P H Bartels

The University of Arizona, Tucson, Arizona, United States

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Publications (337)609.58 Total impact

  • Cancer Research 07/2015; 75(13 Supplement):A83-A83. DOI:10.1158/1538-7445.PANCA2014-A83 · 9.33 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):1362-1362. DOI:10.1158/1538-7445.AM2014-1362 · 9.33 Impact Factor
  • Peter H Bartels · Hubert G Bartels ·
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    ABSTRACT: Classification plays a central role in quantitative histopathology. Success is expressed in terms of the accuracy of prediction for the classification of future data points and an estimate of the prediction error. The prediction error is affected by the chosen procedure, e.g., the use of a training set of data points, a validation set, an independent test set, the sample size and the learning curve of the classification algorithm. For small samples procedures such as the "jackknife," the "leave one out" and the "bootstrap" are recommended in order to arrive at an unbiased estimate of the true prediction error. All of the procedures rest on the assumption that the data set used to derive a classification rule is representative for the diagnostic categories involved. It is this assumption that in quantitative histopathology has to be carefully verified before a clinically generally valid classification procedure can be claimed.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 08/2013; 35(4):181-8. · 0.49 Impact Factor

  • Journal of Surgical Research 02/2013; 179(2):303. DOI:10.1016/j.jss.2012.10.604 · 1.94 Impact Factor
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    ABSTRACT: To establish the karyometric characteristics of the two main nuclear phenotypes in cutaneous squamous cell cancer (cSCC) lesions. The clinical materials comprised 75 cases of cSCC, 38 with aggressive lesions and 37 with nonaggressive lesions. High-resolution images of 100 nuclei per case were recorded. Data were partitioned into four subgroups covering the range of lesion progression. Four discriminant functions were derived to distinguish aggressive from nonaggressive lesions. The most typical nuclei from the phenotype predominant in aggressive lesions and nonaggressive lesions were separated out by thresholding on the discriminant function score axes. For these homogeneous sets of nuclei the karyometric features were computed. The nuclear populations in cSCC lesions are a very heterogeneous set. There are two axes of dispersion, along the line of lesion progression and between aggressive and nonaggressive lesions. The analysis faces the difficulty that lesions from both diagnostic categories contain nuclei of the same two phenotypes with the difference between categories consisting only of differences in proportion of the two phenotypes. The nuclei of the aggressive phenotype I and nonaggressive phenotype II have substantially different chromatin patterns and can be distinguished with > 90% correct recognition rate.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 02/2012; 34(1):1-8. · 0.49 Impact Factor
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    ABSTRACT: Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease.
    Gynecologic Oncology 12/2011; 125(1):129-35. DOI:10.1016/j.ygyno.2011.12.422 · 3.77 Impact Factor
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    ABSTRACT: OBJECTIVE: Presurgical, window of opportunity trials have been proposed as a model to assess the activity of preventive and therapeutic interventions in a cost-effective manner in prostate cancer (CaP). The aim of the study was to explore karyometry as a method for monitoring the efficacy of intervention with preventive agents in patients with CaP. MATERIALS AND METHODS: The material used in this investigation was from the 2F study, i.e., an Italian prospective randomized phase IIb presurgical study of finasteride vs. low-dose flutamide vs. placebo in men with CaP. Image analysis was performed in 16 cases treated with finasteride, 24 with flutamide, and 20 with placebo. For all these cases, CaP and normal looking secretory epithelium were present in the pretreatment biopsies as well as the post-treatment ex-vivo biopsies obtained from the radical prostatectomy specimens. RESULTS: To establish a direction of nuclear change from normal to malignancy, i.e., the so-called line of progression, a discriminant function was derived with the normal looking epithelium in the pretreatment biopsies as one endpoint, and the CaP in the pretreatment biopsies as the other. The discriminant function was then applied to the post-treatment groups. The increase in relative nuclear area was the dominant feature. In the placebo group, 15 out of 20 CaP (75%) cases had a higher discriminant function score at the end of study, with a significant increase of the mean score by 90%. The flutamide treated CaP cases had increased discriminant function scores in 19 out of 24 cases (79%) and an increase of the mean score by 43%; the 5 cases with lower scores involved only minor reductions. In contrast, the finasteride treated CaP cases had increased discriminant function scores for 8 out of 16 cases (50%), but the increase in the mean score was by only 8%. CONCLUSION: This exploratory study establishes that karyometric monitoring can track the results of subtle nuclear changes induced by preventive interventions in men with CaP, thus allowing assessment of agent activity in a cost-effective manner.
    Urologic Oncology 07/2011; 31(5). DOI:10.1016/j.urolonc.2011.02.024 · 2.77 Impact Factor
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    ABSTRACT: By identifying aggressive cutaneous squamous cell carcinoma (cSCC) in patients who are at high risk for recurrences or second primaries after resection, intensive surveillance and therapy may decrease morbidity and mortality. We investigated the role of nuclear morphometry (karyometry) in differentiating between aggressive and nonaggressive cSCC. We retrospectively analyzed cSCC lesions from 40 male patients. Twenty-two patients had evidence of aggressive cSCC (local/regional recurrence or a second primary cSCC), and 18 patients were identified with similar ages and sites of disease as control patients with nonaggressive cSCC (no evidence of recurrence, metastasis, or second primary). We carried out karyometric analysis to identify nuclear features that discriminate between aggressive and nonaggressive cSCC nuclei. We used statistically significant differences (Kruskal-Wallis test, P < 0.0001) to compose a quantitative aggressive classification score (proportion of aggressive nuclei from 0% to 100%). For comparisons, we used Fisher's exact test or Student's t test. The mean age was 79 ± 7 years for aggressive cSCC and 80 ± 9 years for nonaggressive cSCC (P = 0.66). We analyzed a mean of 96 nuclei in each group. The mean classification score for aggressive cSCC was significantly higher (69% ± 6%) than for nonaggressive cSCC (28% ± 5%, P = 0.00002). Overall, the classification score accurately categorized 80% of our patients (P = 0.0004). In most patients, karyometry differentiated between aggressive and nonaggressive cSCC. We found that classification scores, which provide information on individual lesions, could be used for risk stratification.
    Cancer Prevention Research 06/2011; 4(11):1770-7. DOI:10.1158/1940-6207.CAPR-10-0404 · 4.44 Impact Factor
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    ABSTRACT: Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.
    International journal of immunopathology and pharmacology 04/2011; 24(2):489-97. · 1.62 Impact Factor

