Lisa A Rybicki

Lerner Research Institute, Cleveland, Ohio, United States

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Publications (272)1013.87 Total impact

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    ABSTRACT: Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.
    The American journal of surgical pathology. 09/2014; 38(9):1290-7.
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    ABSTRACT: Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; · 4.55 Impact Factor
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    ABSTRACT: Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted.Bone Marrow Transplantation advance online publication, 11 August 2014; doi:10.1038/bmt.2014.150.
    Bone marrow transplantation. 08/2014;
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    ABSTRACT: Hematopoietic cell transplantation (HCT) has become an established standard of care for many older patients with hematologic malignancies. The effect of transplantation on the quality of life (QOL) of older patients, however, has not been well studied. We thus analyzed QOL in patients ⩾60 undergoing an allogeneic HCT compared with patients <60 years. Prospective psychometric instruments were administered to 351 patients who underwent HCT from 2003 to 2010. Psychometric data were assessed longitudinally by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), Coping Inventory and the Profile of Mood State-Short Form. Patients ⩾60 reported better social (P=0.006) and functional well-being (P=0.05) with FACT assessment, and had better total scores, (P=0.043) across all time points. When adjusted for baseline QOL scores as a covariate, social well-being remained significantly better, whereas the other scores became non-significant. With a median follow-up of 49 months, there were no significant differences in OS, relapse-free survival, relapse or chronic GVHD. This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older patients achieved comparable QOL when compared with younger patients.Bone Marrow Transplantation advance online publication, 28 July 2014; doi:10.1038/bmt.2014.166.
    Bone marrow transplantation. 07/2014;
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    ABSTRACT: Background: CCRT results in excellent outcomes in LAHNSCC. This trial compared two CCRT regimens. Methods: Patients with LAHNSCC were treated with radiation(70-74.4 Gy), and randomized to Arm A: cisplatin 100mg/m(2) on RT d1, 22 and 43, or Arm B: cisplatin(20mg/m(2) /day) and 5-FU(1000mg/m(2) /day) continuous 96-hr infusions on RT wks 1 and 4. The primary endpoint was relapse free survival (RFS). Results: Between 2/2008 and 10/2011, 69 patients were enrolled. The study prematurely closed when a scheduled interim analysis showed superior outcomes in both arms and futility of continuation. 83% of patients had oropharynx cancer, of these 86% were HPV/p16+. The 3-yr KM outcome estimates (median follow-up 41 mos) for arms A and B were: RFS 87% vs. 80%(p= 0.24), overall survival 97% vs. 85%(p=0.013), locoregional control 96% vs. 94%(p=0.52), and distant metastatic control 91% vs. 87%(p=0.9). Conclusions: Multiagent was not superior to single agent CCRT. Overrepresentation of HPV/p16+ patients resulted in better than expected outcomes. Head Neck, 2014.
    Head & Neck 06/2014; · 2.83 Impact Factor
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    ABSTRACT: The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m2/day) and cisplatin (20 mg/m2/day) as continuous infusions over days 1–4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4–6 weeks; identical CCRT was given 6–10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003–2006) and the 93 patients on the no-G trial (1999–2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45–0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43–0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45–1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.
    Diseases of the Esophagus 06/2014; · 1.64 Impact Factor
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    ABSTRACT: Persistent fatigue and cognitive dysfunction are poorly understood potential long-term effects of adjuvant chemotherapy. In this pilot study, we assessed the value of electroencephalogram (EEG) power measurements as a means to evaluate physical and mental fatigue associated with chemotherapy. Women planning to undergo adjuvant chemotherapy for breast cancer and healthy controls underwent neurophysiologic assessments at baseline, during the time of chemotherapy treatment, and at 1 year. Repeated measures analysis of variance was used to analyze the data. Compared with controls, patients reported more subjective fatigue at baseline that increased during chemotherapy and did not entirely resolve by 1 year. Performance on endurance testing was similar in patients versus controls at all time points; however, values of EEG power increased after a physical task in patients during chemotherapy but not controls. Compared with controls, subjective mental fatigue was similar for patients at baseline and 1 year but worsened during chemotherapy. Patients performed similarly to controls on formal cognitive testing at all time points, but EEG activity after the cognitive task was increased in patients only during chemotherapy. EEG power measurement has the potential to provide a sensitive neurophysiologic correlate of cancer treatment-related fatigue and cognitive dysfunction.
