The preoperative nutritional and inflammatory indexs as prognostic factors in patients with early-stage resectable extrahepatic bile duct cancer

doi:10.21203/rs.3.rs-4166428/v1

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Research Article

The preoperative nutritional and inflammatory indexs as prognostic factors in patients with early-stage resectable extrahepatic bile duct cancer

https://doi.org/10.21203/rs.3.rs-4166428/v1

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Background

Cancer - associated malnutrition and systemic inflammation have been shown to be strongly linked with poor prognosis in various cancers. The aim of this study was to investigate the prognostic values of the prognostic nutritional index (PNI), nutritional risk index (NRI), advanced lung cancer inflammation index (ALI), and systemic immune-inflammation index (SII) in patients with early-stage resectable extrahepatic bile duct cancer (BDC).

Methods

A total of 155 early-stage resectable extrahepatic BDC were recruited for this retrospective study. Kaplan-Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative PNI, NRI, ALI, and SII in patients with early-stage extrahepatic BDC. Nomogram was developed based on the results of multivariate Cox analyses and were then validated and calibrated.

Results

Receiver operating characteristic curve (ROC) analysis identified the optimal cut-off points for PNI, NRI, ALI, and SII were 48.7, 100.5, 49.9, and 659.8. Low PNI, NRI, ALI, and high SII were related to TNM stage (P < 0.05). Kaplan-Meier analysis showed that low PNI, NRI, ALI, and high SII were related to poor overall survival (OS) and recurrence-free survival (RFS) of patients. Multivariate analyses indicated that lymph nodes metastasis, PNI, NRI, ALI, and SII were significant independent factors for OS and RFS. Nomograms were developed to predict OS and RFS for patients with early-stage resectable extrahepatic BDC.

Conclusion

Preoperative PNI, NRI, ALI, and SII could be used as prospective noninvasive prognostic biomarkers for patients with early-stage resectable extrahepatic BDC.

extrahepatic bile duct cancer

PNI

NRI

ALI

and SII

prognosis

Bile duct cancer (BDC) is a rare neoplasm originating from the epithelial cells of the bile duct with very limited treatment options and poor prognosis^[1]. BDC is typically defined based on the anatomic site as intrahepatic and extrahepatic BDC, extrahepatic BDC is further divided into perihilar, and distal BDC^[2]. Surgical resection remains the first choice of therapy for patients with early-stage extrahepatic BDC. However, even after complete surgical resection, the 5-year survival rate is only 30–40%^[3]. The way to realize individualized treatment is to predict prognosis of extrahepatic BDC patients, then optimize individualized treatment and improve clinical prognosis. Therefore, a noninvasive, cost-effective prognostic marker should be identified to reliably guide personalized treatment of patients with extrahepatic BDC.

Nutrition and inflammatory are associated with oncological survival, disease progression, which affects their quality of life, response to anticancer treatment and postoperative outcomes. In particular, malnutrition increases the likelihood of postoperative complications, and approximately 40–80% of cancer patients may be affected by malnutrition^[4]. The inflammation-related indicators are crucial for tumorigenesis and progression. Therefore, accurate assessment of the malnutrition status and inflammatory of cancer patients is of utmost importance. The prognostic nutritional index (PNI), nutritional risk index (NRI), advanced lung cancer inflammation index (ALI), and systemic immune-inflammation index (SII) based on objective indexes could reflect the nutritional and inflammatory status more accurately are widely used to assess the prognosis of cancer patients, such as lung cancer^{[5, 6]}, hepatocellular carcinoma^[7], and gastric cancer^[8]. However, the relationship between PNI, NRI, ALI, SII and the clinical prognosis of extrahepatic BDC is extremely rare reported.

The present study aimed to investigate the prognostic value of the preoperative PNI, NRI, ALI, and SII in resectable early-stage extrahepatic BDC, and evaluate the correlation among these markers and clinicopathological characteristics. In addition, we developed and validated a nomogram to predict the individual risk of RFS and OS after resection of BDC.

Patients

Between January 2013 to December 2018, a total of 155 patients with resectable early-stage BDC at Harbin Medical University Cancer Hospital were enrolled for this retrospective study. Patient inclusion and exclusion criteria were as follows: a) Patients were > 18 years old; b) Patients did not undergo chemotherapy radiation or immunotherapy prior to surgery; c) Patient did not have any other malignant diseases; d) Patient did not have inflammatory disease, autoimmune disease, chronic metabolic disorders or chronic infectious disorders; e) Postoperative pathology confirmed bile duct adenocarcinomas; f) TNM stage was I-II; g) Patients underwent radical surgical resection. The study was subject to Harbin Medical University Cancer Hospital ethical approval, and all included patients gave written informed consent.

