Prognostic significance of the controlling nutritional status score in patients with biliary tract cancer

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Prognostic significance of the controlling nutritional status score in patients with biliary tract cancer

https://doi.org/10.21203/rs.3.rs-3219792/v1

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Background: Numerous studies have demonstrated the significance of assessing nutritional status, commonly referred to as Controlling Nutritional Status (CONUT), in predicting the prognostic outcomes of diverse malignancies. Nevertheless, its prognostic significance in individuals diagnosed with biliary tract cancer (BTC) remains an area yet to be comprehensively explored. The CONUT score was analyzed in this study to determine its prognostic significance in BTC patients.

Methods: To obtain relevant literature concerning the prognostic implications for patients with BTC and the utilization of the CONUT score, an exhaustive literature search was systematically carried out across multiple databases, including PubMed, Web of Science, and Embase. The search encompassed articles published up to and including April 23, 2023. To amalgamate the data, a comprehensive pooled analysis utilized hazard ratios (HRs) alongside their respective 95% confidence intervals (95% CIs). All statistical computations were performed using STATA 12.0 software.

Results:

The meta-analysis encompassed nine articles, which collectively involved 1363 patients. The collective findings demonstrated a significant association between a high CONUT score and adverse outcomes in terms of overall survival (OS) (HR: 1.94, 95% CI: 1.40-2.69) as well as disease-free survival/recurrence-free survival (DFS/RFS) (HR: 2.17, 95% CI: 1.71-2.75). Sensitivity analysis further substantiated the robustness and reliability of the meta-analysis results.

Conclusions: In patients diagnosed with BTC, a high CONUT score was found to be strongly associated with an adverse prognosis. Patients with BTC may benefit from CONUT scores as prognostic indicators.

Biological sciences/Cancer

Health sciences/Biomarkers

Health sciences/Gastroenterology

CONUT score

Biliary tract cancer

Prognosis

Survival

Meta-analysis

The biliary tract cancer (BTC) is one of the most malignant tumors of the digestive system (1). Based on the tumor location, BTC can be classified into four types: gallbladder carcinomas (GBCs), ampulla carcinomas (AVCs), intrahepatic cholangiocarcinomas (iCCAs), and extrahepatic cholangiocarcinomas (eCCAs). [1]. In recent years, the incidence of BTC has an increasing trend [2]. BTC's occurrence and development are closely related to heredity, chronic history, lifestyle, and environmental factors [3]. Radical resection is the only possible choice to cure the BTC [4]. However, it is common for patients to be diagnosed at an advanced stage of this disease. Despite effective surgical excision, many patients still experience tumor recurrence very quickly [5]. Therefore, stratification and individualized treatment of BTC patients are crucial to improve the short-term and long-term survival outcomes.

Debuting in 2012, the CONUT score has emerged as a valuable metric for evaluating the nutritional status of patients [6]. This scoring system incorporates three pivotal indicators: serum albumin levels, cholesterol levels, and lymphocyte count. The intricate particulars of the CONUT scoring system are delineated in Table 1. An accumulation of research studies has consistently showcased the reliability of the CONUT score as a prognostic marker across a spectrum of malignancies, encompassing both hematologic and solid tumors [7–10].

Table 1

The controlling nutritional status scoring system
Parameters		Degree
	Normal	Light	Moderate	Severe
Serum albumin (g/dL)	≥ 3.5	3.0–3.49	2.50–2.99	< 2.50
Score	0	2	4	6
Total lymphocyte count(/mm³)	≥ 1600	1200–1599	800–1199	< 800
Score	0	1	2	3
Total cholesterol(mg/dL)	≥ 180	140–179	100–139	< 100
Score	0	1	2	3

CONUT score has recently been examined as a prognostic indicator in patients with BTC by many researchers. It has been suggested that patients with BTC can use the CONUT score as a prognostic indicator in some studies [11, 12]. However, other studies show the opposite view [13, 14]. In order to address potential controversies and provide a comprehensive assessment, we conducted an extensive meta-analysis to evaluate the prognostic significance of the CONUT score in patients diagnosed with BTC.

