Molecular detection of lymph node metastasis in breast cancer patients treated with preoperative systemic chemotherapy: a prospective multicentre trial using the one-step nucleic acid amplification assay.

BACKGROUND: For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy. METHODS: In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes. RESULTS: The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively. CONCLUSION: The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.

Dynamic helical CT-guided needle localization of non-palpable and mammographically occult breast lesions. Case reports.

Dynamic helical CT-guided needle localization of non-palpable and mammographically occult breast lesions is described. Dynamic helical CT-technique enabled fast volume scanning of the whole breast during the early contrast enhancement phase, which provided sufficient contrast to localize the target lesions. The procedures were successfully completed without complications.

Quantitative morphometric analysis of fine needle aspirates of breast carcinoma.

BACKGROUND: Reports of morphometric analysis using computerized digitized images of fine needle aspirates of breast cancer are rare. We aimed to evaluate whether quantitative morphometric estimations of cytological nuclear features could be used for preoperative prediction of the risk of recurrence as well as chemosensitivity. METHODS: Seventy consecutive breast cancer patients were treated with preoperative chemotherapy (Doxifluridine 800 mg/body/day, orally) for 4 weeks and subsequently they underwent surgery. Using Papanicolaou-stained cytological materials, computerized morphometric analyses were performed. Mean nuclear area (NA) was measured and the coefficient of variation of NA (NACV) was calculated as the quantitative parameter of nuclear atypism. NA and NACV were compared with prognostic factors (tumor size, histological grade, hormone receptor status, nodal status, and ploidy status), and with the response to the chemotherapy. RESULTS: NA and NACV were significantly associated with hormone receptor status and ploidy status (p<0.05). NACV correlated with histological grade (p<0.05). Neither NA nor NACV were associated with tumor size and nodal status. Patients with high NACV (>35%) had lower rates of disease-free survival (p<0.05) than those with low NACV (< or =35%). Responders to preoperative chemotherapy had statistically larger NA, higher NACV and higher S-phase fraction at the time of diagnosis compared with non-responders (p<0.001, p<0.0005, and p<0.05 respectively). CONCLUSIONS: Morphometric analysis of preoperative fine needle aspirates reflects important clinical information, such as the risk of recurrence, and particularly, chemosensitivity.

Cytomorphometric differentiation of intraductal proliferative breast lesions.

BACKGROUND: Although cytologic examination has been an indispensable procedure for the diagnosis of various breast diseases, it is often difficult to make a precise diagnosis of intraductal proliferative breast lesions preoperatively. The present study attempts to clarify the differentiation of the lesions by the cytologic morphometric approach. METHODS: Cytologic specimens from 21 intraductal lesions, including nine ductal carcinomas in situ (DCIS), seven ductal hyperplasias (DH), and five papillomas were evaluated. Using a microscope connected to a computerized video system, the mean nuclear area, the perimeter, the form factor, the largest to smallest diameter ratio of the nuclei (LS ratio), and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: The mean nuclear area and perimeter were significantly higher in the cases of DCIS than in DH (p < 0.01) and papilloma (p < 0.005). Similarly, DCIS had higher NACV values than the other groups (p < 0.05 and p < 0.005, respectively). There were no significant differences in form factor or LS ratio. CONCLUSIONS: The quantitative estimation of cytologic nuclear features is useful for preoperative differential diagnosis of intraductal proliferative lesions of the breast.

Quantitative ultrasound as a predictor of node metastases and prognosis in patients with breast cancer.

BACKGROUND: A retrospective study was performed to determine whether preoperative quantitative ultrasound assessment could predict axillary lymph node metastases and prognosis in patients with breast cancer. We focused on the presence of a halo, which is one of the features of breast cancer on ultrasound and represents reflections from the invading margin around infiltrating malignancies. METHODS: We evaluated ultrasonography from 187 infiltrating breast carcinoma patients with tumors 5 cm or less in greatest dimension (T1, T2). Using computer image analysis, the halo area (H) and the sum of the area of halo and internal echo (total tumor area (T)) were measured, and the ratio of halo to entire tumor (H/T, halo ratio) was calculated and compared with lymph node status and prognosis. RESULTS: The mean of the halo ratio was 0.38+/-0.13. Using the value of 0.42 as a cut-off, the high halo ratio group had significantly worse prognoses for both overall and disease-free survival at 49 months in median follow-up (p <0.001 and p <0.0005, respectively). The specificity of a high halo ratio in the T1 classification for predicting axillary node metastasis was 83.1%, with a negative predictive value of 86.8%. In patients with tumors 1.0 cm or smaller, the negative predictive value was 100%. In a multivariate analysis, halo ratio was an independent predictor of disease-free survival of breast carcinoma patients (p =0.0232). CONCLUSIONS: Preoperative quantitative ultrasound may be a useful non-invasive method for predicting the presence of axillary lymph node metastases and prognosis in patients with primary breast cancer.

