Publications by authors named "Edmond Sabo"

163 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

Diagnostic Value of C-Reactive Protein in Discrimination between Uncomplicated and Complicated Parapneumonic Effusion.

Diagnostics (Basel) 2020 Oct 15;10(10). Epub 2020 Oct 15.

Department of Internal Medicine A, Bnai Zion Medical Center, Haifa 31048, Israel.

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort.

Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD.

Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group ( < 0.0001). No significant difference was found between the two groups for levels of CRPr ( = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and < 0.0001.

Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.
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http://dx.doi.org/10.3390/diagnostics10100829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602659PMC
October 2020

Association between PSA density and pathologically significant prostate cancer: The impact of prostate volume.

Prostate 2020 12 24;80(16):1444-1449. Epub 2020 Sep 24.

Department of Urology, Rambam Health Center, Haifa, Israel.

Background: The early diagnosis of prostate cancer (PCa) is mainly based on prostate-specific antigen (PSA) blood levels and digital rectal examination. However, this approach may result in a high rate of negative biopsies and increased detection of clinically insignificant PCa (CS-PCa). An important prognostic biomarker, PSA density (PSA-D) demonstrated improved performance in PCa detection compared to PSA. The relationship between prostate volume and the prognostic accuracy of PSA-D remains mostly unclear. The aim of our study is to investigate the PSA-D predictive value of CS-PCa detection at different prostate volumes.

Methods: Using our local radical prostatectomy registry, patients were divided into three prostate size subgroups based on preoperative sonographic prostate volume assessment: less than 50, 50-75, and more than 75 cc. Patients' and PCa characteristics were recorded, including age, body mass index, PSA at diagnosis, prostate volume, PSA-D, D'Amico risk classification, Gleason grade group, and pathological staging following surgery.

Results: The study cohort included 364 patients who underwent Robotic Radical prostatectomy for biopsy-proven clinically localized PCa. 221 (61%) and 143 (39%) patients had PSA-D less than 0.15 and PSA-D more than 0.15, respectively. ISUP GG 1-2 PCa (CS-PCa) was observed in 220 patients (60%), while 144 (40%) had ISUP GG 3-5 PCa at final pathology. PSA-D correlated with CS-PCa only in small and medium-size prostates, but not in large glands (p = .03, p = .01, and p = .36, respectively). The highest sensitivity (72.7%) was observed in small prostates, compared to 3.2% in large prostates. The highest specificity (89.4%) was noted in large prostates. Positive predictive value in small and medium-size prostates was similar (~50%), compared to 20% in large glands. The negative predictive value was slightly better for small and medium-size prostates compared with large glands (68.9%, 73.7%, and 53.1%, respectively). An association between PSA-D and harboring CS-PCa was detected only in small and medium-size glands (72.7% and 43%, respectively).

Conclusion: PSA-D is associated with CS-PCa detection in radical prostatectomy specimens in small and medium-size prostates. The level of PSA-D is directly associated with the ISUP PCa grade group. Therefore, PSA-D is a beneficial, available, and cost-effective tool during decision-making in patients with small and medium-size prostate when considering treatment for PCa.
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http://dx.doi.org/10.1002/pros.24078DOI Listing
December 2020

Computerized image analysis of blood vessels within mucosal defects for the prediction of delayed bleeding following colonic endoscopic mucosal resection: a pilot study.

Endoscopy 2020 Sep 8. Epub 2020 Sep 8.

Rambam Healthcare Campus, Haifa, Israel.

BACKGROUND : Clinically significant post-endoscopic bleeding (CSPEB) is a common complication following colonic endoscopic mucosal resection (EMR). Current prediction tools are clinical and do not use the appearance of the post-EMR mucosal defect. We aimed to predict CSPEB by analyzing blood vessel morphology within the post-EMR mucosal defect. METHODS : 43 patients with CSPEB were matched to 43 non-bleeders for clinical variables associated with CSPEB. Computerized image analysis quantified the morphologic characteristics of the blood vessels in the defect. Variables were measured in relation to the mucosal defect area. Multivariate analysis and a neural network (NNET) were used as prediction models. RESULTS : The CSPEB group vessels had larger maximum diameter (113.07 vs. 69.03;  < 0.001), larger minimum radius (5.09 vs. 3.28;  = 0.002), larger perimeter value (337.82 vs. 193.86;  < 0.001), larger vessel length-of-outline (351.83 vs. 220.68;  = 0.002), and larger fractal dimension (1.11 vs. 1.10;  = 0.005) compared with non-bleeders. Discriminant analysis yielded 86 % sensitivity and 76.7 % specificity and an NNET classifier yielded 100 % sensitivity and 76.9 % specificity for identifying patients at risk. CONCLUSIONS : Blood vessel morphology in the post-EMR defect can be used to predict bleeding following colonic EMR.
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http://dx.doi.org/10.1055/a-1258-8992DOI Listing
September 2020

Spatial heterogeneity of PD-L1 expression and the risk for misclassification of PD-L1 immunohistochemistry in non-small cell lung cancer.

