Prognostic and diagnostic accuracy of [<Superscript>18</Superscript>F]FDG-PET/CT in 190 patients with carcinoma of unknown primary

Purpose The aim of the study was to determine the accuracy of [¹⁸F]fluorodeoxyglucose (FDG) PET/CT in the search for the primary and the presence of a malignancy. The prognostic value of FDG-PET/CT information was tested. Methods A total of 190 patients were retrospectively analysed: 82 with histologically proven metastases (HPM) and 108 with clinical suspicion of the presence of a malignancy (CSM). The sensitivity and specificity were determined. Overall survival was calculated to evaluate the prognostic value of the FDG-PET/CT findings. Results In the search for the primary, the sensitivity and specificity were 62.0% and 81.9%, respectively. In the search for the presence of a malignancy, the sensitivity and specificity were 93.6% and 85.7%, respectively. Between the HPM and CSM groups, no significant difference in sensitivity and specificity was found either in the search for the primary or in the search for the presence of a malignancy. No significant difference in the sensitivity and specificity was found between 78 patients who were investigated by contrast-enhanced FDG-PET/CT and the remaining patients. A significantly shorter overall survival was found among patients with positive FDG-PET/CT findings compared with patients with negative findings (p = 0.00001); no significant difference in survival was found between the HPM and the CSM group (p = 0.770). Conclusion FDG-PET/CT imaging is very helpful in the search for the presence of a malignancy in patients with carcinoma of unknown primary syndrome. FDG-PET/CT is less accurate in identifying exactly the site of a primary. Discovery of a hypermetabolic lesion was associated with the worst survival rate. This study was cited in the Highlights Lecture on the EANM Congress, Athens 2006.     

Typical and atypical neurovascular relations of the trigeminal nerve in the cerebellopontine angle: an anatomical study

The aim of the present study was to anatomically evaluate in adults the neurovascular trigeminal relations in the cerebellopontine angle (CPA), from a morphological and topographical perspective and thus to improve, detail and debate the pre-existing information, with educational and surgical implications. For the present anatomical study we performed bilateral dissections on 20 human adult skull bases, in formalin-fixed cadavers, at the level of the cerebellopontine angle, using the anatomical superior approach; we also studied 20 additional drawn specimens—cerebellum and brainstems, from autopsied cadavers, in order to better document the vasculature at the trigeminal root entry zone (REZ). The most constant but not exclusive neurovascular relations of the trigeminal nerves were those with the superior cerebellar artery (SCA) and the superior petrosal vein (the petrosal vein of Dandy). The regular possibility for the SCA to appear divided into a medial and a lateral branch and these to represent individual trigeminal relations at the level of the pontine cistern or REZ must not be neglected. The petrosal vein tributaries can also represent superior, inferior, or interradicular trigeminal relations. Arterioles emerging from the SCA or the anterior inferior cerebellar artery (AICA) represented trigeminal relations either at the REZ or were coursing between the trigeminal roots. A dissected specimen presented a radicular trigeminal artery emerging from the basilar artery and entering the trigeminal cavum inferior to the nerve. Another specimen presented two bony lamellae superior to the trigeminal nerve at the entrance in the trigeminal cavum—these lamellae were embedded within the lateral border of tentorium cerebelli and the posterior petroclinoid ligament. So we bring here an evidence-based support extremely useful not only for specialists dealing with this area but also for educational purposes. It appears important not only to consider the typical anatomy at this level but also to take into account the atypical and hardly predictable morphologies that may alter the diagnoses and the specific surgical procedures.     

The contribution to the epidemiology of gastrointestinal nematodes of sheep with special focus on the survival of infective larvae in winter conditions

Tracer tests conducted over a 3-year period were aimed at measuring the level and species nematode composition of survival on pastures with a special focus on winter months. The survival of infective larvae in chilly conditions is not significantly affected by Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus and Chabertia ovina. On the contrary, the number of Teladorsagia circumcincta and Nematodirus filicollis significantly increased in milder winter conditions. The results confirmed an epidemiological strategy of overwintering in the arrested stage for Teladorsagia circumcincta and Nematodirus filicollis; the epidemiological strategy of genus Trichostrongylus used both strategies—in particular the tolerance of free-living stages to cold conditions. Part of the population overwintered in the arrested stage as well.     

