NF-kappa B nuclear localization and its prognostic significance in prostate cancer.

OBJECTIVE: To detect the subcellular localization of NF-kappa B (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappa B localization alone, or combined with the histological grade, can be used to predict patient outcome. PATIENTS AND METHODS: Prostate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappa B was visualized by immunohistochemistry using an anti-p65 antibody. RESULTS: The NF-kappa B subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappa B was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappa B was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappa B nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappa B subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappa B) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappa B; P = 0.004). CONCLUSION: NF-kappa B is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappa B as a prognostic factor.

The value of clonality in the diagnosis and follow-up of patients with cutaneous T-cell infiltrates.

The diagnosis of early stages of cutaneous T-cell lymphoma (CTCL) is often difficult, especially for lesions that are at the borderline between reactive and neoplastic skin T-cell infiltrates. T-cell monoclonality in these lesions is considered by some to be an important prognostic factor of neoplastic evolution, whereas others claim that clonality can also be found in benign skin infiltrates and is therefore of limited diagnostic value. To address this controversy, the authors analyzed retrospectively eight patients with lymphocytic skin lesions who progressed to CTCL, and three patients with recurrent T-cell lymphocytic infiltrates who had not developed CTCL. From a total of 65 biopsies of eight progressing patients, 32 were diagnosed as histologically malignant and 33 were diagnosed as benign or borderline. The authors found clonality by either polymerase chain reaction or Southern blot analysis in 88% of malignant and in 79% of nonmalignant lesions. None of the 37 biopsies of non-progressing patients was clonal. These results indicate strongly that the presence of monoclonality in T-cell skin infiltrates is related closely to the risk of developing CTCL. The value of clonality as a marker of malignancy is supported by the absence of T-cell clonal populations in all infiltrates from patients who had not progressed to lymphoma.

Infrarenal aortic stenosis: value of stent placement after percutaneous transluminal angioplasty failure.

PURPOSE: To evaluate the long-term clinical and hemodynamic effectiveness of aortic stent placement in cases of failure of intended infrarenal percutaneous transluminal aortic angioplasty (PTAA). MATERIALS AND METHODS: Fifty-three patients who underwent technically successful PTAA were compared with 24 patients who underwent aortic stent placement because of PTAA failure (19 patients) or ulcerated lesions (five patients) that otherwise would have been treated surgically because of the embolization hazard associated with PTAA alone. Clinical patency was defined as the absence or improvement of symptoms after the intervention. Hemodynamic patency was defined as a normal Doppler waveform in the common femoral arteries, an ankle-brachial index greater than 0.95, or the absence of a thigh-brachial pressure gradient. RESULTS: Three-year clinical and hemodynamic patency rates, respectively, were 85% and 79% for PTAA and 69% and 43% for aortic stent placement. No morbidity was encountered. With use of the Cox proportional hazards model, two significant risk factors were retained for restenosis: unchanged smoking habit (P =.04) and small dilatation diameter (P =.001). Aortic stent placement, performed in patients with a smaller aortic diameter (10.3 vs. 12.7 mm for PTAA), appeared to be a predictive factor for restenosis by using univariate analysis. By using the Cox proportional hazards model, however, the restenosis rates after PTAA and aortic stent placement were not significantly different. CONCLUSION: When aortic diameter is taken into consideration, there is no evidence that clinical outcome after secondary aortic stent placement would be poorer than technically successful PTAA.

Catheter-assisted totally thoracoscopic coronary artery bypass grafting: a feasibility study.

