Abstract

Abstract Despite the general trends towards increased cancer survival, pancreatic ductal adenocarcinoma (PDAC) still has a dismal prognosis. Peritoneal recurrence is a major recurrence pattern after pancreatectomy. Peritoneal lavage cytology (CY) is employed widely in the diagnosis and staging of PDAC to rule out patients with occult peritoneal metastasis. However, the importance of CY status both as a sign of irresectability and as a prognostic factor for PDAC remains controversial. The purposes of this study were to determine whether CY+ status precludes radical resection and to propose novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs). We conducted this study to evaluate use of a new genetically modified telomerase-specific replication-selective adenovirus, expressing GFP (TelomeScan F35) in rapid detection of v-PTC dissemination (Telo-CY). We assessed the clinical utility of high-quality testing of Telo-CY in PDAC patients in comparison with the findings of conventional CY (Conv-CY). This study was approved by the IRB in our Hospital. Patients with resectable cytologically or histologically proven PDAC were enrolled. 100 ml of saline as peritoneal lavage fluid was harvested just after a laparotomy. Half of the fluid was examined by conv-CY, based on Papanicolaou staining and MOC-31 immunostaining, and the remaining half was analyzed to detect v-PTCs by Telo-CY. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 mAb. To further distinguish cells with primary tumor origin, cells were labeled with anti-CEA, anti-CA19-9 and Ep-CAM mAbs. GFP(+) and CD45(-), and either CEA-, CA19-9- or Ep-CAM-(+) cells were counted as v-PTCs. Patients were followed to evaluate its clinical significance. Among 53 patients aged 53-87 years (30 males, 23 females), 5 were conv-CY(+), other 12 were Telo-CY(+). All 53 patients underwent surgical resection (PD/DP/TP=32/14/7). 2 patients were double-CY-(+) [conv-CY(+) and Telo-CY(+)], and peritoneal recurrence occurred at 7-9 months after surgery, despite adjuvant chemotherapy. 3 were conv-CY(+) alone, but Telo-CY(-), and no peritoneal recurrences were observed (0%). Conversely, 10 were Telo-CY(+) alone, but conv-CY(-), and 6 out of 10 patients were relapsed with peritoneal dissemination (60%). Remaining 38 patients were double-CY-negative (conv-CY- and Telo-CY-, conv-CY±), peritoneal recurrence was observed in 3 patients (8.3%). Although CY-positive status predicts poor prognosis and a higher risk of peritoneal dissemination after resection, it is not sufficient to preclude pancreatectomy by conv-CY alone. Combined CY examination with conv-CY and Telo-CY may open the window of opportunity for leading true results, accurately predicting peritoneal recurrence in PDAC patients. The CY status should be confirmed by staging laparoscopy prior to resection. Citation Format: Masahiro Tanemura, Kenta Furukawa, Tadafumi Asaoka, Daiki Marukawa, Hironao Yasuoka, Yasuo Urata, Daisaku Yamada, Shogo Kobayashi, Hidetoshi Eguchi. Clinical impact of high-quality liquid biopsy for peritoneal lavage cytology in resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3794.

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