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Jacob Pe'er

Publications and source records attributed to Jacob Pe'er.

At least 19 recordsLinked to original sources
PubMed2006

Apoptosis inhibitor, survivin, in posterior uveal melanoma: comparison among primary tumors, tumors resistant to brachytherapy, tumors with liver metastases, and liver metastases.

PURPOSE: To study the expression of survivin, an apoptosis inhibitor protein, in human posterior uveal melanoma. METHODS: Specimens were divided according to eyes with tumors that were enucleated primarily, those resistant to brachytherapy, eyes from patients with known liver metastases, and liver metastases. RESULTS: There was only low expression of survivin in uveal melanoma. No difference in survivin positive cell counts per high power field (PCC/HPF) were found among tumors that were enucleated primarily (n = 33), tumors with previous brachytherapy (n = 29), tumors with liver metastases (n = 12) or liver metastases (n = 18). Corresponding counts were 11.8 (+/-14.3), 11.8 (+/-16.8), 7.1 (+/-11.2), and 4.7 (+/-8.8) in the four groups, respectively (p > 0.05). Half of the liver metastases showed no staining for survivin. Twenty patients (24%) had tumor-related death at the end of follow-up. CONCLUSIONS: Survivin is expressed in posterior uveal melanomas that were treated by enucleation, as well as in tumors that were previously treated with brachytherapy or liver metastases; however, its expression by immunostaining did not seem with correlate with the tumor biological activity.

Adult↗
PubMed2006

Iris melanoma: a case report and review.

Iris melanoma is a rare ocular tumour, which can be detected early in its development. This tumour is almost always unilateral and arises usually from a pre-existing naevus. Failure to detect it may be associated with morbid ocular and systemic complications, yet there are successful therapies to treat this condition, if detected early. The patient presented to the eye clinic with symptoms of occasional, brief loss of vision in his left eye for a few weeks prior to his visit. Slit-lamp examination revealed a mass on the inferior part of the iris of the left eye. Intra-ocular pressure measurements were RE 15 mmHg and LE 38 mmHg. It was found that a tumour had spread throughout the iris stroma and invaded the anterior chamber angle. Although enucleation would have been the treatment of choice in the past, the trend today in the treatment of a growing, large circumscribed iris tumour is to excise it. It was successfully excised by irido-cyclo-trabeculectomy.

Aged↗
PubMed2006

Measurement of choroidal melanoma basal diameter by wide-angle digital fundus camera: a comparison with ultrasound measurement.

PURPOSE: To compare the measurement of the basal diameter of choroidal melanoma, an important parameter for planning treatment and as a prognostic factor, by standardized ophthalmic ultrasound versus that obtained using a wide-angle fundus camera. METHODS: The longest and shortest basal diameters of 104 consecutive choroidal melanomas of patients seen at the ocular oncology service of the Hadassah University Hospital were measured by B-scan ultrasound and compared with those measured by a wide-angle fundus camera (Panoret-1000). Each diameter was measured thrice by two ophthalmic photographers, and intra-observer and interobserver reproducibility were calculated as well. RESULTS: The measurements of both the long and short diameters of the choroidal melanomas were significantly larger when measured by Panoret-1000 as compared with the B-scan ultrasound. There was no significant difference among the three measurements of each of the photographers. The interobserver reproducibility between the two photographers was high. CONCLUSIONS: Our findings can be attributed to the larger extent of the pigmentation of the melanoma compared to its recognized elevation. Since pigmentation of choroidal melanoma is easier to recognize than its elevation, we assume that measurement by a wide-angle fundus camera is more accurate in pigmented tumors, and should be adopted for measuring the basal diameter of choroidal melanomas in planning treatment and follow-up.

Choroid Neoplasms↗
PubMed2006

Application of the standard photodynamic treatment protocol for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To describe the results of photodynamic therapy (PDT) using a standard protocol, developed for treating choroidal neovascularization (CNV), for the treatment of circumscribed choroidal hemangioma (CCH). METHODS: A prospective, uncontrolled, consecutive case series of patients with symptomatic CCH that were treated using the standard PDT protocol was evaluated periodically with ophthalmic exams and echography. RESULTS: Nine CCH patients were included in the study. Mean tumor height decreased from 2.7 mm before treatment to 0.8 mm at the end of the follow-up period. Mean visual acuity improved from 6/15 to 6/12. Six patients required one PDT session, two patients two sessions, and one patient three sessions. Side effects included transient visual disturbances in two patients. One patient, who concomitantly presented with age-related macular degeneration, developed CNV. CONCLUSIONS: The standard PDT protocol is effective for the treatment of CCH. Complications are uncommon. Further studies should assess the optimal PDT protocol for the treatment of CCH.

