Hany Elsaleh

Publications (11)148.57 Total impact

• Article: Who profits from neoadjuvant radiochemotherapy for locally advanced esophageal carcinoma?

  Hany Elsaleh, James J Farrell, Christopher H Crane
  Journal of Gastroenterology and Hepatology 06/2009; 24(5):708-10. · 2.87 Impact Factor
• Article: Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.

  James J Farrell, Hany Elsaleh, Miguel Garcia, Raymond Lai, Ali Ammar, William F Regine, Ross Abrams, A Bowen Benson, John Macdonald, Carol E Cass, Adam P Dicker, John R Mackey
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  ABSTRACT: The human equilibrative nucleoside transporter (hENT1) protein transports gemcitabine into cells. Small retrospective studies in pancreatic cancer suggest that levels of hENT1 protein or messenger RNA may have prognostic value. We studied the predictive value of hENT1 levels in a cohort of pancreatic adenocarcinoma patients from the large prospective randomized adjuvant treatment trial RTOG9704. In RTOG9704, 538 patients were assigned randomly, after surgical resection, to groups that were given either gemcitabine or 5-fluorouracil (5-FU). Immunohistochemistry for hENT1 was performed on a tissue microarray of 229 resected pancreatic tumors from RTOG9704 and scored as having no staining, low staining, or high staining. Associations between hENT1 protein and treatment outcome were analyzed by unconditional logistic regression analysis using the chi-square test and the Cox proportional hazards model. HENT1 expression was associated with overall and disease-free survival in a univariate (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.91; P= .02; and HR, 0.57; 95% CI, 0.32-1.00; P= .05) and multivariate model in the group given gemcitabine (HR, 0.40; 95% CI, 0.22-0.75; P= .004; and HR, 0.39; 95% CI, 0.21-0.73; P= .003). hENT1 expression was not associated with survival in the group given 5-FU. In this prospective randomized trial, hENT1 protein expression was associated with increased overall survival and disease-free survival in pancreatic cancer patients who received gemcitabine, but not in those who received 5-FU. These findings are supported by preclinical data; the gemcitabine transporter hENT1 is therefore a molecular and mechanistically relevant predictive marker of benefit from gemcitabine in patients with resected pancreatic cancer.
  Gastroenterology 11/2008; 136(1):187-95. · 11.68 Impact Factor
• Article: Re: Pooled analysis of fluorouracil-based adjuvant therapy of stage II and III colon cancer: who benefits and by how much?

  Hany Elsaleh, Barry Iacopetta
  Journal of Clinical Oncology 02/2005; 23(3):653-4; author reply 654-5. · 18.37 Impact Factor
• Article: Early detection markers in Pancreas Cancer.

  James J Farrell, Marius van Rijnsoever, Hany Elsaleh
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  ABSTRACT: The role of early detection in cancer has shown improved survival for certain cancers, including colon cancer, cervical cancer and breast cancer. The possibility for early detection of pancreatic cancer may be realized by an improved understanding of the histology and molecular genetics of precursor lesions and cancerous lesions in pancreatic cancer and the development of sensitive and specific screening tests (both invasive and non-invasive) to detect early pancreatic cancer. The NIH-NCI Early Detection Research Network (EDRN) in Pancreatic Cancer has been focussed on the development and validation of new biomarkers for the detection of early pancreatic cancer. This review will focus on our understanding of the histologic and molecular model of pancreatic carcinogenesis, current strategies and limitations of screening for pancreatic cancer and the development and validation of new biomarkers for the early detection of pancreatic cancer.
  Cancer biomarkers: section A of Disease markers 02/2005; 1(2-3):157-75. · 1.08 Impact Factor
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  Article: The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects.

