[Anaplastic thyroid carcinoma: a case report]. / Anaplasticheskaya kartsinoma shchitovidnoi zhelezy.

Anaplastic thyroid carcinoma is a high-grade aggressive tumor with a tendency for early metastasis. The paper describes a rare case of Stage IVB anaplastic thyroid carcinoma, including its clinical, instrumental, morphological, and autopsy findings, in a 66-year-old woman.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

[Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency]. / Sakharnyi diabet i nealkogol'naya zhirovaya bolezn' pecheni: grani sopryazhennosti.

AIM: To estimate the incidence of hepatic steatosis (HS) and liver fibrosis (LF) in patients with diabetes mellitus (DM), by applying the noninvasive techniques of liver fibroelastometry (LFE) and a battery of fibrotests (FTs); to determine their diagnostic value and to identify factors influencing the development of LF. SUBJECTS AND METHODS: A comprehensive examination was made in 82 diabetic patients (mean age, 56.7±12.7 years; p=0.033). The data were statistically evaluated using ROC curve analysis, correlation and single-factor analyses of variance, and multiple logistic regression analysis. RESULTS: FTs and LFE revealed that the DM patients had liver cirrhosis (LC) (METAVIR F4) in 12 (14.6%) and 15 (18.2%) patients, respectively. Those showed clinically significant fibrosis (METAVIR fibrosis stages F2-3) in 19 (23.1%) and 23 (28%) patients, respectively. Varying degrees of HS were present in 79 (96.3%) patients. LFE and FTs demonstrated comparable results in detecting LC (the area under the receiver operating characteristics curve (AUROC), 0.83 and 0.81, respectively). The development of LF is influenced by factors, such as the degree of HS, obesity, the activity of an inflammatory process, and the level of alanine aminotransferase and α2-macroglobulin. CONCLUSION: Diabetic patients are at high risk for NAFLD to develop LF and LC. LFE and FTs showed a comparably high accuracy in the diagnosis of LC in patients with DM and these may be used for screening. With allowance made for the existing risk factors of LF and LC, it is necessary to identify groups of patients with DM for further examination and follow-up. Patients who are diagnosed with stage F4 should be examined carefully to evaluate concurrent diseases and to make liver biopsy.

[A new non-invasive method for assessing steatosis in chronic liver diseases].

AIM: To assess the diagnostic accuracy of the controlled attenuation parameter (CAP) to determine the grade of hepatic steatosis (HS) in patients with chronic liver diseases (CLD) of different etiologies and to compare the obtained results with morphological findings. MATERIALS AND METHODS: A total of 45 patients (18 men and 27 women) aged 25 to 73 years with CLD were examined. All the patients underwent liver puncture biopsy for assessing the HS index and fibrosis stage, as well as determination of hepatic elasticity (F, kPa) for estimating the stage of fibrosis and the grade of HS by CAP (S, dB/m) using a FibroScan device. When assessing HS, the CAP values of <229, 230-249, 250-276, and more than 277 dB/m correspond to HS grade 0 (S0), S1, S2, and S3, respectively. This is a pilot study in Russia. RESULTS: CAP is a rather high effective method in determining the absence of steatosis (S0) (the area under the receiver operating characteristics curve (AUROC) was 0.78) and severe steatosis (S3) (AUROC 0.90). AUROC was 0.64 and 0.59 for HS S1 and S2, which is regarded as satisfactory and poor RESULTS: respectively. Only 3 out of the 45 patients had HS, as evidenced by morphological examination; and the results of CAP showed another result; all the other cases had a HS grade corresponding to S1. In the entire cohort of the examinees, the sensitivity, specificity, and accuracy of CAP was 86, 69.5, and 78%, respectively; AUROC was 0.77 (95% CI, 0.6587-0.9006; p=0.40). CONCLUSION: CAP is a promising method for the rapid and non-invasive diagnosis of HS in patients with CLD. At the same time, our findings show that it is necessary to clarify the quantitative indicators of the compliance of CAP and morphological evaluation of HS.

[Seronegative celiac disease: A case report].