Adult↗
PubMed2006

Osteopontin expression and serum levels in metastatic uveal melanoma: a pilot study.

PURPOSE: This was a pilot study conducted to examine the expression of osteopontin in uveal melanoma and to determine whether serum osteopontin can be used in detecting metastatic uveal melanoma. METHODS: Osteopontin mRNA was measured in three uveal melanoma cell lines of various invasive potential by real-time PCR. Tissue sections of primary and metastatic uveal melanomas were stained for osteopontin. Serum osteopontin levels were measured by ELISA assays in 15 patients with metastatic uveal melanoma and in 37 patients who were disease-free for at least 10 years after treatment of the primary tumor. Paired serum samples drawn from eight patients before and after development of metastasis were analyzed. RESULTS: By real-time PCR, highly invasive primary and metastatic uveal melanoma cells expressed 6- and 250-fold excess osteopontin mRNA, respectively, compared with poorly invasive primary uveal melanoma cells. Tissue sections of primary uveal melanomas lacking looping vasculogenic mimicry patterns either did not stain for osteopontin or exhibited weak, diffuse staining. In primary melanomas containing looping vasculogenic mimicry patterns, strong osteopontin staining was detected in the tumor periphery where patterns were located. Diffuse strong expression of osteopontin was detected in eight samples of uveal melanomas metastatic to the liver. Serum osteopontin levels were significantly higher in patients with metastatic uveal melanoma than in patients who had been disease free for at least 10 years after treatment (P = 0.0001) or in age-matched control subjects. Serum osteopontin levels were significantly higher (P = 0.008) after metastasis than before the detection of metastasis in eight patients. When a cutoff of 10 ng/mL was used, the sensitivity and specificity of serum osteopontin in detecting metastatic melanoma was 87.5%, and the area under the receiver operator characteristic curve was 96%. CONCLUSIONS: Osteopontin is expressed diffusely in tissue sections of hepatic metastases from uveal melanoma, and increased serum osteopontin levels correlate with melanoma metastasis to the liver with high specificity and sensitivity.

Aged↗
PubMed2006

Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns.

The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment.

Biomarkers, Tumor↗
PubMed2005

The treatment of primary acquired melanosis (PAM) with atypia by topical Mitomycin C.

PURPOSE: To report our results of 12 consecutive patients with conjunctival primary acquired melanosis (PAM) with atypia who were treated by topical Mitomycin C (MMC). DESIGN: Retrospective interventional consecutive case series. METHODS: Twelve patients with PAM with atypia in one of their eyes who were treated by topical chemotherapy with MMC were included in this case study. Eyes with histologically proven PAM with atypia were treated by two to five courses of 0.04% (0.4 mg/ml) MMC four times a day. Each course lasted 2 continuous weeks. Follow-up was conducted on patients for control of local disease, side effects, and visual acuity in the treated eye. RESULTS: In all patients, there was complete or partial response to treatment. In four patients, the pigmentation disappeared, whereas in eight patients, some remnants of the pigmentation remained. In seven of these eight patients, the remnants of the pigmentation were stable during the follow-up period of 4 months to 9 years, whereas one in whom re-growth of the PAM was noticed was successfully treated again by topical MMC. No patients lost visual acuity at the end of the follow-up. All side effects of the local chemotherapy were resolved after cessation of the treatment. CONCLUSIONS: Topical MMC chemotherapy is a good alternative to surgical excision and cryotherapy in treating conjunctival PAM with atypia.

Administration, Topical↗
PubMed2005

Ocular surface squamous neoplasia.

This article discusses ocular surface squamous neoplasia, a spectrum of malignancy that includes intraepithelial dysplasia, carcinoma in situ of the conjunctiva and cornea, and invasive squamous cell carcinoma.

Carcinoma in Situ↗
PubMed2005

Forecasting the prognosis of choroidal melanoma with an artificial neural network.