Lung Cancer 2020 09 13;147:91-98. Epub 2020 Jul 13.

Institute of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address:

Background: Intra-tumor heterogeneity for PD-L1 expression in non-small cell lung cancer (NSCLC) might lead to inaccurate stratification of patients to immunotherapy. The purpose of this research was to quantitate the effect of different factors on the risk of inaccurate diagnosis of PD-L1 expression.

Methods: MATLAB software was used to model tumor with a different fraction, distribution and clustering of PD-L1 protein expression and their effect on false positive and negative diagnosis in subsets of the modeled tumor (representing biopsies). Additionally, we evaluated the agreement between PD-L1 status in random segments and whole slides of PD-L1 stained clinical NSCLC cases.

Results: Our computer-based model showed a significant increase in error rate when the fraction of PD-L1 positive cells was closer to the cut-off value (error rate of 33.33 %, 0.45 % and 0.74 % for PD-L1 positivity in 40-60%, ≤20 % and ≥80 % of tumor cells, respectively, P < 0.0001). In addition, biopsy size showed negative correlation with error rate (P < 0.0001) and larger clusters of PD-L1 positive cells were associated with higher error rate (P < 0.0001). Analysis of the clinical samples supported those of the computer-based model with higher error rate in cases with positive PD-L1 expression closer to the cutoff value. Based on our computerized model and clinical analysis, we developed a model to predict error rate based on biopsy size and the fraction of PD-L1 positive cells in the biopsy.

Conclusion: Analysis of small biopsies for PD-L1 expression might be associated with significant error rate. The model presented can be used to identify cases with increased risk for error in whom interpretation of the test results should be made with caution.
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http://dx.doi.org/10.1016/j.lungcan.2020.07.012DOI Listing
September 2020

Pericardial Effusion in a Young Man: A Rare Presentation of Thymoma.

Isr Med Assoc J 2020 May;22(5):328-329

Department of Cardiology, Galilee Medical Center, Nahariya, Israel.

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May 2020

Histomorphometric Findings May Help Predicting Response in Patients with Chronic Liver Disease.

Isr Med Assoc J 2020 May;22(5):320-325

Liver Unit, Rambam Health Care Campus, affiliated with Technion-Israel Institute of Technology, Haifa, Israel.

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.
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May 2020

Persistent Extranodal Marginal Zone Lymphoma (MZL) in the Capsule of a Re-explanted Silicone Prosthesis Following Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Isr Med Assoc J 2020 02;22(2):130-131

Institute of Oncology and Hematology, Carmel Medical Center, affiliated with Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

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February 2020

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

Sleeve Gastrectomy in the Elderly.

Obes Facts 2019 14;12(5):502-508. Epub 2019 Oct 14.

General Surgery Department C, Sheba Medical Center, Ramat Gan, Israel.

Background: Even though risks are higher and long-term results may be less favorable, the elderly obese can still benefit from bariatric surgery. Whether the higher surgical risk is worth the benefits is yet to be determined.

Materials And Methods: We reviewed our database and identified all patients aged 65 or older who underwent sleeve gastrectomy between May 2010 and November 2015. We documented patient demographics, obesity-related comorbidities, body mass index (BMI) before and after the procedure, percent excess weight loss, comorbidity improvement or resolution, length of follow-up, postoperative complications, re-operations, and length of hospital stay. We compared our study group to a control group of sleeve gastrectomy patients under the age of 65.

Results: Sixty-six patients (mean age 67.6 ± 2.6 years) underwent laparoscopic sleeve gastrectomy. Patients achieved an average of 53.5% excess BMI loss (EBMIL) after 21 months of follow-up. EBMIL was inferior to that achieved by the control group (EBMIL 77.3%, p < 0.0001). Elderly patients showed significant improvement or resolution in all obesity-related comorbidities. Complication and re-operation rates were similar between the 2 groups.

Conclusion: In an elderly population, laparoscopic sleeve gastrectomy is safe and effective, yet weight loss outcomes are more modest when compared to a younger surgical population. Carefully selected elderly patients can benefit from bariatric surgery.
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http://dx.doi.org/10.1159/000502697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876611PMC
February 2020

Composite breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and extra-nodal marginal zone lymphoma (MZL) in the capsule of a silicone breast implant.

