Cyclin D1 expression as a prognostic parameter in papillary carcinoma of the thyroid

To determine whether ginsenoside-Rd ameliorates the renal injury induced by cephaloridine, the effect of cephaloridine was investigated in rats given ginsenoside-Rd preceding cephaloridine administration and in control rats given no ginsenoside-Rd. In control rats, blood, renal and urinary parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to cephaloridine injection, the activities of the antioxidation enzymes superoxide dismutase and catalase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. The urea nitrogen and creatinine levels in serum were decreased in rats given ginsenoside-Rd. Decreased urine volume, increased urinary osmotic pressure, and decreased urinary levels of glucose, protein, sodium and potassium demonstrated a protective action against the renal dysfunction caused by cephaloridine. In addition, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells exposed to cephaloridine.     

Combined determination of N-myc oncogene amplification and DNA ploidy in neuroblastoma. Complementary prognostic indicators

BACKGROUND: N-myc gene amplification is a well-established prognostic indicator in neuroblastoma. Flow cytometric analysis of nuclear DNA content has shown that an abnormal nuclear DNA content in neuroblastoma is associated with a better prognosis. Because some patients with N-myc unamplified tumors have a poor prognosis, factors other than N-myc amplification may play a role in determining the clinical behavior of neuroblastoma. In the current study, the authors correlated N-myc gene amplification and flow cytometric nuclear DNA content with respect to prognosis. METHODS: Forty-one patients with neuroblastoma, including 15 screened patients, served as subjects. The copy number of the N-myc gene was determined by Southern blot analysis. DNA ploidy analysis was done on nuclei isolated from formalin-fixed, paraffin-embedded blocks. RESULTS: Of 40 specimens of neuroblastoma, 7 involved tumors containing amplification of the N-myc gene and 33 did not; 13 specimens showed DNA diploidy, and 27 showed DNA aneuploidy (including 4 with DNA tetraploidy). The Kaplan-Meier survival analysis indicated a significantly better prognosis in patients with unamplified N-myc tumors compared with those with N-myc amplified tumors (87.3% versus 28.6%, P < 0.05) and in patients with DNA aneuploid tumors compared with those with DNA diploid tumors (96.3% versus 43.0%, P < 0.001). The difference in the survival of the two extreme combinations, (e.g., 25 with N-myc unamplified and DNA aneuploidy [4 tetraploidy] versus 5 with N-myc amplified and DNA diploidy) was more significant (96.0% versus 20.0%, P < 0.001) than any other combination. CONCLUSION: Evaluations of N-myc gene amplification and DNA ploidy are complementary, and the combined determination of these two factors may be one of the most powerful prognostic indicators in neuroblastoma.     

Immunohistochemical study of estrogen receptor and estradiol on papillary thyroid carcinoma in young patients

The Winnipeg Rh Laboratory has reviewed its experiences with maternal CW alloimmunization. From September 24, 1956, to March 31, 1992, 12 women with significant CW alloimmunization underwent 18 pregnancies. In 3 (4 pregnancies) the antibody, despite its strength, was 'naturally occurring' (i.e. there was no known exposure to CW-positive red cells). The remaining 9 women (14 pregnancies) had CW-positive husbands. Two had CW-negative babies and a third infant, probably CW negative, was stillborn and macerated at 43 weeks gestation. Eleven babies were CW positive and had hemolytic disease of the newborn (HDN), with antiglobulin-positive red cells. Five did not require treatment; 2 needed phototherapy only, and 4 (born between 1956 and 1963) required exchange transfusions. No anti-CW screening was carried out until 1977; thereafter it was sporadic, 11 of 51 screening red cells being CW positive in the 39-month period ending March 31st, 1992. From November 1, 1977, to March 31, 1992, 24 women (30 pregnancies, 31 conceptuses) with insignificant anti-CW alloantibodies were identified. Extrapolating these figures to the entire period from September 24, 1956, to March 31, 1992, we estimate that at least 430 women (at least 573 pregnancies) were CW alloimmunized, most of the antibodies being 'naturally occurring'. Only 2% of the conceptuses were CW positive and affected; none were severely affected. Anti-CW is relatively common, occurring in about 1 pregnant Manitoban woman in 1,100. On very rare occasions (11 times in Manitoba in 36 years and 5 months) anti-CW HDN occurs which, although not severe, may end in kernicterus with brain damage or neonatal death unless it is detected promptly and treated appropriately.     

