Clinicopathological study on the relationship between serum-CEA and tissue-CEA of resected lung cancer cases

The clinicopathological correlation between serum-CEA (s-CEA) and immunohistological tissue-CEA (t-CEA) was studies on 63 cases of operated lung cancers. T-CEA was examined by peroxidase anti-peroxidase (PAP) method. T-CEAs were detected in 36/39 cases (92.3%) of adenocarcinoma, 16/16 cases (100%) of epidermoid carcinoma, 2/5 cases (40%) of large cell carcinoma, and 1/3 case (33.3%) of small cell carcinoma. T-CEAs in adenocarcinoma and large cell carcinoma with mucin exhibited moderate to strong reactivity with diffuse distribution, and also s-CEA of these cases indicated high levels. On the contrary, in epidermoid carcinoma t-CEAs showed a weak reactivity with focal distribution, and s-CEAs also demonstrated low levels. In adenocarcinoma it was suggested that the more cancers were differentiated, the more t-CEA and s-CEA were increased, and about two third of cases showed a balance between t-CEA and mucin content in cancer tissue. S-CEAs were not correlated with the size of the primary lesion or the extent of lymph node metastasis, but with the histological types, i.e. high levels of s-CEA in adenocarcinoma and large cell carcinoma with mucin.     

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42–11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.     

Brain temperature modifies glutamate neurotoxicity in vivo

The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.     

The Effect of Carboxyl-Terminal Propeptide of Type I Collagen (c-Propeptide) on Collagen Synthesis of Preosteoblasts and Osteoblasts

Recently we found that the carboxyl-terminal propeptide of type I collagen (c-propeptide) is a major secretory protein of osteoblasts. Mature osteoblasts secreted 64 nM c-propeptide, and it was reported that 40 nM c-propeptide inhibited collagen synthesis at 80% of the control level. In this study, we investigated the effect of c-propeptide on collagen synthesis of preosteoblasts and osteoblasts, and found that preosteoblasts downregulated collagen synthesis by 40 nM c-propeptide, but osteoblasts were not affected by the same condition. When the binding activities of c-propeptide for preosteoblasts and osteoblasts were compared, osteoblasts showed weak affinity to c-propeptide compared with preosteoblasts, and the number of receptors for c-propeptide decreased in osteoblasts. These results imply that a decrease of receptors in osteoblasts might reduce the sensitivity of osteoblasts to c-propeptide. Received: 6 August 1999 / Accepted: 9 May 2000 / Online publication: 22 September 2000     

Health-related quality of life with orthotopic neobladder versus ileal conduit according to the SF-36 survey

OBJECTIVES: To compare health-related quality of life (HRQOL) in patients with a neobladder and in patients with an ileal conduit. METHODS: HRQOL was assessed using the SF-36 survey, supplemented with a questionnaire concerning micturition status. RESULTS: Patients (n = 36) with a neobladder were significantly younger at time of surgery and time of survey than patients with an ileal conduit (n = 20). Mean (+/- SD) follow-up periods for patients with a neobladder and with an ileal conduit were 31.3 +/- 33.1 and 44.8 +/- 30.7 months, respectively. No significant difference was apparent in any scale score between neobladder and ileal conduit groups. Role-physical functioning (RP) and role-emotional functioning (RE) scale scores in both neobladder and ileal conduit patients appeared to be below the general U.S. population norm. Patients with neobladder 65 years old or older (n = 17) showed significantly lower RP and RE scores than those younger than 65 years (n = 19; P <0.05). Duration of follow-up was not related to scale scores. Continence status did not measurably affect HRQOL. CONCLUSIONS: All scales concerning HRQOL except RP and RE were favorable with both neobladder and ileal conduit, and no significant differences were observed between these two types of urinary tract reconstruction. Generally, patients with a neobladder or an ileal conduit were satisfied with their overall quality of life and health.     

Bacterial adherence in a rat bladder augmentation model: ileocystoplasty versus colocystoplasty

