Imaging of Primitive Neuroectodermal Tumor (PNET) by Technetium-99m Tetrofosmin

Purpose. Tc-99m tetrofosmin launched for myocardial studies has recently also shown a good detectability for several tumors. Data on PNET imaging by Tc-99m tetrofosmin are not yet available

Evaluation of [18F]-FDG-Based Hybrid Imaging Combinations for Assessment of Bone Marrow Involvement in Lymphoma at Initial Staging.

The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet

Current surgical status of thyroid diseases

Thyroid nodules are a common clinical problem for surgeons. The clinical importance of nodules is the need to exclude thyroid cancer, which occurs in 5%–15% of patients. If fine needle aspiration cytology is positive, or suspicious for malignancy, surgery is recommended. During the past decade, with the tendency to develop smaller incisions, an endoscopic approach has been applied to thyroid surgery, called minimally invasive video-assisted thyroidectomy. This approach was immediately followed by other minimally invasive or scarless neck techniques, such as the breast approach, axillary-breast approach, and robot-assisted method. All these techniques follow the same principles of surgery and oncology. This review presents the current surgical management of the thyroid gland, including the surgical techniques and compares them by describing benefits and drawbacks of each one

A case of typical pulmonary carcinoid tumor treated with bronchoscopic therapy followed by lobectomy

Carcinoid bronchopulmonary tumors represent approximately 25% of all carcinoid tumors and 1%–2% of all lung neoplasms. The most common symptoms are: persistent cough, asthma-like wheezing, chest pain, dyspnea, hemoptysis and obstructive pneumonitis. We present a case of a young adult diagnosed with a typical carcinoid tumor. The diagnosis was established on the basis of imaging examination and bronchoscopic biopsy. The patient was treated with bronchoscopic electrocautery therapy to relieve the obstructed airway, followed by surgical lobectomy in order to entirely remove the exophytic damage. This approach was not only a palliative management to bronchial obstruction but also avoided pneumonectomy. Recent studies support the use of such interventional resection methods, as they may result in a more conservative surgical resection

Peptic Ulcer Perforation as the First Manifestation of Previously Unknown Primary Hyperparathyroidism

A patient admitted for acute abdomen was incidentally found with elevated serum calcium level. In surgery, under conservative treatment of the hypercalcemia, a perforated duodenal ulcer was found and simple closure was performed. Postoperatively, calcium level continued to rise, parathyroid hormone was elevated and ultrasonographic examination showed a lesion in the right anterior neck, while serum gastrin level was normal, thus documenting the diagnosis of primary hyperparathyroidism. Conservative treatment had no effect on calcium level and the patient was subjected to emergency neck exploration, where a large parathyroid adenoma was removed. After surgery, calcium and PTH levels were normalized and the patient was discharged on the 5th postoperative day. Peptic ulcer and its complications are usual manifestations of primary hyperparathyroidism, with or without increased gastrin level. On the other hand, cases of a perforation of peptic ulcer as the first clinical manifestation of primary hyperparathyroidism are extremely rare

Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]

INTRODUCTION: Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1. METHOD: In a randomized, double-blind study, 31 patients with stage II breast cancer and with no evidence of disease received subcutaneous injections of either placebo or oxidized mannan-MUC1, to immunize against MUC1 and prevent cancer reoccurrence/metastases. Twenty-eight patients received the full course of injections of either oxidized mannan-MUC1 or placebo. Survival and immunological assays were assessed. RESULTS: After more than 5.5 years had elapsed since the last patient began treatment (8.5 years from the start of treatment of the first patient), the recurrence rate in patients receiving the placebo was 27% (4/15; the expected rate of recurrence in stage II breast cancer); those receiving immunotherapy had no recurrences (0/16), and this finding was statistically significant (P = 0.0292). Of the patients receiving oxidized mannan-MUC1, nine out of 13 had measurable antibodies to MUC1 and four out of 10 had MUC1-specific T cell responses; none of the placebo-treated patients exhibited an immune response to MUC1. CONCLUSION: The results suggest that, in early breast cancer, MUC1 immunotherapy is beneficial, and that a larger phase III study should be undertaken

Rise and Fall of an Anti-MUC1 Specific Antibody

So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10) M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology

Study of apoptotic parameters in thyroid gland nodules in vivo

The process of apoptosis in human cells is a normal and complex procedure for the organism in order to maintain the balance between normal cells destruction and rebirth. Potential disorders in the apoptotic paths that can result in the pathogenesis of various diseases, is currently a wide field of research worldwide. AIM: In this prospective clinical immunochistochemical study, an attempt is made to investigate the role of the apoptotic procedures in various thyroid diseases (solitary nodule, non-toxic multinodular goiter). MATERIAL: Fifty-five patients (9 male-46 female, mean age 55 years) were included in this study. The diseases were a) non-toxic multinodular goiter 30/55 (54,54%), b) toxic multinodular goiter 11/55 (20%) c) solitary “cold” nodule 11/55 (20%) and d) toxic adenoma 3/55 (5,46%). Total thyroidectomy was performed in all cases and the postoperative course was uncomplicated. METHODS: The expression of Fas and Bcl-2 proteins and p53 gene and ki67 antigen was studied in cytologic samples extracted by FNA under direct vision of the nodule and in the excised thyroid gland. For the trace and marking of the various targets, the abiding-biotin-hyperoxidase with diamino-benzidine (DAB) method was used. The values of TSH were also studied. The results were analyzed and compared using the fisher’s exact test or the unpaired two tailed t-test. RESULTS: The histology report showed 6 carcinomas (10,91%), 5 colloid nodules (9,1%), 30 follicular adenomas (54,55%), 3 hyperplastic nodules (5,45%), 2 focal thyroiditis (3,63%), 7 Hashimoto’s thyroiditis (12,73%) and 2 Grave’s disease (3,63%). Fas was found to be elevated (mean value 22,29) in Hashimoto’s thyroiditis, while the m.v. in follicular adenomas was 9,7 (p=0,05). In addition, the Fas expression was found to be elevated in normofollicular adenomas, compared to macrofollicular adenomas (p=0,04). The Bcl-2 expression was found to be elevated in Hashimoto’s thyroiditis (m.v. 77,4), while the m.v. in follicular adenomas was 52,14 (p=0,02). The ki67 antigen expression in Hashimoto’s thyroiditis was found m.v. 3,7 while in follicular adenomas was 1,36 (p=0,03). In addition, ki67 was found to be elevated in microfollicular adenomas (m.v. 2,67), compared to non-microfollicular adenomas (p=0,05). The p53 gene expression was found to be of no significance. TSH value was found to be statistically significant elevated in Hashimoto’s thyroiditis, compared to follicular adenomas (p=0,001). The values of the above proteins and genes in the samples extracted from the FNA cytology were found to be inadequate and unreliable. CONCLUSIONS: 1. Fine needle aspiration biopsy (FNAB) even under direct vision seems to be unreliable in defining the apoptotic-immunohistochemical markers in Hashimoto’s thyroiditis, thyroid nodules and thyroid carcinoma. 2. FNAB even under direct vision is also unreliable in the differential diagnosis of macrofollicular adenomas from microfollicular ones and colloid goiter. 3. In the histological examination of Hashimoto’s thyroiditis there is: a) Expression of the Fas protein with mean value 22,29% b) Elevated expression of Bcl-2 with mean value 77,14% c) Expression of ki67 protein with mean value 3,4% d) Statistically significant increased (p=0,05) of TSH, compared to follicular adenomas. 4. In the histological examination of microfollicular adenomas, statistically significant increase of ki67 protein (p=0,05) was found, compared to non-microfollicular ones.Ο μηχανισμός απόπτωσης των κυττάρων αποτελεί πολύπλοκη διαδικασία του οργανισμού προκειμένου να διατηρήσει την ισορροπία φυσιολογικής καταστροφής και αναγέννησης αυτών. Πιθανός ρόλος της διαταραχής του αποπτωτικού μηχανισμού στην παθογένεια διαφόρων παθήσεων του οργανισμού, αποτελεί σήμερα ευρύ πεδίο έρευνας. Σκοπός: Στην παρούσα προοπτική κλινικοανοσοϊστοχημική μελέτη γίνεται προσπάθεια διερεύνησης της αποπτωτικής διεργασίας σε παθήσεις του θυρεοειδούς αδένα (μονήρης όζος, απλή-τοξική βρογχοκήλη). Υλικό: Μελετήθηκαν 55 ασθενείς (9 Α - 46 Γ) Μ.Η:55 έτη. Οι παθήσεις αυτών ήταν: α) απλή πολυοζώδης βρογχοκήλη 30/55 (54,54%), β) τοξική πολυοζώδης βρογχοκήλη 11/55 (20%), γ) μονήρης ψυχρός όζος 11/55 (20%), δ) τοξικό αδένωμα 3/55 (5,46%). Όλοι υπεβλήθησαν σε ολική θυρεοειδεκτομή και η μετεγχειρητική τους πορεία υπήρξε ομαλή. Μέθοδος: Μελετήθηκαν σε κυτταρολογικά επιχρίσματα με FNA υπό άμεση όραση από τη ύποπτη περιοχή και, στο παρασκεύασμα του θυρεοειδούς αδένα, η έκφραση των πρωτεϊνών Fas, Bcl-2 και των γονιδίων p53 και ki67. Για την ανίχνευση και την κατάδειξη των δεικτών χρησιμοποιήθηκε η μέθοδος αβιδίνης-βιοτίνης-υπεροξειδάσης, με χρωμογόνο διαμινοβενζιδίνη (DAB). Επίσης μελετήθηκε η τιμή της TSH στις προαναφερθείσες καταστάσεις. Τα αποτελέσματα αναλύθηκαν και συγκρίθηκαν με το fisher’s exact test ή το unpaired two tailed t-test. Αποτελέσματα: Η ιστολογική εξέταση ανέδειξε την ύπαρξη 6 καρκινωμάτων (10,91%), 5 κολλοειδών όζων (9,1%), 30 θυλακιωδών αδενωμάτων (54,55%), 3 υπερπλαστικών όζων (5,45%), 2 εστιακών θυρεοειδίτιδων (3,63%), 7 θυρεοειδίτιδων Hashimoto (12,73%) και 2 με νόσο Graves (3,63%). Η Fas ανευρέθηκε υψηλή με μέση τιμή (μ.τ.) 22,29 στη θυρεοειδίτιδα Hashimoto ενώ η μ.τ. στα θυλακιώδη αδενώματα ήταν 9,7 (p=0,05). Επίσης η έκφραση της Fas ήταν υψηλή στα αδενώματα με νορμοθυλακιώδη συνιστώσα σε σχέση με αυτά με μεγαλοθυλακιώδη συνιστώσα με p=0,04. H έκφραση της Bcl-2 στη θυρεοειδίτιδα Hashimoto εμφανίστηκε ιδιαίτερα αυξημένη μ.τ. 77,4, ενώ στα θυλακιώδη αδενώματα η μ.τ. ήταν 52,41 (p=0,02). Η έκφραση του μιτωτικού δείκτη ki67 βρέθηκε στη Hashimoto μ.τ. 3,7 ενώ στα θυλακιώδη αδενώματα ήταν 1,36 (p=0,03). Επίσης το ki67 ήταν αυξημένο στα αδενώματα με μικροθυλακιώδη συνιστώσα μ.τ. 2,67 σε σχέση με αυτά χωρίς μικροθυλακιώδη συνιστώσα με p=0,05. Η έκφραση της p53 ήταν αμελητέα σε όλες τις παθολογικές καταστάσεις. Η τιμή της TSH ανευρέθηκε στατιστικά σημαντικά υψηλή στη θυρεοειδίτιδα Hashimoto σε σχέση με τα θυλακιώδη αδενώματα με p=0,001. Οι μετρήσεις που προαναφέρθηκαν της έκφρασης των πρωτεϊνών και των γονιδίων στο υλικό της FNA αποδείχθηκαν αναξιόπιστες και ανεπαρκείς. Συμπέρασματα: 1. Η βιοψία του θυρεοειδούς δια λεπτής βελόνης (FNAB) ακόμη και υπό άμεση όραση φαίνεται να είναι αναξιόπιστη στον προσδιορισμό των αποπτωτικών - ανοσοϊστοχημικών δεικτών στην θυρεοειδίτιδα Hashimoto, στους όζους του και στον καρκίνο του θυρεοειδούς αδένα. 2. Η FNAB ακόμη και υπό άμεση όραση είναι επίσης αναξιόπιστη στη διαφορική διάγνωση μακροθυλακιωδών αδενωμάτων από μικροθυλακιώδη και κολλοειδή βρογχοκήλη. 3. Στην ιστολογική εξέταση στη θυρεοειδίτιδα Hashimoto διεπιστώθησαν τα κάτωθι: α) υπάρχει έκφραση της Fas πρωτεΐνης με μέση τιμή 22,29%, β) υπερέκφραση της Bcl-2 με μέση τιμή 77,14%, γ) έκφραση της ki67 πρωτεΐνης με μέση τιμή 3,4%, δ) στατιστικά σημαντική αύξηση (p=0,05) της TSH σε σύγκριση με την αντίστοιχη στα θυλακιώδη αδενώματα. 4. Στην ιστολογική εξέταση των αδενωμάτων με μικροθυλακιώδη συνιστώσα διεπιστώθη στατιστικά σημαντική αύξηση της ki67 πρωτεΐνης (p=0,05) σε σύγκριση με αυτά χωρίς μικροθυλακιώδη συνιστώσα