Clinical information data

All the patient clinical and pathological information such as sex, age, tumor location, differentiation, lymph nodes metastasis, and TNM stage were collected from the hospital electronic medical records. The preoperative biochemistry and hematology parameters such as albumin, neutrophil, platelet, and lymphocyte (within 7 days before surgery) were also reviewed and retrieved from the hospital electronic medical records. The pathological TNM stage (pTNM) was classified according to the American Joint Committee on Cancer (AJCC) 8th edition guidelines. Patients were followed up every 3 months during the first 2 years after surgery, every 6 months during the next 3 years, and then annually. Patient were followed through December 31, 2022. Overall survival (OS) was calculated from the time of operation to death or last follow up. Recurrence-free survival (RFS) was calculated from the date of surgery until the date of tumor recurrence, progression or death.

Definition of PNI, NRI, ALI, and SII

The prognostic nutritional index (PNI) was defined as follows: PNI = 5 × lymphocyte (10⁹/L) + albumin (g/L), nutritional risk index (NRI) = 1.519 × albumin (g/l) + 41.7 × (weight/ideal weight) (The ideal weight was calculated through the Lorentz equations as follows: male = height-100-[(height-150)/4]; female = height-100-[(height-150)/2.5]), advanced lung cancer inflammation index (ALI) = BMI (kg/m²) × albumin(g/l) × lymphocyte (10⁹/L)/neutrophil (10⁹/L), systemic immune-inflammation index (SII) = platelet (10⁹/L) × neutrophil (10⁹/L)/lymphocyte (10⁹/L). Body mass index (BMI) = weight (kg)/ height²(meter).

Statistical analysis

The results are expressed as the mean ± standard deviation (SD). The best cutoff values of PNI, NRI, ALI, and SII were evaluated using the receiver operating curve (ROC) analysis according to the maximum Youden index, which decided the maximum value (sensitivity + specificity-1) of Youden index. The associations between inflammatory markers and clinicopathological features were evaluated by the chi-square (χ2) test. The prognostic value of PNI, NRI, ALI, and SII for OS and RFS were assessed using the Kaplan–Meier method. Univariate and multivariate Cox regression analysis were performed to evaluate prognostic significance. The nomogram was developed using the nomogram package in R packages. The nomogram was evaluated by ROC, calibration plots, and decision curve analysis (DCA). Statistical analyses were performed with SPSS (version 23, IBM, USA) and GraphPad Prism (version 8.0) software. P < 0.05 was considered statistically significant.

Clinicopathologic characteristics of patients with extrahepatic BDC

A total of 155 patients with early-stage resectable extrahepatic BDC met all inclusion and exclusion criteria were included in this study. The clinicopathologic characteristics of patients were showed in Table 1. The median age at the time of surgery was 61 years old (range 30–75 years). Of these patients, 109 (70.3%) were male and 46 (29.7%) were female. 111/155(71.6%) patients had high bilirubin (total bilirubin ≥ 34umol/L) and presented with jaundice. 71 patients (45.8%) were classified as having TNM stage I and 84 (54.2%) as TNM stage II. The median BMI of patients was 24.2 and 69/155 (44.5%) patients had BMI less than 24.0. The median albumin, lymphocyte, and platelet levels of patients were 38.50 ± 4.53, 1.61 ± 0.56, and 232.00 ± 77.43. The median PNI, NRI, ALI, and SII values was 45.85 ± 5.43, 101.18 ± 9.80, 36.73 ± 27.22, and 570.83 ± 496.50.

Table 1

Clinicopathologic characteristics in patients with early-stage extrahepatic BDC
Groups	BDC
Sex
Male	109(70.3%)
Female	46(29.7%)
Age
< 60	69(44.5%)
≥ 60	86(55.4%)
Bilirubin
Total bilirubin ≥ 34umol/L	111(71.6%)
Total bilirubin < 34umol/L	44(28.4%)
Location
Perihilar	70(45.2%)
Distal	85(54.8%)
Differentiation
High and Moderate	92(59.4%)
Poor	63(40.6%)
Lymph nodes metastasis
Yes	34(21.9%)
No	121(78.1%)
TNM stage
I	71(45.8%)
II	84(54.2%)
BMI (Mean ± SD)	24.20 ± 3.14
Albumin (g/L, Mean ± SD)	38.50 ± 4.53
Lymphocyte (×10⁹/L, Mean ± SD)	1.61 ± 0.56
Platelet (×10⁹/L, Mean ± SD)	232.00 ± 77.43
PNI (Mean ± SD)	45.85 ± 5.43
NRI (Mean ± SD)	101.18 ± 9.80
ALI (Mean ± SD)	36.73 ± 27.22
SII (Mean ± SD)	570.83 ± 496.50

