Publications by authors named "Soha El-Sheikh"

16 Publications

  • Page 1 of 1

Growth and renal function dynamics of renal oncocytomas on active surveillance.

BJU Int 2021 May 28. Epub 2021 May 28.

Division of Surgery and Interventional Science, University College London.

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth associates with renal function over time, the reasons for surgery and ablation, and disease-specific survival.

Patients And Methods: Retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was tested using the Mann-Whitney U and the Chi-square tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR).

Results: Longitudinal data from 98 patients with 101 lesions was analysed. Most patients were male (68.3%), median age was 69 years (IQR 13). The median follow-up was 29 months (IQR 26). Most lesions were small renal masses, 24% measured over 4 cm. Over half (64.4%) grew at a median rate of 2 mm per year (IQR 4). No association was observed between tumour size and eGFR over time (p=0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma.

Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow up of over 2 years. Active surveillance should be considered the gold standard management of renal oncocytomas up to 7cm.
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http://dx.doi.org/10.1111/bju.15499DOI Listing
May 2021

The European Association of Urology COVID Intermediate-priority Group is Poorly Predictive of Pathological High Risk Among Patients with Renal Tumours.

Eur Urol 2021 Aug 20;80(2):265-267. Epub 2021 May 20.

UCL Medical School, University College London, London, UK; Specialist Centre For Kidney Cancer, Royal Free London NHS Foundation Trust, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136273PMC
August 2021

Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma.

World J Urol 2021 Apr 13. Epub 2021 Apr 13.

Division of Surgery and Interventional Science, University College London, London, UK.

Purpose: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death.

Methods: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015-2019) and the international collaborative database RECUR (15 institutes, 2006-2011). Kaplan-Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source.

Results: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death.

Conclusion: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.
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http://dx.doi.org/10.1007/s00345-021-03683-9DOI Listing
April 2021

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

Eur Urol 2021 Apr 6;79(4):480-488. Epub 2021 Jan 6.

Department of Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s.

Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression.

Design, Setting, And Participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel.

Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion.

Outcome Measurements And Statistical Analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves.

Results And Limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review.

Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary.

Patient Summary: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.
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http://dx.doi.org/10.1016/j.eururo.2020.12.033DOI Listing
April 2021

Photodynamic Therapy in Primary Breast Cancer.

J Clin Med 2020 Feb 10;9(2). Epub 2020 Feb 10.

Breast Unit and Royal Free London NHS Foundation Trust, London NW3 2QG, UK.

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer.
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http://dx.doi.org/10.3390/jcm9020483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074474PMC
February 2020

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

Urol Oncol 2020 05 5;38(5):440-448. Epub 2019 Nov 5.

Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria.

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors.

Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points.

Materials And Methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018.

Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP.

Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.
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http://dx.doi.org/10.1016/j.urolonc.2019.10.002DOI Listing
May 2020

First-in-human non-invasive assessment of intra-tumoral metabolic heterogeneity in renal cell carcinoma.

BJR Case Rep 2019 May 5;5(3). Epub 2019 Mar 5.

Intratumoral genetic heterogeneity and the role of metabolic reprogramming in renal cell carcinoma (RCC) have been extensively documented. However, the distribution of these metabolic changes within the tissue has not been explored. We report on the first-in-human non-invasive metabolic interrogation of RCC using hyperpolarized carbon-13 (C) magnetic resonance imaging (HP-MRI) and describe the validation of lactate metabolic heterogeneity against multi-regional mass spectrometry. HP-MRI provides an assessment of metabolism and provides a novel opportunity to safely and non-invasively assess cancer heterogeneity.
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http://dx.doi.org/10.1259/bjrcr.20190003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699984PMC
May 2019

Hepatitis and Solitary Left Renal Mass: Renal Hepatocellular Carcinoma.

Urology 2016 Oct 18;96:114-115. Epub 2016 Jul 18.

Royal Free NHS Foundation Trust, London, United Kingdom.

Solitary renal tumours are often primary clear cell carcinoma. A 48-year-old man with chronic hepatitis, hepatocellular carcinoma (HCC), and orthotropic liver transplant 6 years ago presented with a solitary left renal mass. Histology revealed metastatic HCC of the left kidney with extensive reactive changes in lymph nodes. Interestingly, biopsy of the transplanted liver showed no evidence of HCC recurrence. Metastatic disease to the kidney often disseminate locally through transcelomic spread, or hematogenous affecting both kidneys. It is important to recognize extrahepatic HCC metastases to the contralateral kidney, especially in patients with active hepatitis, and radical lymph node clearance is needed.
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http://dx.doi.org/10.1016/j.urology.2016.07.008DOI Listing
October 2016

A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients.

