Report of the Tenth International Symposium of the Foundation for Promotion of Cancer Research: Basic and Clinical Research in Head and Neck cancer.
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Diagnostic Imaging↗
Biomedical subjects
K Mukai
Publications and source records attributed to K Mukai.
Application of image analysis and neural networks to the pathology diagnosis of intraductal proliferative lesions of the breast.
We studied whether a computer-assisted system using a combination of data collection by image analysis and analysis by neural networks can differentiate benign and malignant breast lesions. Forty-six intraductal lesions of the breast were studied by pathologists and by the computer-assisted system. Histological evaluation was performed independently by three pathologists, and the lesions were classified into pathologically malignant (n = 12), undetermined (n = 13), and benign (n = 21). Computerized nuclear image analysis was performed using the CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear morphometric and textural features. A neural network was constructed using the morphometric and texture data obtained from teaching cases of malignant and benign lesions. Then data for unknown cases were classified by the constructed neural network into neural network-malignant (n = 11), -undetermined (n = 5), and -benign (n = 30). The agreement rate between the diagnosis by pathologists and judgment by the computer-assisted system was 75%, excluding pathologically undetermined lesions. There were four false-negative but no false-positive results. False-negative cases had nuclei that were quite different from those of the teaching cases. The agreement rate obtained using either morphometric data or texture data only was lower than that using a combination of both. Selection of appropriate teaching data and incorporation of both morphometric and textural parameters seemed important for obtaining more accurate results. The present data suggest that development of a computer-assisted histopathological diagnosis system for practical use may be possible.
Breast↗
Microsatellite instability in lung cancer patients 40 years of age or younger.
Lung cancer in the young, which has the characteristics of a higher incidence of adenocarcinoma, lower male-to-female ratio of the patients, and less frequent smoking history in the patients, may possibly be associated with genetic predisposition to cancers. We studied six microsatellite loci (D2S123, D3S659, D3S966, D5S346, WT1, and TP53) in 18 surgically treated lung cancer patients aged 25-40 years and nine control patients aged 62-74 to determine the presence of microsatellite instability (MSI) and to correlate its occurrence with clinicopathological characteristics. Of the 18 patients, 11 were female and seven were non-smokers. There were 15 adenocarcinomas and three squamous cell carcinomas, 15 (83%) of which had vascular invasion. MSI was positive in seven (39%) of 18 young patients and one (11%) of nine control patients. Moreover, MSIs in a half or more of six loci examined were demonstrated in five (28%) young patients, whereas no control patients showed such a high frequency of MSI. We observed no significant differences in clinical or pathologic parameters between cases with and without MSI. This result suggests that genetic factors play an important role in the development of lung cancer in young adults.
Adenocarcinoma↗
Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation.
We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1-3 and > 3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P < 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.
Adult↗
Clinicopathological characteristics of primary breast cancer in older geriatric women: a study of 39 Japanese patients over 80 years old.
The number of primary breast cancers occurring in elderly women is increasing in Japan. Optimization of treatment regimens in this age group requires precise evaluation of the biological aggressiveness of these tumors as well as the performance status and extent of tumor spread. In 39 breast cancer patients who were at least 80 years old, we examined several parameters; the form of surgical therapy, the lymph node status, presence or absence of distant metastases, the histological type and grade of atypia, and overexpression of the c-erbB-2 oncoprotein in the cancer cells. They were correlated with the clinical outcome of the patient. Of the 33 patients who underwent a mastectomy and axillary lymph node dissection, five died from cancer recurrence. Only one out of 22 patients without lymph node metastases died from cancer, while four out of the eight patients with metastases to three or more lymph nodes died from cancer recurrence within 2.7 years of surgery. The overall survival curves also differed between patients with low-risk histological tumors or grade 1 or 2 invasive ductal carcinoma and those with grade 3 invasive ductal/lobular carcinoma. Overexpression of c-erbB-2 also affected survival. Regional recurrence occurred in three out of the six patients for whom only lumpectomy or simple mastectomy was performed. These results indicate that, although primary breast cancer occurring in patients over 80 years old was largely of low-grade malignancy, patients with three or more lymph node metastases, invasive ductal/lobular carcinomas of grade 3, or c-erbB-2 overexpression frequently exhibited an aggressive clinical course.