  Quoc-Chuong Bui, Michael Lieber, H Rodney Withers, Kevan Corson, Marius van Rijnsoever, Hany Elsaleh
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  ABSTRACT: We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the management of patients with radiation-induced late side effects, the majority of whom had failed previous interventions. Of 105 eligible subjects, 30 had either died or were not contactable, leaving 75 who qualified for inclusion in this retrospective study. Patients answered a questionnaire documenting symptom severity before and after treatment (using Radiation Therapy Oncology Group criteria), duration of improvement, relapse incidence, and HBOT-related complications. The rate of participation was 60% (45/75). Improvement of principal presenting symptoms after HBOT was noted in 75% of head-and-neck, 100% of pelvic, and 57% of "other" subjects (median duration of response of 62, 72, and 68 weeks, respectively). Bone and bladder symptoms were most likely to benefit from HBOT (response rate, 81% and 83%, respectively). Fifty percent of subjects with soft tissue necrosis/mucous membrane side effects improved with HBOT. The low response rate of salivary (11%), neurologic (17%), laryngeal (17%), and upper gastrointestinal symptoms (22%) indicates that these were more resistant to HBOT. Relapse incidence was low (22%), and minor HBOT-related complications occurred in 31% of patients. Hyperbaric oxygen therapy is a safe and effective treatment modality offering durable relief in the management of radiation-induced osteoradionecrosis either alone or as an adjunctive treatment. Radiation soft tissue necrosis, cystitis, and proctitis also seemed to benefit from HBOT, but the present study did not have sufficient numbers to reliably predict long-term response.
  International Journal of Radiation OncologyBiologyPhysics 12/2004; 60(3):871-8. · 4.11 Impact Factor
• Article: Microsatellite instability in colon cancer.

  Barry Iacopetta, Hany Elsaleh, Nik Zeps
  New England Journal of Medicine 11/2003; 349(18):1774-6; author reply 1774-6. · 53.30 Impact Factor
• Article: CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer.

  Marius Van Rijnsoever, Hany Elsaleh, David Joseph, Kieran McCaul, Barry Iacopetta
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  ABSTRACT: The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value. Experimental Design: CIMP+ status was evaluated in 103 stage III CRCs from patients treated with surgery alone and for an additional 103 cases from patients treated with surgery and adjuvant 5-FU-based chemotherapy. The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months. CIMP+ status predicted survival benefit from 5-FU treatment independently of microsatellite instability and p53 mutation status (relative risk = 0.22; 95% confidence interval, 0.06-0.84; P = 0.027). Unmeasured, high-risk confounding factors could only account for this association if they were unequally distributed between the two patient cohorts by a factor of at least 2-fold. CIMP+ has independent predictive significance for the survival benefit from 5-FU chemotherapy in CRC. This molecular marker should be incorporated into prospective clinical trials of fluorouracil-based therapies to confirm its clinical value.
  Clinical Cancer Research 09/2003; 9(8):2898-903. · 7.74 Impact Factor
• Article: Extent of nodal involvement in Stage III colorectal carcinoma: relationship to clinicopathologic variables and genetic alterations.

  Hany Elsaleh, Gábor Cserni, Barry Iacopetta
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  ABSTRACT: Recent evidence from our laboratory suggests that the factors of tumor site, patient gender, microsatellite instability, and mutations are important determinants in the survival benefit associated with adjuvant chemotherapy in Stage III colorectal carcinoma. In the present study we investigated whether these factors, as well as Ki- mutations, were also associated with the extent of nodal involvement in Stage III cancers. Nodal involvement was retrospectively evaluated in a series of 645 patients with Stage III colorectal cancer from Sir Charles Gairdner Hospital. The number of involved nodes was correlated with the clinicopathologic features of gender, age, tumor site, and histologic grade, as well as to the genetic alterations of mutation, Ki- mutation, and microsatellite instability. The median number of nodes examined per tumor was 11 (range, 1-53). Forty-nine percent of cases had one or two involved nodes and 51 percent had three or more involved nodes, the latter feature being associated with significantly reduced patient survival. No differences in the extent of nodal involvement were apparent with respect to tumor site, patient gender, or or Ki- mutation status. Tumors from younger patients (P = 0.025) or with poorly differentiated histology (P = 0.007), were associated with significantly higher nodal burden, whereas the microsatellite instability phenotype was associated with less extensive nodal involvement (P = 0.020). Survival benefits from the use of chemotherapy were apparent for both the low and high nodal involvement groups, although the latter seemed to obtain relatively more benefit. Multivariate analysis of patients treated with chemotherapy found that gender, grade, and microsatellite instability, but not nodal involvement, were independently prognostic for survival. The extent of nodal involvement in Stage III colorectal cancer is related to patient age, tumor grade, and microsatellite instability status, but not to tumor site, patient gender, or Ki- mutation. These results indicate that differences in metastatic nodal burden cannot explain previously observed site, gender, and mutation differences in the response to chemotherapy.
  Diseases of the Colon & Rectum 10/2002; 45(9):1218-22. · 3.13 Impact Factor
• Article: Extent of Nodal Involvement in Stage III Colorectal Carcinoma

