Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Management and Treatment Protocol
2.3. Patients with a Background of Metabolic Disorders
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Comparison between Groups According to Metabolic Factors
3.3. Clinical Outcomes and Overall Survival
3.4. Treatment Strategies and Clinical Outcomes
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Total | Metabolic Disorder Group | Non-Metabolic-Disorder Group | p Value |
---|---|---|---|---|
n (%) | 122 | 52 (42.6%) | 70 (57.4%) | |
Median age, years (IQR) | 62 (55–67) | 64 (56–68.5) | 59 (53–64) | 0.199 |
Gender | 0.048 | |||
Woman, n (%) | 72 (59.0%) | 36 (69.2%) | 36 (51.4%) | |
Man, n (%) | 50 (40.9%) | 16 (30.8%) | 34 (48.6%) | |
Conditions | ||||
Weight, kilograms (IQR) | 59 (51.7–68) | 67.5 (59.9–79) | 55 (48–59) | <0.0001 |
Height, centimeters (IQR) | 159 (153–166) | 157.5 (152.5–164.5) | 160 (154–168) | 0.1991 |
BMI, kg/m2 (IQR) | 23 (20–26) | 26 (24.5–29.5) | 21 (18–23) | <0.0001 |
Smoking, n (%) | 54 (44.3%) | 13 (25%) | 41 (58.6%) | <0.0001 |
Alcohol, n (%) | 20 (16.4%) | 6 (11.6%) | 14 (20%) | 0.212 |
PSC, n (%) | 2 (1.7%) | 0 (0%) | 2 (2.9%) | 0.219 |
Cholelithiasis, n (%) | 11 (9.0%) | 4 (7.7%) | 7 (10%) | 0.354 |
Cirrhosis, n (%) | 1 (0.8%) | 0 (0%) | 1 (1.4%) | 0.387 |
Viral hepatitis | 4 (3.2%) | 2 (3.8%) | 2 (2.9%) | 0.742 |
HIV | 2 (1.6%) | 0 (0%) | 2 (2.9%) | 0.219 |
Primary site | 0.691 | |||
Intrahepatic | 48 (39.3%) | 18 (34.6%) | 30 (42.9%) | |
Perihilar | 30 (24.6%) | 13 (25%) | 17 (24.3%) | |
Distal | 41 (33.6%) | 19 (36.5%) | 22 (31.4%) | |
Undefined | 3 (2.5%) | 2 (3.9%) | 1 (1.4%) | |
Performance status | 0.636 | |||
0–1, n (%) | 84 (68.9) | 37 (71.1%) | 47 (67.1%) | |
2–4, n (%) | 38 (31.1%) | 15 (28.9%) | 23 (32.9%) | |
Number of liver nodules | 0.124 | |||
Unicentric, n (%) | 73 (59.9%) | 37 (71.2%) | 36 (51.4%) | |
Multicentric, n (%) | 44 (36.1%) | 13 (25%) | 31 (44.3%) | |
Non-Applicable, n (%) | 5 (4.1%) | 2 (3.9%) | 3 (4.3%) | |
Vascular invasion, n (%) | 44 (36.1%) | 17 (32.7%) | 27 (38.6%) | 0.576 |
Clinical positive node, n (%) | 55 (45.1%) | 26 (50%) | 29 (41.4%) | 0.178 |
Distant metastasis, n (%) | 61 (50%) | 25 (48.1%) | 36 (51.4%) | 0.595 |
Tumor status (pT and/or cT) | 0.100 | |||
T1, n (%) | 9 (7.4%) | 7 (13.5%) | 2 (2.9%) | |
T2, n (%) | 39 (32.0%) | 21 (40.4%) | 18 (25.7%) | |
T3, n (%) | 42 (34.4%) | 14 (26.9%) | 28 (40%) | |
T4, n (%) | 25 (20.4%) | 7 (13.5%) | 18 (25.7%) | |
Tx, n (%) | 7 (5.7%) | 3 (5.8%) | 4 (5.7%) | |
Nodal status (pN or cN) | 0.541 | |||
N0, n (%) | 51 (41.8%) | 18 (34.6%) | 33 (47.1%) | |
N1, n (%) | 53 (43.4%) | 24 (46.2%) | 29 (41.4%) | |
N2, n (%) | 4 (3.3%) | 3 (5.8%) | 1 (1.4%) | |
Nx, n (%) | 14 (11.5%) | 7 (13.5%) | 7 (10%) | |
Metastasis (cM and/or pM) | 0.768 | |||
M0, n (%) | 57 (46.7%) | 27 (51.9%) | 30 (42.9%) | |
M1, n (%) | 65 (53.8%) | 25 (48.1%) | 40 (57.1%) | |
Growth pattern | 0.174 | |||
Mass Forming, n (%) | 72 (59.0%) | 27 (51.9%) | 45 (64.3%) | |
Periductal infiltrating, n (%) | 23 (18.9%) | 10 (19.2%) | 13 (18.6%) | |
Intraductular growth, n (%) | 6 (4.9%) | 1 (1.9%) | 5 (7.1%) | |
Not available, n (%) | 22 (18.0%) | 15 (28.5%) | 7 (10.0%) | |
Laboratory | ||||
AST, U/L median (IQR) | 44.5 (29–76) | 43.5 (24.7–57.2) | 46 (32–75.5) | 0.848 |