Aged↗
Significance of basic fibroblast growth factor and fibroblast growth factor receptor protein expression in the formation of fibrotic focus in invasive ductal carcinoma of the breast.
A fibrotic focus (FF) is a scar-like area within invasive ductal carcinoma (IDC) of the breast, and has been shown to be a marker of high aggressiveness of IDC. In order to investigate the mechanism of FF formation in IDC, expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) was studied. One hundred and forty-nine IDCs were divided into solid tumors and scirrhous tumors. Immunohistochemistry was used to determine the expression of bFGF and FGFR proteins in both tumor cells and fibroblasts forming FF. Scirrhous tumors with FF showed a significantly higher frequency of bFGF protein expression than those without (P = 0.017), whereas, in solid tumors, the presence of FF was not significantly associated with the frequency of bFGF protein expression (P = 0.143). In addition, scirrhous tumors showed a significantly higher frequency of FGFR protein expression than solid tumors (P = 0.001). Among IDCs having FF and expressing bFGF protein, a significantly larger number of fibroblasts expressing FGFR protein within FF was observed in scirrhous tumors than in solid tumors (P = 0.016). The results of this study suggest that in scirrhous tumors the interaction between tumor cells and stromal fibroblasts plays an important role in the formation of FF, and that there is a paracrine mechanism between bFGF protein from tumor cells and FGFR protein in fibroblasts.
Adenocarcinoma, Scirrhous↗
S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: an immunohistochemical study.
S-100 protein, a dimer of S-100 alpha and S-100 beta subunits (S-100 alpha and S-100 beta), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. In the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three medullary) were analyzed immunohistochemically for the expression of S-100 protein, S-100 alpha, S-100 beta, and thyroglobulin. In papillary carcinoma, 188 lesions were studied and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for S-100 protein and S-100 alpha, respectively, according to type were: papillary, 96 and 99%; follicular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 75%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100 alpha expression than poorly differentiated lesions. S-100 alpha expression was weaker in follicular and undifferentiated carcinoma than in papillary carcinoma. Medullary carcinoma also expressed S-100 alpha. S-100 beta was positive in lesions that expressed S-100 alpha strongly. Expression of S-100 protein and S-100 alpha protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S-100 alpha, exists in thyroid follicular cells, that it exists in higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or undifferentiated lesions, and that S-100 protein, especially S-100 alpha, is a differentiation marker in carcinoma of thyroid follicular cell origin.
Adenocarcinoma, Follicular↗
'Ovarian-type' stroma of pancreatic mucinous cystic tumor expresses smooth muscle phenotype.
'Ovarian-type' stroma of nine mucinous cystic tumors (MCT) of the pancreas, six cystadenomas and three cystadenocarcinomas, were studied immunohistochemically. Most of the spindle cells of the 'ovarian-type' stroma were positive for smooth muscle actin and desmin, but were negative for S-100 protein, cytochrome P450 19 and CD34. Similar stroma with smooth muscle differentiation has been described in hepatobiliary MCT. Embryologic similarity between the pancreas and liver suggests a closely related origin of MCT in both organs.
Actins↗
High frequency of K-ras mutations in human colorectal hyperplastic polyps.
BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.
Adenoma↗
Arteriovenous hemangioma of the gallbladder: CT and pathologic findings.
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Gallbladder↗
Metastatic renal cell carcinoma to the gallbladder: color Doppler sonography and CT findings.
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Adult↗
Phonon bottleneck in self-formed InxGa1-xAs/GaAs quantum dots by electroluminescence and time-resolved photoluminescence.
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Journal Article↗
Primary malignant melanoma (clear cell sarcoma) of bone: report of a case arising in the ulna.
