Yukimoto Ishii

Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis

Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis.

Meta-analysis of prophylactic antibiotic use in acute necrotizing pancreatitis.

Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis.

Bioresorbable membrane to reduce postoperative small bowel obstruction in patients with gastric cancer: a randomized clinical trial.

Objective:This randomized controlled trial was designed to assess whether the use of a sodium hyluronate-based bioresorbable membrane reduces small bowel obstruction after gastrectomy for gastic cancer. Summary Background Data:Clinical studies have reported that a bioresorbable membrane significantly reduces the incidence and severity of adhesion after abdominopelvic surgery. Methods:Between 2003 and 2006, a total of 150 patients with gastric cancer who were scheduled to undergo gastrectomy were randomly assigned to a sodium hyaluronate-based bioresorbable membrane (Seprafilm) group or to a control group. Before closing the abdominal incision, 2 sheets of Seprafilm membrane were applied to the surface of the small intestine under the middle abdominal wound in the Seprafilm group. The primary end point was the incidence of bowel obstruction. Secondary end points were intraoperative and postoperative morbidity and mortality. We registered with Clinical Trials.gov using the Protocol Registration System (ID-NCT00529412). Results:We evaluated a total of 144 patients: 70 in the Seprafilm group and 74 in the control group. The overall incidence (Seprafilm group, 5.7% vs. control group, 9.5%; P = 0.534) and the cumulative incidence of small bowel obstruction (6.2% vs. 12.2% at 36 months; P = 0.3789) were slightly but not significantly lower in the Seprafilm group. The incidence of postoperative complications was similar in the groups (32.9% vs. 29.7%; P = 0.722). Seprafilm did not adversely affect bowel, liver, or renal functions. Conclusions:The use of Seprafilm does not significantly reduce the incidence of small bowel obstruction in patients undergoing gastrectomy for gastric cancer.

Clinical Application of Oligonucleotide Probe Array for Full-Length Gene Sequencing of TP53 in Colon Cancer

Objective:TP53 mutations are the most frequent genetic alterations in colon cancer. We studied whether the recently developed oligonucleotide microarray technique, GeneChip p53 assay, can be applied to sensitive detection of TP53 gene mutations in surgical specimens from colon cancer patients. Methods:TP53 gene mutations in exons 2–11 in 20 colon cancers and the corresponding histopathologically normal mucosa at the surgical margins were assessed by GeneChip p53 assay, and the results were further evaluated by direct sequencing of the involved exon or by mutant-allele-specific amplification (MASA). The expression of TP53 protein was also evaluated immunohistochemically and the result was compared with the gene alteration. Results: The GeneChip p53 assay detected TP53 mutations in 65% of primary cancers; 61% of the mutations were within the evolutionarily conserved regions, and 46% of the mutations were within the zinc-binding domains (regions of loop 2 and loop 3). Direct sequencing confirmed these mutations. Immunohistochemical examination detected TP53 protein overexpression in 47% of primary cancers, but this protein did not accumulate with all types of TP53 mutations. In addition, the GeneChip assay detected a mutation identical to that in the primary tumor in 2 samples from the surgical margins, and MASA confirmed both mutations, implying the presence of occult cancer cells. Conclusion: The GeneChip p53 assay is sufficiently sensitive to detect TP53 mutations in surgical specimens from colon cancers and may be applicable to screening examination in clinical laboratories as a routine procedure.

Transcriptional profiling in hepatoblastomas using high-density oligonucleotide DNA array.

