MOLECULAR CHARACTERISTICS OF THE HETEROGENEITY OF NON-INVASIVE PAPILLARY UROTHELIAL CARCINOMAS AND THE MARKERS OF THEIR RECURRENCE.

Urothelial carcinoma represents the most common type of bladder cancer (>90%) and is the most frequent malignancy of the urinary tract. Most of the urothelial carcinomas are non-invasive at the time of diagnosis, however they are characterised with the risk of recurrence after surgical treatment. The aim of our study was to investigate the characteristics of tumor heterogeneity and markers of its progression in urothelial papillary carcinomas. Study included following groups: normal urothelial epithelium, urothelial papilloma, urothelial neoplasms with low malignant potential (PUNLM), non-invasive low grade papillary urothelial carcinomas (LGPUC) and non-invasive high grade papillary urothelial carcinomas (HGPUC). In addition, study included relapsed cases of non-invasive LGPUC and HGPUC. Nuclear features and mitotic counts was assessed using digital pathology software QuPath in standard H&E stained specimens. In addition, the presence of mitosis was detected as PHH3 labelled cells by immunohistochemistry. Proliferation was measured as Ki67 labelling index by immunohistochemistry. Tumor heterogeneity was investigated by the differential expression pattern of CK5, CK7 and CK20 by immunohistochemistry. Study results showed, that Nuclear features, as well as the number of mitosis, proliferation index and intratumoral heterogeneity significantly correlate with the presence of higher grade non-invasive urothelial lesions. In addition, it is possible to distinguish two major groups of non-invasive LGPUC and HGPUC, based on nuclear and phenotypic heterogeneity and mitotic and proliferative activity, I group which is characterised with higher intratumoral heterogeneity, higher mitotic count and higher proliferative activity, represents the high risk group of non-invasive LGPUC and HGPUC recurrence.

DEPENDENCE OF PROSTATE TISSUE PERMEABILITY ON THE WAVELENGTH OF RADIATION IN THE INFRARED RANGE OF THE SPECTRUM.

Prostate biopsy is considered to be one of the most aggressive and invasive methods in the diagnosis of prostate cancer. The researchers' efforts are aimed at using alternative and less invasive methods to manifest this disease at an early stage.The authors propose infrared radiation as a method of such research, which, as studies have shown, is characterized by different permeability to tumorous, healthy and hyperplastic prostate tissue, in particular, the more damaged the prostate tissue, the lower its degree of permeability.Experimentally determined that the highest permeability was found in the wavelength range 840-860 nm. It has been found that cancerous, non-cancerous and healthy prostate tissues are characterized by different permeability to infrared radiation. Healthy tissue has been shown to have the highest permeability to infrared radiation. Cancerous tissue permeability is much lower than that of healthy tissue. Prostate tissue permeability with benign hyperplasia is between the permeability of healthy and tumor tissues.Infrared beam transmittance control can be performed by adjusting the radiation intensity of the emitting source. Dependence of permeability on tissue thickness is linear for healthy tissue and sharply non-linear for tumor tissue.

Urinary IL-33 and galectin-3 increase in patients with interstitial cystitis/bladder pain syndrome (review).

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an enigmatic chronic disorder characterized by vague bladder pain of variable severity accompanied by urinary symptoms. The pathogenesis and etiology of IC/BPS remain incompletely defined. However, there is an emerging consensus about the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC/BPS. Accumulating evidences have suggested that tissue damage is recognized at the cell level via receptor-mediated detection of intracellular proteins (so-called alarmins) released by the necrotic cells. Among these proteins IL-33, galectin-3 (Gal-3) and advanced glycation end products (AGE), may have an important role because they can be participated as cellular components that stimulate the immune system. We determined IL-33, Gal-3, and AGE in 24-hour urine specimens from patients with IC/BPS and healthy subjects. Study participants included 43 woman with IC/BPS and 29 female volunteers. Urinary IL-33, EGF and Gal-3 levels were measured using an enzyme-linked immunosorbent assay, whereas the content of AGE was quantified by natural AGE-specific fluorescence (Ex. 370 nm, Em. 440 nm). Urinary IL-33, and Gal-3 levels were normalized by urinary creatinine (Cr) levels and compared among subgroups. We have found that the levels of IL-33 and Gal-3 were significantly increased in IC/BPS. The level of the IL-33 in the urine of healthy women was equal to 0.32, while the level of IL-33 in IC/BPS patients increases up to 0.58 (p<0.05). Further, the amounts of urine Gal-3 were also elevated in IC/BPS compared to healthy subjects (0.16 versus 0.07; p>0.01) and AGE-specific fluorescence in urine was increased up to 140% in IC/BPS patients. These data suggest on the participation of IL-33, Gal-3 and AGE in the pathogenesis of IC/BPS.

