Publications by authors named "Sarel Halachmi"

67 Publications

Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation.

Biology (Basel) 2021 Feb 3;10(2). Epub 2021 Feb 3.

Proteomic Unit, Division of Clinical Immunology, Bnai Zion Medical Center, Haifa 31048, Israel.

Introduction: Our previous studies showed elevated levels of Semaphorin3a (Sema3A) in the urine of patients with urothelial cancer compared to healthy patients. The aim of this study was to analyze the extent of Sema3A expression in normal and malignant urothelial tissue using immune-staining microscopic and morphometric analysis.

Materials And Methods: Fifty-seven paraffin-embedded bladder samples were retrieved from our pathology archive and analyzed: 14 samples of normal urothelium, 21 samples containing low-grade urothelial carcinoma, 13 samples of patients with high-grade urothelial carcinoma, 7 samples containing muscle invasive urothelial carcinoma, and 2 samples with pure urothelial carcinoma in situ. All samples were immunostained with anti Sema3A antibodies. The area of tissue stained with Sema3A and its intensity were analyzed using computerized morphometry and compared between the samples' groups.

Results: In normal bladder tissue, very light Sema3A staining was demonstrated on the mucosal basal layer and completely disappeared on the apical layer. In low-grade tumor samples, cells in the basal layer of the mucosa were also lightly stained with Sema3A, but Seama3A expression intensified upon moving apically, reaching its highest level on apical cells exfoliating to the urine. In high grade urothelial tumors, Seama3A staining was intense in the entire thickness of the mucosa. In samples containing carcinoma in situ, staining intensity was high and homogenous in all the neoplastic cells.

Conclusions: Sema3A may be serve as a potential non-invasive marker of urothelial cancer.
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http://dx.doi.org/10.3390/biology10020109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913361PMC
February 2021

The Use of Tissue Adhesive for Tumor Bed Closure during Partial Nephrectomy is Associated with Reduced Devascularized Functional Volume Loss.

Curr Urol 2019 Oct 1;13(2):82-86. Epub 2019 Oct 1.

Department of Urology, Bnai-Zion Medical Center, Haifa, Israel.

Objectives: To quantitatively compare the functional renal volume loss, following nephron sparing surgery (NSS) between patients in whom tumor bed closure was done by biological tissue adhesive and those who were managed by standard suture technique.

Methods: From our institutional NSS database we retrospectively collected patients who had two sequential quantitative single-photon emission computed tomography of 99mTc-dimercaptosuccinic acid uptake studies, the first study immediately before surgery and the second one 3-6 months following surgery. The study group included 69 patients: 26 (37.7%) patients in the sealant group (BioGlue®) and 43 (62.3%) patients in the standard suture group.

Results: No statistically significant differences were noted in the baseline clinical and pathological characteristics of the studied groups. However, there were several statistically significant differences in operative variables: patients in the suture group had larger amount of blood loss (3-fold), longer ischemia time (26.6 vs. 21 minutes,) and slightly longer operation time. Patients in whom tumor bed was closed by sutures had nearly 3-fold higher parenchymal loss compared to patients managed by sealant (26.28 vs. 8.92 ml, p = 0.048).

Conclusions: The use of tissue sealant during tumor bed reconstruction is associated with reduced devascularized parenchymal mass loss and should be considered among modifiable surgical factors during NSS.
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http://dx.doi.org/10.1159/000499288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872995PMC
October 2019

Recent Advances in the Race to Design a Rapid Diagnostic Test for Antimicrobial Resistance.

ACS Sens 2018 11 2;3(11):2202-2217. Epub 2018 Nov 2.

Department of Biotechnology and Food Engineering , Technion - Israel Institute of Technology , Haifa , Israel 3200003.

Even with advances in antibiotic therapies, bacterial infections persistently plague society and have amounted to one of the most prevalent issues in healthcare today. Moreover, the improper and excessive administration of antibiotics has led to resistance of many pathogens to prescribed therapies, rendering such antibiotics ineffective against infections. While the identification and detection of bacteria in a patient's sample is critical for point-of-care diagnostics and in a clinical setting, the consequent determination of the correct antibiotic for a patient-tailored therapy is equally crucial. As a result, many recent research efforts have been focused on the development of sensors and systems that correctly guide a physician to the best antibiotic to prescribe for an infection, which can in turn, significantly reduce the instances of antibiotic resistance and the evolution of bacteria "superbugs." This review details the advantages and shortcomings of the recent advances (focusing from 2016 and onward) made in the developments of antimicrobial susceptibility testing (AST) measurements. Detection of antibiotic resistance by genomic AST techniques relies on the prediction of antibiotic resistance via extracted bacterial DNA content, while phenotypic determinations typically track physiological changes in cells and/or populations exposed to antibiotics. Regardless of the method used for AST, factors such as cost, scalability, and assay time need to be weighed into their design. With all of the expansive innovation in the field, which technology and sensing systems demonstrate the potential to detect antimicrobial resistance in a clinical setting?
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http://dx.doi.org/10.1021/acssensors.8b00900DOI Listing
November 2018

Preoperative neutrophil to lymphocyte ratio improves recurrence prediction of non-muscle invasive bladder cancer.

BMC Urol 2018 Oct 22;18(1):90. Epub 2018 Oct 22.

Department of Urology, Bnai Zion Medical Center, Faculty of Medicine, Technion - Israel Institute of Technology, Golomb 47, 31048, Haifa, Israel.

Background: This study aims to prospectively evaluate the ability of Neutrophil-to-Lymphocyte ratio (NLR) to forecast recurrence in patients with non-muscle invasive bladder cancer (NMIBC). This is a continuation of our two previous retrospective studies that indicated the NLR > 2.5 criterion as a predictor of recurrence in patients with NMIBC.

