Role of Non-Coding RNAs in the Etiology of Bladder Cancer.

According to data of the International Agency for Research on Cancer and the World Health Organization (Cancer Incidence in Five Continents, GLOBOCAN, and the World Health Organization Mortality), bladder is among the top ten body locations of cancer globally, with the highest incidence rates reported in Southern and Western Europe, North America, Northern Africa and Western Asia. Males (M) are more vulnerable to this disease than females (F), despite ample frequency variations in different countries, with a M:F ratio of 4.1:1 for incidence and 3.6:1 for mortality, worldwide. For a long time, bladder cancer was genetically classified through mutations of two genes, fibroblast growth factor receptor 3 (FGFR3, for low-grade, non-invasive papillary tumors) and tumor protein P53 (TP53, for high-grade, muscle-invasive tumors). However, more recently scientists have shown that this disease is far more complex, since genes directly involved are more than 150; so far, it has been described that altered gene expression (up- or down-regulation) may be present for up to 500 coding sequences in low-grade and up to 2300 in high-grade tumors. Non-coding RNAs are essential to explain, at least partially, this ample dysregulation. In this review, we summarize the present knowledge about long and short non-coding RNAs that have been linked to bladder cancer etiology.

Perineural invasion in prostatic carcinoma treated with radical prostatectomy: the role of TR systematic biopsy.

Perineural invasion (PNI) is a morphological entity which has been known for many years, though its significance in prostatic neoplasms has only been studied recently. Therefore, we tried to assess, with the help our experience, its presence and its significance. Ninety-four patients, aged between 49 and 74 (average 65.8)--with a PSA between 2.69 and 52 ng/ml (average 11.44)--underwent RP for prostatic carcinoma; 58 patients had stage T2 and 36 had T3. 48 patients had Gleason 7 or higher, and 46 had G 6 or lower. Fifty patients (53,1%) were PNI+ and 44 (46,9%) PNI-. Between the two groups there was no significant difference as to age (1" group: average age 67 years; 2nd group: 68) and PSA (1st group: average 9.73 ng/ml, 2nd group: average 8,17) (Z 0,639). The distribution according to the stage showed that 24 patients (48%) PNI+ were T2 and 26 (52%) PNI+ T3, 34 (77.2%) PNI- T2 and 10 (22%) PNI- T3 and therefore 72,23% of the T3's were PNI+ and 41.3% of the T2's were PNI+; 34 patients (70.8%) with G>7 were PNI+ and 14 (29.16%) PNI-, 16 patients (34,78%) with G<6 were PNI+ and 30 (65.2%) PNI-. Among the PNI+ 50 patients, 36 had undergone biopsy in our hospital, and therefore we re-examined the operation tissue and found out that 16 (44%) were biopsy PNI+ while for 22 (55.5%) it was not possible to assess the PNI on the biopsy tissue. PNI is an important morphological element in the staging of prostatic cancer and is connected with the disease negative prognostic factors: in fact, it can be traced with a high frequency in stage diseases and higher Gleasons. It does not seem to be connected with PSA, above all for values between 4 and 20 ng/ml. We think that a very important element to be stressed is the fact that this condition is not always detected with biopsy (about 45%) and this does not allow, in such cases, an adequate therapy plan. Also our experience seems to confirm that, therefore, in spite of the above said limits, it is advisable to search PNI both with biopsy--in order to have a further prognostic element and therefore arrange the most suitable therapy plan--and on the surgery piece, in order to better determine the biological nature of the disease and to be able to suggest adequate integrative therapies.

The association of TR systematic echobiopsy of the prostate with power Doppler (PDU) in borderline PSA patients.

