Comparison of indium-111 octreotide and thallium-201 scintigraphy in patients mammographically suspected of having breast cancer: Preliminary results

Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21 patients (16 with palpable and five with non-palpable lesions) suspected of having breast malignancies on the basis of mammography. Early (15 min) and late (3 h)²⁰¹Tl (111 MBq) and 4-h and 24-h¹¹¹In-octreotide (111–148 MBq) static planar anterior images (matrix 256×256) were obtained on separate days. Images were evaluated both visually and quantitatively. Biopsy was performed following the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one case of fat necrosis). The means histopathologcial tumour size (mean largest diameter) was 3.38±1.9 cm.¹¹¹In-octreotide detected 16 of the 17 breast cancers (94%) while²⁰¹Tl detected 13 of them (76%). Both¹¹¹In-octreotide and²⁰¹Tl missed one nonpalpable carcinoma showing only an isolated cluster of microcalcifications on mammography. The smallest tumour size detected by both agents 1.5×1.5 cm. Of the four benign lesions, only the breast abscess revealed both²⁰¹Tl and¹¹¹In-octreotide uptake.¹¹¹In-octreotide scan also showed tracer uptake in five of the six patients with histologically proven axillary metastases, while four of these six patients showed²⁰¹Tl uptake. The tumour/background (T/B) ratios of late¹¹¹In-octreotide and²⁰¹Tl images were 1.71±0.38 and 1.46±0.30 respectively (P=0.039). In this preliminary study,¹¹¹In-octreotide yielded more favourable results than²⁰¹Tl in the detection of breast carcinomas. However, the diagnostic efficacy of¹¹¹In-octreotide imaging needs to be investigated in larger patient series.     

Comparison of Sputum and Serum Eosinophil Cationic Protein (ECP) Levels in Nonatopic Asthma and Chronic Obstructive Pulmonary Disease

The aim of the present study was to investigate whether sputum eosinophil cationic protein (ECP) concentrations could be a useful marker in the differential diagnosis between intrinsic asthma and chronic obstructive pulmonary disease (COPD). For this purpose total blood eosinophil counts were obtained and concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild attack and 9 COPD patients with acute exacerbation were measured by radioimmunoassay. Mean serum ECP concentration was 54.3 ± 23.0 g/L in the asthmatic group and 83.3 ± 79.2 g/L in the COPD group (p: n.s.). In the group of asthmatics mean sputum ECP level was 984.5 ± 1245.5 mg/L/g sputum and in the COPD group it was 417.5 ± 363.5 mg/L/g sputum. There was no significant difference in sputum ECP levels between patients with asthma and COPD. We conclude that neither sputum nor serum ECP levels are useful markers in differential diagnosis of asthma attack and acute exacerbation of COPD.     

Interdigitating dendritic cell tumor with breast and cervical lymph-node involvement: a case report and review of the literature

Interdigitating dendritic cell tumor (IDCT) is an extremely rare malignancy. It occurs primarily in lymph nodes, but extranodal involvement has also been reported. A 38-year-old woman with IDCT with breast and cervical lymph-node involvement is reported in this paper. To our knowledge, this is the first case of IDCT originating from the breast. In the breast and lymph node, the tumor displayed diffuse sheets, fascicles and storiform growth pattern. It was composed of oval to spindle cells with pale to eosinophilic cytoplasm, ill-defined cell outlines, oval nuclei with vesicular chromatin and prominent eosinophilic nucleoli. Mitotic activity was three per ten high-power fields. The neoplastic cells were intermingled with small mature lymphocytes and plasma cells. Immunohistochemical studies showed that the tumor cells were strongly and diffusely positive for vimentin, CD68, S-100 protein, CD45/leukocyte common antigen and fascin and focally positive for lysozyme, alpha-1 antitrypsin and CD4. Ki-67 labeling index was 10%. The patient was treated with combined therapeutic approaches, including surgery, radiotherapy and chemotherapy. IDCT has the potential for an aggressive clinical course. However, 32 months after the initial diagnosis, the patient is still alive and being followed with a stable tumor burden.     

