[Gemistocytic astrocytomas]. / Gemistotsitarnye astrotsitomy.

Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016). Like all diffuse astrocytomas, GA recur with time, which is often accompanied by malignant degeneretion into the anaplastic astrocytoma GIII or to the secondary glioblastoma GIV. However, the progression-free survival and overall survival in patients with GA is less than in patients with diffuse astrocytomas. Given that this group of patients, according to the WHO classification (2016), is classified as GII, patients with GA usually do not receive comprehensive treatment. We have conducted a thorough analysis of research on this problem for the period from 1956 to 2017. Differences in the histological pattern, immunohistochemical and molecular-genetic profiles, survival of patients with GA and diffuse astrocytomas GII are shown there. A clinical case of a patient with transformation of a diffuse astrocytoma in GA (GIII) and then into a secondary glioblastoma is presented.

[Acral lentiginous melanoma: the current state of the problem].

This review is aimed at the analysis the current state of acral lentiginous melanoma. This tumor has rather aggressive course and is the main cause of death in skin cancer patients. In Russia the incidence of melanoma during the period 2000-2010 increased from 3.18 to 3.95 cases per 100000 of population. The average annual growth rate was 1.99% and the total growth rate was 21.81%. Although skin melanoma is a visual tumor, more than one third of patients visit oncologists at advanced stages of the disease. Primary melanoma with localizations on the skin of fingers, interdigital spaces, soles, palms and nail plates is especially difficult for early diagnostics.

[Fallopian tube carcinoma: clinical and morphological features, analysis of 69 cases].

Primary fallopian tube carcinoma (PFTC) is a rare gynecological malignancy accounting 0.14-1.8% cases. The purpose of the study was to assess clinical, morphological and immunohistochemical features of PFTC. All the cases of PFTC were detected during 1980-2005. 31 cases of PFTC were analyzed as to Ki-67, HER-2 expression, estrogen receptors (ER), progesterone receptors (PR), grade and stage. 69 cases of PFTC were detected with an average age of 55, 6 years (range 21-73 years). Stage I detected in 34.2% cases, Stages II and III--32.8%, Ca in situ--10%. Among 31 patients ER were positive in 75% (n = 23), PR were positive in 46% (n = 14): ER+PR+ in 12 (38%) cases, ER+PR- in 11 (36%) cases, ER-PR+ in 2 (6%) cases, ER-PR- in 6 (19.4%) cases. Only 2 cases were HER-2 positive with ER+PR+ and ER-PR- status. Ki-67 labeling index (LI, %) values ranged from 15 to 95% (median 60) with average rate 58.03% +/- 4.08. Ki-67 LI values > or = 60% were graded as high and < 60% as low. We did not find any significant differences in Ki-67 LI values among tumors of various Receptor Status. However Ki-67 L1 > 60% was associated with poor 5-year survival (14%), vs 75% in Ki-67 L1 < 60%. Primary fallopian tube carcinoma is mainly HER-2 negative, receptor positive in 79.6%. Ki-67 rate is irrespective of ER PR status. However the level of Ki-67 (> 60%) was a significant survival prognostic factor.

[Mesonephric (clear cell) cervical cancer].

Mezonefric cervical cancer was more prevalent in younger women (mean age 42.2 +/- 1.2 years) with no classic predisposing factors. In most cases (62.1%) the localized stage of the disease (I, II stages) dominated. Regional metastases correlated with depth of tumor invasion (with a depth of invasion of more than 10 mm--57.8%). There was marked low expression of HER2/neu (only in 1 of 14 samples it was revealed light positive reaction. Proliferation index Ki-67 was 37.5% and the signs of mutation in the p53 gene were found in 28.4% of cases. Estimating that two thirds of patients with clear-cervical cancer revealed localized forms of the disease, and that most of the women had received the combination treatment (51.8%)--a 5-year survival rate was quite high and was 79.3%.

