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Buğday İ, İnanç M, Özkan M, Bozkurt O, Coşar R, Firat ST, Mutlu E, Eser M, Dişli AK, Cengiz M. Prognostic impact of elevated C-reactive protein and procalcitonin in patients with extensive-stage small cell lung cancer. Anticancer Drugs 2025; 36:135-139. [PMID: 39601772 DOI: 10.1097/cad.0000000000001670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective was to evaluate the levels of C-reactive protein (CRP) and procalcitonin (PCT) in newly diagnosed extensive-stage SCLC patients without evidence of infection. We aimed to demonstrate that elevated CRP and PCT levels may not solely indicate infection but could also be elevated in malignancies. Furthermore, we sought to correlate these marker levels with patient and disease characteristics to elucidate the relationship between these inflammation markers and disease progression. A total of 115 patients who were pathologically and radiologically diagnosed with extensive-stage SCLC between January 2020 and December 2022 and who had received no prior treatment were included in the study. The Kaplan-Meier analysis revealed a median progression-free survival (PFS) of 7.46 months [95% confidence interval (CI), 6.85-8.07] and a median overall survival (OS) of 10.50 months (95% CI, 8.69-12.30) for all patients. In the group with elevated PCT, the median PFS was 6.73 months (95% CI, 3.92-9.54), whereas it was 7.86 months (95% CI, 7.13-8.59) in the group with normal PCT ( P = 0.002). Similarly, the median OS was 9.10 months (95% CI, 5.61-12.58) in the elevated PCT group and 11.66 months (95% CI, 9.59-13.74) in the normal PCT group ( P = 0.006). Patients with elevated procalcitonin (PRC) levels at the time of diagnosis exhibited shorter PFS and OS durations compared to patients with normal PRC levels. Furthermore, elevated CRP has also been demonstrated to correlate with poorer prognosis in extensive-stage SCLC.
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Affiliation(s)
- İrfan Buğday
- Medical Oncology Department, Erciyes University Medical School, Kayseri, Türkiye
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Kim Y, Kim JS, Kang B, Kim I, Kim H, Lee WS, Sang YB, Jung S, An C, Kim C, Chon HJ. Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for More Than 1 Year. Cancer Res Treat 2024; 56:1231-1239. [PMID: 38810969 PMCID: PMC11491261 DOI: 10.4143/crt.2024.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/24/2024] [Indexed: 05/31/2024] Open
Abstract
PURPOSE Since 2020, atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year. MATERIALS AND METHODS This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group. RESULTS Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden < 25%, Eastern Cooperative Oncology Group 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p < 0.001; median time to onset [mTTO], 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO, 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO, 4.2 months), and proteinuria (69.6% vs. 38.4%, p < 0.001; mTTO, 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87.0% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment. CONCLUSION The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.
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Affiliation(s)
- Youngun Kim
- CHA University School of Medicine, Seongnam, Korea
| | - Jung Sun Kim
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Beodeul Kang
- CHA University School of Medicine, Seongnam, Korea
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Ilhwan Kim
- Division of Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyeyeong Kim
- Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Won Suk Lee
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Yun Beom Sang
- CHA University School of Medicine, Seongnam, Korea
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Sanghoon Jung
- Department of Radiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Chansik An
- Department of Radiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Chan Kim
- CHA University School of Medicine, Seongnam, Korea
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Hong Jae Chon
- CHA University School of Medicine, Seongnam, Korea
- Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
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Kaneko S, Asahina Y, Murakawa M, Ueyama S, Maeyashiki C, Watanabe H, Kusano-Kitazume A, Sato A, Uchidate K, Asakawa T, Watanabe S, Iizuka Y, Shibata I, Oooka S, Karakama Y, Fujii T, Watabe T, Akahoshi K, Tanabe M, Inada K, Mochida T, Watakabe K, Shimizu T, Tsuchiya J, Miyoshi M, Kitahata-Kawai F, Nitta S, Nakagawa M, Kakinuma S, Okamoto R. Prognostic significance of C-reactive protein in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. Hepatol Res 2024; 54:562-574. [PMID: 38133587 DOI: 10.1111/hepr.14001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/26/2023] [Accepted: 12/11/2023] [Indexed: 12/23/2023]
Abstract
AIM C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC). METHODS A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score. RESULTS Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively. CONCLUSIONS CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.
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Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shunsuke Ueyama
- Department of Gastroenterology and Hepatology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hideki Watanabe
- Department of Gastroenterology and Hepatology, Yokosuka Kyosai Hospital, Kanagawa, Japan
| | - Akiko Kusano-Kitazume
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan
| | - Kozue Uchidate
- Department of Gastroenterology and Hepatology, JA Toride Medical Center, Ibaraki, Japan
| | - Takehito Asakawa
- Department of Gastroenterology and Hepatology, Yokohama City Minato Red Cross Hospital, Kanagawa, Japan
| | - Sho Watanabe
- Department of Gastroenterology and Hepatology, Soka Municipal Hospital, Saitama, Japan
| | - Yasuhiro Iizuka
- Department of Gastroenterology and Hepatology, Kashiwa Municipal Hospital, Chiba, Japan
| | - Isamu Shibata
- Department of Gastroenterology, National Hospital Organization Disaster Medical Center, Tokyo, Japan
| | - Shinya Oooka
- Department of Medical Oncology, Showa General Hospital, Tokyo, Japan
| | - Yuko Karakama
- Department of Gastroenterology and Hepatology, Tokyo Kyosai Hospital, Tokyo, Japan
| | - Takashi Fujii
- Department of Gastroenterology and Hepatology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan
| | - Taro Watabe
- Department of Gastroenterology and Hepatology, Ome Municipal General Hospital, Tokyo, Japan
| | - Keiichi Akahoshi
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Inada
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tomohiro Mochida
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Keiya Watakabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Taro Shimizu
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fukiko Kitahata-Kawai
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
- Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryuichi Okamoto
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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Lu Z, Fu S, Li W, Gao X, Wang J. Prognostic role of C-reactive protein to albumin ratio in lung cancer: An updated systematic review and meta-analysis. Chronic Dis Transl Med 2024; 10:31-39. [PMID: 38450307 PMCID: PMC10914016 DOI: 10.1002/cdt3.91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/18/2023] [Accepted: 07/24/2023] [Indexed: 03/08/2024] Open
Abstract
Background C-reactive protein to albumin ratio (CRP/Alb ratio, CAR) has been suggested as a potential prognostic biomarker in lung cancer. This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature. Methods A systematic search of databases was conducted to identify relevant studies published up to April 2023. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between CAR and overall survival (OS) and progression-free survival (PFS) and recurrence-free survival (RF) in lung cancer patients. Results This meta-analysis includes 16 studies with a total of 5337 patients, indicating a significant association between higher CAR and poorer OS, PFS, and RFS in lung cancer patients, with a pooled HR of 1.78 (95% CI = 1.60-1.99), 1.57 (95% CI = 1.36-1.80), and 1.97 (95% CI = 1.40-2.77), respectively. Conclusions This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer, suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner. However, further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.
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Affiliation(s)
- Zhendong Lu
- Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest HospitalCapital Medical UniversityBeijingChina
| | - Siyun Fu
- Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest HospitalCapital Medical UniversityBeijingChina
| | - Wei Li
- Cancer Research Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research InstituteCapital Medical UniversityBeijingChina
| | - Xiang Gao
- Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest HospitalCapital Medical UniversityBeijingChina
| | - Jinghui Wang
- Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest HospitalCapital Medical UniversityBeijingChina
- Cancer Research Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research InstituteCapital Medical UniversityBeijingChina
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma recurrence: Predictors and management. LIVER RESEARCH 2023; 7:321-332. [PMID: 39958776 PMCID: PMC11791921 DOI: 10.1016/j.livres.2023.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 09/14/2023] [Accepted: 11/17/2023] [Indexed: 02/18/2025]
Abstract
Hepatocellular carcinoma (HCC), the sixth most common cancer globally, is associated with high mortality rates and more than 830,000 annual deaths. Despite advances in the available management options including surgical resection and local ablative therapies, recurrence rates after the initial treatment exceed 50%, even among patients who have undergone curative-intent therapy. Moreover, postsurgical HCC recurrence occurs in about 70% of cases five years postoperatively. The management of recurrent HCC remains undefined. This review discusses different predictors for HCC recurrence after each treatment modality and different approaches available to stratify these patients. More specific guidelines for managing HCC recurrence and strict surveillance protocols for such recurrence after initial HCC management are needed.
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Affiliation(s)
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Xu C, Wu F, Du L, Dong Y, Lin S. Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis. Front Immunol 2023; 14:1211399. [PMID: 37809083 PMCID: PMC10551132 DOI: 10.3389/fimmu.2023.1211399] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 09/05/2023] [Indexed: 10/10/2023] Open
Abstract
Objective Whether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In response to the current conflicting data, this meta-analysis was conducted to gain a comprehensive and systematic understanding of prognostic value of NLR in HCC. Methods Several English databases, including PubMed, EMBASE, and the Cochrane Library, with an update date of February 25, 2023, were systematically searched. We set the inclusion criteria to include randomized controlled trial (RCT) studies that reported the prognostic value of serum NLR levels in patients with HCC receiving treatment. Both the combined ratio (OR) and the diagnosis ratio (DOR) were used to assess the prognostic performance of NLR. Additionally, we completed the risk of bias assessment by Cochrane Risk of Bias Assessment Tool. Results This meta-analysis ultimately included 16 studies with a total of 4654 patients with HCC. The results showed that high baseline NLR was significantly associated with poor prognosis or recurrence of HCC. The sensitivity of 0.67 (95% confidence interval [CI]. 0.59-0.73); specificity of 0.723 (95% CI: 0.64-0.78) and DOR of 5.0 (95% CI: 4.0-7.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were calculated with the results of 2.4 (95% CI: 1.9-3.0) and 0.46 (95% CI: 0.39-0.56), respectively. In addition, area under the curve (AUC) of the summary receiver operating characteristic (SROC) reflecting prognostic accuracy was calculated to be 0.75 (95% CI: 0.71-0.78). The results of subgroup analysis suggested that high NLR was an effective predictive factor of poor prognosis in HCC in mainland China as well as in the northern region. Conclusion Our findings suggest that high baseline NLR is an excellent predictor of poor prognosis or relapse in patients with HCC, especially those from high-incidence East Asian populations. Systematic review registration https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023440640.