The paper describes a rare case of celiac disease in the absence of serum anti-tissue transglutaminase (anti-tTG) antibodies. A 51-year-old patient has been suffering from diarrheas for 20 years. He has lost 15 kg gradually; weakness progressed; muscle cramps, leg edemas, and signs of dynamic pseudoobstruction appeared. Morphological examination revealed small intestinal mucosal (SIM) villous atrophy (Marsh IIIC stage). IgA anti-tTG and IgG anti-tTG antibodies were 0.086 and 0.178, respectively. The patient was prescribed a gluten-free diet, water electrolyte solutions to correct metabolic disturbances, and prednisolone. During a control examination after 6 months, the patient had no complaints and gained 22 kg, and the SIM villus height was increased. The specific feature of the case is specific negative serological tests for celiac disease.

Intestinal knockout of Nedd4 enhances growth of Apcmin tumors.

Nedd4 (Nedd4-1) is an E3 ubiquitin ligase that belongs to the HECT family and comprises a C2-WW(n)-HECT domain architecture. Although it has been reported to regulate growth factor receptors and cellular signaling, its role in cancer development has been controversial, with some studies proposing that it promotes cancer while others suggest it inhibits tumor growth. Here, we tested the effect of Nedd4 on intestinal tumor formation and growth using Nedd4-knockout mice (Nedd4 floxed (fl) mice crossed to villin-Cre mice). Although we find that knockout of Nedd4 on its own does not cause tumor growth, its knockout in the context of Apc+/min-derived colorectal tumors leads to augmentation of tumor growth, suggesting that Nedd4 normally suppresses intestinal WNT signaling and growth of colonic tumors. WNT signaling microarray, immunoblotting and immunohistochemistry analyses of tumors derived from the Villin-Cre;Nedd4fl/fl;Apc+/min colons demonstrated elevated expression of the WNT upstream effectors LEF1 (full length) and YY1 in these tumors relative to control (Apc+/min alone) tumors. Together, these results suggest that Nedd4 suppresses colonic WNT signaling and tumor growth, at least in part, by suppressing the transcription factors LEF1 and YY1.

[Clinical and morphological characteristics, diagnostic criteria, and outcomes of surgical treatment of TSH-secreting pituitary adenomas]. / Kliniko-morfologicheskie kharakteristiki, diagnosticheskie kriterii i rezul'taty khirurgicheskogo lecheniya TTG-sekretiruyushchikh adenom gipofiza.

Thyrotropinomas (TSH-secreting tumors) are a rare type of pituitary adenomas, which account for about 0.5-2.0% of all pituitary tumors. The criterion of thyrotropinoma is visualization of the tumor in the presence of a normal or elevated level of the thyroid-stimulating hormone (TSH) in the blood and elevated concentrations of free T4 (fT4) and free T3 (fT3). OBJECTIVE: To study the clinical, diagnostic, and morphological characteristics and treatment outcomes of TSH-secreting pituitary tumors. MATERIAL AND METHODS: The study included 21 patients aged from 15 to 67 years with pituitary adenoma and a normal or elevated blood TSH level combined with elevated fT4 and fT3 levels who were operated on at the Neurosurgical Institute in the period between 2002 and 2015. Before surgery, in the early postoperative period, and 6 months after surgery, the patients were tested for levels of TSH, fT4, fT3, prolactin, cortisol, the luteinizing hormone (LH), the follicle-stimulating hormone (FSH), estradiol/testosterone, and the insulin-like growth factor (IGF-1). The thyroid status was evaluated using the following reference values: TSH, 0.4-4.0 mIU/L; fT4, 11.5-22.7 pmol/L; fT3, 3.5-6.5 pmol/L. An immunohistochemical study of material was performed with antibodies to TSH, PRL, GH, ACTH, LH, FSH, and Ki-67 (MiB-1 clone); in 13 cases, we used tests with antibodies to somatostatin receptors type 2 and 5 and to D2 subtype dopamine receptors. RESULTS: Thyrotropinomas were detected in patients aged from 15 to 67 years (median, 39 years), with an equal rate in males (48%) and females (52%). Before admission to the Neurosurgical Institute, 11 (52%) patients were erroneously diagnosed with primary hyperthyroidism; based on the diagnosis, 7 of these patients underwent surgery on the thyroid gland and/or received thyrostatics (4 cases). Hyperthyroidism symptoms were observed in 16 (76%) patients. The blood level of TSH was 2.47-38.4 mIU/L (median, 6.56); fT4, 22.8-54.8 nmol/L (median, 36); fT3, 4.24-12.9 pmol/L (median, 9.66). Tumors had the endosellar localization in 4 (19%) cases and the endo-extrasellar localization in 17 (91%) cases. Total tumor resection was performed in 7 (33%) patients. All these tumors had the endosellar and endo-suprasellar localization. No total resection was performed in patients with infiltrative growth of adenoma (invading the skull base structures). An immunohistochemical study of tumor resection specimens detected only TSH expression in 3 (14%) cases; 18 (86%) tumors were plurihormonal and secreted TSH and GH and/or PRL. Of 13 tumors, expression of the type 2 dopamine receptor was detected in 9 (69%) cases; expression of somatostatin receptors type 5 and type 2 was found in 6 (46%) and 2 (15%) cases, respectively. CONCLUSION: The criterion for total tumor resection was a postoperative decrease in the TSH level to 0.1 mIU/L or less. Total resection was performed in 33% of patients with tumors of only the endosellar and endo-suprasellar localization. In most cases, tumors were plurihormonal and secreted TSH and GH and/or PRL.