Proteasome inhibitors and Smac mimetics cooperate to induce cell death in diffuse large B-cell lymphoma by stabilizing NOXA and triggering mitochondrial apoptosis

Copy number gains and increased expression levels of cellular Inhibitor of Apoptosis protein (cIAP)1 and cIAP2 have been identified in primary diffuse large B-cell lymphoma (DLBCL) tissues. Second mitochondria-derived activator of caspases (Smac) mimetics were designed to antagonize IAP proteins. However, since their effect as single agents is limited, combination treatment represents a strategy for their clinical development. Therefore, we investigated the Smac mimetic BV6 in combination with proteasome inhibitors and analyzed the molecular mechanisms of action. We discovered that BV6 treatment sensitizes DLBCL cells to proteasome inhibition. We show a synergistic decrease in cell viability and induction of apoptosis by BV6/Carfilzomib (CFZ) treatment, which was confirmed by calculation of combination index (CI) and Bliss score. BV6 and CFZ acted together to trigger activation of BAX and BAK, which facilitated cell death, as knockdown of BAX and BAK significantly reduced BV6/CFZ-mediated cell death. Activation of BAX and BAK was accompanied by loss of mitochondrial membrane potential (MMP) and activation of caspases. Pretreatment with the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) rescued BV6/CFZ-induced cell death, confirming caspase dependency. Treatment with CFZ alone or in combination with BV6 caused accumulation of NOXA, which was required for cell death, as gene silencing by siRNA or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated NOXA inactivation inhibited BV6/CFZ-induced cell death. Together, these experiments indicate that BV6 and CFZ cooperatively induce apoptotic cell death via the mitochondrial pathway. These findings emphasize the role of Smac mimetics for sensitizing DLBCL cells to proteasome inhibition with important implications for further (pre)clinical studies.     

Evaluation of myocardial perfusion in patients with Behçet’s disease

Aim

To estimate the prevalence of silent myocardial ischemia (SMI) in patients with Behçet’s disease (BD) and to identify a subgroup of patients at higher risk for the presence of SMI. Materials and Methods We evaluated 41 patients (mean age 42.8 ± 12.3 years) with BD and 35 healthy control subjects. Treadmill exercise test and thallium-201 myocardial perfusion single photon emission computed tomography (SPECT) were performed in all subjects. Coronary angiography was performed in all patients with a diagnosis of SMI in Behçet’s group.

Results

All subjects had normal resting electrocardiograms. Eight patients with BD (19.5%) had evidence of ischemia on exercise testing and myocardial perfusion SPECT. Only one SMI positivity (2.9%) was recorded in the control group. Significant coronary stenosis was not found with coronary angiography in the patients with a diagnosis of SMI in Behçet’s group. SMI positivity was recorded in 2 of 18 female patients (11%) and in 6 of 23 male patients (26.1%) with BD (p = 0.429). The mean duration of BD was 13.8 ± 2.6 years in patients with SMI and 7 ± 4.1 in patients without it (p < 0.001). Seven of the 8 patients (87.5%) with SMI had a duration of BD of greater than 10 years.

Conclusions

The results of this study show that the prevalence of SMI is high in patients with BD. Based on our findings, screening with myocardial perfusion scintigraphy may be recommended for patients with duration of BD greater than 10 years.     

Serum β2-microglobulin levels in psoriatic patients

β₂-Microglobulin (β₂-M) is a low molecular weight protein forming the light chain of the class I major histocompatibility complex. It is found on the cell surface of all nucleated cells. Its serum concentration is found to be increased in kidney diseases, neoplasia, AIDS, chronic inflammation and autoimmune diseases. Inflammation plays an important role in the pathogenesis of psoriasis, especially psoriatic arthritis and immunological upset is one of the most implicated factors in the etiology of the disease. In this study, the sera β₂-M levels were evaluated in cases diagnosed as psoriasis vulgaris and psoriatic arthritis, and a statistically significant increase was found in cases of psoriatic arthritis compared to those of psoriasis vulgaris and the control group.