Prognostic and predictive value of plasma D-dimer levels in patients with small-cell lung cancer.

BACKGROUND: To investigate the predictive value of plasma D-dimer levels for short-term therapeutic effect and progression-free survival (PFS) in patients with small-cell lung cancer (SCLC); and to analyze the correlation between baseline plasma D-dimer levels and other clinicopathological features. The aim of the study was to investigate whether the levels of plasma D-dimer could serve as a predictive and prognostic factor in patients with SCLC. METHODS: A retrospective review of the clinicopathological data of 160 patients with pathologically confirmed SCLC, who were treated at the Department of Thoracic Oncology of Tianjin Medical University Tumor Institute and Hospital between June 2011 and June 2016, was performed. At the same time, we collected 100 patients with benign pulmonary diseases as a control group. The correlations between baseline plasma D-dimer levels and other clinical features, therapeutic effect and PFS were analyzed statistically. RESULTS: The level of plasma D-dimer in patients with SCLC was significantly higher than that of patients with benign pulmonary diseases (P = 0.001). The PFS of patients with elevated D-dimer levels before therapy were significantly shorter than that of patients with normal D-dimer levels (6.0 versus 7.5 months, P = 0.013). The patients whose plasma D-dimer level always (before and after treatment) in the normal range have the best prognosis, and continuously elevated D-dimer carried out a poor prognosis (8.0 versus 5.0 months). According to multivariate analysis, elevated D-dimer level was confirmed to be an independent prognostic factor for worse survival (P = 0.029). The level of D-dimer was associated with tumor stage, the level of neuron-specific enolase, the presence of distant metastasis, hyponatremia, and the Karnofsky performance status score; and levels decreased when therapy was effective, but increased when the disease progressed. CONCLUSIONS: High levels of baseline plasma D-dimer may indicate advanced disease stage and poor prognosis. Therefore, plasma D-dimer levels could serve as a predictive and prognostic factor in patients with SCLC.

Thrombocytosis is associated with Mycobacterium tuberculosis infection and positive acid-fast stains in granulomas.

Mycobacterium tuberculosis infection is associated with thrombocytosis. We sought to determine if this information might be valuable in evaluating granulomas using acid-fast stains (AFS). Fifty-eight patients with culture-confirmed M tuberculosis infection were compared with 75 patients with atypical mycobacterial infection and 48 patients negative for mycobacteria. Thrombocytosis (platelet count >360 × 10(3)/µL [360 × 10(9)/L]) was significantly more common in patients with M tuberculosis (50%) than those with either atypical mycobacterial infection (12%) or negative for mycobacteria (4%, P < .001 for each). In 67 patients, histologic evaluation of tissue samples showed granulomatous inflammation; 37 (55%) had positive AFS results. Of 19 patients with thrombocytosis, 16 (84%) had a positive AFS result compared with 21 (44%) of 48 without thrombocytosis (P = .003). Fifteen of 16 M tuberculosis cases with thrombocytosis had positive AFS findings on histologic evaluation; the single negative case had a platelet count of 362 × 10(3)/µL (362 × 10(9)/L). However, 3 of these cases of positive results on staining were initially diagnosed as negative and only recognized as positive on review. We conclude that patients whose specimens were sent for mycobacterial culture and thrombocytosis had an increased risk for M tuberculosis. Patients with granulomas and thrombocytosis are more likely to have a positive AFS result usually showing M tuberculosis. Finally, patients with initially negative AFS results and thrombocytosis deserve to have additional evaluation of the AFS specimens.

[Molecular mechanisms of formation of blood eosinophilia under pulmonary tuberculosis].

Molecular factors of pathogenesis of the eosinophilic blood reaction under pulmonary tuberculosis are analyzed in the article. It has been established that the key cytokine providing the development of hemic eosinophilia in patients with pulmonary tuberculosis is IL-5. IL-5 plasma concentration turned out to be increased only in patients with eosinophilia. Increase of eotaxin was determined in patients with tuberculosis despite of the presense of eosinophilia. One-directional nature of the defined changes in eotaxin concentration might be explained by dual properties of this chemokine: on the one hand, eotaxin mediates long-term presence of eosinophils in blood; on the other hand, it initiates the process of adhesion of eosinophilic leucocytes to vascular endothelium with their further migration to the focus of granulomatous inflammation. The established increase in number of IL-5R-positive eosinophils presents one more mechanism which explains the basis of long-term presence of eosinophils in peripheral blood in patients with pulmonary tuberculosis.

Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis.

Vascular endothelial growth factor (VEGF) is a potent angiogenesis mediator. Scant reports are available defining the role of VEGF in active and inactive tubercular meningitis (TBM) with no studies on brain tuberculoma. We quantified VEGF levels by enzyme linked immunoassay (ELISA) in cerebrospinal fluid (CSF) and serum in 20 cases each with active and inactive TBM as well as 22 cases of intraparenchymal tuberculoma. VEGF expression and microvessel angiogenesis quantification was done in 7 cases where tuberculomas were excised. Significantly increased VEGF levels in CSF were found in active TBM cases (106.0+/-50.0 pg/ml) compared to inactive TBM cases (14.7+/-10.0 pg/ml) (p<0.001). Mean serum VEGF levels in active TBM, inactive TBM and tuberculoma were 694.93+/-820.66 pg/ml, 499.61+/-238.33 pg/ml and 541.0+/-389.0 pg/ml, respectively. Immunohistochemical staining of excised tuberculoma demonstrated high expression of VEGF in granulomatous areas with intense positivity in inflammatory mononuclear cells, Langhan's giant cells as well as reactive astrocytes and fibrocytes. A strong positive correlation was observed between microvessel density and VEGF expression. Serial decrease in serum VEGF levels was observed with increasing duration of therapy in tuberculoma. We conclude that increased CSF and serum VEGF levels are a measure of activity of the disease in neurotuberculosis and its gradual decrease over a period of time is probably an indicator of therapeutic response.

Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis.

A 48-yr-old female presented with a 1-yr history of pain in the hypochondrium and epigastrium. All routine investigations and computed tomography (CT) of the abdomen were done. CT findings revealed a well-defined cystic mass in the right ovary, and ascitis with features suggestive of secondaries over the omentum and peritoneal surface. The serum CA125 was 1255 U/mL (normal range 0-35 U/mL), which was indicative of ovarian malignancy. An exploratory laparotomy was performed. Histopathological examination of organs revealed the presence of granuloma. The patient was advised to undergo antitubercular treatment (ATT) and follow-up every month. After 1 mo of ATT, the CA125 level came down to 42 U/mL, which was near normal. As tuberculosis requires only a conservative management, we suggest that in cases of abdominopelvic mass with or without ascitis, high serum CA125 should always raise a suspicion of tuberculosis and a laparoscopy combined with peritoneal biopsy should be performed to confirm the diagnosis. This will prevent unnecessary laparotomies. Moreover, serum CA125 can be used to monitor the response of disease to antitubercular treatment.

Diagnostic utility of estimation of mycobacterial antigen A60 specific immunoglobulins in serum and CSF in adult neurotuberculosis.

An ELISA assay based on mycobacterial antigen A60 (Anda, Biologicals France) was used to detect specific immunoglobulins (IgM, IgA and IgG) in 48 cases of adult neurotuberculosis (24 TBM; 24 Tuberculoma) and in 48 controls (24 diseased controls; 24 healthy controls). Serum was analysed in all the subjects whereas CSF was assayed only in TBM cases and diseased controls. The cut off values used for IgM, IgG and IgA in this study were 1.500 ODI (optical density index) at 1:100 dil, 250 units/ml and 150units/ml respectively in serum; and 1.500 ODI at 1:10 dil, 10 units/ml and 10 units/ml respectively in CSF. The mean titres of all three antibodies were found to be significantly higher in cases as compared to controls. In cases of TBM, in serum, the percentage positivity for IgM, IgG, IgA and combination of IgG or IgA were 41.67, 87.50 87.50 and 95.83 respectively. The corresponding figures in CSF were 62.50, 75.0, 66.67 and 79.16 for IgM, IgG, IgA and 'IgA or IgM' respectively. In tuberculoma cases, in serum, the figures were 37.50, 75.0, 75.0 and 83.33 respectively. Overall, a high sensitivity and specificity were obtained in cases of TBM (Serum: ST = 95.83%: SP = 87.50%; CSF ST = 79.16%. SP = 100%) and Tuberculoma cases (serum: ST = 83.33% SP = 87.50%) employing the combined antibody estimations.

Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report.

Approximately 34 cases of intracranial tuberculomas with paradoxical response to antituberculous chemotherapy have been documented worldwide. In most of the previously reported cases an associated tuberculous meningitis was reported. The majority of these patients were children or young adults, who had inoperable intracranial tuberculomas located in high risk regions that developed a few weeks or months after the start of an appropriate chemotherapy. Fifty-three percent of the patients recovered completely, 37% improved with mild neurological defects and 10% died. It is interesting that these intracranial tuberculomas developed or enlarged at a stage when systemic tuberculosis was being treated successfully. A recent experience with these potentially curable tumors of the central nervous system is reported. The literature is reviewed, and diagnostic and therapeutic considerations are discussed. The possible immunological mechanisms of this phenomenon are analyzed. In conclusion, patients who are suspected to have a CNS-tuberculosis should receive a prolonged (12-30 months) course of effective antituberculous therapy. The evidence of new intracranial tuberculomas or the expansion of older existing lesions does not indicate the need to change the antituberculous drug program. In such cases systemic dexamethasone as adjuvant therapy for 4 to 8 weeks is worthwhile and effective. Surgical intervention may be necessary in situations with acute complications of CNS tuberculosis, such as shunting procedures for the treatment of hydrocephalus. When the diagnosis is not ensured and there is no response to therapy within 8 weeks, a stereotactic biopsy on a suspected tuberculoma could be performed. If the largest lesion is not located in high risk deep regions of the brain, it could be totally removed surgically. With this combined management, a satisfactory outcome can be obtained in the majority of cases.

Multiple intracranial tuberculomas with atypical response to tuberculostatic chemotherapy: literature review and a case report.

Approximately 34 cases of intracranial tuberculomas with paradoxical response to antituberculous chemotherapy have been documented worldwide. In most of the previously reported cases of this entity an associated tuberculous meningitis has been reported. The majority of these patients were children or young adults, who had inoperably located intracranial tuberculomas in high risk regions developing a few weeks or months after the start of appropriate chemotherapy. 53% of them recovered completely, 37% improved with mild neurological deficits and 10% died. It is interesting that these intracranial tuberculomas developed or enlarged at a stage when systemic tuberculosis was being treated successfully. We report our recent experience with these potentially curable tumours of the central nervous system. The literature is reviewed and diagnostic and therapeutic considerations are discussed. The possible immunological mechanisms of this phenomenon are analysed. In conclusion, patients, who are suspected to be suffering from CNS-tuberculosis should receive a prolonged (12-30 months) course of effective antituberculous therapy. Evidence of new intracranial tuberculomas or the expansion of older existing lesions require no change in the antituberculous drug programme. In such cases systemic dexamethasone as adjuvant therapy for 4 to 8 weeks is worthwhile and effective. Surgical intervention may be necessary in situations with acute complications of CNS tuberculosis such as shunting procedures for the treatment of hydrocephalus. When the diagnosis is not firm and there is no response to therapy within 8 weeks, a stereotactic biopsy of a suspected tuberculoma should be performed. If the largest lesion is not located in high risk deep regions of the brain, it should be total removed surgically. With this combined management, a satisfactory outcome can be obtained in the majority of cases.

Usefulness of ELISA using antigen A60 in serodiagnosis of neurotuberculosis.