Autoimmun Rev 2019 05 4;18(5):556-557. Epub 2019 Mar 4.

The Institute of Oncology and Hematology, Technion- Israel Institute of Technology, Haifa, Israel; Lady Davis Carmel Medical Center, Bruce and Ruth Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel.

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http://dx.doi.org/10.1016/j.autrev.2019.03.014DOI Listing
May 2019

Can morphometric analysis of the fallopian tube fimbria predict the presence of uterine papillary serous carcinoma (UPSC)?

PLoS One 2019 28;14(2):e0211329. Epub 2019 Feb 28.

Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel.

Uterine serous papillary carcinoma (UPSC) is an aggressive tumor, often diagnosed as a metastatic disease and characterized by a high recurrence rate and poor prognosis. UPSC represents a distinct subtype of endometrial cancer which is different in clinical and pathological behaviors from endometrioid endometrial carcinoma (EEC) and resembles more to serous ovarian carcinoma. Since tumors of serous papillary of the ovary are hypothesized to stem from cells of the fallopian tube's fimbria, we hypothesized that UPSC may also origin in the fallopian tubes. In our previous study, using a novel method of computerized morphometry of the fimbrial epithelium we have found significant differences between fimbriae of healthy women and serous ovarian cancer patients. In this study we showed the presence of morphologic differences between twenty-four fimbriae from healthy women, and twenty six fimbriae from uterus cancer (13 from UPSC patients and 13 from EEC patients). All fimbriae reported by the pathologist as "normal" were subjected to a computerized histomorphometric analysis. Two-step method of computerized histomorphometry, i.e. Fast Fourier transformation (FFT) followed by a co-occurrence matrix analysis and an additional analysis of the nuclear symmetry of the tubal fimbrial epithelium were applied. Using these novel methods, we were able to show differences in the morphometric characteristics of the fimbriae in UPSC patients compared to EEC and healthy patients. It is yet to be determined the clinical significance of this observation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211329PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394988PMC
November 2019

Effect of weaning age on the small intestine mucosa of rats.

Appl Physiol Nutr Metab 2019 Sep 28;44(9):985-989. Epub 2019 Jan 28.

Rappaport Family Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.

Weaning of mammalian progeny is associated with a change in food composition and mother-offspring separation. Weaning results in a critical period of low voluntary feed intake, during which the animal is adapting to the starter diet. To evaluate the effects of weaning age on morphological changes that occur in the intestines of rats, we assessed intestinal histomorphometry and somatic growth in 21-days-old pups and 90-days-old mature rats that had been weaned early (day 16), normally (day 21), or late (day 26). Early weaning resulted in deeper crypts, lower villous/crypt ratio, and a smaller villous area on day 21. Crown-tail length correlated positively with the crypt depth and negatively with the villous/crypt ratio. At age 90 days, early weaned animals had shallower crypts, a greater villous/crypt ratio, and a smaller villous area compared with their normally weaned counterparts. The rats' crown-tail length correlated negatively with the crypt depth and positively with the villous/crypt ratio. Early weaning significantly affects the intestinal mucosa, which may impact food absorption and lead to differences in somatic growth compared with late weaning. Over time there may be a phase of compensation with increased villus height and crypt depth.
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http://dx.doi.org/10.1139/apnm-2018-0454DOI Listing
September 2019

Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis.

Cell Rep 2018 09;24(12):3296-3311.e6

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Technion Integrated Cancer Center, Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, 31096, Israel. Electronic address:

Inflammatory bowel disease (IBD) is prevalent, but the mechanisms underlying disease development remain elusive. We identify a role for the E3 ubiquitin ligase RNF5 in IBD. Intestinal epithelial cells (IECs) express a high level of RNF5, while the colon of Rnf5 mice exhibits activated dendritic cells and intrinsic inflammation. Rnf5 mice exhibit severe acute colitis following dextran sodium sulfate (DSS) treatment. S100A8 is identified as an RNF5 substrate, resulting in S100A8 ubiquitination and proteasomal-dependent degradation that is attenuated upon inflammatory stimuli. Loss of RNF5 from IECs leads to enhanced S100A8 secretion, which induces mucosal CD4 T cells, resulting in Th1 pro-inflammatory responses. Administration of S100A8-neutralizing antibodies to DSS-treated Rnf5 mice attenuates acute colitis development and increases survival. An inverse correlation between RNF5 and S100A8 protein expression in IECs of IBD patients coincides with disease severity. Collectively, RNF5-mediated regulation of S100A8 stability in IECs is required for the maintenance of intestinal homeostasis.
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http://dx.doi.org/10.1016/j.celrep.2018.08.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185744PMC
September 2018

SATB2 and Hep Par 1 Immunohistochemistry Is Helpful in Distinguishing Between Inflamed and Architecturally Altered Ileal Pouch and Rectal Cuff Mucosa.