Search strategy

A thorough and systematic investigation was conducted, involving a meticulous search of reputable databases such as PubMed, Web of Science, and EMBASE. This exhaustive search was designed to uncover articles examining the relationship between the CONUT score and its prognostic relevance for individuals afflicted by BTC. The search was confined to articles published up to and including April 23, 2023. The search strategy employed in this study encompassed the following keywords: "controlling nutritional status" OR "CONUT" OR "controlling nutritional status score" OR "CONUT score" AND “bile duct adenoma” OR “bile duct neoplasms” OR “bile duct cancer” OR “bile duct tumor” OR “biliary tract cancer” OR “cholangiocarcinoma” OR “cholangiocellular carcinoma” OR “gallbladder cancer” OR “gallbladder carcinoma”. Language was limited in English. We also manually searched the included references for possible studies.

Inclusion and exclusion criteria

Our article selection process adhered to specific criteria, which encompassed the following: (1) inclusion criteria involved studies that investigated the impact of the CONUT score on the survival outcomes of patients diagnosed with BTC. (2) incorporation of studies that furnished statistically significant data, enabling the calculation of Hazard Ratios (HRs) along with their corresponding 95% Confidence Intervals (CIs). Exclusion criteria: (1) case report, review, letter, comment and conference abstract; (2) studies with insufficient data.

Data extraction and quality assessment

The data employed in this study were scrupulously extracted from the selected research articles. Key variables encompassed crucial details, including the primary author's name, publication year, country of origin, study design, sample size, analytical methods, histological classification, and significant clinical endpoints, notably Overall Survival (OS), Disease-Free Survival (DFS), and Recurrence-Free Survival (RFS). In order to assess the methodological quality and rigor of the articles incorporated into our analysis, we utilized the Newcastle-Ottawa Scale (NOS) as a standardized assessment tool [15]. NOS score greater than 6 was considered high quality.

Statistical analysis

All statistical analyses were executed utilizing STATA version 12.0 software (Stata Corporation, College Station, TX, USA). The assessment of heterogeneity was carried out employing the I² statistic. When I² was determined to be less than 50%, a fixed-effects model was employed. Conversely, if I² exceeded 50%, we opted for a random-effects model. Subgroup analysis was systematically carried out to investigate potential origins of heterogeneity. Furthermore, we conducted sensitivity analysis to evaluate the robustness of the meta-analysis results. In addition, to gauge the potential existence of publication bias, we utilized Begg's test, Egger's test, and the trim-and-fill method [16]. A significance level of P < 0.05 was considered statistically significant.

Search results

From our initial search across the pertinent databases, a total of 48 relevant articles were identified, and subsequently, 22 duplicate entries were removed. After a rigorous scrutiny of the titles and abstracts, a further 16 articles were determined to be ineligible and subsequently excluded from the analysis. Subsequently, upon conducting a comprehensive review of the full texts of the remaining articles, we ultimately included nine studies, involving a collective cohort of 1363 patients, in our analysis [11–14, 17–21]. The screening process was shown in Fig. 1.

Study characteristics

In Table 2, we have provided a comprehensive summary of the clinical characteristics of the studies included in our analysis. Among these studies, 5 were conducted in Japan, while 4 originated from China. A total of 9 studies furnished data on OS, and 5 studies presented data on DFS or RFS. It is noteworthy that all studies directly supplied survival outcome information and presented the results of multivariate analysis. Furthermore, it is worth highlighting that all the studies encompassed in our analysis achieved Newcastle-Ottawa Scale (NOS) scores exceeding 6, underscoring their high methodological quality (mean: 6.78).