Optimal cutoff values for PNI, NRI, ALI, and SII

As shown in Fig. 1 and Supplementary Table, the optimal cut-off values of preoperative PNI, NRI, ALI, and SII were 48.7 (AUC = 0.581, 95% CI: 0.475–0.687, sensitivity = 46.7%, specificity = 75.5%), 100.5(AUC = 0.570, 95% CI: 0.473–0.667, sensitivity = 68.9%, specificity = 53.6%), 49.9(AUC = 0.644, 95% CI: 0.547–0.741, sensitivity = 51.1%, specificity = 76.3%), and 659.8 (AUC = 0.656, 95% CI: 0.561–0.752, sensitivity = 82.2%, specificity = 50.0%) according to ROC curve analysis.

The correlation of preoperative PNI, NRI, ALI, and SII with clinicopathologic characteristics

The patients with early-stage resectable extrahepatic BDC were categorized into low (< 48.7) or high (≥ 48.7) PNI groups, low (< 100.5) or high (≥ 100.5) NRI groups, low (< 49.9) or high (≥ 49.9) ALI groups, and low (< 659.8) or high (≥ 659.8) SII groups according to ROC optimal cut-off. The relationship between the four indexes and clinicopathologic indicators was further evaluated. As shown in Table 2, all PNI, NRI, ALI, and SII were significantly associated with TNM stage (P = 0.036, 0.002, 0.009, and 0.024, respectively). PNI and ALI were associated with tumor location (P < 0.001 and P = 0.042) Nevertheless, they had no statistical correlations with age, pathological differentiation, and lymph node metastasis (P > 0.05).

Table 2

Correlation between the nutritional and inflammatory indexs and clinicopathological features in patients with early-stage extrahepatic BDC
Groups	PNI [n (%)]		P			P	ALI [n (%)]		P	SII [n (%)]		P
	≥ 48.7	< 48.7		< 100.5	≥ 100.5		< 49.9	≥ 49.9		< 659.8	≥ 659.8
	48	107		73	82		106	49		92	63
Sex			0.153			0.348			0.015			0.093
Male	30(62.5)	79(73.8)		54(74.0)	55(67.1)		81(76.4)	28(57.1)		60(65.2)	49(77.8)
Female	18(37.5)	28(26.2)		19(26.0)	27(32.9)		25(23.6)	21(42.9)		32(34.8)	14(22.2)
Age			0.293			0.419			0.146			0.731
< 60	25(52.1)	46(43.0)		30(41.1)	39(47.4)		43(40.6)	26(53.1)		42(45.7)	27(42.9)
≥ 60	23(47.9)	61(57.0)		43(58.9)	43(52.4)		63(59.4)	23(46.9)		50(54.3)	36(57.1)
Location			< 0.001			0.108			0.042			0.633
Perihilar	35(72.9)	35(32.7)		28(38.4)	42(51.2)		42(39.6)	28(57.1)		43(46.7)	27(42.9)
Distal	13(27.1)	72(67.3)		45(61.6)	40(48.8)		64(60.4)	21(42.9)		49(53.3)	36(57.1)
Differentiation			0.857			0.667			0.747			0.386
High	29(60.4)	63(58.9)		40(54.8)	52(58.3)		62(58.5)	30(61.2)		52(56.5)	40(63.5)
Poor	19(39.6)	44(41.1)		33(45.2)	30(41.7)		44(41.5)	19(38.8)		40(43.5)	23(36.5)
Lymph nodes			0.288			0.770			0.465			0.389
+	8(17.7)	26(24.3)		16(21.4)	16(19.5)		25(23.6)	9(18.4)		18(19.6)	16(25.4)
-	40(83.3)	81(75.7)		55(78.6)	66(80.5)		81(76.4)	40(81.6)		74(80.4)	47(74.6)
TNM stage			0.036			0.002			0.009			0.024
I	28(58.3)	43(40.2)		24(32.9)	47(57.3)		41(38.7)	30(61.3)		49(53.3)	22(34.9)
II	20(41.7)	64(59.8)		49(67.1)	35(42.7)		65(61.2)	19(38.8)		43(46.7)	41(65.1)