[Mesenteric inflammatory veno-occlusive disease is a rare nosological entity: Literature review and the authors' clinical observation].

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare disease. Its basis is inflammation of the small and medium-sized mesenteric veins, which is generally complicated by thrombosis and intestinal ischemia. Arteries are not therewith involved in the process. According to the location, either ischemic jejunitis (ileitis) or segmental colitis develops. The etiology and incidence of MIVOD are unknown. Only a few tens of descriptions of clinical cases have been published. MIVOD is differentially diagnosed with Crohn's disease and vasculitides (Behçet's syndrome, Buerger's syndrome, rheumatoid arthritis, and systemic lupus erythematosus). The paper presents a MIVOD patient with partial thrombosis of portal, superior mesenteric and splenic veins, pylephlebitis, extrahepatic portal hypertension and with ischemic jejunitis complicated by fistulas, subcompensated stenosis, and seropurulent peritonitis. At laparotomy, an infiltrate with multiple interintestinal abscesses and a 40-cm jejunal segment with 4 fistular openings up to 1.5 cm in diameter and necrotic walls were removed and an interintestinal anastomosis was applied. A morphological examination of the operative material detected thrombi, stases, and pronounced plethora of the veins with fibrinoid changes in their walls. The lumen of arterial vessels of different diameters was free. No signs of systemic vasculitis and Crohn's disease were found. The postoperative period was uncomplicated.

[Breast carcinoma metastasis to the optic nerve: case report and review of literature].

Metastatic tumours of the optic nerve are extremely rare. The review of literature revealed only 12 cases of breast carcinoma metastasis to the optic nerve. All patients survived less then 6 month after surgical treatment. We describe a case of metastatic breast carcinoma to the optic nerve that occurred 8 years after radical mastectomy followed by chemotherapy. The metastasis manifested with progressive decrease in visual acuity in the right eye during 3 month. CT and MRI demostrated enhancing lesion in the muscle cone apex of the right orbit with an extension to the optic canal. The presumable diagnosis was optic nerve sheath meningioma, and surgical resection was performed. The tumour involved the optic nerve and has been resected togeher with the nerve. Histology report confirmed metastatic tumour. Postoperatively, the patient received additional stereotactic radiotherapy. Patient died of tumour dissemination 2,5 years after surgery. Breast carcinoma metastases to the optic nerve usually have unfavorable prognosis both for survival and for visual acuity. Isolated metastatic tumors of the optic nerve remain a diagnostic challenge because of their clinical and radiological similarities to more common primary tumors of the optic nerve.

[Lung cancer metastases to the brain: clinical and morphological prognostic factors].

Brain metastases (BM) are the most frequent intracranial SOL and extremely heterogeneous group of tumours from morphological point of view. Nevertheless, studies devoted to BM up to now paid little attention to the histogenesis of the primary tumour. Lung carcinoma is the most common source of BM; morpologically this is a very heterogeneous group of tumors, and they demostrate different clinical pathway and outcome. The aim of present study was to evaluate clinical and morphological prognostic factors in 126 patients with lung carcinoma metastases to the brain, operated in 2004-2010 at Burdenko Neurosurgical Institute. Statistical analysis demonstrated that age, gender, amount and location of BM, primary operation and even histological tumour type were not significant prognostic factors, meanwhile absence of extracranial metastases and Karnofsky index above 70 were significant factors of the favorable prognosis.

