Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

The clinical use of statistical permutation test methodology: a tool for identifying predictive variables of outcome.

OBJECTIVES: To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). METHODS: A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysis of their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. The patients were included in a comprehensive database with medical history and clinical and pathological data. Five-year survival was used as the dependent variable, and p values were corrected for multiplicity using a closed testing procedure. The newer nonparametric approach was used to evaluate the prognostic importance of the variables. All of the analyses were performed using routines developed in MATLAB© and the significance level was set at α = 0.05. RESULTS: A significant prognostic predictive value (p < 0.01) for tumor clinical staging, hydronephrosis, tumor pathological staging, grading, presence of concomitant carcinoma in situ, regional lymph node involvement, corpora cavernosa invasion, microvascular invasion, lymphatic invasion and prostatic stroma involvement was found. CONCLUSIONS: The NPC test could handle any type of variable (categorical and quantitative) and take into account the multivariate relation among variables. This newer methodology offers a significant contribution in biomedical studies with several endpoints and is recommended in presence of non-normal data and missing values, as well as solving high-dimensional data and problems relating to small sample sizes.

Hepatocyte growth factor/scatter factor and prostate cancer: a review.

Men who die from prostate cancer do so from uncontrolled metastatic disease. A better understanding of the mechanisms involved in the progression and metastasis of prostate cancer may lead to novel therapeutic approaches to prevent its natural progression. Hepatocyte Growth Factor / Scatter factor (HGF/SF) has been demonstrated to elicit a number of key functions in numerous tissues that are important in the progression, invasion and metastasis of cancer. Studies have demonstrated that the activity of HGF/SF and its receptor c-Met are linked to disease progression in numerous cancers. However, research into these functions, which include activities as a mitogen, a motogen and an anti-apoptotic and angiogenic factor in prostate cancer are limited. This article reviews the published evidence of the roles HGF/SF plays in prostate cancer progression and highlights the clinical and therapeutic potential of research into this pleiomorphic cytokine.

Low dose bacillus Calmette-Guerin for carcinoma in situ of the bladder: long-term results.

PURPOSE: Bacillus Calmette-Guerin (BCG) is standard treatment for carcinoma in situ of the bladder. However, its long-term effectiveness is still debated. MATERIALS AND METHODS: From January 1987 to January 1995, 70 consecutive patients with primary or secondary carcinoma in situ with or without concomitant solitary or multifocal papillary tumor were treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after histological diagnosis. An additional induction course was given to patients with relapse. Tumor-free patients were given a maintenance course of monthly instillations for 12 months. RESULTS: At the end of induction course 1, 56 of the 70 patients (80%) were tumor-free. Of 14 patients given induction course 2, 9 had a complete response (64.2%). A total of 65 patients (92.8%) were disease-free after 1 or 2 courses and given the maintenance course. Median followup for disease-free patients was 74 months (range 17 to 134). Subsequently 50 patients (71.4%) were disease-free, 12 (17.1%) had recurrence and 8 (11.4%) had progression. Mean time was 18 months (range 6 to 69) to treatment failure and 13 months (range 7 to 53) to progression. Of the patients 1 died of disease and 10 of other causes. Crude survival was 84.2%, disease specific mortality 1.4% and nondisease specific mortality 14.2%. The risk of treatment failure was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001) or severe dysplasia (p = 0.0005), and the risk of disease progression was significantly greater for carcinoma in situ associated with stage T1 papillary tumor (p = 0.0001). The drug was well tolerated with few side effects. CONCLUSIONS: Intravesical BCG is the best available conservative therapy for patients with carcinoma in situ of the bladder. Low dose BCG is similarly effective, with a lower incidence of side effects and long lasting positive outcome.

Intravesical bacille Calmette-Guérin in Stage T1 grade 3 bladder cancer therapy: a 7-year follow-up.

