CHU Lille, Institute of Pathology, Centre de Biologie Pathologie Lille, France.
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Univ Lille, Lille, France.
Transplantation. 2019 Jan;103(1):177-181. doi: 10.1097/TP.0000000000002419.
Total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to explore the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC.
Patients requiring pancreatectomy for PDAC were prospectively included. Immunocompromised mice were transplanted with pancreatic cells isolated from the nonmalignant part of the surgical specimen (experimental group). Results were compared with pancreatic tumor implants (control group). Pancreatic grafts were explanted at 6 weeks for histological analyses.
Nine patients were included, and 31 mice were transplanted. In the experimental group, explants were microscopically devoid of tumor cell, and no metastasis was observed. In the control group, all explants were composed of tumor.
We report in a preclinical model the absence of local and distant spreading of malignant cells after pancreatic islets xenograft isolated from PDAC patients. These data supports the oncological safety of TPIAT as valuable alternative to partial pancreatectomy for PDAC patients with a high risk of postoperative pancreatic fistula.
对于可切除的胰腺导管腺癌(PDAC)患者,当术后胰瘘的风险得到充分识别时,全胰切除术伴门静脉内胰岛自体移植(TPIAT)而非部分胰切除术可能代表一种治疗策略的重大转变。当胰岛细胞被移植到门静脉时,这种方法理论上存在肿瘤细胞播散的风险。我们的目的是在 PDAC 的小鼠临床前模型中,探索 TPIAT 在因 PDAC 而行部分胰切除术时分离的人胰腺细胞经皮下异种移植后的安全性。
前瞻性纳入需要因 PDAC 而行胰切除术的患者。免疫功能低下的小鼠接受了从手术标本的非恶性部分分离的胰腺细胞(实验组)的移植。将结果与胰腺肿瘤植入物(对照组)进行比较。胰腺移植物在 6 周时被取出进行组织学分析。
共纳入 9 例患者,共移植了 31 只小鼠。在实验组中,移植的胰腺组织在显微镜下没有肿瘤细胞,也没有观察到转移。在对照组中,所有移植的胰腺组织都由肿瘤组成。
我们在临床前模型中报告了从 PDAC 患者中分离的胰腺胰岛异种移植后,恶性细胞无局部和远处播散。这些数据支持 TPIAT 作为一种有价值的替代部分胰切除术的方法,用于术后胰瘘风险较高的 PDAC 患者,具有良好的肿瘤安全性。