Role of the bacterial vaccine Solco-Urovac® in treatment and prevention of recurrent urinary tract infections of bacterial origin.

Urinary Tract Infections (UTI) represent a serious medical problem with considerably high rate of morbidity. Recurrent episodes of urinary tract infection (rUTI) may commonly develop in the way of relapse or reinfection. For patients, rUTI is always associated with costs, discomfort and decreased quality of life. Standard treatment of rUTI is through antibiotics and usually such treatment is required repeatedly. Repeat course of antibiotics leads to increase of resistance of uropathogenic strains. According to the European Association of Urology, "the present state of microbial resistance development is alarming". Our post-marketing trial was designed to demonstrate the substantial effect of the bacterial vaccine Solco-Urovac® both with independent administration and in conjunction with standard antibacterial medication within therapy and prevention of rUTI. Total of 115 patients (men and non-pregnant women) were enrolled in our open-label post-marketing trial. Each patient had more than one year history of rUTI and in the past had already taken appropriate course of standard therapy. The trial group included 50 patients: 32 men, 18 women (average age ± 32.5). 32 patients (men) of the trial group received vaccination with Solco-Urovac® together with the standard antibacterial medication. According to bacteriologic tests, in 62% cases infection was caused by Escherichia coli, and in 38% cases by Morganella morganii, Proteus mirabilis, Klebsiella pneumoniae, Enterococcus faecalis. 18 patients within the trial group were women with no recurrence episode at the start and during the trial period. Each woman was involved as the intercourse partner of the respective man within the trial group. The women received only vaccination with Solco-Urovac®. 65 patients of the control group had more than one year history of rUTI and had been treated earlier, too. Patients of the control group received appropriate antibacterial medication without Solco-Urovac®. After therapy and follow-up examination, results in the both groups were classified, also in consideration of the pathogen-specified subgroups, and then summarized and compared respectively. During the follow-up period no case of rUTI was noticed in women. In total, analysis of the medical records of 50 patients of the trial group demonstrated no case of rUTI in 46 patients during the follow-up period. Altogether, the rate of improvement of symptoms was as follows: the trial group - 92%, the control group - 74%. Through comparison with the past medical histories of patients, the higher rate of improvement and longer absence of rUTI episodes after treatment were certainly associated with the effect of Solco-Urovac®. The results of our post-marketing trial allow recommending Solco-Urovac® for appropriate reference within the Georgian National Guideline on Urologic Infections.

Compartment syndrome, rhabdomyolysis and risk of acute renal failure as complications of the urological surgery.

Current knowledge related to the risk of CS when operating in these positions (Lloyd Davies and Trendelenburg tilt) is such that it can be deemed negligent to keep patients in this position (with legs higher than the heart) when not absolutely necessary. If it means repositioning and redraping, thus adding a few extra minutes to the episode and costing a small amount in additional drapes, surely this is a small price to pay for excellent perioperative care? If repositioning is impossible to execute, the head-down tilt position should be reversed every two hours, for a short period of time, to allow more natural perfusion of the lower limbs to occur. Raza et al recommend that if the anticipated procedure duration is beyond four hours, the legs should be removed from supports every two hours for a short period to prevent reperfusion injury. The use of Allen stirrups is preferred to calf supports or metal skids. Turnbull and Mills suggest that we should certainly review our use of compression stockings and intermittent compression devices when operating on patients in the Lloyd Davies position. It will be deemed negligent to misdiagnose (ie: mistake for a DVT) or delay treatment (by prolonged re-assessment) of CS postoperatively when patients have been subjected to prolonged surgery in these abnormal positions. Delayed or missed diagnosis may not only be limb-threatening (and cause a very protracted hospital stay)--it can be life-threatening. With today's current knowledge, surgeons undertaking prolonged surgery in abnormal positions must be aware of this, fortunately rare, complication. Practice guidelines within perioperative care should reflect current knowledge and ensure that risk is minimized. Patients who take legal action if they have experienced this condition may be awarded substantial costs against negligence if lack of care can be proven or diagnosis has been delayed.

[Quantitative changes of testosterone and prostate-specific antigen at low and high densities of PSA in men with prostate cancer].

In 61 patients with prostate cancer quantitative changes of testosterone and prostate-specific antigen (PSA) in blood serum at low and high densities of PSA have been investigated. It was shown that a high coefficient of correlation has been established in patients with prostate cancer and low density of PSA, but weak correlation was documented for the patients with prostate cancer and high density of PSA.

