Potential of Reduction in Total Tumor Volume Measured with 3D‐MRI as a Prognostic Factor for Locally‐Advanced Breast Cancer Patients Treated with Primary Chemotherapy

Abstract: For accurate assessment of the response to primary chemotherapy (PCT) for locally advanced breast cancer, we measured reduction in total tumor volume (TTV) by using three‐dimensional magnetic resonance imaging (3D MRI), and examined the relationship between this reduction and patient prognosis. Fifty‐one patients with locally advanced breast cancer were treated with four cycles of docetaxel (60 mg/m²) before surgery. Tumor size was measured with calipers, ultrasonography (US) and conventional two‐dimensional (2D) MRI before and after chemotherapy. TTV was measured with 3D MRI. These and other clinicopathological parameters were statistically analyzed to determine the prognosis for the patients. Median follow‐up time was 46 months (1–64 months). Of the 51 patients, 25 developed distant recurrences. Patients whose TTV decreased by 75% or more after PCT showed significantly better prognosis than others, while tumor size measured with calipers, US and 2D MRI showed no significant relationship with patient prognosis. Of the clinicopathological parameters, only reduction in TTV and histological grade showed a significant association with distant recurrence‐free survival (p = 0.03 and 0.02, log‐rank test), while stepwise multivariate Cox’s proportional hazards analysis identified TTV as the strongest independent prognostic factor. Reduction in TTV measured with 3D MRI can be a useful prognostic factor for patients with locally advanced breast cancer treated with PCT.     

Off‐Pump Coronary Artery Bypass Grafting in Patients with End‐Stage Renal Disease on Hemodialysis

Abstract Background: Coronary artery bypass grafting (CABG) for hemodialysis patients is high risk compared with other patient groups. The aim of this study was to analyze the potential benefits of off‐pump CABG for hemodialysis patients. Methods: From April 1994 through December 2000, 26 hemodialysis patients underwent CABG. The off‐pump group consisted of 15 patients operated on without a pump and the on‐pump group consisted of 11 patients operated on with a pump. Results: There was no difference between the two groups with regard to mean age, mean number of diseased vessels and mean number of anastomoses per patient. No patient died in either group during hospitalization. The postoperative complication rate was low in both groups. The postoperative ventilation time was shorter in the off‐pump group (8.5 vs 26.1 hours, p < 0.001, respectively [off‐pump group vs on‐pump group]). The length of ICU stay was shorter in the off‐pump group (1.7 vs 3.5 days, p # 0.01, respectively [off‐pump group vs on‐pump group]). The medial cost was lower in the off‐pump group ($26,200.80 versus $44,024.10 p # 0.0001 respectively [off‐pump group vs on‐pump group]). Conclusions: Off‐pump CABG provided excellent less‐invasive cardiac surgical results for dialysis patients.     

Pharmacokinetics and protein binding of cefazolin and cephalothin in patients with cirrhosis

The effects of liver disease on the pharmacokinetics and protein binding of cefazolin and cephalothin were studied in patients with cirrhosis, chronic active hepatitis or normal liver function. The T1/2 and mean residence time of cefazolin were significantly shorter in cirrhosis. Cephalothin clearance was decreased by cirrhosis. Plasma protein binding of cefazolin, but not cephalothin was significantly reduced in cirrhosis. It is suggested that no dose reduction is necessary for either drug in severe hepatic impairment.     

Left heart pressures can be the key to know the limitation of left ventricular assist device support against progression of aortic insufficiency

Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48?±?2 kg) underwent centrifugal type LVAD, EVAHEART, implantation. The AI model was established by placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial oxygen extraction ratio (O₂ER) were evaluated while changing the degree of AI which was expressed as the flow rate of LVAD-LV recirculation (recirculation rate). Diastolic aortic pressure was decreased with AI progression and correlated negatively with the recirculation rate (p?=?0.00055). Systolic left ventricular pressure (LVP) and mean left atrial pressure (LAP) were increased with AI progression and correlated positively with the recirculation rate (p?=?0.010, 0.023, respectively). LVP and LAP showed marked exponential increases when the recirculation rate surpassed 40%. O₂ER was also increased with AI progression and had a significant positive correlation with the recirculation rate (p?=?0.000043). O₂ER was increased linearly, with no exponential increase. AI progression made it difficult to reduce the cardiac pressure load, worsening myocardial oxygen metabolism. The exponential increase of left heart pressures could be the key to know the limitation of LVAD support against AI progression.     

