== The patients pancreatic cancer was diagnosed as moderately differentiated adenocarcinoma with H&E staining (A). in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence. == Introduction == Complete tumor resection improves overall survival of pancreatic cancer CYFIP1 patients, which is presently 5% at five years[1]. Metastatic relapse often occurs following attempted curative resection of the primary tumor as a result of invisible microscopic tumor deposits left behind. Making tumors fluoresce offers great advantages for tumor detection during surgery in order to achieve complete resection[2],[3]. We have previously shown that fluorescence-guided surgery (FGS) for pancreatic Dulaglutide cancer decreased the residual tumor burden and improved overall and disease-free survival in mouse models using fluorescently-labeled human pancreatic cancer cell lines[4][6]. Patient-derived orthotopic xenografts (PDOX) recapitulate the biological characteristics of the disease of origin, including metastases[7][11]and are a clinically-relevant model for fluorescence-guided surgery[4],[12][14]. Recently, many studies reported positive outcomes with neoadjuvant chemotherapy (NAC) of pancreatic cancer[15][17]. NAC allows for Dulaglutide the identification of those patients with rapidly progressive metastatic disease at the time of preoperative restaging, and can increase the R0 resection rate and reduce the risk of local tumor recurrence[15]. However, a significant number of patients still develop recurrent disease immediately after NAC treatment and subsequent surgical resection[16][18]. Therefore, new strategies in addition to NAC are needed to reduce the recurrence of pancreatic cancer. In this study, we decided the efficacy of CA19-9 conjugated with a fluorescent dye to illuminate pancreatic cancer PDOXs for FGS in combination with NAC. == Materials and Methods == == Animals == Athymicnu/nunude mice (AntiCancer Inc., San Diego, CA), 46 weeks old, were used in this study. Mice were kept in a barrier facility under HEPA filtration. Mice were fed with an autoclaved laboratory rodent diet. All mouse surgical procedures and imaging were performed with the animals anesthetized by intramuscular injection of 50% ketamine, 38% xylazine, and 12% acepromazine maleate (0.02 ml). Animals received buprenorphine (0.10 mg/kg ip) immediately prior to surgery and once a day over the next 3 days to ameliorate pain. CO2inhalation was used Dulaglutide for euthanasia of all animals at 90 days after surgery. To ensure death following CO2asphyxiation, cervical dislocation was performed. All animal studies were conducted with an AntiCancer, Inc. Institutional Animal Care and Use Committee (IACUC)-protocol specifically approved for this study and in accordance with the principals and procedures outlined in the National Institute of Health Guide for the Care and Use of Animals under Assurance Number A3873-1. == Establishment of patient derived orthotopic xenograft (PDOX) of Dulaglutide pancreatic cancer == Pancreatic cancer patient tumor tissues were obtained at surgery and cut into fragments (3-mm3) and transplanted subcutaneously in nude mice[7],[19]. The subcutaneous tumors were then passaged in nude mice both orthotopically and subcutaneously. All patients provided written informed consent and samples were procured and initially transplanted in NOD/SCID under the approval of the Institutional Review Board of MD Anderson Cancer Center. == Orthotopic tumor implantation == A small 6- to 10-mm transverse incision was made on the left flank of the mouse through the skin and peritoneum. The tail of the pancreas was uncovered through this incision, and a single 3-mm3tumor fragment from subcutaneous tumors was sutured to the tail of the pancreas using 8-0 nylon surgical sutures (Ethilon; Ethicon Inc., NJ, USA). On completion, the tail of the pancreas was returned.