Methods: Since December 2013, all patients admitted to our department for TUR-BT and agreed to participate, had a blood drawn for cell count and differential 24 h prior to surgery. Patients with pathological NMIBC were followed prospectively for disease recurrence. The end-point of the follow up was either a cancer recurrence or the termination of the study. Univariate and multivariate Cox regressions were performed to assess the NLR > 2.5 predictive capability for recurrence, versus and in conjunction to the pathologically based EORTC score, among additional statistical analyses.

Results: The study cohort included 96 men and 17 women with a median age of 72 years. Sixty-four patients (56.6%) have had a recurrence during the study occurring at the median time of 9 months (IQR 6, 13), while the median follow-up time for patients without recurrence was 18 months (IQR 10, 29). Univariate Cox regressions for recurrence demonstrated significance for NLR > 2.5 for the whole cohort (p = 0.011, HR 2.015, CI 1.175-3.454) and for the BCG sub-group (p = 0.023, HR 3.7, CI 1.2-11.9), while the EORTC score demonstrated significance for the 'No Treatment' subgroup (p = 0.024, HR 1.278, CI 1.03-1.58). When analyzed together as a multivariate Cox model, the NLR > 2.5 and EORTC score retained their significance for the aforementioned groups, while also improving the EORTC score significance for the whole cohort.

Conclusion: NLR > 2.5 was found to be a significant predictor of disease recurrence and demonstrated high hazard ratio and worse recurrence-free survival in patients with NMIBC, especially in those treated with BCG. Additionally, our data demonstrated statistical evidence that NLR > 2.5 might have an improving effect on the EORTC score's prediction when analyzed together.
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http://dx.doi.org/10.1186/s12894-018-0404-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198354PMC
October 2018

Method Used for Tumor Bed Closure (Suture vs. Sealant), Ischemia Time and Duration of Surgery are Independent Predictors of Post-Nephron Sparing Surgery Acute Kidney Injury.

Urol Int 2018 19;101(2):184-189. Epub 2018 Jul 19.

Department of Urology, Bnai-Zion Hospital, Haifa, Israel.

Introduction: The aim of our study was to examine the influence of tumor complexity and operative variables on the degree and rate of post-nephron sparing surgery (NSS) acute kidney injury (AKI).

Methods: We retrospectively reviewed the records of 477 patients who underwent NSS for enhancing renal masses in our institution. AKI was determined using the latest definition by AKIN and RIFLE criteria. Serum creatinine was assessed daily starting from day 1 post-surgery and until discharge (usually on postoperative day 3). Estimated glomerular filtration was determined using the Modification of Diet in Renal Disease equation.

Results: Overall, 191 patients (40%) developed postoperative AKI, and most of them (88%) were grade 1. Multivariate analysis revealed that the most significant and independent variables associated with AKI were operation time (p = 0.02), ischemia time (p = 0.02), and the use of tissue adhesive for tumor bed closure (p = 0.02). Other important factors (by univariate analysis) were the need for blood transfusion (p = 0.003) and estimated blood loss (p = 0.007).

Conclusions: Operative time, ischemia, and tumor bed closure method are independent predictors of post-NSS AKI. Efforts should be made to limit prolonged ischemia and to reduce viable parenchymal loss. Further studies concerning the functional impact of AKI in these patients will be required.
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http://dx.doi.org/10.1159/000490107DOI Listing
December 2018

Overexpression of semaphorin 3A in patients with urothelial cancer.

Urol Oncol 2018 04 27;36(4):161.e1-161.e6. Epub 2017 Dec 27.

The Department of Urology, Bnai Zion Medical Center, Haifa, Israel. Electronic address:

Objective: A highly sensitive and specific urine marker for the detection of recurrent urothelial cancer and for screening healthy population or people at risk for urothelial cancer has not been found yet. As urine cytology is not sensitive enough, patients with non-muscle-invasive bladder cancer need lifelong follow-up involving multiple invasive cystoscopies. Our aims of study were to examine the expression of semaphorin 3A in urothelial cancer patients and to evaluate semaphorin 3A as a potential marker for urothelial cancer.

Materials And Methods: Urine samples were taken from patients with known bladder tumor, hospitalized for transurethral resection of lesions, from patients with history of urothelial cancer admitted for endoscopic follow up, from patients with other nonmalignant urological conditions such as prostatic hyperplasia, stress incontinence, urethral stricture, ureteral and kidney stones, and from healthy volunteers with no history of urothelial malignancy and no urological symptoms. Semaphorin 3A (sema3A) protein level was measured using enzyme-linked immunosorbent assay in every sample and levels were correlated with endoscopic and pathological findings. In addition, we performed immunohistochemically staining with semaphorin 3A of 15 tissue samples (various tumors and normal bladder tissues).

Results: A total of 183 urine samples were tested. Out of them, 116 patients (mean age 70.7; 94 males and 22 females) had positive cystoscopy, and 67 (mean age 64.7; 51 males and 16 females) had negative cystoscopy. Higher sema3A values were significantly correlated (P = 0.006) with presence of urothelial cancer, as determined by positive cystoscopy or urethroscopy and pathological biopsy. Sema3A levels also showed positive correlation with the number of tumors. Sema3A levels combined with urine cytology showed much higher sensitivity compared with cytology alone (66% vs. 33%), with smaller reduction of specificity (77% vs. 90%). Immunohistochemical staining showed intense staining in high stage and grade tumors, and almost no staining in normal tissue.

Conclusions: Semaphorin 3A is overexpressed in urothelial cancer patients, as evidenced both in its presence in urine and in bladder tissue. Semaphorin 3A in urine is a promising potential urothelial cancer biomarker either independently or in conjunction with cytology. Further tests are needed to elucidate the sex difference in the expression of Sema3A in the urine of bladder cancer patients.
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http://dx.doi.org/10.1016/j.urolonc.2017.12.007DOI Listing
April 2018

Inflammatory Response in Preterm Newborns Born after Prolonged Premature Rupture of Membranes: Is There a Correlation with Placental Histological Findings?

Isr Med Assoc J 2017 Oct;19(10):610-613

Department of Neonatal Intensive Care, Wolfson Medical Center Holon, Israel.

