==inizio objective==

As the use of radiological investigations has increased in the last years, the detection of small renal masses (SRMs) < 4 cm has become more frequent. In most cases the radiological distinction between benign and malignant SRMs cannot be performed. According to the results of recent studies the use of US-guided percutaneous renal biopsy (RTB) or Computerised Tomography (CT)-guided RTB is diagnostic and accurate with low complication rates. ==fine objective== ==inizio methodsresults== We performed a retrospective analysis of our experience with US/CT-guided RTBs of SRMs suspicious for renal cancer from 2010 to 2015. We collected and analysed our data about size, site, histopathology,Fuhrman grade, type of radiological imaging used to perform a biopsy, peri-operative complications (according to Clavien-Dindo classification ), surgical treatment of tumours and number of RTBs required to get a correct diagnosis. Patients whose first RTB was non-diagnostic of renal cell carcinoma were followed up and they got a second biopsy if required. ==fine methodsresults== ==inizio results== 100 patients were enrolled with an average age of 71. SRMs were detected by means of US-guided biopsies and CT-guided biopsies in 19% and 81% of cases respectively. Local anaesthesia was performed in 97% of cases. The lesions were located in the right, left or in both kidneys in 46%, 52% and 2% of cases respectively.
Post-operative complications occurred in 3% of cases ( Clavien Dindo 1 and 2 ) and all were treated conservately. 
66% of the lesions proved to be malignant. Fuhrman grade was assigned by experienced genitourinary pathologist in all renal cell carcinomas and was used to stratify cases into low- and high risk; Fuhrman grade 1-2 or 2-3 were considered to be low-risk renal tumors (n=25) and Fuhrman grade 3 and 4 were classified as high risk (n=5). In the 54% of cases physicians had performed a US-guided RTB, in the 12% a CT-guided RTB.
6% of RTBs were non-diagnostic because they contained insufficient material for the analyses (3% necrotic tissue and/or blood 2%, 1% inflammation/fibrosis), 9% revealed benign lesions and 6% were over diagnoses.
77% (n=51) of patients whose RTBs detected the presence of cancer were treated in our clinical centre: 29% were treated with partial nephrectomy, 48% with tumorectomy.
A strong link (86% rate) was high lighted between the histological findings in the biopsy and the post-operative ones.
We followed up patients with a first non-diagnostic RTB:
21% were diagnostic after a second RTB, 2% were non-diagnostic and 11% were diagnostic after a third biopsy. ==fine results== ==inizio discussions== The use of CT and US-guided biopsy is a safe and accurate method to discriminate between benign and malignant lesions. Its limits reside in the amount of removed tissue. Our study was aimed to assess its efficacy and to find out how many biopsies are required in order to make a correct diagnosis. Thus US or CT-guided renal biopsies are a valid method of investigating suspicious renal lesions (<4 cm) thanks to their high reliability and a low complication rate. ==fine discussions== ==inizio conclusion== The US and TC-guided biopsy is a safe method with 3% rate of complications and has an accuracy of 86% for SRMs diagnosis at the first biopsy and 14% at the second biopsy. ==fine conclusion== ==inizio reference== ==fine reference==