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Affiliation(s)
- Chunhua Xu
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Fenfang Wu
- Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Lailing Du
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Yeping Dong
- Shulan International Medical School, Zhejiang Shuren University, Hangzhou, China
| | - Shan Lin
- Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, Guangdong, China
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Yang S, Zhang Z, Shen L. Prognostic significance of C-reactive protein in patients with cervical cancer: a meta-analysis. Front Oncol 2023; 13:1232409. [PMID: 37731642 PMCID: PMC10507700 DOI: 10.3389/fonc.2023.1232409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 08/08/2023] [Indexed: 09/22/2023] Open
Abstract
Background Numerous studies have investigated the significance of pretreatment C-reactive protein (CRP) levels for determining the prognosis of cervical cancer (CC). The results of these studies, however, have been inconsistent. The present meta-analysis, therefore, focused on identifying the exact relationship of CRP levels with CC prognoses. Methods We searched the following databases from their inception until April 18, 2023: PubMed; Web of Science; Embase; and Cochrane Library. From the search results, we estimated the significance of CRP levels in determining the prognosis of CC, based on combined hazard ratios (HRs) and relevant 95% confidence intervals (CIs). Results The present meta-analysis included 12 studies, encompassing 2,204 patients. Based on combined data, an increased CRP level was significantly related to an unfavorable overall survival (OS) of patients with CC (HR = 1.63; 95% CI = 1.36-1.95; P < 0.001). Moreover, an increased CRP level was significantly associated with shortened progression-free survival (PFS) in patients with CC (HR = 1.68; 95% CI = 1.39-2.03; P < 0.001). According to the subgroup and sensitivity analyses, CRP level was a reliable factor in determining CC prognoses. Conclusion Based on the results of our present analyses, increased CRP levels were significant predictors of poor OS and PFS in patients with CC. CRP level, therefore, could be an independent and inexpensive factor for determining the prognosis of patients with CC in clinical settings. Systematic review registration INPLASY, identifier INPLASY202360074.
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Affiliation(s)
- Sheng Yang
- Clinical Laboratory, Huzhou Maternity and Child Health Care Hospital, Huzhou, Zhejiang, China
| | - Zongxin Zhang
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China
| | - Linglong Shen
- Clinical Laboratory, Huzhou Maternity and Child Health Care Hospital, Huzhou, Zhejiang, China
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Ersal T, Özkocaman V, Pınar İE, Yalçın C, Orhan B, Candar Ö, Çubukçu S, Koca TG, Hunutlu FÇ, Yavuz Ş, Ali R, Özkalemkaş F. Systemic inflammatory indices for predicting prognosis of myelofibrosis. Sci Rep 2023; 13:12539. [PMID: 37532753 PMCID: PMC10397340 DOI: 10.1038/s41598-023-39077-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 07/19/2023] [Indexed: 08/04/2023] Open
Abstract
The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.
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Affiliation(s)
- Tuba Ersal
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey.
| | - Vildan Özkocaman
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - İbrahim Ethem Pınar
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Cumali Yalçın
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Bedrettin Orhan
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Ömer Candar
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Sinem Çubukçu
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Tuba Güllü Koca
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Fazıl Çağrı Hunutlu
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Şeyma Yavuz
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Rıdvan Ali
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
| | - Fahir Özkalemkaş
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, 16059, Bursa, Turkey
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Akinloye DI, Metibemu DS, Shittu MT, Lawal MA, Olatunji FO, Oyediran MA, Akinloye OA. Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt. J Cannabis Res 2023; 5:27. [PMID: 37434213 PMCID: PMC10337064 DOI: 10.1186/s42238-023-00190-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 05/09/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches. METHODS Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups RESULT: The lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes' activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3-5. In groups 3-5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3-5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3-5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC. CONCLUSION C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms. In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored.
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Affiliation(s)
- Dorcas I. Akinloye
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Damilohun S. Metibemu
- Department of Chemistry, Physics, and Atmospheric Sciences, Jackson State University, Jackson, MS 39217-0095 USA
| | - Mujidat T. Shittu
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Mariam A. Lawal
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Faith O. Olatunji
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Muideen A. Oyediran
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
| | - Oluseyi A. Akinloye
- Department of Biochemistry, Phyto-chemistry and Bio-computing Research Laboratory, College of Biosciences, Federal University of Agriculture, Abeokuta, Nigeria
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10
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Zhang L, Feng J, Kuang T, Chai D, Qiu Z, Deng W, Dong K, Zhao K, Wang W. Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies. Int Immunopharmacol 2023; 118:110019. [PMID: 36933492 DOI: 10.1016/j.intimp.2023.110019] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 03/01/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023]
Abstract
OBJECTIVE We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). RESULTS A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.951, P < 0.001) and PFS (HR: 1.632, P < 0.001), lower ORR (OR: 0.484, P < 0.001) and DCR (OR: 0.494, P = 0.027), and higher HPD (OR: 8.190, P < 0.001). The patients with high AFP levels had shorter OS (HR: 1.689, P < 0.001) and PFS (HR: 1.380, P < 0.001), and lower DCR (OR: 0.440, P < 0.001) than those with low AFP levels, however, there was no difference in ORR (OR: 0.963, P = 0.933). We also found that early AFP response was correlated with better OS (HR: 0.422, P < 0.001) and PFS (HR: 0.385, P < 0.001), higher ORR (OR: 7.297, P < 0.001) and DCR (OR: 13.360, P < 0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR: 2.440, P = 0.009) and PFS (HR: 1.373, P = 0.022), lower ORR (OR: 0.618, P = 0.032) and DCR (OR: 0.672, P = 0.049) than those with an ALBI grade 1. CONCLUSION The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.
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Affiliation(s)
- Lilong Zhang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Jiarui Feng
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Tianrui Kuang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Dongqi Chai
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Zhendong Qiu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Wenhong Deng
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Keshuai Dong
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China
| | - Kailiang Zhao
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China.
| | - Weixing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Key Laboratory of Digestive System Disease, Wuhan, China.
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11
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Minici R, Siciliano MA, Ammendola M, Santoro RC, Barbieri V, Ranieri G, Laganà D. Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), Platelet-to-Lymphocyte Ratio (PLR) and Lymphocyte-to-C Reactive Protein Ratio (LCR) in Patients with Hepatocellular Carcinoma (HCC) undergoing Chemoembolizations (TACE) of the Liver: The Unexplored Corner Linking Tumor Microenvironment, Biomarkers and Interventional Radiology. Cancers (Basel) 2022; 15:257. [PMID: 36612251 PMCID: PMC9818978 DOI: 10.3390/cancers15010257] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/04/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
TACE plays a pivotal role in hepatocellular carcinoma, from disease control to downstaging and bridging to liver transplant. Response to TACE is a surrogate marker of tumor aggressive biology, with manifold practical implications such as survival, the need for more aggressive treatments in the intermediate stage, the selection of patients on the transplant waiting list, the dropout rate from the transplant list and the post-transplant recurrence rate. Inflammation-based scores are biomarkers of the relationship between the tumor stromal microenvironment and the immune response. Investigating the connection among the tumor stromal microenvironment, biomarkers, and the response to TACE is crucial to recognize TACE refractoriness/failure, thus providing patients with tailored therapeutics. This review aims to provide a comprehensive overview of the prognostic roles of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-C reactive protein ratio (LCR) in patients with HCC undergoing chemoembolization of the liver. Inflammation-based scores may be convenient, easily obtained, low-cost, and reliable biomarkers with prognostic significance for HCC undergoing TACE. Baseline cut-off values differ between various studies, thus increasing confusion about using of inflammation-based scores in clinical practice. Further investigations should be conducted to establish the optimal cut-off values for inflammation-based scores, consolidating their use in clinical practice.
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Affiliation(s)
- Roberto Minici
- Radiology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | | | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, 88100 Catanzaro, Italy
| | - Rita Carlotta Santoro
- Haemophilia and Thrombosis Center, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Vito Barbieri
- Oncology Division, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy
| | - Girolamo Ranieri
- Interventional and Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
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12
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Adhoute X, De Matharel M, Mineur L, Pénaranda G, Ouizeman D, Toullec C, Tran A, Castellani P, Rollet A, Oules V, Perrier H, Si Ahmed SN, Bourliere M, Anty R. Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib: Multicenter French clinical experience in real-life after matching. World J Gastrointest Oncol 2022; 14:1510-1527. [PMID: 36160737 PMCID: PMC9412937 DOI: 10.4251/wjgo.v14.i8.1510] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/08/2022] [Accepted: 07/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available.
AIM To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time.
METHODS A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups.
RESULTS Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) vs 4 (2.9-11.8) mo (REG), P = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) vs 5.2 (4-7.2) mo (CBZ), P = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) vs 4.9 (1.6-11.7) mo (CP-B), P = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors.
CONCLUSION This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.
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Affiliation(s)
- Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Marie De Matharel
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Laurent Mineur
- Department of Oncology, Institut Sainte-Catherine, Avignon 84000, France
| | | | - Dann Ouizeman
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Clemence Toullec
- Department of Oncology, Institut Sainte-Catherine, Avignon 84000, France
| | - Albert Tran
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Paul Castellani
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Armelle Rollet
- Department of Oncology, Institut Sainte-Catherine, Avignon 84000, France
| | - Valérie Oules
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Hervé Perrier
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Si Nafa Si Ahmed
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Marc Bourliere
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
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13
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Badwei N, Monsef WA, Montasser I, Bahaa M, El Meteini M, Kamel SY. Role of inflammatory markers in predicting hepatocellular carcinoma recurrence after liver transplantation. EGYPTIAN LIVER JOURNAL 2021; 11:40. [DOI: 10.1186/s43066-021-00105-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 05/03/2021] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Liver transplantation (LT) is the best treatment for selected patients with cirrhosis and small hepatocellular carcinoma (HCC) who are not candidates for resection. The proinflammatory effects of systemic inflammatory response have been linked with HCC. Therefore, the measurement of inflammatory markers represents a significant tool to limit recurrence after LT.