Background: Preterm birth is the leading cause of morbidity and mortality among neonates in the United States. Early recognition of sepsis in this population is a challenging task since overt clinical signs can be difficult to determine. C-reactive protein (CRP), one of the most frequently non-specific used laboratory test, can indirectly aid the diagnosis of neonatal sepsis.

Objectives: To evaluate the relationship between histological findings in the placenta of preterm newborns born after prolonged rupture of membranes, CRP levels, and blood cultures.

Methods: Medical records were reviewed of all preterm newborns born after prolonged premature rupture of membranes at a medical center in Israel between 2011 and 2014.

Results: Of 128 newborns with prolonged rupture of membranes, 64 had evidence of histological chorioamnionitis (HCA). Gestational age, birth weight, and Apgar scores were significantly lower, while CRP levels (on admission and 10-12 hours post-delivery) were significantly higher in preterm newborns born to mothers with histological evidence of chorioamnionitis, but values were within normal ranges. Duration of the rupture of membranes and white blood cell counts did not differ between groups.

Conclusions: CRP levels taken on admission and 10-12 hours after delivery were higher when HCA was present, but since there was a substantial overlap between those with and without HCA and the values for most were within normal range, the differences were not enough to serve as a tool to diagnose placental histological chorioamnionitis in preterm infants born after prolonged premature rupture of membranes and exposed to intrapartum antibiotics.
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October 2017

Allium Stents: A Novel Solution for the Management of Upper and Lower Urinary Tract Strictures.

Rambam Maimonides Med J 2017 10 16;8(4). Epub 2017 Oct 16.

Department of Urology, Bnai-Zion Medical Center, Haifa, Israel.

Stents are widely use in endoscopic urological procedures. One of the most important indications is the treatment of urinary tract strictures. Allium™ Medical has introduced several types of stents for the treatment of different types of urinary tract strictures, based on anatomic location. All the stents are made of nitinol and coated with a co-polymer that reduces encrustations. These stents are self-expandable and have a large caliber and a high radial force. They have different shapes, designed especially for the treatment of each type of stricture. One of the most important features of Allium-manufactured stents is the ease of removal, due to their special unraveling feature. The company has introduced the Bulbar Urethral Stent (BUS) for treatment of bulbar urethral strictures; a rounded stent available in different lengths. Initial data on 64 patients with bulbar urethral stricture treated with the BUS showed a significant improvement in symptoms, with minimal complications and few adverse events. For treatment of prostate obstruction in patients unfit for surgery or unwilling to undergo a classical prostatic surgery, the Triangular Prostatic Stent (TPS) was introduced, which has a triangular shape that fits in the prostatic urethra. Its body has a high radial force attached to an anchor (which prevents migration) through a trans-sphincteric wire (which reduces incontinence rate). Initial data on 51 patients showed significant improvement in symptoms and in urinary peak flow rate, with a relatively small number of complications. The Round Posterior Stent (RPS) was designed for treatment of post radical prostatectomy bladder neck contracture. This short, round stent has an anchor, which is placed in the bladder neck. This stent being relatively new, the clinical data are still limited. Ureteral strictures can be treated with the Ureteral Stent (URS), which is round-shaped, available in different lengths, and has an anchor option (for very distal or very proximal strictures). We have previously published data on 107 URSs inserted in patients with ureteral stricture due to several etiologies, including patients who failed previous treatment. All patients were asymptomatic for a long period of follow-up after stent removal, with only one case of re-stenosis. In this paper, we review the urological "covered" stents produced by Allium Medical with the relevant clinical data available at the present time.
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http://dx.doi.org/10.5041/RMMJ.10313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652934PMC
October 2017

Histopathologic Differences between Jewish and Arab Population in Israel at First-Time Presentation with Bladder Cancer.

Biomed Res Int 2017 24;2017:8239601. Epub 2017 Jul 24.

Department of Urology, Bnai-Zion Medical Center, Haifa, Israel.

Background: Pathology of urothelial carcinoma may vary in different populations at diagnosis. Our aim was to evaluate the histopathologic differences between Jewish and Arab patients in Israel at first diagnosis of urothelial cancer.

Patients And Methods: We retrospectively collected data of all patients with confirmed urothelial cancer, treated at our department between January 2010 and January 2015. We examined the distribution of the histopathologic data among the studied populations. To compare the categorical variables we used the Chi-Square Pearson test. Comparison of independent variables was made by Student's -test. value below 0.05 was considered significant.

Results: The study group included 413 patients, 345 Jews and 68 Arabs. The major differences were that Arab patients were younger (62.61 versus 68.55 years, = 0.001), had more aggressive tumors that were detected at a more advanced stage, and had also a higher rate of metastatic disease (7.4% versus 3.2%, = 0.05). Nonurothelial cell tumors were 2.3 times more prevalent in Arab population. Unlike Jewish population, Arab women had higher rate of invasive/metastatic disease compared with Arab men (40% versus 22.4%).

Conclusion: At time of diagnosis the tumors were more aggressive in Arab patients, especially in Arab women. The reasons for those differences constitute a target for a separate research. These results should have an impact on prevention medicine and education of physicians treating mixed populations.
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http://dx.doi.org/10.1155/2017/8239601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546079PMC
April 2018

Unraveling Antimicrobial Susceptibility of Bacterial Networks on Micropillar Architectures Using Intrinsic Phase-Shift Spectroscopy.

ACS Nano 2017 06 16;11(6):6167-6177. Epub 2017 May 16.

Department of Biotechnology and Food Engineering, ‡Department of Urology, Bnai Zion Medical Center, Faculty of Medicine, and §The Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology , Haifa 3200003, Israel.

