Vol 44, No 5 (2016)



Braga E.A., Zhinzhilo T.A., Kolpakov A.V., Mikhaylenko D.S., Kushlinskii N.E.


Renal cancer (RC) is a common malignancy of the genitourinary system. Clear cell renal cell carcinoma is the most common histological type of RC. In most cases diagnosis and prognosis of clear cell renal cell carcinoma are based on the results of instrumental tests, while search for novel molecular RC markers and their characterization remain relevant. Molecular genetic abnormalities accompanied with changes in gene expression underly the RC carcinogenesis; however, diagnostic panels of the expression markers of RC are still not widely used. This review represents the results of recent research in the area of gene expression markers of RC aimed to elaborate prognostic test systems. Application of the NotI-microarray methodology allowed for identification of many novel genes associated with RC pathogenesis. The relationship of alterations of expression level and methylation of chromosome 3 genes with RC progression and metastasis has been shown. Based on this data, a  diagnostic marker system for RC have been proposed with identification of expression and methylation profiles and novel markers, that is an urgent problem in modern urologic oncology.
Almanac of Clinical Medicine. 2016;44(5):546-557
pages 546-557 views


Chikh I.D., Trigolosova I.V., Dreval' A.V., Trigolosov A.V.


Acromegaly is a  rare disease with increased growth hormone secretion most often caused by pituitary adenoma. Not adequately treated acromegaly may lead to early death related to increased rates of acute cardiovascular events, sleep apnea, metabolic disorders and malignancies. Prevalence of malignancies in acromegaly is in the range of 4.5 to 25%, with some specifics in their pathogenesis, and their proportion as mortality cause is 9 to 50%. Overall and cancer-related mortality in acromegaly are associated with activity of the disease. There is a direct correlation between high levels of insulin-like growth factor 1 and the risk of malignancies. The most common types of cancer in patients with acromegaly are colorectal (1 to 20%) and thyroid cancer (7.8 to 11%). This review of literature describes the results of epidemiological studies on malignancies and some aspects of their pathogenesis in patients with acromegaly.
Almanac of Clinical Medicine. 2016;44(5):568-579
pages 568-579 views


Grishina E.E., Mamontov A.O.


Ophthalmic manifestations of leukemia are variable and are predominantly represented by leukemic infiltration of the eye and hemodynamic abnormalities in the retinal vasculature. Leukemic infiltration of the retina should be differentiated from an inflammatory process, such as retinitis, chorioretinitis of viral or fungal origin that are not uncommon in patients with hematological malignancies. Retinal involvement is mainly seen in adult patients with acute myeloid leukemia and is less common in patients with acute lymphoblastic leukemia. Retinopathy is more frequent during relapses of the underlying disease. Also, retinopathy can be the first sign of the disease. Leukemia should be included into the list for differential diagnosis with disorders that can be associated with optical nerve edema and retinal hemorrhages. Fundus abnormalities correlate with peripheral blood parameters. Retinopathy and leukemic optic neuropathy are predictors of unfavorable prognosis. Early diagnostics and timely and adequate treatment may fully eliminate ocular symptoms and improve quality of life in patients with hemoblastoses.
Almanac of Clinical Medicine. 2016;44(5):587-591
pages 587-591 views



Parmon Y.V., Saakyan S.V.


