Giorgio Carmignani

AMS Three–Piece Inflatable Implants for Erectile Dysfunction: A Long–Term Multi–Institutional Study in 200 Consecutive Patients

Objectives: The aim of this study was to assess the longterm mechanical reliability of AMS (American Medical Systems) three–piece inflatable implants and their impact on patient–partner satisfaction in 200 consecutive patients with erectile dysfunction who underwent surgery in five different institutions.Methods: Patient charts included in the study were collected and extensively assessed to record pre– and intraoperative data and postoperative complications. All patients and 120 partners were then seen often in the office at a mean follow–up of 59 months (range 6–130) and they were extensively questioned about function of the device and its impact on the couple’s sexual life.Results: At the long–term follow–up, 185 patients (92.5%) were still engaging in sexual intercourse with a mean frequency of 1.7/week. Patients and partners reported prosthetic erections as excellent, satisfactory or poor in 96 (48%), 100 (50%) and 4 (2%) cases, and in 20 (17%), 80 (66%) and 20 (17%) cases, respectively. Postoperative sexual activity was considered excellent, satisfactory or poor by 140 (70%), 44 (22%) and 16 (8%) patients and by 34 (28%), 81 (68%) and 5 (4%) partners, respectively. Reasons for patients’ complaints included postoperative penile shortening in 60 (30%) cases and poor glandular engorgement in 40 (20%) cases. Partners’ main complaint was unnaturalness of the prosthetic erection, a factor reported by 30 (25%) subjects. Complications requiring surgical exploration included infection in 12 patients (6%) and mechanical failure in 8 patients (4%). Kaplan–Meier estimates demonstrated significantly decreased mechanical survival for the Ultrex type of cylinders compared to the CX type of cylinders.Conclusions: AMS three–piece inflatable implants provide an overall patient and partner satisfaction rate of 92 and 96%, respectively. However, postoperative penile shortening and poor glandular engorgement were the causes of some complaints among the patient population as well as the unnaturalness of prosthetic erection among female partners. In the long–term, mechanically speaking, CX cylinders seem to be more reliable than the Ultrex ones.

CD8+CD28− T Regulatory Lymphocytes Inhibiting T Cell Proliferative and Cytotoxic Functions Infiltrate Human Cancers

Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8+CD28− T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8+CD28− T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4+CD25+ T regulatory lymphocytes associate with CD8+CD28− T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer.

Validation of the 2009 TNM Version in a Large Multi-Institutional Cohort of Patients Treated for Renal Cell Carcinoma: Are Further Improvements Needed?

BACKGROUND A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. OBJECTIVE Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. INTERVENTION Patients underwent either radical or partial nephrectomy. MEASUREMENTS Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. RESULTS AND LIMITATIONS In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. CONCLUSIONS The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version.

Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients : Results of an italian prostate cancer project study

PURPOSE To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSE The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Radical nephrectomy for renal cell carcinoma: long-term results and prognostic factors on a series of 328 cases.

Objectives: A series of 328 evaluable patients with renal cell carcinoma operated by radical transabdominal nephrectomy with regional lymphadenectomy was reviewed to assess the prognostic significance of various pathologic parameters (pT, N, M, G and venous involvement) and the value of lymphadenectomy and of surgery of venous tumor thrombus. Patients and Methods: The complete charts of 328 patients with renal cell carcinoma available to follow-up, who were operated between 1970 and 1993, were reviewed. All patients underwent transabdominal extrafascial nephrosurrenalectomy and in all but 14 metastatic ones a regional retroperitoneal lymphadenectomy was performed. Surgery of venous tumor thrombus was performed in 79 patients. Life expectancy according to pT stage, pN stage, M stage, nuclear grade and venous involvement was calculated by means of the life tables method and differences in survival were evaluated by means of the log rank test. Correlation analysis and multivariate data analysis according to the Cox model were also performed. Results: Overall survival of the 328 patients was 50.70% at 5 years, 35.10% at 10 years and 29% at 15 years. At multivariate data analysis the most important prognostic factors is the presence of metastases (8 % survival at 5 years and no patient surviving more than 7 years after surgery); tumor grade was the second prognostic factor and statistically significant differences were also found at life tables analysis among G1, G2 and G3 tumors. Local tumor stage was the third leading prognostic factor at multivariate data analysis and statistically significant differences were also found at life tables analysis. Nodal and venous involvement had only minor importance at multivariate data analysis although statistically significant differences were found at life tables analysis between the pN+ and the pN0 patients, also in the absence of venous involvement and distant metastases. Anyway survival of the pN+M0V0 patients was satisfactorily high (53,20% at 5 years, 39.10% at 10 years and 16% at 15 and 20 years). In patients with venous involvement no differences in survival were observed depending on the level reached by the tumor thrombus; differences in survival were observed between patients with venous involvement alone (38% surviving at 5 and 10 years) and patients who also had nodal or distant metastases (5.20% at 5 years and 0% at 10 years). Conclusions: From the review of our series it seems that the most important prognostic factors are synchronous metastases, tumor grading and the completeness of tumor exeresis. In fact, the low impact on survival of nodal involvement by itself is probably due to the completeness of lymphadenectomy. The value of regional lymphadenectomy is sustained by the high long term survival of N+M0V0 patients. Regarding venous involvement, it seems that V+ patients free from nodal and distant metastases may benefit from radical surgery, which on the contrary has only minimal impact on survival of V+M+/N+ patients.