==inizio objective==

Clear cell renal cell carcinoma (ccRCC) is the most common (80-90%) and lethal subtype of renal cell carcinoma, which accounts for 80% of all kidney cancers (1).
The most striking morphological feature of ccRCC cells is their clear cytoplasm mainly due to lipid accumulation (2). These intracellular storages suggest the involvement of altered fatty acid metabolism in the development of ccRCC. In fact, transcriptomic, proteomic and metabolomic profiling of ccRCC tissues revealed the presence of a metabolic reprogramming characterized also by increased fatty acid synthesis and by down-regulation of fatty acid b-oxidation (3-4). Of note, gene expression profiling and pathway analysis of ccRCC tissues also evidenced an enrichment of the PPARa pathway that, through the transcription of genes involved in fatty acid mitochondrial uptake (i.e. CPT1) and b-oxidation, is a master regulator of fatty acid metabolism (5). Interestingly, inhibition of ccRCC cell line growth has been obtained by targeting PPARa in vitro and in a xenograft mouse model (6). More recently, by using different –omics approaches, several groups revealed that specific metabolic alterations might correlate with tumor aggressiveness and poor survival in ccRCC patients. In particular, a decrease of specific fatty acid oxidation enzyme expression has been also found to correlate with the increase of tumour stage, size and grade and with the decrease of survival (7). By combining proteomics and metabolomics analysis, we collaborated to reveal a grade-dependent metabolic reprogramming in ccRCC tissues involving also fatty acid metabolism (4). Even if many approved targeted therapeutics have been recently developed (8), at present there is no grade-specific therapy addressing this metabolic reprogramming in ccRCC. For this purpose, an in vitro model of ccRCC that maintains the metabolic features of tumor tissue might be useful. Thus, we established primary cell cultures (PCC) from normal cortex and ccRCC tissue specimens that have been extensively characterized demonstrating to retain, at the early passages, the phenotypic, genomic, proteomic and transcriptomic profile of the corresponding tissues (9-12).
Here we aimed to investigate by cytological, molecular and functional analyses of these PCC: 1) the presence of grade-dependent lipid storages in ccRCC cells; 2) the involvement of PPARa and/or its target CPT1 in these storages; 3) the effect of CPT1 inhibition by Etomoxir on ATP production and cell viability of ccRCC PCC.

==fine objective==

==inizio methodsresults==

PCC established from ccRCC and normal cortex tissue samples were characterized by FACS analysis (10). Functional enrichment analysis of KEGG and Reactome pathways was performed by Cytoscape ClueGO plug-in on transcriptome profiling of ccRCC PCC previously obtained (12). Neutral lipid storage in Fuhrman low- and high-grade tissues and corresponding PCC was evaluated by Oil Red “O” staining and lipid droplet marker PLIN2 expression evaluated by western blot. PPARa expression was evaluated by western blot. Inhibition of CPT1 activity was performed by treatment with 50 uM Etomoxir. ATP production and cell viability in untreated and treated cells were evaluated by a specific commercial kit and FACS analysis after Annexin V/PI staining, respectively.

==fine methodsresults==

==inizio results==

The analysis performed on ccRCC PCC transcriptomic profiling evidenced a significant enrichment of several metabolic pathways mainly related to lipid metabolism and PPARa signaling. Notably, ccRCC cultures maintain at the first passage the lipid storages observed in corresponding tissues and, like in corresponding tissues, the lipid storages were also more abundant in low- (G1-G2) than in high-grade (G3-G4) ccRCC PCC. Moreover, PPARa protein expression was significantly increased in high-grade with respect to low-grade ccRCC PCC, as also described in corresponding tissues (13). Inhibition of CPT1 by Etomoxir induced a significant decrease of ATP production and cell viability only in high-grade ccRCC cells.

==fine results==

==inizio discussions==

Our data show that the PCC maintain the grade-dependent lipid storage of ccRCC tissues and this storage correlates with PPARa expression. Because PPARa regulates fatty acid uptake into mitochondria through CPT1 gene transcription, the increased accumulation of lipids observed in low-grade ccRCC cells might be due to a decreased PPARa-dependent CPT1 expression, which evaluation is in progress. Moreover, the decrease of ATP production induced by CPT1 inhibition with Etomoxir and observed only in high-grade ccRCC cells suggests that PPARa, likely through CPT1 expression modulation, plays a role also in grade-dependent energy metabolism differences in ccRCC. The cytotoxic effect induced only in high-grade ccRCC cells by Etomoxir-dependent CPT1 inhibition also highlights the grade-dependent role of mitochondrial fatty acid uptake and/or metabolism in ccRCC viability and suggests the feasibility of a grade-specific therapeutic approach in ccRCC.