Comprehensive seroprofiling of sixteen B. burgdorferi OspC: Implications for Lyme disease diagnostics design

Early diagnosis of Lyme disease (LD) is critical to successful treatment. However, current serodiagnostic tests do not reliably detect antibodies during early infection. OspC induces a potent early immune response and is also one of the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the amino acid sequence is conserved among all 21 known OspC types. We performed a series of comprehensive seroprofiling studies to select the OspC types that have the most cross-reactive immunodominant epitopes. We found that proteins belonging to seven OspC types detect antibodies from all three infected host species regardless of the OspC genotype of the infecting strain. Although no one OspC type identifies all seropositive human samples, combinations of as few as two OspC proteins identified all patients that had anti-OspC antibodies.     

Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus

Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.     

Lysophosphatidic acid (LPA)—a perspective marker in ovarian cancer

To compare plasma lysophosphatidic acid (LPA) levels in ovarian cancer patients in women with benign ovarian tumors and in women with no ovarian pathology. We correlated clinico-pathological parameters with plasma LPA levels. Capillary electrophoresis with indirect ultraviolet detection was used to analyze the plasma LPA levels of 159 patients (81 patients with ovarian cancer, 27 women without ovarian or uterine pathologies, and 51 patients with benign ovarian tumors) during a 5-year period. Patients with ovarian cancer had a significantly higher plasma LPA level (n = 81; median (med), 11.53 μmol/l; range, 1.78–43.21 μmol/l) compared with controls with no ovarian pathology (n = 27; med, 1.86 μmol/l; range, 0.94–9.73 μmol/l), and patients with benign ovarian tumor (n = 51; med, 6.17 μmol/l; range, 1.12–25.23 μmol/l; P < 0.001). We found that plasma LPA levels were associated with the International Federation of Gynecology and Obstetrics stage. The histological subtype and grade of ovarian cancer did not influence the plasma LPA levels in this study. The plasma LPA level can be a useful marker for ovarian cancer, particularly in the early stages of the disease.     

A prognostic index relating 24-hour ambulatory blood pressure to cardiac events in ischemic cardiomyopathy following defibrillator implantation

Background: We assessed the role of left ventricular ejection fraction and of ambulatory blood pressure monitoring (ABPM) to predict cardiac death and heart failure in patients with defibrillator fulfilling MADIT II criteria. ABPM variables assessed included: mean 24 hours diastolic and systolic blood pressure, mean 24 hours heart rate, and pulse pressure.
Methods: We studied 105 consecutive patients (age 67 ± 11), all with a defibrillator and ejection fraction ≤ 30%).
Results: At 1-year follow-up, there were 29 events (25%), three cardiac deaths, and 26 hospitalizations for heart failure. Age, creatinine, mean 24 hours diastolic blood pressure, and mean 24 hours systolic blood pressure (but not ejection fraction) were associated with events. A prognostic index (PI) was built by age and ABPM variables, according to the formula (120 – age) + (mean 24 hours diastolic blood pressure + mean 24 hours systolic blood pressure). Receiver operating characteristic curves showed the best cutoff for PI = 220 (sensitivity 81%, specificity 71%, positive predictive value 56%, negative predictive value 88%). Cox regression analysis confirmed the significant association between lower PI (< 220) and clinical events (HR 4.8, 95% CI 1.8–12.3, P = 0.0001 for PI). Overall, 12% of patients with high PI values (≥ 220 n = 71) had clinical events at 12-month follow-up, compared with 61% of patients with low PI (< 220 n = 34) (P < 0.0001).
Conclusion: The PI built by mean 24 hours diastolic and systolic blood pressure and age could be a simple method to stratify risk of cardiac death and acute heart failure in MADIT II patients, in whom ejection fraction, uniformly depressed, is not predictive.     

Stem cells and cancer

The cell of origin of cancer has been a strongly debated topic through out the history of cancer research. This review provides a historic framework and a synopsis of how the theories of cancer initiation and progression evolved from early times to the present day. We present the concept of a cancer stem cell, and review for you the literature supporting the existence of cancer stem cells in addition to a brief discussion on our own work supporting a bone marrow-derived source for the cancer stem cell, as well as cells of the cancer stroma.