Background
Methods
Patients and data
Standard pathological assessment
Histologic workup
Immunohistochemistry
Statistics
Results
Clinico-pathological reassessment and baseline data
Parameter | Total | PDAC | DBDAC | AMPAC | DUOAC | p | |
---|---|---|---|---|---|---|---|
N | 198 | 126 | 23 | 40 | 9 | - | |
Male : female | 102:96 | 63:63 | 14:9 | 22:18 | 3:6 | 0.511 | |
Age | 67 (30–89) | 67 (30–89) | 69 (49–83) | 65 (36–84) | 66 (46–78) | 0.137 | |
Distant metastasis (M1) | 7 / 4% | 4 / 3% | 0 / 0% | 2 / 5% | 1 / 11% | 0.448 | |
Neoadjuvant therapy | 14 / 7% | 13 / 10% | 0 / 0% | 1 / 3% | 0 / 0% | 0.126 | |
Resection | PPPD | 163 | 103 | 19 | 34 | 7 | 0.803 |
Whipple | 23 | 14 | 2 | 5 | 2 | ||
total PE | 12 | 9 | 2 | 1 | 0 | ||
PVR | 62 / 31% | 53 /42% | 6 / 26% | 2 / 5% | 1 / 11% |
0.000
| |
Perioperative mortality | 7 / 4% | 5 / 4% | 2 / 9% | 0 / 0% | 0 / 0% | 0.300 | |
Tumor size (mm) | 25 (1–320) | 27 (1–80) | 15 (8–25) | 20 (2–320) | 40 (22–60) |
0.000
| |
Grade G3/4 | 72 / 37% | 48 / 39% | 8 / 35% | 12 / 31% | 4 / 44% | 0.785 | |
Stage T3/4 | 155 / 78% | 109 / 87% | 18 / 78% | 21 / 53% | 7 / 78% |
0.000
| |
Stage N1/2 | 132 / 67% | 89 / 71% | 14 / 61% | 24 / 60% | 5 / 56% | 0.468 | |
Lymph node ratio (LNR) | .09 (0 - .86) | .10 (0 - .86) | .08 (0 - .72) | .07 (0 - .71) | .10 (0 - .28) | 0.694 | |
Lymphangiosis (L1) | 87 / 44% | 60 / 48% | 5 / 22% | 19 / 48% | 3 / 33% | 0.116 | |
Hemangiosis (V1) | 29 / 15% | 22 / 18% | 3 / 13% | 2 / 5% | 2 / 22% | 0.237 | |
Perineural invasion (Pn1) | 113 / 57% | 88 / 70% | 12 / 52% | 13 / 33% | 0 / 0% |
0.000
| |
Associated precursor | Adenoma | 20 / 10% | 1 / 1% | 4 / 17% | 12 / 30% | 3 / 33% |
0.000
|
IPMN | 11 / 6% | 11 / 9% | 0 / 0% | 0 / 0% | 0 / 0% | 0.084 | |
Positive resection margin | 51 / 26% | 41 / 33% | 5 / 22% | 3 / 8% | 2 / 22% |
0.017
| |
Subtype
| |||||||
INT | 39 / 20% | 11 / 9% | 5 / 22% | 18 / 45% | 5 / 56% |
0.000
| |
MIX | 12 / 6% | 8 / 6% | 2 / 9% | 2 / 5% | 0 / 0% | ||
PB | 118 / 16% | 89 / 71% | 12 / 52% | 15 / 38% | 2 / 22% | ||
OTH | 6 / 3% | 5 / 4% | 0 / 0% | 0 / 0% | 1 / 11% | ||
POOR | 23 / 12% | 13 / 10% | 4 / 17% | 5 / 13% | 1 / 11% | ||
Immunohistochemical Markers
| |||||||
% CK7+ | 90 (0–100) | 90 (0–100) | 95 (0–100) | 80 (0–100) | 0 (0–60) |
0.000
| |
% CK20+ | 0 (0–100) | 0 (0–100) | 0 (0–100) | 10 (0–100) | 70 (10–100) |
0.000
| |
% nuclear CDX2+ | 10 (0–100) | 0 (0–100) | 0 (0–100) | 50 (0–100) | 95 (60–100) |
