Kazuteru Watanabe

Transfection of NF-κB Decoy Oligodeoxynucleotides into Macrophages Reduces Murine Fatal Liver Failure After Excessive Hepatectomy

BACKGROUND Macrophages play an important role in the initiation of hypercytokinemia, which is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of nuclear factor kappa B (NF-kappaB) in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy. MATERIALS AND METHODS Ninety percent hepatectomy was performed in 8-wk-old mice. NF-kappaB/decoy/ODN was transfected into the liver by the hemagglutinating virus of Japan-liposome method. The survival rate, serum levels of interleukin (IL)-1beta IL-6, and tumor necrosis factor-alpha, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group). RESULT The control group mice died within 48 h of the operation, while the survival rate in the decoy group at 48 h after the operation was 35%, and at 2 wk, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells in the remnant liver was smaller in the decoy group. CONCLUSION Transfection of NF-kappaB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.

Prostaglandin E1 prevents liver failure after excessive hepatectomy in the rat by up-regulating Cyclin C, Cyclin D1, and Bclxl.

Prostaglandin E1 (PGE1) has wide‐ranging effects on cytoprotection and may play a role in preventing liver failure following excessive hepatectomy. We examined the effect of PGE1 on hepatocyte apoptosis and liver regeneration after 95% hepatectomy in a rat model. PGE1 or vehicle was intravenously administered 30 minutes before and during hepatectomy. The extent of hepatocyte injury was evaluated by serum alanine aminotransferase and aspartate aminotransferase levels. To evaluate hepatocyte apoptosis and liver regeneration, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and Ki67 labeling were performed. The expression levels of Bcl‐xL, Bcl‐2, Bax, Cyclin C, Cyclin D1, Cyclin E, p21, transforming growth factor‐β, plasminogen activator inhibitor‐1, and glyceraldehyde‐2‐phosphate dehydrogenase mRNA were also examined by reverse transcription‐polymerase chain reaction. Survival was improved in the PGE1 group (26.6%), whereas all rats in the vehicle group died within 60 hours. PGE1 significantly suppressed the release of alanine aminotransferase and aspartate aminotransferase at 12 hours postoperatively. Pretreatment with PGE1 significantly increased the Ki67‐positive cell count and decreased the terminal deoxynucleotidyl transferase dUTP nick end labeling positive cell count after hepatectomy, and also significantly increased the expression levels of Bcl‐xL, Cyclin C, and Cyclin D1. Our results suggest that pretreatment with PGE1 may increase survival following hepatectomy by salvaging the remaining liver tissue, which it does by inhibiting apoptosis and stimulating hepatocyte proliferation.

Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regeneration

Background/Aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2‐synthesized NO in post‐PHx liver regeneration remains unclear. We investigated the role of NOS2‐synthesized NO in liver regeneration.

Safety limit of the extent of hepatectomy for rats with moderately fatty liver: Experimental study concerning living liver donor safety

Introduction:  The aim of the present study was to determine whether rats with moderately fatty liver could withstand a 90% hepatectomy, which rats with normal livers can survive.

The potential role of microRNA-31 expression in early colorectal cancer.

The expression of microRNA‐31 (miR‐31) has been implicated in the progression of some human malignancies including colorectal cancer. However, the clinical significance of the expression of miR‐31 in submucosally invasive (T1) colorectal cancer remains unclear. The aim of the present study was to delineate the relationship between clinicopathological features and the oncogenic modulator miR‐31 in submucosally invasive colorectal cancer. We investigated the expression of miR‐31 in 50 submucosally invasive colorectal cancer specimens, along with the corresponding non‐tumoral mucosa specimens, using a real‐time quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). The relationships between miR‐31 expression levels and clinicopathological characteristics were assessed. The miR‐31 host gene locus was investigated using fluorescence in situ hybridization. qRT‐PCR revealed that the expression of miR‐31 was higher in colorectal cancer tissue than in non‐tumoral tissue (P = 0.0002). The up‐regulated expression of miR‐31 may play an oncogenic role in the early stage of carcinogenesis in colorectal cancers.

Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C λ/ι, E‑cadherin, β‑catenin and basement membrane component

Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) λ/ι, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, β-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid-type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC λ/ι, type IV collagen, β-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of β-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC λ/ι expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC λ/ι and β-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of β-catenin, type IV collagen and aPKC λ/ι.

Clinical Characteristics of Rectal Cancer Involving the Anal Canal

BackgroundThis study evaluates the clinical characteristics of rectal cancer involving the anal canal.MethodsA total of 346 consecutive patients with primary low rectal cancer located below the peritoneal reflection were reviewed in this study. Patients were divided into two groups according to whether the lower edge of the tumor came in contact with the anal canal (P group, n = 78) or not (Rb group, n = 268). Clinical and pathological parameters, recurrence rates, and survival rates were compared between the two groups.ResultsThe occurrence of uncommon histological types of tumor was significantly higher in the P group than in the Rb group. P group patients also had a significantly higher lateral pelvic node metastasis rate (p < 0.001), lower 5-year overall survival rate (p = 0.0491), and higher 5-year local recurrence rate (p = 0.0171) than Rb group patients. Multivariate analysis revealed that tumor location was a significant risk factor for local recurrence. In the P group, multivariate analysis showed that uncommon histological tumor types were a significant prognostic factor.ConclusionRectal cancer involving the anal canal should be treated with special care, considering the particularly high lateral pelvic lymph node metastasis rate and high local recurrence rate.

Randomized clinical trial of high versus low inferior mesenteric artery ligation during anterior resection for rectal cancer: High versus low tie of inferior mesenteric artery

The optimal level for inferior mesenteric artery ligation during anterior resection for rectal cancer is controversial. The aim of this randomized trial was to clarify whether the inferior mesenteric artery should be tied at the origin (high tie) or distal to the left colic artery (low tie).

Midterm follow-up of a randomized trial of open surgery versus laparoscopic surgery in elderly patients with colorectal cancer

BackgroundLaparoscopic surgery has been widely accepted for the treatment of colorectal cancer; however, long-term outcomes in elderly patients remain controversial. The midterm results of a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer are presented.MethodsThis was a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer. The primary outcome was complication rate, and secondary outcomes included 3-year recurrence-free survival and overall survival. A total of 200 patients were randomly assigned to open surgery or laparoscopic surgery between 2008 and 2012. The main study objective was to compare the midterm outcomes of open surgery with those of laparoscopic surgery in elderly patients with colorectal cancer. This trial is registered with Clinical Trials.gov (NCT01862562).ResultsThere were no differences between the laparoscopic surgery group and open surgery group in the 3-year overall survival rate (91.5% for laparoscopic surgery vs. 90.6% for open surgery, p = 0.638) or the 3-year recurrence-free survival rate (84.8% for laparoscopic surgery vs. 88.2% for open surgery, p = 0.324). The local recurrence rate was significantly higher in the laparoscopic surgery group than in the open surgery group in rectal cancer (13.8% for laparoscopic surgery vs. 0% for open surgery, p = 0.038). In subgroup analysis according to tumor location, there were no significant differences in the 3-year overall survival rate or 3-year recurrence-free survival rate between the two treatment groups.ConclusionThe midterm outcomes of laparoscopic surgery are similar to those of open surgery in elderly patients with colorectal cancer.

The safety of preoperative amino acid (Elental®) loading in colon cancer surgery: prospective cohort study.

Abstract Objective: The aim of this prospective study was to evaluate the safety of preoperative amino acid plus CHO drink (Elental®) loading in colon cancer surgery. Summary of Background Data: Prolonged preoperative fasting increases insulin resistance and current evidence recommends carbohydrate drinks 2 hours before surgery. Methods: We prospectively enrolled consecutive patients with a preoperative diagnosis of colon cancer who underwent surgery. The patients received 600 ml of Elental® the night before surgery and 300 ml of Elental® 3 h prior to induction of anaesthesia. Primary endpoint was the safety of preoperative amino acid (Elental®) loading in colon cancer surgery. Safety measurement was anastomotic leakage and aspiration pneumonia. Secondary endpoints were incidence rate of incisional surgical site infection, recovery of bowel movement, length of hospital stay, postoperative nutritional status and insulin resistance. Results: A total of 80 consecutive patients were enrolled in this study fro...