Background: Ophthalmologists have a  low oncological vigilance, while oncologists are insufficiently aware of the incidence of choroidal metastases. Aim: To estimate incidence of choroidal metastases in Russia and to analyze prevalence of tumors metastasizing to the choroid. Materials and methods: Based on the literature, we empirically calculated the incidence of choroidal metastases in Russia. Our own study involved 70 patients (56  female and 14  male) with choroidal metastases. All patients underwent complete ophthalmic and physical examination. Results: In Russia, the estimated number of new choroid metastases cases in 2014 was 5561, which is 6-fold higher than the estimated number of primary uveal melanomas. Among 70  patients with choroidal metastases, the primary tumor site was known in 58  (82.8%) patients, whereas in 12 (17.2%) patients with choroidal metastases had an unknown primary tumor. The vast majority of primary tumors were carcinomas (53 patients, 91.4%); 4 patients (6.9%) had melanomas, and one (1.7%) had acute leukemia. Choroidal metastases were the first sign of advanced malignancy in 34 (48.6%) patients. The time periods from the date of diagnosis of the primary tumor to the date of diagnosis of intraocular metastatic tumors varied from  0 to 192  months. Conclusion: Empirical calculation shows that the incidence of choroidal metastasis in the adults is higher than that of the uveal melanoma. Due to the high prevalence of choroidal metastases, they should always be kept in mind if an intraocular neoplasm is detected. When choosing a diagnostic algorithm, special attention should be paid to the cancer history of the patient. The necessity of life-long ophthalmologic screening of patients with malignant neoplasms is hereby justified.
Almanac of Clinical Medicine. 2016;44(5):592-598
pages 592-598 views


Balkanov A.S., Gurov A.N., Katuntseva N.A., Belousova E.A.


Background: The incidence of colorectal cancer ranks the third among all cancer incidence rates. Rectal neoplasms are frequently considered as a separate nosological entity. The incidence of rectal cancer (RC) can be influenced by patient age, gender, lifestyle, diet, genetic factors, as well as by the organization and quality of preventive activities in medical institutions focused on the early cancer diagnosis. Aim: To study changes in RC incidence among residents of the Moscow Region from 2010 to 2014. Materials and methods: The incidence rate of RC was estimated based on the state statistical report data on newly diagnosed cancers in the population of the Moscow Region in 2010–2014. The intensive incidence rates were calculated per 100,000 of respective population in six age and gender groups. Results: From 2010 to 2014, 6079 new RC cases were identified in the Moscow Region, among them 47% men and 53% women. More than half of all RC cases were in the age group of 60 to 79 years old (61.7% of men and 59.2% of women). During the 5-year period, the incidence rate of RC decreased from 18.3 to 17 per 100,000 of the male population and increased from 15.7 to 17.5 per 100,000 among the female population. There was a clear correlation between the RC incidence and the patient age. The peak incidence in men and women was seen in the age group of 70 to 79 years. From the age group of 50 to 59 years and on, the incidence of RC in men was higher than that in women. Conclusion: The results of this study can be used to optimize activities in the public healthcare system aimed at reduction of morbidity and mortality related to RC. Among the priority actions should be allocated to the development and implementation of primary prevention measures, in particular, undergo screening tests (fecal occult blood test or colonoscopy) in age groups at high risk.
Almanac of Clinical Medicine. 2016;44(5):599-605
pages 599-605 views


Babkina I.V., Alferov A.A., Bondarev A.V., Shchupak M.Y., Kuznetsov I.N., Boulytcheva I.V., Solov'ev Y.N., Aliev M.D., Kushlinskii N.E.