Histopathology 2016 May 4;68(6):875-87. Epub 2016 Jan 4.

University of Hertfordshire, Hatfield, UK.

Aims: Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs.

Methods And Results: RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB).

Conclusions: Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.
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http://dx.doi.org/10.1111/his.12863DOI Listing
May 2016

Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: experience from a London teaching hospital.

Breast 2014 Aug 12;23(4):378-84. Epub 2014 Mar 12.

Department of Surgery, University College London, Royal Free London NHS Foundation Trust, UK. Electronic address:

One step nucleic acid (OSNA) is a molecular diagnostic assay for intra-operative detection of sentinel node metastases. This study compared OSNA with standard histopathology in 283 nodes from 170 patients to evaluate sensitivity, specificity and concordance of the two methods. Additional analysis was done to investigate how cytokeratin 19 mRNA copy number affects prediction of non-sentinel node positivity. OSNA sensitivity was 93.2% and specificity 95.8%. Concordance between OSNA and histology was 95.6%. In the patients who had axillary clearance, the OSNA mRNA copy number on the sentinel node had 100% negative predictive value for histologically proven metastasis. mRNA copy numbers <1400 were not associated with histologically proven metastasis in subsequent nodes at axillary clearance. OSNA is a reliable method for the intra-operative evaluation of axillary lymph node metastasis even when half of the lymph node is used. Identification of mRNA copy number threshold predicting the positivity of non-sentinel axillary nodes seems to be feasible and would be clinically important.
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http://dx.doi.org/10.1016/j.breast.2014.02.001DOI Listing
August 2014

Journal rubric. Haemophilic pseudotumour of the carotid artery.

Vasc Med 2012 Jun 13;17(3):193-4. Epub 2012 Jan 13.

Vascular Unit, Royal Free Hampstead NHS Trust Hospital, London, UK.

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http://dx.doi.org/10.1177/1358863X11429998DOI Listing
June 2012

Von Willebrand factor expression in endometrial endothelial cells in women with menorrhagia.

Fertil Steril 2010 Nov 8;94(6):2335-7. Epub 2010 Apr 8.

Department of Obstetrics and Gynaecology, Royal Free Hospital, Hampstead, London, United Kingdom.

This prospective study assessed von Willebrand factor (VWF) expression in the endometrium using immunohistochemical staining in women with menorrhagia with or without von Willebrand disease (VWD) compared with a control group of women with normal menstrual loss. Endometrial VWF expression is significantly lower in women with VWD, which may play a local underlying role in pathogenesis of menorrhagia in these women.
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http://dx.doi.org/10.1016/j.fertnstert.2010.02.055DOI Listing
November 2010

Predictive value of PTEN and AR coexpression of sustained responsiveness to hormonal therapy in prostate cancer--a pilot study.

Neoplasia 2008 Sep;10(9):949-53

Histopathology Department, Royal Free and University College Medical School London NW32QG, UK.

One limitation of current biochemical or histologic analysis of advanced prostate cancer (PC; T(3)/T(4) +/- N(x) M(x)) is the ability to identify on first diagnostic biopsy patients who will make a durable response to hormone ablation therapy. The aim of this study was to assess the predictive value (sustained response to hormonal therapy and clinical outcome (relapse-free and overall survival)) of phosphatase and tensin homolog (PTEN) and the androgen receptor (AR) immunoexpression in the presenting biopsy. Analysis was performed on 47 samples (10 cases of benign prostatic hyperplasia and 37 hormone-naive PCs). Patients selected represented two stages in the natural history of PC: The "clinical metastatic androgen-responsive" (androgen-dependent PC, ADPC) and the "clinical metastatic androgen-resistant" (androgen-independent PC, AIPC). Reduced immunoreactivity (IR) of either or both PTEN/AR in the initial hormone-naive PC samples was observed with increased frequency in AIPCs. In the ADPC group, low PTEN and/or AR-IR was associated with a shorter median relapse-free survival, i.e., at 30 months after surgery, the probability of relapse-free survival for high expressors of PTEN and AR was 85.7% (SEM = 9.3) compared with only 16.6% (SEM = 15.2) in low expressors. At 36 months, only 28.5% (SEM = 9.3) of ADPC high expressors had experienced a biochemical relapse compared with 100% of low expressors (hazard ratio, 4.6; 95% confidence interval, 4.7-146.8). Further studies analyzing the coexpression of PTEN and AR should be undertaken to validate this pilot study and the utility of these biomarkers in routine histopathologic workup of patients with PC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2517639PMC
http://dx.doi.org/10.1593/neo.08582DOI Listing
September 2008

Phosphorylation of both EGFR and ErbB2 is a reliable predictor of prostate cancer cell proliferation in response to EGF.

