Pancreatic acinar cell carcinoma with a ductal adenocarcinoma component: a case report and analysis of the histogenesis of the tumor.

BACKGROUND: Pancreatic cancer composed of acinar cell carcinoma (ACC) and ductal adenocarcinoma (DAC) is rare, and the clinicopathological characteristics of ACC with DAC have yet to be elucidated. Herein, we report a case of ACC with a DAC component of the pancreas and examined the histogenesis of this tumor. CASE PRESENTATION: A 69-year-old man was admitted to our hospital complaining of appetite loss, constipation, epigastric dull pain, and jaundice. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a pancreatic head tumor with dilatation of the bile duct and the distal main pancreatic duct. Under the diagnosis of pancreatic head cancer, a pancreatoduodenectomy was performed. The histology of the resected tumor consisted of mainly ACC with a focus of DAC, which was confirmed by mucin staining and immunohistochemistry for antigens such as BCL10, trypsin, Smad4, p16, p53, and MUC1. There was histological transition between the components of ACC and DAC, and immunostaining of the transitional zone showed equivocal results for the antigens. KRAS was wild-type in both ACC and DAC. The patient was treated with adjuvant chemotherapy with S-1 for 1 year. No evidence of recurrence or metastasis was observed after 9 years of follow-up. CONCLUSIONS: A rare case of pancreatic ACC with a DAC component in a patient with long-term survival after surgery was reported. Immunohistochemical and molecular analysis indicated that DAC might have arisen from ACC through transdifferentiation in this case.

[A Case of Pathological Complete Response Following Neoadjuvant Chemotherapy with Gemcitabine plus Nab-Paclitaxel in Borderline Resectable Pancreatic Cancer].

We report a resected case with a pathological complete response(pCR)after neoadjuvant chemotherapy for borderline resectable pancreatic cancer(BRPC). A 67-year-old woman who had been treated for type 2 diabetes mellitus in our hospital presented with an exacerbation of diabetes. An abdominal CT scan confirmed a hypovascular mass in the pancreas body consistent with BRPC. After 3 courses of chemotherapy with gemcitabine plus nab-paclitaxel(GnP), her elevated DUPAN-2 level normalized. A follow up CT scan revealed that the tumor had decreased in size, and no distant metastasis was detected. Distal pancreatectomy with en-bloc celiac axis resection was performed. Histopathological examination of the resected specimens showed no evidence of residual cancer cells(pCR). The patient remains disease-free 8 months after surgery. Neoadjuvant GnP chemotherapy may be useful for BRPC.

Endocrine gland-derived vascular endothelial growth factor strengthens cell invasion ability via prokineticin receptor 2 in colon cancer cell lines.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) has recently been identified as one of the vascular endothelial growth factors, and it is considered that the overexpression of EG-VEGF in colon cancer is related to hepatic metastasis. In this study, we report our recent novel findings of the involvement of EG-VEGF in cell invasion of colon cancer cells. Colon cancer cell lines (DLD-1 and HCT116) with high expression of prokineticin receptor (PK-R) 1 and 2 were stimulated with the EG-VEGF protein. Furthermore, Matrigel cell invasion assay was performed to examine the changes in cancer cell invasion. In addition, we investigated the mRNA expression of matrix metalloproteinase (MMP)-2, -7 and -9 in cancer cells. Finally, the EG-VEGF receptor on the colon cancer cell membrane was blocked by anti-PK-R1 and -PK-R2 antibodies to study whether cell invasion ability would be altered. In colon cancer cell lines where the expression of PK-R1 and 2 was confirmed, stimulation with EG-VEGF increased cell invasion a maximum of ~3-5 times. Furthermore, an increase in the mRNA and protein expression of MMP-2, -7 and -9 was observed. We also observed that the cell invasion rate decreased only after exposure to the anti-PK-R2 antibody. The study showed that the EG-VEGF protein may act on MMP-2, -7 and -9 via PK-R2 to strengthen cell invasion ability in colon cancer cell lines.

Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor.

Endocrine glands-derived-vascular endothelial growth factor (EG-VEGF) was recently cloned as a new angiogenic factor that selectively acts on the endothelium of endocrine gland cells. We evaluated the involvement of EG-VEGF in colorectal cancer. The expression of EG-VEGF was confirmed in all of the colorectal cancer cell lines. (On the other hand, the expression of EG-VEGF mRNA was not detected in colorectal normal mucosae.) Stable EG-VEGF infectors of colorectal cancer cell line SW620 were produced, EG-VEGF transfectants were implanted into cecum and s.c., and cell proliferation was evaluated. Angiogenesis was evaluated by dorsal air sac method. Liver metastasis was evaluated after the implantation of EG-VEGF transfectants into the mouse spleen. Tumor proliferation (cecum, s.c.) was significantly higher in the EG-VEGF transfectants than in the control cells. The small vessels were significantly increased in EG-VEGF transfectants as compared with those in control cells. Also, liver metastatic ratio was higher in the EG-VEGF transfectants than in the control cells. In this study, EG-VEGF, a new angiogenic factor, may lead to angiogenesis, promoting cell proliferation and liver metastasis in colorectal cancers. When the EG-VEGF gene-overexpressing colorectal cancer cell line that had been treated with phosphorothioate antisense EG-VEGF oligonucleotides was injected s.c. into mice, angiogenesis and tumor growth were inhibited. Although the novel angiogenesis factor EG-VEGF was not expressed in the normal colorectal mucosa, it was expressed in colorectal cancer cells, which indicates that it is a cancer-specific and possibly tissue-specific angiogenesis factor in the large intestine, and which suggests that it can be targeted by a novel antiangiogenesis therapy.