Results
There are eleven patients with HCC recurrence post-transplantation. Pre-transplantation AFP can predict HCC recurrence with the best cutoff value of > 17.8 ng/ml with a sensitivity of 82% and specificity of 70%. Post-transplantation CRP can predict HCC recurrence with the best cutoff value of > 0.85 (mg/dl) with a sensitivity of 73% and specificity of 71%. Other inflammatory markers NLR and PLR were not significant in predicting HCC recurrence. Moreover, HCC recurrence significantly affects the outcome of patients undergoing LT (p value < 0.001) with a worse prognosis.
Conclusion
Our results showed additional benefits of inflammatory markers as CRP to standard parameters in predicting HCC recurrence to refine recipient selection and achieve better survival outcomes post-LT.
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14
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Müller L, Hahn F, Mähringer-Kunz A, Stoehr F, Gairing SJ, Michel M, Foerster F, Weinmann A, Galle PR, Mittler J, Pinto Dos Santos D, Pitton MB, Düber C, Kloeckner R. Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index. Cancers (Basel) 2021; 13:5018. [PMID: 34638502 PMCID: PMC8508385 DOI: 10.3390/cancers13195018] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/27/2021] [Accepted: 10/05/2021] [Indexed: 02/07/2023] Open
Abstract
The novel CRP-albumin-lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p < 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters.
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Affiliation(s)
- Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Fabian Stoehr
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Simon Johannes Gairing
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Maurice Michel
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Friedrich Foerster
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Jens Mittler
- Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | | | - Michael Bernhard Pitton
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Christoph Düber
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
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15
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Wang Y, Lyu J, Jia H, Liang L, Xiao L, Liu Y, Liu X, Li K, Chen T, Zhang R, Zhang H, Tang C, Li T. Clinical utility of the systemic immune-inflammation index for predicting survival in esophageal squamous cell carcinoma after radical radiotherapy. Future Oncol 2021; 17:2647-2657. [PMID: 34008415 DOI: 10.2217/fon-2021-0304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To explore the clinical utility of the systemic immune-inflammation index (SII) for predicting the prognosis of esophageal squamous cell carcinoma (ESCC). Patients & methods: After calculating the SII in 180 patients with ESCC, the relationship between SII values and the pre-/post-radiotherapy SII ratio and overall survival was determined. Results: The median overall survival was 649 days for the entire group and 909 and 466 days for the high and low pre-/post-radiotherapy SII ratio groups, respectively. Multivariate analysis identified Karnofsky performance status (p = 0.045), lymphatic metastasis (p = 0.032), mid-radiotherapy SII (p < 0.001) and pre-/post-radiotherapy SII ratio (p = 0.003) as independent prognostic factors. Conclusion: The pre-/post-radiotherapy SII ratio and mid-radiotherapy SII are potentially effective markers for predicting ESCC prognosis.
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Affiliation(s)
- Yuan Wang
- School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610054, China
| | - Jiahua Lyu
- School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610054, China.,Sichuan Cancer Hospital Institute/Sichuan Cancer Center/School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610041, China
| | - Hongyuan Jia
- Sichuan Cancer Hospital Institute/Sichuan Cancer Center/School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610041, China
| | - Long Liang
- Sichuan Cancer Hospital Institute/Sichuan Cancer Center/School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610041, China
| | - Ling Xiao
- School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610054, China
| | - Yudi Liu
- School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610054, China
| | - Xiao Liu
- School of Clinical Medical Sciences, Southwest Medical University, Luzhou, 646000, China
| | - Ke Li
- School of Clinical Medical Sciences, Southwest Medical University, Luzhou, 646000, China
| | - Taiyu Chen
- School of Clinical Medical, Chengdu Medical College, Chengdu, 610599, China
| | - Rongke Zhang
- School of Clinical Medical Sciences, Southwest Medical University, Luzhou, 646000, China
| | - Hangyue Zhang
- School of Clinical Medical Sciences, Southwest Medical University, Luzhou, 646000, China
| | - Chunhan Tang
- School of Clinical Medical, Chengdu Medical College, Chengdu, 610599, China
| | - Tao Li
- School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610054, China.,Sichuan Cancer Hospital Institute/Sichuan Cancer Center/School of Medicine, University of Electronic Science & Technology of China, Chengdu, 610041, China
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16
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Fan X, Zhang K, Wang X, Zhang X, Zeng L, Li N, Han Q, Liu Z. Sleep disorders are associated with acetaminophen-induced adverse reactions and liver injury. Biomed Pharmacother 2021; 134:111150. [PMID: 33395599 DOI: 10.1016/j.biopha.2020.111150] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/03/2020] [Accepted: 12/14/2020] [Indexed: 12/17/2022] Open
Abstract
Risk factors related to the development of acetaminophen (APAP)-induced adverse reactions and liver injury remain uncertain. Sleep disorders have been linked to some health outcomes. This study examined the associations of sleep disorders with APAP-induced adverse reactions or liver injury and the possible mechanisms. From NIS database, adverse reactions, liver injury and sleep disorders were identified. Factors associated with the risk of the total adverse effects or liver injury were examined with logistic regression. From Gene Expression Omnibus database, datasets GSE111828, containing transcriptome data based on RNA-seq analysis from liver samples extracted from mice post APAP administration, and GSE92913, containing transcriptome data based on microarray analysis from liver samples extracted from mice with sleep deprivation, were analyzed. A total of 4372754 patients without and 91314 patients with sleep disorders were eligible for analyses. Both before and after propensity score matching, APAP-induced adverse reactions were higher in patients with sleep disorders than in patients without. In multivariate regression, sleep disorders were associated with higher odds of APAP-induced adverse reactions (adjusted OR [aOR] 2.005, 95 % CI 1.343-2.995) and liver injury (aOR 2.788, 95 % CI 1.310-5.932). Genes that were enriched in bile secretion and retinol metabolism and PPAR signaling pathways were basically down-regulated in livers of mice after APAP administration and livers of mice with sleep deprivation. This study shows that sleep disorders may be novel independent risk factors for APAP-associated adverse reactions and liver injury and provides bioinformation linking sleep disorders to increased risk of APAP-induced liver injury.
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Affiliation(s)
- Xiude Fan
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Kun Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Xiaoyun Wang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Xiaoge Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Lu Zeng
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Na Li
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Qunying Han
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Zhengwen Liu
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.
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Markozannes G, Koutsioumpa C, Cividini S, Monori G, Tsilidis KK, Kretsavos N, Theodoratou E, Gill D, Ioannidis JP, Tzoulaki I. Global assessment of C-reactive protein and health-related outcomes: an umbrella review of evidence from observational studies and Mendelian randomization studies. Eur J Epidemiol 2021; 36:11-36. [PMID: 32978716 PMCID: PMC7847446 DOI: 10.1007/s10654-020-00681-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 08/25/2020] [Indexed: 02/07/2023]
Abstract
C-reactive protein (CRP) has been studied extensively for association with a large number of non-infectious diseases and outcomes. We aimed to evaluate the breadth and validity of associations between CRP and non-infectious, chronic health outcomes and biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses and a systematic review of Mendelian randomization (MR) studies. PubMed, Scopus, and Cochrane Database of Systematic Reviews were systematically searched from inception up to March 2019. Meta-analyses of observational studies and MR studies examining associations between CRP and health outcomes were identified, excluding studies on the diagnostic value of CRP for infections. We found 113 meta-analytic comparisons of observational studies and 196 MR analyses, covering a wide range of outcomes. The overwhelming majority of the meta-analyses of observational studies reported a nominally statistically significant result (95/113, 84.1%); however, the majority of the meta-analyses displayed substantial heterogeneity (47.8%), small study effects (39.8%) or excess significance (41.6%). Only two outcomes, cardiovascular mortality and venous thromboembolism, showed convincing evidence of association with CRP levels. When examining the MR literature, we found MR studies for 53/113 outcomes examined in the observational study meta-analyses but substantial support for a causal association with CRP was not observed for any phenotype. Despite the striking amount of research on CRP, convincing evidence for associations and causal effects is remarkably limited.
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Affiliation(s)
- Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece
| | - Charalampia Koutsioumpa
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece
- Department of Neurobiology, Harvard Medical School, Boston, MA, USA
- BBS Program, Harvard Medical School, 220 Longwood Avenue, Boston, MA, 02115, USA
| | - Sofia Cividini
- Department of Biostatistics, University of Liverpool, Liverpool, UK
| | - Grace Monori
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Konstantinos K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Nikolaos Kretsavos
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
- Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - John Pa Ioannidis
- Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Biomedical Data Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, 94305, USA
- Meta-Research Innovation Center at Stanford (METRICS), Stanford, CA, 94305, USA
| | - Ioanna Tzoulaki
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, 45110, Ioannina, Greece.
