Enrico Bollito

Multilocular cystic renal cell carcinoma : A report of 45 cases of a kidney tumor of low malignant potential

The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age (P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (<or=4 cm) most likely Fuhrman grade 1 (P = .911). All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%. To rename this tumor as multilocular cystic renal cell neoplasm of low malignant potential might help urologists approach the patients conservatively.

Head-to-Head Comparison of Prostate Health Index and Urinary PCA3 for Predicting Cancer at Initial or Repeat Biopsy

PURPOSE We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery.

PURPOSE We compared the status of the peritumoral parenchyma after open and laparoscopic nephron sparing surgery for renal cell carcinoma. MATERIALS AND METHODS The records of 64 consecutive patients who underwent nephron sparing surgery for renal cell carcinoma of 4 cm or less were reviewed retrospectively. Patients in group 1 underwent open retroperitoneal surgery (1998 to 2000) and patients in group 2 underwent laparoscopic (transperitoneal or retro peritoneal) surgery (2001 to March 2004). A single pathologist was employed to analyze the specimens, and comparative analysis included examination of tumor size, weight, histological cell type, intraoperative histological biopsies and margin status. RESULTS The 2 groups were comparable in terms of clinical data, and mean lesion size was 31.4 mm in group 1 and 32 mm in group 2. Positive margins were found in 1 of 30 patients in group 1 and in 1 of 34 in group 2 (p = 0.9). An analysis of margins was performed by taking measurements at the minimum and maximum points of the section. The minimum mean measurement was 2 mm in group 1 and 2.08 mm in group 2 (p = 0.75). The maximum mean measurement was 4.56 mm in group 1 and 5.2 mm in group 2 (p = 0.09). The difference between minimum and maximum margin thickness was 2.56 mm in group 1 and 3.16 mm in group 2 (p = 0.04). Mean followup for group 1 was 50 months (range 30 to 72) and 16 months (range 2 to 35) for group 2. One local recurrence was recorded in group 1 and treated with radical nephrectomy, while no recurrence was recorded in group 2. CONCLUSIONS In this study we further confirmed the efficiency of resectioning lesions using laparoscopy. In our experience there is no difference between the 2 procedures in terms of efficient surgical margins. However, despite these encouraging results it is necessary to obtain more extensive followup data, which will allow us to be more specific in reporting on laparoscopic margin quality.

Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification

Aims:  Pathological diagnosis of adrenocortical carcinoma relies on several microscopic features commonly used in combination in different scoring systems that are sometimes subjective and/or time consuming. The aim was to investigate the impact of individual pathological parameters in the diagnosis and prognosis of adrenocortical carcinoma.

Diagnostic accuracy and clinical impact of imaging-guided needle biopsy of renal masses. Retrospective analysis on 150 cases.

ObjectiveTo review our method of perform needle biopsies of renal masses.MethodsWe analysed 150 consecutive imaging-guided percutaneous biopsies. The pathological diagnosis was verified on clinical outcome in 129 cases (40 surgical resection, 53 thermal ablation, two medical treatment and 34 watchful waiting). Twenty-six patients underwent fine-needle aspiration biopsy (FNAB), 45 core-needle biopsy (CB) and 58 FNAB + CB. After review by two expert pathologists, cumulative accuracy of all FNAB (84) and all CB (103) was calculated. The rate of complications and mass management other than surgery was estimated.ResultsThe final diagnosis was malignancy in 97 cases (benign mass in 32). FNAB correctly diagnosed 64/84 masses (76.2%), CB 96/103 (93.2%). Of 58 masses submitted for both FNAB and CB, CB provided a 22.5% accuracy improvement. Major and minor complications occurred in 0% and 5.3%. Renal biopsy altered clinical management in 89/129 cases (68.9%), in terms of choosing therapeutic options other than surgery.ConclusionCB is more accurate than FNAB and should be preferred in renal mass biopsy. FNAB may precede CB when an expert pathologist can immediately evaluate the samples. Renal biopsy influences renal mass management.

Multilocular Cystic Renal Cell Carcinoma

The 2004 World Health Organization (WHO) classification of kidney tumors recognizes multilocular cystic renal cell carcinoma (MCRCC) as a rare variant of clear cell renal cell carcinoma with a good prognosis. Available information on its clinical significance is limited. The study cohort included 45 MCRCC cases classified according to 2004 WHO criteria obtained through a multi-institutional international search. Most patients had unilateral MCRCC with no side predominance that was found incidentally; 62% were men, but women had tumors at an earlier age ( P = .385). MCRCC occurred slightly more often in men than in women (1.7:1). At diagnosis, 82% of patients had stage T1 and 16%, stage T2; 1 patient had stage T3. The Fuhrman grade was 1 (62%) or 2 (38%), with smaller tumors (≤4 cm) most likely Fuhrman grade 1 ( P = .911). All 45 patients were alive with no evidence of disease at mean follow-up of 66.1 months, confirming an extremely good prognosis after surgery and a 5-year disease-specific survival rate of 100%. To rename this tumor as multilocular cystic renal cell neoplasm of low malignant potential might help urologists approach the patients conservatively.

The Roles of Multiparametric Magnetic Resonance Imaging, PCA3 and Prostate Health Index—Which is the Best Predictor of Prostate Cancer after a Negative Biopsy?

