Andrea Guttilla

Choline PET or PET/CT and biochemical relapse of prostate cancer: a systematic review and meta-analysis.

Aim The increase of prostate-specific antigen (PSA) after radical retropubic prostatectomy (RP) or external beam radiotherapy (EBRT) is the most sensitive tool for detecting prostate cancer (PCa) recurrence, although this measure cannot distinguish between local, regional, or distant recurrence. The aim of this meta-analysis was to evaluate the diagnostic performance of 18F-choline and 11C-choline PET or PET/CT in detection of locoregional or distant metastases in PCa. Materials and Methods Medline, Web of Knowledge, and Google Scholar search was carried out in order to select English-language articles dealing with diagnostic performance of both 18F-choline and 11C-choline PET for the detection of PCa recurrence after RP or EBRT. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and regarded local, lymph node, and distant metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were re-analyzed thus performing a quantitative analysis. Results From the years 2000 to 2012, we found 53 complete articles that critically evaluated the role of choline PET in restaging patients with PCa recurrence. The meta-analysis was carried out and dealt with 19 selected studies (12 studies for all sites of disease, 3 for lymph node metastases, and 4 for local recurrence), with a total of 1555 patients. The meta-analysis provided a pooled sensitivity of 85.6% (95% CI: 82.9%–88.1%) and pooled specificity of 92.6% (95% CI: 90.1%–94.6%) for all sites of disease (prostatic fossa, lymph nodes, and bone), a pooled sensitivity of 75.4% (95% CI: 66.9%–82.6%) and pooled specificity of 82% (95% CI: 68.6%–91.4%) for prostatic fossa recurrence, and a pooled sensitivity of 100% (95% CI: 90.5%–100%) and pooled specificity of 81.8% (95% CI: 48.2%–97.7%) for lymph node metastases. The heterogeneity ranged between 0.00% and 88.6%. The diagnostic odds ratios were 62.123 (95% CI: 24.783–155.72), 5.869 (95% CI: 1.818–18.946), and 138.57 (95% CI: 11.27–1703.8), respectively, for all sites of disease, local recurrence, and lymph node disease. Conclusions Choline PET and PET/CT represent high sensitivity and specificity techniques for the detection of locoregional and distant metastases in PCa patients with recurrence of disease. Moreover, a high diagnostic odds ratio was found for the identification of lymph node disease in patients with biochemical recurrence of PCa.

Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis.

CONTEXT Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment. OBJECTIVES To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa. EVIDENCE ACQUISITION A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed. EVIDENCE SYNTHESIS From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9-58.4) and pooled specificity 95% (95% CI, 92-97.1). The area under the curve was 0.9446 (p<0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109-50.773). CONCLUSIONS Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted.

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group

OBJECTIVE Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

The Relationship between Characteristics of Inguinal Lymph Nodes and Pelvic Lymph Node Involvement in Penile Squamous Cell Carcinoma: A Single Institution Experience

PURPOSE We determined predictors of pelvic lymph node metastases in patients with penile cancer. MATERIALS AND METHODS We retrieved a total of 188 node positive inguinal groins from 142 patients treated for penile cancer. Logistic regression models were fitted to test for predictors of pelvic lymph node metastases. The minimum p value method was used to determine the most significant cutoff values of each predictor. RESULTS Pelvic lymph node metastases were observed in 45 cases (31.7%). The 5-year cancer specific survival rate was 71.0% vs 33.2% in patients with inguinal vs pelvic lymph node metastases. The most significant cutoff values were 3 inguinal lymph node metastases and a metastasis diameter of 30 mm. According to univariable logistic regression models the number of inguinal metastases (OR 1.92, p <0.001), the diameter of the metastases (OR 1.03, p = 0.001) and extranodal extension (OR 8.01, p <0.001) were significant predictors of pelvic lymph node metastases. These variables were also independent predictors of metastases in multivariable logistic regression models (p ≤ 0.012). Patients with 3 or more inguinal lymph node metastases and those with a metastasis diameter of 30 mm or greater were at 4.77 and 2.53-fold higher risk, respectively, of harboring pelvic lymph node metastases (p ≤ 0.006). The proportion of metastases increased significantly from 0% in cases with no risk factors to 57.1% when all 3 risk factors were observed (p <0.001). CONCLUSIONS The number and diameter of inguinal lymph node metastases as well as extranodal extension are significantly associated with pelvic lymph node metastases. These variables should be considered to determine the need for pelvic lymph node dissection. Patients with no risk factors may be spared this dissection.