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
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Liu D, Chen Y, Wang Y, Lei M, Chen L, Liang R, Cheng Z, Shi W, Wang H, Lin L, Wang L, Lin F, Lin H, Liu W. Combination of Serum Amyloid A and C-Reactive Protein Exhibit Synergistic Effect in Angiogenesis by Inducing Inflammation and Vascular Network. Front Oncol 2020; 10:576207. [PMID: 33364190 PMCID: PMC7753214 DOI: 10.3389/fonc.2020.576207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 10/19/2020] [Indexed: 01/08/2023] Open
Abstract
The role of angiogenesis in tumor progression has been recognized as one of the hallmarks of cancer, but the mechanism of its action remains unclear. Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are proposed to play causal roles in the development of various disorders, including malignancies. Previously, we identified the complex of CRP and SAA (CRP-SAA) with diagnostic and prognostic value better than either one of them in the serum of lung cancer patients. In this study, we further explored the stimulation function of CRP-SAA on angiogenesis and inflammation. To explore possible mechanisms, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and multi-bioinformatics analysis revealed that THP-1 and human umbilical vein endothelial cells (HUVECs) responded to SAA stimulation with upregulation of two pro-angiogenic cytokines in common, i.e., C-X-C motif ligand 6 (CXCL6) and CXCL8, which were validated by subsequent experiments in vitro. CRP had weak effects as a single stimulus, but it can efficiently potentiate the SAA induction of cytokines, which was stronger than the sum of the both (P < 0.001). The synergistical effect of the combination of CRP and SAA enhanced HUVECs transwell and constricted morphology by upregulating the pro-angiogenic genes. These results indicated that the binding of CRP and SAA acted synergistically in pro-angiogenesis by increasing inflammation and inducing vascular network.
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Affiliation(s)
- Dan Liu
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.,Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yonghe Chen
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yunxiu Wang
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Mangjuan Lei
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lin Chen
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Rongliang Liang
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Zhaomin Cheng
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Wen Shi
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Huimin Wang
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Li Lin
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Lina Wang
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Fujia Lin
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Haibiao Lin
- Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Wanli Liu
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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19
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Chen Y, Cong R, Ji C, Ruan W. The prognostic role of C-reactive protein in patients with head and neck squamous cell carcinoma: A meta-analysis. Cancer Med 2020; 9:9541-9553. [PMID: 33201589 PMCID: PMC7774749 DOI: 10.1002/cam4.3520] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 09/04/2020] [Accepted: 09/14/2020] [Indexed: 12/22/2022] Open
Abstract
Background The prognostic role of the C‐reactive protein (CRP) in head and neck squamous cell carcinoma (HNSCC) has not been well investigated. This meta‐analysis aimed to evaluate the prognostic relevance of elevated CRP levels in patients with HNSCC. Methods A relevant literature search was performed in PubMed, Web of Science, and Embase up to September 1, 2020. The pooled odds ratio and hazard ratio (HR) with 95% confidence interval (CI) were applied to evaluate the difference in overall survival (OS), progress‐free survival (PFS), and cancer‐specific survival (CSS) between patients with high CRP and those without. The pooled odds ratio (OR) with 95% CI were used to assess the association between CRP and clinicopathological features. Results A total of 17 studies, including 4449 patients, were included. Pooled results showed that an elevated CRP was associated with worse OS (HR = 1.48, 95% CI: 1.24‐1.77), CSS (HR = 1.85, 95% CI: 1.38‐2.46), and PFS (HR = 1.73, 95% CI: 1.38‐2.17). Male patients, lymph node metastases, and higher tumor stage were related to elevated CRP level (OR = 1.67, 95% CI: 1.34‐2.09; OR = 2.40, 95% CI: 1.44‐3.99; OR = 1.39, 95% CI: 1.12‐1.74). Conclusion Our meta‐analysis demonstrated that an elevated pretreatment of CRP indicates poor prognosis in HNSCC. Therefore, CRP is an indicator of the prognosis of patients with HNSCC and can be recommended for assessing prognoses in clinical work.
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Affiliation(s)
- Yanglan Chen
- Department of Stomatology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, China
| | - Rong Cong
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chengjian Ji
- Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenhua Ruan
- Department of Stomatology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, China
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Donlon NE, Mohan H, Free R, Elbaghir B, Soric I, Fleming C, Balasubramanian I, Ivanovski I, Schmidt K, Mealy K. Predictive value of CRP/albumin ratio in major abdominal surgery. Ir J Med Sci 2020; 189:1465-1470. [DOI: 10.1007/s11845-020-02238-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/16/2020] [Indexed: 01/06/2023]
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Post-diagnostic C-reactive protein and albumin predict survival in Chinese patients with non-small cell lung cancer: a prospective cohort study. Sci Rep 2019; 9:8143. [PMID: 31148582 PMCID: PMC6544765 DOI: 10.1038/s41598-019-44653-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 05/21/2019] [Indexed: 01/18/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80–3.04) and 2.64 (95% CI: 1.35–5.16) for patients in the second and the highest tertiles of CRP (P-trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29–0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15–7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.
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22
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Shimura T, Shibata M, Gonda K, Murakami Y, Noda M, Tachibana K, Abe N, Ohtake T. Prognostic impact of interleukin-6 and C-reactive protein on patients with breast cancer. Oncol Lett 2019; 17:5139-5146. [PMID: 31186728 DOI: 10.3892/ol.2019.10183] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 02/27/2019] [Indexed: 12/13/2022] Open
Abstract
The prognostic impacts of preoperative C-reactive protein (CRP) and interleukin (IL)-6 expression levels in patients with breast cancer remain controversial. A total of 55 female patients with invasive breast cancer were enrolled, and preoperative prognostic parameters including IL-6 and CRP were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and candidates' prognostic factors were examined using a Cox proportional hazard model. Using receiver operating characteristic curve analysis, IL-6 at 10.0 pg/ml and CRP at 0.12 mg/dl were determined as threshold values to predict OS and RFS, respectively. Patients with IL-6 ≥10.0 pg/ml had poorer OS compared with those with IL-6 <10.0 pg/ml (P=0.003), and patients with CRP ≥0.12 mg/dl had poorer RFS compared with those with CRP <0.12 mg/dl (P<0.001). Serum IL-6 level (hazard ratio, 13.230; 95% confidence interval, 1.285-136.214; P=0.030) and triple-negative subtype (hazard ratio, 11.739; 95% confidence interval, 1.415-97.362; P=0.023) were independent prognostic factors for OS, and CRP expression level was an independent prognostic factor for RFS in patients with breast cancer (hazard ratio, 18.571; 95% confidence interval, 2.240-153.949; P=0.007). In patients with invasive breast cancer, preoperative serum IL-6 and triple-negative subtype may be independent prognostic factors for OS, while for RFS, preoperative CRP may be a more accurate prognostic factor compared with those currently established.
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Affiliation(s)
- Tatsuo Shimura
- Department of Progressive DOHaD Research, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Masahiko Shibata
- Department of Advanced Cancer Immunotherapy, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Kenji Gonda
- Clinical Oncology Center, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Yuko Murakami
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Masaru Noda
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Kazunoshin Tachibana
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Noriko Abe
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Tohru Ohtake
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
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Citores MJ, Lucena JL, de la Fuente S, Cuervas-Mons V. Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation. World J Hepatol 2019; 11:50-64. [PMID: 30705718 PMCID: PMC6354126 DOI: 10.4254/wjh.v11.i1.50] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.
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Affiliation(s)
- Maria J Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda 28222, Spain.
| | - Jose L Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Sara de la Fuente
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Valentin Cuervas-Mons
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
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24
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Kornberg A, Schernhammer M, Kornberg J, Friess H, Thrum K. Serological Risk Index Based on Alpha-Fetoprotein and C-Reactive Protein to Indicate Futile Liver Transplantation Among Patients with Advanced Hepatocellular Carcinoma. Dig Dis Sci 2019; 64:269-280. [PMID: 30259282 DOI: 10.1007/s10620-018-5296-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 09/17/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to establish a preoperatively available serological risk index using alpha-fetoprotein (AFP) and C-reactive protein (CRP) for predicting oncologically futile liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. METHODS A total of 119 liver transplant patients with HCC were retrospectively analyzed. The prognostic impact of clinical and histopathologic factors including pre-LT serum AFP and CRP values was determined. RESULTS Apart from microvascular tumor invasion (MVI; odds ratio [OR] 15.77), pretransplant serum levels of AFP > 100 ng/ml (OR 13.31) and CRP > 0.8 mg/dl (OR 13.97) were identified as independent predictors of HCC recurrence. The cumulative risk of HCC relapse at 5 years post-LT was 2.3% in low serological tumor activity (STA) index (AFP ≤ 100 ng/ml + CRP ≤ 0.8 mg/dl), 17.1% in intermediate STA (AFP ≤ 100 ng/ml or CRP ≤ 0.8 mg/dl), and 91.6% in high STA index (AFP > 100 ng/ml + CRP > 0.8 mg/dl; p < 0.001), respectively. High STA index was identified as most powerful pre-LT available predictor of MVI (OR 15.31) and posttransplant HCC recurrence (OR 54.44). Five-year recurrence-free survival rate in Milan Out patients with high STA was 0%, compared to 91.7% and 83.6% in those with low or intermediate STA index (p < 0.001), respectively. CONCLUSION Our proposed serological risk index based on pretransplant serum AFP and CRP values is able to predict oncologically futile LT among advanced HCC patients.
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Affiliation(s)
- Arno Kornberg
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, 81675, Munich, Germany.
| | - Martina Schernhammer
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Jennifer Kornberg
- Department of Anaesthesiology, Klinikum Großhadern, LMU Munich, Munich, Germany
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, 81675, Munich, Germany
| | - Katharina Thrum
- Institute of Pathology, Helios Klinikum Berlin, Berlin, Germany
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Amado V, Rodríguez-Perálvarez M, Ferrín G, De la Mata M. Selecting patients with hepatocellular carcinoma for liver transplantation: incorporating tumor biology criteria. J Hepatocell Carcinoma 2018; 6:1-10. [PMID: 30613572 PMCID: PMC6306074 DOI: 10.2147/jhc.s174549] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is the optimal therapeutic option for patients with liver cirrhosis and hepatocellular carcinoma (HCC). Due to universal donor shortage, only the patients with limited tumor burden (under the so-called Milan criteria) are considered as potential candidates for LT in most institutions. It is expected that in the near future, more liver grafts will be available for patients with HCC due to the implementation of new direct antivirals against hepatitis C, leaving a prone scenario to consider expanding Milan criteria. A moderate expansion of Milan criteria could be implemented without increasing the risk of tumor recurrence if patients with favorable biological behavior are carefully selected. Incorporating information regarding tumor biology in the decision-making algorithm would result in a more rational use of LT in patients with HCC. In the present review, surrogate markers of tumor biology are critically evaluated as potential tools to be combined with existing radiological criteria. In addition, the current state of liquid biopsy is discussed, as this cutting-edge technology may reshape the management of HCC in the upcoming years.
