Clinical usefulness of PI3K/Akt/mTOR genotyping in companion with other clinical variables in metastatic renal cell carcinoma patients treated with everolimus in the second and subsequent lines.

BACKGROUND: The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS: In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials.

Recognition and classification of colon cells applying the ensemble of classifiers.

The paper presents the application of an ensemble of classifiers for the recognition of colon cells on the basis of the microscope colon image. The solved task include: segmentation of the individual cells from the image using the morphological operations, the preprocessing stages, leading to the extraction of features, selection of the most important features, and the classification stage applying the classifiers arranged in the form of ensemble. The paper presents and discusses the results concerning the recognition of four most important colon cell types: eosinophylic granulocyte, neutrophilic granulocyte, lymphocyte and plasmocyte. The proposed system is able to recognize the cells with the accuracy comparable to the human expert (around 5% of discrepancy of both results).

[Clinical and immunohistoenzymatic investigations in patients with vasomotor and perennial allergic rhinitis]. / Badania kliniczne i immunohistoenzymatyczne u chorych z naczynioruchowym i calorocznym alergicznym niezytem nosa.

The aim of our study was evaluation of the results of clinical examination in patients with vasomotor and perennial allergic rhinitis and assessment of number of blood vessels, nerve fibres and mast cells on the basis of immunohistoenzymatic examination. There were 42 patients examined aged from 18 to 50 and divided into three groups: I--16 patients with vasomotor rhinitis and II--14 patients with perennial allergic rhinitis and III--12 patients (control) with nasal septum deviation. On the basis of the patient's history data, clinical otorhinolaryngologic examination and active anterior rhinomanometry the patients were qualified to bilateral inferior turbinectomy. The nasal mucosa removed during surgery underwent immunohistoenzymatic examination using the monoclonal antibody against the tryptase of mast cells (MCT company, DAKO), the endothelin of blood vessels (EC - DAKO) and the neurospecific enolase (NSE - DAKO). In examined groups of patients with vasomotor and perennial allergic rhinitis and control group similar escalation of clinical symptoms expressed by means of points index were stated. In immunohistoenzymatic studies the differences in mean number of blood vessels and nerve fibres between examined groups were not statistically significant, however statistically significant difference concerned higher number of mast cells patients with vasomotor rhinitis in comparison to perennial allergic rhinitis.

Pectus excavatum: increase of right ventricular systolic, diastolic, and stroke volumes after surgical repair.

OBJECTIVE: The study was undertaken to assess how a surgical correction of funnel chest modifies right ventricular structure and function. METHODS: Before and 6 months after surgery in 42 patients (27 male and 15 female patients, aged 5-31 years), a pectus index was calculated and echocardiographic examinations of the right ventricle were performed, with calculation of systolic, diastolic, and stroke volume indices. Right ventricular volume was estimated by subtracting the left ventricular volume from that of the entire heart. The values of the right ventricular volumes and the pectus index before and after the operation, as well as the changes in the indices, were compared. RESULTS: Statistically significant changes in the pectus index and the right ventricular volume indices after surgery were noted. No correlation was observed between the changes in the pectus index and the changes in any right ventricular volume indices. CONCLUSION: Surgical treatment of funnel chest causes an increase in right ventricular systolic, diastolic, and stroke volumes, although there is no correlation between these changes and the degree of sternocostal elevation.

[Evaluation of morphologic changes of the rabbit supraspinal muscle]. / Ocena zmian morfologicznych miesnia nadgrzebieniowego królika po odcieciu jego sciegna.

The aim of this study was to evaluate morphologic changes within rabbit supraspinatus after detachment of its tendon from the greater tubercle along with infraspinatus and subscapularis tenotomy. Stained with hematoxylin and eosin muscle sample has been examined after 6 weeks (group A), 3 months (group B) and 6 months (group C). There were 10 rabbits in each group. The muscle atrophy was accompanied by statistically significant increase of the interstitium volume in group B (24.5%) and C (26.3%) as opposed to A (15.4%). Statistically significant differences were also found in interstitium volume of tenotomized and contralateral supraspinatus muscle.

Grading of gastric epithelial dysplasia. An interobserver study and analysis of diagnostic criteria.

One of the fundamental problems in the pathology of gastric epithelium is differentiation of reactive or regenerative proliferations, which are not precancerous from precancerous proliferations (i.e. dysplasia) and cancer. Diagnostic and interpretational difficulties, a need for a close cooperation between pathologists and clinicians and an attempt to more precisely assess gastric epithelial dysplasia prompted us to evaluate the usefulness of the current morphological criteria in the diagnosis and grading of gastric epithelial proliferations. The present study indicates that there are no sufficient grounds for grading of dysplasia, although the current morphological criteria permit establishment of a correct diagnosis. Therefore, the currently used three-grade classification of dysplasia may be successfully replaced with an easier two-grade classification or resigned totally.

