==inizio objective==

To evaluate the safety and efficacy due to use of only hemostatic matrix in course of laparoscopic partial nephrectomy.

==fine objective==

==inizio methodsresults==

From July 2013 to December 2014 36 patient underwent partial nephrectomy for small renal masses were recruited into the study. Exclusion criteria were lesion major than 4 cm, completely endophytic lesion or lesion that infiltrate the urinary tract. Median age of 58,5 years (37-71yr). 19 patient were male and 17 woman. The median size of the tumor were 2,8cm (1,9-3,5cm).Left kidney were interested in 24 patients while in 12 patients the right one were interested. The tumor were localized at the lower pole in 25 patients, 7 in the middle part and 4 in the upper pole,all the lesion were exophytic . All the patients undergone laparoscopic partial nephrectomy with the palcement of two 10mm trocars and three 5mm trocars . All the procedures were perferomed with anatomic zero ischemia and no preparation of renal vessels. The tumors were isolated and removed using monopolar scissor and advaced bipolar forceps.Surgiflo were put immediatly after the tumor excision on the resection bed.At the end of the procedures we perform a reconstruction of the posterior parietal peritoneum. Surgiflo is a topical thrombin indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques (such as suture, ligature or cautery) is ineffective or impractical.

==fine methodsresults==

==inizio results==

No patients required an intraoperatory open conversion. Intraoperatory blood loss were less then 100cc in 22 patients (61,1%) 100cc -200cc in 10 patients (31,2%) more than 200 cc in 4 cases (12,5%). All the surgical procedure were performed by the same surgeon. The median operative time were 79 minutes (67-107min).3 patients required blood trasfusion No major complication occurred. The median recovery was 3,2 days (2-5). 28 of the tumor were renal cell carcinoma (RCC) Grade 2 , 4 RCC Grade 3, 1 angiomyolipoma, 3 patients present a Bosniak type 3 lesion with cellular atypia.Surgical resection margins were negative in 34 patient in 2 patients surgical margins were focal involved by the tumor. After at least 12 month no patient present local recurrence or progression of the disease.

==fine results==

==inizio discussions==

Partial nefrectomy rappresent the gold standard therapy for kidney tumor with size lower than 4 cm . The use of suture the ensecure hemostasis on bed resection is the most frequent tecnique used . Hemostasis control and collecting system suturing are the most difficult parts during a laparoscopic procedure. For best outcomes with nephron sparing surgery, several tissue sealants were developed to be associated with, or even replace sutures of the renal parenchyma . In this study we demostred that the use of Surgiflo were safety and efficacy in all the patients undergone partial nefrectomy both intraoperatively that postoperatively . No surgical procedure required emostatic suture to stop resection bed bleeding.

==fine discussions==

==inizio conclusion==

Laparoscopic partial nephrectomy is an effective surgical alternative in NSS in which the ultimate goal is to achieve the “trifecta” of a negative cancer margin, minimal decrease in renal function and an absence of complication. The biological glue is an important tool in laparoscopic partial nephrectomies. This data shows that during laparoscopic partial neprectomy for small lesions in selected cases the use of Surgiflo is sufficient to ensure a good hemostasis and the non-use of sutures on the renal parenchyma could ensure less damage to the parenchyma with a consequent improvement on renal function. Human clinical trials with larger numbers are needed to confirm our results in patients with small renal tumors that could lead us to better outcomes, by decreasing bleeding, when performing minimally invasive partial nephrectomy.

==fine conclusion==

==inizio references==

a

==fine references==

==inizio objective==

A key challenge for the improvement of ccRCC management could derive from a deeper molecular characterization of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. In several tumors, miRNAs expression profile is emerging as a relevant marker for diagnosis, prognosis and treatment of cancer . miRNAs are 22 nucleotides-long double strand small RNAs, typically excised from 60 to 110 nucleotide RNA precursor structures, which modulate gene expression generally at post-trascriptional level [6]. In fact, miRNAs show a developmental stage- and tissue-specific expression pattern and are present in complex regulatory circuits to regulate stem cells function, tissue differentiation and maintenance of cell identity during embryogenesis and adult life [7]. Notably, miRNA activity has also been correlated to the pathogenesis of cancer, since miRNAs have also been recently identified as a new class of genes with tumor-suppressor and oncogenic functions. To date, a molecular characterization of ccRCC is under investigation and several high-throughput analyses have been recently performed in order to identify miRNAs putatively involved in ccRCC tumorigenesis and progression. By using a retrospective cohort of 20 formalin-fixed paraffin-embedded (FFPE) tissue samples, we evaluated the levels of specific miRNAs differentially expressed in ccRCC vs. matched normal tissues. We evidenced miR-21-5p and miR-210-3p as the most significantly up-regulated in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC carcinogenesis.