Int J Surg Pathol 2019 Apr 7;27(2):159-165. Epub 2018 Sep 7.

2 Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The management of patients with ulcerative colitis after proctocolectomy with ileal pouch-anal anastomosis includes independent histological assessments of inflammation in the ileal pouch and the rectal cuff. However, the distinction between pouchitis and cuffitis can be impeded both endoscopically and histologically by the combined effects of inflammation and regeneration. We investigated the use of 2 markers, hepatocyte paraffin 1 (Hep) and SATB2 (special AT-rich sequence-binding protein 2), which are expressed immunohistochemically in the small and large bowel epithelium, respectively, as ancillary methods to deal with this problem. Immunohistochemical staining was performed retrospectively on 20 consecutive pairs of post-ileal pouch-anal anastomosis biopsies with varying degrees of histological inflammation and architectural distortion, which had each been designated as "ileal pouch" or "rectal cuff" by the referring endoscopists. Expression was graded as focal (10% to 74% stained cells) or diffuse (75% to 100%). Among the ileal pouch biopsies, 20 (100%) expressed Hep either diffusely (75%) or focally (25%), whereas SATB2 staining was either negative in 15 (75%) or focal in 5 (25%), the latter group all expressing Hep diffusely. Among the rectal cuff biopsies, 14 expressed SATB2 diffusely. Of these, Hep was either negative in 11 (79%) or focally positive in 3 (21%), the latter group all expressing SATB2 diffusely. Six ostensibly rectal cuff biopsies (30%) expressed Hep diffusely and were negative for SATB2, suggesting endoscopic misidentification. None of the 40 biopsies expressed both markers diffusely. We conclude that in doubtful cases, diffuse expression of either Hep or SATB2 can be helpful in discriminating between ileal pouch and rectal cuff mucosa, respectively.
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http://dx.doi.org/10.1177/1066896918797429DOI Listing
April 2019

Effects of Timing of Extracorporeal Shock Wave Therapy on Mandibular Distraction Osteogenesis: An Experimental Study in a Rat Model.

J Oral Maxillofac Surg 2019 Mar 24;77(3):629-638. Epub 2018 Jul 24.

Department Head, Department of Oral and Maxillofacial Surgery, Rambam Medical Care Center, Haifa, Israel; and Ruth & Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Purpose: Distraction osteogenesis (DO) is an established method for bone lengthening in the craniofacial skeleton. Its major drawback is the long consolidation period with attendant morbidity and possible complications. Several methods have been suggested to shorten the consolidation period. We evaluated the timing and effects of extracorporeal shock wave therapy (ESWT) on bone mineralization and extracellular bone matrix proteins during mandibular DO.

Materials And Methods: Twenty-seven rats underwent mandibular DO (latency period, 3 days; distraction period, 10 days; 0.5 mm/day) and were divided into 3 groups according to the timing of ESWT application: group I (control) received no treatment, whereas groups II and III received ESWT (0.18 mJ/mm) before and after the active distraction period, respectively. The distracted mandibles were harvested after 4 weeks of consolidation and analyzed radiographically, histologically, and immunohistochemically.

Results: Group III showed significantly increased mineral density, enhanced bone formation, a higher collagen orientation index, and greater expression of type I collagen and osteocalcin proteins.

Conclusions: Application of ESWT after active distraction enhances bone maturation and mineralization.
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http://dx.doi.org/10.1016/j.joms.2018.07.018DOI Listing
March 2019

Severe cytomegalovirus enterocolitis developing following daratumumab exposure in three patients with multiple myeloma.

Eur J Haematol 2018 Aug 18. Epub 2018 Aug 18.

Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel.

Objectives: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib-based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT.

Methods: We herein report three cases of heavily pretreated MM patients, receiving daratumumab-containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV-related gastrointestinal disease.

Results: All the three patients had a prolonged CMV disease course requiring a long-term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis.

Conclusion: Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow-up is needed to explore long-term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients.
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http://dx.doi.org/10.1111/ejh.13164DOI Listing
August 2018

Characterization of Factors Affecting the Detection Limit of EGFR p.T790M in Circulating Tumor DNA.