OBJECTIVES: To assess the long-term results of intravesical bacille Calmette-Guérin (BCG) treatment for Stage T1 grade 3 (T1G3) transitional cell carcinoma (TCC) of the bladder. METHODS: Fifty-one patients with T1G3 TCC were treated with induction plus maintenance BCG courses after transurethral resection and followed up for at least 5 years or until death. RESULTS: The median follow-up of progression-free patients was 85 months (range 64 to 108). During this period 32 (62.7%) of 51 patients remained progression free, 9 (17.6%) progressed, 8 (15.7%) died of other causes, and 2 (3.9%) were lost to follow-up. Seven patients had extravesical involvement: 5 (9.8%) of 51 had an upper urinary tract tumor and 3 (7.9%) of 38 had prostatic involvement (1 of the 7 had both). The risk of disease progression was significantly higher for patients with a tumor measuring 3 cm or more and those with tumor associated with carcinoma in situ (CIS) in multivariate analyses and for patients with recurrent tumors, solid tumors, or early T1G3 recurrence after BCG in univariate analyses. At last follow-up, 34 patients (66.7%) were alive; 8 (15.7%) had died of causes unrelated to the disease, 7 (13.7%) had died of bladder cancer, and 2 (3.9%) had been lost to follow-up. Disease-specific survival was 86.3%. CONCLUSIONS: Intravesical BCG is an effective conservative treatment for T1G3 bladder cancer. Patients with negative prognostic factors such as coexisting CIS or large, solid, or recurrent tumor should be followed up closely and if T1G3 recurs early after the BCG induction course, immediate cystectomy should be performed.

Upper urinary tract tumors developing after treatment of superficial bladder cancer: 7-year follow-up of 591 consecutive patients.

OBJECTIVES: To evaluate upper urinary tract tumor (UUTT) incidence and characteristics in 591 consecutive patients with low-, intermediate-, or high-risk superficial bladder cancer, who were followed up for at least 5 years or until death. METHODS: From 1986 to 1992, 591 patients were treated for superficial bladder cancer: 216 patients with primary, solitary, low-grade (G1-G2), and low-stage (Ta-T1) superficial bladder cancer were considered at low risk of disease recurrence and treated with transurethral resection (TUR) alone; 182 patients with recurrent or multifocal superficial bladder cancer were considered at intermediate risk of disease recurrence or progression and treated with intravesical chemotherapy after TUR; 193 patients with carcinoma in situ, high-grade (G3) superficial bladder tumor, or intravesical chemotherapy failure were considered at high risk of disease recurrence or progression and treated with bacille Calmette-Guérin (BCG). RESULTS: After a median follow-up of 86 months (range 20 to 143), 2 (0.9%) of 216 patients at low risk, 4 (2.2%) of 182 patients at intermediate risk, and 19 (9.8%) of 193 patients at high risk developed UUTTs. The incidence of UUTTs is significantly higher in patients at high risk than in those at low risk (P = 0.0004, odds ratio = 11.6, 95% confidence interval [CI] 2.5 to 40.7) or at intermediate risk (P = 0.004, odds ratio = 4.8, 95% CI 1.5 to 17.2), or both (P = 0.000006, odds ratio = 7.3, 95% CI 2.6 to 20.3). The difference between patients at low risk and those at intermediate risk was not statistically significant (P = 0.5, odds ratio = 0.4, 95% CI 0.02 to 2.6). After a median time of 36 months (range 9 to 119) from UUTT diagnosis, 5 (20%) of 25 patients have died of the disease. CONCLUSIONS: The incidence of metachronous UUTTs is low in patients with superficial bladder cancer at low or intermediate risk of disease recurrence or progression and significantly higher for patients at high risk. Because UUTT is often asymptomatic, and mortality is high, frequent and lifelong examination of the upper urinary tract is suggested, with an annual intravenous urogram and urinary cytologic analysis every 4 months in patients with superficial bladder cancer at high risk of disease recurrence or progression.

Intravesical instillation of mitomycin-C in 242 patients with superficial bladder cancer at high risk of recurrence: long-term results.

