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The invasiveness of pancreatic cancer and its resistance to anticancer drugs define its malignant potential, and are considered to affect the peritumoral microenvironment. Cancer cells with resistance to gemcitabine exposed to external signals induced by anticancer drugs may enhance their malignant transformation. Ribonucleotide reductase large subunit M1 (RRM1), an enzyme in the DNA synthesis pathway, is upregulated during gemcitabine resistance, and its expression is associated with worse prognosis for pancreatic cancer. However, the biological function of RRM1 is unclear. In the present study, it was demonstrated that histone acetylation is involved in the regulatory mechanism related to the acquisition of gemcitabine resistance and subsequent RRM1 upregulation. The current in vitro study indicated that RRM1 expression is critical for the migratory and invasive potential of pancreatic cancer cells. Furthermore, a comprehensive RNA sequencing analysis showed that activated RRM1 induced marked changes in the expression levels of extracellular matrix-related genes, including N-cadherin, tenascin-C and COL11A. RRM1 activation also promoted extracellular matrix remodeling and mesenchymal features, which enhanced the migratory invasiveness and malignant potential of pancreatic cancer cells. The present results demonstrated that RRM1 has a critical role in the biological gene program that regulates the extracellular matrix, which promotes the aggressive malignant phenotype of pancreatic cancer.

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Rationale: Splenic artery originating from the superior mesenteric artery is extremely rare. Because of this, its significance in laparoscopic distal pancreatectomy has never been reported. Here, we present the first case of laparoscopic distal pancreatectomy in a patient with a splenic artery arising from the superior mesenteric artery. Patient concerns: A 46-year-old Japanese woman with type 2 diabetes mellitus presented with worsening glycemic control. Abdominal ultrasonography revealed a pancreatic tail mass. Diagnoses: The patient was diagnosed with pancreatic neuroendocrine tumor by endoscopic ultrasound-guided fine needle aspiration. Preoperative computed tomography showed that the splenic artery with branches of dorsal pancreatic artery originated from the superior mesenteric artery. Interventions: The patient underwent laparoscopic distal pancreatectomy. Prior to pancreatectomy, the splenic artery and its dorsal pancreatic branches were clamped using the superior and inferior approaches, respectively, to avoid bleeding and congestion. Outcomes: The postoperative course was uneventful. Lessons: Preoperative evaluation of anatomical variants and development of strategies are important to avoid intraoperative complications in pancreatic surgery. Our results revealed that laparoscopic distal pancreatectomy can be performed safely by strategic approach even in a patient with a rare aberrant splenic artery.