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Michele Lodde

Publications and source records attributed to Michele Lodde.

14 recordsLinked to original sources
PubMed2006

Molecular biological analysis of the heterogeneous prostate cancer group Gleason score 7.

BACKGROUND: On the basis of a multicolor-FISH test we aimed at verifying whether there is any molecular biological background for the different behavior of Gleason Score 7 prostate cancer (PCa). PATIENTS AND METHODS: Biopsies of 44 patients with histological verified PCa, 20 with Gleason score 3 + 4 (group A) and 24 with 4 + 3 (group B), were analyzed using FISH. RESULTS: In group A, FISH detected a unique gain of 8q24 in 2 patients (10.0%) and a unique loss of 8p22 in 9 patients (45.0%). No concurrent loss and gain of both sites were found in this group. Of group B (4 + 3) a unique loss of 8p22 was observed in 14 patients (58.3%) and a concurrent loss of 8p22 and gain of 8q24 in 6 patients (25.0%). CONCLUSION: Different molecular genetic patterns could explain the different biological behavior of the 2 groups. The analysis of chromosomal aberrations could therefore influence the clinical decision process in the future.

Aged↗
PubMed2006

uCyt+/ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on 1991 analyses.

BACKGROUND: The authors provide an update on the clinical value and role of the uCyt+/ImmunoCyt test as a noninvasive tool for the detection of recurrent urothelial carcinoma. METHODS: Between January 2002 and October 2004, 942 patients (mean age, 72.6 yrs; range, 32-87 yrs) were enrolled in this prospective study. These patients mostly had been followed for superficial urothelial carcinoma (UC) confined to the mucosa and lamina propria (pathologic tumor [pT] classification pTa, pT1, and pTis [carcinoma in situ]) for a mean of 15.62 months (range, 4-28 mos). Voided urinary cytology and the uCyt+/ImmunoCyt test for all patients were performed on liquid-based cytology slides. Patients underwent subsequent cystoscopy when cytology or uCyt+/ImmunoCyt results were positive and when they underwent biopsy evaluation of any suspicious lesion. Altogether, 1991 uCyt+/ImmunoCyt analyses were performed. RESULTS: Two hundred ninety-eight patients who had adequate samples available were diagnosed with histologically proven UC. The sensitivity of cytology increased from 8.3% for Grade 1 tumors to 75.3% for Grade 3 tumors; whereas, with the uCyt+/ImmunoCyt, the sensitivity was 79.3% for Grade 1 tumors, 84.1% for Grade 2 tumors, and 92.1% for Grade 3 tumors. For cytology and uCyt+/ImmunoCyt combined, the sensitivity was 79.3% for Grade 1 tumors, 90.9% for Grade 2 tumors, and 98.9% for Grade 3 tumors. CONCLUSIONS: The current data confirmed the clinical usefulness of the uCyt+/ImmunoCyt test in the follow-up of patients with recurrent UC. Used as a noninvasive tool, cytology escorted by uCyt+/ImmunoCyt may reduce the morbidity and cost of follow-up for patients who have a low risk of recurrence while avoiding superfluous cystoscopic examinations. However, additional studies will be necessary to establish and compare the morbidity and cost of each method.

Adult↗
PubMed2006

uCyt+ test: alternative to cystoscopy for less-invasive follow-up of patients with low risk of urothelial carcinoma.