OBJECTIVE: The present study evaluated the long-term results of intravesical mitomycin C (MMC) instillation after transurethral resection (TUR) in 242 consecutive patients with superficial bladder cancer at high risk of recurrence (stage Ta, grade 1-3, or stage T1, grade 1 and 2, primary multiple or recurrent tumor). MATERIALS AND METHODS: 242 patients were treated with weekly instillations of 40 mg MMC for 8 weeks after TUR. Tumor-free patients then followed a maintenance course with monthly instillations for 3 months. RESULTS: Median follow-up of disease-free patients is 43.5 (range 23-112) months. The incidence of first recurrence is 59.5% (144/242 patients) with a median time to first recurrence of 29 months. 95 patients (39.3%) remained disease-free. Three had disease progression as the first event. The risk of recurrence was significantly higher for multifocal tumors (p = 0.0023, hazard ratio 1.79, 95% CI 1.23-2.59). Overall, patients have been followed for a median time of 57 (range 10-114) months. During this period the recurrence rate was 4.9. Eleven more patients had disease progression. The progression rate is 5.8% (14/242), with a mean time to progression of 34 months. At present 209 patients are alive, 6 have died of bladder cancer, 16 of causes unrelated to the disease and 11 (4.5%) have been lost to follow-up. Thus the crude survival rate is 86.4%, disease-specific mortality 2.5%, and non-disease-specific mortality 6.6%. CONCLUSIONS: Patients with multiple tumors seem to benefit the least from MMC instillation. Probably recurrent disease could be better prevented with intravesical bacillus Calmette-Guérin.

[Conservative therapy of renal parenchymal neoplasia]. / Terapia conservativa della neoplasia renale parenchimale.

We review our overall experience in 1375 patients, who underwent surgery for renal cell carcinoma in the Departments of Urology of Brescia and Bergamo from 1983 to 1996. 185 (13.4%) patients had nephron-sparing surgery: imperative procedure was performed in 74 cases, while an elective surgery was done in 111 patients. Three years minimal follow up was considered in order to evaluate the outcome of surgical treatment in 48 patients who underwent imperative nephron-sparing surgery and in 73 with an elective procedure. Disease specific survival was 80.8% in the first group and it was 97% in the latter.

Low dose Pasteur bacillus Calmette-Guerin regimen in stage T1, grade 3 bladder cancer therapy.

PURPOSE: We assessed the effectiveness of intravesical bacillus Calmette-Guerin (BCG) for high risk transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A total of 51 patients with stage T1, grade 3 disease was treated with weekly instillations of 75 mg. Pasteur strain BCG for 6 weeks after transurethral resection for bladder cancer. An additional induction course was given to patients with relapse. Tumor-free patients followed a maintenance course with monthly instillations for 12 months. RESULTS: After the initial induction course 37 of 51 patients (72.5%) remained tumor-free. A second induction course was necessary in 13 patients. After 1 or 2 induction courses 44 of 51 patients (86.3%) were tumor-free. The maintenance course was administered to 44 patients, with 41 remaining tumor-free. After a median followup of 33 months (range 3 to 63) 28 patients (54.9%) were disease-free, 12 (23.5%) had recurrent tumors and 7 (13.7%) had progression. The risk of treatment failure was significantly greater for solid than papillary tumors (p = 0.0006), recurrent than primary tumors (p = 0.0052) and coexisting carcinoma in situ (p = 0.124) in multivariate analysis, and for early recurrence (p = 0.0001) in univariate analysis only. The drug was well tolerated with few side effects. CONCLUSIONS: Our data suggest that this low dose Pasteur BCG regimen is effective in the treatment of high risk superficial bladder cancer. Some tumor characteristics, such as solid appearance, coexisting carcinoma in situ, history of superficial transitional cell carcinoma and early relapse after the initial induction course, seem to be negative prognostic factors.

[T1G3 transitional cell carcinoma of the bladder: our experience with 44 patients treated with intravesical BCG after TUR]. / Carcinoma a cellule transizionali della vescica T1G3: la nostra esperienza in 44 pazienti trattati con BCG intravescicale dopo TUR.

Forty-four patients affected by poorly differentiated (G3) superficial TCC invading lamina propria (stage T1) were treated with intravesical BCG. They underwent weekly instillations of 75 mg BCG for six week after trans-urethral resection (TUR) of bladder cancer. An additional induction course was given to patients who relapsed. A maintenance course with monthly instillations for twelve months followed in complete responder patients. After the first induction course, 34/44 patients (77.2%) showed complete response. In 10 patients a second induction course was necessary, with complete response in four. After one or two induction course, 38/44 patients (86.5%) showed complete response. The maintenance course was administered to 38 patients with 35/38 complete responses. After a median follow-up of 30 months, there were 29/44 (65.9%) disease free patients, 11/44 (25%) tumor recurrences and 4/44 (9%) tumor progressions. The drug has been well tolerated with few side effects. Our data suggest that intravescical BCG after TUR is effective in the treatment of high-risk superficial bladder cancer and we believe that it can be used a first approach in treating patients affected by T1G3 bladder cancer.