[Morphological, immunohistochemical and spectral characteristics of dysplasia, preinvasive and invasive forms of lung cancer].

An analysis of modern methods of diagnostics such as morphological, immunohistochemical and spectral, which included the bronchoscopy and spectrometry by using reflectance and autofluorescent regime, was made. The data involved the results of prospective follow-up study of 167 patients (620 biopsies). An obligatory spectrometry of suspicious area was carried out before the forceps biopsy. The microslides, which met the requirements of criteria of one of the carcinogen steps (n=201), were subjected to the in-depth morphological and immunohistochemical investigations. The tendency of angiogenesis (CD31 and CD34), proliferative activity (Ki-67), level of apoptosis (P53), EGFR expression were estimated. The sensitivity of combined endoscopic method was 94,74% by specificity 79,95% and high prognostic value of negative endoscopic diagnosis - 99,4%.

[Use of simultaneous double-tracer SPECT with 99m-Tc-technetril and 67-Ga-citrate for follow-up of patients with non-small cell lung cancer].

In 20 primary patients with focal abnormalities on conventional CT we evaluated diagnostic properties of simultaneous double-tracer SPECT. Scintigraphy was performed as a single examination with simultaneous registration of 67Ga and 99mTc-MIBI. Image acquisition was started 48-74 hours after IV injection of 130-175 MBq 67Ga-citrate and immediately after IV injection of 500-740 MBq of 99mTc-MIBI. All images for each agent were classified as positive and negative for primary tumor, N1 and N2 lymph-nodes (LN). According to histology 18 of 20 evaluated patients had non-small cell lung cancer (NSCLC), the other two patients had tuberculosis and nonspecific inflammation. SPECT with 99mTc-MIBI correctly visualized tumor in 18, 67Ga allowed correct visualization in 16 cases. Both tracers were truly negative in a patient with tuberculosis and false positive in a patient with nonspecific inflammation. Double-tracer SPECT was slightly more specific than CT in primary lesions. In 18 patients histological verification of LN status was obtained: NO was revealed in 9 cases, N1 in 4 and N2 in 5 cases. Both tracers correctly discriminated LN-positive and LN-negative cases with 94% specificity. On the contrary, CT was false-positive in 3 and false-negative in another 5 patients. Differentiation between N1 and N2 LN involvement is crucial for therapy planning. 99mTc MIBI and 67Ga revealed N1 in 2 cases and N2 in 4 cases, the diagnosis was later verified by postoperative morphology. In 2 patients SPECT overestimated extent of LN involvement and LN status was changed after surgery from N2 to N1. In 18 patients results of 99mTc-MIBI and 67Ga augmented each other. Accuracy of LN staging by SPECT with 99mTc-MIBI and 67Ga was 83%. CT accurately determined LN stage only in 7 patients, it was overestimated in 7 and underestimated in 4 cases. SPECT with 99mTc-MIBI and 67Ga demonstrated high overall accuracy in diagnostics of regional LN invasion for patients with NSCLC. Diagnostic value of conventional CT was significantly lower. Correct level of LN involvement was determined by SPECT in 83% of cases.

[Pharmacoeconomic analysis of gefitinib therapy in patients with non-cell cell lung cancer].

We performed a treatment efficacy analysis for non-small cell lung cancer (NSCLC) patients' population with EGFR mutation aimed at optimization of pharmacoeconomic factors. The employment of gefitinib leads to an increase in patients' life expectancy for a median of 1.05 years. The average cost-effectiveness of this therapy is 934.8 thousand rubles per additional year (903.9-1100.5 thousand rubles for each year). If gefitinib therapy is given only to patients with proved EGFR mutation it can decrease the average expenses by 211.6-251.8 thousand rubles per patient in comparison to undiagnosed patients's population receiving gefitinib without a decrease in clinical effect. Comparison of selective gefitinib administration with isolated chemotherapy (CT) yields an incremental cost-effectiveness ratio of 960.7 to 1010.0 thousand rubles per additional year. Therefore, the strategy of EGFR gene mutations testing in patients with inoperable NSCLC with consequent gefitinib therapy administration in patients positive for mutation lead to an increase in life expectancy and is characterized by acceptable cost-effectiveness.