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (±SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6±2.8 and 6.8±2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P<0.05) lower than those from dyspeptic patients (13.6±6.9 and 10.9±3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2±125.6 pg/mg tissue) was significantly (P<0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1±188.2 pg/mg tissue) and from dyspeptic patients (276.8±138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.This study was supported by a grant-in-aid from the Ministry of Human Health and Welfare, Tokyo.     

Accelerated expression of a Myc target gene Mina53 in aggressive hepatocellular carcinoma

Aim: Expressions of the myc target genes Mina53 and mimitin are high in esophageal squamous cell carcinoma and colon cancer, and their relationship to cell proliferation and patient prognosis has been reported. Because c‐myc gene expression is closely related to hepatocellular carcinoma (HCC) growth or formation and/or maintenance, we examined the Mina53 and mimitin expressions in HCC. Methods: Surgically resected 53 HCC tissues were immunohistochemically examined for Mina53 and mimitin expressions and their relationship to clinicopathological factors. Results: Diffuse Mina53 expression was observed in the nuclei of cancer cells in the tumor nodule, but was often strong at the periphery of tumor nodules. Diffuse or scattered expression of mimitin was observed in the cytoplasm of HCC cells in tumor nodules. Mina53 expression was higher in poorly differentiated HCC than in well‐differentiated HCC, and significant relationship to histological grade was observed. The cases with a high Mina53 expression also had a high expression of a proliferation marker MIB‐1. This suggested the involvement of Mina53 in cell proliferation. Mina53 expression was high in the tumors of >2 cm of diameter than in ≤2 cm (P < 0.01). Mimitin expression tended to be high in tumors of >2 cm, but no significant relationship was observed either to histological grade, MIB‐1 expression, or the other clinicopathologic factors. Conclusions: Our findings suggested that Mina53 expression is accelerated in HCC with a lower histological grade, with cell proliferation capability, or with a larger diameter, and Mina53 is related to biological malignancy of HCC.     

Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells

Purpose

Mina53, whose expression is directly induced by c-Myc, is overexpressed in various cancers and plays an important role in cell growth. To clarify the involvement of Mina53 in lung cancers, we investigated its expression in human lung cancer tissues as well as in various lung cancer cell lines.

Methods

Mina53 expression was determined by real-time RT-PCR, western blotting, and immunohistochemistry using lung cancer cell lines, normal human bronchial epithelial cells, and lung cancer tissues. Biological effects of Mina53 were evaluated by soft agar colony formation assay and tumorigenicity in nude mice using Mina53-transfected NIH/3T3 cells. cDNA microarray analysis was performed to determine the gene alteration by Mina53 and confirmation was made using real-time RT-PCR with mina53 expression plasmid or mina53 shRNA-transfected NIH/3T3 cells.

Results

We observed that 62% of patients evidenced overexpression of Mina53 from the early clinical stages of lung cancer. Differences according to gender, smoking status, or histologic type were not statistically significant. Forced expression of Mina53 in NIH/3T3 cells induced cell transformation, and mina53-transfected NIH/3T3 clones produced tumors in nude mice, demonstrating that Mina53 has oncogenic potential. cDNA microarray revealed that 254 genes had altered expression in a mina53-transfected NIH/3T3 clone. Mina53 regulates several genes related to cell adhesion and metabolism, which have also been reported to be regulated by c-Myc. Genes regulated by Mina53, but not by c-Myc included cytokine/growth factor related genes such as EGFR, IL-6, and HGF.

Conclusion

Our results suggest that Mina53 plays an important role in carcinogenesis and may be a target for cancer prevention.     

Placement of a plastic biliary stent tube with primary closure of the common bile duct after laparoscopic common bile duct exploration

Laparoscopic common bile duct exploration (LCBDE) is one of the standard surgical procedures for treating choledocholithiasis. Several methods of biliary drainage following LCBDE have been advocated to prevent bile leakage. We report herein a surgical procedure using a plastic biliary stent tube following LCBDE for biliary drainage. Our method is technically simple, feasible and an ideal procedure for biliary drainage with LCBDE.     

Blocking effect of NIP-142 on the KCNQ1/KCNE1 channel current expressed in HEK293 cells

We examined the effect of NIP-142, a benzopyran compound with terminating effect on experimental atrial arrhythmia, on the KCNQ1/KCNE1 channel, which underlies the slow component of the cardiac delayed rectifier potassium channel (I(Ks)). NIP-142, as well as chromanol 293B, showed concentration-dependent blockade of the current expressed in HEK293 cells; the EC(50) value of NIP-142 and chromanol 293B for the inhibition of tail current was 13.2 μM and 4.9 μM, respectively. These results indicate that NIP-142 has blocking effect on the KCNQ1/KCNE1 channel current.