[Primary and metastatic Ewing sarcoma of the skull base - case reports and comparative analysis].

UNLABELLED: The aim of the present study was to evaluate and compare diagnostic/and treatment modalities of primary and metastatic Ewing sarcoma (ES) of the skull base. MATERIAL AND METHODS: We analyzed nine cases of the skull base ES patients operated in Burdenko Neurosurgical Institute from 2003 to 2011. Among them there were five cases of primary ES, the other four were of metastatic origin. Clinical history, neuroimaging and pathology data together with IHC are presented. Treatment options and results are discussed. Seven patients were operated transcranially, in the other two cases endoscopic endonsnasal operations/were performed. Mean follow up was 11-92 months. RESULTS: We did not reveal arW pathological or IHC differences between primary and metastatic tumors. The labeling index Ki-67 was insignificantly higher in the metastatic tumors gro'Vip. In one case the patient developed relapse of the metastatic tumour in the temporal bone; he underwent second surgery and died 7 months after the operation. CONCLUSION: Despite both metastatic and primary ES of the skull base are of maMignant behavior, the long-term relatively good prognosis can be achieved when combined treatment, including surgery, chemotherapy and radiation is applied.

[Biology of the craniopharyngioma].

In the recent years a considerable number of different studies devoted to craniopharyngioma morphology were performed. There are more than 35 factors known up to date that could be related to the craniopharyngioma growth (Ki-67, p53, beta-catenin, p63, Retinoid acid receptors, Galectin-3, MIF, MVD, CK et al.). Despite the such a variety of factors, none of them, except for the Ki-67, strongly correlates with the risk of tumour recurrence and none can be associated with a particular tumour type. Most studies, by the way, focused on a very small number of factors and were performed in relatively small groups of patients. Most publications are devoted to the Ki-67, beta-catenin and p53 studies, and the highest number of patients enrolled to the study was 67. This survey made an attempt to review the literature on the craniopharyngioma biology and to identify further areas of research to obtain data that could affect the choice of treatment and outcome in this complex disease.

[Orbitosphenopetroclival meningeomas: clinical and topographic features and results of combined treatment]. / Orbitosfenopetroklival'nye meningiomy: kliniko-topo-grafi-cheskie osobennosti i rezul'taty kombinirovannogo lecheniia.

UNLABELLED: The aim of the study was to access clinical and topographic features of orbitosphenopetroclival meningeomas and the results of surgical and combined treatment in patients with meningeaomas of that location. Orbitosphenopetroclival meningeomas comprise a peculiar group of tumors and are the result of infiltrative sphenopetroclival meningeomas progression, when the latter extend into the orbit and temporal fossa. Development of neurosurgery, use modern approaches and adjuvant therapies such as stereotaxic radiosurgery and radiotherapy in the past years markedly improve treatment results in these patients. However, difficulties in treatment strategy choice remain. One attempting to excise a tumor radically encounters with the risk of damage to critically important neurovascular structures. When a tumor is excised partially the risk of complication dwindles, however risk of relapse increases. Palliative surgery improve patients' quality of life. Radiosurgery and irradiation of residual tumors allow to establish control on a tumor growth. MATERIAL AND METHODS: Twenty three patients were studied, of them 20 received surcery, 9 - stereotaxic irradiation, 5 - conventional irradiation. The follow-up interval comprised 8-84 months (median 37 months). RESULTS: Manifestations of orbitosphenopetroclival meningeomas are combined from signs and symptoms of cranioorbital and petroclival meningeomas, and in many patients include signs of skull base external surface involvemevt, marked cosmetic deficits and psychological distress. Orbitosphenopetroclival meningeomas originate from cavernous sinus and medial parts of sphenoid bone wings. During its progression a tumor extends onto orbit and onto clivus, and then onto infratemporal and sphenopalatine fossae, nasopharynx and posterior cranial fossa. CONCLUSION: If a residual tumor is present patients with orbitosphenopetroclival meningeomas should undergo adjuvant irradiation after the first surgery.

[Transformation of trigeminal nerve tumor into malignant peripheral nerve sheath tumor (MPNST)].