    Supportive Care in Cancer 03/2014; · 2.09 Impact Factor
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    ABSTRACT: The clinical relevance of mismatches at the major histocompatibility complex class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes following unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II-IV acute GvHD was greater for patients with MICA mismatch (hazard ratio (HR) 1.73, p=0.02) than for HLA-DPB1 mismatch (HR 1.62, p=0.07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR 2.51, p<0.01) and those mismatched at only one locus had somewhat greater risk (HR 1.53, p=0.12) than patients matched at both loci; this remained significant in multivariable analysis. 100-day incidence was 66%, 45%, and 31% (p=0.03). Results were similar for grade III-IV acute GvHD, with 100-day incidence 34%, 16%, and 8% (p=0.01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GvHD.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
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    ABSTRACT: Cytomegalovirus (CMV) is a common infection after myeloablative allogeneic hematopoietic stem cell transplant (M-alloHSCT). Achievement of complete donor T-cell chimerism (CDC-T) post transplant is a measure of immune reconstitution. We investigated the association between CDC-T post M-alloHSCT and the incidence of CMV viremia. We retrospectively reviewed all CMV and chimerism results of 47 patients for the first 6 months post M-alloHSCT. CDC-T was analyzed as a time-varying covariate for association with post M-alloHSCT CMV viremia. CMV viremia occurred in 15 (32%) and CDC-T was achieved in 38 (81%) recipients within the first 6 months post M-alloHSCT. On univariable analysis, increased CMV viremia was seen among patients with CDC-T (hazard ratio 2.81 [P = 0.07, 95% confidence interval = 0.93-8.52]). A 30-day landmark analysis showed that the incidence of CMV viremia at 6 months (regardless of recipient CMV serostatus) was 50% among those who had achieved CDC-T by day 30, and 23% among those who had not (P = 0.06). We conclude that shorter time to CDC-T may be associated with higher risk of CMV viremia. If confirmed in a larger cohort, this might be a marker for risk stratification in the management of CMV in this population.
    Transplant Infectious Disease 11/2013; · 1.98 Impact Factor
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    ABSTRACT: Background:Care of the dying is a significant component of nursing practice particularly in hospitals. Nurses who work in certain areas like oncology, intensive care unit (ICU) face the care of the dying, more so than other units.Objectives:The survey was conducted to assess nurses' self-perception of their professional capability and comfort in the care of the actively dying. Determine if professional capability and comfort was associated with any of the six demographics characteristics (age, gender, clinical experience, education level, nursing unit, continuing education). Identify areas of clinical challenge to promote educational initiatives to stimulate best nursing practice in the actively dying.Design:The survey comprised of two parts: Part I with demographic characteristics and a single open-ended question, Part II with twenty questions on the domains recommended by the NCP. Older age and greater clinical experience were associated with greater levels of capability/comfort. Most nurses felt professionally capable and comfortable in domains such as knowledge, physical and psychosocial care but bioethics, communication, cultural, spiritual and bereavement issues challenged ≥ 40%. Nurses self-perceived professional capability and comfort levels in caring for the dying were positively influenced by older age, greater clinical experience and extensive continuing education. Bioethics, communication and grief impacted nurses personally and emotionally. Continuing education, organized debriefing, grief-counseling, and preceptors support should be routine for nurses who work in units with predictable high mortality.
