Table 2.
Univariate and multivariate analyses of OS with TIL in patients with DBDC
| Variable (n = 405) | Univariate |
Multivariate |
||
|---|---|---|---|---|
| Median (months) | P value | HR (95% CI) | P value | |
| sTIL density | 0.99 (0.98-0.99)a | <0.001∗ | ||
| sTILLow (≤5%) | 31.3 | 0.009∗ | 1 | 0.006∗ |
| sTILHigh (>5%) | 49.1 | 0.71 (0.56-0.91) | ||
| iTIL count | 0.95 (0.91-1.00)a | 0.039∗ | ||
| iTILLow (≤3) | 37.4 | 0.036∗ | 1 | 0.179 |
| iTILHigh (>3) | 61.4 | 0.80 (0.58-1.11) | ||
| Operation method | 0.011∗ | 0.033∗ | ||
| Pancreaticoduodenectomy including Whipple | 41.2 | 1 | ||
| Bile duct resection | 18.2 | 1.55 (1.04-2.31) | ||
| Age (years) | 1.01 (1.00-1.03)a | 0.022∗ | 1.02 (1.00-1.03) | 0.011∗ |
| Tumor size (cm) | 1.16 (1.06-1.27)a | 0.001∗ | 1.11 (1.01-1.23) | 0.031∗ |
| Sex | 0.187 | |||
| Male | 36.3 | |||
| Female | 50.7 | |||
| Gross pattern | <0.001∗ | 0.073 | ||
| Papillary | 106.2 | 1 | ||
| Nodular | 88.5 | 0.78 (0.42-1.45) | 0.439 | |
| Sclerosing | 32.7 | 1.17 (0.67-2.06) | 0.579 | |
| Tumor location | 0.042∗ | 0.489 | ||
| Extrapancreatic | 26.4 | 1 | ||
| Intrapancreatic | 41.2 | 0.77 (0.46-1.28) | 0.310 | |
| Diffuse (both extra- and intrapancreatic) | 35.1 | 0.65 (0.31-1.35) | 0.247 | |
| Histologic subtypeb | 0.134 | |||
| Tubular adenocarcinoma | 37.9 | |||
| Adenocarcinoma arising from IPNB | 107.0 | |||
| Undifferentiated carcinoma | 13.6 | |||
| Histologic differentiation | 0.003∗ | 0.017∗ | ||
| Well differentiated | 100.2 | 1 | ||
| Moderately differentiated | 36.3 | 1.39 (1.00-1.95) | 0.053 | |
| Poorly differentiated | 21.1 | 1.87 (1.24-2.82) | 0.003∗ | |
| Undifferentiated | 13.6 | 2.44 (0.73-8.16) | 0.103 | |
| Lymphovascular invasion | 0.001∗ | 0.258 | ||
| Absent | 53.3 | 1 | ||
| Present | 31.5 | 1.16 (0.90-1.49) | ||
| Perineural invasion | 0.018∗ | 0.639 | ||
| Absent | 62.1 | 1 | ||
| Present | 36.3 | 0.93 (0.67-1.28) | ||
| Pancreatic invasion | 0.025∗ | 0.473 | ||
| Absent | 62.7 | 1 | ||
| Present | 31.0 | 1.12 (0.82-1.54) | ||
| Duodenal invasion | <0.001∗ | 0.244 | ||
| Absent | 50.3 | 1 | ||
| Present | 25.7 | 1.19 (0.89-1.61) | ||
| Gallbladder invasion, absent versus present | 40.6 versus 26.3 | 0.055 | ||
| Bile duct resection margin, R0 versus R1 | 45.8 versus 20.5 | <0.001∗ | 1.67 (1.19-2.35) | 0.003∗ |
| Postoperative chemotherapy, absent versus present | 41.1 versus 39.1 | 0.387 | ||
| Number of metastatic nodes | 1.21 (1.15-1.28) | <0.001∗ | ||
| Nodal metastasis, absent versus present | 63.6 versus 20.8 | <0.001∗ | ||
| T category | <0.001∗ | 0.008∗ | ||
| T1 | 72.2 | 1 | ||
| T2 | 37.4 | 1.17 (0.86-1.59) | 0.320 | |
| T3 | 21.0 | 1.80 (1.22-2.25) | 0.003∗ | |
| N category | <0.001∗ | <0.001∗ | ||
| N0 | 63.6 | 1 | ||
| N1 | 22.6 | 1.67 (1.27-2.19) | <0.001∗ | |
| N2 | 17.0 | 3.26 (2.14-4.96) | <0.001∗ | |
| Stage grouping | <0.001∗ | |||
| I | 90.6 | |||
| II | 32.3 | |||
| III | 17.0 | |||
| IV | 16.9 | |||
CI, confidence interval; DBDC, distal extrahepatic bile duct carcinoma; HR, hazard ratio; IPNB, intraductal papillary neoplasm of the bile duct; iTIL, intraepithelial tumor-infiltrating lymphocyte; iTILHigh, high level of iTIL count; iTILLow, low level of iTIL count; OS, overall survival; R0, microscopically free of tumor; R1, microscopically positive margin; sTIL, stromal tumor-infiltrating lymphocyte; sTILHigh, high level of sTIL density; sTILLow, low level of sTIL density; TIL, tumor-infiltrating lymphocyte.
a
Displayed as a form of HR with 95% CI.
b
Excluding cases with mucinous (n = 1) and adenosquamous (n = 2) carcinomas.
∗
Significant at the level of P < 0.05.