With global antimicrobial resistance becoming increasingly detrimental to society, improving current clinical antimicrobial susceptibility testing (AST) is crucial to allow physicians to initiate appropriate antibiotic treatment as early as possible, reducing not only mortality rates but also the emergence of resistant pathogens. In this work, we tackle the main bottlenecks in clinical AST by designing biofunctionalized silicon micropillar arrays to provide both a preferable solid-liquid interface for bacteria networking and a simultaneous transducing element that monitors the response of bacteria when exposed to chosen antibiotics in real time. We harness the intrinsic ability of the micropillar architectures to relay optical phase-shift reflectometric interference spectroscopic measurements (referred to as PRISM) and employ it as a platform for culture-free, label-free phenotypic AST. The responses of E. coli to various concentrations of five clinically relevant antibiotics are optically tracked by PRISM, allowing for the minimum inhibitory concentration (MIC) values to be determined and compared to both standard broth microdilution testing and clinic-based automated AST system readouts. Capture of bacteria within these microtopologies, followed by incubation of the cells with the appropriate antibiotic solution, yields rapid determinations of antibiotic susceptibility. This platform not only provides accurate MIC determinations in a rapid manner (total assay time of 2-3 h versus 8 h with automated AST systems) but can also be employed as an advantageous method to differentiate bacteriostatic and bactericidal antibiotics.
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http://dx.doi.org/10.1021/acsnano.7b02217DOI Listing
June 2017

Laparoscopic Surgery of Urachal Anomalies: A Single-Center Experience.

Isr Med Assoc J 2016 Nov;18(11):673-676

Department of Urology, Bnai Zion Medical Center, Haifa, Israel.

Background: The traditional surgical approach to the excision of persistent urachal remnants is a lower midline laparotomy or semicircular infraumbilical incision.

Objectives: To report our experience with laparoscopic/open urachus excision as a minimally invasive diagnostic and surgical technique.

Methods: This was a retrospective study involving patients who were diagnosed with persistent urachus and underwent laparoscopic/open excision. The morbidity, recovery, and outcomes of surgery were reviewed.

Results: Eight patients (males:females 6:2) with an age range of 1 month to 17 years underwent laparoscopic or open excision (six and two patients respectively). All patients presented with discharge from the umbilicus. Although three patients had no sonographic evidence of a patent urachus, diagnostic laparoscopy detected a patent urachus that was excised laparoscopically. The operative time of laparoscopic surgery ranged from 19 to 71 minutes (the last case was combined with bilateral laparoscopic inguinal hernia repair), and the mean duration of hospital stay was 2.0 ± 0.36 days. Pathological examination confirmed a benign urachal remnant in all cases.

Conclusions: Laparoscopy is a useful alternative for the management of persistent or infected urachus, especially when its presence is clinically suspected despite the lack of sonographic evidence. The procedure is associated with low morbidity, although a small risk of bladder injury exists, particularly in cases of severe active inflammation.
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November 2016

Bovine serum albumin-glutaraldehyde (BioGlue) tissue adhesive standard renorrhaphy following renal mass enucleation: a retrospective comparison.

Ther Adv Urol 2017 Mar-Apr;9(3-4):67-72. Epub 2017 Feb 1.

Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel.

Background: To present the operative and post-operative comparison between patients who underwent tumor-bed closure with sutures compared with bovine serum albumin-glutaraldehyde (BioGlue) tissue sealant only.

Methods: We retrospectively analyzed data from our ongoing database of 507 eligible patients who underwent open NSS nephron-sparing surgery in our department between January 1995 and May 2014. Patients had tumor-bed closure with sealant adhesive (255 patients) or standard suture technique (252 patients). Demographic, clinical and perioperative data were compared between the two groups, by Chi-square test or by Fisher-Irwin exact test for categorical variables, and by test for differences in means or by Wilcoxon rank sum test for continuous variables. A multivariate analysis was also done.

Results: Patients' baseline characteristics showed similar distribution of the analyzed parameters among both groups, with few differences: younger age in the sealant group (65.4 68.4 years, = 0.01) and slightly larger mass size in the suture group (4.0 3.9 cm, = 0.03). Ischemia time was significantly shorter in the sealant group (21.8 27.0 minutes, = 0001). Blood loss and transfusion rate (0.8% 11.9%, = 0.0001) were significantly less in the sealant group. A multivariate analysis showed date of surgery and blood loss as the major parameters affecting transfusion rate.

Conclusions: Closing the tumor bed with BioGlue tissue adhesive is feasible, safe, can shorten ischemia time and potentially reduce transfusion rate.
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http://dx.doi.org/10.1177/1756287217697662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378098PMC
February 2017

Late-onset Uretero-vesical Junction Obstruction Following Endoscopic Injection of Bulking Material for the Treatment of Vesico-ureteral Reflux.

Urology 2017 Mar 16;101:60-62. Epub 2016 Dec 16.

Department of Urology, Bnai-Zion Medical Center, Haifa, Israel.

Objective: To characterize patients who develop late obstruction after subureteral injection of bulking agent for the treatment of pediatric vesicoureteral reflux (VUR).

Methods: We retrospectively evaluated the medical records of all patients who underwent endoscopic injection for the correction of VUR during 2008-2015 in 2 centers in Israel: Bnai-Zion Medical Center, Haifa, and Schneider Children's Medical Center, Petah Tikva. Nine patients who developed late-onset obstruction were included in the study, and their data were reviewed and analyzed.

Results: Three boys and 6 girls with mean age of 3 years were included in the study. All patients had moderate-to-high grade VUR. Following injection, all children had a radiographic evidence showing resolution of the reflux. During follow-up, patients were diagnosed with late obstruction in a mean time of 13.4 months. All patients underwent open re-implantation.

Conclusion: Late-onset obstruction may develop in patients treated with subureteral injection for VUR. Patients with high grade reflux and dilated ureters are at risk of late obstruction. Long-term follow-up with ultrasound is mandatory following endoscopic treatment of VUR.
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http://dx.doi.org/10.1016/j.urology.2016.12.018DOI Listing
March 2017

Giant Congenital Hydronephrosis Obstructing the Gastro Intestinal System and the Contralateral Kidney in a New Born.