Survival analysis and prognostic impact of PNI, NRI, ALI, and SII

In this study, Kaplan-Meier analysis was conducted to identify the prognostic significance of P PNI, NRI, ALI, and SII. As shown in Fig. 2, short OS was demonstrated to be significantly associated with low PNI (P = 0.013, HR = 1.70 (1.15–2.52)), NRI (P = 0.005, HR = 1.69 (1.16–2.48)), ALI (P = 0.003, HR = 1.70 (1.15–2.52)), and high SII (P = 0.002, HR = 1.76 (1.19–2.60)). Short RFS was demonstrated to be significantly associated with low PNI (P = 0.021, HR = 1.63 (1.11–2.39)), NRI (P = 0.003, HR = 1.70(1.17–2.47)), ALI (P = 0.005, HR = 1.80 (1.23–2.64)), and high SII (P = 0.002, HR = 1.74 (1.18–2.51)).

Cox proportional hazards model was selected for further survival analysis to evaluate the prediction models of baseline characteristics and preoperational PNI, NRI, ALI, and SII. As shown in Table 3, lymph node metastasis (HR = 2.28, 95% CI: 1.50–3.48, p < 0.001), pathological differentiation (HR = 1.47, 95% CI: 1.01–2.148, p = 0.045), TNM stage (HR = 1.55, 95% CI: 1.05–2.27, p = 0.026), PNI (HR = 1.72, 95% CI: 1.11–2.66, p = 0.014), NRI (HR = 1.72, 95% CI: 1.18–2.50, p = 0.005), ALI (HR = 1.94, 95% CI: 1.25–3.02, p = 0.003), and SII (HR = 1.79, 95% CI: 1.23–2.61, p = 0.002) were determined as statistically significant prognostic factors for OS by univariate analysis. Lymph node metastasis (HR = 2.36, 95% CI: 1.56–3.59, p < 0.001), pathological differentiation (HR = 1.52, 95% CI: 1.05–2.20, p = 0.028), TNM stage (HR = 1.60, 95% CI: 1.10–2.34, p = 0.026), PNI (HR = 1.65, 95% CI: 1.07–2.51, p = 0.022), NRI (HR = 1.73, 95% CI: 1.20–2.51, p = 0.003), ALI (HR = 1.84, 95% CI: 1.20–2.82, p = 0.005), and SII (HR = 1.77, 95% CI: 1.22–2.56, p = 0.003) were determined as statistically significant prognostic factors for RFS by univariate analysis. Multivariate analysis identified lymph node metastasis, PNI, NRI, ALI, and SII as independent prognostic factors for OS and RFS. The sex, age, and location had no significant association with OS and RFS in either univariate or multivariate analysis.

Table 3

Univariate and multivariate analysis of OS and RFS in patients with early-stage extrahepatic BDC
	OS				RFS
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
Variable	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P	HR (95% CI)	P
Sex (female vs. male)	1.15(0.76–1.75)	0.517			1.15(0.76–1.72)	0.514
Age (≤ 60 vs. > 60)	0.95(0.65–1.38)	0.784			1.06(0.73–1.54)	0.758
Location (distal vs. perihilar)	0.89(0.61–1.30)	0.557			0.89(0.62–1.29)	0.531
Lymph nodes metastasis (yes vs. no)	2.28(1.50–3.48)	< 0.001	1.93(1.21–3.08)	0.006	2.36(1.56–3.59)	< 0.001	1.94(1.22–3.07)	0.005
Differentiation (poor vs. well)	1.47(1.01–2.15)	0.045	1.31(0.88–1.94)	0.183	1.52(1.05–2.20)	0.028	1.35(0.91–1.98)	0.132
Stage (II vs. I)	1.55(1.05–2.27)	0.026	1.21(0.81–1.83)	0.353	1.60(1.10–2.34)	0.026	1.26(0.84–1.89)	0.269
PNI (≥ 48.7 vs. < 48.7)	1.72(1.11–2.66)	0.014	1.70(1.10–2.63)	0.018	1.65(1.07–2.51)	0.022	1.57(1.02–2.42)	0.040
NRI (≥ 100.5 vs. < 100.5)	1.72(1.18–2.50)	0.005	1.56(1.06–2.29)	0.023	1.73(1.20–2.51)	0.003	1.61(1.10–2.34)	0.013
ALI (≥ 49.9vs. < 49.9)	1.94(1.25–3.02)	0.003	1.98(1.27–3.10)	0.003	1.84(1.20–2.82)	0.005	1.84(1.20–2.84)	0.006
SII (< 659.8vs. ≥659.8)	1.79(1.23–2.61)	0.002	1.84(1.24–2.73)	0.002	1.77(1.22–2.56)	0.003	1.77(1.21–2.60)	0.004