OBJECTIVES: To assess the utility of ImmunoCyt/uCyt+ in combination with cytology to reduce the number and cost of cystoscopies in the follow-up of patients with urothelial cancer of the bladder. METHODS: A total of 216 patients under follow-up after transurethral resection of the bladder for urothelial cancer were enrolled in the present study. The mean follow-up time was 26 months (range 3 to 96). Patients were tested for bladder cancer with ImmunoCyt/uCyt+, urinary cytology, and cystoscopy every 3 months. All patients with positive cystoscopy results for recurrence or suspect areas underwent transurethral resection of the bladder. Cystoscopy was considered the reference standard to establish the bladder tumor diagnosis. The patients were divided into low, intermediate, and high risk groups for progression according to the European Association of Urology criteria. RESULTS: A total of 195 patients were suitable for evaluation. The urine samples from 21 patients were considered not evaluable for ImmunoCyt/uCyt+, and those patients were excluded from the study. Of all the control patients, 69.7% had negative cystoscopy findings. In the low-risk group, 84 patients underwent 131 cystoscopies, which diagnosed 30 Stage pTaG1 recurrences but no progression. Cytology and ImmunoCyt/uCyt+ together had a sensitivity of 86.6% and a negative predictive value of 95.2%. CONCLUSIONS: Of the cystoscopies performed during the 26 months of follow-up, 69.7% were negative. In the low-risk group, 30 Stage pTaG1 tumors and no progression was detected at a total cost of 14,672 Euros (USD 17,606). ImmunoCyt/uCyt+ and cytology every 6 months combined with annual cystoscopy reduced the morbidity and cost of follow-up in this group.

Antibodies, Monoclonal↗
PubMed2006

Effect of doxazosin on oxidative stress-related proteins in benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVES: Oxidative stress can induce cell mutations or proliferation which then can progress to carcinogenesis or remodeling. The same oxidative stress-mediated mechanism could participate in prostate cell proliferation and remodeling present in benign prostatic hyperplasia (BPH). Doxazosin induces prostate epithelial and stromal cell apoptosis through production of transforming growth factor-beta (TGF-beta), but cellular mechanisms are not completely clarified. In 10 prostate samples from BPH untreated patients who underwent TUR, we have assessed the gene and protein expression of: p22(phox) (subunit of NAD(P)H oxidase essential for O(2)(-) production); heme oxygenase-1 (HO-1) (induced by oxidative stress and antiapoptotic); TGF-beta (inhibitor of prostatic epithelial and stromal cell growth); the in vitro effect of doxazosin on expression of these markers. METHODS: RT-PCR and Western blot with specific primers and antibodies. p22(phox), HO-1 and TGF-beta were quantified by the ratio between their PCR and Western blot products and GAPDH. RESULTS: Doxazosin significantly reduced p22(phox) gene and protein expression (0.61 +/- 0.04 vs. 0.36 +/- 0.04 d.u., p < 0.0002; 0.85 +/- 0.03 vs. 0.47 +/- 0.03, p < 0.0001, respectively). Doxazosin concentration dependently reduced HO-1 gene and protein expression (0.57 +/- 0.07 vs. 0.49 +/- 0.06 d.u. (1 microM) p < 0.04, vs. 0.22 +/- 0.08 (10 microM) p < 0.0001; 0.78 +/- 0.04 vs. 0.44 +/- 0.1 (10 microM) p < 0.003 respectively) and increased TGF-beta protein expression (0.58 +/- 0.05 vs. 0.74 +/- 0.16 (1 microM) n.s. vs. 0.81 +/- 0.07 (10 microM) p < 0.01). CONCLUSIONS: Induction of oxidative stress-related proteins seems to be involved in the prostate cell proliferation and remodeling present in BPH. Doxazosin may reduce oxidative stress through reduction of p22(phox). Surprisingly, HO-1, which is induced and protected by oxidative stress, is also reduced by doxazosin. HO-1 is a potent antiapoptotic factor and downregulator of TGF-beta. From the results of this preliminary study it could be proposed that the proapoptotic effect of doxazosin could be mediated, at least in part, through the contemporary inhibition of HO-1.

Aged↗
PubMed2005

Four years experience in bladder preserving management for muscle invasive bladder cancer.

