchial carcinoma: an epidemiological study. Euro J Respir Dis. 1985;66:141–6. Gislason T, Nou E. Sedimentation rate, leucocytes, platelet count and haemoglobin in bronchial carcinoma: an epidemiological study. Euro J Respir Dis. 1985;66:141–6.
31.
Zurück zum Zitat Karpatkin S, Pearlstein E. Role of platelets in tumor cell metastases. Ann Intern Med. 1981;95:636–41.PubMed Karpatkin S, Pearlstein E. Role of platelets in tumor cell metastases. Ann Intern Med. 1981;95:636–41.PubMed
32.
Zurück zum Zitat Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989;338:557–62.PubMed Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, et al. Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989;338:557–62.PubMed
33.
Zurück zum Zitat Cox G, Walker RA, Andi A, Steward WP, O'Byrne KJ. Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer. Lung Cancer (Amst, Neth). 2000;29:169–77. Cox G, Walker RA, Andi A, Steward WP, O'Byrne KJ. Prognostic significance of platelet and microvessel counts in operable non-small cell lung cancer. Lung Cancer (Amst, Neth). 2000;29:169–77.
34.
Zurück zum Zitat Gu ML, Yuan CJ, Liu XM, Zhou YC, Di SH, Sun FF, et al. Pre-treatment elevated platelet count associates with HER2 overexpression and prognosis in patients with breast cancer. Asian Pac J Cancer Prev. 2015;16:5537–40.PubMed Gu ML, Yuan CJ, Liu XM, Zhou YC, Di SH, Sun FF, et al. Pre-treatment elevated platelet count associates with HER2 overexpression and prognosis in patients with breast cancer. Asian Pac J Cancer Prev. 2015;16:5537–40.PubMed
35.
Zurück zum Zitat Xin-Ji Z, Yong-Gang L, Xiao-Jun S, Xiao-Wu C, Dong Z, Da-Jian Z. The prognostic role of neutrophils to lymphocytes ratio and platelet count in gastric cancer: a meta-analysis. Int J Surg (Lond, Engl). 2015;21:84–91. Xin-Ji Z, Yong-Gang L, Xiao-Jun S, Xiao-Wu C, Dong Z, Da-Jian Z. The prognostic role of neutrophils to lymphocytes ratio and platelet count in gastric cancer: a meta-analysis. Int J Surg (Lond, Engl). 2015;21:84–91.
36.
Zurück zum Zitat Long Y, Wang T, Gao Q, Zhou C. Prognostic significance of pretreatment elevated platelet count in patients with colorectal cancer: a meta-analysis. Oncotarget. 2016;7:81849–61.PubMedPubMedCentral Long Y, Wang T, Gao Q, Zhou C. Prognostic significance of pretreatment elevated platelet count in patients with colorectal cancer: a meta-analysis. Oncotarget. 2016;7:81849–61.PubMedPubMedCentral
37.
Zurück zum Zitat Chadha AS, Kocak-Uzel E, Das P, Minsky BD, Delclos ME, Mahmood U, et al. Paraneoplastic thrombocytosis independently predicts poor prognosis in patients with locally advanced pancreatic cancer. Acta Oncol (Stockh, Swed). 2015;54:971–8. Chadha AS, Kocak-Uzel E, Das P, Minsky BD, Delclos ME, Mahmood U, et al. Paraneoplastic thrombocytosis independently predicts poor prognosis in patients with locally advanced pancreatic cancer. Acta Oncol (Stockh, Swed). 2015;54:971–8.
38.
Zurück zum Zitat Xie X, Luo KJ, Hu Y, Wang JY, Chen J. Prognostic value of preoperative platelet-lymphocyte and neutrophil-lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer. Dis Esophagus. 2016;29:79–85.PubMed Xie X, Luo KJ, Hu Y, Wang JY, Chen J. Prognostic value of preoperative platelet-lymphocyte and neutrophil-lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer. Dis Esophagus. 2016;29:79–85.PubMed
39.
Zurück zum Zitat Jung J, Park SY, Park SJ, Park J. Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma. Tumour Biol. 2016;37:7149–54.PubMed Jung J, Park SY, Park SJ, Park J. Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma. Tumour Biol. 2016;37:7149–54.PubMed
40.
Zurück zum Zitat Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19:68–74.PubMed Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19:68–74.PubMed
41.
Zurück zum Zitat Otowa Y, Nakamura T, Takiguchi G, Tomono A, Yamamoto M, Kanaji S, et al. Changes in modified Glasgow prognostic score after neoadjuvant chemotherapy is a prognostic factor in clinical stage II/III esophageal cancer. Dis Esophagus. 2016;29:146–51.PubMed Otowa Y, Nakamura T, Takiguchi G, Tomono A, Yamamoto M, Kanaji S, et al. Changes in modified Glasgow prognostic score after neoadjuvant chemotherapy is a prognostic factor in clinical stage II/III esophageal cancer. Dis Esophagus. 2016;29:146–51.PubMed
Metadaten
Titel
Prognostic significance of platelet × C-reactive protein multiplier in patients with esophageal squamous cell carcinoma
verfasst von
Yuji Shishido
Hiroaki Saito
Shota Shimizu
Yusuke Kono
Yuki Murakami
Kozo Miyatani
Tomoyuki Matsunaga
Manabu Yamamoto
Yoji Fukumoto
Soichiro Honjo
Yoshiyuki Fujiwara
Publikationsdatum
30.08.2019
Verlag
Springer Singapore
Erschienen in
Surgery Today / Ausgabe 2/2020
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-019-01865-y

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