==fine objective==

==inizio methodsresults==

This study was conducted on a retrospective cohort of ccRCC formalin-fixed paraffin-embedded (FFPE) tissue samples from 20 patients who underwent surgery between October 2011 and November 2013. For all the patients, FFPE-matched normal peritumoral kidney tissues were also considered. The patients were not treated with any neo-adjuvant therapy before surgery. Five patients were female (25%) and 15 patients were male (75%) with a mean age of 68.9 years old and a mean Body Mass Index (BMI) of 27.4 kg/m2. All the cases presented a clear cell histotype of RCC at the histological examination. The surgery procedures performed as treatments for these patients were: (i) open radical nephrectomy in 4 cases (20%); (ii) laparoscopic radical nephrectomy in 12 cases (60%); (iii) laparoscopic partial nephrectomy in 4 cases (20%). According to the tumor, node, and metastasis (TNM) classification, 10 patients have been identified as Stage I (50%), 5 patients have been identified as Stage II (25%), and 5 patients as Stage III (25%). Fuhrman’s grade has also been evaluated with 15% of cases belonging to the G1 grade (3 patients), 50% of cases belonging to G2 (10 patients) and 30% of cases to the G3 grade (6 patients). Only 1 patient actually showed a G2/3 grade. PCR quantification analysis of the SCARNA17 and miRNAs miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p and miR-145-5p, was performed using the miScript SYBR Green PCR kit (Qiagen, Chatsworth) with the miScript Primer Assay Hs-SCARNA17 (#MS00014014), Hs-miR-21-5p (#MS00009079), Hs-miR-210-3p (#MS00003801), Hs-miR-185-5p (#MS00003647), Hs-miR-221-3p (#MS00003857), Hs-miR-145-5p (#MS00003528) (Qiagen, Chatsworth, CA, USA).
The expression analyses of RNU19 and RNU66 were performed by TaqMan MicroRNA RT assay and TaqMan MiRNA® Assays according to the manufacturer’s protocol.
The p value was calculated by using a non-parametric Wilcoxon test with paired data and miRNAs whose differential expression was statistically significant (< 0.01) was indicated. ==fine methodsresults== ==inizio results== Among the miRNAs deregulated in several human cancers, we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) to evaluate their expression in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues obtained from 20 ccRCC patients undergoing surgical nephrectomy resection. The characteristics of ccRCC patients and tumor specimens are reported in the Patients and Methods section and summarized in Table 1. A total of 20 matched ccRCC and adjacent normal tissue samples were collected. Interestingly, miR-21-5p and miR-210-3p resulted significantly up-regulated in ccRCC vs. normal tissues, with a p value of 0.0083 and 0.0010, respectively (Figure 1). miR-185-5p and miR-221-3p, although did not show any statistically significant modulation between tumor and normal tissues, show a trend of expression similar to miR-21-5p and miR-210-3p (Figure 1). Moreover, we analyzed miR-145-5p expression that usually results particularly down-regulated in several tumor samples compared to normal tissues. We evidenced that miR-145-5p did not show any statistically significant modulation between tumor and normal tissues. ==fine results== ==inizio discussions== In this study we observed that specific miRNAs, previously reported as up-regulated in ccRCC vs. autologous normal tissues, also show increased expression levels in our series of 20 FFPE tumor samples relatively to their matched normal counterparts. Specifically, among the up-regulated miRNAs, we confirmed increased levels of miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p. miR-21-5p and miR-210-3p resulted significantly up-regulated in this patient cohort highlighting these onco-miRNAs as relevant players involved in ccRCC tumorigenesis. Interestingly, the increased expression of miR-21, miR-210, miR-185, miR-221 was previously reported in ccRCC patients and their contribution to ccRCC tumorigenesis is currently under investigation. miR-221 was significantly increased in ccRCC tissues and cell lines, while its knock-down inhibited cell proliferation, migration and invasion of renal cancer cells [25]. miR-210 was significantly overexpressed in ccRCC relatively to normal kidney and patients with high levels of miR-210 show a statistically higher incidence of disease recurrence . Moreover, the down-regulation of miR-210 also reduced the migratory and invasive potential of metastatic RCC cells. Using ccRCC and matched normal kidney samples, it was also evidenced that the increased levels of miR-185 and miR-21 in tumors correlate with the loss of function of specific tumor suppressors such as PTPN13, SLC12A1 and TCF21. Noteworthy is that miR-21 not only shows up-regulated expression in tumor tissues but also its serum levels resulted to be significantly correlated with the clinical staging of ccRCC patients. ==fine discussions== ==inizio conclusion== The selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression were evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in clear cell Renal Cancer Cell tumori - genesis. Concluding, this study confirms the deregulation of specific oncogenic miRNAs in renal tumor, reporting the identification of specific oncogenic miRNAs that are altered in ccRCC tissues, and further supports the potential clinical usefulness of these miRNAs in ccRCC management. ==fine conclusion== ==inizio references== 1. Wu, X.; Weng, L.; Li, X.; Guo, C.; Pal, S.K.; Jin, J.M.; Li, Y.; Nelson, R.A.; Mu, B.; Onami, S.H.; et al. Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis. PLoS ONE 2012, 7, e35661 2. Xiao, H.; Zeng, J.; Li, H.; Chen, K.; Yu, G.; Hu, J.; Tang, K.; Zhou, H.; Huang, Q.; Li, A.; et al. miR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis. Oncotarget 2015, 6, 13201–13215. 3. Samaan, S.; Khella, H.W.; Girgis, A.; Scorilas, A.; Lianidou, E.; Gabril, M.; Krylov, S.N.; Jewett, M.; Bjarnason, G.A.; El-said, H.; et al. miR-210 is a prognostic marker in clear cell renal cell carcinoma. J. Mol. Diagn. 2015, 17, 136–144. 4. Lu, G.J.; Dong, Y.Q.; Zhang, Q.M.; Di, W.Y.; Jiao, L.Y.; Gao, Q.Z.; Zhang, C.G. miRNA-221 promotes proliferation, migration and invasion by targeting TIMP2 in renal cell carcinoma. Int. J. Clin. Exp. Pathol. 2015, 8, 5224–5229. 5. Cheng, T.; Wang, L.; Li, Y.; Huang, C.; Zeng, L.; Yang, J. Differential microRNA expression in renal cell carcinoma. Oncol. Lett. 2013, 6, 769–776. ==fine references==

