Response prediction of neoadjuvant chemoradiation therapy in locally advanced rectal cancer using CT-based fractal dimension analysis

OBJECTIVES: There are individual variations in neo-adjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer (LARC). No reliable modality currently exists that can predict the efficacy of nCRT. The purpose of this study is to assess if CT-based fractal dimension and filtration-histogram texture analysis can predict therapeutic response to nCRT in patients with LARC. METHODS: In this retrospective study, 215 patients (average age: 57 years (18-87 years)) who received nCRT for LARC between June 2005 and December 2016 and underwent a staging diagnostic portal venous phase CT were identified. The patients were randomly divided into two datasets: a training set (n = 170), and a validation set (n = 45). Tumor heterogeneity was assessed on the CT images using fractal dimension (FD) and filtration-histogram texture analysis. In the training set, the patients with pCR and non-pCR were compared in univariate analysis. Logistic regression analysis was applied to identify the predictive value of efficacy of nCRT and receiver operating characteristic analysis determined optimal cutoff value. Subsequently, the most significant parameter was assessed in the validation set. RESULTS: Out of the 215 patients evaluated, pCR was reached in 20.9% (n = 45/215) patients. In the training set, 7 out of 37 texture parameters showed significant difference comparing between the pCR and non-pCR groups and logistic multivariable regression analysis incorporating clinical and 7 texture parameters showed that only FD was associated with pCR (p = 0.001). The area under the curve of FD was 0.76. In the validation set, we applied FD for predicting pCR and sensitivity, specificity, and accuracy were 60%, 89%, and 82%, respectively. CONCLUSION: FD on pretreatment CT is a promising parameter for predicting pCR to nCRT in patients with LARC and could be used to help make treatment decisions. KEY POINTS: • Fractal dimension analysis on pretreatment CT was associated with response to neo-adjuvant chemoradiation in patients with locally advanced rectal cancer. • Fractal dimension is a promising biomarker for predicting pCR to nCRT and may potentially select patients for individualized therapy

Ablation of Mrds1/Ofcc1 Induces Hyper-γ-Glutamyl Transpeptidasemia without Abnormal Head Development and Schizophrenia-Relevant Behaviors in Mice

Mutations in the Opo gene result in eye malformation in medaka fish. The human ortholog of this gene, MRDS1/OFCC1, is a potentially causal gene for orofacial cleft, as well as a susceptibility gene for schizophrenia, a devastating mental illness. Based on this evidence, we hypothesized that this gene could perform crucial functions in the development of head and brain structures in vertebrates. To test this hypothesis, we created Mrds1/Ofcc1-null mice. Mice were examined thoroughly using an abnormality screening system referred to as “the Japan Mouse Clinic”. No malformations of the head structure, eye or other parts of the body were apparent in these knockout mice. However, the mutant mice showed a marked increase in serum γ-glutamyl transpeptidase (GGT), a marker for liver damage, but no abnormalities in other liver-related measurements. We also performed a family-based association study on the gene in schizophrenia samples of Japanese origin. We found five single nucleotide polymorphisms (SNPs) located across the gene that showed significant transmission distortion, supporting a prior report of association in a Caucasian cohort. However, the knockout mice showed no behavioral phenotypes relevant to schizophrenia. In conclusion, disruption of the Mrds1/Ofcc1 gene elicits asymptomatic hyper-γ-glutamyl-transpeptidasemia in mice. However, there were no phenotypes to support a role for the gene in the development of eye and craniofacial structures in vertebrates. These results prompt further examination of the gene, including its putative contribution to hyper-γ-glutamyl transpeptidasemia and schizophrenia

Vapor-liquid equilibria for binary systems carbon dioxide 1,1,1,2,3,3-hexafluoro-3-(2,2,2-trifluoroethoxy)propane or 1-ethoxy-1,1,2,2,3,3,4,4,4-nonafluorobutane at 303.15-323.15 K

The phase behavior of binary mixtures of carbon dioxide (CO2) and hydrofluoroethers (HFEs) has been studied. In particular, experimental vapor-liquid equilibrium (VLE) data for CO2 + 1,1,1,2,3,3-hexafluoro-3-(2,2,2-trifluoroethoxy)propane (HFE-449mec-f) and 1-ethoxy-1,1,2,2,3,3,4,4,4-nonafluorobutane (HFE-7200) at temperatures of 303.15, 313.15, and 323.15 K are reported. The VLE data were measured using a static-type apparatus and then correlated using the Peng-Robinson equation of state with the van der Waals one fluid and Wong-Sandler-NRTL mixing rules. Reasonable correlation results were obtained from the Peng-Robinson equation of state with both the van der Waals one fluid and the Wong-Sandler-NRTL mixing rules. The GC-SAFT-VR equation also gave good predictions of the phase behavior. Additionally, the group contribution SAFT-VR (GC-SAFT-VR) equation was used to predict the experimental VLE in good agreement with the experimental data, as well as the full p,T phase diagram for both systems

Incidence and risk factor of outlet obstruction after construction of ileostomy

There are several reports on the usefulness of diverting ileostomy for decreasing the incidence of anastomotic leakage and the severity of pelvic peritonitis. However, a number of complications induced by ileostomy itself have also been reported, including a special condition induced by obstruction at the outlet of the stoma known as “outlet obstruction.” In this study, we examined the frequency and risk factors of this complication based on the data of ileostomy cases in our institution. Methods: One hundred and seven patients who received ileostomy creation at our department from January 2010 to December 2015 were included. The incidence of outlet obstruction and risk factors were analyzed. Results: Outlet obstruction occurred in 18 cases (16.8%). The incidence was significantly higher in total colectomy or proctocolectomy cases as well as in those with left side construction and laparoscopic surgery than in other patients in a univariate analysis. However, in a multivariate analysis, no risk factors were extracted. Conclusions: To determine the true cause of this disease, a prospective study with a large number of cases is needed. Since multiple terms are used for this condition, resulting in confusion, a consensus on the appropriate terms is also important

Indirect effects of low-impact thinning on insect communities in forest floor of coniferous plantations

To reveal the effects of low-impact thinning of coniferous planted forests on insects’ diversity, we investigated the relationship among cover degree and the number of plant species and the number of insect species in eight functional groups of herbivorous beetles, ants and carabid beetles at 63 sites of Japanese cedar and cypress which were thinned or unthinned and located in the middle of Japan. We found that when low thinning was applied to approximately 30% of the stand density, the number of plant species increased from the following year, and cover degree moderately increased in the years following thinning, although canopy openness did not significantly change. Using structural equation modeling, we found that the number of herbivorous beetle species increased with the cover degree increment of feeding-intended plants (woody-plants and herbs/vines) in the 4–8 years after thinning. The number of species of woody-plant feeding beetles also increased with an increase in the number of herb/vine plant species. For ant species, the number of habitat generalist species increased in the 4–8 years after thinning or with cover degree increment, although no response was observed in woodland specialist and open-habitat specialist species. For carabid beetle species, only the number of large-size species, not including open-habitat specialists, increased with cover degree increment. It was considered that there were moderate, and yet sustainable, positive effects of low-impact thinning on species diversity of forest-floor-inhabiting insects via understory vegetation increment with a lag-time, and no promotion of migration of non-forest-habitat ant and carabid beetle species.</p

Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study

Objectives: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. Methods: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m2/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. Results: The S-1 recommended dose was 80 mg/m2/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. Conclusions: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present