BACKGROUND: The purpose of this study is to examine the feasibility of performing totally thoracoscopic internal mammary-to-coronary artery bypass grafting with the assistance of radiologically guided catheter intervention. METHODS: Fourteen dogs were subjected to mobilization of the internal mammary artery and anastomosis of it to the left anterior descending coronary artery over an angiographic catheter inserted into the internal mammary artery under fluoroscopy. The anastomosis was completed over the catheter using sutures and the application of fibrin glue. Eight animals underwent the anastomosis after their sacrifice. The other 6 animals were put on closed chest cardiopulmonary bypass and had their anastomosis done after intraaortic balloon occlusion and cardioplegic arrest of the heart. All animals had an angiographic and pathologic examination at the completion of the anastomosis. RESULTS: Anastomosis was completed in all dogs. Three anastomoses leaked and two were noted to be stenosed at completion of the anastomosis. One leak was sealed by application of fibrin glue. Both stenotic anastomoses were caused by suturing of the back wall when a short angiographic catheter could not be positioned across the anastomosis. CONCLUSIONS: Minimally invasive totally thoracoscopic mammary-to-coronary artery bypass grafting with catheter assistance is feasible. Technical improvement and appropriate instrumentation are required to minimize anastomotic failure.

Human immunodeficiency virus-infected multinucleated histiocytes in oropharyngeal lymphoid tissues from two asymptomatic patients.

Human immunodeficiency virus (HIV)-infected multinucleated giant cells previously were detected only in the central nervous system of HIV-positive patients. Reported here are the first cases in which such infected cells were observed outside the central nervous system, in the oropharyngeal lymphoid tissues. Tonsils and adenoids were removed individually from two asymptomatic homosexual men. Follicular hyperplasia and many interfollicular multinucleated giant cells most often in contact with or in close proximity of the mucous membrane were seen. The latter were positive for lysozyme, alpha-1 anti-chymotrypsin, OKM1, and S-100 protein in accordance with a histiocytic origin. In situ hybridization with an HIV envelope-specific RNA probe demonstrated the presence of viral RNA in these multinucleated giant cells. These findings support the role of peripheral histiocytes as a primary virus reservoir early in the disease. They also underline the potential role of oropharyngeal tissue as a primary target in some cases.

Immunological distinction of ovine follitropin agonist and antagonist.

The presence of antennary carbohydrate structure(s) in ovine follitropin is required for full biologic activity. In order to explore the biochemical basis for the conversion of the glycosylated agonist form of the hormone into one that is antagonistic in nature when it is deglycosylated, we have produced antisera in rabbits to these preparations. All antisera produced in rabbits against deglycosylated ovine follitropin (DG-oFSH) (antagonist) contained antibodies that were specific to the deglycosylated hormones with the native hormones showing weak and non-parallel cross-reaction (less than 10%) but with rabbit antibodies to the native hormone the DG hormone, which is an antagonist, was fully reactive. Using oFSH, asialo-FSH (A-FSH), and DG-oFSH we have shown that removal of sugars internal to sialic acid is required to produce these specific antibodies. This is in complete agreement with the observation that extensive deglycosylation of these hormones is necessary to induce changes in biological activity at the cellular level. By affinity chromatography on divinylsulfonyl Sepharose immobilized oFSH, antibodies that recognize both agonist/antagonist could be separated from immunoglobulins that preferentially bound the labeled antagonist. Based on these data, we suggest that chemical deglycosylation may result in changes in antigenic structure of follitropin by generation of new determinants and thus specific antibodies become available for distinguishing the agonistic and antagonistic forms of the hormone.

Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases.