Background: The progress in cancer treatment, including bone malignancies, is associated with advances in molecular biology. Based on the results of a  number of studies, treatment of bone sarcomas have been expanded with targeted therapy that uses drugs with targeted actions, including anti-angiogenic and bevacizumab, in particular. It inhibits the binding of a key activator of neoangiogenesis, vascular endothelial growth factor (VEGF), with its receptors type 1 and 2 (Flt-1 and KDR) on the surface of endothelial cells, which results in a  decrease in vascularization and in inhibition of tumor growth. Beyond VEGF, other activators of neoangiogenesis have been identified, such as interleukin 16 (IL-16). Aim: To compare baseline serum IL-16 and VEGF in patients with malignant, borderline and benign bone tumors. Materials and methods: Serum IL-16 and VEGF levels was compared in 138 patients with primary bone tumors: benign (n=10); borderline (giant cell bone, n=22); malignant (n=106), aged 14 to 50 years, by immunoenzyme assay (Biosource, USA for IL-16 and R&D, USA for VEGF) before any specific treatment. Bone malignancies were identified as osteosarcoma (n=45, among them 35  typical, 6 parosteal, and 4 periosteal), chondrosarcoma (n=24), Ewing sarcoma (n=27), and undifferentiated pleomorphic sarcoma (n=7) and chordoma (n=3). Results: The rate of IL-16 identification in the serum of bone tumors patients was 93%, with no significant differences depending on the histological structure of the tumor. No association between the size of primary tumors and IL-16 serum levels was found. Overall 3 and 5-year survival of patients with malignant bone tumors with IL-16 serum levels>33 pg/mL was significantly lower than in those IL-16 levels of≤33 pg/mL. Overall 5-year survival in osteosarcoma patients with higher IL-16 serum levels 1.6-fold lower, in Ewing sarcoma patients, 1.7-fold lower, and in chondrosarcoma patients, 1.8-fold lower than that the patients with IL-16 levels of≤33 pg/mL. VEGF levels in bone sarcomas patients were significantly higher than in those with borderline and benign tumors, whereas statistical analysis did not find any significant difference in VEGF levels depending on the histological structure of the primary tumor. Maximal VEGF levels were found in periosteal osteosarcoma, minimal ones, in parosteal osteosarcoma. Overall 3 and 5-year survival of patients with bone malignancies and serum VEGF concentrations above the mean for the group (> 493 pg/mL) was higher than that in the patients with low VEGF levels. Similar results were obtained in osteosarcoma, whereas in Ewing sarcoma and chondrosarcoma higher 3 and 5-year survival rates were observed in patients with serum VEGF levels below 493 pg/mL. Conclusion: These data suggest that IL-16 and VEGF expression could be associated with pathophysiological changes related to growth and metastatic process of bone sarcomas, and may be a subject for further studies to determine the levels of these biomarkers and their predictive value in bone malignancies.
Almanac of Clinical Medicine. 2016;44(5):606-612
pages 606-612 views


Gurevich L.E., Korsakova N.A., Voronkova I.A., Kazantseva I.A., Ashevskaya V.E., Titov A.G., Kogoniya L.M., Mazurin V.S., Shabarov V.L.


Background: Neuroendocrine tumors of the lung (NETL) are a wide range of tumors with various malignancy grades and prognosis. Despite their prevalence being 20 to 25% of all lung cancers, many aspects that impact their clinical course and prognosis are not well understood. Aim  – to identify morphological and immunophenotypic characteristics of various NETL types would that more accurately reflect their biological potential and allow for prediction of their unfavorable clinical outcomes. Materials and methods: We performed immunohistochemical assessment of the diagnostic biopsies and surgical specimens from 152 patients with NETL aged 53 ± 13 years and identified 49  typical carcinoids, 32 atypical carcinoids, 60  small cell neuroendocrine carcinomas and 11  large cell neuroendocrine carcinomas, which accounted for 32.2, 21.1, 39.5 and 7.2%, respectively. Markers of neuroendocrine differentiation, such as synaptophysin, chromogranin A  and CD56, as well as cytokeratins 7 and 19, thyroid transcription factor-1 (TTF-1), and Ki67 were used. The results were analyzed with analysis of variance (ANOVA), chi-square test (χ²), and post-hoc comparisons with the Bonferroni correction. Results: Most often, the expression of cytokeratins 7 and 19 was found in large cell neuroendocrine carcinoma (72.7 and 90.9%, respectively), less frequently, in atypical carcinoids and small cell neuroendocrine carcinomas (50 and 53.3%; 41.7 and 64.6% of cases, respectively), whereas in typical carcinoids it was rare (5.9 and 15.9%, respectively). The rates of cytokeratin 7 and 19 expression were significantly lower in the typical carcinoids, compared to the atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.05, χ²). The expression of cytokeratin 19 was significantly more common for large cell neuroendocrine carcinomas, than for small cell neuroendocrine carcinomas and atypical carcinoids (р < 0.01, χ²). The expression of TTF-1 was very rare in the typical carcinoid cells (6.5% of cases) and significantly more often in atypical carcinoids (61.5%) and in small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (82.7 and 77.8% of cases, respectively). TTF-1 expression was significantly less frequent in typical than in atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.01, χ²). The mean index of tumor cell proliferation (Ki67) was the lowest in typical carcinoids (2.6%), amounted to 12% in atypical carcinoids, to 44% in large cell neuroendocrine carcinomas and reached the maximum of 61% in small cell neuroendocrine carcinomas. There were significant differences in the mean Ki67 index in the NETL 4 groups (р < 0.001, ANOVA). Conclusion: Expression of TTF-1, cytokeratin 7 and 19 in the neuroendocrine tumors of the lung is characteristic for a  less differentiated cell immunophenotype and allows for identification of the risk group with unfavorable clinical outcome among low-grade typical and atypical carcinoids.
Almanac of Clinical Medicine. 2016;44(5):613-623
pages 613-623 views


