The prognostic impact of differentiation at the invasive front of biliary tract cancer

Okubo, Satoshi; Mitsunaga, Shuichi; Kato, Yukio; Kojima, Masaru; Sugimoto, Motokazu; Gotohda, Naoto; Takahashi, Shinichiro; Hayashi, Ryuichi; Konishi, Masaru

doi:10.1002/jso.24946

Cited by 22 publications

(32 citation statements)

References 34 publications

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“…Several reports used immunohistochemistry by cytokeratin to easily identify TB at stroma [8,25]. Okubo et al [12] demonstrated the strong correlation between TB counts cytokeratinstained tissue and the H&E-stained tissue sections in In patients with neoadjuvant therapy, patients in high TB group had significantly poor survival as compared to patients in low TB group (p < 0.001 in DSS, p = 0.001 in RFS). Similarly, in patients without neoadjuvant therapy, patients in high TB group had significantly poor DSS and had a tendency with poor RFS, as compared to patients in low TB group (p = 0.004 in DSS, p = 0.127 in RFS).…”

Section: Discussionmentioning

confidence: 99%

“…Primary tumor staging (pT) and regional lymph node metastasis (pN) were defined according to Union for International Cancer Control (UICC) 8th edition. TB was defined as an isolated cancer cell or clusters composed of fewer than 5 cancer cells at the site of tumor invasive front according to previous studies [10][11][12][13]. The invasive front was defined as the peripheral to whole primary tumor and in the most severe extended area of tumor to the surrounding tissue according to previous studies.…”

Section: Histology and Assessment Of Tumor Buddingmentioning

confidence: 99%

“…The maximal value of tumor budding was defined as TB counts for each tumor. Based on previous studies [10,12,13], TB counts were classified into two groups: low TB (TB counts < 5) and high TB (TB counts≥5). In addition, Sub-analysis for comparison between groups with TB counts 5-9 vs TB counts ≥5 was performed.…”

Section: Histology and Assessment Of Tumor Buddingmentioning

confidence: 99%

“…In addition, it has been identified as a novel prognostic factor in various types of cancer such as esophageal [7], pancreatic [8], as well as, cancer of the ampulla [9], and gall bladder [10]. With regards to cholangiocarcinoma, three reports on the impact of TB have recently been published [11][12][13]. Ogino et al [11] demonstrated that high TB grade was an independent adverse prognostic factor in 195 perihilar cholangiocarcinoma patients by multivariate analysis.…”

Section: Introductionmentioning

confidence: 99%

“…Ogino et al [11] demonstrated that high TB grade was an independent adverse prognostic factor in 195 perihilar cholangiocarcinoma patients by multivariate analysis. Okubo et al [12] reported the prognostic significance of TB in resected 299 patients with biliary tree carcinoma (intrahepatic: n = 47 (16%), extrahepatic: n = 144 (48%), gallbladder: n = 50 (17%), ampulla: n = 58 (19%)). In addition, Tanaka et al [13] demonstrated that TB tumor budding was a significant prognostic factor in 107 cases of intrahepatic cholangiocarcinoma and 54 cases of perihilar cholangiocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

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High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

et al. 2020

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Background: Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy. Methods: Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5). Results: In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001). Conclusion: This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Histology and Assessment Of Tumor Buddingmentioning

confidence: 99%

Section: Histology and Assessment Of Tumor Buddingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

et al. 2020

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Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study

Kosaka

Ishida

Ueno

et al. 2022

Annals of Gastroent Surgery

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Purpose This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC). Methods We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition. Results Patients with ICC with high budding showed significantly shorter disease‐specific survival (DSS) and disease‐free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2‐2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05). Conclusions High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.

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Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection

Cao

Yan

et al. 2023

Cancer Medicine

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BackgroundThe influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC.MethodsWe retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease‐free survival (DFS), surgery‐related outcomes, and surgical approaches were collected.ResultsA total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p < 0.001). There was no significance in OS (p = 0.790), DFS (p = 0.580), and surgery‐related outcomes (all p > 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery‐related outcomes between different TTT groups of incidental GBC patients (all p > 0.05).ConclusionsPositive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery‐related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

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The prognostic impact of differentiation at the invasive front of biliary tract cancer

Abstract: Poor differentiation at the invasive front of tumor was associated with poor prognosis and early relapse in BTC patients.

Cited by 22 publications

References 34 publications

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study

Estimating the influencing factors for T1b/T2 gallbladder cancer on survival and surgical approaches selection

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