Occurrence of papillary carcinoma in a hyperfunctioning thyroid nodule: report of a case and diagnostic considerations

HIV-infected patients commonly experience haematological disturbances including anemia, neutropenia or thrombocytopenia. Bone marrow failure may be caused by HIV itself, or by secondary involvement by opportunistic pathogens and malignancy. The need for multiple concomitant suppressive treatments may increase the risk of cytopenias. Strategy to reduce both anemia and neutropenia as well as to improve the haematological tolerance to myelotoxic agents have been developed by using haematological growth factors. So far, erythropoietin and granulocyte(macrophage) colony-stimulating factors have been successfully used in clinical trials including HIV-patients with either zidovudine-associated anemia or severe HIV or drug-induced neutropenia. However, according to the cost of these palliative approaches, there is a need for more reliable data showing that these growth factors could really have a major impact on the patient's compliance to therapy, reduction of hospitalization and infection rate and improvement of the overall survival.     

Description of a human papillary thyroid carcinoma cell line. Morphologic study and expression of tumoral markers

BACKGROUND: The establishment of cell lines from thyroid carcinomas can provide an in vitro model of oncogenesis. B-CPAP is a new cell line that has been obtained from a differentiated papillary thyroid carcinoma. The data presented give a broader characterization and expression of tumoral markers of this cell line and identify the differentiated functions that are preserved. METHODS: An ultrastructural study was performed to confirm the thyroid nature of the new cell line. The cellular markers (thyroglobulin, S100, neuron-specific enolase [NSE]) and the oncogenes (mutated p53, H-ras, c-myc, PTC, trk) were studied by immunohistochemistry, Southern blot, or in situ hybridization. RESULTS: The cells were of a differentiated ultrastructural thyroid type. All of the cells proved immunoreactive with antibodies specific to thyroglobulin, S100 proteins, NSE, and mutant p53 protein. Mutations of H-ras, PTC, and trk were not observed. The c-myc gene was not amplified. CONCLUSIONS: The cell line described in these data provides a suitable model for the study of thyroid carcinogenesis, given that the cells present thyroid characteristics, and metabolic disorders not previously found in such cell lines. In addition, the coexpression of S100 proteins and mutant p53 proteins in the cells should permit the study of the interaction between these two proteins.     

Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients

Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were estimated in 55 cancer patients and 25 control volunteers to evaluate their prognostic significance. Cancer patients comprised head and neck cancer (11), breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I-IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/- 71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001] cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39 cells/cumm. In cancer stages I through IV, these counts decreased significantly (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99 cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5% positive in stage II, and negative in stages III and IV. CIC of intermediate size were estimated by polyethylene glycol precipitation (PEG pptn) technique, which detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5 +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/- 44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which constitute the opposite polar end of CIC spectrum. LAI titers in control group were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6 +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001), respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable prognosis in cancer patients, and also precede clinical manifestation of increased tumor mass in vivo.     

Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma

Despite its predilection for multifocal growth and regional metastasis, papillary thyroid carcinoma (PTC) is a clinically indolent malignancy with an exceptionally favorable long-term prognosis. Together with the often striking inflammatory reaction present in PTC, its quiescent behavior has been suggested to reflect the activation of a tumor-induced immune response. To examine this possibility, we have studied the deposition of immunoglobulins and complement in PTC tissue. Samples from 70 cases of neoplastic and autoimmune thyroid diseases, including PTC (n = 41), follicular, anaplastic, and medullary carcinomas (n = 12), follicular adenoma (n = 6), Graves' disease (n = 8), and Hashimoto's thyroiditis (n = 3) were analyzed immunohistochemically. Cellular deposits of immunoglobulin G (IgG), particularly subclasses IgG1 and IgG4, and complement factors C3d, C4d, and C5 were shown in up to 80% of the PTC cases, whereas the other thyroid diseases studied showed little or no cellular deposition. Nonneoplastic tissue of PTC-containing thyroid glands (n = 22) lacked staining for IgG in 50% of the cases, and 82% were devoid of complement. The results suggest a tumor-specific immune response in PTC with activation of the classical complement cascade.     

Heterogeneity of DNA ploidy pattern in carcinoma of the gallbladder: primary and metastatic sites

There are few detailed reports on the heterogeneity of the nuclear DNA ploidy pattern in carcinoma of the gallbladder. We studied twelve autopsied cases who died of extended gallbladder carcinoma. Multiple samples were taken from the primary site (Pri), from direct invasion of the liver (Hinf), from hematogenous metastasis to the liver (H), from lymphatic metastasis (LN) and from peritoneal dissemination (P). The DNA ploidy pattern was investigated by image cytometry. Heterogeneity of the DNA ploidy pattern in Pri, Hinf, H, LN and P was found in 7/11, 2/10, 5/10, 2/6 and 3/6 cases, respectively. Aneuploidy was more frequently found in Hinf than at the Pri. The DNA index of Hinf was significantly higher than that of Pri. Several stemlines, with different quantities of DNA, were found in Pri. Most of these stemlines were also observed in other sites. These facts may suggest that polyclonal cancer cells rather than one cancer cell or monoclonal cancer cells of a Pri metastasize or infiltrate, and that various polyclonal cancer cells proliferate to different degrees under different circumstances.     