Chernykh Y.B., Golenkov A.K., Shushanov S.S., Kravtsova T.A., Rybalkina E.Y., Karamysheva A.F., Mitina T.A., Trifonova E.V., Kataeva E.V., Vysotskaya L.L., Stavrovskaya A.A.


Background: Implementation of a proteasome inhibitor bortezomib into treatment of multiple myeloma has helped to improve survival of patients with this malignancy that is characterized by continuous relapsing course as a clinical manifestation of multidrug resistance (MDR). Previous studies have resulted in contradictory data on the effects of various MDR genes expression on efficacy of bortezomib. Aim: To evaluate an impact of MDR1, MRP1, LRP, BCRP gene mRNA expression responsible for the development of MDR in bone marrow aspirates from patients with newly diagnosed multiple myeloma before bortezomib-containing therapy on the clinical course of the disease, response to treatment and overall survival. Materials and methods: MDR gene expression was assessed in a  group of 15  patients with newly diagnosed multiple myeloma Durie-Salmon stage  III before initiation of a bortezomib-based chemotherapeutic regimen. The assessment was done in bone marrow mononuclear cell fraction containing plasmocytes. MDR gene expression was measured by reverse transcription polymerase chain reaction test. Results: MDR gene expression was found in all patients with newly diagnosed multiple myeloma before initiation of cytostatic therapy: MDR1 was expressed in 14 (93%) of patients, MRP1 and LRP  – in 11 (73%), BCRP  – in 15  (100%). There was no difference between patient subgroups with high and low MDR gene expression in their clinical parameters, such as hemoglobin level, erythrocyte counts, total calcium, creatinine, total protein, lactate dehydrogenase, and albumin. At diagnosis of multiple myeloma, only absolute levels of paraprotein were significantly lower in patients with high MDR1 gene expression (31.52±3 vs  44.27±3.62  g/L, p<0.05). After 6  cycles of induction, there was a  significant decrease of paraprotein levels in the group with low MDR1 gene expression (from 44.3±3.6 to 16.8±5.2 g/L, p<0.05). Overall survival was negatively associated with high LRP gene expression only (median of overall survival in patients with high LRP gene expression was 17 months and in those with low expression – 62 months, р<0.05). Conclusion: High expression of MDR genes in patients with newly diagnosed multiple myeloma is not associated with clinical characteristics of the disease but may deteriorate the immediate response to bortezomib-based regimens and overall survival.
Almanac of Clinical Medicine. 2016;44(5):624-630
pages 624-630 views


Britvin T.A., Krivosheev A.V.