0.000
|
Basic pathology and histological subtype analysis
Diagnostic value of immunohistochemical markers
Location | Marker | % Positive tumor cells | % Correct prediction | p | ||
---|---|---|---|---|---|---|
Median (Range) | ||||||
INT | NON-INT | INT | NON-INT | |||
PDAC / DBDAC | CK7 | 90 (0–100) | 90 (0–100) | 0% | 100% | 0.288 |
CK20 | 10 (0–100) | 0 (0–100) | 0% | 100% | 0.034 | |
CDX2 | 45 (0–100) | 0 (0–90) | 13% | 100% | 0.000 | |
CK7, CK20, CDX2 | - |
19%
|
100%
|
0.002
| ||
multivariate | ||||||
AMPAC / DUOAC | CK7 | 20 (0–100) | 85 (0–100) | 57% | 75% | 0.024 |
CK20 | 80 (0–100) | 8 (0–100) | 65% | 79% | 0.002 | |
CDX2 | 90 (20–100) | 30 (0–100) | 87% | 79% | 0.000 | |
CK7, CK20, CDX2 | - |
87%
|
75%
|
0.000
| ||
multivariate | ||||||
ALL | CK7, CK20, CDX2 | - |
51%
|
95%
|
0.000
| |
multivariate |
Baseline data and biology of the intestinal subtype
Parameter | INT | NON-INT | p | |
---|---|---|---|---|
N | 39 | 159 | - | |
Male : female | 25:14 | 77:82 | 0.079 | |
Age | 69 (36–81) | 67 (30–89) | 0.569 | |
Distant metastasis (M1) | 1 (3%) | 6 (4%) | 0.714 | |
Neoadjuvant therapy | 1 (3%) | 13 (8%) | 0.220 | |
Resection | PPPD | 31 (80%) | 132 (83%) | 0.701 |
Whipple | 6 (15%) | 17 (11%) | ||
TPE | 2 (5%) | 10 (6%) | ||
PVR | 8 (21%) | 54 (34%) | 0.105 | |
Perioperative mortality | 2 (5%) | 5 (3%) | 0.548 | |
Tumor size (mm) | 23 (1–320) | 25 (3–70) | 0.779 | |
Grade G3/4 | 6 (15%) | 66 (42%) |
0.002
| |
pT Stage 3/4 | 21 (54%) | 134 (84%) |
0.000
| |
pN Stage 1/2 | 16 (41%) | 116 (73%) |
0.000
| |
Lymph node ratio (LNR) | .00 (.00-.58) | .12 (.00-.86) |
0.018
| |
Lymphangiosis (L1) | 12 (31%) | 75 (47%) | 0.064 | |
Hemangiosis (V1) | 1 (3%) | 28 (18%) |
0.017
| |
Perineural invasion (Pn1) | 13 (33%) | 100 (63%) |
0.001
| |
Positive resection margin | 3 (8%) | 48 (30%) |
0.004
| |
Location | PDAC / DBDAC | 16 (41%) | 133 (84%) |
0.000
|
AMPAC / DUOAC | 23 (59%) | 26 (16%) | ||
% CK7 | 85 (0–100) | 90 (0–100) | 0.070 | |
% CK20 | 45 (0–100) | 0 (0–100) |
0.000
| |
% nuclear CDX2 | 80 (0–100) | 0 (0–100) |
0.000
| |
Associated precursor lesion | Adenoma | 8 (21%) | 12 (8%) |
0.016
|
IPMN | 3 (8%) | 8 (5%) | 0.516 |
Survival analysis for tumor location and histological subtype
Location | Type | N | Events | Survival (months) | p | |
---|---|---|---|---|---|---|
(Deaths) | Median | Mean | ||||
Comparison of tumor locations versus PDAC
| ||||||