    The American journal of hospice & palliative care 10/2013;
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    ABSTRACT: Introduction:Low creatinine and albumin are found among the chronically ill patients. This study retrospectively reviewed albumin and creatinine levels for survival in patients upon admission. Records of patients admitted over 2 months were reviewed. Recursive partitioning analysis (RPA) identified cutpoints in albumin and creatinine that predicted survival. Kaplan-Meier survival, Cox proportional hazards, and stepwise Cox analyses identified prognostic factors. Of 83 patients, 81 were assessable. Variables for worse survival were albumin <3.1 g/dL, creatinine >0.93 mg/dL, and male gender. Albumin by continuous, median, RPA, and tertiles was significant; creatinine by RPA. Hazard ratio for albumin >3.1 was 0.28 (P < .001) and for creatinine >0.91 mg/dL was 1.8 (P = .046).Discussion and Conclusion:Albumin and creatinine are prognostically important.
    The American journal of hospice & palliative care 08/2013;
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    ABSTRACT: Tumor human papillomavirus (HPV) status has emerged as one of the most powerful prognostic factors for disease control and survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). We reviewed our experience in patients with OPSCC and known tumor HPV status treated with definitive chemoradiotherapy (CRT). Patients with stage III-IVb OPSCC and known tumor HPV status treated with CRT between 2006 and 2011 were identified from an IRB approved registry for this retrospective review. Outcomes were estimated using the Kaplan-Meier method and compared between HPV-positive and negative patients using the log-rank test. Of the 121 pts (89% male, 93% Caucasian) included in this study, median age was 57 (range: 40--73) and median follow-up was 21 months (range: 6--63). Ninety-seven (80%) patients were HPV-positive and 24 (20%) were HPV-negative. Primary site was base of tongue (55%), tonsil (44%), and oropharyngeal wall (2%). Two year rates of locoregional recurrence (3% vs. 26%; p = 0.002), disease free survival (93% vs. 64%; p = 0.001) and overall survival (94% vs 73%; p = 0.002) were superior in HPV-positive patients, while rates of distant recurrence were similar (3% vs. 5%; p = 0.98). While acute toxicities were similar between both groups, patients with HPV-positive disease were more likely to resume a normal diet (90% vs. 65%; p = 0.017) at last follow up. Also, no HPV-positive patient required a feeding tube beyond 6 months after treatment, compared with 24% of HPV-negative patients. Definitive CRT produces excellent rates of disease control with minimal late toxicity for patients with HPV-positive OPSCC. Studies of OPSCC should account for tumor HPV status when identifying factors prognostic for outcome.
    Radiation Oncology 07/2013; 8(1):174. · 2.11 Impact Factor
  • Bone marrow transplantation 06/2013; · 3.00 Impact Factor
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    ABSTRACT: Polymerase chain reaction (PCR)-based assays using stool samples are currently the most effective method of detecting Clostridium difficile. This study examines the feasibility of this assay using mucosal biopsy samples and evaluates the interobserver reproducibility in diagnosing and distinguishing ischemic colitis from C difficile colitis. Thirty-eight biopsy specimens were reviewed and classified by 3 observers into C difficile and ischemic colitis. The findings were correlated with clinical data. PCR was performed on 34 cases using BD GeneOhm C difficile assay. The histologic interobserver agreement was excellent (κ= 0.86) and the agreement between histologic and clinical diagnosis was good (κ = 0.84). All 19 ischemic colitis cases tested negative (100% specificity) and 3 of 15 cases of C difficile colitis tested positive (20% sensitivity). C difficile colitis can be reliably distinguished from ischemic colitis using histologic criteria. The C difficile PCR test on endoscopic biopsy specimens has excellent specificity but limited sensitivity.
