Repeat liver resection for recurrent colorectal liver metastases

BACKGROUND: This study aimed to delineate the role of surgery for recurrent colorectal cancer in the liver and to identify prognosticators for better patient selection and outcome. METHODS: Data from 90 repeat hepatectomies (second = 75; third = 12; fourth = 3) for recurrent colorectal cancer were collected. RESULTS: After the second hepatectomy, the 3-and 5-year survival rates were 48% and 31%, respectively. Twenty-seven percent (20 of 75) of patients are alive without recurrence after a median follow-up of 27 months, and 9 survived more than 5 years. Four or more tumors, positive regional lymph node metastases, concomitant extrahepatic disease, and residual tumor were independent poor prognostic factors after the second hepatectomy. CONCLUSIONS: Repeat hepatectomy should be applied for recurrent colorectal cancer, when curative removal of the tumor is possible, although the benefit from treatment was limited in a patient with regional lymph node metastases, 4 or more metastases, or extrahepatic disease.     

No ethnic difference between Caucasian and Japanese hepatic samples in the expression frequency of CYP3A5 and CYP3A7 proteins

Ethnic differences in the pharmacokinetics of nifedipine, a substrate of CYP3A, and in CYP3A7 expression have been reported. The aim of the present study was to measure the protein levels of CYP3A4, CYP3A5, and CYP3A7 and nifedipine oxidation activity in hepatic microsomes from 15 Caucasian and 15 Japanese patients for comparison between the two ethnic groups. Nifedipine oxidation activity and CYP3A4 protein level were well correlated. No significant difference between Caucasian and Japanese microsomal samples was found in nifedipine oxidation activity or in the CYP3A4 protein level. CYP3A5 was detected in 6 of 15 Caucasian samples and in 5 of 15 Japanese samples, but no ethnic difference was found in either the frequency of expression or its protein level. CYP3A7 was found in 10 of 15 Caucasian samples and in 14 of 15 Japanese samples. Although the estimated CYP3A7 protein level was higher in the Japanese than in the Caucasian samples, its protein level was much lower than that of CYP3A4. These results imply that the contribution of CYP3A5 or CYP3A7 to the purported Caucasian-Japanese ethnic difference in the overall CYP3A activity seems to be small.     

Vertebral decancellation for severe scoliosis

STUDY DESIGN: The results of staged surgery including vertebral decancellation were reviewed retrospectively for 21 patients with severe scoliosis. OBJECTIVES: To evaluate the benefits and limitations of vertebral decancellation as new anterior surgical procedure. SUMMARY OF BACKGROUND DATA: The curvatures of severe scoliosis are often very rigid, and surgical correction using the anterior or posterior approach may not achieve the desired correction. Some studies reported neurologic complications might appear due to the aggressive approach or excessive correction force. METHODS: Twenty-one patients (average age, 17.0 years) with severe scoliosis, in whom Cobb angle was over 80 degrees (average angle, 107 degrees), underwent staged anterior and posterior spinal reconstruction. Vertebral decancellation was performed as anterior procedure, and until posterior instrumentation, halo traction was carried out. The transition of curvatures in coronal and sagittal planes was assessed in this series. RESULTS: The average correction rate of lateral curvature at the final follow-up was 46%. The average loss of correction was 2.5 degrees. Kyphosis, measured between T5 and T12, changed from 41 degrees to 36 degrees. Lordosis, measured between L1 and S1, changed from 56 degrees to 45 degrees. Transient neurologic deficit was seen in one case after vertebral decancellation. CONCLUSIONS: Staged surgery including vertebral decancellation is an effective surgical method for patients with severe scoliosis, where an inflexible rigid curve or the risk of occurrence of neurologic complications due to temporary correction may exist.     

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer

Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.      

Correlation between bone marrow edema and collapse of the femoral head in steroid-induced osteonecrosis

OBJECTIVE: The purpose of this study was to clarify whether bone marrow edema is detectable on initial MR imaging of steroid-induced osteonecrosis of the femoral head. SUBJECTS AND METHODS: Forty-eight hips with osteonecrosis were examined consecutively with MR imaging and radiography. In a previously reported screening program, osteonecrosis was diagnosed on MR imaging when subchondral bands of abnormal signals were present. In the screening program, the MR images of 200 hips of 100 patients receiving high-dose steroid therapy were examined prospectively. Subchondral bands were detected in 48 hips at a mean of 14 weeks after the initiation of steroid therapy. RESULTS: On follow-up MR imaging of 47 hips (one hip excluded) bone marrow edema was initially observed in 13 hips after the onset of hip pain. MR imaging of the remaining 34 hips did not reveal bone marrow edema and the patients were all asymptomatic. MR imaging of 31 of the 34 hips continued to show subchondral bands and MR imaging of the other three hips indicated that the subchondral bands had disappeared. When bone marrow edema was detectable, abnormal findings on radiography were slight but 11 (85%) of the 13 hips progressed to advanced osteonecrosis. Bone marrow edema was highly correlated with the subsequent collapse of the femoral head (p<0.0001). CONCLUSION: Bone marrow edema was not present on initial MR imaging of osteonecrosis. Bone marrow edema should be considered a marker for potential progression to advanced osteonecrosis, and careful examinations for osteonecrosis are necessary when bone marrow edema is seen.     

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.     

Functional involvement of endogenous anxiogenic neuropeptide in brains]

Neuronal GABA(A)/benzodiazepine and monoamine receptors participate in anxiety. Diazepam binding inhibitor (DBI), an endogenous anxiogenic neuropeptide, significantly increases in brains only after treatment with psychological stress, and this increase is completely abolished by benzodiazepines. Therefore, it is through that DBI may be involved in anxiogenesis produced by psychological stress. Furthermore, increases in cerebral DBI are observed in patients with several disorders accompanying anxiety and fear, which suggest that cerebral DBI may be an essential factor for anxiogenesis, and that it may be, at least in part, a biological index to evalulate anxiety.     

Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry

Aims/IntroductionThe evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.Materials and MethodsA total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m² were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m² during the follow‐up period.ResultsDuring follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m². Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m² with no coffee consumption, −1.89 mL/min/1.73 m² with less than one cup per day, −1.80 mL/min/1.73 m² with one cup per day and −1.78 mL/min/1.73 m² with two or more cups per day (P for trend 0.03).ConclusionsCoffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.