  • Cancer Prevention Research 12/2010; 3(12 Supplement):PR-03-PR-03. DOI:10.1158/1940-6207.PREV-10-PR-03 · 4.44 Impact Factor

  • Cancer Prevention Research 12/2010; 3(12 Supplement):CN02-06-CN02-06. DOI:10.1158/1940-6207.PREV-10-CN02-06 · 4.44 Impact Factor
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    ABSTRACT: The chemopreventive and antitumor properties of perillyl alcohol (POH) that were studied preclinically indicate that topical POH inhibits both UVB-induced murine skin carcinogenesis (squamous cell tumor models) and 7,12-dimethylbenz(a)anthracene-induced murine melanoma (transgenic models involving tyrosinase-driven Ras). A previous phase 1 clinical trial in participants with normal-appearing skin showed that topical POH cream was well tolerated at a dose of 0.76% (w/w). Here, we performed a 3-month, double-blind, randomized, placebo-controlled phase 2a trial of two different doses of topical POH in individuals with sun-damaged skin. Participants applied POH cream twice daily to each dorsal forearm. Baseline and end-of-study biopsies were taken from each participant to evaluate whether the topical application of POH was effective in reversing actinic damage as evidenced by normalization of quantitative skin histopathologic scores and change in nuclear chromatin pattern as measured by karyometric analysis. There was a borderline reduction in the histopathologic score of the lower-dose POH group compared with the placebo (P = 0.1), but this was not observed in the high-dose group. However, in the high-dose group, a statistically significant reduction in the proportion of nuclei deviating from normal was observed by the use of karyometric analysis (P < 0.01). There was no statistical significance shown in the lower-dose group. No changes were observed in p53 expression, cellular proliferation (by proliferating cell nuclear antigen expression), or apoptosis in either treatment group compared with the placebo group. These results suggest that whereas our karyometric analyses can detect a modest effect of POH in sun-damaged skin, improved delivery into the epidermis may be necessary.
    Cancer Prevention Research 02/2010; 3(2):160-9. DOI:10.1158/1940-6207.CAPR-09-0183 · 4.44 Impact Factor
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    ABSTRACT: To determine whether low-dose topical applications of difluoromethylornithine (DFMO) with or without Triamcinolone (Fougena, Melville, New York, U.S.A.) to moderately sun-damaged skin with actinic skin keratoses are efficacious. There were 4 topically administered, 6-month treatments, DFMO + Eucerin (Beiersdorf Inc., Hamburg, Germany), DFMO + Triamcinolone, Triamcinolone + Eucerin and Eucerin + Eucerin (to serve as double placebo). Participant eligibility included evidence of at least 2 actinic keratoses on each posterolateral forearm as well as moderate to severe evidence of sun-damaged skin, as evaluated by a board certified dermatologist. High resolution digitized imagery of nuclei from histologic sections of 4-mm punch biopsies from sun-damaged skin on the posterolateral forearms was recorded, at baseline and at the end of 6 months of study. With 102 participants and 185 skin biopsies, a total of 16,395 skin cell nuclei were recorded. The nuclei were analyzed to assess the changes in the pattern of the nuclear chromatin. Two specific measures of end point evaluation were computed, including the percentage of nuclei with high values of nuclear abnormality and the reduction of the percentage of nuclei assigned by a discriminant function to the baseline data set. All 3 active interventions, including low-dose topical DFMO, topical Triamcinolone and topical DFMO + Triamcinolone, led to statistically significant reductions of both the number of nuclei with high nuclear abnormality as well as the number of nuclei assigned to the baseline data set. These reductions were found for all 3 treatments involving DFMO or Triamcinolone. For the placebo data sets only small, statistically insignificant increases or decreases of these percentages were observed. The low-dose, topical drug interventions were all effective in reducing skin biopsy nuclear abnormality by a statistically significant 15-20%, whereas there was no evidence of a double placebo effect by karyometric assessment. These effects were greater than the case-to-case sampling error.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 12/2009; 31(6):355-66. · 0.49 Impact Factor
  • Peter H Bartels · Hubert G Bartels ·
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    ABSTRACT: To present a fully worked numerical example for the derivation of a discriminant function in order to provide insight into the processing steps and origin of the function coefficients. The example begins with the reduction of a set of raw data to the values needed to calculate the variance/covariance matrix. Next the inversion of the covariance matrix by pivotal condensation is carried through. This is followed by the calculation of the coefficients. All calculations are carried out on a simple hand calculator. While discriminant analysis is routinely and widely used in the analysis of karyometric data, the process of deriving the discriminant function and its coefficients has not been demonstrated in detail, by a numerical example, in over 50 years. It is clearly not practical to conduct, by hand, a discriminant analysis on data sets as commonly encountered in karyometry. However, the use of a computer algorithm without a full understanding of the processing steps has always been deeply unsatisfactory. This tutorial article should remedy that situation.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 10/2009; 31(5):247-54. · 0.49 Impact Factor