Technol Cancer Res Treat 2018 01;17:1533033818793653

1 Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objective: Circulating tumor DNA is a promising noninvasive tool for cancer monitoring. One of the challenges in applying this tool is the detection of low-frequency mutations. The detection limit of these mutations varies between different molecular methods. The aim of this study is to characterize the factors affecting the limit of detection for epidermal growth factor receptor p.T790M mutation in circulating tumor DNA of patients with lung adenocarcinoma.

Methods: DNA was extracted from plasma samples of 102 patients. For sequencing the DNA, we used 2 different next-generation sequencing-based platforms: Ion Torrent Personal Genome Machine (56 cases) and Roche/454 (46 cases). Serially diluted synthetic DNA samples carrying the p.T790M mutation were sequenced using the Ion Torrent Personal Genome Machine for validation. Limit of detection was determined through the analysis of non-hot-spot nonreference reads, which were regarded as sequencing artifacts.

Results: The frequency of the non-hot-spot nonreference reads was higher in Ion Torrent Personal Genome Machine compared to Roche/454 (0.07% ± 0.08% and 0.03% ± 0.06%, respectively, P < .001). We found that different base type substitutions occur with different frequency. Since the base substitution leading to p.T790M mutation is C>T transition, its frequency was used to determine the limit of detection for the assay. Based on the C>T non-hot-spot nonreference allele frequency, we found that the limit of detection is 0.18% in Ion Torrent Personal Genome Machine and 0.1% in Roche/454. Based on these values, 48% and 56% of the cases were positive for T790M mutation in Ion Torrent Personal Genome Machine and Roche/454 groups, respectively. Agreement between duplicates was 76% in Ion Torrent Personal Genome Machine and 72% in Roche/454. Using serially diluted synthetic DNA samples carrying the p.T790M mutation, we could identify mutations with allele frequency of 0.18% or more using the Ion Torrent Personal Genome Machine, supporting our approach to determine the detection limit.

Conclusion: Both the sequencing platform and the specific nucleotide change affect the limit of detection and should therefore be determined in the validation process of new assays.
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http://dx.doi.org/10.1177/1533033818793653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090485PMC
January 2018

Heparanase inhibition attenuates atherosclerosis progression and liver steatosis in E mice.

Atherosclerosis 2018 09 24;276:155-162. Epub 2018 Jul 24.

Department of Internal Medicine E, Rambam Health Care Campus and Rappaport Faculty of Medicine Haifa, Israel; Lipid Research Laboratory, Rappaport Faculty of Medicine, Technion, Haifa, Israel. Electronic address:

Background And Aims: Increased oxidative stress is associated with accelerated atherosclerosis. Emerging evidence highlights the role of heparanase in atherogenesis, where heparanase inhibitor PG545 reduces oxidative stress in apolipoprotein E deficient mice (E mice). Herein, we studied the effects of PG545 on atherosclerosis progression in E mice.

Methods: Male E mice fed a high-fat diet (n = 20) were divided into 3 groups treated with weekly intraperitoneal injections of either low (0.2 mg/mouse) or high dose (0.4 mg/mouse)PG545 or normal saline (controls) for twelve weeks. Body weight and food intake were measured weekly. At the end of the treatment period, blood pressure was measured, animals were sacrificed and serum samples were collected and assessed for biochemical parameters and oxidative stress. Aortic vessels and livers were collected for atherosclerotic plaques and histopathological analysis, respectively.

Results: Blood pressure decreased in mice treated with low, but not high dose of PG545. In addition, heparanase inhibition caused a dose-dependent reduction in serum oxidative stress, total cholesterol, low-density lipoproteins, triglycerides, high-density lipoproteins, and aryl esterase activity. Although food intake was not reduced by PG545, body weight gain was significantly attenuated in PG545 treated groups. Both doses of PG545 caused a marked reduction in aortic wall thickness and atherosclerosis development, and liver steatosis. Liver enzymes and serum creatinine were not affected by PG545.

Conclusions: Heparanase inhibition by PG545 caused a significant reduction in lipid profile and serum oxidative stress along with attenuation of atherosclerosis, aortic wall thickness, and liver steatosis. Moreover, PG545 attenuated weight gain without reducing food intake. Collectively, these findings suggest that heparanase blockade is highly effective in slowing atherosclerosis formation and progression, and decreasing liver steatosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.026DOI Listing
September 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

Semaphorin3A: A Potential Therapeutic Tool for Lupus Nephritis.

Front Immunol 2018 4;9:634. Epub 2018 Apr 4.

The Division of Allergy and Clinical Immunology, Bnai-Zion Medical Center, Haifa, Israel.

Background: The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechanisms.