An analysis of lymphocyte subsets in the regional lymph nodes of patients with papillary thyroid carcinoma

Lymphocyte subsets in the lymph nodes regional to papillary thyroid carcinoma were determined using flow cytometry to ascertain the differences in local immunological responses between elderly and young patients. Lymph nodes from age-matched patients with benign thyroid tumors were used as controls. No significant alterations in lymphocyte subsets were observed in the lymph nodes from the young patients regardless of whether metastasis was present, whereas those from the elderly patients showed significant decreases in pan T cell (CD2+, CD3+) and cytotoxic T cell (CD8+, CD8+CD11b-) populations, and a significant increase in B cells (CD19+) compared with those from both the young patients and the age-matched controls. These results indicate that local immunological alterations occur in elderly patients with papillary thyroid carcinoma, and we believe that immunological changes are one of the clinical characteristics of this tumor.     

Functional adrenal cortical tumors in childhood: a study of ploidy, p53-protein and nucleolar organizer regions (AgNORs) as prognostic markers

The Washington State Patrol Crash Database and computerized hospitalization records for 1989-1993 were used to determine total hospital charges billed for motor vehicle collision injuries to drivers whose crash reports contained any indication of alcohol use. In this population-based study, total hospital charges were summed, and mean charges and lengths of stay were computed within alcohol use and insurance coverage status categories in an attempt to evaluate the hospital charges billed to public funding and private insurance. Of the total hospital charges for drivers with injuries from motor vehicle collisions for which a police-reported indicator of alcohol use status was available, 43% (U.S.$64.8 million) were for drivers who reportedly had been drinking. At the time of discharge, Medicaid was identified as the payor for 47% of these hospitalizations. The mean hospital charge billed per collision was greater for drinking (U.S.$18,258) than nondrinking drivers (U.S.$14,181). Drinking drivers also had longer hospital stays, even after adjustment for patient age, gender and injury severity. During this time in Washington state, the average annual amount billed at discharge for initial inpatient care of injuries to drivers who reportedly had been drinking at the time of the motor vehicle collision was U.S.$13 million. This includes only the amount assessed by the hospital at the time of discharge for treatment of the initial injury and does not include other related medical charges for rehabilitation or outpatient care, or for doctors' or laboratory fees. As increasing pressures of managed and capitated care lead to a shift of financial risk from the federal government and insurers to states and providers, the financial burden of specific, potentially preventable conditions such as this will receive greater attention.     

Preoperative CEA level: a prognostic test in patients with colorectal carcinoma

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were evaluated in 42 patients with colorectal carcinoma. Preoperative CEA values correlated inversely with survival at a statistically significant level and provided prognostic information not available by pathologic staging. Postoperative plasma CEA can accurately predict recurrent disease and may, when serial values are elevated, serve as an indication for a second-look procedure.     

Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content

Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.     

Giant cell tumor of bone: a clinicopathologic study of prognostic factors

Symptomatic autonomic neuropathy is a devastating occasional complication of diabetes mellitus, especially Type 1. Although the full-blown clinical syndrome is not common, dysfunction of the autonomic nerves is detectable in up to 40% of Type 1 diabetic patients but its aetiopathogenesis is poorly understood. There is evidence to suggest that the damage to the autonomic nerves may be immune-mediated. This evidence is reviewed in the following article.     

Autonomous thyroid adenoma, papillary thyroid carcinoma, and ectopic parathyroid adenoma in a patient with primary hyperparathyroidism and a nontoxic multinodular goiter

OBJECTIVE: To discuss the method for nipple-areola preserved mastectomy with one-stage breast reconstruction in cancer surgery. METHODS: Because of the merits of sufficient blood supply and plasticity of rectus abdominis musculocutaneous flap, we used one-stage breast reconstruction after modified radical mastectomy. The incision line was covered and the nipple-areola was preserved. The reconstructed breast was naturally in contour. RESULTS: 21 cases were treated from 1990 to 1995, and 18 of them received horizontal-rhombus shaped rectus abdominis musculocutaneous flaps and 3 longitudinal-rhombus flaps for breast reconstruction. Nipple-areola was preserved in 16 cases. Objective evaluation after operation showed that the excellent and satisfied rate reached to 90.5%; and subjective evaluation showed that the excellent and satisfied rate reached to 95.2%. Thirteen cases have been followed up for 3 years, and 9 for 5 years. Three-year survival rate was 100% (13/13), and 5-year 88.9% (8/9). CONCLUSION: The method is recommendable for the treatment of stage I-II breast cancer.     

