Validation of T Stage According to Depth of Invasion and N Stage Subclassification Based on Number of Metastatic Lymph Nodes for Distal Extrahepatic Bile Duct (EBD) Carcinoma

Abstract

According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: ≥ 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1–3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs ≥ 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more accurate evaluation of N stage in distal EBD carcinoma. We propose an alternative T classification using DoI and 3-tier sub-classification of N stage for distal EBD carcinoma.

Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth

“…This heterogeneity required the predefinition of measurement methods according to the gross tumour morphology, an approach that is frequently applied for tumours such as cutaneous melanoma and early‐stage colorectal cancer. To date, two measurement methods have been reported for depth assessment in cholangiocarcinoma: DOI and ITT. It was reported previously that the measurability of DOI depended on tumour morphology, size and direction of sectioning of the resected specimen, but the measurability of ITT did not.…”

“…Invasive tumour thickness (ITT) was defined as the vertical distance from the top of the tumour to the deepest invasive cells ( Fig . ), as reported previously. Microscopic perineural, lymphatic and venous invasion were not considered for this measurement.…”

Proposal of the minimal number of retrieved regional lymph nodes for accurate staging of distal bile duct cancer and clinical validation of the three‐tier lymph node staging system (AJCC 8th edition)

“…Therefore, retrieving enough regional LNs and accurately determining the cancer stage is important to determine the prognosis. The 5th AJCC staging system recommended to examine at least three LNs, but no evidence of the [26,27]. However, these reports did not mention the rate of LN positivity, according to the number of retrieved LNs, and the number of enrolled patients was too small.…”

“…However, studies reporting the superiority of the 8th AJCC T stage over the 7th are limited. Two external validation studies failed to show significant survival discrimination among the proposed 8th T stage criteria [27,29], and one of these studies proposed different cutoff values for tumor invasion depth, based on T stage [29]. A previous study revealed that the new 8th AJCC T stage did not have better prognostic predictability than the 7th [30].…”

Reappraisal of classification of distal cholangiocarcinoma based on tumour depth

“…However, the bile duct, unlike the gastrointestinal tract, has a thin wall with a frequently obscured outermost boundary, potentially leading to an uncertain T assignment. In addition, the layer‐based T classification fails to stratify postoperative survival in patients with DCC. Thus, the conventional layer‐based T system has limited value in DCC.…”