Malignant peripheral nerve sheath tumor (MPNST) is a rare entity with only 18 cases of trigeminal nerve MPNST described by now and only one report of malignant transformation of trigeminal nerve tumor into MPNST published up to date. One more case of malignant transformation of trigeminal nerve (1st division) tumor into MPNST is demonstrated.

[Thyrotropin secreting pituitary adenoma in a child: case report and literature review].

We present a case of 11-year old boy with Type 1 Autoimmune Polyglandular Syndrome and thyrotropin secreting pituitary adenoma, which was diagnosed by elevated TSH and thyroid hormones levels and MRI signs of pituitary tumor and without clinical symptoms of hyperthyroidism. He underwent partial resection of the tumor via transnasal approach and subsequent radiation therapy. Consequently 1 year after XRT patient developed growth hormone deficiency, 3.5 years later patient became euthyroid, and 5.5 years after treatment - hypothyroid. This is the first described case of coexistence of this 2 rare endocrine diseases in the same patient.

[Hormonally inactivated pituitary adenoma: morphological, immunohistochemical and electron-microscopic characteristic].

Morphology of hormonally inactivated pituitary adenoma can be different types of tumors. Morphological immunohistochemical and electron-microscopic researches of 23 hormonally inactivated pituitary adenomas has been carried out. We shown that more frequent morphological substrate was gonadotropinoma or "zero-cells" adenoma. According to our results, gonadotropinomas, "zero-cells" adenomas and oncocytomas have similar features and can be put into the same group of tumor Pathomorphologist has to differentiate this group of tumors from others "silent" pituitary adenomas because they have different prognosis for a disease. A research of somatostatin and dopamine receptors expression would be new area for differential diagnosis of these types of adenomas.

[Differential diagnosis between melanotic schwannoma of gasserian ganglion and metastatic melanoma of middle cranial fossa].

We present a case of a rare tumor--melanotic schwannoma of trigeminal nerve root and gasserian ganglion. Differential diagnosis between metastatic melanoma and melanotic schwannoma (MS) is associated with serious difficulties and high responsibility. Metastatic melanoma is a high grade tumor while most MS are benign lesions with good outcome. By the date 105 cases of these tumors are described in the world literature, 3 of them originated from trigeminal nerve root and gasserian ganglion. MS predominantly occur in relatively young patients, they are characterized by presence of Carney's complex and psammomatous bodies and absence of primary focus. MS and metastatic melanoma have similar appearance on MRI due to presence of melanin granules. Indirect signs evident for MS include cystic structure and dumbbell-shaped growth. Metastatic melanoma of cranial nerves is more typical in people older than 40, primary focus in the face in the zone of innervation of affected nerve is common. In case of absence of the listed features differential diagnosis is based on immunohistochemical analysis and electron microscopy of tissue samples.

[Stereotactic radiotherapy for cerebral metastases using CyberKnife].

During recent decade development of frameless techniques of fixation enabled introduction of stereotactic radiation therapy in metastatic brain lesions and made possible irradiation of large foci involving or proximal to eloquent and critical brain areas. This paper focuses on comparative analysis of effectiveness of hypofractionation (HRST) and radiosurgery (SRS) using CyberKnife system in cerebral metastases. Since November 2009 till June 2011 54 patients with cerebral metastases were treated using CyberKnife system. Age of patients ranged between 25 and 77 years (mean 54 years). 16 patients received radiosurgical treatment (mean total dose was 22.5-35 Gy, number of fractions varied from 2 to 7, mean volume of irradiation was 22.69 cm3) and 8 patients were treated by HRST with RS of selected foci (mean total dose reached 23 and 30 Gy, mean volume of irradiation was 1.02 cm3 and 11.19 cm3, respectively). Indices of overall regression and stabilization of disease for HRST and SRS groups were 81% and 79%, respectively. With mean follow-up period of 12.3 (1-16.1) months median survival for SRS and HRST reached 6.38 (1-15.8) and 6.2 (0.2-16.1) months and median recurrence-free survival was 3.6 (1-13.6) and 5.5 (2-14.2) months, respectively. Obtained results confirmed biological advantages of fractionated stereotactic radiotherapy of large cerebral tumors in comparison with radiosurgery. Prospective studies with rigid criteria of inclusion are required to determine optimal dose/volume/fractionation interrelations in stereotactic radiation treatment of cerebral metastases.