OBJECTIVES: To evaluate the bladder preservation strategy in invasive bladder cancer particularly relapse, progression and complications. MATERIALS AND METHODS: From January 2000 to May 2004 a total of 24 patients (mean age of 81 years; range 68-92) with muscle invasive bladder cancer who had refused or were not eligible for cystectomy were followed up for a period of up to four years. RESULTS: 24 (21 M/3 F) patients were followed up for a mean time of 680 (182-1253) days. All patients complained of frequency, urgency and severe nocturia. The second most frequent complication was bleeding which required a salvage cystectomy in 7 cases. Other major complications were intestinal occlusion in three cases, an enterovesical fistula, brain metastasis requiring neurosurgical intervention and radiation therapy of the brain, bone metastasis in the cervical spinal column and chronic renal failure. The mean re-admission rate was 8 per patient and the mean time spent at the hospital was 109 (range 13-253) days. CONCLUSION: In our series the bladder preserving strategy does not confirm the optimistic results of other authors. The complications forced us to carry out a salvage cystectomy in nearly half of the cases. The other half of the patients complained of other severe complications reducing the quality of life of the remaining life span.

Aged↗
PubMed2005

Uretero-ureterocutaneostomy (wrapped by omentum).

UNLABELLED: The tubularized-incised plate urethroplasty has traditionally been used in children for repairing hypospadias. As shown here, it can also be used successfully in adults, with very good results. The rate of wound healing, infection and complications is the same as in children, as are the cosmetic and functional outcomes. OBJECTIVES: To evaluate the outcome of uretero-ureterocutaneostomy (UUC) wrapped by omentum for palliative cystectomy in symptomatic elderly high-risk patients with high-stage bladder cancer. PATIENTS AND METHODS: The study included 15 patients (14 men and one woman, aged 72-87 years, American Society of Anesthesiology score 3) with symptomatic recurrent bleeding bladder cancer (T2/T3) who were treated with palliative cystectomy. UUC was performed by mobilizing the right pre-vesical divided ureter up to the pelvi-ureteric junction and a high retroperitoneal crossover to the divided left ureter. A stoma was created with a circular 2-cm skin excision and resecting the fatty subcutaneous tissue. Wrapped by the omentum, both well-vascularized ureteric stumps were pulled through a cross-like fascia incision up to skin level. Spatulated and everted, the 'butterfly' flaps were fixed to the skin and underlying omentum. Soft splints were inserted for 21 days and a Karaya ring placed. RESULTS: The postoperative course and stoma healing was normal in 14 of the 15 patients; the sigmoid was resected because of sigmoid diverticulitis in one. The median (range) follow-up was 15 (6-24) months. There was pyelonephritis in one patient, and the dilatation of the upper tract (grade 3) in two returned to grade 2, with new asymptomatic grade 1 dilatation in one other. All patients were without stents and stoma care was provided at home. CONCLUSIONS: This modified UUC by omental wrapping in 15 high-risk patients after palliative cystectomy was simple and safe, and their recovery was uneventful. To date the few patients with stomal obstruction were managed by J catheters, changed every 4-6 months.

Aged↗
PubMed2004

The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced prostate cancer.

The androgen receptor co-activator CREB (cAMP-response element binding protein)-binding protein (CBP) enhances androgen receptor activity after stimulation by androgenic hormones and androgen receptor antagonists. The aim of the present study was to investigate the regulation of CBP expression by steroid and peptide hormones in prostate cancer. For this purpose, LNCaP cells were treated with the synthetic androgen methyltrienolone (R1881), epidermal growth factor, insulin-like growth factor-I or interleukin-6 (IL-6). CBP protein and mRNA expression were studied by western blotting and real-time PCR, respectively. CBP expression was also investigated in tissue specimens obtained from 26 patients with therapy-resistant carcinoma of the prostate. In LNCaP cells, CBP protein was down-regulated by R1881 or IL-6. The non-steroidal anti-androgen bicalutamide antagonized the effects of R1881 and the Janus kinase inhibitor AG 490 reversed the effects of IL-6. In contrast, neither R1881 nor IL-6 caused any effect on CBP expression in the PC-3 cell line. In LNCaP cells, the inhibition of CBP expression by R1881 or IL-6 was also observed at the mRNA level. CBP protein was detected in all 26 specimens by immunohistochemistry. The results suggest that up-regulation of CBP during androgen ablation may be relevant to the failure of endocrine therapy in patients with prostate carcinoma.