Objectives: This study was designed in order to assess the possible therapeutic benefits of sema3A following its injection into female NZB/W mice.

Methods: Forty-eight NZB/W mice were recruited for this study. Thirty mice were treated as a "prevention group" and 18 were used as a "treatment group." Eight-week-old mice were acclimated and then divided into the two abovementioned groups.

Results: The injection of sema3A into young mice (at week 12) before the onset of disease (the prevention group) delayed the appearance of proteinuria. Here, the median time to severe proteinuria was 110 days, 95% CI: 88-131. However, in mice in which the empty vector was injected, the median time to severe proteinuria was 63 days, 95% CI: 0-139. sema3A treatment, significantly reduced renal damage, namely, it prevented the deposition of immune complexes in the glomeruli. When sema3A was injected at the onset of proteinuria (the treatment group), aiming to treat rather than to prevent disease in these mice, survival was increased and the deterioration of proteinuria was delayed.

Conclusion: Semaphorin3A is highly beneficial in reducing lupus nephritis in NZB/W mice. It delays the appearance and deterioration of proteinuria, and increases the survival rates in these mice. The regulatory mechanisms of sema3A involve both innate and adaptive immune responses. Further studies will establish the idea of applying sema3A in the treatment of lupus nephritis.
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http://dx.doi.org/10.3389/fimmu.2018.00634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893899PMC
June 2019

The impact of comorbidities, sex and age on the occurrence of acute kidney injury among patients undergoing nephron-sparing surgery.

Ther Adv Urol 2018 Mar 8;10(3):103-108. Epub 2018 Jan 8.

Department of Urology, Bnai Zion Hospital, Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Background: The aim of this study was to report the impact of patients' baseline characteristics on the incidence of acute kidney injury (AKI) after nephron-sparing surgery (NSS) for localized kidney cancer.

Patients And Methods: Data from our kidney cancer database were retrospectively extracted to include 402 patients who underwent NSS between March 2000 and June 2016, and had sufficient data. Definition of AKI was based on the postoperative serum creatinine levels and estimated glomerular filtration rate (eGFR) magnitude, which were measured during the 72 h after surgery.

Results: Based on RIFLE and AKIN criteria, the overall rate of postoperative AKI was 35%. The average decrease in eGFR among patients who developed AKI was 20% as compared with the non-AKI subgroup (2%). In univariate analysis, variables that were associated with AKI included right-sided tumors ( = 0.014), male sex ( = 0.01), hypertension ( = 0.003), baseline eGFR ( = 0.009) and history of nephrolithiasis ( = 0.039). However, multivariate analysis revealed that the only independent predictors of postoperative AKI were hypertension ( = 0.009) and cigarette smoking ( = 0.024).

Conclusion: AKI is a common complication of NSS affecting about one-third of the patients. The most important risk factors are hypertension and smoking.
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http://dx.doi.org/10.1177/1756287217747190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896859PMC
March 2018

Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD.

Gut 2019 04 4;68(4):604-614. Epub 2018 Apr 4.

Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Objective: Although anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value.

Design: We analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition. Insights from this in silico approach were experimentally validated in biopsies and blood samples of three independent test cohorts.

Results: We found the proportion of plasma cells as a robust pretreatment biomarker of non-response to therapy, which we validated in two independent cohorts of immune-stained colon biopsies, where a plasma cellular score from inflamed biopsies was predictive of non-response with an area under the curve (AUC) of 82%. Meta-analysis of the cell proportion-adjusted gene expression data suggested that an increase in inflammatory macrophages in anti-TNFα non-responding individuals is associated with the upregulation of the triggering receptor expressed on myeloid cells 1 (TREM-1) and chemokine receptor type 2 (CCR2)-chemokine ligand 7 (CCL7) -axes. Blood gene expression analysis of an independent cohort, identified TREM-1 downregulation in non-responders at baseline, which was predictive of response with an AUC of 94%.

Conclusions: Our study proposes two clinically feasible assays, one in biopsy and one in blood, for predicting non-response to anti-TNFα therapy prior to initiation of treatment. Moreover, it suggests that mechanism-driven novel drugs for non-responders should be developed.
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http://dx.doi.org/10.1136/gutjnl-2017-315494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580771PMC
April 2019

Clinical significance of preoperative imaging in oral squamous cell carcinoma compared with lymph node status: a comparative retrospective study.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 05 11;125(5):423-430. Epub 2017 Dec 11.

Attending at the Department Maxillofacial Surgery, Rambam Medical Campus; and Head of the Oral Cancer Research Laboratory, The Faculty of Medicine, Technion, Haifa, Israel.