Table 2

Basic information of the included studies **Abbreviations**: iCCA: intrahepatic cholangiocarcinoma; eCCA: extrahepatic cholangiocarcinoma; GBC: gallbladder cancer; BTC: bile duct cancer; OS, overall survival; DFS, disease-free survival; RFS, recurrence free survival;
Study	Year	Coutry	Study type	Sample	Treatment methods	Analysis type	Survival analysis	Histological type	NOS socore
Asakura	2022	Japan	Retrospective	169	Surgery	Multivariate	OS	eCCA	7
Cui	2018	China	Retrospective	73	Non-surgery	Multivariate	OS	eCCA	6
Mito	2022	Japan	Retrospective	224	Surgery	Multivariate	OS,RFS	BTC	7
Miyata	2017	Japan	Retrospective	71	Surgery	Multivariate	OS,RFS	iCCA	7
Sun	2021	China	Retrospective	371	Surgery	Multivariate	OS	BTC	7
Terasaki	2021	Japan	Retrospective	149	Surgery	Multivariate	OS,RFS	eCCA	7
Utsumi	2019	Japan	Retrospective	45	Surgery	Multivariate	OS	GBC	6
Wang	2021	China	Retrospective	94	Surgery	Multivariate	OS,DFS	eCCA	7
Zheng	2020	China	Retrospective	167	Surgery	Multivariate	OS,RFS	iCCA	7

Impact of CONUT score on OS

In the investigation of the relationship between the CONUT score and OS, our analysis incorporated a total of nine studies. Due to the noticeable heterogeneity detected among these studies (I² = 81.5%), we opted for a random-effects model for the implementation of this meta-analysis. The collective results derived from this analysis demonstrated a significant association between a high CONUT score and an unfavorable prognosis for individuals diagnosed with BTC (HR:1.94, 95% CI:1.40–2.69) (Fig. 2).

Subgroup analysis for OS

We implemented subgroup analysis by country, treatment methods, and histological type (Fig. 3). We found that high CONUT score had prognostic significance in the subgroups of China(HR:1.74, 95% CI:1.07–2.84) or Japan(HR:2.00, 95% CI:1.52–2.64). High CONUT score had prognostic value in both surgical group(HR:1.94, 95% CI:1.37–2.75) and non-surgical group(HR:2.02, 95% CI:1.37–2.75). In terms of pathological type, high CONUT score had survival value in eCCA(HR:2.29, 95% CI:1.40–3.76), BTC(HR:1.57, 95% CI:1.14–2.16) and GBC(HR:4.69, 95% CI:1.50–15.10). In addition, it is noteworthy that the heterogeneity observed in this meta-analysis may primarily stem from the diversity of countries in which the included studies were conducted.

Impact of CONUT score on DFS/RFS

Within a subgroup comprising 5 articles, encompassing a total of 705 patients, the association between the CONUT score and DFS or RFS was investigated. Remarkably, individuals with elevated CONUT scores consistently displayed a propensity towards poorer DFS/RFS outcomes (HR:2.17, 95% CI:1.71–2.75) (Fig. 4).

Sensitivity analysis

We performed a sensitivity analysis to assess the robustness and stability of the meta-analysis results (Fig. 5). We found that the deletion of any study has no effect on the combined results. Thus, the outcomes of the meta-analysis were found to be both stable and reliable.

Publication bias

Publication bias in this study was assessed by Begg’s test and Egger’s test. The p value of Begg’s test and Egger’s test for OS was 0.016 and 0.003, respectively. The result displayed that there was the publication bias for OS (Fig. 6A). Therefore, we assessed the stability of the combined results using the trim-and-fill method, which showed the result for OS was not affected (HR: 1.54,95CI%:1.12–2.09) (Fig. 6B). The p value of Begg’s test and Egger’s test for DFS/RFS was 0.221 and 1.43, respectively (Fig. 6C). There was no significant publication bias for DFS/RFS because p value was greater than 0.05.

The CONUT score functions as a widely embraced nutritional screening tool, facilitating the evaluation of patients' nutritional states. Numerous meta-analyses have consistently affirmed the effectiveness of the CONUT score in prognostic assessments of individuals across various tumor types [22, 23].

In comparison to alternative indicators such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI), the CONUT score demonstrates a heightened level of predictive accuracy [21, 24]. However, the comprehensive scope of the prognostic potential of the CONUT score in the context of BTC remains inadequately elucidated.