==inizio objective==

Kidney cancer is one of the top ten most common cancers (1). Many renal masses remain asymptomatic until the late stages of the disease (2). As a consequence more than 50% of kidney cancers are detected incidentally. Otherwise it can be detected in an advanced stage when the patient reach an emergency department with a massive hemorrhage, flank pain, gross haematuria, or general decadency (3). A multidisciplinary approach seems particularly useful for patients with malignancy of kidney (4).
PDTA is a path of diagnosis, therapy, follow up and research of patients (pts) with kidney cancer, based on a multidisciplinary approach in order to have the highest quality of patient care.
Our aim is to improve and make more easily accessible path to the person facing the disease, and to improve patient satisfaction regarding the relationship with the hospital.

==fine objective==

==inizio methodsresults==

All patients who come to our hospital, with suspect or certain kidney cancer are evaluated in a specific multidisciplinary path.
Protocols of diagnosis, staging, surgical or medical treatment and follow-up are defined. Indicators of process and result have been identified and will be periodically verified in order to evaluate the implementation of the path and the improvement of patient care. The main indicators are summarized below:

– median time between access to the hospital and starting medical treatment or
surgery
– hospitalization rate in emergency for suspected kidney cancer
– ratio between number of pts who have suspended or interrupted drug therapy
autonomously and number of pts treated
– IP1: time between the date of the radiological findings of localized renal mass and
surgery
– IP2-IP3: time between the date of the radiological findings of metastatic disease
and cytoreductive surgery or medical treatment
– IR1-2: time to recurrence after radical or conservative surgery
– IR3: % overall survival (OS)
– IR4-IR5: % G3 or G4 toxicity (CTCAE=Common Terminology Criteria for Adverse Events)
– IR6-IR7: time to disease progression during 1° or 2° line treatment
– IR8: % of OS after starting of medical treatment
– IA1: % adherence to guidelines
– IA2: % pts evaluated by the multidisciplinary team
The degree of satisfaction of the patient is evaluated through a questionnaire and results will allow us to improve the path.

==fine methodsresults==

==inizio results==

From November 2014 to December 2015, 94 patients were included in the path. The main
results are:
– Median age: 60 years old;
– Median time between access to the hospital and starting medical treatment or
surgery: 32 days and 48 days, respectively;
– Rate of hospitalization in emergency for suspected kidney cancer: 56%;
– Metastatic disease at the time of diagnosis: 22%;
– Patients who underwent renal surgery as first therapeutic step: 13%;
– Patients who underwent nephron-sparing surgery: 43%;
– Patients who underwent radical surgery: 57%;
– Ratio between number of patients who have suspended or interrupted drug therapy
autonomously and number of patients treated: 10/94.
It is still too early to collect data on recurrence and survival.

==fine results==

==inizio discussions==

In the last year we have experienced a growth in the number of patients who have reached our hospital for diagnosis and treatment of kidney cancer of 15%. As a consequence, actually the median time between access to the hospital and starting medical treatment or surgery was slightly higher than the previous year (30 days in September 2014 versus 32 days in December 2015 for medical treatment, 46 days in September 2014 versus 48 days in December 2015 for surgery). The rate of patients who underwent hospitalization at our emergency department with the unique aim to achieve a diagnosis of kidney cancer was 95% in the 2014. With a multidisciplinary approach to kidney cancer we have reduced this rate from 95% to 56%. In the future, our aim will be to reduce the median time of access to medical and surgical cure also if we expect a progressive growth of patients who will reach our hospital for the diagnosis and for the therapy of kidney cancer. Another target will be to reduce the rate of patients who underwent hospitalization at our emergency department with the unique aim to achieve a diagnosis of kidney cancer. Last but not least another target will be to reduce the number of patients who autonomously interrupt drug therapy improving the monitoring of drug adverse events and providing more information to the patients about the management of drug adverse events.

==fine discussions==

==inizio conclusion==

Our experience of creation of PDTA with the detection of indicators of process and result to monitor the path and a periodic activity of clinical audit may become an important tool to ensure quality care. Overall, we have experienced a growth in the number of patients who have reached our hospital and we have reduced the rate of patients who underwent hospitalization at our emergency department with the unique aim to achieve a diagnosis of kidney cancer. In December 2014, we received the certification of excellence IS0 9001-2008 for diagnosis, treatment and research of kidney cancer through a multidisciplinary approach and in December 2015 the certification has been confirmed.

==fine conclusion==

==inizio references==

1- Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013 Apr;49(6):1374-403.

2- Novara G, Ficarra V, Antonelli A, Artibani W, Bertini R, Carini M, Cosciani Cunico S, Imbimbo C, Longo N, Martignoni G, Martorana G, Minervini A, Mirone V,Montorsi F, Schiavina R, Simeone C, Serni S, Simonato A, Siracusano S, Volpe A, Carmignani G. Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma: are further improvements needed? Eur Urol 2010 Oct;58(4):588-95.

3- Patard JJ, Leray E, Rodriguez A, Rioux-Leclercq N, Guillé F, Lobel B. Correlation between symptom graduation, tumor characteristics and survival in renal cell carcinoma. Eur Urol 2003 Aug;44(2):226-32.

4- Pelikaan L, Vriesema JL, Brusse-Keizer MG, Cornel EB Value of a multidisciplinary team for patients with a urological malignancy. Ned Tijdschr Geneeskd. 2015;159:A8590.

==fine references==

==inizio objective==

As time goes by, renal tumours surgery has had a trend towards parenchymal sparing and minimal invasive approach. It has been always debated what are renal tumours who are fit and unfit for this kind of surgery. Most recent guidelines suggest as limit for partial nephrectomy (PN) 7 cm of highest diameter of tumour (t1b tumours) (1). In any case the complications and the outcomes of partial nephrectomy is associated with the treatment center’s learning curve and surgeon’s experience, and is correlated with the anatomical features of each case (2).
The aim of our study was to describe our technique in clampless LPN analyzing the intraoperative and postoperative complications of patients who underwent this procedure at our institute and the feasibility of our technique.

==fine objective==

==inizio methodsresults==

From January 2005 to December 2015, 265 patients underwent clampless LPN for a renal tumour at our institution. According to R.E.N.A.L (radius; exophytic/endophytic; nearness; anterior/posterior; location) NS (nephrometry scoring), 119 patients had low tumour complexity (score 4-6), 77 patients had moderate tumour complexity (score 7-9) and 69 patients had high tumour complexity (score 10-12).
Intraoperative and postoperative complications have been classified according to standardized reporting systems such as the Satava (3) and the Clavien-Dindo system (4).
In our technique we perform a clampless LPN without isolation of the renal pedicle except where required by specific technical necessity like intrahilar or perihilar tumors. A transperitoneal approach was used in all cases except for three cases (retroperitoneal approach). We usually isolate the tumour and surrounding fat, with a small portion (about one centimeter) of healthy parenchyma around its circumference, in order to control potential hemorrhages with transfixing parenchymal sutures. Usually we do not isolate all surface of the kidney. During the enucleation, a cleavage plane between pseudocapsule and normal parenchyma is usually created by monopolar scissors. Tumour is removed and hemostasis is controlled by using a bipolar dissector and “hem-o-lok®” clips. Complete hemostasis is usually achieved by “floseal® hemostatic matrix” and “surgicel®”. We perform a sliding hem-o-lok ® clips absorbable suture when we need to achieve a better emosthasis and for kidney reconstruction. Finally Gerota’s fascia is closed.

==fine methodsresults==

==inizio results==

Mean operating time was 116,8 minutes. Mean intraoperative blood loss was 220 millilitres (range 30-1200 millilitres). Intraoperative blood transfusions were not necessary (according to intraoperative blood count analysis). Postoperative blood transfusions were necessary in 8 out of 265 patients (3%). The mean length of hospital stay was 4,8 days (range 3-11 days). Drains were removed at a mean time of 4,3 after surgery (range 3-7). All operations were performed laparoscopically without conversion to open surgery.
6 out 265 patients (2,3%) experience intraoperative complications. 59 out of 265 patients (22,3%) experienced postoperative complications.
Table 1 shows in detail the intraoperative and the postoperative complications according to Satava classification and Clavien-Dindo classification, respectively.

==fine results==

==inizio discussions==

The robotic technology seems to allow a safer and more precise excision of complex renal tumours, which are most commonly removed using an open approach, with a technique that has a shorter learning curve and some technical advantages instead of classical laparoscopy (5). Our present results indicate that LPN is feasible and safe in experienced hands compared to open surgery also for high-surgical risk tumours when a robotic device is not avaible. Thompson RH et all. (2010) demonstrate that “every minute counts” when the renal hilum is clamped and warm ischemia time (WIT) is a well-known predictor of postoperative estimated glomerular filtration rate (eGFR) (6) . Based on this, it should be important to perform a clampless partial nephrectomy. We usually start the procedure superficially with an enucleoresection of the tumour, but when we are more deep the procedure becomes a simple enucleation, who has been previously described as a safe technique with oncologic equivalence to standard partial nephrectomy (7).
Postoperative complications rate was 22,3%. The rate is smaller (8,8%) if we do not include Clavien-Dindo I grade complications.
Despite this, estimated blood loss and overall postoperative complication rate were similar to the previous series in which both clamped and clampless LPN are enrolled (8).

==fine discussions==

==inizio conclusion==

Current evidences suggest that the amount of residual functional parenchyma represents an important factor that impacts postoperative renal function and that WIT is a well-known predictor of postoperative eGFR. As a consequence it is important to perform a clampless partial nephrectomy removing the danger risk of sacrificing healthy parenchyma. Clampless LPN without isolation of the pedicle is a feasible procedure for renal tumours with a low rate of intraoperative and postoperative complications in high volume centers. Moreover clampless LPN is a feasible procedure for renal tumours of high surgical complexity in high laparoscopic experience centers, when robotic devices are not available.

==fine conclusion==

==inizio references==

1- Simmons MN et all. Laparoscopic radical versus partial nephrectomy for tumors >4 cm: intermediate-term oncologic and functional outcomes. Urology 2009 May;73(5):1077-82.
2-Porpiglia F et all. Margins, ischaemia and complications rate after laparoscopic partial nephrectomy: impact of learning curve and tumour anatomical characteristics. BJU Int. 2013 Dec;112(8):1125-32. doi: 10.1111/bju.12317. Epub 2013 Aug 13.
3-Kazaryan AM et all. Morbidity assessment in surgery: refinement proposal based on a concept of perioperative adverse events. ISRN Surg. 2013 May 16;2013:625093. doi: 10.1155/2013/625093. Print 2013.4- Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R,Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug; 250 (2): 187-96.
5-Hanzly M et all. Learning curves for robot-assisted and laparoscopic partial nephrectomy. J Endourol. 2015 Mar;29(3):297-303. doi: 10.1089/end.2014.0303. Epub 2014 Oct 21.
6- Thompson RH, et all. Every minute counts when the renal hilum is clamped during partial nephrectomy. Eur Urol. 2010 Sep;58(3):340-5. doi: 10.1016/j.eururo.2010.05.047. Epub 2010 Jun
7- Longo N, et all. Simple enucleation versus standard partial nephrectomy for clinical T1 renal masses: perioperative outcomes based on a matched-pair comparison of 396 patients (RECORd project). Eur J Surg Oncol. 2014 Jun;40(6):762-8.
8-Choi JE et all. Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol. 2015 May;67(5):891-901. doi: 10.1016/j.eururo.2014.12.028. Epub 2015 Jan 6.

==fine references==