Objective: The accuracy and sensitivity of commonly used imaging modalities in evaluating oral cavity cancer was evaluated by comparing the preoperative radiologic findings and the postoperative pathology report.

Study Design: Patients with oral squamous cell carcinoma, who had undergone at least 1 imaging test 2 weeks before surgery were included. Radiologic findings were compared with the dissected neck findings to assess the lymph node status. Sensitivity and specificity of the imaging modalities were calculated by using the χ test.

Results: Sensitivities for detecting metastatic neck lymph nodes at a threshold of 1 cm were 48% (P = .02) and 43.8% (P = .3) for computed tomography (CT) and magnetic resonance imaging respectively. Specificities were 76.3% and 70%, respectively. As for the 1.5 cm threshold, sensitivities were 36% (P = .002) and 31.3% (P = .5), respectively, and specificities were 91.5% and 76.7%, respectively. PET-CT was the most sensitive modality in the present study, with a P value of .02.

Conclusions: The different studied imaging modalities used for preoperative neck staging are not sensitive enough and would lead to underdiagnoses of a significant proportion of patients. Thus, prophylactic neck dissection for occult neck disease is of extreme importance and remains the gold standard for oral cancer treatment.
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http://dx.doi.org/10.1016/j.oooo.2017.11.021DOI Listing
May 2018

The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma.

Med Oncol 2018 Jan 31;35(3):25. Epub 2018 Jan 31.

Division of Oncology, Rambam Health Care Campus, Haifa, Israel.

Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy. The study included 30 patients with melanoma and 26 with NSCLC. An association was found between CD8+/CD4+ TILs ratio and response to anti-PD1 treatment in both cancers. Regarding melanoma patients, ratios of CD8+/CD4+ lower than 2 predicted lack of response to treatment (0%) (p = 0.006), while CD8+/CD4+ ratios higher than 2.7 had an 81.3% response rate (p = 0.0001). In addition, we found that the presence of more than 1900/mm of CD8+ lymphocytes in the melanoma tumor predicted a 90% response to therapy. In the metastatic NSCLC group, tumors with CD8+ lymphocyte count under 886/mm showed low response rates (16.7%, p = 0.046). When the CD8+ lymphocyte count was in the range of 886-1899/mm, the response rate was high (60%, p = 0.017). In CD8+/CD4+ ratios lower than 2, the response rate was low (13.3%), and in ratios higher than 2, response rates ranged between 43 and 50% (p = 0.035). The use of CD8+/CD4+ TILs ratios in tumor biopsies may predict response to anti-PD1 treatment in metastatic melanoma and NSCLC.
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http://dx.doi.org/10.1007/s12032-018-1080-0DOI Listing
January 2018

PAX8 activates a p53-p21-dependent pro-proliferative effect in high grade serous ovarian carcinoma.

Oncogene 2018 04 30;37(17):2213-2224. Epub 2018 Jan 30.

Clinical Research Institute at Rambam, Division of Oncology, Rambam Health Care Campus, Technion-Israel Institute of Technology, Haifa, Israel.

High grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer and it is now widely accepted that this disease often originates from the fallopian tube epithelium. PAX8 is a fallopian tube lineage marker with an essential role in embryonal female genital tract development. In the adult fallopian tube, PAX8 is expressed in the fallopian tube secretory epithelial cell (FTSEC) and its expression is maintained through the process of FTSEC transformation to HGSC. We now report that PAX8 has a pro-proliferative and anti-apoptotic role in HGSC. The tumor suppressor gene TP53 is mutated in close to 100% of HGSC; in the majority of cases, these are missense mutations that endow the mutant p53 protein with potential gain of function (GOF) oncogenic activities. We show that PAX8 positively regulates the expression of TP53 in HGSC and the pro-proliferative role of PAX8 is mediated by the GOF activity of mutant p53. Surprisingly, mutant p53 transcriptionally activates the expression of p21, which localizes to the cytoplasm of HGSC cells where it plays a non-canonical, pro-proliferative role. Together, our findings illustrate how TP53 mutations in HGSC subvert a normal regulatory pathway into a driver of tumor progression.
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http://dx.doi.org/10.1038/s41388-017-0040-zDOI Listing
April 2018

Mutant Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

Oncologist 2018 05 25;23(5):566-572. Epub 2018 Jan 25.

Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Background: Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of hotspot mutations in PDAC suggests that mutant can be an efficient ctDNA marker for PDAC monitoring.

Subjects, Materials, And Methods: Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival.

Results: Plasma mutations were detected in 5/17 (29.4%) patients. ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival.

Conclusion: Our results confirm that mutant ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring.

