Predictive Value of the Time–Intensity Curves on Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Lymphatic Spreading in Breast Cancer

Purpose Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a promising diagnostic modality in various breast cancer treatments. However, little is known about the correlation between the pattern of time to signal intensity curves (TIC) on the CE-MRI and clinicopathologic features. This study was designed to investigate these correlations and evaluate the predictive value of TIC on CE-MRI in order to identify high-risk patients.Methods Between 2001 and 2003, 101 lesions were evaluated to detect malignancy on CE-MRI in 101 women who were suspected of having breast tumors based on either clinical findings or conventional imaging studies. Moreover, the clinicopathologic findings were compared with the pattern of TIC for the 69 surgically treated malignant lesions.Results In detecting malignancy, the sensitivity, specificity, and accuracy were 78.7%, 88.5%, and 81.2%, respectively, in the 101 breast lesions. Especially for the 69 surgically treated malignant lesions, in comparison with breast cancer tumors with the benign pattern of TIC, the breast cancer tumors with a malignant pattern were found more frequently in lymphatic invasion (P < 0.01) and lymph node metastasis (P < 0.005), although no statistical correlation regarding the histological type, tumor size, vascular invasion, extensive intraductal component, hormone receptor status, or pathological stage was noted between the two groups. According to a logistic regression model, lymph node metastasis was found to be a significant independent variable.Conclusion The pattern of TIC could be used to predict lymphatic spreading associated with lymph node metastasis prior to surgery as well as to detect malignancy. Therefore, a more detailed evaluation should be made to identify the presence of lymphatic spreading in patients with a malignant pattern of TIC.This study was presented at the 103rd Annual Congress of the Japan Surgical Society, Sapporo, Hokkaido, June 4–6, 2003     

Investigation about the homogeneity of nasopharyngeal microflora at the different location of nasopharynx of children with acute otitis media

OBJECTIVE: Nasopharynx is thought to be a very important site as becterial reservoir for acute otitis media (AOM). In this study, we investigated on the homogeneity of nasopharyngeal microflora at the different location of nasopharynx of children with AOM. METHODS: Thirty nasopharyngeal samples of 15 children with AOM, two samples harvested from both nostrils of each child, were cultured and analyzed by patterns of antibiotic susceptibility and pulsed-field gel electrophoresis analysis (PFGE). RESULTS: A total of 30 nasopharyngeal samples were cultured and 19 isolates of Streptococcus pneumoniae from 10 children (66.7%), 8 isolates of Haemophilus influenzae from 4 children (26.7%), and 12 isolates of Moraxella catarrhalis from 7 children (46.7%) were obtained. In all children except three, the nasopharyngeal microflora at right and left orifice of the eustachian tubes showed no obvious differences in the bacterial species and quantities. Furthermore, in children with the same species of were cultured from right and left orifice of the eustachian tubes at the same time, all nine couples of S. pneumoniae isolates, four couples of H. influenzae isolates, and five couples of M. catarrhalis isolates showed about the same susceptibility and PFGE patterns. CONCLUSION: These results suggest that the microflora at the different location of nasopharynx of children with AOM is almost homogeneous, irrespective of the clinical signs.     

Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma

Activation of the epidermal growth factor receptor (EGFR) has a role in oncogenesis and may correlate with prognosis. The aim of this study was to examine EGFR expression in esophageal adenocarcinoma and correlate EGFR status with pathologic and clinical prognostic features. An exploratory retrospective review of 38 patients with surgically resected esophageal adenocarcinoma was performed. All patients underwent an esophagogastrectomy with regional lymphadenectomy; 24 patients underwent primary resection and 14 patients had surgery after preoperative chemoradiation therapy. Immunohistochemical analysis was performed on paraffin-embedded tissue samples using an EGFR monoclonal antibody. Low- and moderate-grade tumors were positive for EGFR expression in 2 of 15 patients; poorly differentiated tumors were positive for EGFR expression in 13 of 23 patients (p = 0.02). The median survival was 35 months (confidence interval [CI]: 29–40) for EGFR negative patients (n = 23) and 16 months (CI: 10–22) for EGFR positive patients (n = 13) (p = 0.10). Disease recurred in 3 of 21 EGFR negative patients and 6 of 13 EGFR positive patients (p = 0.06). Poorly differentiated adenocarcinomas of the esophagus demonstrated higher EGFR expression compared to low-grade tumors based upon immunohistochemical analysis. A trend toward improved disease-free and overall survival was seen in EGFR negative patients.     