Aged↗
PubMed2004

Intermediate-risk urothelial carcinoma: an unresolved problem?

OBJECTIVES: To perform a biologic characterization of the urothelial neoplasms of patients in the intermediate-risk group using multicolor-fluorescence in situ hybridization (FISH). A general consensus has not been reached with regard to the optimal therapy and follow-up of patients with urothelial neoplasms at intermediate risk of progression. On the basis of the chromosomal pattern, we developed a new follow-up algorithm for this group and report our preliminary results. METHODS: Voided urine samples of 51 consecutive patients (mean age 72.2 years, range 52 to 93) under follow-up after complete transurethral resection of intermediate-risk urothelial carcinoma were evaluated by liquid-based cytology (ThinPrep) and uCyt+. From the residual material, Multicolor-FISH (Urovysion) was performed. Any cystoscopically suspicious lesion was biopsied or removed transurethrally. The mean follow-up time was 14.2 months (range 6 to 30, SD 5.5). RESULTS: Two of the 51 patients were not evaluated because of the presence of intense granulocytosis and insufficient urothelial cells. Of the 49 remaining patients, the results of the Multicolor-FISH analysis were negative (diploid chromosomal pattern) in 14; 20 patients showed the loss of one or both alleles of p16 and/or an aneuploidy of chromosome 3, and 15 patients had aneuploidy of chromosome 7 and/or 17. Of the 14 FISH-negative patients, 2 (14.3%) had histologically verified recurrence, and 3 (15.0%) of the 20 p16/3-positive patients had recurrence and 9 (60.0%) of the 15 7/17-positive patients had either recurrence or progression. CONCLUSIONS: Using the Urovysion test, it is possible to predict the biologic behavior of urothelial cancer with a significant impact on the follow-up of patients. The intermediate-risk group of urothelial cancer can be eliminated in the routine workup by classifying these patients according to their chromosomal pattern and defining those patients who can follow the low-risk scheme and those who must be monitored according to the guidelines for high-risk superficial lesions.

Aged↗
PubMed2004

Effect of intravesical instillation on performance of uCYT+ test.

OBJECTIVES: To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guérin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells. METHODS: A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series. RESULTS: Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity (P = 0.512) and specificity (P = 0.558) for the uCyt+ test in the two groups of patients. CONCLUSIONS: The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.

Administration, Intravesical↗
PubMed2003

Role of uCyt+ in the detection and surveillance of urothelial carcinoma.

OBJECTIVES: To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma. METHODS: Included in this prospective study were 235 patients (mean age 71.5 years, range 32 to 86). Of these, 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer (UC). All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep (thin layer). All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy. RESULTS: A total of 102 patients had histologically proven UC. In the group of patients with signs and symptoms suspicious of UC, the sensitivity of cytology increased from 5% for G1 to 84.6% for G3 tumors; for uCyt+, it was 85% for G1, 100% for G2, and 92.3% for G3 tumors. Combining cytology and uCyt+, the sensitivity was 85% for G1 and 100% for G2 and G3. In the group of follow-up patients, the sensitivity of cytology increased from 4.3% for G1 to 94.4% for G3 tumors; for uCyt+, it was 78.2% for G1, 70% for G2, and 94.4% for G3 tumors. Combining both tests, the sensitivity was 78.2% for G1, 90% for G2, and 100% for G3. CONCLUSIONS: The uCyt+ is a valid test in the detection of UC of all grades and stages. It improves the sensitivity of cytology in low-grade tumors. The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance.

Adult↗
PubMed2003

Teaching transurethral resection of the bladder: still a challenge?

