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Estimated functional remnant pancreatic volume predicts nonalcoholic fatty liver disease after pancreaticoduodenectomy : use of computed tomography attenuation value of the pancreas.

MAEHIRA Hiromitsu 0000-0003-3064-5216 IIDA Hiroya 30733901 0000-0001-6245-4583 MAEKAWA Takeru YASUKAWA Daiki 80765074 MORI Haruki 40803945 TAKEBAYASHI Katsushi KAIDA Sachiko 70710234 0000-0002-1279-5942 MIYAKE Toru 70581924 MATSUBARA Akiko 80626325 TANI Masaji 60236677 0000-0003-1270-6003 滋賀医科大学

2020.10.10

概要

Background:
Nonalcoholic fatty liver disease (NAFLD) is a late complication of pancreaticoduodenectomy (PD). However, this complication is difficult to predict preoperatively. This study aimed to assess the association between NAFLD and preoperative computed tomography (CT) findings.
Methods:
Medical records of 112 patients who had undergone PD and had CT scans preoperatively and 6 months postoperatively were retrospectively reviewed. We evaluated several CT findings, including the CT attenuation value of the remnant pancreas, remnant pancreatic volume (RPV), and the estimated functional remnant pancreatic volume (eFRPV) on preoperative CT. The variables, including the CT findings and histopathological findings, were compared between the patients with and without NAFLD after PD.
Results:
The NAFLD group included 21 patients (18.8%). The CT attenuation value of the remnant pancreas was correlated with the pancreatic acinar cell density (r = 0.537), and was lower in the NAFLD group than in the non-NAFLD group (p = 0.007). The eFRPV was lower in the NAFLD group than in the non-NAFLD group (p = 0.002). An eFRPV ≤47 mL·HU was an independent predictive factor for NAFLD (p = 0.007; odds ratio: 6.73; 95% confidence interval: 1.70-26.70).
Conclusion:
The eFRPV can be used to preoperatively predict NAFLD after PD.

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参考文献

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Figure Legends

Figure 1 Measurement of CT findings and pancreatic acinar cell density

(a) The CT attenuation value of the liver was defined as the mean of the attenuation value of four ROIs

in different sectors in the liver. (b) The CT attenuation value of the remnant pancreas was defined as

the mean of two ROIs in the remnant pancreas on preoperative unenhanced CT. (c) The vessels were

excluded by reviewing the preoperative enhanced CT. (d) The cut line of the pancreas was determined

by the location of the pancreatojejunostomy in the postoperative CT images. (e) Subsequently, the

remnant pancreatic parenchyma was manually outlined on each CT slice using a free-hand region of

interest in the preoperative CT images and the volume of the remnant pancreas was calculated using all

10

outlined areas and the slice thickness. (f) The pancreatic acinar cell density was measured by Image J

11

(f, except red area) at 100x magnification of hematoxylin and eosin stained tissue (g).

12

Abbreviations: CT, computed tomography; ROI, region of interest

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Figure 2 Relationship between the preoperative CT attenuation value of the remnant pancreas and the

15

pancreatic acinar cell density

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(a) The scatter diagram shows the relationship between the preoperative CT attenuation value of the

17

remnant pancreas and the pancreatic acinar cell density. These two factors are positively correlated,

18

with a Pearson’s correlation coefficient of 0.537. (b) The ROC curve of the CT attenuation value of

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the remnant pancreas for the analysis of the pancreatic acinar cell density ≥ 50% has an area under the

25

curve of 0.829. A cutoff value of 37.0 HU predicts pancreatic acinar cell density ≥ 50% with a

sensitivity and specificity of 71.4% and 85.2%, respectively. (c) The scatter diagram shows the

relationship between the preoperative CT attenuation value of the remnant pancreas and the fibrotic

score. These two factors are negatively correlated, with a Pearson’s correlation coefficient of -0.532.

Abbreviations: CT, computed tomography; HU, Hounsfield units; ROC, receiver operating

characteristic

Figure 3 The estimated functional remnant pancreatic volume as a predictor of nonalcoholic fatty liver

disease.

10

The ROC curve of the eFRPV for the prediction of NAFLD has an area under the curve of 0.721. A

11

cut-off value of 47.0 mL·HU predicts NAFLD with a sensitivity and specificity of 81.0% and 65.6%,

12

respectively. Abbreviations: eFRPV, estimated functional remnant pancreatic volume; NAFLD,

13

nonalcoholic fatty liver disease; ROC, receiver operating characteristic; HU, Hounsfield units

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26

Tables

Table 1. Clinical features of the NAFLD and non-NAFLD groups

NAFLD group

non-NAFLD group

P-value

(n=21)

(n=91)

Background

63 (69.2%)

Sex, male / female

10 / 11

0.077

/ 28 (30.8%)

Age, years

68 (62-71)

69 (62-75)

0.438

22.0 (19.4-23.3)

21.48 (19.6-23.8)

0.864

Prevalence of hypertension

31 (34.1%)

0.444

Prevalence of diabetes mellitus

21 (23.1%)

0.099

Alcohol intake >20g/day

28 (30.8%)

1.000

Use of steroid agent

2 (2.2%)

1.000

Preoperative biliary drainage

10

41 (45.1%)

1.000

Neoadjuvant chemotherapy

3 (3.3%)

0.006

Preoperative NAFLD

1 (1.1%)

0.341

Prevalence of liver dysfunction

3 (3.3%)

0.038

Body mass index, kg/m2

Pathological diagnosis

< 0.001

27

Pancreatic cancer

19

30 (33.0%)

Intraductal papillary mucinous neoplasm

14 (15.4%)

Chronic pancreatitis

2 (2.2%)

