PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

Galectin-3 expression in thyroid fine needle cytology (t-FNAC) uncertain cases: validation of molecular markers and technology innovation.

Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis.

The dual Aurora kinase inhibitor ZM447439 prevents anaplastic thyroid cancer cell growth and tumorigenicity.

The anaplastic thyroid cancer (ATC) is among the most aggressive human tumors which fail to respond to all the currently available therapeutic approaches. As a consequence most patients die within a few months from diagnosis. In the present preclinical study, the effects of the ZM447439, a functional inhibitor of Aurora kinases, on the growth and tumorigenicity of a panel of ATC derived cell lines (CAL-62, 8305C, 8505C and BHT-101) were evaluated. The treatment of the different ATC cells with ZM447439 inhibited proliferation in a time- and dose-dependent manner, with IC50 comprised between 0.5 mM and 5 mM. Moreover, the drug remarkably impaired the formation of colonies in soft agar of all the cell lines. Consistently with Aurora inhibition, immunofluorescence and immunoblotting experiments demonstrated that Aurora auto-phosphorylation following drug treatment was completely abrogated, and treated cells were characterized by the presence of multiple spindles with short microtubules. In the same experiments we observed the loss of histone H3 phosphorylation on Ser10, specifically due to Aurora-B, after ZM447439 treatment. Time-lapse videomicroscopy and flow cytometric analysis demonstrated that in presence of ZM447439 the cells were able to enter mitosis but not to complete it, becoming polyploid. Almost all the ATC cell lines studied showed increased apoptosis after only 48 h of treatment. In conclusion, our data demonstrate that ZM447439 is effective in reducing cell growth and tumorigenicity of different ATC derived cell lines, and further investigations are needed to exploit its potential therapeutic value for ATC treatment.

Diagnostic utility of thyroglobulin measurement in the fine needle aspirates from cervical lymph nodes: a case report.

Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.

Subfascial endoscopic perforator surgery (SEPS) in chronic venous insufficiency. A 14 years experience.

INTRODUCTION: Subfascial Endoscopic Perforator Surgery (SEPS) enables the direct visualization and section of perforating veins. Morbidity and duration of hospitalization are both less than with conventional open surgery (Linton's or Felder's techniques). PATIENTS AND METHODS: A total of 322 legs from 285 patients with a mean age of 56 years (range 23-90) were treated at our Department from May 1996 to January 2010. In 309 cases, an endoscope (ETM Endoskopische Technik GmbH, Berlin, Germany) was introduced through a transverse incision approximately 1.5 cm in length and 10 cm from the tibial tuberosity, as with Linton's technique. A spacemaker balloon dissector for SEPS, involving a second incision 6 cm from the first, was used in only 13 cases. RESULTS: The procedure used in each case was decided on the basis of preoperative evaluation. SEPS and stripping were performed in 238 limbs (73.91%), SEPS and short stripping in 7 limbs (2.17%), SEPS and crossectomy in 51 limbs (15.84%), and SEPS alone in 26 limbs (8.07%). 103 patients presented a total of 158 trophic ulcers; the healing time was between 1 and 3 months, with a healing rate of 82.91% after 1 month and 98.73% after 3 months. CONCLUSION: Subfascial ligature of perforating veins is superior to sclerotherapy and minimally invasive suprafascial treatment for the treatment of CVI. It is easy to execute, minimally invasive and has few complications.

[Micromedullary thyroid carcinoma: school experience]. / Il microcarcinoma midollare della tiroide: esperienza di Scuola.

Medullary microcarcinomas occurrence are rare and fortuitous, it's usually related to the calcitonin measurement, that's the gold standard for the diagnosis. In other cases performing a thyroidectomy for a benign thyroid disease it's found a sub-centimeter tumor. Actually it's not clear the most appropriate surgical treatment for those kind of tumors because the number of cases in literature is limited and because there are different surgical approaches. In this study 17 patients were operated for medullary thyroid microcarcinoma and the Authors found central lymph node metastases in 33.3% of cases. The Authors, analyzing those results, think that total thyroidectomy with lymphadenectomy of the central compartement is the best choice in a sporadic microcarcinoma, while a total thyroidectomy without lymphadenectomy should be performed when the microcarcinomas are incidentals.

[Case-mix index and length of hospitalization]. / L'indice di case-mix e la durata della degenza.