PDAC | ALL | 121 | 64 | 23 | 31 |
-
|
DBDAC | 21 | 14 | 29 | 39 | 0.430 | |
AMPAC | 40 | 14 | 64 | 72 |
0.000
| |
DUOAC | 9 | 6 | 71 | 46 | 0.169 | |
Comparison of tumor subtypes versus INT
| ||||||
ALL | INT | 37 | 8 | NR | 83 |
-
|
MIX | 12 | 8 | 30 | 37 |
0.002
| |
OTH WHO | 6 | 4 | 25 | 38 |
0.017
| |
PB | 115 | 66 | 22 | 34 |
0.000
| |
POOR | 21 | 12 | 13 | 28 |
0.000
| |
NON-INT | 154 | 90 | 22 | 35 |
0.000
| |
Comparison INT vs NON-INT stratified for tumor location
| ||||||
PDAC | NON-INT | 111 | 63 | 20 | 29 |
0.034
|
INT | 10 | 1 | 39 | 74 | ||
DBDAC | NON-INT | 17 | 12 | 12 | 37 | 0.563 |
INT | 4 | 2 | 29 | 55 | ||
AMPAC | NON-INT | 22 | 11 | 38 | 56 |
0.019
|
INT | 18 | 3 | NR | 90 | ||
DUOAC | NON-INT | 4 | 4 | 4 | 10 |
0.003
|
INT | 5 | 2 | 75 | 75 |
Univariate and multivariate survival analysis
Parameter | Condition | Median survival (months) | Hazard ratio | Univariate | Multivariate | |
---|---|---|---|---|---|---|
With condition | Without condition | (95% CI) | p | p | ||
All patients (n = 191) | -26- | - | ||||
Gender | Male | 30 | 25 | 0.953 (0.641–1.417) | 0.812 | NI |
Age (years)1
| > 67 | 26 | 27 | 1.050 (0.706–1.561) | 0.811 | NI |
Distant metastasis | Yes | 11 | 27 | 2.044 (0.892–4.688) | 0.091 | NI |
Neoadjuvant tx | Yes | 25 | 26 | 1.536 (0.741–3.182) | 0.248 | NI |
PVR | Yes | 25 | 27 | 1.640 (1.068–2.517) | 0.024 | 0.510 |
Tumor size (mm)1
| > 25 | 26 | 26 | 1.069 (0.699–1.635) | 0.759 | NI |
Tumor grade | G3/4 | 17 | 31 | 1.808 (1.199–2.726) |
0.005
| 0.075 |
pT stage | pT3/4 | 23 | 41 | 1.938 (1.160–3.238) |
0.012
| 0.905 |
pN stage | pN1/2 | 22 | 52 | 1.883 (1.198–2.959) |
0.006
| 0.211 |
LNR1
| > 0.09 | 20 | 48 | 2.291 (1.515–3.465) |
0.000
|
0.019
|
Lymphangiosis | Present | 22 | 30 | 1.557 (1.035–2.342) |
0.033
| 0.398 |
Hemangiosis | Present | 12 | 29 | 1.900 (1.161–3.109) |
0.011
| 0.384 |
Perineural invasion | Present | 25 | 29 | 1.322 (0.881–1.984) | 0.177 | NI |
Precursor lesion | Present | NR | 25 | 0.362 (0.175–0.748) |
0.006
| 0.169 |
Resection margins | Positive | 19 | 37 | 2.368 (1.551–3.617) |
0.000
| 0.132 |
Tumor subtype2
| See Table 4
| 1.487 (1.253–1.765) |
0.000
|
0.006
| ||
Tumor location2
| See Table 4
| 1.471 (1.175–1.843) |
0.001
| 0.270 | ||
CK7 + (%)1
| > 90 | 20 | 38 | 1.757 (1.161–2.657) |
0.008
| 0.869 |
CK20 + (%)1
| > 0 | 29 | 23 | 0.311 (0.538–1.218) | 0.311 | NI |
CDX2 + (%)1
| > 10 | 48 | 20 | 0.562 (0.368–0.858) |
0.008
| 0.767 |