OBJECTIVES: To report on our 2-year experience in teaching transurethral resection (TUR) of bladder tumors to five trainees. We analyzed their problems, as well as those of the teachers, and present our solutions. METHODS: Between April 2000 and March 2002, five residents and three members of the staff took part in a training program to teach TUR of the bladder. From a total of 692 patients with bladder tumors admitted for treatment to our department, 417 were selected for the study. These 417 had papillary tumors of small to medium size (maximum 25 mm in diameter). The mean patient age was 61 years (range 32 to 92) for men (n = 322; 77%) and 68.4 years (range 48 to 91) for women (n = 95; 33%). RESULTS: A total of 417 teaching TURs were performed during a 24-month period. A total of 65 complications (16%) occurred and were analyzed from the database. The most common complication was postoperative bleeding, occurring in 33 cases (8%), followed by extraperitoneal perforation, which occurred in 16 cases (4%). CONCLUSIONS: Despite careful patient selection and the use of video-assisted equipment and permanent supervision by an experienced resectionist, a significant number of complications occurred. The question: "How to teach the teacher to teach TUR of the bladder?" remains open.

Adult↗
PubMed2003

En bloc transurethral resection of bladder tumors: use and limits.

OBJECTIVES: To evaluate the feasibility and safety of transurethral en bloc resection of bladder tumors using a flat loop. Transurethral en bloc resection of bladder tumors facilitates pathologic evaluation. METHODS: A total of 37 patients with papillary transitional cell carcinoma of the bladder underwent transurethral en bloc resection with the use of a flat loop electrode. RESULTS: In 37 patients, 62 lesions were removed using a flat loop to perform the en bloc technique. This method is safe to perform in the case of papillary tumors with a diameter of up to 25 mm and that are found in specific areas of the bladder. CONCLUSIONS: It is both safe and feasible to perform en bloc resection with a flat loop electrode but attention must be paid to the limitations of this technique. Excellent pathologic evaluation of the grade and stage of the removed specimen is possible.

Aged↗
PubMedDate not supplied

The value of the ImmunoCyt/uCyt+ test in the detection and follow-up of carcinoma in situ of the urinary bladder.

BACKGROUND: Urine bound tests, which have been developed for the early detection of urothelial cancer (UC), do not seem to match cytology in the detection of carcinoma in situ (CIS) as their sensitivity in the case of CIS is poor. ImmunoCyt/uCyt+ in CIS seems promising, but the number of analysed CIS is still small. The aim of the present study was to assess the value of this test in the detection and follow-up of carcinoma in situ of the urinary bladder. PATIENTS AND METHODS: Thirty-five patients, with histologically verified CIS of the urinary bladder, were included in the study. At the first diagnosis, patients underwent cytology, cystoscopy, bioptical bladder mapping and ImmunoCyt/uCyt+. All patients underwent BCG instillation therapy. The patients were followed with cytology, ImmunoCyt/uCyt+, cystoscopy and bladder mapping after every BCG cycle and then every 3 months. RESULTS: At the first CIS diagnosis, the sensitivity of cytology and ImmunoCyt/uCyt+ was 100%. At the first control after therapy, cytology detected 81.8% of recurrences and ImmunoCyt/uCyt+ detected 90.9%. At the second control, both tests each detected 50% of recurrences. At every control, the combination of both the tests together gave a sensitivity of 100%. The specificity of cytology after therapy improved from 88.2% at the first control up to 100% at the third control. The specificity of ImmunoCyt/uCyt+ after BCG initially decreased from 70.6% to 55.5% and finally increased to 88.9%. CONCLUSION: ImmunoCyt/uCyt+ is as sensitive as cytology in the first diagnosis of CIS. In the follow-up, even if it is less sensitive, its combination with cytology leads to detection of 100% of the recurrences. Despite decreasing specificity after therapy, the value remains acceptable and increases during maintenance therapy. The ImmunoCyt/uCyt+ test could play an important role in controlling the response of patients to instillation therapies or in the modification of their application schedules.

Aged↗