Comparison between conventional imaging (abdominal–pelvic computed tomography and bone scan) and [18F]choline positron emission tomography/computed tomography imaging for the initial staging of patients with intermediate- tohigh-risk prostate cancer: A retrospective analysis

Abstract Objective. The aim of this study was to evaluate the efficiency of [18F]fluorocholine positron emission tomography/computed tomography (FCH PET/CT) in detecting lymph-node and bone involvement in comparison with conventional imaging, such as abdominal–pelvic CT and bone scan, in the initial staging of prostate cancer (PCa). Materials and methods. The study retrospectively evaluated 48 patients who had FCH PET/CT for the initial staging of PCa. At the same time, 32 of the 48 patients had a bone scan and 26 of the 48 patients had abdominal–pelvic diagnostic CT. Diagnostic performance of FCH PET/CT, i.e. sensitivity, specificity and accuracy, was evaluated on a per-patient basis for the whole population and then separately on a per-risk classification, and later in comparison with conventional imaging. Histological specimens or follow-up data were used as the standard of reference. Results. The overall accuracy of FCH PET/CT for lymph-node involvement was 83.3%. The sensitivity of FCH was higher in the high-risk subset (83.3%) than in the intermediate-risk group (33.3%), whereas FCH specificity was similar. In comparison with dedicated CT scan, FCH PET/CT showed a higher sensitivity and a similar specificity (46.2% vs 69.2% and 92.3% vs 92.3%, respectively). Moreover, the sensitivity and specificity of PET/CT were higher than those of bone scan (100% vs 90% and 86.4% vs 77.2%, respectively). In contrast with conventional imaging, PET/CT changed the staging of the PCa in 33.3% patients. Conclusions. The efficiency of FCH PET/CT in detecting both bone and lymph-node involvement of PCa at initial staging was found to be higher than that of conventional imaging. Prospective clinical trials are needed to confirm these findings.

18F-fluoromethylcholine or 18F-fluoroethylcholine pet for prostate cancer imaging: which is better? A literature revision

INTRODUCTION The present review was conceived for describing the differences in biodistribution and diagnostic performance of two types of (18)F-radiolabeled choline for positron emission tomography (PET) imaging in prostate cancer (PCa), such as fluoromethylcholine (FCH) and fluoroethylcholine (FEC). MATERIALS AND METHODS A collection of published data about two radiopharmaceutical agents was made by using PubMed, Web of Knowledge databases and Trip Database, and then a critical revision was discussed. RESULTS FCH was injected in 338 and 1164 patients, while FEC was injected in 20 and 139 patients, respectively for basal staging and re-staging. The diagnostic performances of FCH and FEC for the detection of lymph node metastasis before the surgical approach are typically around 50% or less and between 0% and 39%, respectively. Conversely, both the tracers appear useful for the detection of recurrent PCa in case of increase in absolute PSA value or in case of high levels of PSA velocity and PSA doubling time (sensitivity ranged between 42.9% and 96% for FCH and between 62% and 85.7% for FEC). CONCLUSIONS In according with the available information, FCH appears to be a more appropriate radiocompound as compared to FEC, although more comparative data are mandatory. A well designed and prospective trial for the evaluation of biokinetic data and diagnostic performance of both radiopharmaceutical agents seems essential. ADVANCES IN KNOWLEDGE AND IMPLICATION FOR PATIENT CARE FCH seems to be an appropriate radiopharmaceutical agent as compared to FEC. Anyway both the radiocompounds are useful in the evaluation of recurrent disease in case of a serial increase in PSA value and their performance improves when a correct preparation and acquisition protocol is employed.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial

BackgroundThe optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer.MethodsThis was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method.ResultsAcute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥3 toxicity was observed. Median follow-up was 63 months (interquartile range 31–79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively.ConclusionsIn our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

Spermatic Cord Sarcoma: Our Experience and Review of the Literature

Introduction: Spermatic cord tumors represent 4% of scrotal tumors. The most common neoplasms are lipomas. Spermatic cord sarcomas (SCS) of the genitourinary tract account for 2% of all urological tumors. Herein we presented our experience in the treatment of these tumors and a review of the literature. Patients and Methods: A review of the literature was performed using the Medline database with no restriction on language and date of published papers. The literature search used the following terms: epidemiology, surgery, chemotherapy, radiotherapy and spermatic cord sarcomas. Four cases treated from December 2009 to May 2010 are described. Results: All patients were treated with radical orchiectomy. The final pathological report showed different types of sarcomas. Two of the patients were treated with adjuvant chemotherapy. 12 months after surgery, 2/4 patients were alive without signs of relapse. Conclusion: SCS are very rare tumors with a poor prognosis. SCS’s prognostic factors have been identified in grading, size, depth of invasion and surgical margin status. Age and performance status of the patient are however very important. Lymphatic and hematogenous dissemination is uncommon. Surgery is the most important treatment both in the first approach and in local relapse. The role of adjuvant chemotherapy and radiation therapy is still debated.

Urinary Markers in the Everyday Diagnosis of Bladder Cancer

Bladder cancer (BC) represents the fourth most common neoplasia in men and the ninth most common cancer in women, with a significant morbidity and mortality. Cystoscopy and voided urine cytology (involving the examination of cells in voided urine to detect the presence of cancerous cells) are currently the routine initial investigations in patients with hematuria or other symptoms suggestive of BC. Around 75-85% of the patients are diagnosed as having non-muscle-invasive bladder cancer (NMIBC). Despite the treatment, these patients have a probability of recurrence at 5 years ranging from 50 to 70% and of progression to muscle invasive disease of 10-15%. Patients with NMIBC must undergo life-long surveillance, consisting of serial cystoscopies, possibly urine cytology and ultraso-nography. Cystoscopy is unsuitable for screening because of its invasiveness and costs; serial cystoscopies may cause discomfort and distress to patients. Furthermore, cystoscopy may be inconclusive, falsely positive or negative. Although urine cytology has a reasonable sensitivity for the detection of high-grade BC, it lacks sensitivity to detect low-grade tumors (sensitivity ranging from 4 to 31%). The overall sensitivity and specificity of urine cytology range from 7 to 100 and from 30 to 70%, respectively. There is a need for new urine biomarkers that may help in BC diagnosis and surveillance. A lot of urinary biomarkers with high sensitivity and/or specificity have been investigated. Although none of these markers have proven to be powerful enough to replace standard cystoscopy, some of them may represent accurate predictors of BC. A review of recent studies is presented.

The Endourological Treatment of Renal Matrix Stones

Objective: To report our experience with the endourological treatment of renal matrix stones, an infrequent form of urinary calculi whose diagnosis and treatment are often difficult. Methods: From 1990 to 2010 we treated 9 female patients with matrix calculi using the endourological approach; 4 presented with renal colics, 3 with symptomatic urinary tract infection and 2 with asymptomatic bacteriuria. Six patients underwent percutaneous lithotripsy and 3 retrograde intrarenal surgery as first-line therapy. Three cases needed a multidisciplinary approach. Results: The six percutaneous procedures were successful after a single session, while the retrograde approach required multiple treatments; a single case needed a shock wave session to complete the fragmentation, in another one a percutaneous lithotripsy was necessary after the first procedure, and a third case needed multidisciplinary treatment. Conclusions: Percutaneous lithotripsy has been confirmed as the first option for matrix stones. The retrograde approach - by confirming the suspected diagnosis and being minimally invasive - may be employed to treat either lower-size stones or stones at high risk of recurrence.