OBJECTIVE: TR systematic biopsy of the prostate is currently a method to diagnose prostate cancer, though with limited reliability. Many ancillary procedures have been put forward to improve its effectiveness, and PDU appears a very promising one Wehave attempted to verify whether PDU and eighth core TR biopsy together can ihcrease reliability especially in those patients with PSA values between 4 and 10 ng/ml. MATERIAL AND METHODS: Two groups of patients suffering from altered PSA and/or a palpable prostatic nodule underwent eighth core TR biopsy of the prostate. The first group was composed by 56 patients aged 55-82 (av.69.39) with PSA values ranging between 0.87 and 94.91 ng/ml (11.45 +/- 10.14) of which 29 had a palpable nodule. The second group was constituted by 96 patients aged 49-84 (av.69.84) with PSA values ranging between 1.14 and 59.7 ng/ml (12.8 +/- 11.66) of which 55 had a palpable nodule. The first group underwent eighth core TR biopsy, the second group TR biopsy and PDU. RESULTS: Twenty-five patients of the first group (44.64%) showed prostate cancer and 48 of the second (50%) were prostate cancer positive. We then divided them according to their PSA: 33 belonging to the first group (biopsy without PDU) had PSA values ranging between 4 and 9.6 ng/ml (7.59 +/- 1.61) and 13 (39.39%) were positive to Ca; 56 patients belonging to the second group (biopsy with PDU) had PSA values ranging between 4.09 and 9.66 ng/ml (7.02 +/- 1.56) and 26 (46.42%) were positive to Ca. We also ran tests with other groups of patients according to their PSA values although the above findings remained the most significant. CONCLUSIONS: Compared to other similarly interesting but more complex procedures, PD is easy to learn and easy to perform. Literature already shows how it can effectively be associated with systematic TR biopsy. On the basis of the above data we can conclude that PDU realistically improves reliability of eighth core TR biopsy--though not replace it--especially for those patients with PSA values between 4 and 10 ng/ml.

A more effective TR systematic biopsy of the prostate associated with power doppler ultrasonography (PDU): technical and morphological aspects.

OBJECTIVES: It is by now ascertained how PDU improves the effectiveness of systematic biopsy of the prostate. We have attempted to find better technical and imaging methods to optimise results. MATERIAL AND METHODS: We associated echo-biopsy with PDU on 131 patients. 64 patients (48.85%) showed prostate Ca. Their age was between 53 and 84 (av. 71.7) with PSA ranging from 1.14 and 59.7 (r. 9.,55 +/- 11.99 ng/ml). We then tried to locate in each sector areas of altered vascularization. RESULTS: In 34 cases (53.12%) we found hypo/hyper/iso reflecting areas surrounded by numerous vessels and crossed by one or more vascular branches (usually 2-3). In 8 cases (12.5%) we found hypo/hyper vascular echogenic virtually avascular, i.e. only a small perforating or surrounding branch. In 13 cases (20%) we found an aspecific and often widespread hyper-vascularization not associated to echographically atypical areas, bilateral in 4 cases. In 9 cases (14%) we did not find evident vascular alterations during PDU. Through the correlation of power Doppler ultrasonography images with histology we noticed that the area of altered vascularization was positive to Ca in 38 patients (59.37%) whereas the same was not true in 5 patients (7.8%), and finally in 21 patients (32.8%) the echo-doppler results (12 hypervascular and 9 "normal") was too aspecific to allow any kind of histomorphologic correlation. DISCUSSION: There are no pathognomonic patterns detectable through PDU for prostate Ca; although in the light of the above data it is safe to assume the existence of PDU detectable vascular alterations that in a good number of cases are not always neoplastic but prostatic disease which often coincide (about 60%) with cancer. The association of systematic biopsy and PDU helps highlight these areas thereby considerably improving diagnoses.

Power Doppler ultrasonography (PDU) as an additional tool to increase reliability of systematic biopsy of the prostate: a brief evaluation.

PDU is currently being tested as an aid to diagnosing prostate cancer. Our attempt has been to verify its usefulness to improve effectiveness of eight core TR biopsy. Two groups of patients were examined for increased PSA with or without a palpable prostatic nodule. The first group was composed by 52 patients between 55 and 83 years of age (mean 69.57) with PSA values between 0.87 and 94.91 ng/ml (8.085 +/- 14.056) of which 29 (55.75%) showed a palpable nodule. All patients underwent prostatic eight core TR echobiopsy. The second group was composed by 56 patients between 49 and 84 years of age (mean 69,19) with PSA values between 1.14 and 59.7 ng/ml (8.74 +/- 12.977) of which 33 (58.97%) showed a palpable nodule. This group of patients underwent a PDU just before TR biopsy in order to assess prostatic blood supply and locate possible alterations. Prostatic volume in both groups was never higher than 50 cc. Of the first group 25 patients (48.08%) were prostate cancer positive. Of the second group 31 patients (55.36%) were positive to a biopsyfor prostate cancer. In addition 22 out of the 31 showed a palpable nodule and vascular irregularity. PDU is being tested in order to reduce the number of biopsies and tissue samplings. The above results (tests carried out by the same operator with two homogeneous groups of patients) show how PDU was useful in diagnosing a higher number of prostate cancers. We could therefore safely conclude that the use of PDU in association with TR biopsy greatly increases diagnostic sensitivity and specificity.

[The meaning and usefulness of spiral CT for radiolucent ureteric stones diagnosis: our experience]. / The meaning and usefulness of spiral TC for radiolucent ureteric stones diagnostic: our experience.

The aim of this work was to report some case histories on the usefulness of spiral TC, used for several years both to diagnose renal colic and urinary lithiasis and to study radio lucent stones that are often difficult to be detected with traditional radiology. 13 patients, aged between 31 and 76 (average age: 54.2), were therefore examined. Eight of them had a ureteral colic when examined, while five patients had shown symptoms some days before being hospitalised in our ward. In all cases, ultrasonography showed a significant hydronephrosis, while direct radiography of the urinary tract could not detect any images that could be associated with radio-opaque lithiasis. All patients therefore underwent an abdominal spiral TC with no contrast medium within 24 hours after hospitalisation. The confrontation between the results obtained by ultrasonography and those obtained by spiral TC, showed the usefulness of the former method to detect stones located in the proximal ureter or in its intramural tract, while the latter could detect the lithiasis of the proximal ureter in 3 cases (23%), of the mid ureter in 2 cases (15.3%), and of the distal ureter in 8 cases (61%). The stones had, approximately, a 5 mm diameter in 5 cases. In 6 cases the diameter was between 6 and 10 mm, and more than 1 cm in 2 cases. Both methods proved to be equally accurate in the assessment of the hydronephrosis degree and of the thickness of the renal parenchyma. The therapy was medical in 2 cases and open surgery in 3 cases, while 8 patients were treated with ureterolitholapaxy with a ballistic searcher. The usefulness of TC in the study of urolithiasis nowadays is supported by a large literature which clearly supplies with documentary evidence the high sensitivity and specificity of such a method in diagnosing the presence of urolithiasis in general and above all of ureteric stones. Such a method not only makes an accurate evaluation of the stones location possible, but it can also assess the calculi dimensions and the indirect signs of the functionality of the kidney affected, without having to use the contrast medium. This method needs very limited execution times and allows a diagnostic of possible collateral pathologies. The main disadvantage of spiral TC, if compared to conventional radiology, is that the patient is exposed to a larger quantity of ionizing radiations, although such an inconvenience will be overcome by the new and more technologically advanced machines. According to our experience, though based on a limited number of cases, spiral TC allowed us to get a quick diagnosis of radio-lucent lithiasis, to see the seat and dimensions of the calculi and finally to chose the most effective treatment. We can therefore think of a diagnostic protocol, for ureteral colics with hydronephrosis or complicated by hyperpyrexia or sepsis, with spiral TC in order to have a quick diagnosis and start the most effective therapy in case an ultrasonographic research should not result diriment.

[Acceptability and safety of transrectal prostatic 8-core biopsy]. / Accettabilità e sicurezza della biopsia prostatica TR per ottavi.

The safety of sextant prostate biopsy has already been documented since the end of the 90's. As a higher efficacy of biopsy has been proved when increasing the number of samples taken, we have tried to assess the safety and tolerability of prostatic 8-core biopsy. From January to December 2001, 204 patients, aged between 50 and 88 (average 70) with a PSA between 0.74 and 196 ng/ml (10 +/- 9.25), underwent in 8-core prostate biopsy. After biopsy, the patients were given an oral antibacterial for 3 days. After taking the samples, patients were interviewed about the tolerability of the biopsy, and especially about the following: I. A feeling of irritation (77 patients, 37.7%); 2. A slight pain (72 patients, 35.29%); 3. A moderate pain (32 patients, 15.68%); 4. Intense pain (23 patients 11.27%). After 20 days all patients came back and were interviewed again about possible complications (biopsy was Ca positive in 86 cases, 42.15%). 153 patients (75%) reported a slight hematuria for an average period of 5 days; 88 patients (43.13%) showed slight anal-rectal hematic discharges, mainly after defecation efforts. It was never necessary to hospitalize any patients because of complications. 71 patients (34.8%) reported a perineal pain which disappeared after 24-48 hours. 175 patients reported having had an ejaculation after biopsy and 158 (90.2%) of them showed hematospermia. 4 patients (2%) had a short period temperature and only 2 (0.98%) were hospitalized for hyperpyrexia with symptoms of genitourinary sepsis. It has been proved that TR prostate biopsy is almost exclusively followed by minor complications, major ones being an exception. A biopsy with more than six samples (8-10-12) shows a higher number of minor complications (hematospermia and hematuria). The fact that a higher number of samples proves this method to be significantly more suitable, pays off all the problems. Also, such a casistics makes us think that prostatic 8-core biopsy is generally well tolerated (73% of patients reported either irritation or slight pain) and fairly safe, as complications are mainly minor ones. We must therefore underline the suitability, good tolerability and safety of the TR prostatic 8-core biopsy.