Urol Case Rep 2016 Sep 1;8:1-3. Epub 2016 Jun 1.

Urology, Bnai-zion Medical Center, Haifa, Israel.

A 5 day old baby, with known left hydronephrosis which discovered by prenatal US presented with gastrointestinal tract obstruction. Laboratory work up demonstrated abnormal renal function and metabolic acidosis combined with hyperkalemia. Radiology tests showed bilateral hydronephrosis with huge left renal pelvis crossing the midline and causing deviation of the gut laterally. This acute presentation beside inability to receive oral feeding made us prefer immediate left renal drainage with pyelostomy in order to restore renal function, relieve the pressure effect of the huge renal pelvis and stabilize the baby. Dismembered pyeloplasty was done at age of 3 months.
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http://dx.doi.org/10.1016/j.eucr.2016.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898913PMC
September 2016

[INTERMEDIATE-TERM FOLLOW-UP OF PATIENTS UNDERGOING ACTIVE SURVEILLANCE FOR SMALL RENAL MASS: INDICATIONS FOR SURGICAL INTERVENTION].

Harefuah 2016 Jan;155(1):37-40, 67

Introduction: The increase in the use of imaging studies led to an increase in the diagnosis of small renal masses. However, most of the small renal masses are asymptomatic, grow slowly, and will not metastasize due to their relative benign biology. We still cannot differentiate malignant from benign masses using imaging studies, hence there is a dilemma between excision and follow-up.

Objective: To report our intermediate-term results of active surveillance in patients with small renal masses in our urology department at the Bnai-Zion Medical Center.

Patients And Methods: Retrospective analysis of 70 patients diagnosed at our department with renal mass < 4cm in its maximal diameter between 2003 and 2012. The maximal diameter of the masses at diagnosis was measured using computed tomography and diameter was recorded during follow-up.

Results: Seventy patients with 78 small renal masses met the inclusion criteria. Mean age at diagnosis was 68 years. The mean folow-up period was 34 months; 54 of 78 masses grew in size, of them 8 were excised. All patients who had surgery had a nephron-sparing procedure. The growth rate and the size at diagnosis were both higher in the group of patients who underwent surgery.

Conclusion: Most of the small renal masses can be managed safely by active surveillance.

Discussion: Only 4% of the masses were upstaged, and none to stage > 2. None of the patients developed metastasis or died from renal cancer during the follow-up period.

Summary: Active surveillance is a safe and reliable option for some patients with small renal mass.
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January 2016

[EPIDIDYMO-ORCHITIS IN PREPUBERTAL CHILDREN--PREVALENCE, ETIOLOGY, SUGGESTED DIAGNOSIS ALGORITHM].

Authors:
Sarel Halachmi

Harefuah 2015 Dec;154(12):799-803

Gonadal inflammation (GI) is a common disease that may affect prepubertal boys. Neonates may suffer from bacterial infection due to congenital or aging processes affecting the urinary tract. This inflammatory process is also prevalent in prepubertal boys. However, in this group, the etiology, the needed imaging modalities and proper management have not yet been clearly defined. This manuscript will systematically review the various etiologies causing GI in pre-pubertal boys, discuss the proper imaging needed, and image interpretation and will provide treatment and follow-up recommendations.
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December 2015

[MULTICENTER EXPERIENCE WITH ALLIUM URETERAL STENT FOR THE TREATMENT OF URETERAL STRICTURE AND FISTULA].

Harefuah 2015 Dec;154(12):753-6, 806

Introduction: Chronic ureteral stricture and ureteral fistula are treated with urinary diversion using percutaneous nephrostomy or double pigtail stent. Both of these techniques require replacement of the tube every few months in order to prevent encrustations and obstruction.

Objectives: To report the long-term efficacy of the new Allium Ureteral Stent (URS) in the treatment of ureteral stricture and fistula.

Methods: The Allium URS is a newly-developed ureteral stent made of nickel-titanium (Nitinol), which is inserted in a small diameter and spontaneously expands into and preserves a large-caliber. The stent is coated with a biochemical co-polymer which prevents tissue ingrowth and incrustations. The stent is inserted antegradely or retrogradely with intraoperative x-ray guidance after dilation of the stricture. The Allium URS stent was inserted into 107 ureters of 92 patients in 5 different centers worldwide; 69 patients carried a percutaneous nephrostomy before the procedure and 38 patients had a ureteral stent. The etiologies underlying the strictures were: gynecological cancer (with or without irradiation), bladder cancer, iatrogenic stricture, ureteroileal stenosis, stricture following uretero-pelvic junction obstruction repair and iatrogenic ureteral fistula.

Results: During a mean follow-up of 27 months, only one stent was obstructed after eleven-indwelling months; 21 patients died of their primary disease carrying the stent. Stent migration was seen in 11 patients within 8 months after its insertion, and these stents were removed. In 4 patients with early stent migration, the stents were replaced. In 18 patients the stents were removed as planned after one year of indwelling time, and these patients were asymptomatic in a follow-up period of up to 59 months.

Conclusion: The results of our study show that the use of Allium URS for the treatment of ureteral strictures is feasible, safe and effective. The relative ease of its insertion could encourage its use in a wide range of other indications.

Discussion: Due to its unique structure, the Allium URS is superior to the regular pigtail stents in the treatment of ureteral strictures. Stent migration was seen in only 10.7% of the patients, mainly in patients with stricture of the mid-ureter.

Summary: The use of the Allium URS stent in the treatment of proximal and distaL ureteral strictures is safe and effective.
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December 2015

Nephron Sparing Surgery for Renal Mass: Is There Any Difference between Oncocytoma and Malignant Lesions.

Urol Int 2017 19;98(2):134-137. Epub 2016 Feb 19.

Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel.

