MicroRNA-9-5p-CDX2 Axis: A Useful Prognostic Biomarker for Patients with Stage II/III Colorectal Cancer.

A lack of caudal-type homeobox transcription factor 2 (CDX2) protein expression has been proposed as a prognostic biomarker for colorectal cancer (CRC). However, the relationship between CDX2 levels and the survival of patients with stage II/III CRC along with the relationship between microRNAs (miRs) and CDX2 expression are unclear. Tissue samples were collected from patients with stage II/III CRC surgically treated at Kyoto University Hospital. CDX2 expression was semi-quantitatively evaluated by immunohistochemistry (IHC). The prognostic impacts of CDX2 expression on overall survival (OS) and relapse-free survival (RFS) were evaluated by multivariable statistical analysis. The expression of miRs regulating CDX2 expression and their prognostic impacts were analyzed using The Cancer Genome Atlas Program for CRC (TCGA-CRC). Eleven of 174 CRC tissues lacked CDX2 expression. The five-year OS and RFS rates of patients with CDX2-negative CRC were significantly lower than those of CDX2-positive patients. Multivariate analysis of clinicopathological features revealed that CDX2-negative status is an independent marker of poor prognosis in stage II/III CRC. miR-9-5p was shown to regulate CDX2 expression. TCGA-CRC analysis showed that high miR-9-5p expression was significantly associated with poor patient prognosis in stage II/III CRC. In conclusion, CDX2, the post-transcriptional target of microRNA-9-5p, is a useful prognostic biomarker in patients with stage II/III CRC.

F-Box/WD Repeat Domain-Containing 7 Induces Chemotherapy Resistance in Colorectal Cancer Stem Cells.

Although the cancer stem cell (CSC) concept has provided a reasonable explanation for cancer recurrence following chemotherapy, the relationship between CSCs and chemotherapy resistance has not been thoroughly investigated, especially in solid tumors. We aimed to identify the mechanism underlying colorectal cancer (CRC) chemoresistance focusing on the cell cycle mediator F-Box/WD repeat domain-containing 7 (FBXW7). From 55 consecutive CRC cases who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NACRT) at Kyoto University Hospital, pre-treatment endoscopic biopsy specimens were collected and divided into two groups upon immunohistochemical (IHC) analysis: 21 cases of FBXW7 high expression (FBXW7-high group) and 34 cases of low expression (FBXW7-low group). High FBXW7 expression in pre-treatment biopsy specimen was significantly associated with poor pathological therapeutic effect (p = 0.019). The proportion of FBXW7-positive cells in surgically resected CRC specimens from patients who underwent NAC or NACRT was significantly higher than that in the pre-treatment biopsy specimens (p < 0.001). The expression of FBXW7 was inversely correlated with that of Ki67 in both pre-treatment biopsy specimens and surgically resected specimens. FBXW7 expression in the EpCAMhigh/CD44high subpopulation isolated by flow cytometry from CRC samples was significantly higher than that in the EpCAMhigh/CD44low subpopulation. Cell-cycle analysis in CRC cell lines revealed that, upon FBXW7 silencing, the proportion of G0/G1 cells was significantly lower than that in control cells. Moreover, knockdown of FBXW7 in CRC cell lines increased the sensitivity to anti-cancer drugs in vitro and in vivo. A subset of CRC stem cells possesses chemoresistance through FBXW7 expression. Cell cycle arrest induced by FBXW7 expression should be considered as a potential therapeutic target to overcome chemoresistance in CRC stem cell subsets.

[A case of stage IV rectal cancer successfully resected after chemotherapy (mFOLFOX6 plus panitumumab)].