BACKGROUND: To the authors' knowledge, there has been no previous report of primary malignant melanoma of bone. METHODS: A 33-year-old woman presented with a tumorous lesion in the olecranon of the right ulna. The histologic diagnosis was malignant melanoma with close similarity to clear cell sarcoma. To exclude the possibility of malignant melanoma metastatic to the bone, clinical investigations including gallium 67-citrate scintigraphy, brain, chest, and abdominal computed tomography, and upper and lower gastrointestinal endoscopic examinations were performed. Conventional histopathologic, immunohistochemical, and electron microscopic studies were also performed. RESULTS: Clinical investigations showed no lesion suggestive of a primary melanoma other than that in the right ulna. Histologically, the tumor was comprised of polygonal or fusiform cells with clear or granular cytoplasm and vesicular nuclei containing one or two prominent nucleoli. The features were similar to those of clear cell sarcoma (malignant melanoma of soft parts). Fontana preparations and immunohistochemical staining for S-100 protein and HMB-45 (melanoma specific antigen) also revealed that the tumor cells had the characteristics of malignant melanoma. The patient has remained alive and well for more than 5 years after the initial treatment. CONCLUSIONS: The clinicopathologic findings in this case strongly suggested that the lesion was a primary malignant melanoma of bone. Therefore, this is the first report to indicate that malignant melanoma and related diseases can occur even in bone tissue.
Adult↗
An aggressive therapeutic approach to carcinoma of the body and tail of the pancreas.
BACKGROUND: Prognosis of patients with adenocarcinoma of the pancreatic body and tail is extremely poor. Anatomically, this part of the pancreas is thin, and cancerous invasion to the retropancreatic structures occurs easily. The majority of patients have residual tumor in the retroperitoneal tissues after conventional distal pancreatectomy. METHODS: Between 1962 and 1979, 10 patients with carcinoma of the pancreatic body underwent simple distal pancreatectomy. Between 1980 and 1990, 22 patients including 7 with distant metastasis underwent a more aggressive approach intended to achieve longer survival: distal pancreatectomy with extended dissection of the lymph nodes and adjacent structures, especially into the retropancreatic space. After 1984, intraoperative ŕadiation (IORT) by electron beam and chemotherapy by hepatic infusion plus systemic injection of mitomycin C (MMC) were added for 7 patients without distant metastasis. RESULTS: The 10 patients who underwent pancreatectomy between 1962 and 1979 all died within 20 months after their operations. Conversely, the patients treated with an aggressive approach between 1980 and 1990 survived longer; the 5-year survival rate for 15 patients without distant metastasis was 29%, though the 7 patients with distant metastasis died within 10 months of their operations. There were 4 long term survivors (> or = 5 years); 3 of whom received IORT and chemotherapy with MMC. Invasion to the retropancreatic soft tissues was present in 95% of the resected specimens from the 22 patients. However, invasion to the surgical margin at the posterior surface of the resected specimen was present in only 36% after extended resection of the retropancreatic structures. CONCLUSIONS: Survival improved for this disease after distal pancreatectomy with extended dissection, especially of the retropancreatic structures, adjuvant IORT, and chemotherapy had been performed.
Adenocarcinoma↗
CT diagnosis of intraductal papillary neoplasm of the pancreas in comparison with histopathologic findings.
CONCLUSION: The existence of excrescent nodules in the cystic component of intraductal papillary neoplasms (IPN) on computed tomography (CT) is useful for differentiating between malignant and benign lesions. BACKGROUND: We sought to evaluate the ability of CT to differentiate malignant from benign lesions in IPN of the pancreas. METHODS: CT findings in 20 cases of IPN (11 benign and 9 malignant lesions) were compared with histopathological findings from subsequent surgery. RESULTS: The size of the cystic portion on CT did not correlate with the malignant potential of the lesion. Seven (78%) of 9 malignant lesions had excrescent nodules on CT, whereas 1 (9%) of 11 benign lesions did.
Adenoma↗
Serous cystadenoma of the pancreas communicating with a pancreatic duct.
CONCLUSION: To differentiate serous cystadenoma from other cystic lesions communicating with the pancreatic duct, careful radiological examination is necessary. BACKGROUND: Communication between the cystic cavity and the pancreatic duct in an ordinary serous cystadenoma is uncommon, although it is not uncommon in other cystic lesions, such as pseudocyst, mucinous cystadenoma/adenocarcinoma, and intraductal papillary tumor. METHODS. A serous cystadenoma of the pancreas communicating with main pancreatic duct in a 76-yr-old male is reported. RESULTS: The communication was preoperatively demonstrated by endoscopic retrograde cholangiopancreatography and confirmed by histopathological examination of the resected specimen.