PURPOSE: To develop an artificial neural network (ANN) that will forecast the 5-year mortality from choroidal melanoma. DESIGN: Retrospective, comparative, observational cohort study. PARTICIPANTS: One hundred fifty-three eyes of 153 consecutive patients with choroidal melanoma (age, 58.4+/-14.6 years) who were treated with ruthenium 106 brachytherapy between 1988 and 1998 at the Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. METHODS: Patients were observed clinically and ultrasonographically (A- and B-mode standardized ultrasonography). Metastatic screening included liver function tests and liver imaging. Backpropagation ANNs composed of 3 or 4 layers of neurons with various types of transfer functions and training protocols were assessed for their ability to predict the 5-year mortality. The ANNs were trained on 77 randomly selected patients and tested on a different set of 76 patients. Artificial neural networks were compared based on their sensitivity, specificity, forecasting accuracy, area under the receiver operating curves, and likelihood ratios (LRs). The best ANN was compared with the results of logistic regression and the performance of an ocular oncologist. MAIN OUTCOME: The ability of the ANNs to forecast the 5-year mortality from choroidal melanoma. RESULTS: Thirty-one patients died during the follow-up period of metastatic choroidal melanoma. The best ANN (one hidden layer of 16 neurons) had 84% forecasting accuracy and an LR of 31.5. The number of hidden neurons significantly influenced the ANNs' performance (P<0.001). The performance of the ANNs was not significantly influenced by the training protocol, the number of hidden layers, or the type of transfer function. In comparison, logistic regression reached 86% forecasting accuracy, with a very low LR (0.8), whereas the human expert forecasting ability was <70% (LR, 1.85). CONCLUSIONS: Artificial neural networks can be used for forecasting the prognosis of choroidal melanoma and may support decision-making in treating this malignancy.

Brachytherapy↗
PubMed2005

Ultrasonographic tissue characteristics of mushroom-shaped uveal melanoma.

PURPOSE: To evaluate the ultrasonographic tissue characteristics of mushroom-shaped versus dome-shaped uveal melanoma and to compare them with the tumor vasculature. METHODS: We examined clinically and ultrasonically 18 dome-shaped and 11 mushroom-shaped uveal melanomas (29 consecutive patients; mean age 57 years) and compared their normalized A-scan patterns. Using histological sections from a different set of patients (12 dome- and 17 mushroom-shaped tumors), we calculated the percentage of area covered by blood vessels. RESULTS: A-scans of dome-shaped tumors presented low homogeneous reflectivity, whereas the heads of mushroom-shaped tumors had high and irregular reflectivity (p < 0.001). The reflectivity of their bases was low and similar to dome-shaped tumors. The blood vessel area in the histological sections was significantly larger in the heads of mushroom-shaped tumors (0.88 +/- 0.14%), compared both to their bases (0.29 i 0.06%) (p < 0.001) and to dome-shaped tumors (0.07 i 0.03%) (p < 0.0001). CONCLUSIONS: The ultrasonographic pattern suggests vascular congestion in the heads of mushroom-shaped tumors,probably due to strangulated blood vessels in the tumor neck.

Adult↗
PubMed2005

Increased expression of inflammatory cytokines and matrix metalloproteinases in pseudophakic corneal edema.