==fine discussions==

==inizio conclusion==

These ccRCC PCC, retaining also the metabolic features of corresponding tissues, are a useful tool to shed light on the complex molecular mechanisms involved in grade-dependent metabolic reprogramming and lipid storage of ccRCC. Moreover, the grade-dependent impact of lipid metabolism inhibition on ccRCC cell viability suggests the feasibility of a grade-specific metabolic targeted therapy in ccRCC.

==fine conclusion==

==inizio reference==

1. Rini et al., Lancet 2009
2. Gebhard et al., J Lipid Res 1987
3. Cancer Genome Atlas Research Network, Nature 2013
4. Wettersten et al., Cancer Res 2015
5. Tun et al., PLOS one 2013
6. Abu Aboud et al., Am J Physiol Cell Physiol 2015
7. Zhao et al., Tumor Biology 2016
8. van der Mijn et al., Cancer and Metabolism 2016
9. Perego et al., J Proteome Res 2005
10. Bianchi et al., Am J Pathol 2010
11. Cifola et al., BMC Cancer 2011
12. Di Stefano et al., Am J Pathol 2016.
13. Abu Aboud et al., PLOS one 2013

==fine reference==

==inizio objective==

Percutaneous embolization represents one of the feasible treatments of voluminous angiomyolipomas, because of the haemorragic risks related to this type of renal lesion.
We described the story of a woman with an angiomyolipoma with a maximum diameter of 8 cm, treated with percutaneous embolization. Additionally, we reviewed the literature about this field.

==fine objective==

==inizio methodsresults==

We described our case report. We searched in Medline and Embase using the following key words: ” kidney angiomyolipoma” and “percutaneous embolization”.

==fine methodsresults==

==inizio results==

RESULTS-DISCUSSION
61 year-old woman described nonspecific abdominal pain. The US reported a “Solid hyperechoic lesion with a maximum diameter of 8 cm, located in the cortical part of the inferior third of right kidney, with uncertain significance”.
The abdominal CT scan with contrast medium evidenced an esophitic lesion with in the inferior part of the left kidney, in its anterior side, with maximum axial and logitudinal diameter of 75 mm and 86 mm, respectively. The content was mainly fatty, with several vascular branches inside the lesion itself, with arterial ones directly derived from the renal artery. The lesion was surrounded by a thin capsule. There were no solid components with contrast enhancement. The appereance suggested an angiomyolipoma (fig.2).
The patient executed percutaneous embolization of the lesion using endo-coils The duration of treatment was about 35 minutes (fig.3-6). The were no technical complications. She had fever until 38°C, responsive to antibiotic therapy with ceftriaxone during the first day after the procedure. Additionally, she described mild lumbar pain during the 2 days after the procedure, treated with paracetamol. The patient was discharged in 5th day after the embolization.
The CT two months after the procedure demostrated a stable lesion (fig. 7); the patient was asymptomatic.
We found several reports about the procedure, with different materials used for embolization.

==fine results==

==inizio discussions==

RESULTS-DISCUSSION
61 year-old woman described nonspecific abdominal pain. The US reported a “Solid hyperechoic lesion with a maximum diameter of 8 cm, located in the cortical part of the inferior third of right kidney, with uncertain significance”.
The abdominal CT scan with contrast medium evidenced an esophitic lesion with in the inferior part of the left kidney, in its anterior side, with maximum axial and logitudinal diameter of 75 mm and 86 mm, respectively. The content was mainly fatty, with several vascular branches inside the lesion itself, with arterial ones directly derived from the renal artery. The lesion was surrounded by a thin capsule. There were no solid components with contrast enhancement. The appereance suggested an angiomyolipoma (fig.2).
The patient executed percutaneous embolization of the lesion using endo-coils The duration of treatment was about 35 minutes (fig.3-6). The were no technical complications. She had fever until 38°C, responsive to antibiotic therapy with ceftriaxone during the first day after the procedure. Additionally, she described mild lumbar pain during the 2 days after the procedure, treated with paracetamol. The patient was discharged in 5th day after the embolization.
The CT two months after the procedure demostrated a stable lesion (fig. 7); the patient was asymptomatic.
We found several reports about the procedure, with different materials used for embolization.

