The Significance of Histopathological Evaluation of Pancreatic Fibrosis to Estimate Pancreas Cancer Progression

Objective To estimate the importance of the role of pancreatic stellate cells in pancreas cancer progression, their properties were evaluated in relation to clinical details and patient prognosis. Patients and Methods Among patients who underwent surgical treatment from 2004 to 2013, the texture of the pancreatic specimens was evaluated by histopathological measurement length of fibrosis, fibrosis grade and the intensity of pancreatic stellate cell activity. Results 1. The histopathological measurement length of inter- and intralobular fibrosis increased significantly with progression of FG from grade 0 to 3 (22.0±4.5 vs. 23.7±1.9 vs. 53.5±6.0 vs. 203.7±18.6 and 2.0±0.4 vs. 2.7±0.3 vs. 8.2±1.0 vs. 21.7±3.1, respectively). 2. The histopathological measurement length of inter- and intralobular fibrosis was also significantly longer with the increase in pancreatic stellate cell activity score from 0 to 3 (29.7±5.9 vs. 37.4±7.2 vs. 68.4±9.5 vs. 204.7±20.5 and 3.1±0.5 vs. 5.1±1.1 vs. 9.7±1.1 vs. 21.6±3.4, respectively). 3. The histopathological measurement length of both inter- and intralobular fibrosis correlated with the preoperative level of HbA1c but not with pathological invasion of cancer in lymphatic vessels and the nervous system. 4. Fibrosis grade and pancreatic stellate cell activity did not correlate with pancreas function and clinical factors. 5. Significantly higher rates of positive lymph node metastases were detected in the patients with high fibrosis grade or pancreatic stellate cell activity. 6. There were no significant differences in either fibrosis grade or pancreatic stellate cell activity in whole pancreas cancer cases, and in T3 patients only, 2-year survival rate and median survival term were similar among the different fibrosis grades. However, pancreatic stellate cell activity in T3 patients had a significantly different effect on patient prognosis. 7. Specifically for stage II/III patients, survival rates were similar for different fibrosis grades but clearly different depending on the severity of pancreatic stellate cell activity. When limiting the cancer site to the pancreas head, survival rate and median survival term in T3 patients were clearly poorer as pancreatic stellate cell activity increased but not as fibrosis grade increased. Conclusion Fibrotic change as measured by the amount of fibrotic tissue present favors prediction of pancreatic function, whereas pancreatic stellate cell activity favors prediction of cancer progression.

Author(s): Shinji Osada, Kaoru Tanaka, Satoshi Matsui, Yoshiyuki Sasaki, Hiroyuki Tomita, Yoshihiro Tanaka, Naoki Okumura, Nobuhisa Matsuhashi, Kazuhiro Yoshida

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