Hepatoblastoma is a common hepatic tumor in children. Although evidence regarding cytogenetic and molecular genetic alterations in hepatoblastomas has been reported, the molecular events affecting the biologic characteristics of this tumor, including alterations of the gene expression profile, are largely unknown. To identify genes differentially expressed between nondiseased liver (NDL) and hepatoblastoma tumor (HBT), we analyzed the gene expression profile in 14 NDL and 16 HBT samples using a high-density oligonucleotide DNA array. Using Mann-Whitney U test followed by the k-nearest neighbor algorithm, we identified 26 genes (predictor genes) that were able to assign unknown samples derived from NDL and HBT to either the NDL group or HBT group with 100% accuracy. Using a cross-validation approach, we confirmed that the k-nearest neighbor algorithm assigned the particular samples derived from NDL and HBT to either the NDL or HBT group with 93.3% (28/30 samples) accuracy. In the 26 predictor genes, we found alteration of the expression of genes regulating cell division (NAP1L1, STMN1, CCNG2, and CDC7L1) and tumor cell growth (IGF2 and IGFBP4) in HBT. Four predictor genes (ETV3, TPR, CD34, and NR1I3) were also found to be mapped to the chromosomal region 1q21 approximately q32, which has been reported to be frequently involved in the development of hepatoblastoma. The findings obtained in this study suggest that alteration of the expression of some genes regulating cell division and tumor cell growth may be characteristics of the gene expression profile in HBT, and that alteration of the expression of the four predictor genes mapped to chromosomal region 1q21 approximately q32 may also contribute to the differences in gene expression profile between NDL and HBT.

L-[1-13C] phenylalanine breath test reflects histological changes in the liver

OBJECTIVE Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change. MATERIALS AND METHODS PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring. RESULTS The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively. CONCLUSION PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Efficacy of antibiotic combination therapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases.

Background and Aims:  We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Herein, we assessed whether antibiotic combination therapy is effective for active UC, including cases with steroid refractory or dependent disease.

Analysis of MYC and Chromosome 8 Copy Number Changes in Gastrointestinal Cancers by Dual-Color Fluorescence In Situ Hybridization

We performed dual (two-color) fluorescence in situ hybridization (FISH) by using direct fluorescent labeling probes for C-MYC and chromosome 8 in six gastrointestinal (three stomach and three colon) cancers. There are several reports of increased C-MYC copy numbers in solid tumors. To date, however, genetic rearrangements including those of the C-MYC gene have not actually been detected by FISH. Metaphase FISH demonstrated the C-MYC gene on other chromosomes (i.e., in addition to chromosome 8) in one gastric cancer. Somatic mutations such as chromosome translocation or insertion including the C-MYC gene are assumed to have occurred in this case. Our results suggest that genetic rearrangements, in addition to an increased C-MYC copy number, may be a mechanism of MYC oncogene activation in solid tumors.

Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a multiple-treatments meta-analysis.

OBJECTIVE Frequentist meta-analyses have demonstrated that immunoenhancing parenteral nutrition (IMPN) and enteral nutrition (IMEN) reduce the incidence of infection and shorten the length of hospital stays compared with standard parenteral nutrition (SPN) and enteral nutrition (SEN). The aim of this study was to evaluate which kind of nutrition-SPN, SEN, IMPN, and IMEN-is most efficacious for reducing the incidence of complications after gastrointestinal surgery. METHODS An English literature search was carried out for randomized controlled trials published from January 1990 to February 2013 that evaluated the clinical efficacy of 4 kinds of nutrition after gastrointestinal surgery. A Bayesian framework was used to calculate the odds ratio between each treatment and the rank order. RESULTS Seventy-four studies (7572 participants) were included. According to the surface below the cumulative ranking curve (SUCRA) ordering from the best to the worst, IMEN was ranked first for reducing the incidence of 7 complications-any infection (SUCRA = 0.86), overall complication (SUCRA = 0.88), mortality (SUCRA = 0.81), wound infection (SUCRA = 0.79), intra-abdominal abscess (SUCRA = 0.98), anastomotic leak (SUCRA = 0.79), and sepsis (SUCRA = 0.92). Also, IMEN was ranked second for pneumonia and urinary tract infection. IMPN was ranked first for pneumonia (SUCRA = 0.81) and urinary tract infection (SUCRA = 0.86), third for mortality, and fourth for both intra-abdominal abscess and anastomotic leak. SPN showed an inferior efficacy for almost all outcomes. CONCLUSIONS This study suggests that IMEN outperformed other nutrition types for reducing complications and IMEN should be considered the best available option.