[Concurrent chemoradiotherapy with moderate dose brachytherapy as remission induction for patients surgically treated for esophageal cancer].

The locally advanced cancer of thoracic esophagus was treated by induction chemo-irradiation therapy (IHRT) with intraluminal medium dose-rate brachytherapy (IMBT). From July 2009 to February 2012 twenty five patients (mean age 54.3 +/- 1.3 years) were included in the study. The length of the primary tumor was up to 6 cm in 10 pts and more than 6 cm in 15 pts. Induction therapy consisted of three IMBT sessions (7 Gy X 3; q7d) and two cycles of chemotherapy (PF; q28d), 26-31 days later the surgery was performed. Subtotal resection of the esophagus type of I Lewis was performed in 23 pts, transtracheal extirpation of the esophagus was performed in 2 pts.In all the cases 3F lymphodissection was performed. After IHRT in 15 of 25 pts. was obtained complete or partial response, in 10 of 25 pts was obtained disease stabilization. Perioperative complications occurred in 17 (68%) patients receiving conservative treatment, one patient (4%) died of treatment complications. In 6 cases (24%) morphology had shown the complete regression of primary tumor. Thus, the combination of intraluminal medium dose-rate brachytherapy and chemotherapy lead to reduction of primary tumor local spread and can be an efficient factor in improving the results of surgical treatment.

[Use of autofluorescence bronchoscopy and spectrometry in the diagnosis of central lung cancer].

The paper evaluates the available data as well as our own on use of autofluorescence bronchoscopy in conjunction with spectrometric examination. We used qualitative and quantitative assessment of images obtained by conventional and autofluorescence (ClearVu Elite) means in real time. Our double-stage study evaluated sensitivity and specificity of autofluorescence bronchoscopy in diagnosing lung cancer as well as constructed spectrometric curves (ROC) and areas under them (AUC). Endoscopy was used in 171 patients with central lung cancer. Autofluorescence bronchoscopy established high sensitivity--94.74% (95%CI: 80.9-99%) and sufficient specificity--79.95% (95%CI: 75.8-83.6%). Application of a wide range of spectrometric coefficients contributed to high specificity thus reducing the number of biopsies as well as the injury from the treatment. The AUC for a best predictive index was 0.89 (99%: 0.83-0.95).

[The gastrointestinal stromal tumor of the stomach in child: characteristic of diagnostics].

The observation of stromal gastric tumor of 12 years old girl has been investigated. The diagnostics was carried out on tumor biopsy taken by a laparoscopy. An evident edema of stroma caused "pseudo-papillary" organization of epithelioid cell neoplasm prevented the right diagnosis established only by immunohistochemical staining of CD117 and CD34 markers. The absence of mutations in C-kit and PGFRA genes uncovered by molecular-genetic analysis is typical for stromal gastric tumors in child. The next gastric resection allowed to estimate tumor appearance and localization, histological organization, and to repeat immunohistochemical studying. This observation confirmed the correctness of diagnosis and established high level of Ki67 proliferative activity (12-15%) determined prescriptions of target medicamental therapy.

[Significant regression of glioblastoma with low level of Mgmt gene expression following radiotherapy].

Radiochemotherapy is leading the universal research effort in fighting lethality: it is improving relapse-free survival of patients with inoperable glioblastoma, the most pernicious brain tumor in adults. Its effectiveness was found to depend on expression of Mgmt gene of tumor DNA reparation following radiochemotherapy and adequate medication based on the molecular phenotype of tumor. Our study involved a 40-year old male with a low level of Mgmt gene expression as established by stereotactic biopsy. The patient received hypofractionated three-dimensional conformational proton therapy with the benefit of temozolomide (140 mg/24 hr). Subsequently, the dose was raised to 360 mg/24 hr, on days 1-5 of the cycle. Contrast-enhanced MRI examination established significant diminishing of the size of tumors on completion of cycles 7 and 8; patients felt better, memory and blood indices improved. As of the time this paper was written, relapse-free survival was 17.5 months, as compared with the literature data on inoperable glioblastoma--5.5 months.

