Tumor Necrosis Impacts Prognosis of Patients Undergoing Curative-Intent Hepatocellular Carcinoma

Abstract

Background. The impact of tumor necrosis relative to prognosis among patients undergoing curative-intent resection for hepatocellular carcinoma (HCC) remains illdefined. Methods. Patients who underwent curative-intent resection for HCC without any prior treatment between 2000 and 2017 were identified from an international multi-institutional database. Tumor necrosis was graded as absent, moderate (\ 50% area), or extensive (C 50% area) on histological examination. The relationship between tumor necrosis, clinicopathologic characteristics, and long-term survival were analyzed. Results. Among 919 patients who underwent curative-intent resection for HCC, the median tumor size was 5.0 cm (IQR, 3.0-8.5). Tumor necrosis was present in 367 (39.9%) patients (no necrosis: n = 552, 60.1% vs \ 50% necrosis: n = 256, 27.9% vs C 50% necrosis: n = 111, 12.1%). Extent of tumor necrosis was also associated with more advanced tumor characteristics. HCC necrosis was associated with OS (median OS: no necrosis, 84.0 months vs \ 50% necrosis, 73.6 months vs C 50% necrosis: 59.3 months; p \ 0.001) and RFS (median RFS: no necrosis, 49.6 months vs \ 50% necrosis, 38.3 months vs C 50% necrosis: 26.5 months; p \ 0.05). Patients with T1 tumors with extensive C 50% necrosis had an OS comparable to patients with T2 tumors (median OS, 62.9 vs 61.8 months; p = 0.645). In addition, patients with T2 disease with necrosis had long-term outcomes comparable to patients with T3 disease (median OS, 61.8 vs 62.4 months; p = 0.713).

Low serum magnesium concentration is associated with the presence of viable hepatocellular carcinoma tissue in cirrhotic patients

“…However, when we also included larger tumors outside the transplantation criteria, the correlation does not remain, because very large tumors are associated with a lower than expected reduction effect on magnesium levels. The explanation for this particular behavior of larger tumors could be that, as already demonstrated, large HCCs are associated with severe spontaneous necrosis of the lesions and therefore have fewer viable cells capable of internalizing Mg than those expected based on the size of the lesions 42 . Regarding the change in magnesemia after locoregional treatment, we did not find a relationship either with the total tumor volume before treatment or with the residual tumor tissue after therapy.…”

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

“…For example, Wei et al recently demonstrated the prognostic impact of tumor necrosis among 919 patients who underwent curative-intent resection for HCC. 12 In this study, tumor necrosis was a strong predictor of poor outcomes following HCC resection irrespective of T stage. 12 In another study, Atanasov et al demonstrated that tumor necrosis was the only independent prognostic factor among individuals with resected hilar cholangiocarcinoma (n = 47) after adjusting for other clinicopathologic characteristics.…”

“…12 In this study, tumor necrosis was a strong predictor of poor outcomes following HCC resection irrespective of T stage. 12 In another study, Atanasov et al demonstrated that tumor necrosis was the only independent prognostic factor among individuals with resected hilar cholangiocarcinoma (n = 47) after adjusting for other clinicopathologic characteristics. 27 The same group later reported on the impact of tumor necrosis among 88 patients with ICC in a single-center analysis.…”

“…One possible explanation is that rapid tumor growth may contribute to the relative hypoperfusion in the core areas of tumors leading to hypoxia, and subsequent cell death. 12,14,23 Necrotic cells release cellular contents, which may then act as proinflammatory and tumor-promoting cytokines. Tumor necrosis attenuates local and systemic inflammatory response, remodeling the tumor microenvironment to promote immune evasion.…”

“…10,11 Tumor necrosis has been associated with worse prognosis among individuals with a variety of solid tumors, including HCC and pancreatic and breast cancer. [12][13][14] Due to the rarity of the disease, there is a paucity of data regarding the association of tumor necrosis with long-term outcomes among patients with resectable ICC. 15 To this end, the objective of this study was to define the prognostic impact of tumor necrosis among patients who underwent resection of ICC utilizing a large multi-institutional database.…”