[Histologic examination of slow epiphyseal distraction in the femur of rabbits]. / Badania mikroarchitektoniki powolnie rozciaganej chrzastki nasadowej kosci udowej królika.

Slow, symmetric epiphyseal distraction of the distal femur has been performed in 30 immature rabbits aged 10 weeks (group 1) and 16 weeks (group 2). Histological examination has been carried out after 2, 4, 12 and 24 weeks of distraction in both groups. In all animals hyperplasia and hypertrophy of the distracted epiphysis and regular remodeling of the bony growth zone were found after 4 weeks of follow-up. No premature closure of the physis has been noted compared to the controls. Histological differences observed were attributed to various, age related biological potential and they resulted from physiological involution.

[Gelatinous cyst of the common peroneal nerve]. / Torbiel galaretowata nerwu strzalkowego wspólnego.

The authors report two cases of gelatinous cyst of the common peroneal nerve. They present two different approaches to surgical treatment used in their cases--decompression of the nerve trunk by simple drainage of the cyst in one case and total excision of the cyst and its wall with reconstruction of fascicles damaged by the lesion in another. Experiences and results of treatment by other authors are presented as well as their views on pathology and etiology of this rare entity.

Morphometric evaluation of myofibrillar mitochondria in experimental administration of ethylene glycol.

The authors carried out morphometric analysis of the surface, area, circumference and shape of myofibrillar mitochondria in rats submitted for acute experimental intoxication with ethylene glycol. The measurements were taken at 12 and 24 hours after intoxication and compared with those in the control group. A significant increase in mitochondrial circumference and surface area was seen as early as 12 hours with their shape being more rounded than elongated. At 24 hours of the experiment the parameters further increased. The use of computer image analysis permitted an objective and measurable confirmation of changes in electronograms and revealed the presence of disorders in the phase in which traditional methods were useless.

An analysis of extramuscular branches of the coronary arteries in relation to size and weight of heart.

There is close relationship between the size and weight of the heart and the angles of branching of coronary arteries. The velocity of flow of liquids through a system of branching ducts may be related to the valued function of angles of branching ducts. We estimated the effect of the phenomenon on blood flow through the extramuscular branches of the coronary arteries. The estimation was based on measurements of angles of division of the arteries in 48 human hearts. It was also correlated with weight and dimensions of the heart.

Computer image analysis of toxic fatty degeneration in rat liver.

Fatty degeneration of the liver is one of the most frequently observed pathological changes in the experimental estimation of the toxicity of chemical compounds. The intensity of this kind of damage is most often detected by means of a generally accepted scale of points, whereas the classification is performed according to the subjective "feeling" of the pathologist. In modern pathological diagnostics, computer analysis of images is used to perform an objective estimation of the degree of damage to various organs. In order to check the usefulness of this kind of method, comparative biochemical and morphometrical studies were undertaken in trichloroethylene (TRI)-induced fatty degeneration of the liver. TRI was administered to rats intragastrically, in single doses: 1/2; 1/3; 1/4; 1/6 and 1/18 DL50. 24 hours after the administration, the animals were sacrificed. The content of triglycerides in the liver was determined according to Folch et al. (1956). Simple lipids in the histochemical samples were detected by means of staining with a lipotropic, Fat Red 7B. The area of fatty degeneration was estimated in the microscopic samples by the use of an automatic image analyser IBAS 2000 (Kontron). The morphometrical data concerning the area of fatty degeneration in the liver amplified a high degree of correlation with the content of triglycerides (r = 0.89) and the dose of TRI (r = 0.96). The degree of correlation between the biochemical data and the dose of TRI was 0.88. The morphometrical studies performed have proved to be of great use in estimating the degree of fatty degeneration in the liver. This method enables precise, quantitative measuring of this sort of liver damage in the material prepared for routine histopathological analysis. It requires, however, the application of a specialized device for quantitative image analysis.

Experimental evaluation of the net "Dallop" covered with collagen as the dural substitute.

Evaluation of the usefulness of the net "Dallop" produced by Tricomed Lódz covered with collagen to the dural defects reparation was analysed. This new original product of Lódz Technical University was compared with widely used in neurosurgery "Zenoderm" produced by Ethicon and "Duratexol" produced by Czechoslovakia. The trial was conducted on 38 rabbits: 4 as a control group (just an original dura sutured after incision with Mersilk Ethicon sutures), 19 with implanted the net "Dallop" covered with collagen, 11 with the "Zenoderm" and 4 with the "Duratexol". Animals were sacrificed after 3, 14, 30 or 90 days after surgery. There were no significant differences between all analysed groups in clinical, macroscopical and morphological investigations. No negative local reactions in histopathological evaluation of the net "Dallop" covered with collagen were observed. The results of our investigations show that the net "Dallop" covered with collagen seems to be the "Zenoderm" and the "Duratexol" dural substitute.