The meta-analysis encompassed a total of nine studies, comprising 1363 patients. The aggregated findings from these studies revealed that individuals with elevated CONUT scores exhibited poorer OS and DFS/RFS outcomes. Subgroup analysis revealed that country may be one of the sources of heterogeneity. In addition, among different histological type of BTC, CONUT score had better predictive value for eCCA, GBC or BTC.

The CONUT score has demonstrated notable advantages in prognostic prediction through its assessment of the nutritional and immune status of cancer patients. Nevertheless, the precise mechanism by which the CONUT score influences the prognosis of tumor patients remains elusive. We tried to explain this phenomenon in terms of the component parameters of the CONUT score.

Albumin constitutes a vital constituent of human plasma, serving as a robust indicator of both liver function and nutritional status. Studies have shown that hypoproteinemia can lead to immune suppression [25, 26]. In addition, albumin can effectively inhibit the development of inflammation in the body [27]. Inflammation has been recognized as one of the hallmarks of tumors. Evidence have displayed that hypoalbuminemia could predict adverse survival outcomes of different tumors, and increasing the serum albumin level of cancer patients is obviously beneficial to improve the survival time [28, 29].

Lymphocytes represent a crucial component of the immune system, exerting a pivotal role in the body's anti-tumor immune defense mechanisms. Lymphocytes can restrain tumor progression by directly inhibiting tumor cell proliferation. Studies have suggested that high levels of lymphocytes in the blood are beneficial to the prognosis of tumor patients[30, 31]. In addition, lymphocytopenia could reveal poorer survival outcomes in tumors [32, 33].

Cholesterol, as a pivotal constituent of cell membranes, actively participates in intracellular signal transduction processes. Cholesterol has been shown to be involved in inflammatory responses and immune response [34, 35]. Low cholesterol level can diminish the anti-tumor capacity of immune cells [36]. Oxysterols, which result from the oxidation of cholesterol, exert a notable inhibitory influence on the proliferation of numerous tumor cell types [37]. In addition, reduced blood cholesterol levels have been consistently documented across a range of malignancies and are correlated with unfavorable tumor prognoses [38, 39].

A high CONUT score signifies reduced levels of albumin, diminished lymphocyte count, and decreased cholesterol levels. The high CONUT score show poor nutritional status and immune dysfunction of tumor patients. Therefore, it is readily comprehensible that an elevated CONUT score is closely correlated with an unfavorable prognosis in patients diagnosed with BTC.

This study was subject to several limitations. Firstly, all the included articles were retrospective in nature, which may introduce inherent biases. Additionally, the overall sample size of patients was relatively small. Furthermore, it's important to note that the studies selected for this analysis were exclusively from China and Japan, potentially limiting the generalizability of the findings to a broader international context. Studies from other regions and countries were needed to further explore this issue. Finally, there was publication bias for OS, the result need be treated with caution.

Our study possesses several notable strengths. First and foremost, this meta-analysis represents a groundbreaking endeavor, delving into the prognostic importance of the CONUT score in individuals diagnosed with BTC. Secondly, the conducted subgroup analysis provided additional substantiation for the prognostic significance of the CONUT score. Moreover, sensitivity analysis underscored the robustness and consistency of our findings. Finally, the application of the trim-and-fill method confirmed that the outcomes of our meta-analysis remained unaffected by potential publication bias.

In conclusion, the results of our study robustly demonstrate a noteworthy association between an elevated CONUT score and adverse OS and DFS/RFS outcomes in patients afflicted with BTC. The CONUT score emerges as a promising and potentially valuable prognostic indicator for individuals diagnosed with BTC. This metric equips clinicians with the means to assess the nutritional status, immune function, and overall prognosis of BTC patients, facilitating timely clinical intervention and guidance. Nevertheless, it is important to acknowledge the study's limitations. In order to bolster the credibility and significance of the CONUT score as a prognostic indicator for patients with BTC, it is imperative to amass a more extensive body of high-quality research in this particular field.

Funding: None

Data Availability Statement: All data was in the manuscript and can be obtained from the corresponding author.

Ethics approval and consent to participate: Not applicable.

Consent for publication: Not applicable.

