Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic Cholangiocarcinoma

Tsilimigras, Diamantis I.; Ejaz, Aslam; Cloyd, Jordan M.; Guglielmi, Alfredo; Aldrighetti, Luca; Weiss, Matthew J.; Bauer, Todd W.; Alexandrescu, Sorin; Poultsides, George A.; Maithel, Shishir K.; Martel, Guillaume; Pulitano, Carlo; Shen, Feng; Soubrane, Olivier; Koerkamp, Bas Groot; Endo, Itaru; Pawlik, Timothy M.

doi:10.1245/s10434-022-11462-y

Cited by 10 publications

(4 citation statements)

References 30 publications

(45 reference statements)

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“…Given the poor prognosis of CCA, especially iCCA, efforts have recently focused on improving prognostication and optimising selection criteria to identify the best candidates for surgery. 36 , 37 , 38 , 39 Traditional predictors of outcomes among patients with iCCA include tumour burden, differentiation, grade, microvascular invasion, lymph node metastasis and tumour markers (CA). 40 , 41 However, so far, available prognostic factors have not accurately predicted the prognoses of patients with iCCA.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of JAM3 occurs in cholangiocarcinoma by hypermethylation: A potential molecular marker for diagnosis and prognosis

Shi,

Feng,

Zhang

et al. 2023

J Cellular Molecular Medi

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Junctional adhesion molecular 3 (JAM3) is downregulated by hypermethylation in cancers but is unclear in cholangiocarcinoma. The JAM3 expression level was checked in cholangiocarcinoma cell lines and tissues. Methylated JAM3 was detected in cell lines, tissues and plasma cell‐free DNAs (cfDNA). The roles of JAM3 in cholangiocarcinoma were studied by transfection of siRNA and pCMV3‐JAM3. The survival analysis was based on the Gene Set Cancer Analysis (GSCA) database. JAM3 was downregulated in HCCC‐9810 and HuCCT1 cell lines and tissues by hypermethylation. Methylated JAM3 was detected in cfDNAs with 53.3% sensitivity and 96.6% specificity. Transfection of pCMV3‐JAM3 into HCCC‐9810 and HuCCT1 induced apoptosis and suppressed cell proliferation, migration and invasion. The depletion of JAM3 in RBE cells using siRNA decreased apoptosis and increased cell proliferation, migration and invasion. Hypermethylation of JAM3 was associated with tumour differentiation, metastasis and TNM stage. Downregulation and hypermethylation of JAM3 were related to poor progression‐free survival. Junctional adhesion molecular 3 may function as a tumour suppressor in cholangiocarcinoma. Methylated JAM3 DNA may represent a non‐invasive molecular marker for the early detection of cholangiocarcinoma and prognosis.

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Section: Discussionmentioning

confidence: 99%

Downregulation of JAM3 occurs in cholangiocarcinoma by hypermethylation: A potential molecular marker for diagnosis and prognosis

Shi,

Feng,

Zhang

et al. 2023

J Cellular Molecular Medi

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“…Third, there may be some risks of selection bias. Our study pulled worldwide population-based cohort studies with relatively large numbers of patients, 30,31 and these studies were assigned great weight. As a result, the pooled effect sizes tended to be consistent with the results of these population-based cohort studies.…”

Section: Publication Biasmentioning

confidence: 99%

“…After excluding 1818 duplicate studies, the titles and abstracts of the 4574 reports were scanned to exclude irrelevant research. In the end, 59 studies were pulled for full-text evaluation and 10 matching the inclusion criteria were finally included in the metaanalysis [23][24][25][26][27][28][29][30][31][32] (Figure 1). The characteristics and details of all included studies are shown in Table 1.…”

Section: Literature Research and Characteristics Of Studiesmentioning

confidence: 99%

Is tumor necrosis a clinical prognostic factor in hepato‐biliary‐pancreatic cancers? A systematic review and meta‐analysis