    American Journal of Clinical Pathology 06/2013; 139(6):730-735. · 2.88 Impact Factor
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    ABSTRACT: PURPOSE: To assess distribution, correlations, and prognostic effect of tumor (T), node (N), and metastasis (M) staging on relapse and survival. DESIGN: Retrospective clinical review. PARTICIPANTS: Sixty-three patients diagnosed with primary ocular adnexal lymphoma (OAL) between January 1986 and November 2011. METHODS: Complete ocular examination and systemic evaluation were performed. Patients were staged according to the American Joint Committee on Cancer (AJCC) seventh edition tumor-node-metastasis (TNM) clinical staging system for OAL and followed every 6 to 12 months (median follow-up, 27.9 months). MAIN OUTCOME MEASURES: Relapse defined as lymphoma recurrence in the initial site of presentation, the contralateral ocular adnexal structures, or other systemic site and overall survival. RESULTS: There were 40 men (63.5%). The median age was 65 years (range, 24-85 years). The affected site was the conjunctiva in 27 patients (42.9%), orbit in 38 patients (60.3%), and eyelid in 3 patients (4.8%). The histologic subtype was extranodal marginal zone lymphoma (EMZL) in 51 patients (81.0%). A total of 14 patients (23.3%) had T1, 42 patients (70.0%) had T2, 1 patient (1.7%) had T3, and 3 patients (5.0%) had T4 disease. A total of 48 patients (82.8%) had N0 disease, and 10 patients (17.2%) had N1-4 disease. M stage was M0 in 47 patients (81.0%) and M1 in 11 patients (19.0%). With advanced T stage, there was an increase in both N1-4 (P = 0.045) and M1 disease (P = 0.041). M1 disease was greater among patients with N1-4 disease compared with N0 stage (50.0% vs. 12.5%, P = 0.003). Overall, 18 patients (28.6%) relapsed and 6 patients (9.5%) died. In Cox analysis, relapse was not associated with T stage (hazard ratio [HR], 1.14 per 1 level increase, P = 0.71), N stage (HR, 1.47; P = 0.51 N1-4 vs. N0), or M stage (HR, 1.22; P = 0.76 M1 vs. M0). T stage was not associated with survival (HR, 0.86; P = 0.81), whereas N1-4 had marginally worse survival than N0 (HR, 5.35; P = 0.07), and M1 had worse survival than M0 (HR, 9.27; P = 0.008). CONCLUSIONS: The TNM staging system for primary OAL is useful for precise characterization of extent of local disease. Although T stage does not predict relapse or survival, N1-4 and M1 stages indicated less favorable survival. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
    Ophthalmology 05/2013; · 5.56 Impact Factor
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    ABSTRACT: Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified sixty polyps with histologic consensus. Microarray analysis was performed on 6 distal consensus MVHPs <9mm, 6 proximal consensus SSA/Ps >9mm and 6 normal colon biopsies (3 proximal, 3 distal). Comparative gene expression analysis confirms the close relationship between SSA/Ps and MVHPs as there is overlapping expression of many genes. However, the gene expression profile in SSA/Ps has stronger and more numerous associations with cancer related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immuno-histochemical expression of ANXA10 was not identified in separate samples of normal colon and in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p<0.0001). An ANXA10 score ≥3 has a sensitivity of 73% and specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.