Implications For Practice: Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers, suggest that ctDNA can be an effective marker for disease monitoring and that ctDNA level over time is a better predictor of survival than the dynamics of the commonly used biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring PDAC treatment response. These results should be further validated in larger sample numbers.
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http://dx.doi.org/10.1634/theoncologist.2017-0467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947453PMC
May 2018

Evaluation of Microscopic Changes in Fallopian Tubes of BRCA Mutation Carriers by Morphometric Analysis of Histologic Slides: A Preliminary Pilot Study.

Int J Gynecol Pathol 2018 Sep;37(5):460-467

Department of Obstetrics and Gynecology (A.A., P.I., R.A., M.E., K.G.) Institute of Pathology (S.E., Z.Y., K.G.), Rambam Health Care Campus Technion-Israel Institute of Technology, Faculty of Medicine (S.E., Z.Y., T.E.), Haifa, Israel.

Mutations in BRCA genes increase the risk of ovarian cancer, yet no method for early diagnosis is available. Some serous ovarian tumors are hypothesized to stem from cells of the fallopian tube fimbria. Using a novel method of computerized morphometry of the fimbrial epithelium, this study aimed to detect morphologic differences in noncancerous fimbriae between BRCA mutation carriers and noncarriers, and between healthy and serous ovarian cancer patients. Twenty-four fimbriae from healthy women (13 BRCA+, 11 BRCA-) and 21 fimbriae from women with serous ovarian cancer (10 BRCA+, 11 BRCA-), all reported as "normal" by hematoxylin and eosin examination, were subjected to computerized histomorphometric analysis. A Fast Fourier Transformation was applied to images of fimbrial epithelium and the Fast Fourier Transformation 2-dimensional frequency maps were subsequently quantified for nuclear orientation and planar distribution by a cooccurrence matrix analysis. Additional analysis of nuclear contour was applied to the fimbriae of the healthy women. Among the healthy women, significant differences were found in morphometric characteristics between the BRCA mutation carriers and noncarriers. Among the women with ovarian cancer, no significant differences were found between BRCA mutation carriers and noncarriers. Between healthy women and those with ovarian cancer, significant differences were detected, regardless of BRCA mutational status. A novel method, which combined Fast Fourier Transformation with cooccurrence matrix analysis, demonstrated differences in morphometric characteristics in the fimbriae between healthy and ovarian cancer patients, and between BRCA mutation carriers and noncarriers. The clinical significance of these observations should be investigated.
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http://dx.doi.org/10.1097/PGP.0000000000000440DOI Listing
September 2018

Early histological findings may predict the clinical phenotype in Crohn's colitis.

United European Gastroenterol J 2017 Aug 21;5(5):694-701. Epub 2016 Oct 21.

Department of Pathology, Rambam Health Care Campus, Haifa, Israel.

Background And Aims: Predicting the clinical course of Crohn's disease (CD) is relevant for treatment selection. Currently, such diagnostic tools are lacking. In a previous pilot study, morphometric tissue image analysis showed promise in predicting the clinical phenotype and need for surgery. In this study, we aimed to validate our previous results on a larger cohort.

Methods: Colonic biopsies from CD patients with colonic or ileocolonic disease and at least five years of post-biopsy clinical follow-up were analyzed. The results were used to predict post-biopsy clinical phenotypes and outcomes. Data analysis was performed using multivariate regression models, discriminant score (DS) computations and Neural Network (NNET).

Results: Multivariate analysis of morphometric variables differentiated between B1 and B2 phenotypes (sensitivity 81%, specificity 74%, accuracy on cross-validation 75%; area under the curve (AUC) of 0.74 (CI 0.6-0.84; NNET model sensitivity 87%, specificity 67% on the testing population)). Differentiation between B1 and B3 phenotypes was also possible (sensitivity 69%, specificity 76%, accuracy 70.5% on cross-validation; AUC 0.78 (CI 0.68-0.89); NNET model sensitivity 78%, specificity 77% on the testing population)). Differentiating between B2 and B3 phenotypes was not possible using morphometric variables. Multivariate analysis predicted surgery (sensitivity 67%, specificity 72.5%, accuracy 69%; AUC 0.72 (CI 0.61-0.82); NNET model sensitivity 80%, specificity 91% on the testing population)).

Conclusions: This study validates previous results and suggests that morphometric image analysis of early biopsies from Crohn's colitis patients may contribute to the prediction of future outcomes such as clinical phenotype and surgery. Prospective validation on larger cohorts is still needed.
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http://dx.doi.org/10.1177/2050640616676435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548348PMC
August 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