Aged↗
A retrospective analysis of different modalities for treatment of primary orbital non-Hodgkin's lymphomas.
We have reviewed 37 patients with primary orbital lymphoma, using the Ann Arbor criteria and the Working Formulation and its modification. Thirty-one patients had stage I disease, four stage II, one stage III and one stage IV. The male to female ratio was 2.7:1. There were 34 low-grade tumours (including 24 mantle zone) and three intermediate-grade. Patients were divided into three groups according to their primary treatment. Group 1: radiotherapy (17 cases); Group 2: surgery alone (13 cases); Group 3: chemotherapy (seven cases). Patients were followed up from 5 months to 24.3 years, with a mean and median of 7.6 and 6.2 years, respectively. The BMDP software package was used for survival estimation (Kaplan-Meier) and determination of prognostic variable (univariate Cox regression). Local relapse-free survival at 10 years was 100% in Group 1, 0% in Group 2 and 42% in Group 3 with a statistically significant difference (p < 0.01) in favour of radiotherapy. Statistically significant good prognostic features were: complete remission (CR) in response to initial treatment, primary radiotherapy and older age. For stage I cases, there was no difference in distant relapse-free survival in the three groups. The overall cause-specific survival for stage I patients at 10 years was 100% for each group and at 20 years was 100, 67 and 0% for Groups 1, 2 and 3. The difference between the primary radiotherapy and chemotherapy-treated groups was significant at the p = 0.08 level. Statistically significant prognostic factors were early stage, low-grade histology and primary radiotherapy. In one patient, ptosis and diplopia appeared after surgery. One case of glaucoma required enucleation, one patient suffered severe dry eye syndrome. All patients (11/11) in whom the lens received direct radiation developed cataracts of different degrees if follow-up was long enough. Cataract formation was prevented by adequate lens shielding. One patient in CR from a stage I low-grade tumour died from chemotherapy-induced marrow aplasia. Primary orbital lymphoma is an indolent, usually stage I disease, showing low to intermediate-grade histology. After biopsy the best treatment is 30 (low-grade) to 40 Gy (intermediate-grade) carefully planned, lens-sparing megavoltage radiation without adjuvant chemotherapy.
Adult↗
Effects of long term stimulation of ACTH and angiotensin II-secretions on the rat adrenal cortex.
In the rat adrenal cortex, aldosterone synthase cytochrome P450 (P450aldo), a mineralocorticoid synthesizing enzyme, localizes in the zona glomerulosa (zG), while cytochrome P45011 beta (P45011 beta), a glucocorticoid synthesizing enzyme, localizes in the zonae fasciculata-reticularis (zFR). In between zG and zF, a cell-layer which contains neither P450aldo nor P45011 beta is present, where replicating cells were abundant as judged by the incorporation of bromodeoxyuridine (BrdU) and/or by detecting PCNA in their nuclei. When plasma ACTH level of the rat was raised 3-fold for 2-3 weeks by the administration of metyrapone, a potent inhibitor of glucocorticoid formation, most of zG cells containing P450aldo disappeared, while zF cells with P45011 beta increased. Under the conditions, the cell-layer without P450aldo and P45011 beta became very thin, and replicating cells were mainly in the outermost portion of zF. When angiotensin II secretion was also stimulated for 2-3 weeks by feeding the rats on Na-deficient diet, the P450aldo-containing cells proliferated to form a thicker zG (7-8 cells-thick from 1-2), while the width of zF containing P45011 beta decreased slightly. Coincidently the cell-layer devoid of P450aldo and P45011 beta became thin, though slightly, and numbers of replicating cells significantly increased in and around the inner edge of the proliferated zG. When both ACTH and angiotensin II secretions were stimulated simultaneously, the cell-layer without P450aldo and P45011 beta almost disappeared and replicating cells were around the boundary of zG and zF. Based on these results we propose that the cell-layer between zG and zF devoid of P450aldo and P45011 beta is the stem cell layer of rat adrenal cortex.
Adrenal Cortex↗