Introduction: A relatively high proportion of patients who undergo partial or radical nephrectomy for enhancing renal mass actually have oncocytoma, a benign renal tumor. Several parameters have been shown to be typical for oncocytoma, but only a small number of patients present with these parameters. The aim of our study was to report the clinical, operative and postoperative characteristics of patients who underwent nephron-sparing surgery in our center with a histopathological diagnosis of oncocytoma compared to patients with malignant renal tumor.

Patients And Methods: Sixty-three out of 530 patients who underwent nephron-sparing surgery for enhancing renal mass were diagnosed with oncocytoma. Clinical and radiological features and operational data of these patients were compared with patients who had malignant renal tumors.

Results: Mean age of patients with histologically proven non-malignant oncocytoma was significantly higher than that in patients with malignant renal cell carcinoma (66.7 vs. 61.4 years). All other analyzed variables showed no significant difference between the 2 groups.

Conclusions: No reliable clinical, operative or radiological parameters can differentiate preoperatively between oncocytoma and malignant renal neoplasms.
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http://dx.doi.org/10.1159/000444332DOI Listing
October 2017

Endothelial Function Assessment in Patients with Erectile Dysfunction.

Isr Med Assoc J 2015 Nov;17(11):682-6

Background: Erectile dysfunction (ED), a common problem in males of all ages, can be of organic, psychogenic or combined etiology. Organic ED is mainly caused by vascular and neurological disorders. One of the available tests for differentiating organic from inorganic ED is measuring penile tumescence and rigidity during the REM phase of sleep. However, this test lacks the ability to differentiate between a vascular and non-vascular cause of organic ED.

Objectives: To compare the results of the EndoPAT test and the nocturnal penile tumescence (NPT) test in patients with erectile dysfunction.

Methods: Twenty patients with ED were recruited for the study. Each participant was evaluated by the SHIM score, RigiScan during polysomnography, and two EndoPAT tests (at the beginning and end of the study).

Results: Seventeen patients had a SHIM score 21; 4 of them had organic ED with a mean EndoPAT score of 1.49, significantly lower than the 1.93 mean EndoPAT score of the 11 patients in the psychogenic ED group (P = 0.047). Two participants had a neurological impairment (spinal trauma and herniated disk). The average SHIM score in the vascular organic group was 6.25 points as compared to 11.69 for the psychogenic group (P = 0.027). The positive predictive value was 43% and the negative predictive value 90%.

Conclusions: EndoPAT could be helpful in excluding organic ED.
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November 2015

The role of hyperthermia as a treatment for non-muscle invasive bladder cancer.

Expert Rev Anticancer Ther 2016 19;16(2):189-98. Epub 2015 Dec 19.

a Department of Urology, Bnai-Zion Medical Center, Faculty of Medicine , Technion- Institute of Technology , Haifa , Israel.

Non-muscle invasive bladder cancer (NMIBC) has a high tendency for recurrence and progression. Currently, all known intravesical agents are associated with adverse effects (AEs) and limited efficacy. The combination of hyperthermia (HT) with intravesical Mitomycin C (MMC) chemotherapy has been shown to improve outcomes. The added efficacy of HT to MMC was first shown in preclinical studies. The reports on patients with NMIBC have indicated that the treatment is safe and well tolerated. Several clinical studies reported the efficacy of radiofrequency-induced chemotherapy effect (RITE) in the treatment of patients with NMIBC. This modality was shown to be superior to MMC alone. RITE was effective also in patients with high-risk NMIBC, including those who failed Bacillus Calmette-Guérin (BCG). This study provides an updated review of literature regarding the use of RITE in patients with NMIBC.
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http://dx.doi.org/10.1586/14737140.2016.1126515DOI Listing
September 2016

Allium™ TPS--A New Prostatic Stent for the Treatment of Patients with Benign Prostatic Obstruction: The First Report.

J Endourol 2016 Mar 17;30(3):319-22. Epub 2015 Nov 17.

2 Department of Urology, Faculty of Medicine, Bnai-Zion Medical Center, Technion Institute of Technology , Haifa, Israel .

Introduction: Several prostatic stents were developed in the last three decades, none of which were able to provide a real alternative in patients unfit or unwilling to undergo classical prostatic surgeries. In this study, we report the results of the use of a newly developed prostatic stent--the Allium™ Triangular Prostatic Stent (TPS).

Patients And Methods: The Allium TPS is a highly flexible, nitinol-built polymer-covered stent, which prevents tissue ingrowth and reduces encrustations. Between 2008 and 2014, at two centers (Israel and Turkey), the stent was inserted under local or regional anesthesia in 51 patients with benign prostatic obstruction (BPO) who are unwilling or unfit for surgery. Patients were followed for 12 months from surgery. The primary outcome was symptom improvement as measured by the international prostate symptom score (IPSS) and improvement in peak urinary flow.

Results: Stent insertion was successful in all patients. The mean IPSS decreased from 26.4 to 7.7 on the last follow-up. The mean peak flow increased from 5.5 mL/second before stent insertion to 16.0 mL/second 1 year thereafter. The main adverse effect was transient pain in nine patients. No stent migration or obstruction was seen. Patients reported satisfaction and improvement in quality of life.

Conclusion: Our short-term results show that Allium TPS is safe and effective for the treatment of patients with BPO.
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http://dx.doi.org/10.1089/end.2015.0593DOI Listing
March 2016

Functional and oncological outcomes of open nephron-sparing surgery for complex renal masses.

Urol Oncol 2015 Oct 3;33(10):427.e11-6. Epub 2015 Jul 3.

Bnai-Zion Medical Center, Haifa, Israel; Faculty of Medicine, Technion, Haifa, Israel.

Objective: To present our long-term functional and oncological outcomes in open nephron-sparing surgery for complex renal masses.

Patients And Methods: We enrolled 584 patients who underwent open partial nephrectomy between January 1995 and May 2014 at our institution; 108 (18.4%) patients had hilar or completely intraparenchymal tumors or both. We compared change in renal function, perioperative complications, and survival outcomes between complex and noncomplex renal masses.