[Our current indications for radical prostatectomy]. / Le nostre attuali indicazioni alla prostatectomia radicale.

Radical prostatectomy is the golden standard for localized prostate cancer. The identification of patients with intraprostatic disease who can be cured and will live long enough to benefit from a surgical therapy represents the primary goal of the authors. Target of this article is underlining the importance of an accurate preoperative staging through ultrasound-guided biopsy of seminal vesicles and periprostatic spaces. The positivity of the surgical margin after radical prostatectomy is also taken into account as it represents, according to the authors, an extremely important but often overlooked parameter.

[Surgical treatment of benign prostatic hypertrophy: what and when TURP vs adenomectomy]. / Terapia chirurgica dell'ipertrofia prostatica benigna. Quale e quando TURP vs adenomectomia.

Surgical treatment is the gold standard for Benign Prostatic Hyperplasia (BPH) therapy. At the present diagnostic approach allows better patient selection and treatment assignment. In this work we have studied retrospectively the outcome of 120 BHP patients who underwent trans urethral resection (TURP) and of 145 BPH patients underwent "open" prostatectomy. In all the patients surgical time, prostate weight, indwelling catheter standing, rest in bed, early and late complications were evaluated. Irritative symptoms occurred after TURP in 10% of the cases. The two therapeutical options are not comparable for they technically different. The choice between the two depends on the accurate patient characterization and selection.

[Nerve-sparing retroperitoneal lymph node dissection in patients with non-seminomatous testicular tumors at clinical stage 1]. / La LAD retroperitoneale nerve sparing nei pazienti con tumori non seminomatosi del testicolo in primo stadio clinico.

Retroperitoneal lymph node dissection (RPLND) for low stage testicular cancer involves a low rate of dry ejaculation. The nerve-sparing technique avoids the damage of sympathetic fibers. 7 cases of non seminomatous testicular cancer have been treated by the Author. Through midline incision and intestinal derotation the vascular plane and the sympathetic fiber are identified before starting lymph node dissection. All the patients report physiological ejaculation; the post-operative follow-up is still short but at the present all patients are tumor free. In low stage testicular cancer nerve-sparing lymphadenectomy preserve physiological ejaculation and reducing surgical morbidity as well.

[Conservative therapy of parenchymal renal carcinoma]. / Terapia conservativa del carcinoma renale parenchimale.

From January 1987 to October 1990, 20 patients (16 M. 4 F.) affect by localized renal cell carcinoma, underwent a conservative surgical treatment. This case study includes 8 patients with bilateral (4 synchronous-4 asynchronous), and 12 patients with unilateral renal carcinoma. In the latter group only two patients had a pathological contralateral kidney. A parenchyma sparing operation was performed electively in 10 cases and was necessary in the other 10. The tumors were found to be PT1 or pT2 in all the elective cases, except one unexpected pT3a; 1pT1, 5pT2, 1pT3a and 3pT3b in the remaining group. The follow up ranges between 1 and 36 months, two deaths in bilateral tumors cases were observed. No local recurrences have been detected up to now.

[Evaluation of the activity of the bladder detrusor muscle and analysis of bladder function in subjects with diabetes mellitus under insulin treatment]. / Valutazione dell'attività del muscolo detrusore della vescica ed analisi della funzione vescicale in soggetti affetti da diabete mellito in trattamento insulinico.

The present report concerns investigations of detrusor muscle adrenergic innervations in patients affected by bladder neuropathy secondary to diabetes without obstructive disturbances. Detrusor contractile activity evoked by NE is markedly reduced which can probably be attributed to receptor deficit. Urodynamic evaluation demonstrated a prevalence of sensory peripheral neuropathy than a motor conduction abnormality. In vitro study demonstrated that motor conduction abnormality of detrusor contractile activity is present early without bladder disturbances. Therefore early urodynamic measurements are necessary to evaluate bladder dysfunction and neuropathy in diabetic patients.