  Hany Elsaleh, Gábor Cserni, Barry Iacopetta
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  ABSTRACT: PURPOSE: Recent evidence from our laboratory suggests that the factors of tumor site, patient gender, microsatellite instability, and TP53 mutations are important determinants in the survival benefit associated with adjuvant chemotherapy in Stage III colorectal carcinoma. In the present study we investigated whether these factors, as well as Ki-ras mutations, were also associated with the extent of nodal involvement in Stage III cancers. METHODS: Nodal involvement was retrospectively evaluated in a series of 645 patients with Stage III colorectal cancer from Sir Charles Gairdner Hospital. The number of involved nodes was correlated with the clinicopathologic features of gender, age, tumor site, and histologic grade, as well as to the genetic alterations of TP53 mutation, Ki-ras mutation, and microsatellite instability. RESULTS: The median number of nodes examined per tumor was 11 (range, 1–53). Forty-nine percent of cases had one or two involved nodes and 51 percent had three or more involved nodes, the latter feature being associated with significantly reduced patient survival. No differences in the extent of nodal involvement were apparent with respect to tumor site, patient gender, or TP53 or Ki-ras mutation status. Tumors from younger patients (P = 0.025) or with poorly differentiated histology (P = 0.007), were associated with significantly higher nodal burden, whereas the microsatellite instability phenotype was associated with less extensive nodal involvement (P = 0.020). Survival benefits from the use of chemotherapy were apparent for both the low and high nodal involvement groups, although the latter seemed to obtain relatively more benefit. Multivariate analysis of patients treated with chemotherapy found that gender, grade, and microsatellite instability, but not nodal involvement, were independently prognostic for survival. CONCLUSION: The extent of nodal involvement in Stage III colorectal cancer is related to patient age, tumor grade, and microsatellite instability status, but not to tumor site, patient gender, TP53 or Ki-ras mutation. These results indicate that differences in metastatic nodal burden cannot explain previously observed site, gender, and TP53 mutation differences in the response to chemotherapy.
  Diseases of the Colon & Rectum 08/2002; 45(9):1218-1222. · 3.13 Impact Factor
• Article: Microsatellite instability in colorectal cancer: prognostic, predictive or both?

  Marius van Rijnsoever, Hany Elsaleh, Barry Iacopetta
  American Journal Of Pathology 02/2002; 160(1):384-5; author reply 385-6. · 4.89 Impact Factor
• Article: Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer

  Hany Elsaleh, David Joseph, Fabienne Grieu, Nik Zeps, Nigel Spry, Barry Iacopetta
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  ABSTRACT: BackgroundAdjuvant chemotherapy can improve 5-year survival in Dukes' C colorectal carcinoma. Improved selection of patients who will respond to adjuvant treatments is required. We investigated whether site of tumour origin, sex, and presence of microsatellite instability (MSI) phenotype were associated with a survival benefit from adjuvant chemotherapy.MethodsWe analysed data for 656 consecutive patients with Dukes' C colorectal carcinoma, with median follow-up of 54 months (range 7–104) and mean age 66·7 years (SD 12·9). We screened tumour samples by PCR for deletions in the BAT-26 mononucleotide repeat to establish MSI status. Details of chemotherapy and survival were obtained by review of hospital and health-department records. Adjuvant chemotherapy (fluorouracil and levamisole) was given with curative intent to 272 (42%) patients.FindingsStriking survival benefits were seen for patients who had right-sided tumours and who received adjuvant chemotherapy compared with those who did not (48 vs 27% alive at end of study [95% Cl 0·25–0·56], p<·0001), for women (53 vs 33% [0·25–0·56], p<0·0001), and for patients with MSI tumours (90 vs 35% [0·01–0·53], p=0·0007). MSI-positive tumours were slightly more frequent in women than in men (10 vs 7%). Right-sided tumours were more frequently MSI positive than left-sided tumours (20 vs 1%). Men with right-sided tumours benefited from chemotherapy (37 vs 12% [0·24–0·69], p=0·0007) but men with left-sided tumours did not.InterpretationThe survival benefits seen in patients treated with adjuvant chemotherapy suggest that data from previous trials of adjuvant chemotherapy should be reassessed and the predictive value of MSI status confirmed. Validation of our results will allow better selection of patients for chemotherapy.
  The Lancet 06/2000; · 38.28 Impact Factor