The Tongue as an Alternative Donor Site for Graft Urethroplasty: A Pilot Study

PURPOSE Urethroplasty with a buccal mucosal graft provides excellent clinical results but it may also cause oral complications in some cases. The mucosa covering the lateral and under surface of the tongue is identical in structure with that lining the rest of the oral cavity. We evaluated LMGs for urethroplasty. MATERIALS AND METHODS From January 2001 to September 2004, 8 men 34 to 65 years old (mean age 46.1) with urethral strictures 1.5 to 4.5 cm long were selected for 1-stage dorsal onlay urethroplasty. The site of the harvest graft was the lateral mucosal lining of the tongue. Postoperatively all patients were followed with urethrography, uroflowmetry, cystourethrography and flexible urethroscopy after 3 and 12 months. Successful reconstruction criteria were peak flow rate greater than 15 ml per second and no need for postoperative urethral dilation. RESULTS Median followup was 18 months (mean 22.1, range 3 to 47). Seven cases were successful. One patient had a partial urethral stricture. In successful cases cystourethrography revealed no significant graft contractures or sacculations and at flexible urethroscopy LMG was almost indistinguishable from native urethra. There were no pain, esthetic or functional complications at the donor site. CONCLUSIONS Harvesting the LMG is feasible and easy to perform. Compared with the buccal mucosal graft the LMG seems to be associated with less postoperative pain and a minor risk of donor site complications. These preliminary functional and esthetic data are satisfactory.

Hyperbaric Oxygen Therapy in the Treatment of Fournier's Disease in 11 Male Patients

PURPOSE Optimal tissue oxygenation, as obtained by hyperbaric oxygen therapy, potentiates or restores the hosts bactericidal mechanisms and wound healing activity in patients afflicted by serious synergeic aerobic and anaerobic infections of the cutaneous and subcutaneous tissues. Furthermore, hyperbaric oxygen therapy has a direct toxic effect on anaerobic bacteria. We describe our experience with hyperbaric oxygen therapy in the treatment of 11 patients with Fourniers syndrome. MATERIALS AND METHODS The average age of our patients was 59.5 years; the most common predisponsing condition was diabetes. All patients were treated with antibiotic therapy and hyperbaric oxygen therapy (minimum 5 and maximum 24 cycles, consisting of 90 minutes 2.5 atmosphere absolute pressure). Furthermore, 6 of these patients underwent surgical débridement of the wounds and 3 patients underwent delayed reconstructive surgery. RESULTS The results we obtained with hyperbaric oxygen therapy as an adjunctive measure for the treatment of these infections were excellent; our mortality rate for Fourniers disease was 0. Moreover, no complications whatsoever were observed. Furthermore, the 3 patients who underwent delayed corrective surgery presented with well healed tissues and their operations were not complicated by infections or other pathological conditions. CONCLUSIONS We believe that our findings, although limited in number, underline the excellent results that can be obtained with hyperbaric oxygen therapy as an adjunct treatment in Fourniers disease.

Combined oral therapy with sildenafil and doxazosin for the treament of non-organic erectile dysfunction refractory to sildenafil monotherapy

The purpose of this work was to investigate the efficacy and safety of sildenafil in combination with doxazosin for the treatment of non-organic erectile dysfunction in patients who did not respond to sildenafil. We enrolled 28 patients with non-organic erectile dysfunction, for whom 3 months of sildenafil monotherapy had failed. They were divided in two random and homogeneous groups: 14 were treated with doxazosin (4 mg daily) and sildenafil (100 mg 1 h before sexual intercourse); the other 14 patients received sildenafil and placebo. The results were assessed by means of the IIEF questionnaire before the beginning of the study, after 30 days of therapy and after 60 days. Of the 14 patients treated with doxazosin and sildenafil, 11 (78.6%) showed a statistically significant increase of IIEF; in the placebo group, only one patient (7.1%) recorded a significant IIEF increase. The differences observed in the two groups were statistically very significant (P=0.0016). Blood pressure did not show significant alterations. Side effects were minimal and even present during sildenafil monotherapy. The combination therapy with sildenafil and doxazosin resulted in the safe and effective treatment of men with non-organic erectile dysfunction for whom sildenafil alone had failed.

Traumatic rupture of the corpora cavernosa : New physiopathologic acquisitions

OBJECTIVES To investigate the physiopathologic mechanisms of the rupture of the corpora cavernosa by means of a histologic study of the tunica albuginea. METHODS In 6 patients (age range 28 to 49 years, mean 38) with traumatic penile rupture, samples of the tunica albuginea were taken during corrective surgery far from the site of the lesion. These specimens were analyzed with light microscopy by the same pathologist and compared with other samples of tunica albuginea taken from 7 patients who underwent penile surgery for other reasons. RESULTS Five of the 6 patients with traumatic penile rupture had histologic anomalies of the tunica albuginea (fibrosclerosis in all 5 patients [83%] and phlogistic cellular infiltrations composed of lymphocytes or histiocytes in 3 patients [50%]). Only 1 patient (17%) with traumatic rupture of the corpus cavernosum had a completely healthy tunica albuginea. None of the control specimens revealed any histologic alterations. CONCLUSIONS Structural anomalies could alter the mechanical properties of the tunica albuginea, representing a weakening factor of the corpora cavernosa and thus a predisposing factor for traumatic rupture of the penis. Therefore, patients with anomalous albuginea could undergo penile rupture even at intracavernous pressures inferior to pressures usually necessary to cause rupture in patients with healthy albuginea.