Lobular involvement: prognostic indicator for invasive ductal carcinoma of the breast.

One of the striking microscopic appearances of breast carcinoma is malignant transformation of the epithelium of an entire lobule, although the lobular architecture is still preserved. We termed this pathological feature 'lobular involvement'. An investigation was carried out to determine whether lobular involvement would be a useful prognostic indicator for invasive ductal carcinoma. One hundred and fifty cases of invasive ductal carcinoma were included in this study. The lobular involvement, as well as the conventional prognostic factors, was evaluated to find out the correlation with the overall and relapse-free survivals by univariate and multivariate analyses. The lobular involvement was identified in 31 of 150 patients (20.6%). Of the patients with lobular involvement, two had experienced recurrence (6.5%) and one had died (3.2%). The lobular involvement and lymph node metastases were significantly and independently correlated with the overall and relapse-free survivals. The presence of lobular involvement was statistically correlated with the favorable outcome. Lobular involvement can be assumed as a new prognostic indicator for invasive ductal carcinoma.

Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose.

BACKGROUND: Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG) can provide quantitative information about tumor glucose metabolism. The prognostic value of this technique was evaluated for breast carcinoma patients. METHODS: FDG PET was performed on 70 patients with primary breast carcinoma, and the differential absorption ratio (DAR) was calculated as an index of FDG uptake. Overall and relapse free survival curves were created by the Kaplan-Meier method, and differences between the curves were analyzed with the log rank test. For multivariate analysis, the Cox proportional hazards regression model was used. RESULTS: The mean DAR was 2.61+/-1.61 standard deviation (range, 0.65-9.39). According to the grade of DAR, patients were then classified into high DAR (> or =3.0) and low DAR (<3.0) groups. The high DAR group had significantly worse prognoses for both overall and relapse free survival (P < 0.0005 and P < 0.0001, respectively). In multivariate analysis, DAR was an independent predictor of the relapse free survival of breast carcinoma patients (P=0.0377). CONCLUSIONS: DAR, as determined by FDG PET, may be useful as a prognostic indicator for patients with primary breast carcinoma.

Morphometry in the cytologic evaluation of thyroid follicular lesions.

BACKGROUND: The current study was undertaken to evaluate the quantitative estimation of cytologic features on aspirated smears for the preoperative differential diagnosis of follicular lesions of the thyroid. METHODS: The subjects were 60 patients with follicular lesions of the thyroid (including 20 follicular carcinomas, 15 follicular adenomas, and 25 adenomatous goiters) whose histopathologic explorations were conducted fully postoperatively. Using a microscope connected to a computerized video system, the mean nuclear area, the mean nuclear perimeter, the circular rate, the largest to the smallest dimension ratio (LS ratio) of the nuclei, and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: Among the quantitative morphometric parameters of nuclei, the circular rate was significantly higher in the group with adenomatous goiters than those with follicular carcinomas (P < 0.00001) and adenomas (P < 0.005). The group with follicular carcinomas had a higher LS ratio than the group with adenomatous goiters (P < 0.0005). The NACV value increased as the malignant potential of the lesion increased and showed significant differences between the groups. When a NACV of 21.5% was chosen as the cutoff point, the incidence of malignancy was significantly higher in patients with high NACV values than in those with low NACV values (P < 0.00001). Using this borderline value, it was possible to distinguish malignant from benign diseases with a sensitivity of 85.0%, a specificity of 82.5%, and an accuracy of 83.3%. CONCLUSIONS: Preoperative quantitative estimations of cytologic nuclear features are useful for the preoperative differential diagnosis of follicular lesions of the thyroid.

Interleukin-11 Gene Expression in Human Lymphoid Malignancy.