    The Journal of Pathology 04/2013; · 7.59 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Gastrointestinal polyposis is a common clinical problem, yet there is no consensus on how to best manage patients with moderate-load polyposis. Identifying genetic features of this disorder could improve management, and especially surveillance, of these patients. We sought to determine the prevalence of hamartomatous polyposis associated mutations in the susceptibility genes PTEN,BMPR1A, SMAD4, ENG, andSTK11 in individuals with 5 or more gastrointestinal polyps, including at least 1 hamartomatous or hyperplastic/serrated polyp. METHODS: We performed a prospective, referral-based study of 603 patients (median age 51 y; range, 2-89 y), enrolled from June 2006 through January 2012. Genomic DNA was extracted from peripheral lymphocytes and analyzed for specific mutations and large rearrangements in PTEN,BMPR1A,SMAD4, and STK11, as well as mutations in ENG. Recursive partitioning analysis was used to determine cutoffs for continuous variables. The prevalence of mutations was compared using Fischer's exact test. Logistic regression analyses were used to determine univariate and multivariate risk factors. RESULTS: Of 603 patients, 119 (20%) had a personal history of colorectal cancer and most (461; 76%) had fewer than 30 polyps. Seventy-seven patients (13%) were found to have polyposis-associated mutations, comprising 11 inENG (1.8%), 13 inPTEN (2.2%), 13 inSTK11 (2.2%), 20 inBMPR1A (3.3%), and 21 inSMAD4 (3.5%). Univariate clinical predictors for risk of having these mutations included age at presentation less than 40 years (19% vs 10%;P =.008), a polyp burden of 30 or more (19% vs 11%;P =0.014), and male sex (16% vs 10%;P =.03). Patients who had 1 or more ganglioneuromas (29% vs 2%;P <.001) or presented with polyps of 3 or more histologic types (20% vs 2%;P =.003) were more likely to have germline mutations inPTEN. CONCLUSIONS: Age less than 40 years, male sex, and specific polyp histologies are significantly associated with risk of germline mutations in hamartomatous-polyposis associated genes. These associations could guide clinical decision making and further investigations.
    Gastroenterology 02/2013; · 12.82 Impact Factor
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    ABSTRACT: Central line-associated blood stream infections (CLABSI) commonly complicate the care of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients following allogeneic stem cell transplantation (HCT). We developed a modified CLABSI (MCLABSI) definition which attempts to exclude pathogens usually acquired due to disruption of mucosal barriers during the vulnerable neutropenic period following HCT that are generally included under the original definition (OCLABSI). We conducted a retrospective study of all AML and MDS patients undergoing HCT between August 2009 and December 2011 at the Cleveland Clinic (n=73), identifying both OCLABSI and MCLABSI incidence. The median age at transplantation was 52 years (range, 16-70); 34 had a high (≥3) HCT comorbidity index (HCT-CI); 34 received bone marrow (BM), 24 received peripheral stem cells (PSC), and 15 received umbilical cord blood cells (UCB). Among these 73 patients, 23 (31.5%) developed OCLABSI, of whom 16 (69.6%) died, and 8 (11%) developed MCLABSI, of whom 7 (87.5%) died. OCLABSI was diagnosed a median of 9 days from HCT: 5 days (range, 2-12) for UCB and 78 days (range, 7-211) for BM/PSC (p<.001). MCLABSI occurred a median of 12 days from HCT, with similar earlier UCB and later BM/PSC diagnosis (p=.030). Risk factors for OCLABSI in univariate analysis included CBC (p<.001), HLA-mismatch (p=.005), low CD34+ count (p=.007), low total nucleated cell dose (p=.016), and non-Caucasian race (p=.017). Risk factors for OCLABSI in multivariable analysis were UCB (p<.001) and high HCT-CI (p=.002). There was a significant increase in mortality for both OCLABSI (HR 7.14, CI 3.31 - 15.37, p<.001) and MCLABSI (HR 6.44, CI 2.28-18.18, p<.001). CLABSI is common and associated with high mortality in AML and MDS patients undergoing HCT, especially in UCB recipients and those with high HCT-CI. We propose the MCLABSI definition to replace the OCLABSI definition given its greater precision for identifying preventable infection in HCT patients.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
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    ABSTRACT: The presence of high-grade dysplasia (HGD) or villous component (VC) defines an advanced adenoma (AA) in patients with 1 or 2 adenomas <1 cm in size. Current consensus guidelines recommend that patients with AA undergo more intense postpolypectomy surveillance. In these clinical situations, the interobserver reliability in determining VC and HGD would play a major role in the credibility of these consensus guidelines. Therefore, the purpose of this study was to evaluate interobserver variability of VC and HGD in polyps <1 cm before and after the development of consensus criteria among gastrointestinal (GI) pathologists. Five GI pathologists independently evaluated 107 colorectal adenomas <1 cm, and classified them into tubular adenomas or adenomas with a VC (A-VC) and into low-grade dysplasia or HGD. Then a consensus conference was held and consensus criteria for VC and HGD were developed by group review. The same set of 107 slides were rereviewed independently by the same 5 GI pathologists. Interobserver variability using κ statistical analysis before and after the application of consensus criteria was assessed. A 1-sided z-test was used to determine whether κ scores increased after the consensus conference. Interobserver agreement before and after the consensus conference was poor for assessment of A-VC, HGD, and AA. These data calls into question the validity of basing clinical decisions on this distinction.