==fine discussions==

==inizio conclusion==

Our case report is similar to those described in literature. The percutaeous embolization represents a valid method for the treatment of amgiomyolipomas with big dimensions, especially considering the risk-benefit ratio for the patient.

==fine conclusion==

==inizio reference==

1. Thulasidasan N, Sriskandakumar S, Ilyas S, Sabharwal T. Renal Angiomyolipoma: Mid- to Long-Term Results Following Embolization with Onyx. Cardiovasc Intervent Radiol. 2016; 39(12):1759-1764
2. Guziński M, Kurcz J, Tupikowski K, Antosz E, Słowik P, Garcarek J. The Role of Transarterial Embolization in the Treatment of Renal Tumors.. Adv Clin Exp Med 2015; 24 (5):837-43.
3. Flum AS, Hamoui N, Said MA, Yang XJ, Casalino DD, McGuire BB, Perry KT, Nadler RB. Update on the Diagnosis and Management of Renal Angiomyolipoma. J Urol 2016;195 (4P1): 834-46.

==fine reference==

==inizio objective==

The elective indication for off-clamp (Off-C) partial nephrectomy (PN) in patients with good baseline renal function remains controversial. The aim of this study is to compare the risks of developing a severe (stage ≥3b) chronic kidney disease (CKD) in patients with cT1-2/N0/M0 renal tumors and baseline estimated glomerular filtration rate (eGFR) >60 ml/min after either Off-C or on-clamp (On-C) PN.

==fine objective==

==inizio methodsresults==

A prospective “renal cancer” database of two high volume centers was queried for “cT1-2/N0/M0” tumors, “PN” and “baseline eGFR>60 mL/min”. Overall 1073 patients met the inclusion criteria (483 Off-C and 588 On-C). A 1:2 propensity score-matched (PSM) analysis was employed to minimize the selection bias of non-random treatment assignment of patients.
Kaplan–Meier method was used to compare the PSM cohorts specific risks of developing a CKD stage ≥ 3b during follow-up in the PSM cohorts, and the log-rank test was applied to assess statistical significance between groups. Univariable and multivariable Cox regression analyses were performed to identify independent predictors of developing a CKD stage ≥3b.

==fine methodsresults==

==inizio results==

On-C patients were significantly younger (p=.001), less frequently smokers (.01), with a lower incidence of diabetes (.001) and hypertension (.001), lower ASA scores (<.001), higher baseline eGFR values (.003), smaller tumor sizes (<.001), and higher incidence of positive surgical margins (.021). After applying the PSM analysis, the two cohorts of 221 On-C and 485 Off-C PN cases did not differ for all clinical and pathologic covariates (Table 1; all p ≥ .06). The probability of developing a CKD stage ≥ 3b was significantly higher (log rank p=.006, Figure 1) in the On-C cohort (2, 5 and 8yr risk 0.9, 5.1 and 12.8% vs 0.6, 1.2 and 1.2% in the Off-C cohort, respectively). On-C technique was associated with a 5.2 fold increased risk of developing CKD stages ≥3b compared with the Off-C approach (HR 5.2 [95% CIs 1.4–18.9]; p=.012). At multivariable regression analysis, eGFR at discharge and Off-C PN were independent predictors of outcomes. For each increasing mL/min of eGFR at the discharge the risk of developing a CKD stage ≥3b was reduced by 5% (HR 0.95 [95% CIs 0.93–0.97]), while On-C approach was associated with a 5.8 fold increased risk of developing a CKD stage ≥3b (HR 5.8 [95% CIs 1.6-20.8]). ==fine results== ==inizio discussions== ==fine discussions== ==inizio conclusion== This study highlights the beneficial role of an Off-C approach in patients with cT1-2/N0/MO renal tumors and good baseline renal function candidate to elective PN. ==fine conclusion== ==inizio reference== -Indications, techniques, outcomes, and limitations for minimally ischemic and off-clamp partial nephrectomy: a systematic review of the literature. Simone G, Gill IS, Mottrie A, Kutikov A, Patard JJ, Alcaraz A, Rogers CG. Eur Urol. 2015 Oct;68(4):632-40. doi: 10.1016/j.eururo.2015.04.020. Review -To clamp or not to clamp? Long-term functional outcomes for elective off-clamp laparoscopic partial nephrectomy. Shah PH, George AK, Moreira DM, Alom M, Okhunov Z, Salami S, Waingankar N, Schwartz MJ, Vira MA, Richstone L, Kavoussi LR. BJU Int. 2016 Feb;117(2):293-9. doi: 10.1111/bju.13309 ==fine reference==