Neoplasia 2004 Nov-Dec;6(6):846-53

Department of Histopathology, Imperial College, Hammersmith Hospital Campus, Ducane Road, London W12 0NN, UK.

Despite multiple reports of overexpression in prostate cancer (PC), the reliance of PC cells on activated epidermal growth factor receptor (EGFR) and its downstream signaling to phosphoinositide 3'-kinase/Akt (PI3K/Akt/PTEN) and/or mitogen-activated protein kinase (MAPK/ERK) pathways has not been fully elucidated. In this study, we compared the role of EGF-mediated signaling in nonmalignant (BPH-1, PNT1A, and PNT1B) and PC cell lines (DU145, PC3, LNCaP, and CWR22Rv1). EGF-induced proliferation was observed in all EGFR-expressing PC cells except PC3, indicating that EGFR expression does not unequivocally trigger proliferation following EGF stimulation. ErbB2 recruitment potentiated EGF-induced signals and was associated with the most pronounced effects of EGF despite low EGFR expression. In this way, the sum of EGFR and ErbB2 receptor phosphorylation proved to be a more sensitive indicator of EGF-induced proliferation than quantification of the expression of either receptor alone. Both Akt and ERK were rapidly phosphorylated in response to EGF, with ERK phosphorylation being the weakest in PC3 cells. Extrapolation of these findings to clinical PC suggests that assessment of phosphorylated EGFR + ErbB2 together could serve as a marker for sensitivity to anti-EGFR-targeted therapies.
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http://dx.doi.org/10.1593/neo.04379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1531689PMC
April 2005

Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation.

BMC Clin Pathol 2003 Oct 16;3(1). Epub 2003 Oct 16.

Department of Histopathology, L Block, Hammersmith Hospital Campus, Imperial College, London W12 0NN, UK.

BACKGROUND: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined. METHODS: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2alpha and PI3K-C2beta) enzymes in 104 formalin-fixed, paraffin embedded normal adult human (age 33-71 years, median 44 years) tissue specimens including those from the gastrointestinal, genitourinary, hepatobiliary, endocrine, integument and lymphoid systems. Antibody specificity was verified by Western blotting of cell lysates and peptide blocking studies. Immunohistochemistry intensity was scored from undetectable to strong. RESULTS: PI3K enzymes were expressed in selected cell populations of epithelial or mesenchymal origin. Columnar epithelium and transitional epithelia were reactive but mucous secreting and stratified squamous epithelia were not. Mesenchymal elements (smooth muscle and endothelial cells) and glomerular epithelium were only expressed PI3K-C2alpha while ganglion cells expressed p85 and PI3K-C2beta. All three enzymes were detected in macrophages, which served as an internal positive control. None of the three PI3K isozymes was detected in the stem cell/progenitor compartments or in B lymphocyte aggregates. CONCLUSIONS: Taken together, these data suggest that PI3K enzyme distribution is not ubiquitous but expressed selectively in fully differentiated, non-proliferating cells. Identification of the normal in vivo expression pattern of class IA and class II PI3K paves the way for further analyses which will clarify the role played by these enzymes in inflammatory, neoplastic and other human disease conditions.
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http://dx.doi.org/10.1186/1472-6890-3-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC280660PMC
October 2003

Androgen-independent prostate cancer: potential role of androgen and ErbB receptor signal transduction crosstalk.

Neoplasia 2003 Mar-Apr;5(2):99-109

Department of Histopathology, Imperial College, Hammersmith Hospital Campus, London, UK.

In prostate cancer (PC), increasing evidence suggests that androgen receptor (AR) signalling is functional under conditions of maximal androgen blockade. PC cells survive and proliferate in the altered hormonal environment possibly by interactions between growth factor-activated pathways and AR signalling. The present review article summarizes the current evidence of this crosstalk and focuses on the interactions among the ErbB receptor network, its downstream pathways, and the AR. The potential role of this crosstalk in the development of androgen independence and in relation to antiandrogen therapy is discussed. Such interactions provide insight into possible complementary or additional strategies in the management of PC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502396PMC
http://dx.doi.org/10.1016/s1476-5586(03)80001-5DOI Listing
December 2003
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