Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma

BACKGROUND: Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported to depict areas with active bone disease in multiple myeloma (MM) with both high sensitivity and specificity. This observation was explained by the uptake of Tc-99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m-MIBI imaging and magnetic resonance imaging (MRI) perform equally well in detecting myelomatous bone marrow lesions. METHODS: In 21 patients with MM, MRIs of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were done. RESULTS: Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87 vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24 vertebrae infiltrated according to MRI. In patients with disease stage III, Tc-99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic disease. CONCLUSION: Tc-99m-MIBI scanning underestimated the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage

Persisting right-sided chylothorax in a patient with chronic lymphocytic leukemia: a case report

Introduction Chylothorax caused by chronic lymphocytic leukemia is very rare and the best therapeutic approach, especially the role of modern immunochemotherapy, is not yet defined. Case presentation We present the case of a 65-year-old male Caucasian patient with right-sided chylothorax caused by a concomitantly diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab were administered. In addition, our patient received total parenteral nutrition for the first two weeks of treatment. Despite the very good clinical response of the lymphoma to treatment, the chylothorax persisted and percutaneous radiotherapy of the thoracic duct was applied. However, eight weeks after the radiotherapy the chylothorax still persisted and our patient agreed to a surgical intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy was performed, resulting in a complete cessation of the pleural effusion. Apart from the first two weeks our patient was treated on an out-patient basis for nearly six months. Conclusion In this case of chylothorax caused by chronic lymphocytic leukemia, immunochemotherapy in combination with conservative treatment, and even consecutive radiotherapy, were not able to stop pleural effusion, despite the very good clinical response of the chronic lymphocytic leukemia to treatment. Out-patient management using repetitive thoracocenteses can be safe as bridging until definitive surgical ligation of the thoracic duct

Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

<p>Abstract</p> <p>Background</p> <p>Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-<it>ras </it>mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.</p> <p>Methods</p> <p>Cytokine determinations were performed by commercially available ELISA kits, while K12-<it>ras </it>mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.</p> <p>Results</p> <p>Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-<it>ras </it>mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.</p> <p>Conclusion</p> <p>IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.</p

External Ocular Surface Bacterial Isolates and their Antimicrobial Susceptibility Patterns among Pre-operative Cataract Patients at Mulago National Hospital in Kampala, Uganda.

Endophthalmitis is a severe complication of cataract surgery which leads to high ocular morbidity and visual loss even with antibiotic treatment. Bacterial ocular floras are the implicated causative agents. This study was undertaken to evaluate the external ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital. This cross sectional study enrolled consecutively 131 patients scheduled for routine cataract surgery in the Department of Ophthalmology at Mulago National Hospital in Kampala, Uganda. Eyelid margin and conjunctival swabs were collected and processed using standard microbiological procedures to identify bacterial isolates and their respective antimicrobial susceptibility patterns. Of 131 patients involved (mean age 63.3 ± 14.5 years), 54.2% (71/131) were females. The eyelid margin and conjunctival samples were culture positive in 59.5% (78/138) and 45.8% (60/138) respectively. The most common organisms identified were Coagulase-negative Staphylococci (CoNS) [65.9% (91/138)] and Staphylococcus aureus [21.0% (29/138)]. CoNS showed the highest resistance to tetracycline (58.2%, 53/91) and erythromycin (38.5%, 35/91), whereas in S. aureus the resistance to tetracycline and erythromycin were 55.2% (16/29) and 31.0% (9/29) respectively. Methicillin resistant CoNS (MRS) and Methicillin resistance S. aureus (MRSA) were 31.9% (29/91) and 27.6% (8/29) respectively. There were low resistance rates for CoNS, S. aureus and other bacterial isolates to ciprofloxacin (11.1%-24.2%), gentamicin (5.6-31.0%), tobramycin (17.2% -25.3%) and vancomycin (0.0%). CoNS and S. aureus are the most common bacterial isolates found on the external ocular surface of the pre-operative cataract patients. Ciprofloxacin, gentamicin, tobramycin and vancomycin showed the lowest resistance rates to all bacterial isolates, therefore may be used to reduce bacteria load in the conjunctiva sac among cataract patients prior to surgery

Association Analysis of IL-17A and IL-17F Polymorphisms in Chinese Han Women with Breast Cancer

Background: Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women. Methodology and Principal Findings: We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P = 0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype A rs2275913G rs3819025G rs3748067, located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471 after correction for multiple testing)