Intraperitoneal chemotherapy against peritoneal carcinomatosis of gastric cancer with activated carbon particles adsorbing mitomycin C for four patients

Activated carbon particles adsorbing mitomycin C (MMC-CH) was administered to four patients with peritoneal carcinomatosis of gastric cancer into their abdominal cavities. Tumor markers of CEA, CA19-9, CA125, CA72-4 and STN were measured before and after the administration. The waist of each patient was also measured. After the administration of MMC-CH, tumor markers of three out of the four patients were decreased and a large amount of ascites of all patients had disappeared. The appetite of all four patients had increased and complaints such as nausea and vomiting had decreased. The mean survival of the four patients was 291.2 days (123-542 days). Our results suggested that MMC-CH had an anti-tumor effect of peritoneal carcinomatosis and improved the QOL of patients with a large amount of ascites.     

Active Specific Chemoimmunotherapy of Lymph-node Metastasis from a Poorly Immunogenic Murine Fibrosarcoma

The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/ HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific Chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 fig weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte snbpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2⁺ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.     

Overexpression of Necl‐5 correlates with unfavorable prognosis in patients with lung adenocarcinoma

Nectin‐like molecule‐5 (Necl‐5) is an immunoglobulin (Ig)‐like molecule that is up‐regulated in many types of cancer cells. It was shown experimentally that Necl‐5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl‐5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl‐5. The relationship between expression of Necl‐5 and clinicopathological features was analyzed, and the influence of Necl‐5 expression on outcomes in these patients was assessed. A strong expression of Necl‐5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl‐5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease‐free survival rate in patients with positive Necl‐5 overexpression was significantly lower than that in patients with negative Necl‐5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl‐5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease‐free survival rate of the Necl‐5‐positive group was significantly lower than that of the Necl‐5‐negative group (P = 0.0192). These results indicate that Necl‐5 plays a role in mediating tumor cell invasion and that the overexpression of Necl‐5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma. (Cancer Sci 2010; 101: 1326–1330)     

Absorption,distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects

1.?Alectinib is a highly selective, central nervous system-active small molecule anaplastic lymphoma kinase inhibitor.

2.?The absolute bioavailability, metabolism, excretion and pharmacokinetics of alectinib were studied in a two-period single-sequence crossover study. A 50?μg radiolabelled intravenous microdose of alectinib was co-administered with a single 600?mg oral dose of alectinib in the first period, and a single 600?mg/67?μCi oral dose of radiolabelled alectinib was administered in the second period to six healthy male subjects.

3.?The absolute bioavailability of alectinib was moderate at 36.9%. Geometric mean clearance was 34.5?L/h, volume of distribution was 475?L and the hepatic extraction ratio was low (0.14).

4.?Near-complete recovery of administered radioactivity was achieved within 168?h post-dose (98.2%) with excretion predominantly in faeces (97.8%) and negligible excretion in urine (0.456%). Alectinib and its major active metabolite, M4, were the main components in plasma, accounting for 76% of total plasma radioactivity. In faeces, 84% of dose was excreted as unchanged alectinib with metabolites M4, M1a/b and M6 contributing to 5.8%, 7.2% and 0.2% of dose, respectively.

5.?This novel study design characterised the full absorption, distribution, metabolism and excretion properties in each subject, providing insight into alectinib absorption and disposition in humans.