Results: Mean tumor diameter was 4.3 and 3.5cm in patients with hilar and completely intraparenchymal lesions, respectively. R.E.N.A.L. nephrometry scores were significantly higher in patients with complex tumors as compared with patients with exophytic tumors. There was no significant difference between mean estimated glomerular filtration rate at last follow-up compared with preoperative mean estimated glomerular filtration rate in any of the groups. The incidence of perioperative complications was similar across all patients groups. Estimated 10-year cancer-specific survival probabilities were 100% in patients with hilar and intraparenchymal tumors. The 10-year recurrence-free survival probabilities were 96% and 95% in patients with hilar and intraparenchymal tumors, respectively. The main limitations include retrospective design and the lack of kidney-specific functional scan.

Conclusion: Open nephron-sparing surgery should be considered for complex renal masses yielding excellent functional and oncological outcomes without higher incidence of complications.
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http://dx.doi.org/10.1016/j.urolonc.2015.04.016DOI Listing
October 2015

The natural history and predictors for intervention in patients with small renal mass undergoing active surveillance.

Adv Urol 2015 15;2015:692014. Epub 2015 Apr 15.

Department of Urology, Bnai Zion Medical Center, 3339414 Haifa, Israel ; Faculty of Medicine, Technion-Israel Institute of Technology, 3200003 Haifa, Israel.

Aim. To describe the natural history of small renal mass on active surveillance and identify parameters that could help in predicting the need for intervention in patients with small renal masses undergoing active surveillance. We also discuss the need for renal biopsy in the management of these patients. Methods. A retrospective analysis of 78 renal masses ≤4 cm diagnosed at our Urology Department at Bnai Zion Medical Center between September 2003 and March 2012. Results. Seventy patients with 78 small renal masses were analyzed. The mean age at diagnosis was 68 years (47-89). The mean follow-up period was 34 months (12-112). In 54 of 78 masses there was a growth of at least 2 mm between imaging on last available follow-up and diagnosis. Eight of the 54 (15%) masses which grew in size underwent a nephron-sparing surgery, of which two were oncocytomas and six were renal cell carcinoma. Growth rate and mass diameter on diagnosis were significantly greater in the group of patients who underwent a surgery. Conclusions. Small renal masses might eventually be managed by active surveillance without compromising survival or surgical approach. All masses that were eventually excised underwent a nephron-sparing surgery. None of the patients developed metastases.
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http://dx.doi.org/10.1155/2015/692014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413980PMC
May 2015

Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model.

Math Med Biol 2016 06 16;33(2):159-88. Epub 2015 Apr 16.

Quantitative Oncology and Medicine Association, Rte de l'Etoile 37, 202, Gorgier, Switzerland.

One of the treatments offered to non-invasive bladder cancer patients is BCG instillations, using a well-established, time-honoured protocol. Some of the patients, however, do not respond to this protocol. To examine possible changes in the protocol, we provide a platform for in silico testing of alternative protocols for BCG instillations and combinations with IL-2, to be used by urologists in planning new treatment strategies for subpopulations of bladder cancer patients who may benefit from a personalized protocol. We use a systems biology approach to describe the BCG-tumour-immune interplay and translate it into a set of mathematical differential equations. The variables of the equation set are the number of tumour cells, bacteria cells, immune cells, and cytokines participating in the tumour-immune response. Relevant parameters that describe the system's dynamics are taken from a variety of independent literature, unrelated to the clinical trial results assessed by the model predictions. Model simulations use a clinically relevant range of initial tumour sizes (tumour volume) and tumour growth rates (tumour grade), representative of a virtual population of fifty patients. Our model successfully retrieved previous clinical results for BCG induction treatment and BCG maintenance therapy with a complete response (CR) rate of 82%. Furthermore, we designed alternative maintenance protocols, using IL-2 combinations with BCG, which improved success rates up to 86% and 100% of the patients, albeit without considering possible side effects. We have shown our simulation platform to be reliable by demonstrating its ability to retrieve published clinical trial results. We used this platform to predict the outcome of treatment combinations. Our results suggest that the subpopulation of non-responsive patients may benefit from an intensified combined BCG IL-2 maintenance treatment.
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http://dx.doi.org/10.1093/imammb/dqv007DOI Listing
June 2016

Primary angiosarcoma of urinary bladder: 13th reported patient.

Case Rep Oncol Med 2015 26;2015:652870. Epub 2015 Jan 26.

Bnai-Zion Medical Center, 3339313 Haifa, Israel ; Faculty of Medicine, Technion Institute of Technology, 3200003 Haifa, Israel.

Angiosarcoma of the urinary bladder is an extremely rare and poorly characterized tumor. We are presenting the 13th reported patient who was an 89-year-old man initially presented with massive hematuria. His past medical history included external-beam radiation for prostate cancer 12 years ago. His PSA was 0.26 ng/dL. His CT-Urography demonstrated a highly vascular mass originating from the bladder base. The mass was partially resected, transurethrally. The pathology was consistent with primary angiosarcoma of the urinary bladder. Bone scan and CT-U showed metastasis to spine. The patient was treated with palliative radiotherapy for back pain due to metastasis, and he refused chemotherapy. The patient died 3 months after his initial diagnosis.
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http://dx.doi.org/10.1155/2015/652870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321076PMC
February 2015

Giant abdominoscrotal hydrocele obstructing the right kidney.

Isr Med Assoc J 2014 Sep;16(9):593-4

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September 2014

Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle-invasive bladder cancer.

Urol Oncol 2015 Feb 21;33(2):67.e1-7. Epub 2014 Jul 21.

Department of Urology, Bnai Zion Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Objective: Neutrophil-to-lymphocyte ratio (NLR) predicts advanced stage disease and decreased survival in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. The predictive value of NLR in non-muscle-invasive bladder cancer (NMIBC) has not been well studied. We aimed to evaluate whether NLR predicted disease recurrence and progression in NMIBC.

Materials And Methods: The medical records of 122 consecutive, newly diagnosed, patients with NMIBC treated with transurethral tumor resection, between the years 2003 and 2010, were reviewed. Patients with hematological malignancies (n = 4) and without preoperative NLR (n = 11) were excluded. Cutoff points for NLR were tested separately for recurrence and progression using the standardized cutoff-finder algorithm. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and disease recurrence and progression.

Results: The study cohort comprised 91 men and 16 women at a median age of 68 years. The median NLR was 2.85 (interquartile range: 2-3.9). In total, 68 patients (64%) had an NLR>2.41. Patients with NLR>2.41 were more often men (P = 0.02) and had T1 category tumors (P = 0.034). Analyzed as a continuous variable, higher NLR showed a weak positive association with high tumor grade (R = 0.21, P = 0.028). The median follow-up for patients without disease recurrence was 40 months (interquartile range: 23-51). The estimated 3-year progression-free survival rate in patients with an NLR>2.41 was 61%, compared with 84% in patients with an NLR≤2.41 (P = 0.004). On multivariate analysis, an NLR>2.41 (hazard ratio [HR] = 3.52; 95% CI: 1.33-9.33; P = 0.012) and high-risk tumors compared with low-intermediate-risk tumors (HR = 4.83; 95% CI: 1.31-17.77; P = 0.018), as defined by the European Organization for Research and Treatment of Cancer risk tables, were associated with disease progression. An NLR>2.43 (HR = 1.75; 95% CI: 1.05-2.92; P = 0.032) and treatment with intravesical instillations (HR = 0.49; 95% CI: 0.28-0.85; P = 0.011) were associated with disease recurrence on multivariate analysis.

Conclusions: NLR is an independent predictor of disease progression and recurrence in patients with NMIBC without hematological malignancies. Prospective studies are required to validate the role of NLR as a prognostic marker in NMIBC.
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http://dx.doi.org/10.1016/j.urolonc.2014.06.010DOI Listing
February 2015

DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer.

J Urol 2014 Jun 14;191(6):1697-702. Epub 2013 Dec 14.

Hebrew University, Jerusalem, Israel.

Purpose: H19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial.

Materials And Methods: A total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months.

Results: All patients were evaluable for adverse effects and 39 were evaluable for efficacy. Complete tumor ablation was achieved in 33% of patients and in 64% there were no new tumors at 3 months. Median time to recurrence was 11.3 months in all cases but significantly longer (22.1 months) when analyzed by response status at 3 months. Adverse events were mild. The study was limited by the small number of patients.

Conclusions: BC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.
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http://dx.doi.org/10.1016/j.juro.2013.12.011DOI Listing
June 2014

Factors associated with adverse outcome following urologic surgery in patients aged 80 years and older.

Aging Clin Exp Res 2013 Apr 3;25(1):75-9. Epub 2013 Apr 3.

Department of Anesthesiology, The Bruce Rappaport Faculty of Medicine, Rambam Health Care Campus, Technion-Israel Institute of Technology, 31096, Haifa, Israel.

Background And Aims: This study was designed to find predictors for adverse post-operative outcomes in elderly patients aged 80 years and older, who underwent urologic surgery.

Methods: In this prospective observational study, we analysed data, including age, gender, American Society of Anesthesiologists (ASA) class, co-morbidities, number of regular medications, type and extent of surgery, type of anesthesia, duration of surgery and hospitalization, post-operative morbidity and mortality. We studied the correlations between each pre- and intra-operative parameter to the consequence, to find predictors for adverse outcome.

Results: During a 12-month period, 217 patients underwent 294 urologic procedures in our institution. Ninety-eight procedures (33%) were followed by complications and 11 patients (5%) died. Patients who had uneventful surgery and hospitalization were significantly younger than those who experienced morbidity or mortality. There was a significantly higher complication rate among patients with a higher ASA class or with ischemic heart disease, following higher graded or longer operations, and after emergency surgery.

Conclusions: Older age is a significant risk factor. Patients with higher ASA class or ischemic heart disease are at higher risk for post-operative complications and thus, require careful follow-up. In this age population, extensive or prolonged surgery should be carefully considered.
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http://dx.doi.org/10.1007/s40520-013-0011-3DOI Listing
April 2013

Urinary NGAL and KIM-1: potential association with histopathologic features in patients with renal cell carcinoma.

World J Urol 2013 Dec 22;31(6):1541-5. Epub 2013 Feb 22.

Department of Surgery and Research Unit, Rambam Medical Center, 31096, Haifa, Israel.

Purpose: NGAL and KIM-1 are suggested to play a key role in the carcinogenesis and progression of renal cell carcinoma. Attention is currently focused on the potential use of the urinary level of NGAL and KIM-1(uNGAL and uKIM-1, respectively) in making an early diagnosis, establishing a prognosis and determination of the histologic characteristics.

Methods: Forty-six patients underwent surgical treatment for renal lesions (n = 37) and for non-functioning kidney (n = 9). uNGAL and uKIM-1 levels were evaluated for clear cell, papillary and chromophobe subtypes of renal cancer patient and also for the control patients. The concentrations were determined by ELISA.

Results: uNGAL and uKIM-1 in the control group were not significantly different from those of the patients with kidney cancer. There was no association between tumor size or histologic grade and the uNGAL and uKIM-1 levels. All patients with papillary type RCC had KIM-1 level below 2 ng/mgUcr and uNGAL concentration above 50 ng/mgUcr. Using the same threshold values enables prediction of 100% of patients with chromophobe subtype; 91.6% of the patients with clear cell histology have uNGAL concentration below 50 ng/mgUcr and KIM-1 concentration below 5 ng/mgUce.

Conclusion: Combined analysis of uNGAL and uKIM-1 allowed high prediction rate of the histologic subtype of the radiographic-detected masses among cases with kidney cancer. These biomarkers may enable to select the proper therapeutic agents in cases with metastatic disease without the need of pretreatment biopsy.
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http://dx.doi.org/10.1007/s00345-013-1043-1DOI Listing
December 2013