We studied the morphologic and immunologic features of 29 cases of primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum. The patients ranged in age from 15 to 73 years, with a median of 32 years. The mean age for the 11 men (50 years) was significantly higher than that for the 18 women (32 years) (p less than 0.05). All had diffuse large cell lymphomas (six immunoblastic, 14 large cell not otherwise specified, six large cell noncleaved, one large cell cleaved, and two not subclassifiable). Sclerosis was prominent in 11 cases, none of them immunoblastic, and did not correlate with superior vena cava syndrome. The mean age (54 years) of patients with immunoblastic lymphomas was higher than that for patients with other subtypes (35 years) (p less than 0.02). Frozen-section immunoperoxidase staining disclosed monotypic immunoglobulin in 13 cases, with a high frequency of heavy-chain class switching (seven IgG, two IgA, four IgM). Sixteen cases were immunoglobulin negative; 14 of 15 cases expressed B-lineage antigens, and none expressed T-lineage antigens. Three of four cases showed immunoglobulin heavy- or light-chain gene rearrangement by the Southern blot technique. None showed rearrangement of the T-cell receptor beta-chain-gene constant region. There was no correlation between immunophenotype and morphologic subtype. The immunoglobulin-negative group was predominantly female (13 of 16 cases; p less than 0.02), and younger (mean age, 34 years versus 44 years; p = NS) than the immunoglobulin-positive group; however, the difference in age was not statistically significant. The actuarial 5-year survival was 57%, and there was no correlation between survival and either histologic subtype or immunophenotype. Mediastinal large cell lymphoma is a B-cell tumor, which frequently lacks immunoglobulin, may be primary in the thymus, has a predilection for young women, and can be cured with aggressive therapy.

Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene.

Transgenic mice carrying the activated c-neu oncogene under the control of the mouse mammary tumor virus (MMTV) long terminal repeat were produced. Epithelial hyperplasia of epididymis, seminal vesicles, and salivary glands, and dysplasia of harderian glands, were induced. Moreover, in females of our four lines, independent but multiple mammary tumors arose asynchronously, between 5 and 10 months of age, as stochastic events. Histologically, poorly differentiated adenocarcinomas, with intratumor necrosis and calcifications, arose adjacent to morphologically normal epithelium. High transgene expression was detected in all mammary tumors tested and in normal mammary glands before the appearance of the tumors. Together these results suggest that the expression of the activated c-neu oncogene was necessary but not sufficient to induce malignant transformation of the mammary epithelial cells. These tumors appear to be an adequate model for human breast cancers overexpressing c-neu.

Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy.

Thirty adults with large cell lymphoma predominantly localized to the mediastinum diagnosed at the Massachusetts General Hospital between 1976 and 1985 were identified. The median age of the 20 females and 10 males was 34 years. All but one presented with symptoms due to an enlarging mediastinal mass, which was localized in 22 patients (73%) and exceeded 10 cm in maximal diameter in 65%. Superior vena cava syndrome and large pleural and pericardial effusions were common. Employing CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) and consolidation radiation therapy in most cases, 80% achieved a complete remission and 59% survive failure-free at 5 years by actuarial calculation. The size of the mediastinal mass adversely affected failure-free survival (89% vs. 40%, P less than 0.05). No other pretreatment risk factor predicted outcome, but more intense chemotherapy was associated with improved survival (P = 0.035). Large cell mediastinal lymphoma is a locally invasive, often bulky malignancy with a predilection for young women; disease of low or moderate bulk is curable with full dose CHOP chemotherapy and consolidation radiation, but bulky disease requires more aggressive treatment.

Drug disposition in patients with HBsAg-positive chronic liver disease.

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (-31%) and in the clearance of antipyrine (-53%), lidocaine (-49%), and ICG (-54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.

Sonographic appearances of the wall of ovarian dermoid cysts.

A review of the sonograms of 25 patients with proven ovarian benign cystic teratomas was undertaken to study the appearance of the tumor wall. It was partially or completely identified in 12 (48%), being most often thin and hypoechoic, relative to the more echogenic contents of the tumor and of the surrounding tissues. In one patient the dermoid cyst demonstrated a circumferential hyperechoic wall due to a thick layer of adipose tissue. This latter appearance is most specific but is rarely seen in dermoid tumors.

Mucosal diaphragm and enteroliths of the small bowel causing obstruction in an adult.

A case of an ileal mucosal diaphragm with enteroliths causing obstruction in a 67-year-old man is reported. The distal site of the mucosal diaphragm, its relative patency, and the late formation of enteroliths, are thought to be the reasons for the delayed clinical manifestations of intestinal obstruction leading to the diagnosis of the abnormality.