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Background For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. Methods We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin–eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. Results Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). Conclusions This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

Background Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis. Methods Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues. Results MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan–Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P = 0.0344). Conclusions Down-regulation of miR-132 is associated with poor prognosis in CRC. ANO1 could be one of the crucial targets of miR-132 in CRC. Electronic supplementary material The online version of this article (doi:10.1245/s10434-016-5133-3) contains supplementary material, which is available to authorized users.

We previously reported that the one-step nucleic acid amplification (OSNA) assay provided a judgment performance for colorectal cancer equivalent to a 2-mm-interval histopathological examination of lymph nodes (concordance 97.1 %, n = 385 lymph nodes). In this prospective multicenter study, we uncovered an OSNA-assisted pathology to detect lymph node metastasis. A total of 204 (50 stage I, 74 stage II, and 80 stage III) colorectal cancer patients. All 4324 lymph nodes were examined by the standard histology (one-slice H&E staining) and 1925 lymph nodes (44.5 %) of them were also subject to the OSNA analysis. The concordance rate between 1 slice hematoxylin/eosin and OSNA assay was 95.7 % (1,842/1925 lymph nodes). The sensitivity and specificity of the OSNA assay were 86.2 % (125/145) and 96.5 % (1717/1780), respectively. Among 124 node-negative patients (pN0), the respective upstaging rates of pStages I, IIA, IIB, and IIC were 2.0 % (1/50), 17.7 % (11/62), 12.5 % (1/8), and 25 % (1/4). OSNA-positive patients had deeper invasion to the colonic wall and severe lymphatic invasion (P = 0.048 and P = 0.004, respectively). The sum of the quantitative results of OSNA and total tumor load increased as the number of metastasized lymph nodes increased: 1550 copies/μL in pN0, 24,050 copies/μL in pN1, and 90,600 copies/μL in pN2. The present study on colorectal cancer provided fundamental data regarding OSNA-assisted pathology of lymph node metastasis in Japan.

The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy. Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days × 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed. After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04). A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.

Recent studies have suggested that microRNA-29 (miR-29) family members may play important roles in human cancer by regulating cell proliferation, differentiation, apoptosis, migration, and invasion. The present study aimed to investigate the clinical significance and biological function of miR-29b in colorectal cancer (CRC). Real-time polymerase chain reaction was used to quantify miR-29b expression. The association between miR-29b and survival was evaluated in 245 patients with CRC. We transfected an miR-29b mimetic into CRC cells to explore the functional role of miR-29b in vitro, based on a proliferation assay, flow cytometry, and Western blotting. In clinical samples of CRC, miR-29b expression was significantly reduced in tumor tissues compared with normal mucosa (p

Background: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as “segmental resection” (SR). Methods: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B). Results: Blood loss was less in group A (239±180 ml) than in group B (342±176 ml) (P

The safety of laparoscopic surgery (LAP) in elderly patients with colorectal cancer has not been demonstrated. The aim of this study was to compare the outcomes of LAP and open surgery (OP) and estimate the feasibility of LAP in colorectal cancer patients aged ≥80 years. We conducted a propensity scoring matched case–control study of colon and rectal cancer patients aged ≥80 years using data from 41 hospitals between 2003 and 2007. A total of 1,526 colon cancer patients and 282 rectal cancer patients underwent surgery and were included in the analysis. The primary end point was 3-year overall survival (OS). Secondary end points included disease-free survival (DFS), cancer-specific survival (CSS), and postoperative complications. LAP and OP were compared in 804 colon cancer patients (402 pairs) and 114 rectal cancer patients (57 pairs) after all covariates were balanced, and no significant differences were observed, except for tumor size in colon cancer. OS, DFS, and CSS did not differ between the groups for either colon cancer (P = 0.916, 0.968, and 0.799, respectively) or rectal cancer (P = 0.765, 0.519, and 0.950, respectively). In colon cancer cases, LAP was associated with fewer morbidities than was OP (24.9 vs. 36.3 %, P

The detection of intraperitoneal free cancer cells in colorectal cancer (CRC) patients is associated with a poorer prognosis. The aim of this study was to investigate the effects of intraperitoneal chemotherapy (IPC) with mitomycin C (MMC) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings.A total of 52 CRC patients who had no clinically confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated. Conventional peritoneal lavage cytology was performed. Overall, 31 of the 52 patients (59.6%) were administered IPC with MMC. Before closure of the abdomen, 4 silicon catheters were inserted into peritoneal cavity. After closure, the perfusate (diluting 20 mg MMC with 500 ml saline) was instilled from the catheter, and all catheters were clumped. All catheters were opened 1 h later.The mean follow-up period was 83.1 months. According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors, patients with IPC had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC (P0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients.It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination, but who have positive peritoneal lavage cytology. It is necessary to verify the effectiveness of IPC with MMC in a prospective trial.