Interleukin-11 (IL-11) has diverse biological effects in hematopoiesis has been shown to share important functions with IL-6. However, unlike IL-6, there has been little information about the expression of IL-11 in lymphoid malignancy. Using reverse transcriptase polymerase chain reaction, IL-11 transcript was found in a number of lymphoid cell lines. A high level of expression was found in follicular lymphoma cell line FL18, and this was also detectable by Northern blotting. When TPA/A23187 were added to the culture of bone marrow stromal cell line KM102, IL-11 transcripts were rapidly upregulated. In contrast, levels of IL-11 transcripts were not increased in FL18 even upon the stimulation. The addition of actinomycin D to the cultures showed that the half life of the transcripts was similar in both FL18 and KM102. This suggests that posttran scriptional processes might not be involved in the constitutive expression of FL18. The results of IL-11 bioassay and enzymed-linked immunosorbent assay showed that FL18 did not secrete biologically active IL-11 into the medium. IL-11 transcript was also found in lymphoma cells in patient with malignant lymphoma, but not in B and T lymphocytes from reactive hyperplasia. Our results indicate that IL-11 transcripts can sometimes be produced in the neoplastic transformation of lymphoid cells.

[The relationship between infiltrating grade and prognosis by the preoperative diagnosis in ultrasonogram in breast carcinoma].

To evaluate peripheral infiltrative growth (inf) of breast catrcinomas as a prognostic factor, overall survival probabilities in 169 patients with tumor less than 5 cm in diameter were analysed in relation to the degree of inf (alpha, beta, gamma) using Kaplan-Meier method. There were statistically significant correlations between inf alpha and beta, inf alpha and gamma. On the other hand, the boundary echo (BE) observed at the peripheral margin of tumor in ultrasonogram is considered to reflect inf patterns of breast carcinomas. Therefore, BE was classified into three types as follows. Type I; negligible or regular thin marginal hyperecho. Type II; irregular thick marginal hyperecho. Type III; radiating boundary echo. These three types were matched to the patterns of infiltration so as to find any correlation between ultrasonogram and a corresponding histrogical specimen. Three types of ultrasonographic infiltrative grades (U-INF alpha, beta, gamma) were defined as follows. U-INF alpha; Type I BE is observed almost all surface of tumor. U-INF beta; Type II or III BE is observed in less than 50% of tumor surface. U-INF gamma; Type II or III BE is observed in over 50% of tumor surface. Total of 108 cases with tumor less than 3cm in diameter were received preoperative ultrasonographic studies. U-INF had highly significant correlation with inf and the occurrence of lymph node metastasis.

Changes of heart rate during administration of local anesthetics in the oral region.

In an attempt to clarify the mechanism of shock in dental patients, the effects on the heart rate of the injection of an anesthetic agent into the oral mucosa were studied. The heart rates of the subjects decreased by an average of 12.6% during infiltration anesthesia, which was greater than that induced by the mandibular block or breathholding. The response was completely blocked by general anesthesia and partially blocked by inhalation of nitrous oxide and oxygen or previous administration of atropine, indicating the possible participation of trigeminal-vagal reflex in producing these changes of heart rate.

Negative chronotropic effect of propanidid on the SA node of the dog heart in vivo.

Effect of propanidid on the pacemaker activity of the SA node was investigated in anesthetized dogs by injecting 30 microgram to 3 mg into the SA node artery in a single dose in a period of 4 sec. The doses of more than 100 microgram usually induced a negative chronotropic response. The injection of more than 1 mg frequently caused a sinus arrest followed by AV nodal rhythm. The initial sinus rhythm, however, was restored within 2 min after the propanidid administration. Its negative chronotropic response was not altered by pretreatment with atropine which completely blocked the action of acetylcholine. Bilateral vagotomy also did not affect the response induced by propanidid. A control solution or histamine failed to cause such a depressant effect on the SA node as observed after the propanidid injection. Thus, we conclude that propanidid supresses the SA nodal activity by a direct local action.

Surgical treatment of chronic osteomyelitis of the mandible resistant to intraarterial infusion of antibiotics: report of case.

A 47-year-old man with chronic osteomyelitis of the mandible is described. The patient had frequent episodes of acute and subacute exacerbation at varying intervals for a period of six years in spite of extended antibiotic therapy. Intraarterial infusion of antibiotics through the superficial temporal artery also failed to cause any improvement. He was finally treated successfully by surgical intervention.