==inizio objective==

Radical nephrectomy with Inferior vena cava (IVC) thrombectomy for renal cancer is one of the most challenging urologic surgical procedures. We describe surgical technique and present perioperative and oncologic outcomes of 35 consecutive cases of completely intracorporeal robot-assisted radical nephrectomy with IVC level I (5.7%) II (65.7%) and III (28.6%) tumor thrombectomy treated at two tertiary referral centers.

==fine objective==

==inizio methodsresults==

Thirty-five consecutive patients with renal tumor and IVC thrombus were treated between July 2011 and September 2016. Baseline, perioperative and follow-up data were collected into prospectively maintained IRB approved databases. Key steps of surgery include: a meticulous isolation of IVC; the isolation and sealing of all lumbar and collateral vessels, a full monolateral retroperitoneal dissection for staging purpose and to have a complete control of IVC; isolation of left renal vein, Tourniquet placement and infrarenal IVC control. IVC incision and thrombectomy; cava suture with 3/0 visi-black monocryl or 5/0 goretex; restoration of IVC flow; nephrectomy. We report perioperative and oncologic outcomes of 35 consecutive patients treated in two tertiary referral centers.

==fine methodsresults==

==inizio results==

All procedures were successfully completed; open conversion was necessary in one case (2.8%). Median operative time was 300 minutes. Twenty-one patients (68.6%) did not experience any complication. Ten patients (28.6%) required blood transfusion (Clavien grade 2); one patient (2.8%) had a Clavien grade 3a complication (gastroscopy); two patients (5.7%) had Clavien grade 3b complications (reintervention due to bleeding from adrenal gland and subphrenic ascess requiring drainage, respectively); one patient (2.8%) experienced a PRESS syndrome requiring ICU admission (Clavien 4a).
Out of 13 patients who underwent cytoreductive nephrectomy and IVC thrombectomy, only one patient died of disease progression 14 months postoperatively. Both 2-yr cancer specific and overall survival rates in this subpopulation were 88.9%.
Twenty-two patients received surgery with curative intent and 5 of these experienced disease recurrence: 2-yr metastasis free, cancer specific and overall survival rates were 56%, 100% and 94.4%, respectively.

==fine results==

==inizio discussions==

==fine discussions==

==inizio conclusion==

Robotic IVC thrombectomy is a challenging surgical procedure. In tertiary referral centers this procedure is feasible, safe and associated with favorable perioperative outcomes and encouraging short term oncologic outcomes.

==fine conclusion==

==inizio reference==

– Advances in Robotic Vena Cava Tumor Thrombectomy: Intracaval Balloon Occlusion, Patch Grafting, and Vena Cavoscopy.
Kundavaram C, Abreu AL, Chopra S, Simone G, Sotelo R, Aron M, Desai MM, Gallucci M, Gill IS.
Eur Urol. 2016 Nov;70(5):884-890. doi: 10.1016/j.eururo.2016.06.024.

– Robot-assisted Level II-III Inferior Vena Cava Tumor Thrombectomy: Step-by-Step Technique and 1-Year Outcomes.
Chopra S, Simone G, Metcalfe C, de Castro Abreu AL, Nabhani J, Ferriero M, Bove AM, Sotelo R, Aron M, Desai MM, Gallucci M, Gill IS.
Eur Urol. 2016 Sep 20. pii: S0302-2838(16)30578-4. doi: 10.1016/j.eururo.2016.08.066.