[Prostate-specific antigen in serum and prostate epithelium in benign prostatic hyperplasia].

The aim of our investigation was the simultaneous study of concentration of prostate-specific antigen (PSA) in serum and its immune-histochemical expression in the adenomatous prostatic tissue. 50 patients have been investigated. In 48 patients benign prostatic hyperplasia (BPH) has been diagnosed, and 2 patients served as controls. Investigated patients were divided by 2 groups: 1st group--patients with moderate IPSS (n=6); 2nd group--patients with expressed IPSS (n=42). The results of our investigations shown that at any variant of BPH lumine epithelium, as a rule, were PSA-positive. Negativity of immune-histochemical reaction was observed in areas of epithelium atypical hyperplasia, when proliferated epithelium is presented by basal cells. Expression degree varied between weak, moderate and high. The comparison of PSA expression degrees in tissue and its blood levels shown that the change of blood concentrations was more variable, than expression in tissue. Quantitative imbalance between them indicates that determination of blood PSA without immune-histochemical investigation is less reliable and does not give a valuable insight about the essence prostate pathology.

[Cases of Leydig cell tumor in male infertility].

1745 patients at the Department of Urology of Tenon Hospital (Paris, France) from 1990 to 2006 and at the department of urology of Tbilisi State Medical University (Georgia) during last several months have been examined and counseled on male infertility. Leydig cell tumor was found in 4 patients, among them 3 by palpation and testicle echography, fourth patient (at the age of 33) with bilateral varicocele (III stage at the left, II stage at the right) was more interesting for us. Leydig cell tumor was found out at the scrotum exploration. Oligoteratozoospermia (OATS) has been distinguished from his spermogram. Microsurgical bilateral correction of varicocele and scrotum exploration, and double-sided double biopsy of testicle have been carried out. During examination of the left testis the hardly palpable node has been found out in the lower pole. We became compelled to make enlarged incision of tunica alba of the testicle lower pole. After that it was found out the solid, well encapsulated and yellow-brown node (8 mm in diameter). The node enucleation away from tumor by 0.5 cm has been carried out. Exact histological investigation confirmed the presence of Leydig cell tumor. In 6 years after surgical operation the tumor node 1.8 mm in diameter has been found out in right (contra lateral) testis. The patient was urgently operated, ex-tempo investigation confirmed the presence of Leydig cell tumor in right testicle--high orchidectomy at the right has been carried out. Now, patient has not any symptoms of disease during 3.5 years of observation. Given case shows that the enucleation of Leydig cell tumor proves to be equivalent alternative of orchidectomy, which is suggested by many authors. Taking into account the presence of encapsulation and tumor benignity it is important to have opportunity of the testicle preservation due to infertility problems. However, this tactics must be carried out under strong observation due to the opportunity of relapse even in several days after surgical operation.

Creatine kinase mb, cardiac troponin T and cardiac troponin I as the markers of rhabdomyolysis in chronic hemodialysis patients.

We designed this study to compare serum markers of myocardial injury creatine kinase MB (CK-MB), as well, as serum contractile proteins, especially cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in dialysis patients without acute ischemic heart disease. 24 patients on chronic hemodialysis were studied by history and physical examination, electrocardiography, and two-dimensional echocardiography. These patients had no evidence of ischemic heart disease. Biochemical markers were measured in serial predialysis blood samples with specific monoclonal antibody-based immunoassays. For several patients at least one sample measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA cTnT, 17 of 24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%). Chronic dialysis patients without acute ischemic heart disease frequently had increased serum CK-MB and cTnT. Our finding are in agreement with the conclusions that cTnT and CK-MB detected in the serum of patients on chronic hemodialysis originates from the skeletal muscle and not from the heart.

[Correlational studies of urine interleukin 6, interleukin 8 and nitric oxide in the patients with pyelonephritis and hydronephrosis].

The urine concentration of IL-6, IL-8 and nitric oxide (NO) were determined in the patients with pyelonephritis and hydronephrosis. Correlations between urine levels of IL-6 and IL-8 and amount of nitric oxide in the hydronephrosis patients were not found. However, in the patients with both acute and chronic pyelonephritis the coefficient of correlation was high, r((IL-6/NO)) = 0,94 and r((IL-8/NO)) = 0,86 for acute and r((IL-6/NO)) = 0,72 and r((IL-8/NO)) = 0,40 for chronic forms, respectively. These data suggest that secretion of NO during hydronephrosis has a compensatory character and acted on renal microvascular tone, whereas during pyelonephritis NO produced inflammatory mediators by recruiting leukocytes and has pathogenic character.