Yang

et al. 2023

Cancer Medicine

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Background It has been proven that tumor necrosis is associated with poor prognoses in various solid malignant tumors. However, the prognostic effect of tumor necrosis in hepato‐biliary‐pancreatic cancers is still unclear. Therefore, this study was performed to evaluate the associations of tumor necrosis with survival outcomes and clinicopathological features in patients with hepato‐biliary‐pancreatic cancers. Methods Based on the PRISMA statement, eligible studies were identified from PubMed, Embase, Cochrane Library, and Web of Science from inception until January 2023. The pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs) were calculated to assess the connection between tumor necrosis and hepato‐biliary‐pancreatic cancers. We then choose which effects model to use to generate pooled HRs and 95% CIs, depending on data heterogeneity. Results In total, 6497 articles were identified, 10 of which were included in this meta‐analysis. Our results suggested that the presence of tumor necrosis predicted a poorer outcome for overall survival (HR = 1.54, 95% CI = 1.35–1.77, p < 0.001) and recurrence‐free survival (HR = 1.69, 95% CI = 1.37–2.08, p < 0.001). In addition, tumor necrosis was correlated with larger tumor size, a higher frequency of lymph node metastasis, poorer histologic differentiation, and higher recurrence and metastasis rates. Conclusion Our meta‐analysis suggests that hepato‐biliary‐pancreatic cancer patients with tumor necrosis have dismal survival outcomes, and that their tumors have aggressive biological behaviors. Tumor necrosis has the potential to be a promising biomarker for forecasting poor prognosis in these patients.

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“…Recent studies suggest that PNI may indicate a worse prognosis for ICC patients ( 10 - 12 ). Due to the varying prognoses within different subgroups of early ICC patients ( 13 , 14 ), despite the existing research on PNI in this population, the impact of PNI on the prognosis of early ICC patients still requires further exploration.…”

Section: Introductionmentioning

confidence: 99%

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study

Zou,

Sheng,

Ruan

et al. 2023

J Gastrointest Oncol

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Background Intrahepatic cholangiocarcinoma (ICC) poses a significant clinical challenge, demanding a thorough understanding of prognostic indicators for effective patient management. Despite reports suggesting the impact of perineural invasion (PNI) on the prognosis of early-stage ICC patients, there has been a dearth of comprehensive research specifically targeting this subgroup. This study seeks to investigate the influence of PNI on survival outcomes in early-stage ICC patients and aims to enhance the prognostic value of the American Joint Committee on Cancer (AJCC) T category. Methods A cohort of 268 early-stage (T1-T2N0M0) ICC patients, who underwent curative-intent resection (R0) between 2011 and 2015 at the Eastern Hepatobiliary Surgery Hospital, were enrolled in this study. Lasso and Cox regression analyses were employed to explore differences in clinical and prognostic data. Kaplan-Meier curves were generated to illustrate the clinical significance of the combination of PNI and T category. Results Among the 268 patients, 24.6% exhibited PNI. Patients with PNI demonstrated shorter recurrence-free survival (RFS) [median RFS: 16 months (interquartile range, 9.5–19 months)] and overall survival (OS) [median OS: 16.53 months (interquartile range, 10–25 months)]. PNI emerged as an independent risk factor for both RFS and OS in T1- and T2-stage patients (all P<0.05), whereas tumor size was only an independent risk factor for OS (P=0.004). PNI was associated with all prognostic markers for ICC patients, including gender, jaundice, cholangitis, hepatitis B virus (HBV) infection, cancer antigen 199 (CA199), preoperative serum albumin, and preoperative platelet count (all P<0.05). However, there was no significant difference in RFS (P=0.270) and OS (P=0.360) between T2 patients without PNI and T1 patients with PNI. Conclusions This study underscores PNI as a robust prognostic factor in early-stage ICC, emphasizing the necessity of incorporating PNI into the AJCC T category for precise risk stratification. Clinically, understanding the impact of PNI on survival outcomes can guide tailored treatment strategies for early ICC patients.

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Tumor Necrosis Impacts Prognosis of Patients Undergoing Resection for T1 Intrahepatic Cholangiocarcinoma

Cited by 10 publications

References 30 publications

Downregulation of JAM3 occurs in cholangiocarcinoma by hypermethylation: A potential molecular marker for diagnosis and prognosis

Downregulation of JAM3 occurs in cholangiocarcinoma by hypermethylation: A potential molecular marker for diagnosis and prognosis

Is tumor necrosis a clinical prognostic factor in hepato‐biliary‐pancreatic cancers? A systematic review and meta‐analysis

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study

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