Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success.

BACKGROUND: We aimed to investigate the difference in engraftment rates depending on the transplant site for a patient-derived xenograft (PDX) of pancreatic ductal adenocarcinoma (PDAC) and the effects of the microenvironment on engraftment. MATERIALS AND METHODS: Frozen cancer tissues from PDAC tumors were used, and tumor fragments were directly implanted into the subcutaneous, orthotopic pancreas, peritoneum, and liver of X-linked severe combined immunodeficiency (XSCID) rats. We assessed the success of engraftment in each organ. Additionally, to evaluate the effect of the microenvironment in each organ, we performed immunohistochemical analysis. RESULTS: Subcutaneous transplantation was successful in 8 of 10 PDAC cases (16 of 30 rats). This was a higher rate than for other organ transplants. The vascular endothelial cells in the stroma were replaced with those from rats instead of humans. Vascular endothelial growth factor-A (VEGF-A) and cluster of differentiation-31 (CD31) was significantly more strongly expressed in the subcutaneous transplantation model (VEGF-A: p<0.001, CD31: p=0.0036). CONCLUSION: The engraftment rate was significantly higher for the subcutaneous PDX model than for the orthotopic pancreatic, peritoneal, and liver PDX models. Blood vessels of the PDX stroma had been replaced by rat-derived vessels instead of the original human vessels, suggesting that angiogenesis in the PDX microenvironment may be a major factor in engraftment.

Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. RESULTS: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). CONCLUSION: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Preoperative Neutrophil-to-lymphocyte Ratio Predicts Tumor-infiltrating CD8+ T Cells in Biliary Tract Cancer.

BACKGROUND/AIM: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). PATIENTS AND METHODS: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. CONCLUSION: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.

Predicting difficulty in extending the ileal pouch to the anus in restorative proctocolectomy: investigation of a simple predictive method using computed tomography.

AIM: This study aimed to assess the ability of preoperative axial computed tomography (CT) to predict surgical difficulty in bringing the ileal pouch to the level of the anus during restorative proctocolectomy (RPC). METHOD: Patients who underwent RPC with an ileal pouch-anal anastomosis (or ileal pouch-anal canal anastomosis) in our institution between January 2008 and April 2014 were enrolled. The patients were divided into two groups, including those in whom CT indicated potential difficulty in extending the pouch downwards (extension difficult (ED) group) and patients with no CT evidence of potential difficulty (normal group). The groups were compared for clinical factors and the thickness of the slices of CT showing the root of the superior mesenteric artery, the point of communication of the ileocaecal artery with the marginal artery (tICA) and the anal verge (AV). Receiver-operating characteristic analysis was performed, and a cut-off value was calculated for predicting the degree of difficulty in bringing the ileal pouch down to the anal canal. RESULTS: Thirty-four patients were entered in the study. The ED group included significantly taller patients and more with familial adenomatous polyposis than the normal group. The distance between tICA and AV was significantly longer in the ED group, with a cut-off of 21 cm giving a sensitivity of 100% and a specificity of 83.3%. CONCLUSION: The distance between tICA and AV measured by axial CT can be a useful predictor for the difficulty in bringing the ileal pouch down to the anus during RPC.

Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.

Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.

Hemoperitoneum secondary to exophytic leiomyoma: report of a case.

We report herein the case of a 63-year-old male with hemoperitoneum secondary to exogastric leiomyoma. The patient had been receiving anticoagulation therapy for a cerebral embolism and complained of sudden, severe abdominal pain. A sonogram and computed tomography scan showed an exogastric mass and massive ascites. A peritoneal puncture proved the presence of an intraperitoneal hemorrhage. An emergency laparotomy revealed a pedunculated bleeding tumor, thus confirming the preoperative diagnosis of a ruptured exogastric tumor. A microscopic analysis of the excised tumor demonstrated gastric leiomyoma. Other authors have reported hemoperitoneum secondary to gastric myogenic tumors, but no cases of leiomyomas could be found in the literature.