ALT, U/L median (IQR) | 44 (30–68) | 45 (29–74) | 44.5 (30–76.8) | 0.202 |
ALP, U/L median (IQR) | 272 (141–569) | 226 (143–429) | 289 (134.5–588) | 0.189 |
GGT, U/L median (IQR) | 423 (158–752) | 413 (132.7–630.5) | 423 (165–793) | 0.098 |
Bilirubin, mg/dL median (IQR) | 1.03 (0.45–4.50) | 0.98 (0.43–4.01) | 1.25 (0.45–4.48) | 0.707 |
Cholesterol, mg/dL median (IQR) | 148 (132–201) | 201 (181–213) | 141 (130–143.5) | 0.404 |
LDL, mg/dL median (IQR) | 93 (94–129) | 127 (109–140) | 87 (74–91) | 0.383 |
TG mg/dL, median (IQR) | 118.5 (92–188) | 132 (112–199) | 92 (71–114) | 0.777 |
AFP, ng/mL median (IQR) | 3.1 (2–5.7) | 3 (2.2–4.0) | 3.35 (2.05–5.37) | 0.157 |
CEA, ng/L median (IQR) | 3.61 (2.08–14.5) | 3.62 (2.05–12.87) | 3.65 (2.1–16.87) | 0.223 |
CA19.9, ng/L median (IQR) | 145 (35.6–614) | 112.45 (38.82–461.75) | 151.85 (26.64–675.2) | 0.855 |
Glucose, mg/dL median (IQR) | 104 (100–106) | 111 (98.5–125) | 95 (83–107.5) | 0.542 |
Albumin, g/dL median (IQR) | 3.6 (3.3–4.1) | 3.5 (3.1–4.1) | 3.7 (3.3–4.1) | 0.164 |
Neutrophils, /mm3 median (IQR) | 6620 (5800–7400) | 6600 (5800–7400) | 6700 (5700–7405) | 0.621 |
Lymphocytes, /mm3 median (IQR) | 2100 (1400–2950) | 2300 (1500–3020) | 1900 (1395–2950) | 0.701 |
Hemoglobin, g/dL median (IQR) | 11.9 (10.8–12.9) | 12.05 (11.0–13.07) | 11.6 (10.4–12.7) | 0.456 |
Platelets, 103 median (IQR) | 270 (201–351) | 279 (185–347) | 266 (212–354) | 0.173 |
INR, median (IQR) | 1.15 (1.05–1.26) | 1.13 (1.05–1.24) | 1.16 (1.05–1.28) | 0.576 |
Therapeutic management | ||||
Curative intent resection, n (%) | 29 (23.8%) | 15 (28.8%) | 14 (20%) | 0.256 |
Recurrence after surgery, n (%) | 21 (17.2%) | 8 (15.4%) | 13 (18.6%) | 0.039 |
Chemotherapy, n (%) | 104 (85.2%) | 45 (76.9%) | 59 (84.3%) | 0.256 |
Best supportive care, n (%) | 11 (9%) | 1 (1.9%) | 10 (14.3%) | 0.018 |
Biliary stent, n (%) | 66 (54.1%) | 25 (48.1%) | 41 (58.6%) | 0.25 |
Biliary drainage, n (%) | 19 (15.5%) | 9 (17.3%) | 10 (14.3%) | 0.328 |
Subgroups (n) | n | Median Overall Survival (95% CI) | Univariate p | HR (95% CI) Multivariate, p Value |
---|---|---|---|---|
Man | 50 | 11.5 (8.6–20.6) | 0.88 | |
Woman | 72 | 14.6 (9.4–17.4) | ||
Obesity | 13 | 15.5 (5.8–NR) | 0.77 | |
No obesity | 109 | 13.4 (9.6–17.3) | ||
Diabetes | 24 | 22.8 (5.8–38.2) | 0.04 | 0.54 (0.25–1.15), p = 0.111 |
No diabetes | 98 | 11.9 (9.4–15.5) | ||
Smoking | 54 | 10.1 (7.4–15.3) | 0.17 | |
No smoking | 68 | 16.5 (11.1–21.8) | ||
Alcohol | 20 | 16.2 (5.7–22.4) | 0.93 | |
No alcohol | 102 | 14.0 (9.6–17.3) | ||
Undefined primary site | 3 | 3.5 (3.5–NR) | 0.539 | |
Distal | 41 | 20.6 (14.8–25.3) | ||
Intrahepatic | 48 | 10.5 (7.4–14.6) | ||
Perihilar | 30 | 8.9 (5.4–26.7) | ||
PS0 | 42 | 16.8 (14.2–29.2) | <0.001 | 1.86 (1.43–2.41), p < 0.0001 |
PS1 | 42 | 13.4 (9.4–20.6) | ||
PS2 | 25 | 11.1 (5.5–22.0) | ||
PS3 | 12 | 3.0 (2.1–5.4) | ||
PS4 | 1 | NR (NR–NR) | ||
Vascular invasion | 44 | 5.9 (4.5–11.4) | 0.0012 | 1.61 (1.01–2.58), p = 0.048 |
No vascular invasion | 74 | 16.5 (11.9–22.4) | ||
Node positive | 55 | 8.9 (5.8–15.3) | 0.14 | |
Node negative | 62 | 16.5 (10.9–26.9) | ||
Metastasis | 61 | 8.9 (5.4–14.0) | 0.001 | 1.47 (0.91–2.41), p = 0.118 |
No metastasis | 59 | 21.8 (13.4–26.9) | ||
Biliary stent | 66 | 13.4 (7.2–17.3) | 0.07 | |
No biliary stent | 56 | 15.5 (9.6–25.3) | ||