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Affiliation(s)
- Víctor Amado
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Manuel Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Gustavo Ferrín
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Manuel De la Mata
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
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Magistri P, Rosenblatt R, Halazun KJ. Liver Transplantation for HCC Beyond Milan. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0212-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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27
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Heudobler D, Rechenmacher M, Lüke F, Vogelhuber M, Pukrop T, Herr W, Ghibelli L, Gerner C, Reichle A. Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue. Int J Mol Sci 2018; 19:ijms19113540. [PMID: 30424016 PMCID: PMC6274845 DOI: 10.3390/ijms19113540] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 10/27/2018] [Accepted: 11/06/2018] [Indexed: 02/08/2023] Open
Abstract
In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called ‘master modulators’ of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogramming of tumor tissues, i.e., anakoinosis, meaning ‘communication’ in ancient Greek. The concerted activity of master modulators may multifaceted diversify palliative care or even induce continuous complete remission in refractory metastatic tumor disease and hematologic neoplasia by establishing novel communicative behavior of tumor tissue, the hosting organ, and organism. Re-modulation of gene expression, for example, the up-regulation of tumor suppressor genes, may recover differentiation, apoptosis competence, and leads to cancer control—in contrast to an immediate, ‘poisoning’ with maximal tolerable doses of targeted/cytotoxic therapies. The key for uncovering the therapeutic potential of Peroxisome proliferator-activated receptor γ (PPARγ) agonists is selecting the appropriate combination of master modulators for inducing anakoinosis: Now, anakoinosis is trend setting by establishing a novel therapeutic pillar while overcoming classic obstacles of targeted therapies, such as therapy resistance and (molecular-)genetic tumor heterogeneity.
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Affiliation(s)
- Daniel Heudobler
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Michael Rechenmacher
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Florian Lüke
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Martin Vogelhuber
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Tobias Pukrop
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Wolfgang Herr
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
| | - Lina Ghibelli
- Department Biology, Universita' di Roma Tor Vergata, 00173 Rome, Italy.
| | - Christopher Gerner
- Institut for Analytical Chemistry, Faculty Chemistry, University Vienna, Vienna A-1090, Austria.
| | - Albrecht Reichle
- Department of Internal Medicine III, University Hospital Regensburg, Hematology and Oncology, 93042 Regensburg, Germany.
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Hartrumpf KJ, Marquardt S, Werncke T, Murray T, Kirstein MM, Vogel A, Wacker F, Rodt T. Quality of life in patients undergoing repetitive TACE for the treatment of intermediate stage HCC. J Cancer Res Clin Oncol 2018; 144:1991-1999. [PMID: 30008024 DOI: 10.1007/s00432-018-2704-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 07/05/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE With a limited overall survival (OS) of 20 months in patients diagnosed with intermediate stage hepatocellular carcinoma (HCC), the preservation of quality of life (QoL) during transarterial chemoembolization (TACE) procedures remains a primary goal. The aim of our study was to evaluate the change in QoL amongst patients undergoing repetitive TACE and to identify specific risk factors that may predict change in QoL. METHODS QoL was assessed in 82 patients undergoing at least two TACE, before and 14 days after TACE, using validated EORTC QLQ-C30 and EORTC HCC18 questionnaires. Tumour response was assessed using established response criteria. Laboratory and clinical parameters were analysed. RESULTS Functional scores decreased due to first TACE treatment (p < 0.01), conversely symptom scores increased significantly (p < 0.01). During repetitive TACE no statistically significant changes were observed. Higher Global Health- and Physical Functioning scores at baseline were identified as independent prognostic factors for greater decrease in QoL. Tumour response did not alter QoL at all. Furthermore higher symptom scales including pain (p = 0.00), nausea and vomiting (p = 0.00) and fever (p < 0.01 for repetitive TACE) at baseline were predictive of a significantly lesser increase of symptom severity, and a greater reduction in pain during a course of TACE. Higher C-reactive protein (CRP) at baseline and female gender were associated with a greater decrease of functional scales and increase of symptom scales. CONCLUSION QoL amongst patients receiving repetitive TACE showed neither significant nor clinically relevant changes over time. Pre-treatment assessment of QoL-scores, clinical and laboratory parameters can improve patient selection for TACE whilst optimizing QoL.
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Affiliation(s)
- K J Hartrumpf
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - S Marquardt
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - T Werncke
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - T Murray
- Beaumont Hospital, Beaumont Rd, Dublin 9, Ireland
| | - M M Kirstein
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - A Vogel
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - F Wacker
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - T Rodt
- Department of Diagnostic and Interventional Radiology, Hanover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.
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Schlabritz-Loutsevitch N, Carrillo M, Li C, Nathanielsz P, Maguire C, Maher J, Dick E, Hubbard G, Stanek J. A first case of hepatocellular carcinoma in the baboon (Papio spp.) placenta. J Med Primatol 2018; 48:68-73. [PMID: 30246873 DOI: 10.1111/jmp.12382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 07/17/2018] [Accepted: 08/22/2018] [Indexed: 12/01/2022]
Abstract
We present a case of hepatocellular carcinoma (HCC) in the placenta of healthy baboon (Papio spp.). Grossly, the fetal, maternal, and placental tissues were unremarkable. Histologically, the placenta contained an unencapsulated, poorly demarcated, infiltrative, solidly cellular neoplasm composed of cells that resembled hepatocytes. The neoplastic cells were diffusely positive for vimentin and focally positive for Ae1/Ae3, Arginase -1, glutamine synthetase, and CD10, and negative for ER, vascular markers (CD31 and D240), S100, glypican, C-reactive protein, FABP, desmin, and beta-catenin; INI1 positivity was similar to non-neoplastic tissues. The case likely represents a unique subtype of HCC.
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Affiliation(s)
| | - Maira Carrillo
- Texas Tech University Health Sciences Center at the Permian Basin, Odessa, Texas
| | - Cun Li
- University of Wyoming, Laramie, Wyoming.,Texas Biomedical Research Institute, San Antonio, Texas
| | - Peter Nathanielsz
- University of Wyoming, Laramie, Wyoming.,Texas Biomedical Research Institute, San Antonio, Texas
| | - Christopher Maguire
- Texas Tech University Health Sciences Center at the Permian Basin, Odessa, Texas
| | - James Maher
- Texas Tech University Health Sciences Center at the Permian Basin, Odessa, Texas
| | - Edward Dick
- Texas Biomedical Research Institute, San Antonio, Texas
| | - Gene Hubbard
- University of Texas Health Sciences Center at San Antonio, San Antonio, Texas
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30
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Yang R, Chang Q, Meng X, Gao N, Wang W. Prognostic value of Systemic immune-inflammation index in cancer: A meta-analysis. J Cancer 2018; 9:3295-3302. [PMID: 30271489 PMCID: PMC6160683 DOI: 10.7150/jca.25691] [Citation(s) in RCA: 253] [Impact Index Per Article: 36.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 07/25/2018] [Indexed: 12/21/2022] Open
Abstract
Systemic immune-inflammation index (SII), on the basis of lymphocyte, neutrophil and platelet counts had been published to be a good prognostic factor in multiple cancers. Nevertheless, the prognostic value of SII in cancer patients remains inconsistent. Therefore, we carried out a meta-analysis to evaluate the prognostic value of SII in these patients with cancer. A total of 22 articles with 7657 patients enrolled in this meta-analysis. The combined result revealed that a high SII was evidently correlated with poor overall survival (OS) (HR=1.69, 95%CI=1.42-2.01, p<0.001), poor time to recurrent (TTR) (HR=1.87, p<0.001) , poor progress-free survival (PFS) (HR=1.61, p=0.012) ,poor cancer-specific survival (CSS) (HR=1.44, p=0.027) , poor relapse-free survival (RFS) (HR=1.66, p=0.025) and poor disease-free survival (DFS) (HR=2.70, p<0.001) in patients with cancers. Subgroup analysis indicated that SII over the cutoff value could predict worse overall survival in Hepatocellular carcinoma (p<0.001), Gastric cancer (p=0.005), Esophageal Squamous Cell Carcinoma (p=0.013), Urinary system cancer (p<0.001), Small cell lung cancer (p<0.001), Non-Small cell lung cancer (p<0.001) and Acral Melanoma (p<0.001). The largest effect size was observed in the Hepatocellular carcinoma (HR=2.11). In addition, these associations did not vary significantly by the cutoff value, sample size and ethnicity. Therefore, high SII may be a potential prognostic marker in patients with various cancers and associated with the poor overall outcomes.
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Affiliation(s)
| | | | | | | | - Wanhai Wang
- Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan Province, Zhengzhou, Henan, People's Republic of China
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31
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Shimura T, Shibata M, Gonda K, Matsumoto Y, Nakano K, Iwadate M, Suzuki S, Suzuki S. Prognostic impact of elevated preoperative C-reactive protein on patients with differentiated thyroid carcinoma. J Surg Res 2018; 231:338-345. [PMID: 30278950 DOI: 10.1016/j.jss.2018.05.070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 05/15/2018] [Accepted: 05/31/2018] [Indexed: 11/25/2022]
Abstract
BACKGROUND C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). CONCLUSIONS Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4.