Construction of prognostic nomogram models

Based on the results of multivariate Cox analyses, we developed a nomogram to assess OS and RFS at 1-, 3-, and 5-years for early-stage resectable extrahepatic BDC, in which each signature was assigned points according to its risk contribution to OS and RFS (Fig. 3A − 3B). The C-index of the nomogram for OS and RFS were 0.747 and 0.761. Moreover, the area under the ROC of the nomogram for OS and RFS were 0.769 (CI: 0.669–0.870) and 0.784(CI: 0.687–0.882) in patients with early-stage BDC (Fig. 4A − 4B). The calibration plot for the nomograms showed optimal agreement between our model's prediction and the actual observation (Fig. 4C − 4D). DCA was performed to evaluate the clinical application of the nomogram by quantifying the net benefits at different threshold probabilities (Fig. 4E − 4F).

Surgical resection is the preferred treatment of choice for early-stage extrahepatic BDC, and fluorouracil-based chemotherapy remains a common treatment choice for patients undergoing resection. However, early systemic metastasis is a major feature of BDC even after resection with a negative margin. Accumulating evidence reveals that patients’ nutritional status, systemic inflammation, and autoimmune regulation play important roles in tumor progression, metastasis, and prognosis^[9]. When cancer patients with malnutrition, which leading poor postoperative recovery, body’s immunity, resistance, and treatment tolerance, and higher risk of postoperative recurrence and disease progression, result in poor prognosis. Hamura et al. showed that preoperative low cachexia index (CXI) was an independent and significant risk factor for recurrence and poor prognosis, suggesting that cachexia may progress to tumor development and recurrence in patients with extrahepatic biliary tract cancer^[10]. Lymphocyte count and serum albumin level were used to reflect systemic immunity and nutritional status of patients^{[11, 12]}. Neutrophils and platelets are parts of the inflammatory network, which promotes tumor progression and metastasis. Gu’ study showed that circulating neutrophils, and monocytes were significantly higher while albumin, lymphocytes were significantly lower in patients with pancreatic cancer compared to those of HCs and other pancreatic tumors^[13]. Li’ study showed that patients with resectable early-stage BDC had significantly higher levels of neutrophils, monocytes, lower levels of lymphocytes, and albumin than healthy controls (HCs) which suggest that inflammation may already exist at early stages of tumorigenesis^[14].

Inflammatory response to cancer promote pro-tumor cytokines, such as tumor necrosis factor (TNF), interleukin-1(IL-1), IL-6, and IL-8 secretion, which can directly suppress the function of hepatic cells to generate albumin^[15].Previous studies have found low serum albumin concentration have been correlated with poor prognoses in cancer patients in various cancers. Graziano et al. found that lower serum albumin concentration was an independent prognostic factor for poorer overall survival among patients with breast cancer regardless of the tumor stage^[16]. Umehara’ study showed that low serum albumin is a poor prognostic factor in patients with non-small cell lung cancer^[17]. Neutrophils may restrain the immune system by releasing of cytokines to suppress the cytolytic activity of activated T-cells, lymphocytes, and natural killer cells^[18]. Some studies demonstrated that cancer could induce T cell apoptosis by activating Fas/FasL pathway, overexpressed tumor-derived antigens could stimulate lymphocytes which lead their apoptosis, and TNF-α could exhibit lymphopenia^[19]. Cancer cells promote platelet production and activation by secreting active substances such as interleukin-6, while activated platelets secrete vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor-β to promote cancer angiogenesis^[20]. Neutrophil–lymphocyte ratio could predict prognosis of patients with breast cancer and hepatocellular carcinoma^{[21, 22]}. Previous studies have also shown that platelet–lymphocyte ratio exhibits reliable prognostic value in various tumors, such as those of ovarian cancer, pancreatic cancer, and bladder cancer^[23].