PURPOSE: To evaluate the expression of inflammatory cytokines and matrix metalloproteinases in the corneal epithelium in pseudophakic corneal edema (PCE). METHODS: Tissue sections were prepared from formalin-fixed, paraffin-embedded blocks of corneal buttons removed from 20 patients with PCE during penetrating keratoplasty (PKP) and from 11 age-matched control eyes enucleated because of uveal melanoma. Expression of interleukin (IL)-1beta, -6, and -8; vascular endothelial growth factor (VEGF); and matrix metalloproteinase (MMP)-1, -3, and -9 proteins in the corneal epithelium was evaluated by immunohistochemistry. Digital image analysis was performed to quantify the expression of the various cytokines and MMPs. A mean intensity stain index (ISI), based on the staining density and the area stained, was calculated from digital images captured from sequential areas of the corneal epithelium. RESULTS: The expression of most of the inflammatory cytokines and MMPs was significantly higher in the corneal epithelium of PCE corneal buttons than in the control specimens. MMP-9 had the highest expression when compared with the control (ISI = 55.08 +/- 23.71 in PCE compared with 0.169 +/- 0.156 in the control; P < 0.0001). Significantly higher ISIs were also recorded for MMP-1 (16.14 +/- 8.49 vs. 1.13 +/- 1.79; P < 0.0001), IL-1beta (62.62 +/- 27.23.97 vs. 1.61 +/- 1.27; P < 0.0001), IL-8 (37.91 +/- 21.18 vs. 4.24 +/- 3.60; P < 0.0001), and VEGF (81.67 +/- 26.22 vs. 19.40 +/- 16.85; P = 0.0001). The expression of MMP-3, IL-6, and TNF-alpha in PCE was not different from control expression. Significant positive correlations were found between the expression of IL-1beta and MMP-9 (r(2) = 0.37; P = 0.015), between VEGF and IL-8 (r(2) = 0.22; P = 0.042), and a significant correlation was found between the expression of MMP-3 and TNF-alpha (r(2) = 0.5197; P = 0.0007). The expression of TNF-alpha correlated significantly with the patient's age (r(2) = 0.28; P = 0.0195). CONCLUSIONS: The corneal epithelium in PCE expresses high levels of cytokines and matrix-degrading enzymes, which are associated with inflammation, wound healing, angiogenesis, and tissue degradation. The expression of these mediators may partially explain the pathologic features associated with this disease, such as bulla formation, recurrent epithelial desquamation, and corneal neovascularization.

Adult↗
PubMed2005

T1799A BRAF mutations in conjunctival melanocytic lesions.

PURPOSE: To gain a better understanding of the molecular events leading to the development of conjunctival melanocytic lesions and conjunctival melanoma, this study was conducted to investigate the presence of T1799A BRAF oncogenic mutation in these lesions. METHODS: Forty-eight surgically excised conjunctival melanocytic lesions from 48 patients were examined for the presence of the BRAF T1799A mutation. Twenty-eight lesions were conjunctival nevi, of which 20 were excised from children younger than 18 years. Fifteen lesions were conjunctival primary acquired melanosis (PAM; 11 without atypia and 4 with atypia) and five were conjunctival melanomas. To detect the BRAF T1799A mutation, both a newly developed kit (Mutector; TrimGen, Sparks, MD) and direct DNA sequence analysis of exon 15 after PCR amplification were used. RESULTS: The T1799A BRAF mutation was identified in 14 of 28 (50%) conjunctival nevi analyzed, but in none of the 15 conjunctival PAMs, with and without atypia. The T1799A BRAF mutation was identified in two of the five (40%) conjunctival melanomas. There was no difference in the BRAF mutation detected in conjunctival nevi in children or adults, as the BRAF mutation was detected in 50%. CONCLUSIONS: The results showed that conjunctival nevi, similar to skin nevi, have a high frequency of oncogenic BRAF mutations. Furthermore, the results suggest that the oncogenic event leading to BRAF mutations affect only conjunctival nevi and not conjunctival PAM. The clinical significance of these observations remains to be determined.

Adolescent↗
PubMed2005

Distinguishing fibrovascular septa from vasculogenic mimicry patterns.

CONTEXT: Molecular analyses indicate that periodic acid-Schiff (PAS)-positive (laminin-rich) patterns in melanomas are generated by invasive tumor cells by vasculogenic mimicry. Some observers, however, consider these patterns to be fibrovascular septa, generated by a stromal host response. OBJECTIVE: To delineate differences between vasculogenic mimicry patterns and fibrovascular septa in primary uveal melanomas. DESIGN: Frequency distributions, associations with outcome, and thicknesses of trichrome-positive and PAS-positive looping patterns were determined in 234 primary uveal melanomas. Sequential sections of 13 additional primary uveal melanomas that contained PAS-positive/trichrome-negative looping patterns were stained for type I and type IV collagens, laminin, and fibronectin. Real-time quantitative polymerase chain reaction was performed on RNA from cultured uveal melanoma cells for the expression of COL1A1, COL4A2, and fibronectin. RESULTS: Trichrome-positive loops were encountered less frequently than PAS-positive loops (10% vs 56%, respectively). Death from metastatic melanoma was strongly associated with PAS-positive (P < .001) but not with trichrome-positive (P = .57) loops. Trichrome-positive loops were significantly thicker than PAS-positive loops (P < .001). The PAS-positive patterns stained positive for laminin, type I and type IV collagens, and fibronectin. Type I collagen was detected within melanoma cells and focally within some PAS-positive patterns. Real-time quantitative polymerase chain reaction revealed 3-fold, 25-fold, and 97-fold increases, respectively, in expression of COL4A2, fibronectin, and COL1A1 by invasive pattern-forming primary melanoma cells compared with poorly invasive non-pattern-forming cells. CONCLUSIONS: Fibrovascular septa are rare and prognostically insignificant in uveal melanomas, whereas vasculogenic mimicry patterns are associated with increased mortality. Type I collagen, seen focally in some vasculogenic mimicry patterns, may be synthesized by tumor cells, independent of a host stromal response.