Background: Adrenocortical cancer (ACC) is a rare adrenal neoplasm with aggressive clinical course and poor prognosis, and with many unresolved problems of diagnostics, treatment and predictive factors. Aim: To identify the most significant clinical and morphological predictors of the outcome based on assessment of long-term results of surgical treatment of ACC patients. Materials and methods: This retrospective study included data on diagnosis and results of treatment of 73 ACC patients from 1999 to 2015. Results: Radical surgery was performed in 59 patients, and long-term results assessed in 52 of them (maximal duration of the follow-up was 12 years). The most favorable treatment results were seen in stages I and II of the disease, with a 5-year survival rate of 87%. The 5-year overall survival in patients with ACC stage III was significantly (p=0.042, multiple comparisons) lower (48%). Two patients who had been operated with ACC stage IV (adrenalectomy with excision of a solid liver metastasis and atypical lung resection) died of progressive tumor within 13 months after surgery. The survival rates in patients with stage III of the tumor were evaluated depending on the main clinical characteristics of the tumor. It was shown that the 5-year overall survival in non-functioning adrenocortical carcinomas was 59%, being significantly (p<0.05) better than that in patients with functionally active malignancies (22%). In the group of patients without metastases in the regional lymphatic nodes, the 5-year overall survival was 56%, whereas all patients with regional lymphatic metastases by the time of the surgery died from progression within 4 years after the intervention. There was an association between 5-year overall survival and the size of primary tumor, with significantly (p<0.05) lower numbers of 5-year overall survivors (29%) among those with tumors of more than 10 cm in diameter, compared with 65% survival rate in those with tumors of less than 10 cm. Conclusion: The results obtained confirm that the stage of ACC by the time of diagnosis is the major prognostic factor. Functional activity of the tumor, its size and regional lymphatic node metastases also have some prognostic value. At present, surgical intervention remains the single radical treatment approach to ACC; however, its results are far from being satisfactory. Patients with ACC stage III and IV require an individual approach to assessment of prognosis and to the choice of the treatment strategy after potentially curative surgery, which is possible based on immunohistochemical molecular biologic tests of the tumor.
Almanac of Clinical Medicine. 2016;44(5):631-634
pages 631-634 views


Balkanov A.S., Petrushkina N.N.


Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging) was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years), depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3), brain metastases are identified much earlier (p<0.05) than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively). Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.
Almanac of Clinical Medicine. 2016;44(5):635-639
pages 635-639 views


Somonova O.V., Elizarova A.L., Matveeva I.I.


Rationale: Extended resections or extended lobectomies are the most common types of surgical interventions in patients with liver malignancies, and they are associated with serious post-operative complications. Aim: To characterize the role of hemostasis abnormalities in the pathophysiology of post-operative hepatic insufficiency, as well as that of thrombotic and hemorrhagic complications in patients with liver malignancies. Materials and methods: One hundred and twenty patients with liver malignancies were recruited into the study (20  patients with primary hepatic tumors and 100  with colorectal cancer and liver metastases). Extended liver resections (right and left simple and extended lobectomies, both simple and extended) were performed in 100  (84%) of patients; multi-segmental liver resections, in 20  (16%). Assessment of hemostasis was done pre-operatively and at days 1  to 20  after surgery (hemostasis analyzer system STA-R Evolution and Chrono-log aggregometer). Results: After surgical intervention in the liver, subacute disseminated intravascular coagulation (DIC) was found in 34 patients. It was most common (65%) after the right lobectomy and was associated with a  decrease in fibrinogen levels to 121 mg/dL (p<0.01), prothrombin complex factors, to 45%  (р<0.05), antithrombin III to 48%  (р<0.05), with a  significant increase in D dimmer levels of up to 14.5 mcg/mL (р<0.05). Twelve patients with subacute DIC developed deep venous thrombosis of the lower extremities, and 9  patients had severe hepatic insufficiency. Patients with severe hepatic insufficiency had a  statistically significant decrease in prothrombin activity to 45%  (p<0.05), antithrombin III to 44%, plasminogen<50%, with high D dimer (>20  mcl/mL) and von Willebrand factor levels. Conclusion: Surgical interventions in patients with liver malignancy may lead to the development of DIC. Early diagnosis and correction of hemostasis-related risk factors of hepatic insufficiency allows for improvement of the results of surgery in patients with secondary hepatic malignancies.
Almanac of Clinical Medicine. 2016;44(5):640-646
pages 640-646 views



Grishina E.E., Kazantseva I.A., Ryabtseva A.A., Stepanova E.A.