Anti-mycobacterial antibody to A60 antigen were quantified in the sera and cerebrospinal fluid (csf) samples of one hundred patients of neurotuberculosis and twenty non-tubercular controls by immunoenzymatic (ELISA) assay. Sixty three patients (63%) had "significant" antibody titres in serum and/or CSF samples. In contrast, none of the samples from the control group showed this level of antibody concentration. The evaluation of this assay in tuberculoma (group A, 79 cases) vis-a-vis tubercular meningitis or TBM (group B, 21 patients) revealed significant antibody levels in the former 46 (58.2%) in comparison to 17 (77.3%) in the latter group. A positive relationship was observed in the titres of anti-mycobacterial antibodies in serum and in CSF both in cases of tuberculoma and TBM. This study indicates the utility of A60 antigen ELISA assay in categorising these patients into tubercular aetiology specially in the absence of bacteriological isolation from CSF which still remains the gold standard diagnostic criterion.

[Immunogenetic factors in pulmonary tuberculosis surgery]. / Immunogeneticheskie faktory vo ftiziokhirurgii.

Distribution of HLA antigens, haptoglobin phenotypes (Hp), ABO blood groups and rhesus factor was investigated in 60 patients with fibrocavernous tuberculosis and 50 patients with tuberculomas. All the patients were Russian and had a history of surgery for tuberculosis. Carriers of antigens B27, DR2 of HLA system, HP 2-2 and blood group 0 (I) were encountered more often in the group of tuberculosis patients. Antigens A1, B12, DR3 and A2 occurred among tuberculoma patients more frequently and less frequently, respectively. Among those who developed postoperative complications carriers of blood group A (II) were found significantly less frequently. Antigens HLA and Hp types were unrelated to the incidence of pleuropulmonary and infectious postoperative complications. Tuberculosis reactivation in the postoperative period and postoperative recurrences occurred more often in carriers of HLA antigen DR2.

[Role of tumor necrosis factor in immunopathogenesis of pulmonary tuberculosis]. / Rol faktora nekroza opukholei v immunopatogeneze tuberkulëza lëgkikh.

The activity of TNF-alpha in the serum was determined with ELISA basing on 2 monoclonal antibodies varying by epitopic specificity in 25 patients with pulmonary tuberculosis and 4 patients with chronic nonspecific respiratory diseases. TNF-alpha varied with tuberculosis severity and prognostic factors. Its level appeared the highest in fibrocavernous tuberculosis (405.0 +/- 82.9 pg/ml) against 355.0 +/- 32.5 pg/ml in tuberculoma. In the progressive disease TNF-alpha serum level was lower than in stabilization or inactive tuberculosis (334.6 +/- 36.8 pg/ml against 443.7 +/- 32.1). Low TNF-alpha concentrations indicate an adverse run of tuberculosis associated with destruction, intoxication and bacterial discharge.

[Blood coagulation function in pulmonary tuberculosis patients at the stages of surgical treatment]. / Sostoianie gemokoaguliatsii u bol'nykh tuberkulezom legkikh na étapakh khirurgicheskogo lecheniia.

The results of studying the coagulative properties of blood in 25 patients with pulmonary tuberculosis before surgical operations and at the stages of the postoperative period are presented. It was shown that, unlike the patients mainly with processes of productive nature and insignificant extent of the specific process, the patients with extended fibrocavernous tuberculosis of the lungs even before the operations were characterized by markedly increased thrombin formation. During surgical operations the hemocoagulation impairments in such patients could be aggravated up to development of coagulopathy.

[Antiproteolytic activity of the blood serum in adolescents with pulmonary tuberculosis]. / Antiproteoliticheskaia aktivnost' syvorotki krovi u podrostkov, bol'nykh tuberkulezom legkikh.

The antiproteolytic activity of the blood serum was examined in the course of hospital treatment of 128 adolescents with prevailingly torpid forms of pulmonary tuberculosis and in 19 adolescents with tubercular infection (control). A direct correlation has been found between the degree of clinico-roentgenological manifestations of the disease and level of serum alpha 1-inhibitor of proteinases as well as between the efficacy of treatment and normalization of the antiproteolytic activity of the blood of the patients. It proposed to use the determination of alpha 1-inhibitor of proteinases as an additional criterion of evaluation of the clinical course and outcomes of the disease in adolescents.