BACKGROUND Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium‐labeled octreotide (111In‐DTPA‐D‐Phe1‐octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. METHODS Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow‐up). In 8 cases, octreotide was replaced by the long‐acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. RESULTS The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow‐up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). CONCLUSIONS Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long‐acting analog lanreotide, which requires fewer injections, improves patients' compliance. Cancer 2002;94:1414–20. © 2002 American Cancer Society. DOI 10.1002/cncr.10374

In the course of a molecular genetic investigation of a double inhumation, presumably a mother/child burial from Aschheim (Upper Bavaria, 6th century A.D.), which included analysis of mitochondrial DNA, molecular sexing, and polymorphic nuclear DNA, Yersinia pestis‐specific DNA was detected. Molecular analyses were performed on DNA extracts obtained from two teeth of one skeleton and four teeth of the other. The use of the primer pair YP12D/YP11R (Raoult et al. [2000] Proc. Natl. Acad. Sci. 97:12800–12803), able to amplify part of the Y. pestis plasmid pPCP1 pla sequence, resulted in amplification products of the expected fragment size. Using BLASTN 2.2.2, the sequences of these amplification products shared 100% identity with that of the modern Y. pestis pla sequence in GenBank, with the exception of one amplification product which revealed a single base substitution. The application of a “suicide PCR” with the independent primer pair YP11D/YP10R (Raoult et al. [2000] Proc. Natl. Acad. Sci. 97:12800–12803) resulted in amplification products which shared a 96–98% homology with that of the modern Y. pestis pla sequence in GenBank. The observed deviations were presumably due to miscoding lesions in the template DNA. No modern Y. pestis DNA was introduced into the institute, and thus no positive controls were carried along. All extraction and PCR controls remained negative. The identification of Y. pestis‐specific DNA sequences in these two skeletons, buried in the second half of the 6th century A.D., constitutes molecularly supported evidence for the presence of Y. pestis, the causative agent of plague, during the first pandemic recorded. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.

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AimTo evaluate whether the histology and grading of solitary pulmonary nodules (SPNs) correlated with the results of dynamic multiphase multidetector CT (MDCT) and the [18F]fluorodeoxyglucose standardised uptake value (SUV) in 30 patients.MethodsChest x-rays of 270 patients with incidentally detected SPNs were retrospectively evaluated. Thirty patients with histologically proven SPNs were enrolled. On MDCT and positron emission tomography (PET)/CT images, two experts measured the density of nodules in all perfusion phases and the SUV. Net enhancement (NE) was calculated by subtracting peak pre-contrast density from peak post-contrast density. The Pearson test was used to correlate nodule NE, SUV, grading, histology and diameter.ResultsOf the 30 malignant SPNs, six were classified as G1 (median NE, 31.5 Hounsfield units (HU); median SUV, 4.8 units), 15 were classified as G2 (median NE, 49 HU; median SUV, 6 units), and nine were classified as G3 (median NE, 32 HU; median SUV, 4.5 units). A highly negative correlation was found in G3 SPNs between NE and the corresponding diameters (r=−0.834; p=0.00524). NE increased with the increase in diameter (r=0.982; p=0.284). SUV increased as the SPN diameter increased (r=0.789; p=0.421). NE and SUV were higher in G2 than G1 SPNs, and lower in G2 than G3 SPNs (r=0.97; p=0.137).ConclusionsThe significant correlation in dedifferentiated (G3) SPNs between NE and diameter (r=−0.834; p=0.00524) supports the theory that stroma and neoangiogenesis are fundamental in SPN growth. The highly negative correlation between NE and diameter demonstrates a net decrease in perfusion despite an increase in dimension. The multidisciplinary approach used herein may result in a more precise prognosis and consequently a better therapeutic outcome, particularly in patients with undifferentiated lung cancer.

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Objective To evaluate the prevalence and factors associated with the neuropathic pain features in a cohort of patients with psoriatic arthritis (PsA). Methods A cross-sectional evaluation was conducted in consecutive patients having PsA with prevalent peripheral joint involvement, referred to 3 rheumatological centers. For each patient, a comprehensive assessment of disease activity, physical function, and disease effect was carried out. The presence of comorbid fibromyalgia syndrome (FMS) was evaluated. Acute-phase reactants were also recorded. The neuropathic pain features were investigated through the PainDETECT Questionnaire (PDQ). A logistic regression analysis was therefore conducted using the PDQ as the dependent variable. Results The final evaluation included 118 patients. A comorbid FMS was detectable in 30 of the 118 patients with PsA (25.4%). Probable characteristics of neuropathic pain (PDQ ≥ 19) were found in 30 (25.4%) patients overall, ambiguous (PDQ > 12 and < 19) in 21 (17.8%) patients, and unlikely (PDQ ≤ 12) in 67 (56.8%) patients. Using logistic regression analysis, the only independent variable among those investigated that could explain the neuropathic pain features was the presence of a comorbid FMS (p = 0.0127). Excluding patients with comorbid FMS, an association with disability (measured by Health Assessment Questionnaire–Disability Index) emerges (p = 0.0489). In patients with PsA and comorbid FMS, PDQ scores were significantly higher than in patients without comorbid FMS. Conclusion Neuropathic pain features are common in patients with PsA, and the presence of pain sensitization (comorbid FMS) seems to be its main predictor.

Objective To investigate CT morphologic and densitometric features and 18-FDG PET findings of surgically excised lung adenocarcinomas “mixed subtype” with predominant lepidic component, appearing as solid solitary pulmonary nodules (SPNs) on CT scan. Materials and Methods Approval for this study was given from each local institutional review board according to its retrospective nature. Nodules pathologically classified as lung adenocarcinoma mixed subtype with bronchioloalveolar otherwise lepidic predominant component, in three different Italian institutions (Napoli; Varese; Parma), were retrospectively selected. Results 22 patients were identified. The number of SPNs with smooth margins was significantly lower with respect to the number of SPNs with spiculated margins (p: 0.033), radiating spiculations (p: 0.019), and notch sign (p: 0.011). Mean contrast enhancement (CE) was 53.34 HU (min 5.5 HU, max 112 HU); considering 15 HU as cut-off value, CE was positive in 20/22 cases. No significant correlation was found between size and CE. Mean SUVmax was 2.21, ranging from 0.2 up to 7.5 units; considering 2.5 units as cut-off, SUVmax was positive in 7/22 cases. The number of SPNs with positive CE was significantly higher than the number of SPNs with positive SUVmax (p: 0.0005). Conclusion CT generally helps in identifying solid SPN suspicious for malignancy but 18-FDG PET may result in false-negative evaluation; when 18-FDG PET findings of a solid SPN are negative even though CT morphology and CE suggest malignancy, radiologist should consider that lepidic component may be present inside the invasive tumor, despite the absence of ground glass.

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