We present a rare combination of a solitary fibrous orbital tumor and uterine cancer in a  female patient with type I  neurofibromatosis. This 77-year old patient developed a  left painless exophthalmos within 2 years and decreased visual acuity of the left eye. At the age of 20  she was diagnosed with type I neurofibromatosis. Half a year ago she underwent hysteron-oophorectomy due to uterine adenocarcinoma. The visual acuity of her left eye was decreased to 0.3, with an increase of intraocular pressure to 30 mm Hg. She had a 13-mm left-sided exophthalmos with misplacement of the eye downwards and laterally at 40°. Reposition of the left eye was severely impaired, with limitation of the eye movements to all directions. Ophthalmoscopy showed optic disc discoloration and blunting of its inner border. The patient underwent trans-conjunctival orbitotomy, with removal of three encapsulated tumor nodules. Histological and immunochemical studies of the removed tissue identified solitary fibrous tumor of the left orbit with an undetermined malignant potential. In the post-operative period, visual acuity of the left eye was 0.2, with no exophthalmos and right position of the eye. There was a non-significant limitation of the left eye movement to the left and to the right. X-ray computed tomography confirmed radical tumor excision. Conclusion: Solitary fibrous tumor is a  rare orbital neoplasm. Nevertheless, it should be included into the differential diagnosis list of spin-cell orbital tumors. It is necessary to aim at tumor removal through the least traumatic orbital access. Relapsing course of the tumor is the rationale for a  long-term follow-up of patients after removal of solitary fibrous orbital tumor.
Almanac of Clinical Medicine. 2016;44(5):647-651
pages 647-651 views



Mikhaylenko D.S., Teleshova M.V., Efremov G.D., Alekseev B.Y.


In the recent years, the full exome sequencing helped to reveal a  set of mutations in the genes that are not oncogenes or tumor suppressor genes by definition, but play an important role in carcinogenesis and encode proteins involved in chromatin remodeling. Among chromatin remodeling systems, which operate through the ATP-dependent mechanism, the complex SWI/ SNF attracts the great attention. The complex consists of the catalytic ATPase (SMARCA2/4), a group of conservative core subunits (SMARCB1, SMARCC1/2), and variant subunits. Abnormalities in the genes coding for each of these components have been identified as driver mutations in various human tumors. The SMARCB1 gene is of interest for practical oncogenetics, with its typical genotype-phenotype correlations. Germinal inactivating mutations (frameshift insertions/deletions, full deletions of the gene, nonsense mutations) lead to development of rhabdoid tumors in the kidneys and the brain in children in their first years of life, or even in utero. These tumors are highly malignant (Rhabdoid Tumor Predisposition Syndrome 1 – RTPS1). If a mutation carrier survives his/hers four years of life without manifestation RTPS1 with a missense mutation or has the mutation in the "hot spot" of the first or the last exon, then he/she will not develop rhabdoid tumors, but after 20 years of life, shwannomatosis may develop as multiple benign tumors of peripheral nerves. Finally, some point mutations in the exons 8–9 can result in Coffin-Siris syndrome characterized by mental retardation and developmental disorders, but no neoplasms. In this regard, rational referral of patients for direct DNA diagnostics of each of the described disease entities plays an important role, based on respective minimal criteria, as well as necessity of further development of NGS technologies (full genome and full exome sequencing) that are able to sequence not only individual exons, but all candidate genes of the disorders.
Almanac of Clinical Medicine. 2016;44(5):558-567
pages 558-567 views


Rozanov I.D., Rozanova E.A., Shirikov E.I., Balkanov A.S., Gaganov L.E., Stepanova E.A.


Pulmonary embolism in breast cancer is one of the causes of major deterioration of health status of the patients. Pulmonary artery occlusion is most often a  consequence of venous thromboembolism; this condition is referred to as "pulmonary thromboembolism". Significantly less common cause of occlusion of the pulmonary artery branches can be embolism by a  cluster of tumor cells, accompanied by development of pulmonary tumor thrombotic microangiopathy. This paper reviews data on the etiology and pathogenesis of pulmonary embolism in breast cancer, and approaches to its prevention and treatment.
Almanac of Clinical Medicine. 2016;44(5):580-586
pages 580-586 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies