Paolo Fornara

Martin Luther University Halle-Wittenberg, Halle-on-the-Saale, Saxony-Anhalt, Germany

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Publications (290)815.07 Total impact

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    ABSTRACT: This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (P<0.001). Additionally, suPAR levels differed between the Gleason sum groups GS=7 vs. GS>7, with higher levels in the latter group (P=0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (P=0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS) (P=0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (P=0.00026 and P=0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (P=0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 03/2015; DOI:10.1002/ijc.29505 · 6.20 Impact Factor
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    ABSTRACT: Abstract Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 = 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients’ survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DR+ and CXCR3+ T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.
    OncoImmunology 01/2015; 4(1). DOI:10.4161/2162402X.2014.985082 · 6.28 Impact Factor
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    ABSTRACT: Members of the urokinase-type plasminogen activator (uPA) system including uPA, its receptor uPAR and the plasminogen activator inhibitor 1 (PAI-1) play an important role in tumour invasion and progression in a variety of tumour types. Since the majority of clear cell renal cell carcinoma (ccRCC) shows distant metastasis at time of diagnosis or later, the interplay of uPA, uPAR and PAI-1 might be of importance in this process determining the patients' outcome. Corresponding pairs of malignant and non-malignant renal tissue specimens were obtained from 112 ccRCC patients without distant metastasis who underwent tumour nephrectomy. Tissue extracts prepared from fresh-frozen tissue samples by detergent extraction were used for the determination of antigen levels of uPA, uPAR and PAI-1 by ELISA. Antigen levels were normalised to protein concentrations and expressed as ng per mg of total protein. Antigen levels of uPA, uPAR, and PAI-1 correlated with each other in the malignant tissue specimens (rs=0.51-0.65; all P<0.001). Antigen levels of uPA system components were significantly higher in tissue extracts of non-organ confined tumours (pT3+4) compared to organ-confined tumours (pT1+2; all P<0.05). Significantly elevated levels of uPAR and PAI-1 were also observed in high grade ccRCC. When using median antigen levels as cut-off points, all three uPA system factors were significant predictors for disease-specific survival (DSS) in univariate Cox's regression analyses. High levels of uPA and uPAR remained independent predictors for DSS with HR=2.86 (95%CI 1.07-7.67, P=0.037) and HR=4.70 (95%CI 1.51-14.6, P=0.008), respectively, in multivariate Cox's regression analyses. A combination of high antigen levels of uPA and/or uPAR further improved the prediction of DSS in multivariate analysis (HR=14.5, 95%CI 1.88-111.1, P=0.010). Moreover, high uPA and/or uPAR levels defined a patient subgroup of high risk for tumour-related death in ccRCC patients with organ-confined disease (pT1+2) (HR=9.83, 95%CI 1.21-79.6, P=0.032). High levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases.
    BMC Cancer 12/2014; 14(1):974. DOI:10.1186/1471-2407-14-974 · 3.32 Impact Factor
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    G Pini, F Greco, N Mohammed, P Fornara
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    ABSTRACT: We present our first minilaparoscopic-assisted laparoendoscopic single-site bilateral nephrectomies (b-LESS-N) performed in a patient with bilateral atrophic kidney, right malignant renal tumor of 4.5 cm that developed in a native kidney after multiple bilateral renal transplantations and renovascular hypertension. The mean operative time was 233 minutes, with a mean blood loss of 180 mL. A single umbilical incision (5.5 cm) was performed to remove both kidneys. No significant difference in glomerular filtration rate was observed postoperatively. The postoperative recovery was uneventful with favorable short-term outcomes and high patient satisfaction. The 10-month follow-up showed effective arterial pressure improvement, absence of tumor relapse, and stable graft function. We believe that b-LESS-N for renal cancer after a renal transplantation can be performed without increased risks for the patients or for the transplanted kidney.
    Transplantation Proceedings 09/2014; 46(7):2391-5. DOI:10.1016/j.transproceed.2014.03.013 · 0.95 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e431. DOI:10.1016/S1569-9056(14)60425-5 · 3.37 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e291. DOI:10.1016/S1569-9056(14)60286-4 · 3.37 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e308. DOI:10.1016/j.juro.2014.02.752 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e315. DOI:10.1016/j.juro.2014.02.813 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e936-e937. DOI:10.1016/j.juro.2014.02.2521 · 3.75 Impact Factor
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    ABSTRACT: 2008) Sofort-und Spätfunktion des Transplantats nach laparoskopisch-handassistierter Donornephrektomie: Vergleich zur offenen Donornephrekto-mie. Tx Med 20: 13-17 Sofort-und Spätfunktion des Transplantats nach laparoskopisch-handassistierter Donor-nephrektomie: Vergleich zur offenen Donornephrektomie Einleitung: Die laparoskopische Donornephrektomie hat sich zum Verfahren der Wahl in der Lebendnieren-Transplantation entwi-ckelt. Längere Warm-Ischämiezeit und Anwendung des Pneumope-ritoneums ließen zuletzt Fragen über die Sofort-und Spätfunktion des Transplantats aufkommen. Wir berichten über unsere Erfahrun-gen mit laparoskopisch-handassistierter Donornephrektomie, ins-besondere betreffend der Transplantatfunktion verglichen mit offe-ner Donornephrektomie. Patienten und Methoden: Diese Studie ist eine retrospektive, nicht-randomisierte Single-center Analyse. Zwischen 1995 und März 2008 wurde bei 72 Patienten mit terminaler Niereninsuffi-zienz eine Lebendspende-Niere transplantiert. Davon waren 35 Donornieren offen-chirurgisch und 37 laparoskopisch-handassis-tiert entnommen. Erfasst wurden neben der Transplantat-Sofort-funktion die biochemischen Marker der glomerulären Filtrations-rate (GFR), Serum-Creatinin und Serum-Cystatin C 1 Jahr nach Transplantation. Ergebnisse: Sowohl die Rate der Transplantat-Sofortfunktion als auch die Nierenfunktionsparameter Serum-Creatinin und Serum-Cystatin C ein Jahr nach Transplantation zeigten in beiden Patien-tengruppen keinen statistisch signifikanten Unterschied. Schlussfolgerungen: Die laparoskopisch-handassistierte Donor-nephrektomie hatte verglichen mit offener Donornephrektomie kei-nen negativen Einfluss auf die Transplantatfunktion des Lebend-spende-Empfängers. Introduction: The laparoscopic donor nephrectomy has become the procedure of choice in the living related kidney transplantation. Longer warm ischemia time and application of pneumoperitoneum have raised questions about the early and late function of the trans-plant graft. We report on our experience with laparoscopic hand-assisted donor nephrectomy, in particular concerning the graft function compared with open donor nephrectomy.
  • F Greco, P Fornara, V Mirone
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    ABSTRACT: Renal transplantation represents actually the most effective therapy in patients with end-stage renal failure as it is cost effective, allows for a normal life style and reduces the risk of mortality from dialysis related complications. Renal transplantation can be classified in deceased- donor or living-donor transplantation, depending on the source of the donor organ. The short-term results of transplants with kidneys from donors over 65 years old are almost similar to those with younger organs, but in these patients it is mandatory to reduce cold ischemia time. In the last years, the demand for kidney transplantation has increased dramatically, which has been associated with an increase in living-donor organ procurement, which presents several advantages. Moreover, new operative techniques have been recently developed in order to improve surgical outcomes and graft survival and to reduce the complications' rate after renal transplantation. The purpose of the present review is to evaluate the published literature regarding the technical aspects and the urological complications associated with renal transplantation.
    Panminerva medica 03/2014; 56(1):17-29. · 2.28 Impact Factor
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    C. Doehn, P. Fornara, D. Jocham
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    ABSTRACT: In der vorliegenden Arbeit wird ein Überblick zum Einsatz laparoskopischer Operationstechniken bei “marginalen” Patienten gegeben, die insbesondere durch die Faktoren “fortgeschrittenes Alter” und “Niereninsuffizienz” gekennzeichnet sind. Die Laparoskopie muss sich an der technischen Machbarkeit, aber auch an (post)operativen Parametern im Vergleich zum (offenen) Standardeingriff messen lassen. Vor allem für die laparoskopische Nephrektomie dürfte ein Großteil dieser Anforderungen als geprüft und überwiegend positiv beurteilt gelten. Dennoch liegen nur wenige Publikationen zur laparoskopischen Nephrektomie bei sehr alten Patienten oder Patienten mit Niereninsuffizienz vor. Die Belastung durch das Pneumoperitoneum dürfte einen spezifischen Faktor der Laparoskopie darstellen und mag im Einzelfall den offenen Eingriff als geeigneter erscheinen lassen. Hiervon abgesehen zeigt die Analyse der verfügbaren Literatur, dass die Effektivität der Laparoskopie auch bei Vorliegen eines gewissen Risikoprofils bestehen bleibt. Gerade marginale Patienten dürften von den Vorteilen profitieren, die insbesondere im postoperativen Verlauf evident sind. Obgleich die Datenlage hinsichtlich anderer urologischer Operationen spärlicher ist, dürften die Ergebnissen der laparoskopischen Nephrektomie prinzipiell auch auf andere Eingriffe übertragbar sein. This paper describes the use of urological laparoscopy in borderline patients, focussing on geriatric patients and those with renal failure. Laparoscopy must not only be feasible but also at least as effective concerning operative and postoperative parameters when compared to standard open surgery. For laparoscopic nephrectomy most of these factors have tested positive. However, only a few papers have been published concerning borderline patients. In some cases the pneumoperitoneum may not be suitable for borderline patients and open operative techniques are preferred. Apart from this, the current literature supports the effectiveness of laparoscopy even when certain risk factors are present. Especially borderline patients can benefit from the laparoscopic approach for nephrectomy. Although data are scarce concerning other laparoscopic procedures in borderline patients, the results of laparoscopic nephrectomy should probably apply to other laparoscopic procedures.
    Der Urologe 03/2014; 41(2):123-130. DOI:10.1007/s00120-002-0181-7 · 0.44 Impact Factor
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    01/2014; 37 Suppl 3:29-37. DOI:10.1159/000363756
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    ABSTRACT: To analyse intraoperative costs and healthcare reimbursements of partial/radical nephrectomy in open and minimal invasive surgery (MIS), as laparoscopy and laparoendoscopic single-site surgery (LESS), for the treatment of renal tumour. In a non-randomized retrospective study, we selected 90 patients who underwent (01/2010-12/2011) partial and radical nephrectomy for clinical renal masses ≤7 cm (cT1N0M0) and divided them into laparoscopic [laparoscopic partial nephrectomy (LPN), laparoscopic radical nephrectomy (LRN)], LESS [laparoendoscopic single-site partial nephrectomy (LESS-PN), laparoendoscopic single-site radical nephrectomy (LESS-RN)] and open groups [open partial nephrectomy (OPN), open radical nephrectomy (ORN)]. Patients were matched for age, sex, body mass index, ASA score and tumour side. Primary endpoints were evaluation of intraoperative costs (general, laparoscopic, sutures, haemostatic agents, anaesthesia, and surgeon/nurses fee), total insurance and estimated daily reimbursement. MIS showed longer operative time (p ≤ .02) and shorter hospital stay (p ≤ .04). Total costs were higher (p ≤ .03) in MIS (LRN: 4,091.5 ; LPN: 4,390.4 ; LESS-RN: 3,866 ; and LESS-PN: 3,450 ) if compared with open (OPN: 2,216.8.8 , ORN: 1,606.4 ). Laparoscopic materials incised mainly in total costs of MIS (38-58.1 %). Reusable instruments reduced LESS laparoscopic costs (LESS-PN: 1,312.2 vs. LRN: 2,212.2 , p < .0001). Intraoperative frozen section and DJ ureteric stenting (general costs) (p ≤ .008) and haemostatic agents use (p ≤ .01) were higher in nephron sparing surgery (NSS), due to more frequent use of ancillary procedures necessary for a safe management of such an approach. Estimated anaesthesia costs and doctor/nurses fee were higher in MIS (p ≤ .02). Whereas total final reimbursements were comparable (p ≥ .8), estimated daily reimbursements were lower in MIS (p < .001) due to higher intraoperative costs and longer operative time. Well-known advantages offered by MIS/NSS face higher total intraoperative costs and 'paradoxical' reduced healthcare reimbursement. We believe that local health systems should consider a subclassification with different compensations, which will incentive NSS and MIS approaches.
    World Journal of Urology 12/2013; 32(6). DOI:10.1007/s00345-013-1223-z · 3.42 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):368-368. DOI:10.1158/1538-7445.AM2013-368 · 9.28 Impact Factor
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    ABSTRACT: Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery.
    European Urology 08/2013; 65(5). DOI:10.1016/j.eururo.2013.07.033 · 10.48 Impact Factor
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    ABSTRACT: To report a large multi-institutional series of LESS-PN and to analyze the effect on renal function and short-term oncologic outcomes. Consecutive cases of LESS-PN done between November 2007 and March 2012 at 11 participating institutions were included in this retrospective analysis. Demographic data, main perioperative outcome parameters, and perioperative complications were gathered and analyzed. The function of the kidney was evaluated by measuring serum creatinine and estimated glomerular filtration rate (eGFR). Moreover, chronic kidney disease (CKD) of each patient was defined in stages according to National Kidney Foundation, Kidney Disease Outcomes Quality Initiative. A total of 190 cases were included in this analysis. Mean renal tumor size was 2.6, and PADUA score 7.2. Median operative time was 170 min with a median EBL of 150 ml. A clampless technique was adopted in 70 cases (36.8%) and the median WIT was 16.5 min. PADUA score independently predicted length of WIT (low vs high score: OR 5.11, CI 1.50-17.41, p=0.009; intermediate vs high score: OR 5.13, CI 1.56-16.88, p=0.007). The overall postoperative complication rate was 14.7%. In presence of a clamping, a significant increase of serum creatinine and a significant decrease of the eGFR were observed postoperatively and at 6 months. On multivariate analysis only PADUA score was the only predicting factor. The overall survival was found to be 99%, 97%, 88% at 12, 24 and 36 month follow-up, respectively, whereas the disease-free survival was 98% at 12 and 97% at 24 and 36 month follow-up, respectively. This study could demonstrate that LESS-PN is effective in renal function preservation and oncological control at a short and intermediate follow up interval.
    BJU International 07/2013; 113(2). DOI:10.1111/bju.12376 · 3.13 Impact Factor
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    ABSTRACT: To report the surgical outcomes of laparoscopic radical cystectomy (LRC) with extracorporeal orthotopic ileal neobladder (OIN) in patients with muscle-invasive urothelial carcinoma of the bladder (UCB). Between October 2009 and December 2011, 37 patients with muscle-invasive UCB underwent a LRC with OIN. Indications included (a) muscle-invasive UCB T2-4a, N0-Nx, M0; (b) high-risk and recurrent non-muscle-invasive tumors; (c) T1G3 plus CIS; and (d) extensive non-muscle-invasive disease that could not be controlled by transurethral resection and intravesical therapy. Demographic data, perioperative, and postoperative variables were recorded and analyzed. The median operating time was 330 min, with a median estimated blood loss of 410 ml. Median length of stay was 12 days, and the mean length of the skin incision to extract the specimen and for the configuration of the neobladder was 7 ± 1 cm. The complication rate was 21.6 % (Clavien II). No Clavien III-V complications were reported. Daytime and nocturnal continence were preserved in 95 and 78 %, respectively. No local recurrence or port site metastasis occurred. Median time to disease recurrence was 14 months (IQR 9-24), and 1-year cancer-specific survival was 91.9 %. Laparoscopic radical cystectomy with extracorporeal ileal neobladder is a challenging procedure but technically feasible, allowing low morbidity and oncological safety. Long-term oncological results are required to definitely recognize this procedure as a standard treatment for bladder cancer.
    World Journal of Urology 07/2013; DOI:10.1007/s00345-013-1122-3 · 3.42 Impact Factor
  • Urologia 05/2013; 80(Suppl. 22):16-23. DOI:10.5301/RU.2013.11097
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    ABSTRACT: Over the last few years, many urological laparoscopic operations have been successfully performed by LESS. However, the actual role of LESS in the field of minimally invasive urologic surgery remains to be determined with controversial data about postoperative pain control and almost no results on cosmetic data. The aim of the present study is to describe the technique and report the surgical outcomes of LESS radically nephrectomy (RN) in the treatment of renal cell carcinoma with special emphasis for postoperative pain control and almost no results on cosmetic data. LESS-RN was performed in 33 patients with renal tumors. The indications to perform a LESS-RN were represented by renal tumors not greater than T2, and without evidence of lymphadenopathy or renal vein involvement. The Endocone (Karl Storz, Tuttlingen, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and bent grasper and scissors was used. The step sequence of LESS-RN was comparable to standard laparoscopic RN. Demographic data and perioperative and postoperative variables were recorded and analyzed. The mean operative time was 143.7 ± 24.3 min, with a mean estimated blood loss of 122.3 ± 34.1 mL and a mean hospital stay of 3.8 ± 0.8 d. The mean length of skin incision was 4.1 ± 0.6 cm; all patients were discharged from hospital with minimal discomfort, as demonstrated by their pain assessment scores (visual analogue scale: 1.9 ± 0.8). The definitive pathologic results revealed a renal cell carcinoma in all cases and a stage distribution of four T1a, 27 T1b, and 2 T2 tumors. All patients were very satisfied with the appearance of the scars, and at a median follow-up period of 13.2 ± 3.9 mo, all patients were alive without evidence of tumor recurrence or port-site metastasis. LESS is a safe and feasible surgical procedure for RN in the treatment of renal cell carcinoma and has excellent cosmetic results.
    Urologia 04/2013; 80 Suppl 22:16-23.

Publication Stats

3k Citations
815.07 Total Impact Points

Institutions

  • 2001–2015
    • Martin Luther University Halle-Wittenberg
      • Clinic for Urology
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2013
    • Hanyang University Medical Center
      Sŏul, Seoul, South Korea
  • 2006–2013
    • Universitätsklinikum Halle (Saale)
      Halle-on-the-Saale, Saxony-Anhalt, Germany
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2010
    • University of California, San Diego
      San Diego, California, United States
    • Krankenhaus Düren gem. GmbH
      Düren, North Rhine-Westphalia, Germany
    • Università degli Studi di Messina
      Messina, Sicily, Italy
    • Università degli Studi di Palermo
      Palermo, Sicily, Italy
  • 1999–2009
    • University Hospital Essen
      • Klinik für Urologie
      Essen, North Rhine-Westphalia, Germany
  • 2005–2006
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 2004
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2002
    • Democritus University of Thrace
      • Department of Internal Medicine I
      Komotiní, Anatoliki Makedonia kai Thraki, Greece
  • 1996–2002
    • Universität zu Lübeck
      • • Department of Urology
      • • Department of Obstetrics and Gynecology
      • • Klinik für Urologie
      Lübeck Hansestadt, Schleswig-Holstein, Germany