PURPOSE: Various intestinal segments are used to reconstruct the urinary tract. For unclear reasons asymptomatic chronic bacteriuria is common in patients treated with reconstruction. We compared bacterial adherence in ileum, colon and bladder in rats with ileal and colonic bladder augmentation. MATERIALS AND METHODS: Bladder augmentation using ileum or colon was performed in 8-week-old rats. After 3 months urinary pH was measured and urine was cultured. Urovirulence factors of Escherichia coli aspirated from the augmented bladders were detected by polymerase chain reaction. In rats with negative urine culture after augmentation experimental cystitis was induced by the transurethral inoculation of E. coli C5, with type I pili and aerobactin or E. coli C92 with type I pili, P fimbriae and aerobactin at a concentration of 10(5) colony forming units per 0.3 ml. After 14 days we counted the colony forming units per cm.(2) of bladder and cm.(2) of intestinal augmentation tissue. RESULTS: When cultures were negative, mean urinary pH plus or minus standard deviation for ileocystoplasty (7.35 +/- 0.33) was significantly higher than that for colocystoplasty (6.80 +/- 0.45) or in controls (6.67 +/- 0.30). Bacterial colonization occurred in 60 of 96 ileocystoplasties (62.5%) and 36 of 68 colocystoplasties (52.9%). All 32 E. coli strains aspirated from ileocystoplasties had type I pili. In colocystoplasties 14 strains had type I pili, 4 had P fimbriae and type I pili, and 1 had no virulence factor. In experimental cystitis in the ileal patch and bladder there were 10(3.2) to 10(6.2) (log mean 4.9) and 10(1.1) to 10(5.1) (log mean 3.5) colony forming units of E. coli C5, respectively. In the colonic patch and bladder there were 10(2.2) to 10(6.2) (log mean 3.9) and 10(2.1) to 10(5.1) (log mean 3.7) colony forming units of E. coli C5, respectively. In the ileal patch and bladder versus the colonic patch and bladder there were 10(3.2) to 10(6.2) (log mean 5.0) and 10(3.1) to 10(6.1) (log mean 4.5) versus 10(3.2) to 10(6.2) (log mean 4.3) and 10(2.1) to 10(6.1) (log mean 3.8) colony forming units of E. coli C92, respectively. E. coli C5 adhered to more ileum than bladder, while bacterial adherence did not differ for colon and bladder. Adherence of E. coli C92 did not differ significantly in bladder and implanted ileum or colon. CONCLUSIONS: The colonic segment offers more resistance to E. coli than the ileal segment in urinary diversion.     

A comparative study of the antioxidant/prooxidant activities of eugenol and isoeugenol with various concentrations and oxidation conditions

Eugenol (compound 1 in Fig. 1, 4-allyl-2-methyoxyphenol) and isoeugenol (compound 2 in Fig. 1, 4-propenyl-2-methoxyphenol), both used as a flavor agent in cosmetic and food products, have both prooxidant and antioxidant activities. Their adverse effects such as allergic and inflammatory reaction may be due to their prooxidant activity. To clarify the mechanisms of their cytotoxicity and the factors affecting their antioxidant/prooxidant activities, we investigated the cytotoxicity, ROS production, and cellular glutathione (GSH) levels induced by eugenol and isoeugenol in a human submandibular cell line. The cytotoxicity (MTT method) of eugenol was 1 order of magnitude lower than that of isoeugenol (CC₅₀: eugenol, 0.395 mM; isoeugenol, 0.0523 mM); and ROS production (CDF staining) was induced significantly by isoeugenol, but not by eugenol. Under treatment with H₂O₂ (100 μM) plus horseradish peroxidase (1 μg/ml) for 30 min or with visible light irradiation for 5 min, eugenol caused biphasic ROS production characterized by enhanced at lower eugenol concentrations (5–10 μM) and decreased at higher concentrations (500 μM). In contrast, isoeugenol enhanced ROS production over a wide range of concentrations (5–500 μM). Isoeugenol at 1000 μM significantly reduced GSH levels compared with eugenol at the same concentration. The high cytotoxicity of isoeugenol may be attributed to its induction of high ROS production and low GSH levels, possibly as a result of benzyl radical formation. In contrast, the cytotoxicity of eugenol is likely to be mediated by ROS-independent mechanisms, possibly involving phenoxyl radicals and/or eugenol quinone methide.     

Combined Use of Texture Features and Morphological Classification Based on Dynamic Contrast-enhanced MR Imaging: Differentiating Benign and Malignant Breast Masses with High Negative Predictive Value

Purpose: We evaluated the diagnostic performance of the texture features of dynamic contrast-enhanced (DCE) MRI for breast cancer diagnosis in which the discriminator was optimized, so that the specificity was maximized via the restriction of the negative predictive value (NPV) to greater than 98%.Methods: Histologically proven benign and malignant mass lesions of DCE MRI were enrolled retrospectively. Training and testing sets consist of 166 masses (49 benign, 117 malignant) and 50 masses (15 benign, 35 malignant), respectively. Lesions were classified via MRI review by a radiologist into 4 shape types: smooth (S-type, 34 masses in training set and 8 masses in testing set), irregular without rim-enhancement (I-type, 60 in training and 14 in testing), irregular with rim-enhancement (R-type, 56 in training and 22 in testing), and spicula (16 in training and 6 in testing). Spicula were immediately classified as malignant. For the remaining masses, 298 texture features were calculated using a parametric map of DCE MRI in 3D mass regions. Masses were classified into malignant or benign using two thresholds on a feature pair. On the training set, several feature pairs and their thresholds were selected and optimized for each mass shape type to maximize specificity with the restriction of NPV > 98%. NPV and specificity were computed using the testing set by comparison with histopathologic results and averaged on the selected feature pairs.Results: In the training set, 27, 12, and 15 texture feature pairs are selected for S-type, I-type, and R-type masses, respectively, and thresholds are determined. In the testing set, average NPV and specificity using the selected texture features were 99.0% and 45.2%, respectively, compared to the NPV (85.7%) and specificity (40.0%) in visually assessed MRI category-based diagnosis.Conclusion: We, therefore, suggest that the NPV of our texture-based features method described performs similarly to or greater than the NPV of the MRI category-based diagnosis.     

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa,Japan

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.