Pancreatic neuroendocrine neoplasm

4 (4.4%)

Bile duct cancer

21 (23.1%)

Cancer of the papilla of vater

12 (13.2%)

Others

8 (8.7%)

13.0 (11.8-13.6)

12.6 (11.9-13.8)

0.911

5000 (4400-7500)

5300 (4350-6400)

0.765

22.2 (18.9-28.7)

21.5 (17.9-26.1)

0.293

Prothrombin activity, %

99 (88-103)

94 (87-103)

0.740

Aspartate aminotransferase, U/L

29 (20-41)

22 (19-33)

0.174

Alanine aminotransferase, U/L

24 (18-65)

22 (16-48)

0.365

343 (241-433)

267 (200-440)

0.256

Total bilirubin, g/dL

0.93 (0.59-1.56)

0.84 (0.58-1.34)

0.472

Creatinine, mg/dL

0.59 (0.52-0.81)

0.74 (0.63-0.90)

0.015

Preoperative laboratory data

Hemoglobin, g/dL

White blood cell count, /μL

Platelet count, /μL

Alkaline phosphatase, U/L

28

Amylase, U/L

68 (45-116)

79 (63-128)

0.093

Lipase, U/L

58 (15-109)

46 (31-99)

0.486

Creatine kinase, U/L

50 (30-69)

59 (38-74)

0.132

0.10 (0.05-0.32)

0.12 (0.05-0.37)

0.765

Total protein, g/dL

6.4 (6.2-6.8)

6.6 (6.4-7.1)

0.091

Albumin, g/dL

3.5 (3.4-4.0)

3.7 (3.4-4.0)

0.598

Cholinesterase, U/L

275 (244-292)

263 (221-295)

0.351

Total cholesterol, mg/dL

195 (164-235)

187 (148-216)

0.310

Triglyceride, mg/dL

118 (87-140)

120 (92-148)

0.967

Hemoglobin A1c, %

6.0 (5.7-6.6)

5.9 (5.6-6.7)

0.916

Total lymphocyte count, /μL

1442 (1220-1895)

1531 (1210-2056)

0.685

Prognostic nutritional index

43.73 (40.26-49.49)

45.06 (42.53-48.23)

0.679

2 (1-3)

2 (1-3)

0.774

689 (500.0-1491)

791 (469.5-1435)

0.929

C-reactive protein, mg/dL

Preoperative nutritional status

CONUT score

Intraoperative findings

Blood loss, mL

29

Operation time, minutes

537 (489.0-566)

463 (403.5-586)

0.106

Presence of transfusion

18 (19.8%)

0.765

Diameter of MPD, mm

5 (2-6)

3 (3-5)

0.060

53 (58.2%)

Pancreatic stiffness, soft / hard

4 / 17

0.001

/ 38 (41.8%)

Postoperative findings

Complication ≥ grade3

45 (49.5%)

0.635

Postoperative pancreatic fistula grade B/C

30 (33.0%)

0.114

16

45 (49.5%)

0.031

17

34 (37.4%)

<0.001

9/17

22/34

0.545

10 (8.9%)

1.000

Postoperative pancreatic enzyme

supplementation

Adjuvant chemotherapy

Adjuvant chemotherapy completely

Recurrence within 6 months

Postoperative nutritional status (6 months after surgery)

Total protein, g/dL

6.3 (5.6-6.7)

6.8 (6.3-7.1)

0.006

Albumin, g/dL

3.5 (3.2-3.7)

3.8 (3.2-4.0)

0.049

30

Cholinesterase, U/L

183 (138-220)

213 (164-269)

0.077

Total cholesterol, mg/dL

123 (110-129)

148 (126-178)

0.001

Triglyceride, mg/dL

79 (71-102)

77 (67-115)

1.000

Hemoglobin A1c, %

5.7 (5.3-6.2)

5.8 (5.4-6.4)

0.368

Total lymphocyte count, /μL

1084 (930-1288)

1385 (933-1774)

0.057

Prognostic nutritional index

40.14 (36.83-43.28)

43.98 (39.21-48.34)

0.014

5 (3-9)

3 (2-4)

0.037

55.9 (51.2-60.2)

57.7 (52.7-62.4)

0.222

31.0 (27.7-38.8)

39.3 (33.1-45.7)

0.007

Remnant pancreatic volume, mL

10.3 (5.8-15.3)

15.4 (9.6-23.8)

0.007

eFRPV, mL·HU

32.8 (17.1-46.6)

60.6(32.2-104.6)

0.002

44.6 (19.9-71.6)

69.7 (57.9-78.4)

0.003

10 (3-12)

3 (2-6)

0.003

CONUT score

Preoperative CT findings

CT attenuation value of the liver, HU

CT attenuation value

of the remnant pancreas, HU

Histopathological findings

Pancreatic acinar cell density, %

Fibrotic score

31

Data are expressed as median with interquartile range for continuous data or as number and

percentage for categorical data.

Abbreviations: NAFLD, nonalcoholic fatty liver disease; CONUT, controlling nutritional status;

MPD, main pancreatic duct; CT, computed tomography; HU, Hounsfield units; eFRPV, estimated

functional remnant pancreatic volume

32

Table 2. Multivariate analysis of preoperative evaluable factors

Factors

Odd’s ratio

95% confidence interval

P-value

Neoadjuvant chemotherapy

3.98

0.74-21.40

0.108

Prevalence of liver dysfunction

10.70

1.15-98.80

0.037

Creatinine

0.19

0.01-2.79

0.224

eFPRV ≤ 47 mL·HU

6.73

1.70-26.70

0.007

Abbreviations: eFRPV, estimated functional remnant pancreatic volume

33

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