Acknowledgements: None

Competing interest: The authors declare that they have no confict of interest

Authors’ contributions: Weixing Wang, Yanbing Zhang and Kailiang Zhao contributed to the study's inception and design. Rongqiang Liu, Chenxuan Zhang and Jianguo Wang equally contributed to the literature search, analysis and writing of the manuscript. Other authors contributed to the study design and study supervision. All authors approved the final version of the manuscript.

Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397:428–44.
Ouyang G, Liu Q, Wu Y, et al. The global, regional, and national burden of gallbladder and biliary tract cancer and its attributable risk factors in 195 countries and territories, 1990 to 2017: A systematic analysis for the Global Burden of Disease Study 2017. Cancer. 2021;127:2238–50.
Marcano-Bonilla L, Mohamed EA, Mounajjed T, Roberts LR. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. Chin Clin Oncol. 2016;5:61.
Lamarca A, Edeline J, McNamara MG, et al. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat Rev. 2020;84:101936.
Marino D, Leone F, Cavalloni G, Cagnazzo C, Aglietta M. Biliary tract carcinomas: from chemotherapy to targeted therapy. Crit Rev Oncol Hematol. 2013;85:136–48
González-Madroño A, Mancha A, Rodríguez FJ, Culebras J, de Ulibarri JI. Confirming the validity of the CONUT system for early detection and monitoring of clinical undernutrition: comparison with two logistic regression models developed using SGA as the gold standard. Nutr Hosp. 2012;27:564–71
Lu C, Chen Q, Fei L, Wang J, Wang C, Yu L. Prognostic impact of the controlling nutritional status score in patients with hematologic malignancies: A systematic review and meta-analysis. Front Immunol. 2022;13:952802.
Chen J, Song P, Peng Z, Liu Z, Yang L, Wang L, et al. The Controlling Nutritional Status (CONUT) Score and Prognosis in Malignant Tumors: A Systematic Review and Meta-Analysis. Nutr Cancer. 2022;74:3146–63.
Ma X, Zou W, Sun Y. Prognostic Value of Pretreatment Controlling Nutritional Status Score for Patients With Pancreatic Cancer: A Meta-Analysis. Front Oncol. 2022;11:770894.
Kuroda D, Sawayama H, Kurashige J, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer. 2018;21:204–12.
Mito M, Sakata J, Hirose Y, et al. Preoperative controlling nutritional status score predicts systemic disease recurrence in patients with resectable biliary tract cancer. Eur J Surg Oncol. 2023;49:399–409.
Miyata T, Yamashita YI, Higashi T, et al. The Prognostic Impact of Controlling Nutritional Status (Conut) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study. World journal of surgery .2018;42:1085–91.
Asakura R, Yanagimoto H, Ajiki T, et al. Prognostic Impact of Inflammation-Based Scores for Extrahepatic Cholangiocarcinoma. Dig Surg. 2022;39:65–74.
Zheng Y, Wu F, Rong W, et al. Prognostic value of the controlling nutritional status (CONUT) score in intrahepatic cholangiocarcinoma patients especially who had long-time alcohol consumption. J Clin Biochem Nutr. 2020;67:323–31.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.
Han CL, Meng GX, Ding ZN, et al. The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis. Front Immunol. 2022;13:827788.
Cui P, Pang Q, Wang Y, et al. Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: A retrospective observational study. Medicine (Baltimore). 2018;97:e11000
Sun L, Su S, Xiong J, et al. Controlling nutritional status score as a prognostic marker to predict overall survival in resected biliary tract cancers. Ann Transl Med. 2021;9:644
Terasaki F, Sugiura T, Okamura Y, et al. Use of preoperative controlling nutritional status (CONUT) score as a better prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy. Surg Today. 2021;51:358–65
Utsumi M, Aoki H, Nishimura S, et al. Safety of Surgical Treatment for Elderly Patients with Gallbladder Carcinoma. Acta Med Okayama. 2019;73:241–46