Resection | 29 | 34.2 (22.0–43.5) | <0.0001 | 0.42 (0.21–0.86), p = 0.018 |
No resection | 93 | 10.5 (7.5–14.0) | ||
Family history of neoplasia | 50 | 20.7 (11.9–25.2) | 0.11 | |
No family history of neoplasia | 67 | 11.5 (7.7–16.2) | ||
CA19.9 < 150 U/mL | 64 | 17.5 (11.5–22.4) | 0.0003 | 1.47 (0.91–2.36), p = 0.112 |
CA19.9 ≥ 150 U/mL | 58 | 8.1 (5.7–14.3) | ||
Metabolic disorder group | 52 | 15.5 (10.9–33.9) | 0.048 | 1.09 (0.62–1.94), p = 0.745 |
Non-metabolic-disorder group | 70 | 11.5 (8.4–16.5) |
Overall Survival | n | Median (95% CI) |
Total cohort, months (95% CI) | 122 | 14.3 months (10.1–17.3) |
Treated with surgery, months (95% CI) | 8 | 35.5 months (35–NR) |
Treated with surgery plus CT at recurrence, months (95% CI) | 21 | 26.9 months (17.3–43.5) |
Treated with chemotherapy only, months (95% CI) | 82 | 11.5 months (8.4–14.8) |
Best supportive care only, months (95% CI) | 11 | 3.5 months (0.2–5.3) |
“Non-metabolic group” treated with surgery, months (95% CI) | 14 | 21.8 months (95% CI 8.6–26.9) |
“Metabolic group” treated with surgery, months (95% CI) | 15 | 43.4 months (95% CI 33.9–NR) |
“Non-metabolic group” treated with chemotherapy, months (95% CI) | 46 | 11.5 months (95% CI 6.7–16.2) |
“Metabolic group” treated with chemotherapy, months (95% CI) | 36 | 11.5 months (95% CI 5.8–15.3) |
Progression-Free Survival (PFS) | n | Median (95% CI) |
PFS to first-line chemotherapy, months (95% CI) | 82 | 4.3 months (3.5–5.1) |
PFS to first-line chemotherapy “metabolic group”, months (95% CI) | 36 | 5.8 months (3.8–8) |
PFS to first-line chemotherapy “non-metabolic group”, months (95% CI) | 46 | 4.2 months (2.6–4.7) |
Recurrence-Free Survival after Surgery (RFS) | n | Median (95% CI) |
RFS after surgery, months (95% CI) | 21 | 14 months (8.2–19.8) |
RFS after surgery “metabolic group”, months (95% CI) | 8 | 15.6 months (8.2–24.6) |
RFS after surgery “non-metabolic group”, months (95% CI) | 13 | 13.5 months (3.5–19.8) |
Survival according to Radiologic Response | n | Median (95% CI) |
Partial response, months (95% CI) | 28 | 17.4 months (14.6–38.21) |
Stable disease, months (95% CI) | 39 | 20.5 months (11.9–22.8) |
Progressive disease, months (95% CI) | 30 | 7.4 months (5.4–9.6) |
No assessment, months (95% CI) | 7 | 2.8 months (1.6–4.4) |
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Da Fonseca, L.G.; Hashizume, P.H.; de Oliveira, I.S.; Izquierdo-Sanchez, L.; Saud, L.R.d.C.; Xerfan, M.P.; Alves, V.A.F.; de Mello, E.S.; Herman, P.; Banales, J.M.; et al. Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence. Cancers 2022, 14, 3483. https://doi.org/10.3390/cancers14143483
Da Fonseca LG, Hashizume PH, de Oliveira IS, Izquierdo-Sanchez L, Saud LRdC, Xerfan MP, Alves VAF, de Mello ES, Herman P, Banales JM, et al. Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence. Cancers. 2022; 14(14):3483. https://doi.org/10.3390/cancers14143483
Chicago/Turabian StyleDa Fonseca, Leonardo G., Pedro H. Hashizume, Irai Santana de Oliveira, Laura Izquierdo-Sanchez, Lisa Rodrigues da Cunha Saud, Mariana Pinheiro Xerfan, Venancio Avancini Ferreira Alves, Evandro Sobroza de Mello, Paulo Herman, Jesus M. Banales, and et al. 2022. "Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence" Cancers 14, no. 14: 3483. https://doi.org/10.3390/cancers14143483