    The American journal of surgical pathology 01/2013; · 4.06 Impact Factor
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    ABSTRACT: Background Lymphoma rarely presents in the ocular adnexa and usually is extranodal marginal zone (ENMZ) lymphoma when it does. Involved field radiation (IFRT) is the standard of care in unilateral disease but optimal management of more extensive disease is unclear. Patients and methods We retrospectively evaluated clinical characteristics and outcomes of 95 patients with ocular adnexal lymphoma (OAL) or uveal lymphoma treated or diagnosed at our institution. All patients identified were included in risk factor analysis for progression free survival (PFS). Initial treatment-related outcomes were assessed for ENMZ OAL only (n=62). Results With a median follow-up of 32 months, risk factors for PFS after initial treatment were age (HR 1.33, CI 1.02-1.74), female gender (HR 2.04, CI 1.04-4.00) and prior history of lymphoma (HR 2.31, CI 1.12-4.78). In ENMZ, the treatment with IFRT was associated with an improved PFS (median 5.4 years, p<0.001). Progression occurred in 23% (7 of 39) with 86% (6 of 7) of progressions at systemic sites. Single-agent rituximab was typically utilized in bilateral-ocular or systemic presentations of ENMZ OAL. Progression occurred in 64% (7 of 11) with no progressions at systemic sites. All progression events in those initially treated with rituximab occurred in the ocular adnexa. Conclusions This study confirms IFRT as the standard for unilateral ENMZ OAL. Single-agent rituximab is an effective agent for bilateral-ocular or systemic presentations of ENMZ OAL, particularly for systemic control. Ocular progression should be closely monitored after single-agent rituximab. Combined modality therapy should be further studied in bilateral or systemic ENMZ OAL.
    Clinical lymphoma, myeloma & leukemia 01/2013;

Publication Stats

5k Citations
1,013.87 Total Impact Points

Institutions

  • 2008–2014
    • Lerner Research Institute
      Cleveland, Ohio, United States
    • Ohio Health
      Columbus, Ohio, United States
  • 1995–2014
    • Cleveland Clinic
      • • Department of Hematologic Oncology and Blood Disorders
      • • Department of Anatomic Pathology
      • • Department of Internal Medicine
      • • Department of Solid Tumor Oncology
      • • Department of Gastroenterology
      • • Department of Hematology and Oncology
      Cleveland, Ohio, United States
  • 2006–2012
    • Cleveland State University
      • School of Social Work
      Cleveland, OH, United States
    • Cancer Research and Biostatistics
      Seattle, Washington, United States
  • 2011
    • Massachusetts General Hospital
      • Division of Hematology and Medical Oncology
      Boston, MA, United States
  • 2008–2011
    • Universitätsklinikum Freiburg
      • Preventive Medicine Unit
      Freiburg, Lower Saxony, Germany
  • 2010
    • Fairbanks Memorial Hospital
      Fairbanks, Alaska, United States
  • 2009
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2007
    • University of Miami Miller School of Medicine
      • Division of Hematology and Oncology
      Miami, FL, United States
  • 2003
    • Michiana Hematology Oncology
      Indiana, Pennsylvania, United States
  • 2002
    • Henry Ford Health System
      Detroit, Michigan, United States