==fine reference==

==inizio objective==

Nontraumatic, spontaneous parenchymal kidney rupture is a rare clinical entity that can cause extensive haemorrhage and lead to the development of a Wunderlich’s syndrome. It has been previously described in patients with systemic lupus erythematosus (SLE) (1) or in patients with Castleman’s Disease (2). Sometimes an incidental renal carcinoma can be found in the kidney. We report our experience of spontaneous rupture of the kidney without a clear cause, in a single high-volume center.

==fine objective==

==inizio methodsresults==

We retrospectively evaluated all the patients that reached our emergency department for a kidney rupture from January 2012 to December 2016. 62 patients experience a parenchymal kidney rupture due to a clear cause and 10 patients experience a spontaneous parenchymal kidney rupture without a clear cause. All patients with an anamnesis of abdominal trauma were excluded from the analysis. All patients were evaluated with an abdominal ultrasonography and then an abdominal computed tomography.

==fine methodsresults==

==inizio results==

The mean age of the patients (four women and six men) was 52,1 years (range 18-69). All patients reached our emergency department with abdominal pain. 6 out of 10 patients experience a diffuse abdominal pain and 4 out of 10 patients experience a pain that simulated a renal colic, probably related to the occupation of the pelvis by blood clots. 5 out of 10 patients experience haematuria. 6 out of 10 patient experience a typical Wunderlich’s syndrome with hypovolemic shock Stage 3 (marked tachycardia and tachypnea, low systolic blood pressure (mean 66,6 mmHG), confusion state, sweating with cool and pale skin. In the youngest patient the systolic blood pressure was 120 mmHG. Despite this the blood sample showed a lower hematocrit (Hemoglobin=6,7 g/dL). The mean hemoglobin level was 6,54 g/dL (range 5,8-7,1). All patients underwent blood transfusions. 6 out of 10 patients had a renal injury grade 3 (Fig.1) and 4 out of 10 patients had a renal injury grade 2. The management was conservative for seven patients. Three patients experience the embolization of a subsegmental renal artery. One patients with a renal injury grade 3 experienced an infected retroperitoneal abscess and required a surgical drainage.

==fine results==

==inizio discussions==

A lot of conditions can cause a parenchymal kidney rupture (misunderstood renal cell cancer, acute purulent pyelonephritis secondary to stone, polycystic kidney disease, etc). Only few cases about spontaneous rupture of the kidney are reported in the scientific literature (3). The management of these patients is critical because the condition may go unrecognised in the early stages and can result in death. In our experience the youngest patient had a normal systolic blood pressure despite of the low levels of haemoglobin. It can be related to the high level of catecholamine that increased the blood pressure. In our experience the management was conservative but if the collecting system or the vascular pedicle are involved it is imperative to choose a surgical approach.

==fine discussions==

==inizio conclusion==

The spontaneous parenchymal kidney rupture is a rare but life-threatening entity. It is critical for clinicians in the Emergency Department to be aware of this entity to avoid diagnostic error. It is important to exclude all the causes of the kidney rupture. Moreover, in the young patients the condition can be misunderstood. In conclusion, we suggest to pay attention to old people that more probably can have consequences after a severe hemorrhage.

==fine conclusion==

==inizio reference==

1- Ufuk F, Herek D. Life-threatening spontaneous kidney rupture in a rare case with systemic lupus erythematosus: Prompt diagnosis with computed tomography. Hemodial Int. 2016 Jan;20(1):E9-11.

2- Kremer A, Kremer V, Lee SK.Spontaneous kidney rupture with incidental renal cell cancer in patient with Castleman’s disease. Urology. 2009 Oct;74(4):787-8.

3- Dangle P, Pandya L, Chehval M.Idiopathic non-traumatic spontaneous renal hemorrhage/laceration: a case report and review of the literature. W V Med J. 2012 Nov-Dec;108(6):24-6.

==fine reference==