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Affiliation(s)
- Tatsuo Shimura
- Department of Progressive DOHaD Research, Fukushima Medical University, Fukushima, Japan.
| | - Masahiko Shibata
- Department of Advanced Cancer Immunotherapy, Fukushima Medical University, Fukushima, Japan
| | - Kenji Gonda
- Clinical Oncology Center, Fukushima Medical University, Fukushima, Japan
| | - Yoshiko Matsumoto
- Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan
| | - Keiichi Nakano
- Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan
| | - Manabu Iwadate
- Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan
| | - Satoshi Suzuki
- Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan
| | - Shinichi Suzuki
- Department of Thyroid and Endocrinology, Fukushima Medical University, Fukushima, Japan
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32
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Chen MC, Hsu WL, Hwang PA, Chen YL, Chou TC. Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice. Oncotarget 2018; 7:51608-51618. [PMID: 27323407 PMCID: PMC5239500 DOI: 10.18632/oncotarget.9958] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 05/17/2016] [Indexed: 01/06/2023] Open
Abstract
Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction. Moreover, myostatin, activin A, and pro-inflammatory cytokine production, FoxO3 expression and activation, NF-κB activation, MuRF-1 and MAFbx/atrogin-1 expression, and proteasome activity in muscle were significantly decreased in the TGCF group compared with the TGC group. In addition, insulin-like growth factor 1 (IGF-1) expression and formation, and IGF-1-regulated mTOR/p70S6k/4EBP-1 protein synthesis signalling were elevated in the TGCF group compared with the TGC group. Taken together, these results suggest that LMWF is a potential agent for preventing cancer cachexia-associated muscle atrophy during chemotherapy. Furthermore, the beneficial effect of LMWF may be attributed to suppressing NF-κB-evoked inflammation, myostatin and activin A production, and subsequent muscle proteolysis, and enhancing IGF-1-dependent protein synthesis.
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Affiliation(s)
- Meng-Chuan Chen
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Lin Hsu
- School of Medicine, Tzu Chi University, Hualien, Taiwan.,Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Pa-An Hwang
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan
| | - Yen-Lin Chen
- Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Tz-Chong Chou
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,Department of Biotechnology, Asia University, Taichung, Taiwan.,China Medical University Hospital, China Medical University, Taichung, Taiwan
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33
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Recent advances in design of electrochemical affinity biosensors for low level detection of cancer protein biomarkers using nanomaterial-assisted signal enhancement strategies. J Pharm Biomed Anal 2018; 147:185-210. [DOI: 10.1016/j.jpba.2017.07.042] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/28/2017] [Accepted: 07/29/2017] [Indexed: 12/12/2022]
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34
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Katano A, Takahashi W, Yamashita H, Yamamoto K, Ando M, Yoshida M, Saito Y, Abe O, Nakagawa K. The impact of elevated C-reactive protein level on the prognosis for oro-hypopharynx cancer patients treated with radiotherapy. Sci Rep 2017; 7:17805. [PMID: 29259311 PMCID: PMC5736698 DOI: 10.1038/s41598-017-18233-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 12/08/2017] [Indexed: 12/20/2022] Open
Abstract
The purpose of this study was to investigate an association between the prognosis for oro-hypopharynx squamous cell carcinoma treated with radiation therapy and the pre-therapeutic level of C-reactive protein (CRP). Patient with oro-hypopharyngeal squamous cell carcinoma who underwent definitive radiotherapy in our institution from January 2002 to August 2016 were enrolled. The patient were divided into elevated CRP (over 0.3 mg/dl) group and normal CRP groups, according to pre-treatment serum levels. There were 276 evaluable patients, and the median follow up was 41 months, ranging from 2 to 171 months. The 3-year OS and CSS for all enrolled patients were 67.0% and 72.8%, respectively. The OS and CSS rates were significantly worse in the elevated CRP group than in the normal CRP group, according to Kaplan-Meier survival curves analysed by a Log-rank test (p = 0.005 and p < 0.001, respectively). Multivariate analyses indicated that serum CRP levels remained independent predictors for both OS (HR: 1.588, p = 0.022) and CSS (HR: 1.989, p = 0.005). The pre-treatment CRP level is an independent predictor of treatment prognosis in patients with oro-hypopharyngeal cancer who underwent definitive radiotherapy. Especially, it is curious that an elevated CRP serum level is a significant predictor of loco-regional recurrence.
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Affiliation(s)
- Atsuto Katano
- Department of Radiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Wataru Takahashi
- Department of Radiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hideomi Yamashita
- Department of Radiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Kentaro Yamamoto
- Department of Radiology, Japan Self Defense Force Central Hospital, 1-2-24 Ikejiri, Setagaya-ku, Tokyo, 154-8532, Japan
| | - Mizuo Ando
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Masafumi Yoshida
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yuki Saito
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Osamu Abe
- Department of Radiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Keiichi Nakagawa
- Department of Radiology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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35
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Pang Q, Jin H, Man Z, Wang Y, Yang S, Li Z, Lu Y, Liu H, Zhou L. Radical versus conservative surgical treatment of liver hydatid cysts: a meta-analysis. Front Med 2017; 12:350-359. [PMID: 29170917 DOI: 10.1007/s11684-017-0559-y] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 05/03/2017] [Indexed: 12/12/2022]
Abstract
To date, the efficacy of radical surgery (RS) versus conservative surgery (CS) for liver hydatid cysts (LHC) remains controversial. This meta-analysis was conducted to compare the two interventions. PubMed, Embase, and Web of Science were searched from their inceptions until June 2016. Meta-analysis was performed using STATA 12.0 software. We identified 19 eligible studies from 10 countries by retrieval. In total, 1853 LHC patients who received RS were compared with 2274 patients treated by CS. The risk of postoperative overall complication, biliary fistula, and recurrence was significantly lower, and operation time was significantly longer in the RS group. However, no statistically significant differences were found in terms of mortality risk and the duration of hospital stay between RS and CS. No significant publication biases were observed in all the above analyses. In conclusion, RS reduces the rates of postoperative complications and recurrence, whereas no trend toward such a reduction in mortality was observed in LHC patients.
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Affiliation(s)
- Qing Pang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Hao Jin
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Zhongran Man
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Yong Wang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Song Yang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Zongkuang Li
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Yimin Lu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China
| | - Huichun Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China.
| | - Lei Zhou
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, China.
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Rosenblatt RE, Tafesh ZH, Halazun KJ. Role of inflammatory markers as hepatocellular cancer selection tool in the setting of liver transplantation. Transl Gastroenterol Hepatol 2017; 2:95. [PMID: 29264433 DOI: 10.21037/tgh.2017.10.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 10/17/2017] [Indexed: 12/12/2022] Open
Abstract
Since the advent of the Milan criteria in 1996 and its widespread adoption for selection of patients with hepatocellular carcinoma (HCC) who would benefit from transplant, there has been an extensive hunt for the ideal clinical biomarker to predict HCC recurrence. This is because Milan lack does not include tumor biology indices and recurrence rates remain in the 15-20% range worldwide. While a 'silver-bullet' biomarker has not been found, several useful inflammatory markers have been identified and used in scoring systems that supersede Milan in their ability to predict HCC recurrence post liver transplantation (LT). In this review, we aim to summarize the role of inflammatory markers paly in the selection of HCC patients awaiting LT.
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Affiliation(s)
- Russell E Rosenblatt
- Division of gastroenterology and hepatology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
| | - Zaid H Tafesh
- Division of gastroenterology and hepatology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
| | - Karim J Halazun
- Department of surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
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37
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Xuan ZD, Zhou L, Wang Y, Zheng X. Prognostic value of the combination of serum levels of vascular endothelial growth factor, C-reactive protein and contrast-enhanced ultrasound in patients with primary liver cancer who underwent transcatheter arterial chemoembolization. Expert Rev Anticancer Ther 2017; 17:1169-1178. [PMID: 29048943 DOI: 10.1080/14737140.2017.1395284] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Zhi-Dong Xuan
- The 3rd Department of Ultrasound, Cangzhou Central Hospital, Cangzhou, P.R. China
| | - Li Zhou
- The 3rd Department of Ultrasound, Cangzhou Central Hospital, Cangzhou, P.R. China
| | - Yu Wang
- The 3rd Department of Ultrasound, Cangzhou Central Hospital, Cangzhou, P.R. China
| | - Xue Zheng
- The 3rd Department of Ultrasound, Cangzhou Central Hospital, Cangzhou, P.R. China
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38
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Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial. Med Oncol 2017; 34:192. [PMID: 29098441 PMCID: PMC5668342 DOI: 10.1007/s12032-017-1040-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 09/14/2017] [Indexed: 12/15/2022]
Abstract
Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6-3.79) for all evaluable patients and 8.4 months (95% CI: 0-18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08-9.31) and 9.4 months (95% CI: 4.82-13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24-15.35) versus 2.7 months (95% CI: 1.03-4.36; P = 0.002), and 9.8 months (95% CI: 3.23-16.37) versus 4.4 months (95% CI: 3.14-5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of < 5 cm. The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control. Biomodulatory therapy in advanced HCC may be a low toxic, efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC.
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39
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Fang Y, Xu C, Wu P, Zhang LH, Li DW, Sun JH, Li WF, Liao ZS. Prognostic role of C-reactive protein in patients with nasopharyngeal carcinoma: A meta-analysis and literature review. Medicine (Baltimore) 2017; 96:e8463. [PMID: 29137033 PMCID: PMC5690726 DOI: 10.1097/md.0000000000008463] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND C-reactive protein (CRP) has been shown to be associated with several tumors. However, its association with nasopharyngeal carcinoma (NPC) is not well characterized. We performed a literature review and meta-analysis to assess the prognostic relevance of elevated CRP levels in patients with NPC. METHODS A literature search for relevant studies was performed on PubMed (Medline), the Cochrane Library, and Web of Science databases. Hazard ratios (95% confidence intervals) were calculated to assess the association between elevated CRP levels and survival outcomes. RESULTS Five studies with a combined study population of 5215 patients with NPC were included. Pooled hazard ratios for overall survival and distant metastasis-free survival were 1.84 (95% CI = 1.57-2.17) and 1.81 (95% CI = 1.53-2.14), respectively. Subgroup analyses showed that types of indicators and treatment before inclusion had no significant impact on the observed association. CONCLUSION Elevated serum CRP levels in patients with NPC were associated with worse prognosis.
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Affiliation(s)
| | - Chang Xu
- Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University
| | - Peng Wu
- Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University
| | - Ling-Hao Zhang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University
| | | | - Jie-Hao Sun
- Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University
| | - Wen-Feng Li
- Department of Radiochemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhi-Su Liao
- Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University
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40
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Liu G, Dong C, Liu L. Integrated Multiple "-omics" Data Reveal Subtypes of Hepatocellular Carcinoma. PLoS One 2016; 11:e0165457. [PMID: 27806083 PMCID: PMC5091875 DOI: 10.1371/journal.pone.0165457] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 10/12/2016] [Indexed: 12/29/2022] Open
Abstract
Hepatocellular carcinoma is one of the most heterogeneous cancers, as reflected by its multiple grades and difficulty to subtype. In this study, we integrated copy number variation, DNA methylation, mRNA, and miRNA data with the developed “cluster of cluster” method and classified 256 HCC samples from TCGA (The Cancer Genome Atlas) into five major subgroups (S1-S5). We observed that this classification was associated with specific mutations and protein expression, and we detected that each subgroup had distinct molecular signatures. The subclasses were associated not only with survival but also with clinical observations. S1 was characterized by bulk amplification on 8q24, TP53 mutation, low lipid metabolism, highly expressed onco-proteins, attenuated tumor suppressor proteins and a worse survival rate. S2 and S3 were characterized by telomere hypomethylation and a low expression of TERT and DNMT1/3B. Compared to S2, S3 was associated with less copy number variation and some good prognosis biomarkers, including CRP and CYP2E1. In contrast, the mutation rate of CTNNB1 was higher in S3. S4 was associated with bulk amplification and various molecular characteristics at different biological levels. In summary, we classified the HCC samples into five subgroups using multiple “-omics” data. Each subgroup had a distinct survival rate and molecular signature, which may provide information about the pathogenesis of subtypes in HCC.
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Affiliation(s)
- Gang Liu
- Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China
| | - Chuanpeng Dong
- Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China
| | - Lei Liu
- Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China
- * E-mail:
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Nakanishi H, Kurosaki M, Tsuchiya K, Yasui Y, Higuchi M, Yoshida T, Komiyama Y, Takaura K, Hayashi T, Kuwabara K, Nakakuki N, Takada H, Ueda M, Tamaki N, Suzuki S, Itakura J, Takahashi Y, Izumi N. Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment. Liver Cancer 2016; 5:257-268. [PMID: 27781198 PMCID: PMC5075810 DOI: 10.1159/000449337] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. METHODS A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. RESULTS The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. CONCLUSIONS A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Namiki Izumi
- *Namiki Izumi, MD, PhD, Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo (Japan), Tel. +81 422 32 3111, E-Mail
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Li Z, Xue TQ, Chen XY. Predictive values of serum VEGF and CRP levels combined with contrast enhanced MRI in hepatocellular carcinoma patients after TACE. Am J Cancer Res 2016; 6:2375-2385. [PMID: 27822426 PMCID: PMC5088300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 09/15/2016] [Indexed: 06/06/2023] Open
Abstract
This study explored the predictive value of serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) levels combined with enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). One hundred and seventeen patients who received TACE from June 2010 to December 2012 in our hospital were included in this study. Serum VEGF and CRP levels before and after TACE were determined by ELISA and single immunodiffusion method for analyzing the association of serum levels with pathological features. Enhanced MRI was utilized before and after TACE to measure tumor size and ADC value in enhanced region and non-enhanced region. MRI data were combined with serum VEGF and CRP levels to analyze the predictive value in efficacy and prognosis for HCC patients after TACE. The serum VEGF and CRP levels after TACE were increased, but can return to normal levels in a certain time. VEGF and CRP levels were not statistically associated with tumor location, tumor staining or presence of membrane (all P > 0.05), but closely correlated with combined portal vein tumor thrombus, combined arteriovenous fistula and distant metastasis (all P < 0.05). Low levels of serum VEGF and CRP, small tumor size and low ADC value before treatment indicated a better prognosis. The sensitivity and specificity of serum VEGF and CRP levels, tumor size and ADC value were respectively 92.31% and 88.46%, 93.85% and 90.38%, 81.54% and 78.85% as well as 47.69% and 84.62%. Serum VEGF and CRP levels, tumor size and ADC value could predict the efficacy of TACE for HCC patients. Serum VEGF and CRP levels combined with enhanced MRI may serve as markers for efficacy and prognosis evaluation in HCC patients after TACE.
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Affiliation(s)
- Zhi Li
- Department of Interventional Radiology, The First Affliated Hospital of Soochow UniversitySuzhou 215006, P. R. China
| | - Tong-Qing Xue
- Department of Interventional Radiology, The First Affliated Hospital of Soochow UniversitySuzhou 215006, P. R. China
- Department of Pain and Interventional Radiology, The Second People’s Hospital of Huai’anHuai’an 223300, P. R. China
- Department of Pain and Interventional Radiology, Huaiyin Hospital of Huai’anHuai’an 223300, P. R. China
| | - Xiao-Yu Chen
- Department of Radiology, The Second People’s Hospital of Huai’anHuai’an 223300, P. R. China
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Lee HW, Suh KS. Liver transplantation for advanced hepatocellular carcinoma. Clin Mol Hepatol 2016; 22:309-318. [PMID: 27729631 PMCID: PMC5066382 DOI: 10.3350/cmh.2016.0042] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 08/10/2016] [Indexed: 12/12/2022] Open
Abstract
There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future.
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Affiliation(s)
- Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.,Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Rekik S, Guyot E, Bhais M, Ajavon Y, Grando V, Bourcier V, Nkontchou G, Nahon P, Sellier N, Seror O, Ganne-Carrie N, Nault JC. The CRP level and STATE score predict survival in cirrhotic patients with hepatocellular carcinoma treated by transarterial embolization. Dig Liver Dis 2016; 48:1088-1092. [PMID: 27375209 DOI: 10.1016/j.dld.2016.06.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 05/19/2016] [Accepted: 06/08/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Prognostic biomarkers are needed in a heterogeneous population of patients with intermediate hepatocellular carcinoma (HCC) treated by transarterial (chemo)embolization. We aimed to validate the prognostic value of serum CRP levels and the STATE score, combining CRP, albumin and tumor burden. METHODS All cirrhotic patients with HCC treated by a first transarterial (chemo)embolization (2007-2013) in our institution were included. Overall survival was assessed using the Kaplan-Meier method, log rank, univariate and multivariate Cox analyses. RESULTS Among 157 patients included, 87% were men, 86% had Child Pugh A. Etiologies of liver disease included alcohol (57%), hepatitis C (32%), hepatitis B (11%) and/or metabolic syndrome (32%); 89% of patients were classified BCLC B. 33% of the patients had a CRP >1mg/dl and 33% a STATE score conferring poor prognosis (<18). Patients with CRP <1mg/dl had better overall survival than patients with CRP >1mg/dl (20 vs. 8 months, P=0.00186). Median overall survival was 6.73 months for patients with a STATE score <18 vs. 22.23 months for patients with STATE-score ≥18 (P=0.0002). In multivariate analysis, a STATE score <18 was independently associated with increased mortality (HR: 2.06 (CI95%: 1.28-3.34), P=0.0031). CONCLUSION In cirrhotic patients with HCC who underwent transarterial treatment, serum CRP level and STATE score at baseline can predict overall survival.
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Affiliation(s)
- Samia Rekik
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France
| | - Erwan Guyot
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Biochemistry Department, Bondy, France
| | - Mohannad Bhais
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France
| | - Yves Ajavon
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Radiology Department, Bondy, France
| | - Véronique Grando
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France
| | - Valérie Bourcier
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France
| | - Gisèle Nkontchou
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France
| | - Pierre Nahon
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France; Inserm, UMR-1162, Functional Genomic of Solid Tumors, Team "Ligue Contre le Cancer", Paris, France; Paris Descartes University, Labex Immuno-Oncology, Sorbonne Paris Cité, Paris, France; Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France; Paris Diderot University, Paris, France
| | - Nicolas Sellier
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Radiology Department, Bondy, France; Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France
| | - Olivier Seror
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Radiology Department, Bondy, France; Inserm, UMR-1162, Functional Genomic of Solid Tumors, Team "Ligue Contre le Cancer", Paris, France; Paris Descartes University, Labex Immuno-Oncology, Sorbonne Paris Cité, Paris, France; Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France; Paris Diderot University, Paris, France
| | - Nathalie Ganne-Carrie
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France; Inserm, UMR-1162, Functional Genomic of Solid Tumors, Team "Ligue Contre le Cancer", Paris, France; Paris Descartes University, Labex Immuno-Oncology, Sorbonne Paris Cité, Paris, France; Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France; Paris Diderot University, Paris, France
| | - Jean-Charles Nault
- APHP, Hôpitaux universitaires Paris - Seine Saint-Denis, Jean Verdier, Liver Unit, Bondy, France; Inserm, UMR-1162, Functional Genomic of Solid Tumors, Team "Ligue Contre le Cancer", Paris, France; Paris Descartes University, Labex Immuno-Oncology, Sorbonne Paris Cité, Paris, France; Paris 13 University, Sorbonne Paris Cité, UFR SMBH, Bobigny, France; Paris Diderot University, Paris, France.
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45
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Expansion of the criteria for living donor liver transplantation for hepatocellular carcinoma. Curr Opin Organ Transplant 2016; 21:231-7. [PMID: 26918880 DOI: 10.1097/mot.0000000000000294] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Several expanded criteria for liver transplantation for hepatocellular carcinoma (HCC) have been suggested out of concern that the Milan criteria may be too strict, and thereby exclude patients who could benefit from this surgical procedure. However, most expanded criteria were designed for deceased donor liver transplantation. Living donor liver transplantation (LDLT) differs from that of deceased donor liver transplantation primarily because LDLT liver grafts are not public resources. RECENT FINDINGS In Asian countries, where HCC is endemic, LDLT is the main currently available treatment option for HCC. High-volume LDLT centers throughout Asia have adopted their own expanded selection criteria for LDLT for HCC with acceptable long-term results. Some centers utilize tumor markers as one of the criterion to help select suitable candidates. Indeed, such adjunctive biomarkers may have prognostic relevance for patients with HCC. The use of both biological and histomorphologic parameters may increase the number of transplantable patients. SUMMARY The overall chance of survival, and recipient/donor preferences as well as the risk of recurrence are considered in the LDLT setting. Therefore, the selection criteria for liver transplantation for HCC could benefit from expansion for LDLT.
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Craig SM, Fry JK, Rodrigues Hoffmann A, Manino P, Heilmann RM, Suchodolski JS, Steiner JM, Hottinger HA, Hunter SL, Lidbury JA. Serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease. J Small Anim Pract 2016; 57:459-64. [PMID: 27271454 DOI: 10.1111/jsap.12504] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 03/03/2016] [Accepted: 03/04/2016] [Indexed: 01/19/2023]
Abstract
OBJECTIVES To describe serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease and to determine whether there is a relationship between the concentration of either and the severity of hepatic necroinflammation. METHODS Serum C-reactive protein and S100A12 concentrations were measured in 46 dogs undergoing hepatic biopsy. Dogs were divided into three groups: congenital portosystemic shunts, chronic hepatitis and hepatic neoplasia. The histological severity of hepatic necroinflammation was scored. RESULTS C-reactive protein and S100A12 concentrations were greater than the upper limit of the reference intervals in 39 and 26% of dogs, respectively. There was no association of disease group with C-reactive protein (P=0·1733) or S100A12 (P=0·1513) concentrations. There was a positive correlation between serum C-reactive protein concentration and hepatic necroinflammatory activity (rs =0·428, P=0·006). CLINICAL SIGNIFICANCE Increased serum C-reactive protein and S100A12 concentrations were observed in a subpopulation of dogs with various types of hepatic diseases, suggesting acute-phase inflammation and activation of phagocytic cells, respectively. Dogs with higher hepatic necroinflammatory activity scores tended to have higher serum C-reactive protein concentrations. Further studies are needed to confirm this finding in a larger group of dogs.
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Affiliation(s)
- S M Craig
- Gulf Coast Veterinary Specialists, Houston, Texas, 77027, USA
| | - J K Fry
- Gulf Coast Veterinary Specialists, Houston, Texas, 77027, USA
| | - A Rodrigues Hoffmann
- Department of Pathobiology, College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, 77843-4474, USA
| | - P Manino
- Gulf Coast Veterinary Specialists, Houston, Texas, 77027, USA
| | - R M Heilmann
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, 77843-4474, USA
| | - J S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, 77843-4474, USA
| | - J M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, 77843-4474, USA
| | - H A Hottinger
- Gulf Coast Veterinary Specialists, Houston, Texas, 77027, USA
| | - S L Hunter
- Gulf Coast Veterinary Specialists, Houston, Texas, 77027, USA
| | - J A Lidbury
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, College Station, Texas, 77843-4474, USA
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47
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Liver transplantation for hepatobiliary malignancies: a new era of "Transplant Oncology" has begun. Surg Today 2016; 47:403-415. [PMID: 27130463 DOI: 10.1007/s00595-016-1337-1] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 04/06/2016] [Indexed: 01/10/2023]
Abstract
The indications of liver transplantation for hepatobiliary malignancies have been carefully expanded in a stepwise fashion, despite the fundamental limitations in oncological, immunological, and technical aspects. A new era of "Transplant Oncology," the fusion of transplant surgery and surgical oncology, has begun, and we stand at the dawn of a paradigm shift in multidisciplinary cancer treatment. For hepatocellular carcinoma, new strategies have been undertaken to select recipients based on biological and dynamic markers instead of conventional morphological and static parameters, opening the doors for a more deliberate expansion of the Milan criteria and locoregional therapies before liver transplantation. Neoadjuvant chemoradiation therapy followed by liver transplantation for unresectable perihilar cholangiocarcinoma developed by the Mayo Clinic provided excellent outcomes in a US multicenter study; however, the surgical indications are not necessarily universal and await international validation. Similarly, an aggressive multidisciplinary approach has been applied for other tumors, including intrahepatic cholangiocarcinoma, hepatoblastoma, liver metastases from colorectal and neuroendocrine primary and gastrointestinal stromal tumors as well as rare tumors, such as hepatic undifferentiated embryonal sarcoma and infantile choriocarcinoma. In conclusion, liver transplantation is an important option for hepatobiliary malignancies; however, prospective studies are urgently needed to ensure the appropriate patient selection, organ allocation and living donation policies, and administration of antineoplastic immunosuppression.
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48
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Hobusch GM, Bodner F, Walzer S, Marculescu R, Funovics PT, Sulzbacher I, Windhager R, Panotopoulos J. C-reactive protein as a prognostic factor in patients with chordoma of lumbar spine and sacrum--a single center pilot study. World J Surg Oncol 2016; 14:111. [PMID: 27091202 PMCID: PMC4836072 DOI: 10.1186/s12957-016-0875-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Accepted: 04/13/2016] [Indexed: 12/24/2022] Open
Abstract
Study design This is a retrospective, diagnostic study, level IV. Background It appears to be necessary to identify prognostic markers for individual risk estimation for progression and survival in patients with chordoma, a rare disease. Are pre-operative serum levels of C-reactive protein (CRP) associated with disease progression and survival? Methods Survival rates of 24 patients (18 males, 6 females) (mean age 67 years (SD ± 16; range 20–85 years); minimum follow-up 2 years, mean follow-up 5 years (SD ± 5; range 2–19 years)) with chordoma of the lower spine and sacrum were assessed with a focus on pre-operative CRP levels. Results The survival rate of patients with pre-operative CRP level of >1.0 mg/dl was lower than that of patients with a CRP level <1.0 mg/dl (p = 0.01). The estimated 10-year survival of patients with pre-operative CRP values <1.0 and >1.0 mg/dl was 76 and 25 %, respectively. CRP remained as an independent survival factor (p = 0.025; CI 95 % 1.0–2.6) in multivariable analysis. Conclusions Pre-operative CRP levels appear to be a biomarker for disease-specific survival in patients with chordoma of the lumbar spine and sacrum. A validation of our finding with larger cohorts and integration of putative risk factor would further elucidate CRP a surrogate for tumor progression.
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Affiliation(s)
- Gerhard Martin Hobusch
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria.
| | - Florian Bodner
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria
| | - Sonja Walzer
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria
| | - Rodrig Marculescu
- Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
| | - Philipp T Funovics
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria
| | - Irene Sulzbacher
- Clinical institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Reinhard Windhager
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria
| | - Joannis Panotopoulos
- Department of Orthopaedics, Medical University of Vienna, Waehringer Guertel 18 - 20, A-1090, Wien, Austria
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Strojny B, Kurantowicz N, Sawosz E, Grodzik M, Jaworski S, Kutwin M, Wierzbicki M, Hotowy A, Lipińska L, Chwalibog A. Long Term Influence of Carbon Nanoparticles on Health and Liver Status in Rats. PLoS One 2015; 10:e0144821. [PMID: 26657282 PMCID: PMC4681315 DOI: 10.1371/journal.pone.0144821] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 11/24/2015] [Indexed: 12/12/2022] Open
Abstract
Due to their excellent biocompatibility, carbon nanoparticles have been widely investigated for prospective biomedical applications. However, their impact on an organism with prolonged exposure is still not well understood. Here, we performed an experiment investigating diamond, graphene oxide and graphite nanoparticles, which were repeatedly administrated intraperitoneally into Wistar rats for four weeks. Some of the animals was sacrificed after the last injection, whereas the rest were sacrificed twelve weeks after the last exposure. We evaluated blood morphology and biochemistry, as well as the redox and inflammatory state of the liver. The results show the retention of nanoparticles within the peritoneal cavity in the form of prominent aggregates in proximity to the injection site, as well as the presence of some nanoparticles in the mesentery. Small aggregates were also visible in the liver serosa, suggesting possible transportation to the liver. However, none of the tested nanoparticles affected the health of animals. This lack of toxic effect may suggest the potential applicability of nanoparticles as drug carriers for local therapies, ensuring accumulation and slow release of drugs into a targeted tissue without harmful systemic side effects.
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Affiliation(s)
- Barbara Strojny
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Natalia Kurantowicz
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Ewa Sawosz
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Marta Grodzik
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Sławomir Jaworski
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Marta Kutwin
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Mateusz Wierzbicki
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Anna Hotowy
- Division of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Ludwika Lipińska
- Department of Chemical Technologies, Institute of Electronic Materials Technology, Warsaw, Poland
| | - André Chwalibog
- Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
- * E-mail:
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Kornberg A, Witt U, Kornberg J, Müller K, Friess H, Thrum K. Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma. Biomarkers 2015; 21:152-9. [PMID: 26643974 DOI: 10.3109/1354750x.2015.1118548] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
CONTEXT C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies. OBJECTIVE To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC). METHODS AND RESULTS In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus ≤ 3.5 mg/dl) was identified as an independent predictor of poor recurrence-free survival (p = 0.01; HR = 4.04; CI = 1.399-11.640). CONCLUSION Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.
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Affiliation(s)
- Arno Kornberg
- a Department of Surgery, Klinikum Rechts Der Isar, Technical University , Munich , Germany
| | - Ulrike Witt
- a Department of Surgery, Klinikum Rechts Der Isar, Technical University , Munich , Germany
| | - Jennifer Kornberg
- b Department of Anaesthesiology , Klinikum Großhadern, LMU Munich , Germany
| | | | - Helmut Friess
- a Department of Surgery, Klinikum Rechts Der Isar, Technical University , Munich , Germany
| | - Katharina Thrum
- d Institute of Pathology , Helios Klinikum, Berlin , Germany
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