A 6 6-year-old woman with hematochezia was admitted to our hospital. A colonoscopy detected KRAS wild-type rectal cancer. An abdominal computed tomography (CT) scan revealed a liver metastasis, and invasion to the uterus was suspected. The patient underwent a laparotomy, and intraoperative cytology and peritoneal dissemination proved positive. The tumor had invaded the uterus. We administered chemotherapy consisting of 5-fluorouracil, Leucovorin, and oxaliplatin(mFOL FOX6)plus panitumumab. A CT scan and colonoscopy performed after 10 courses of chemotherapy indicated remarkable tumor regression. An abdominal CT scan did not detect any liver metastases, and we performed a laparoscopic low anterior resection. In the second operation, peritoneal dissemination and washing cytology were negative. The pathological diagnosis of the surgically resected specimen was ypStageII. The patient is recurrence-free 7 months after surgery.

[A case of resection for a huge pancreatic acinar cell carcinoma with tumor thrombus in the portal vein].

A 6 3-year-old man with a huge pancreatic tumor was referred to our hospital. Abdominal computed tomography revealed a heterogeneously enhanced encapsulated mass, 14 cm in diameter, in the pancreas head. The tumor thrombus extended to the bifurcation of the portal vein. The tumor, which had invaded the descending duodenum, was diagnosed as a probable case of acinar cell carcinoma, based on the biopsy results. Prior to resection, we prepared an ileocecal vein-umbilical vein bypass. Initially, we planned to perform a pancreatoduodenectomy, however, a total pancreatectomy had to be performed due to the atrophy of the residual pancreas tail. Since the tumor thrombus was visible, floating up from the portal vein wall at the upper level of pancreas, we dissected the portal vein at this level. The thrombus was extracted after securing the main tract and both (right and left) branches of the portal vein with vessel tape. About 5 cm of portal vein was resected and reconstructed. Since patients who undergo resection of acinar cell carcinoma have a better prognosis and long-term survival is often reported for cases of resected tumor thrombus of the portal vein, it is advisable to resect acinar cell carcinomas even in cases as advanced as reported here.

[Curative resection for Stage IV advanced gastric cancer that responded to combination chemotherapy with docetaxel, cisplatin, and S-1].

A 50-year-old man was diagnosed with advanced gastric cancer(Borrmann type 3)accompanied with N3.Staging laparoscopy revealed invasion to the transverse mesocolon and positive cytology from peritoneal washing (CY1). After the patient underwent gastrojejunostomy, we administered DCS combination chemotherapy consisting of docetaxel (40 mg/m² intravenously on day 1), cisplatin(60 mg/m² intravenously on day 1), and S-1 (orally 80 mg/m² on days 1 to 14).Four courses of this treatment were provided every 4 weeks, and it resulted in a partial response (PR).We performed curative distal gastrectomy with transverse mesocolon resection and D2 plus 14v lymph node dissection. Cytological analysis of the samples obtained after peritoneal washing showed negative results.Histopathologically, no variable cancer cells remained in the primary lesion, but a few degenerated cancer cells remained in one of the lymph nodes.Pathological features were classified as Grade 3 for the primary lesion and Grade 2 for the lymph node lesions.S -1 and S-1/cisplatin were administered as adjuvant chemotherapy.One year and 6 months after surgery, the patient is alive and free of disease.

[A case of advanced gastric cancer successfully treated with trastuzumab, capecitabine, and Cisplatin therapy followed by curative resection].

We report a case of human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer successfully treated with combination therapy of trastuzumab, capecitabine, and cisplatin, followed by a curative resection. A 23-year-old woman was diagnosed with advanced type 3 gastric cancer, and the clinical findings were T3N0M0, StageIIA. A laparoscopic exploration revealed that it was a CY1 unresectable StageIV cancer. Initially, docetaxel, cisplatin, and S-1 therapy was chosen. However, the patient's HER2 status proved to be positive (IHC 3+), and so trastuzumab, capecitabine and cisplatin therapy was administered. After four cycles, the tumor significantly decreased in size, suggesting a partial response(PR). A further laparoscopic exam showed no apparent dissemination or metastatic cancer cells. We performed a curative resection consisting of a laparoscopic distal gastrectomy and D2 lymphadenectomy. The patient's postoperative course has been uneventful. She has been alive for 4 months and is receiving adjuvant chemotherapy comprising trastuzumab and S-1.