Wang A, He Z, Cong P, et al. Controlling Nutritional Status (CONUT) Score as a New Indicator of Prognosis in Patients With Hilar Cholangiocarcinoma Is Superior to NLR and PNI: A Single-Center Retrospective Study. Front Oncol. 2021;10:593452
Peng L, Meng C, Li J, et al. The prognostic significance of controlling nutritional status (CONUT) score for surgically treated renal cell cancer and upper urinary tract urothelial cancer: a systematic review and meta-analysis. Eur J Clin Nutr. 2022;76:801–10.
Peng J, Li X, Huang M, et al. Prognostic value of prognostic nutritional index score and controlling nutritional status score in patients with glioblastoma: A comprehensive meta-analysis. Front Oncol. 2023;13:1117764.
Zheng Y, Bao L, Wang W, Wang Q, Pan Y, Gao X. Prognostic impact of the Controlling Nutritional Status score following curative nephrectomy for patients with renal cell carcinoma. Medicine (Baltimore). 2018;97:e13409
Jayarajan S, Daly JM. The relationships of nutrients, routes of delivery, and immunocompetence. Surg Clin North Am. 2011;91:737 – 53, vii.
Cohen S, Danzaki K, MacIver NJ. Nutritional effects on T-cell immunometabolism. Eur J Immunol. 2017;47:225–35.
Sheinenzon A, Shehadeh M, Michelis R, Shaoul E, Ronen O. Serum albumin levels and inflammation. Int J Biol Macromol. 2021;184:857–62.
Bekos C, Polterauer S, Seebacher V, et al. Pre-operative hypoalbuminemia is associated with complication rate and overall survival in patients with vulvar cancer undergoing surgery. Arch Gynecol Obstet. 2019;300:1015–22.
Guven DC, Sahin TK, Erul E, et al. The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Front Mol Biosci. 2022;9:1039121.
Liu A, Xia Y, Li W, et al. The Predictive Value of Changes in the Absolute Counts of Peripheral Lymphocyte Subsets for Progression and Prognosis in Breast Cancer Patients. Contrast Media Mol Imaging. 2022;2022:3444360
Xia Y, Li W, Li Y, et al. The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer. Transl Oncol. 2020;13:100849.
Tatara T, Suzuki S, Kanaji S, et al. Lymphopenia predicts poor prognosis in older gastric cancer patients after curative gastrectomy. Geriatr Gerontol Int. 2019;19:1215–19.
Lee YJ, Chung YS, Lee JY, et al. Pretreatment lymphocytopenia is an adverse prognostic biomarker in advanced-stage ovarian cancer. Cancer Med. 2019;8:564–71
King RJ, Singh PK, Mehla K. The cholesterol pathway: impact on immunity and cancer. Trends Immunol. 2022;43:78–92.
Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15:104–16.
Chimento A, Casaburi I, Avena P, et al. Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment. Front Endocrinol (Lausanne). 2019;9:807.
de Weille J, Fabre C, Bakalara N. Oxysterols in cancer cell proliferation and death. Biochem Pharmacol. 2013;86:154–60
Kang HW, Seo SP, Kim WT, et al; KORCC (KOrean Renal Cell Carcinoma) group. Low preoperative serum cholesterol level is associated with aggressive pathologic features and poor cancer-specific survival in patients with surgically treated renal cell carcinoma. Int J Clin Oncol. 2018;23:142–50.
Zhang G, Zhang D, Wu J, et al. Low Serum Levels of Pre-Surgical Total Cholesterol are Associated with Unfavorable Overall Survival in Patients with Operable Non-Small Cell Lung Cancer. Clin Lab. 201;64:321–27.

No competing interests reported.

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Prognostic significance of the controlling nutritional status score in patients with biliary tract cancer

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Version 1

Abstract

Figures

Introduction

Material and methods

Search strategy

Inclusion and exclusion criteria

Data extraction and quality assessment

Statistical analysis

Results

Search results

Study characteristics

Impact of CONUT score on OS

Subgroup analysis for OS

Impact of CONUT score on DFS/RFS

Sensitivity analysis

Publication bias

Discussion

Declarations

References

Additional Declarations

Supplementary Files

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