The PNI, NRI, ALI, and SII based on lymphocyte, platelet, neutrophil count, serum albumin, and patients’ BMI could quantify the nutritional and immunological statuses of patients, which can be obtained easily from clinical tests. These indexs has been established as a useful tool to evaluate nutritional status, and it is closely related to the prognosis of various cancers^[6]. Gao et al. reported that Pretreatment PNI values can be used as a feasible predictor of clinical efficacy and prognosis for patients with cervical cancer^[24]. Takahashi et al. reported that low preoperative PNI level was proved to be an independent unfavorable factor affecting the OS and RFS of the patients with resectable NSCLC^[25]. A recent report suggested the nutritional status may be correlated with the proportion and function of immune cells (such as T and memory cells) in the tumor microenvironment, therefore affecting the clinical efficacy of the immunotherapies^[26]. Yan’s study reported that PNI is a reliable prognostic factor for advanced lung cancer patients receiving immune checkpoint inhibitors-based therapies^[27]. Yamada’s study showed that low pretreatment PNI was an effective independent prognostic factor for shorter OS of patients with metastatic hormone-sensitive prostate cancer^[28]. Liu’s study showed that geriatric NRI (GNRI) was significantly associated with progression-free survival (PFS) of patients with hepatocellular carcinoma who receive immune checkpoint inhibitors^[7]. Deng’s study reported that ALI was an effective indicator for predicting short- and long-term outcomes in patients with right-sided colon cancer (RCC)^[29]. Zhang’s study reported that SII could predict survival patients with advanced BDC treated with immune checkpoint inhibitors (ICIs)^[30]. As far as we know, this is the first study to assess the prognostic relevance of PNI, NRI, ALI, and SII to patients with early-stage BDC after surgical resection. In this study, we found that low level of PNI, NRI, ALI and high level of SII were related to poor prognosis for patients with early-stage resectable extrahepatic BDC, which was consistent with previous studies.

Combination of prognostic biomarker based on indicators of preoperative inflammation, immunity, and nutritional status could be a superior prognostic indicator for patients compared with single biomarker. The nomogram is simple, easy to understand, and apply to clinical practice. It provided more accurate and reliable prognostic information in comparison with traditional staging system. In the current study, nomograms merging pathological, inflammation, and nutritional parameters were built to evaluate RFS rates and the 1-, 3‐, and 5‐year OS probabilities of patients with early-stage resectable extrahepatic BDC. The identification and calibration of the nomograms were confirmed, and these nomograms have a wide range of applications. The nomogram could be used as a convenient tool for clinicians to evaluate the prognosis facilitate better individualized treatment strategy and decision-making. A close follow-up, altering the inflammatory and nutritional status and improving the immune function of cancer patients are necessary in patients with a high risk of recurrence.

This study was the first to investigate the prognostic value of PNI, NRI, ALI, and SII for patients with early-stage resectable extrahepatic BDC. Nevertheless, our study has several limitations. This is an observational and retrospective study in a single centre with small sample size, which may cause selection bias. The relationship between the change in PNI, NRI, ALI, and SII after surgery and the prognosis of these patients was not been studied. Further multicentric studies will be needed to validate the conclusions.

In conclusion, preoperative PNI, NRI, ALI, and SII can be convenient and valuable prognostic marker for patients with early-stage resectable extrahepatic BDC. In addition, the nomogram could help clinicians predict the prognosis on early-stage resectable extrahepatic BDC patients’ clinical data and optimize their therapeutic strategies.

Ethics statement

The studies involving human participants were reviewed and approved by the Harbin Medical University Cancer Hospital Ethics Committee.

Consent to Participate declaration

Every patient/participant provided their written informed consent to participate in this study.

Authors contributions

XZ conceived and designed the study. YG collected the samples and worked on the experiment. HL, LC and JZ performed statistical analysis and wrote the manuscript. DZ reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

None

Availability of data and materials

The data are available from the corresponding author on reasonable request.

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No competing interests reported.

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The preoperative nutritional and inflammatory indexs as prognostic factors in patients with early-stage resectable extrahepatic bile duct cancer

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Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Patients

Clinical information data

Definition of PNI, NRI, ALI, and SII

Statistical analysis

Results

Clinicopathologic characteristics of patients with extrahepatic BDC

Optimal cutoff values for PNI, NRI, ALI, and SII

The correlation of preoperative PNI, NRI, ALI, and SII with clinicopathologic characteristics

Survival analysis and prognostic impact of PNI, NRI, ALI, and SII

Construction of prognostic nomogram models

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1