Neural networks as a prognostic tool for patients with non-small cell carcinoma of the lung

Patients with non-small cell carcinoma of the lung (NSCLC) have a poor prognosis (64 and 41% survival rates in Stages I and II). It is currently not possible to predict which patients with Stage I or II NSCLC will survive the disease. Sixty-seven patients with NSCLC, including 49 patients with Stage I NSCLC and 18 with Stage II disease (11 with squamous cell carcinomas, 35 with adenocarcinomas, and 21 with large cell carcinomas) were treated with lobectomy and followed for a minimum of 5 years. The tumors were studied with DNA flow cytometry and quantitative immunocytochemical studies for proliferation cell nuclear antigen, p53 protein, and MIB-1. The data were analyzed with backpropagation neural networks, univariate analysis of variance, the Kaplan-Meier survival method, and Cox proportional hazards model. The dependent variables were "free of disease" and "recurrence or dead from disease." Twenty neural network models were trained, using all cases but one, after 1883 to 2000 training cycles. At 5 years, 30 patients were free of disease and 37 were dead or had recurrence. Proliferating cell nuclear antigen was the only statistically significant prognostic factor by univariate analysis of variance and Cox proportional hazards analysis. The S phase was statistically significant by univariate analysis of variance (P <.05). All of the 20 models classified the test cases correctly. Study with backpropagation neural networks using multiple prognostic features from patients with NSCLC suggests that this technology might be useful for prediction of survival. This preliminary study must be validated with data from a larger group of patients with NSCLC before its clinical adequacy is established.     

The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of alpha-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. RESULTS: When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI < or =18% and AFP < or =200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS: The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC.     

Morphology of incipient mesoderm formation in the rabbit embryo: a light- and retrospective electron-microscopic study

Mesoderm formation is a hallmark of vertebrate gastrulation and, at the same time, one of the prime examples for epithelio-mesenchymal transformation. Recent advances in experimental embryology and molecular biology have clarified the role of growth factors and genes in this process; however, its microscopic anatomy in higher vertebrates is still far from clear. Therefore, the present study describes the morphology of mesoderm formation in the rabbit embryo, a species which may be representative for both the avian and the mammalian embryo in this respect. Serial semithin sections were correlated with topographical landmarks in surface views of embryonic discs at 6.4, 6.5, and 6.6 days post conceptionem, and selected semithin sections were reembedded for ultrastructural analysis. Mesoderm cells are shown to be generated by ingression of bottle-shaped epiblast cells in the area of the posterior node and the primitive streak. Here, basal endocytotic pits and absence or discontinuity of the basal lamina are taken as suggestive evidence for specific removal of extracellular matrix material. Within the bottle-shaped cells most organelles are concentrated in a narrow apical neck which will subsequently constitute the 'trailing end' of the ingressing mesoderm cells. These features support the assumption that most principles of epithelio-mesenchymal transformation seen during primary mesenchyme formation in the sea urchin also apply to mesoderm formation in vertebrates. However, transient tripartite zonula adherens-type junctions are formed apically between ingressing mesoderm cells and the neighboring epiblast cells. They are interpreted here as being responsible for maintaining supracellular integrity of the embryonic disc during the shedding of mesoderm cells in the amniote embryo.     

Polymyalgia rheumatica and temporal arteritis: a retrospective study of 111 patients

There is no unanimity as to whether polymyalgia rheumatica (PMR) and temporal arteritis (TA) are two distinct diseases or different features of one disease. The objective of this study was to assess the value of histological findings of temporal artery biopsy and the efficacy and complications of drug therapy as well as the frequency of malignancies. It was carried out as a retrospective follow-up study. One hundred eleven patients (89 PMR, 14 TA and 8 PMR+TA) were studied. In 56 patients with PMR a temporal artery biopsy was performed; in none of these biopsies was active arteritis found. Of the 19 patients with TA or PMR+TA, where a temporal artery biopsy was performed, arteritis was found in 15 patients. Reactivation occurred in 27 patients: 4 patients using NSAIDs and 23 patients using corticosteroids. Side effect of the medication included vertebral compression in 10 patients, most of whom were using corticosteroids. Malignancies were diagnosed in 12 of the 111 patients. Most malignancies were diagnosed long before or after the diagnosis of PMR. In case of a PMR diagnosed by the clinician a biopsy of the temporal artery has no value, while the yield of this diagnostic procedure is high in TA. Reactivation was seen quite often and warrants a prolonged period of medical treatment.