PURPOSE In patients with a negative prostate biopsy and persistent suspicion of prostate cancer, additional analyses such as the PCA3 score, PHI and multiparametric magnetic resonance imaging have been proposed to reduce the number of unnecessary repeat biopsies. In this study we evaluate the diagnostic accuracy of PCA3, PHI, multiparametric magnetic resonance imaging and various combinations of these tests in the repeat biopsy setting. MATERIALS AND METHODS A total of 170 patients with an initial negative prostate biopsy and persistent suspicion of prostate cancer were enrolled in this prospective study. The patients underwent measurements of the total prostate specific antigen and free prostate specific antigen rate, along with PHI, PCA3 tests and multiparametric magnetic resonance imaging before standard repeat biopsy that was performed by urologists blinded to the multiparametric magnetic resonance imaging results. Multivariate logistic regression models with various combinations of PCA3, PHI and multiparametric magnetic resonance imaging were used to identify the predictors of prostate cancer with repeat biopsy, and the performance of these models was compared using ROC curves, AUC analysis and decision curve analysis. RESULTS In the ROC analysis the most significant contribution was provided by multiparametric magnetic resonance imaging (AUC 0.936), which was greater than the contribution of the PHI+PCA3 model (p <0.001). In the multivariate logistic regression analysis only multiparametric magnetic resonance imaging was a significant independent predictor of prostate cancer diagnosis with repeat biopsy (p <0.001). The results of the decision curve analysis confirmed that the most significant improvement in the net benefit was provided by multiparametric magnetic resonance imaging. CONCLUSIONS Multiparametric magnetic resonance imaging provides high diagnostic accuracy in identifying patients with prostate cancer in the repeat biopsy setting compared with PCA3 and PHI.

Cyclic Cushing’s syndrome due to ectopic ACTH secretion by an adrenal pheochromocytoma

Pheochromocytoma is a rare cause of ectopic Cushing’s syndrome. We report on such a patient in whom ectopic ACTH secretion displayed a cyclic pattern. A 35-year-old woman was referred to us with a diagnosis of ACTH-dependent Cushing’s syndrome. A 3.3 cm left-sided adrenal mass was noted at abdominal computerized tomography. At admission, clinical and hormonal data were unrewarding, so it was decided to continue to observe the patient. Four months later, she became symptomatic with hypertensive and psychotic crises and glycemic decompensation. By that time, a full-blown Cushing picture was evident. Severe hypercortisolism was documented with urinary free Cortisol ranging 1500–2200 μg/24 h, serum Cortisol 143–160 μg/dl and plasma ACTH 167–218 pg/ml. Neither ACTH nor Cortisol values were significantly modified after high-dose dexamethasone, oCRH or metyrapone. Urinary catecholamine and vanilyl mandelic acid excretion were moderately elevated. Chest CT and total body MIBG scan were negative and magnetic resonance of the sella region was inconclusive. No center to periphery ACTH gradient was observed by inferior petrosal sinus catheterization, whereas a significant left to right gradient was found on selective adrenal vein catheterization. A left adrenalectomy was performed and a 4 cm medullary neoplasia was removed. The cells were immunostained for ACTH, neuron-specific enolase and A chromogranin. Signs and symptoms of Cushing’s syndrome resolved with normalization of basal and dynamic endocrine evaluations. The patient is considered cured 10 months after surgery.

Human ASH1 expression in prostate cancer with neuroendocrine differentiation

Neuroendocrine differentiation in prostate cancer correlates with overall prognosis and disease progression after androgen-deprivation therapy, although its specific mechanisms are currently poorly understood. A role of Notch pathway has been reported in determining neuroendocrine phenotype of normal and neoplastic tissues. The aim of this study was to analyze whether this pathway might affect neuroendocrine differentiation in prostate cancer. Human achaete-scute homolog 1 (hASH1), a pivotal member of the Notch pathway, was investigated in 80 prostate cancers selected and grouped according to chromogranin A immunohistochemistry, as follows: prostate cancers without neuroendocrine differentiation, untreated (25 cases); prostate cancers with neuroendocrine differentiation, untreated (40 cases); prostate cancers with previous androgen-deprivation therapy, all having neuroendocrine differentiation (15 cases). Human ASH1 protein was analyzed by immunohistochemistry, whereas the presence of hASH1 mRNA transcripts was investigated on paraffin material by real-time PCR. By immunohistochemistry, hASH1 was colocalized with chromogranin A in neuroendocrine cells of normal prostatic gland. It was absent in all but one prostate cancers without neuroendocrine differentiation, whereas it was positive in 25% of prostate cancers with neuroendocrine differentiation/untreated, with a significant correlation with the extent of neuroendocrine features (P=0.02). Moreover, comparing untreated and treated prostate cancers with neuroendocrine differentiation, a positive association with androgen-deprivation therapy was observed (P=0.01). In prostate cancers with neuroendocrine differentiation, RNA analysis confirmed the association of higher transcript levels in androgen deprivation-treated compared with untreated patients (P=0.01). In addition, hASH1 mRNA analysis in microdissected chromogranin A-positive and chromogranin A-negative areas within the same tumor demonstrated a two- to sevenfold increase of hASH1 mRNA expression in chromogranin A-positive tumor cell populations.

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer

BACKGROUND An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). OBJECTIVE To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. DESIGN, SETTING, AND PARTICIPANTS Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). INTERVENTION In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. RESULTS AND LIMITATIONS The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. CONCLUSIONS A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. PATIENT SUMMARY In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway.