Revisiting the prognostic role of gallium scintigraphy in low-grade Non-Hodgkin’s lymphoma

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin’s lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the ⁶⁷Ga uptake by the tumour, and to establish the contribution of ⁶⁷Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic ⁶⁷Ga score at diagnosis. In addition to ⁶⁷Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. ⁶⁷Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1–146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27.4%±14.9% (mean ±SD) in the former and 8.9%±7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that ⁶⁷Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables. Received 1 May and in revised form 6 August 1997     

Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection

Lymph node (LN) metastases represent the most important negative prognostic factor in squamous cell carcinoma (SCC) of the oral cavity, even though controversies still exist regarding their management. The aim of this study was to retrospectively analyze our experience in surgical management of SCC of the oral cavity with particular focus on the prevalence and localization of lymph nodal metastases and recurrences. The clinical records of 89 consecutive patients treated from 1983 to 2002 by concomitant surgery on both the T and N sites, excluding those undergoing salvage surgery, were reviewed. A total of 119 neck dissections (ND) were performed. Survival outcomes were calculated by the Kaplan–Meier method, while univariate comparisons by the log-rank and non-parametric tests were performed between different groups of patients. Five-year overall and determinate survivals were 50 and 57%, respectively. LN metastases were observed in 52% (56% of these showing extracapsular spread) and their presence strongly correlated with determinate survival (p < 0.0001). The prevalence of clinical and occult nodal disease was not related to the pT status. Neck levels II (59%) and I (56%) were most frequently involved. Metastases to level IV accounted for 15% of positive LN, even though 28% of them turned out to be skip metastases. Five neck recurrences were observed, only one of which was salvaged by surgery. The high prevalence of clinical and occult LN metastases in this setting suggests that ND should be performed on a nearly routine basis, even for lesions with a low-T category and a cN0 neck. Moreover, ND should always encompass level IV due to the possibility of skip metastases, particularly in tumors involving the oral tongue. In patients with a cN+ neck, levels from I to V should be addressed, particularly in the presence of metastases at levels III and IV.     

Infection of mesothelial cells with human herpes virus 8 in human immunodeficiency virus-infected patients with Kaposi's sarcoma, Castleman's disease, and recurrent pleural effusions.

Recurrent pleural effusions are common complications of hospitalized patients with human immunodeficiency virus (HIV) infection and may pose difficult diagnostic dilemmas. A common cause of recurrent pleural effusions in up to 30% of HIV-seropositive patients is pulmonary involvement by Kaposi's sarcoma, a human herpesvirus 8 (HHV 8)-related neoplasm. The pathogenesis of these effusions is unclear. These recurrent effusions, although benign, have shown significant mesothelial atypia/reactive changes of uncertain etiology. We attempted to evaluate these effusions morphologically and molecularly for the presence of HHV 8, with particular attention to mesothelial cells. All recurrent pleural effusions, as defined by any effusion tapped for cytological examination on more than two occasions, in HIV-positive patients at the National Institutes of Health were examined from 1998 to the present. Cases were stratified according to patients with and without histologically confirmed HHV 8 disease manifestations. Five patients with HHV 8 diseases (four with disseminated Kaposi's sarcoma and one with Castleman's disease) were identified. As a control group, five effusions from HIV-seropositive patients without known HHV 8-related diseases were identified. Cytological examination of effusions in patients with HHV 8-related diseases demonstrated atypical/markedly reactive mesothelial cells accompanied by a polymorphous background of lymphocytes. Molecular studies for B- and T-cell clonality in microdissected whole samples showed no definitive clones in these cases. Conversely, polymerase chain reaction (PCR) studies for the HHV 8 virus was positive in these samples. PCR studies on pure populations of microdissected mesothelial cells from the HHV 8-related effusions were positive for HHV 8 sequences, whereas those from HIV patients with non-HHV 8 related diseases were negative. Immunohistochemistry for HHV 8 (monoclonal antibody to latent nuclear antigen (LNA-1; ORF-73) on cellblock material demonstrated scattered positive mesothelial cells in three of the five cases of HHV 8-associated effusions. HHV 8 has been recently implicated in the pathogenesis of Kaposi's sarcoma and primary effusion lymphoma. Mesothelial cells in recurrent pleural effusions from patients with Kaposi's sarcoma and Castleman's disease appear to be infected with HHV 8. Additional studies need to be done to define the role of mesothelial cell infection in the pathogenesis of these HHV 8-associated effusions and define the prognostic significance.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Drinking History Is Related to Persistent Blood Pressure Dysregulation in Postwithdrawal Alcoholics

We have previously demonstrated that alcoholics with transitory (< 72 hr) elevations in blood pressure (BP) during withdrawal continue to show residual cardiovascular dysregulation up to 4 weeks of abstinence. The present study replicates and extends these findings. Alcoholic inpatients were divided into three subgroups ( ns = 14) based on BP during the first 72 hr of withdrawal: transitory hypertensives (tHTs; BP > 160/95 mm Hg), transitory borderline hypertensives (tBHs; 140/90 BP < 160/95), and normotensives (NTs; all BPs < 140/90). All patients had normal resting pressures after 72 hr of withdrawal. At 3–4 weeks postadmission, the alcoholics and 14 nonalcoholic controls (CONTs) were tested at rest and during a 5-min handgrip task. The tHTs showed an exaggerated systolic and diastolic BP response to handgrip compared with NTs and CONTs, with tBHs intermediate ( ps < 0.05). Drinking history showed the tHTs had the highest reported level of alcohol consumption and severity of withdrawal symptoms ( ps < 0.05). Regression analyses indicated that consumption of hard liquor was the variable most predictive of admission BPs; further, parental history of hypertension potentiated this relationship for systolic BP. Age and consumption of nicotine and caffeine were not significant predictors of admission BP. The results suggest a persistent cardiovascular dysregulation in alcoholics showing transient hypertensive withdrawal BPs. These alcoholics may be at increased risk for future alcohol-related cardiovascular disorder.     

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.     

In vivo measurements of fibrin formation and degradation in nephrotic patients

Summary Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radio-immunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P<0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis “in vivo.” A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64,P<0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.