[Expression of Ki-67, p53, bcl-2, estrogen receptors alpha in patients with clear cell renal carcinoma and epidermal growth factor receptor mutation].

Three hundred and thirty-six cases of clear-cell renal carcinoma (CCRC) were examined for epidermal growth factor receptor (EGFR) mutation: exon 19 deletion and L858R mutation in exon 21 of the EGFR gene. The expression of Ki-67, bcl-2, p53, and estrogen receptors alpha was studied in CCRC with EGFR mutation. There were 4 cases of CCRC with EGFR exon 19 deletion. The frequency of EGFR gene mutations was 1.2%. L858R missense mutations in exon 21 of the EGFR gene were absent. In CCRC, EGFR gene mutation (exon 19 deletion) was detected in 3 men and 1 woman with an age range of 50 to 60 years and Fuhrman differentiation grade 2 or 3. The Ki-67 index varied from 4 to 23%. The expression of bcl-2 and p53 was negative. A moderate estrogen receptor alpha expression was revealed in 1 of 4 cases.

[Use of Taxotere in neoadjuvant therapy of breast cancer].

Wide-range research in the efficacy of neoadjuvant therapy of breast cancer has been conducted worldwide for over two decades. Promising end results have been reported on completion of clinical and pathomorpologic response. It has become a standard practice in managing relatively operable and inoperable breast cancer. However, preoperative chemotherapy in operable disease is still a subject of discussion. For many years anthracycline-based treatment has remained a therapy of choice in the neoadjuvant setting. Higher efficacy of its combined use with taxotere and anthracycline was demonstrated. It was followed by higher rates of complete pathomorphologic response and survival. Besides, regimens using taxotere and target therapies are being investigated. Tentative results suggest that better survival may be achieved due to decreased toxicity profiles.

[Effectiveness of gefitinib (Iressa) as first-line therapy for inoperable non-small-cell lung cancer with mutated EGFR gene (phase II study)].

Tumor regression was reported in 20-30% of patients with inoperable non-small-cell lung cancer (NSLC) following standard first-line chemotherapy. Clinical trials with second-line gefitinib (Iressa) showed a strikingly high response in patients with mutated EGFR. However, clinical experience with gefitinib as first-line therapy had been limited to small-scale trials mostly among subjects of Asian origin. Our study was not associated with the drug manufacturer and included 25 chemotherapy-naive patients with mutated EGFR inoperable lung adenocarcinoma. Standard dose was 250 mg/day. Complete response was observed in 1 patient (4%), partial--11 (44%), sustained stabilization--13 (52%); median time until tumor progression--186 days. Median overall survival failed to be registered within the duration of the study. Among most frequent side-effects were skin rash (19; 76%) and diarrhea (14; 56%): marked side-effect -toxicity grade III (4; 16%). Gefitinib appeared highly efficient and tolerable and may be recommended as first-line treatment of mutated EGFR inoperable NSLC.

[Morphologic and differential diagnosis of sclerosing perineurioma].

The paper discusses morphologic and immunohistochemical characteristics of sclerosing perineurioma. Generally, it is well circumscribed and consists of tiny spindle-shaped plump epitheloid cells embedded in collagenous hyalinized matrix. Immunohistochemically, it was represented by EMA+, S-100, AE1/AE3, CAM 5.2, smooth muscle actin and desmin. Being benign, tumor was identified by differential diagnosis using fibroma of tendon sheath, sclerosing one, glomal tumor, giant cell tumor and sclerosing epitheloid cell sarcoma.