The ACG (Adjusted Clinical Groups) case-mix system is a classification method of diseases of patients, focused on the person. Depending on the pattern of these morbid conditions, the ACG system assigns each patient to a single group (an ACG group), which allows to capture the effects of a group of diseases in estimates of resource use. Diseases are classified into a diagnostic group (ADG) according to 5 clinical dimensions: duration (acute, recurrent or chronic), severity (minor/major vs stable/unstable), diagnostic assessment (symptoms vs diseases), etiology (infectious, traumatic or other), specialty (medical, surgical, obstetric, ...). All diseases can be classified into these dimensions and into one of 32 groups. The ACG case-mix system uses an algorithm to classify each patient into one of 93 ACG categories. Each person is assigned to an ACG according to his ADG combination, his age and his gender. With the repayment system "case-mix", surgery has become central for all great hospitals in virtue of its great productive potential. The case-mix index is one of the factors which influence the duration of hospitalization. The case-mix system has emphasized the importance of the duration of hospitalization, encouraging the planning of programs in order to discharge patients early after surgical operations. It has also stimulated the surgical activity in operating units with "budget" forecasts in which resources are provided according to an expected level of specialist surgery.

Angiomegaly and arterial aneurysms.

Angiomegaly is characterized by an alteration in the elastic component of arterial and venous vessels determining their elongation and tortuousness. This involves an increased risk of thromboembolism and aneurysmal degeneration in affected subjects, even if they have been asymptomatic for a long time. The aim of this study is to demonstrate the correlation between angiomegaly and aneurysmal disease. A total of 163 patients suffering from a peripheral arterial aneurysm were included, 74 of these with an iliac aneurysm, 41 with a femoral aneurysm and 48 suffering from popliteal aneurysm. All patients were examined by color Doppler ultrasonography (CDU) and angio-CT with contrast medium. Eighteen cases of arteriomegaly were diagnosed, and the prevalence in the examined population was 11%. This study demonstrates the close association existing between aneurysms in peripheral arteries and arteriomegaly. Peripheral arterial aneurysms in association with arteriomegaly involve an increased risk of complications like thrombosis, embolism and rupture. The showed familiarity in the arteriomegaly incidence leads to predisposition of screening programs, using CDU, among relatives of patients affected by arteriomegaly and/or peripheral arterial aneurysms.

Thyroid tissue remnants after "total thyroidectomy".

Total Thyroidectomy (TT) is a gold standard for benign bilateral pathologies and malignant pathologies of the thyroid. TT has numerous advantages over less radical approaches, such as the resolution of the thyroid pathology, avoidance of recurrences, and improved response to life-long substitutive organotherapy. TT has a negligible rate of recurrence. Near Total Thyroidectomy (NTT) is associated with a low rate of recurrence. Subtotal Thyroidectomy (ST), in which a portion of the thyroid gland is deliberately left in the thyroid lodge, has a considerably higher rate of recurrence. The incidence of complications with TT is similar to that with other techniques of thyroid exeresis. However, despite the radical intent of surgeons, a real TT is not always carried out. The complete removal of all the thyroid tissue employing TT is not the norm and micro/macroscopic remnants almost always remain. The literature on these tissue remnants is often based on techniques that are not very accurate in terms of determining the diameters of the tissue remaining. In our study, conducted by colour echo-doppler of the thyroid lodge in 102 patients who had undergone TT for benign thyroid pathologies, we demonstrated significant thyroid tissue remnants after TT in 34 cases of 102 (33,3%). Therefore, out of a total of 102 so-called "total thyroidectomies", only 68 (66,7%) were really total, whereas 12 patients (11,76%) had near total thyroidectomy, leaving tissue remnants < 1 cm, and 22 patients (21,57%) had subtotal thyroidectomy, with tissue remnants > or = 1 cm.

[Retroperitoneal giant mixed sarcoma. Case report]. / Un caso di sarcoma misto retroperitoneale gigante.

The Authors present a rare case of voluminous retroperitoneal tumor in a 41 years old woman. CT scan showed a solid abdominal expansive mass, with compression and displacement of the left lobe of the liver, spleen, stomach, pancreas, and left kidney. The patient underwent surgery for excision of a giant retroperitoneal mass. Surgery was uneventful. The patients recovered well. Histology showed a mixed liposarcoma and angiosarcoma with high grade of malignancy and positivity for vimentin, factor VIII, CD34, CD31 and negativity for S-100, CD68, AMS, AML. The prognosis of these tumours is closely related to local recurrence, histological type, size and radical surgery. A low-grade malignancy tumor, small sized and completely resected leads to a good prognosis. Radiation therapy and chemotherapy do not seem to have a strong influence on the prognosis. An aggressive surgical approach is the first choice for the treatment of such tumors. The resection of adjacent organs may be required for radical surgery.

[Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery. 1st Consensus Conference]. / Protocolli Gestionali Diagnostico-Terapeutico-Assistenziali in Chirurgia Paratiroidea. 1 feminine Consensus Conference.

AIM: The aim of the study was to draw up a management protocol in parathyroid surgery promoted by the Italian Association of Endocrine Surgery Units (UEC Club), based on the guidelines of the main international scientific societies and shared by the experts and applied by the operators in the sector. METHODS AND CONSENSUS: The management protocols, already presented in 2003, on the occasion of the current review were examined by the 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC). The Conference comprised two distinct sessions, the first in November 2006 within the framework of the 5th National Congress of the UEC Club in Verona, and the second in September 2007 within the framework of the 10th Multidisciplinary Scanno Prize Meeting. A selected board of endocrinologists and endocrine surgeons examined the individual chapters and submitted the consensus text for the approval of several experts. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in parathyroid surgery approved by the 1st Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by October, 2009.

Differential expression of the components of the plasminogen activating system in human thyroid tumour derived cell lines and papillary carcinomas.

We characterised the expression of the plasminogen activators (uPA and tPA), the uPA receptor (uPAR) and the PAs inhibitors (PAI-1 and PAI-2) in human thyroid cell lines derived from normal thyroid, follicular adenoma, follicular, papillary and anaplastic carcinomas. Urokinase PA activity was detected in the supernatant of normal thyrocytes and augmented in those of all tumour cells. Quantitative RT-PCR analysis showed that uPA, uPAR and PAI-1 mRNAs increased in all carcinoma cells. Similar results were found in 13 papillary thyroid carcinoma (PTC) tissues which were mirrored in Western blot experiments. A correlation was found between tumour size and uPA mRNA increase, and higher levels of uPA and uPAR mRNAs were found in metastatic PTC. In conclusion, thyroid carcinoma cell lines and PTC overexpress uPA, uPAR and PAI-1 and the correlation of uPA and its cognate receptor with tumour size and metastasis may suggest their potential prognostic relevance in thyroid cancer.

Radiolabelled monoclonal antibodies in clinical and surgical oncology: a review.

Over the past decade, the role of immunoscintigraphy using radiolabelled monoclonal antibodies has been steadily growing in clinical oncology, and in particular, in radioimmunotherapy and radioimmunoguided surgery for the treatment of primary, recurrent, and metastatic colorectal, ovarian, gastric, and prostate cancer. Herein, the authors review the requirements for successful tumour radioimmunodetection and related procedures.

Scintigraphy with 99mTc-MIBI and echography in the study of primitive hyperparathyroidism.

BACKGROUND: The authors analyse the value of the exams preoperative for the identification of the pathological parathyroid glands. METHODS: The authors examined 58 patients affected by primitive hyperparathyroidism (HPTp) who had undergone surgical treatment for primary hyperparathyroidism at the Third Surgical Department of University "La Sapienza" of Rome, in 175 patients affected by primitive hyperparathyroidism observed between January 1970 and June 2000; all patients had undergone echotomography of the neck and 99mTc-MIBI scintigraphy in the diagnostic phase. The histological valuation confirmed the diagnosis by I.P. RESULTS: 99mTc-MIBI scintigraphy demonstrated the pathological glands in 56 cases (96.6%), the echography in 57 cases (98.2%). The comparison of the two exams demonstrated the pathological glands in 100% of the cases. In 45 cases the scintigraphy localized the side (77.6%), and the echography in 41 cases (70.7%). In one case demonstrated I.P. persistent (1.7%) and never one case demonstrated relapsed. CONCLUSIONS: The authors think that the scintigraphy together with the echography show high sensibility to identification the pathological glands. Neck surgical exploration can still give the side good when the diameter of the parathyroids is inferior to 5 mm.

Angiomegaly.

The authors report a clinical and ultrastructural study on a group of patients with angiomegaly, a vascular disorder characterized by elongated and distended blood vessels affecting the arterial (arteriomegaly) and/or venous system (venomegaly). The arterial group, drawn from a large arteriographic series, focuses on a comparison between atherosclerotic arteriopathy and arteriomegaly. The venous group, drawn from a large ultrasound series of vein disorders, is made up of patients with venomegaly. Venomegaly gives rise to few or no symptoms and it appears to be less frequent than arteriomegaly but as the latter proved to be associated in the majority of cases studied. Based on ultrastructural findings, the chief abnormality of angiomegaly seems to lie in a specific alteration of the elastic component of the vessel wall. We found slightly osmiophil amorphous elastic material neighbouring the basement membrane of the myocytes of the vessel walls. In the superficial parts of these myocytes occurred a great number of pinocytotic vesicles indicating for a rich creation of the new elastic material. Middle or highly osmiophil thick elastic fibers with irregular side protrusions were also found among myocytes remembering the moth-eaten picture. Results from a large ultrasonographic study on patients' relatives suggest an inheritability of this vascular disorder.

Hepatic echinococcus disease: our experience over 22 years.

BACKGROUND/AIMS: It is important to single out the indications for surgery of hydatid disease of the liver at an early stage. For this, a fully comprehensive diagnostic work up of the patient is required. Surgery represents the most effective therapy and involves resection of the cysts and their outer capsule. This must be as complete as possible. MATERIAL AND METHODS: Between 1970 and June 1992, 95 patients received this combined treatment for hydatid disease although only those presenting from 1985 were followed up. RESULTS: No serious complications were noted apart from pyrexia due to secondary cholangitis or reactive pleuritis. This responded quickly to antibiotics and there was no mortality. No cases of relapse occurred although one case did show evidence of reappearance of the disease on serological testing alone, all other tests being negative. CONCLUSION: The most effective treatment for echinococcus cystic disease of the liver is radical surgery. Results are best when surgery is combined with medical therapy of benzoimidazole drugs given pre- and post-operatively. From our experience, we are now confident that surgical treatment must always be preceded and then followed by treatment with benzoimidazole antihelminthics.

Surgical controversies in the treatment of recurrent achalasia of the esophagus.

BACKGROUND/AIMS: Surgery remains the first choice for achalasia of the esophagus with good results in 90% of cases. METHODOLOGY: We studied the cause of failure for surgical treatment and the results of a second operation in 20 patients that were followed up for at least three years. RESULTS: The results were good in 70% of the cases. CONCLUSIONS: To improve this procedure, according to the authors, it is essential for a careful presurgery evaluation, an early reoperation in case of failure and a careful surgical technique in order to avoid periesophageal sclerosis.

Venous drainage of the stomach in the laboratory mouse (Mus musculus v. alba) and the laboratory rat (Rattus norvegicus v. alba).

The authors studied the venous drainage pattern of the stomach in 30 adult laboratory mice (Mus musculus v. alba) and in 31 adult laboratory rats (Rattus norvegicus v. alba) of both sexes. In mice, two basic patterns of the venous drainage of the stomach have been found, the first one (50.0% of cases) with a vena gastroepiploica dextra, while in the second pattern (50.0% of cases) the vena gastroepiploica dextra is absent and the venous blood from the curvatura major ventriculi and fundus ventriculi is drained only via the v. lienalis. In rats, three basic patterns of venous drainage of the stomach were found, the first group (35.2%) with the v. gastroepiploica dextra, the second group (38.4%) with prevalence of the v. gastrica sinistra and the third group with various tributaries of the v. lienalis from the stomach (25.6%). The vena gastrica sinistra is the only constant venous channel in both animals examined. Between interorganic venous anastomoses in the mouse and the rat no great differences exist. In spite of the great variability of veins the results indicate that it is possible to differentiate some basic patterns of the venous drainage of the stomach in the animals studied.

Venous drainage of the stomach in the domestic rabbit (Oryctolagus cuniculus f. domestica, breed large Chinchilla) and the domestic cat (Felis catus L. f. domestica).

Two basic patterns of venous drainage of the stomach were found in rabbits. In the first, which is highly prevalent (27 cases-90.0%), the v. gastroepiploica dextra is present while no such vein is present in the second one. Other venous channels are represented by the v. gastrica sinistra and by tributaries of the v. lienalis. In cats there are also two basic patterns of the stomach venous drainage. The first highly prevalent type without the v. gastroepiploica dextra was found in 23 cases (76.0%); in the second type this vein was present. In rabbits the v. gastroepiploica sinistra was observed in 25 cases (82.5%), in cats in only two cases (6.6%). The v. gastroepiploica dextra in the rabbit is usually a tributary of the v. portae, while in cats it is a tributary of the v. lienalis. In ten rabbits (33.3%) there was a venous arch around the curvatura ventriculi major, while in cats it was absent. The great difference in the stomach venous pattern in rabbits and cats can be explained by the different zoological position of these two kinds of animals.