The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer

Although weight loss is often a dominant symptom in patients with upper gastrointestinal malignancy, there is a lack of objective evidence describing changes in nutritional status and potential associations between weight loss, food intake, markers of systemic inflammation and stage of disease in such patients. Two hundred and twenty patients diagnosed with gastric/oesophageal cancer were studied. Patients underwent nutritional assessment consisting of calculation of body mass index, measurement of weight loss, dysphagia scoring and estimation of dietary intake. Serum acute-phase protein concentrations were determined by enzyme-linked immunosorbent assay. In all, 182 (83%) patients had lost weight at diagnosis (median loss, 7% body weight). Weight loss was associated with poor performance status, advanced disease stage, dysphagia, reduced dietary intake and elevated serum C-reactive protein (CRP) concentrations. Multiple regression identified dietary intake (estimate of effect, 38%), serum CRP concentrations (estimate of effect, 34%) and stage of disease (estimate of effect, 28%) as independent variables in determining degree of weight loss. Mechanisms other than reduced dietary intake or mechanical obstruction by the tumour appear to be involved in the nutritional decline in patients with gastro-oesophageal malignancy. Recognition that systemic inflammation plays a role in nutritional depletion may inform the development of appropriate therapeutic strategies to ameliorate weight loss, making patients more tolerant of cancer-modifying treatments such as chemotherapy

Preoperative elevation of serum C – reactive protein is predictive for prognosis in myeloma bone disease after surgery

We investigated whether preoperative levels of serum C-reactive protein (CRP) and its correlation with tumour clinicopathological findings adds prognostic information beyond the time of diagnosis in patients with myeloma bone disease (MM) to facilitate the surgical decision-making process. Six hundred and fifty-eight myeloma patients were evaluated retrospectively for surgery. Clinicopathological variables of patients who underwent surgery (n=71) were compared between patients with preoperative CRP ⩾6 mg l−1 and those with CRP <6 mg l−1. Univariate and multivariate analyses were performed to identify prognostic factors after surgery. Patients with an increase of CRP prior to surgery showed inferior survival compared to patients with normal levels. Patients with normal CRP levels at diagnosis but elevations prior to surgery do seem to have a similar unfavourable overall survival (OS) than patients with an increase both, at diagnosis and at surgery. Conversely, patients with normal CRP levels prior to surgery still have the best OS, irrespective of their basic values. Multivariate analysis revealed preoperative CRP levels above 6 mg l−1 Lactate dehydrogenase (LDH) above normal, and osteolyses in long weight bearing bones as independent predictors of survival. These findings suggest that in patients with MM serum levels of CRP increase during disease activity and might be significantly correlated with specific disease characteristics including adverse prognostic features such as osteolyses in long weight bearing bones. Thus, preoperative elevated CRP serum levels might be considered as independent predictor of prognosis and could provide additional prognostic information for the risk stratification before surgical treatment in patients with myeloma bone disease

Ascitic complement system in ovarian cancer

Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis and therapy often become delayed. As the complement (C) system may provide a cytotoxic effector arm for both immunological surveillance and mAb-therapy, we have characterised the C system in the intraperitoneal ascitic fluid (AF) from ovarian cancer patients. Most of the AF samples showed alternative and classical pathway haemolytic activity. The levels of C3 and C4 were similar to or in the lower normal range when compared to values in normal sera, respectively. However, elevated levels of C3a and soluble C5b-9 suggested C activation in vivo. Malignant cells isolated from the AF samples had surface deposits of C1q and C3 activation products, but not of C5b-9 (the membrane attack complex; MAC). Activation could have become initiated by anti-tumour cell antibodies that were detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC was probably due to the expression of C membrane regulators CD46, CD55 and CD59 on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the alternative pathway inhibitors factor H and FHL-1 were present in the AF at concentrations higher than in serum samples. Despite the presence of soluble C inhibitors it was possible to use AF as a C source in antibody-initiated killing of ovarian carcinoma cells. These results demonstrate that although the ovarian ascitic C system fails as an effective immunological surveillance mechanism, it could be utilised as an effector mechanism in therapy with intraperitoneally administrated mAbs, especially if the intrinsic C regulators are neutralised

Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

<p>Abstract</p> <p>Background</p> <p>Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them.</p> <p>Methods</p> <p>We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts).</p> <p>Results</p> <p>4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC.</p> <p>Conclusions</p> <p>Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.</p