Azo Compounds↗
PubMed2004

The clinicopathological spectrum of benign peripunctal tumours.

PURPOSE: Because of the rarity of peripunctal tumours and their clinical classification as conjunctival or eyelid tumours, they have gained little attention in the literature. We conducted a retrospective study to illustrate the different clinical and histopathological spectrum of peripunctal tumours seen at two oculoplastics clinics. METHODS: In a retrospective interventional clinicopathologic case series study, all the charts of patients with peripunctal tumours presented at an ophthalmic oncology clinic in Jerusalem, Israel and an oculoplastics clinic in Boston, USA were reviewed. The tumours were classified as epithelial and non-epithelial tumours. The symptoms caused by these tumours, their pattern of growth and their management were evaluated. RESULTS: Fourteen peripunctal tumours were identified. Eleven out of 175 (6.3%) peripunctal disorders and out of approximately 4,000 (0.27%) surgical oculoplastics patients were seen at Massachusetts Eye & Ear Infirmary, Boston. Three were seen at Hadassah University Hospital, Jerusalem. Seven histopathological types of peripunctal tumours of epithelial, subepithelial or melanocytic origin causing punctal occlusion or displacement were identified. The tumours included compound and junctional naevi, non-pigmented compound naevus, epithelial, subepithelial inclusion cysts, verrucous and squamous papilloma, pyogenic granuloma and oncocytoma. All the tumours were benign. They involved the peripunctal or canalicular epithelium, the adjacent skin, the glandular epithelium or the subepithelium. They presented as a peripunctal mass or were accidentally disclosed but none of them resulted in epiphora. CONCLUSIONS: Peripunctal tumours are rare. They exhibit different clinical types of growth and may be difficult to diagnose based on their clinical appearance alone. The location of peripunctal tumours potentially allows their extension from the conjunctival sac into the canaliculus and vice versa. Therefore, it is best to ascertain free margins when the tumour is excised.

Adenoma, Oxyphilic↗
PubMed2004

Liver function tests in metastatic uveal melanoma.

PURPOSE: To evaluate trends in liver function tests before detection of liver metastases from uveal melanoma. DESIGN: Retrospective, comparative, observational case control study. METHODS SETTING: The Israel uveal melanoma center at the Hadassah University Hospital. PATIENT POPULATION: A total of 307 uveal melanoma patients who were diagnosed with uveal melanoma and followed between the years 1988 and 1998. Of them, 30 metastatic patients who had regular follow-up by liver function tests (LFTs) and liver imaging were included in this study. Eighty nonmetastatic patients were randomly chosen as controls. OBSERVATION PROCEDURE: The medical records of the metastatic and control groups were reviewed documenting LFTs and liver imaging results. MAIN OUTCOME MEASURES: The mean level of each LFT, its sensitivity, specificity, and likelihood ratio at various time periods before the detection of metastases by liver imaging. RESULTS: At the time of diagnosis of liver metastases by imaging, 50% of patients had at least one abnormal LFT (compared with only 5% of the control group). While no change was noted in the mean serum levels of bilirubin, mean lactate dehydrogenase (LDH), alkaline-phosphatase, gamma glutamyl transpeptidase (gamma GTP) aspartate-aminotrasferase, and alanine-aminotrasferase levels seem to rise, even within normal limits, during the 6 months before the detection of metastases. Based on likelihood ratios, alkaline-phosphatase and lactate dehydrogenase were the most predictive tests. Lactate dehydrogenase and aspartate-aminotransferase were already predictive at 80% of the upper normal limit, whereas alkaline-phosphatase and gamma-glutamyltransferase were most predictive at the upper normal limit. CONCLUSIONS: Monitoring the changes in selected LFTs, even within normal limits, can help predict metastatic uveal melanoma.

Adult↗