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    ABSTRACT: To present the rationale for applying different sequences of multivariate analysis algorithms to determine if and where, in the large and high-dimensional data space, events have led to change in karyometric features. Clinical materials and results from the analysis of 4 studies were used: the demonstration of chemopreventive efficacy of letrozole in a situation where only a small subset of cells is affected, the detection of a preneoplastic lesion in colorectal tissue, data processing to document clues that predict risk of recurrence of a bladder lesion and the use of metafeatures and second-order discriminant analysis in a study of efficacy of vitamin A in the chemoprevention of skin lesions. Evidence for chemopreventive efficacy was demonstrated in the first example only after processing identified the small subpopulation of affected nuclei in a study of breast epithelial cells. Detection of a preneoplastic development is linked to a progression curve connecting nuclei from normal tissue to nuclei from premalignant colorectal lesions. The prediction of risk of recurrence of papillary bladder lesions is possible by detecting changes in nuclei of a certain phenotype. Efficacy of vitamin A as a chemopreventive agent for skin cancer could be demonstrated with a dose-response curve after a second-order discriminant analysis was employed. In none of these instances would the information of biologic interest have been revealed by a straightforward, single algorithmic analysis.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 07/2009; 31(3):125-36. · 0.49 Impact Factor
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    ABSTRACT: Recent advances in computer and information technologies have allowed the integration of both numeric and non-numeric data, that is, descriptive, linguistic terms. This has led at 1 end of the spectrum of technology development to machine vision based on image understanding and, at the other, to decision support systems. This has had a significant impact on our capability to derive diagnostic and prognostic information from histopathological material with prostate neoplasms. Cancer 2009;115(13 suppl):3068–77. © 2009 American Cancer Society.
    Cancer 07/2009; 115(S13):3068 - 3077. DOI:10.1002/cncr.24345 · 4.89 Impact Factor
  • Peter H Bartels · Hubert G Bartels · David S Alberts ·
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    ABSTRACT: To describe an algorithm that allows the correction of differences in staining of histopathologic sections while preserving chromatin texture. In order to preserve the texture of the nuclear chromatin in the corrected digital imagery, it is necessary to correct the images pixel for pixel. This is accomplished by mapping each pixel's value onto the cumulative frequency distribution of the data set to which the image belongs, to transfer to the cumulative frequency distribution of the data set serving as standard and to project the intersection down onto the pixel optical density scale for the corrected value. Feature values in the corrected imagery, for the majority of features used in karyometry, are between < 1% and a few percent of the feature values in standard imagery. For some higher-order statistical features involving multiple pixels, sensitivity to a shift in the cumulative frequency distribution may exist, and a secondary small correction by a factor may be required. The correction algorithm allows the elimination of the effects of small staining differences on karyometric analysis.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 04/2009; 31(2):63-73. · 0.49 Impact Factor
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    ABSTRACT: To assess the changes in the nuclear chromatin pattern concomitant with progressive sun damage in skin biopsies ranging from sun-exposed, normal-appearing skin to squamous cell carcinoma (SCC). Biopsies were taken from 140 cases with sun-exposed but histopathologically normal skin, from 20 cases visually assessed as pre-actinic keratosis (pre-AK) or early AK, from 30 cases of AK, and from 21 cases of SCC. A total of 21,094 nuclei were recorded from these biopsies. High-resolution digital imagery was recorded, and features descriptive of the nuclear chromatin pattern were computed. Both supervised learning and unsupervised learning algorithms were employed to derive progression plots. With increased sun exposure, the proportion of nuclei exhibiting changes in the nuclear chromatin pattern rises notably. Using karyometry, no significant differences could be substantiated between nuclei collected from early AK sites and AK lesions. Cases of SCC fell into 2 distinct groups. A larger group (approximately 66.7% of cases) had characteristics similar to AK. A smaller group (approximately 33.3% of cases) represented much more progressed lesions. Karyometric assessment can provide a numeric measure of progression for sun damage and of the deviation from normal in both AK and SCC lesions.
    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 03/2009; 31(1):17-25. · 0.49 Impact Factor
  • Peter H Bartels · Rodolfo Montironi ·

    Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 03/2009; 31(1):1-4. · 0.49 Impact Factor
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    ABSTRACT: Aromatase inhibitors are currently being evaluated as preventive agents in post-menopausal women at high risk for breast cancer. A phase II trial of 42 women on hormone replacement therapy (HRT) treated with letrozole for 6 months showed Ki-67 was reduced by 66% but showed no change in cytomorphology or Masood score. Subsequent image analytical procedures (karyometry) conducted on a subset of the samples captured subvisual information that showed reduced cellular abnormality after 6 months of letrozole. In the present study we expanded on the preliminary karyometry study to determine if the change in karyometric measurements corresponded to changes in risk biomarkers quantified in the Phase II trial; and secondly, whether these biomarkers might be used together to serve as markers of response in individual cases. Pap stained slides from the Phase II trial were used. Epithelial cell images were digitized on a CCD video-microphotometer and the nuclei were segmented from the field using a semiautomatic algorithm. Nine out of 37 cases analyzed showed a numerical decrease in all three markers, although only three of these exhibited changes substantial enough to be considered as an improvement. However, 12 cases showed improvement by cytology (a decrease in Masood score of at least 2), an additional 13 cases demonstrated a reduction in Ki-67 expression by 50% of the median baseline value, and an additional five cases exhibited a decrease of at least 10% in abnormal cells by nuclear morphometry. Thus, a total of 30 of 37 cases (81%) showed improvement in at least one marker. There was no correlation between changes in Ki-67%, karyometric abnormality, and Masood score change other than specimens that exhibited an improvement in cytology also displayed greater decreases in nuclear morphometry abnormalities. Given the heterogeneity of mechanisms leading to malignancy, the quantitative analysis of nuclear chromatin patterns may be valuable as a global, or integrating, biomarker of change in chemoprevention studies in conjunction with additional markers. Correlation with long term clinical outcome is needed to validate meaningful combinations of informative biomarkers.
    Breast Cancer Research and Treatment 02/2009; 115(3):661-8. DOI:10.1007/s10549-008-0274-0 · 3.94 Impact Factor

Publication Stats

4k Citations
609.58 Total Impact Points


  • 1973-2012
    • The University of Arizona
      • • College of Optical Sciences
      • • Department of Pathology
      Tucson, Arizona, United States
  • 1994-2003
    • Queen's University Belfast
      • Centre for Cancer Research and Cell Biology
      Béal Feirste, Northern Ireland, United Kingdom
    • Thomas Jefferson University
      • Department of Pathology, Anatomy & Cell Biology
      Philadelphia, PA, United States
  • 2001
    • Universidade Federal do Rio Grande do Sul
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 2000
    • University of Udine
      Udine, Friuli Venezia Giulia, Italy
  • 1996
    • King's College London
      Londinium, England, United Kingdom
    • Università Politecnica delle Marche
      • Institute of Pathological Anatomy
      Ancona, The Marches, Italy
  • 1995
    • University of Turku
      • Department of Pathology
      Turku, Varsinais-Suomi, Finland
  • 1981-1992
    • University of Chicago
      • • Department of Pathology
      • • Department of Obstetrics & Gynecology
      • • Section of Cardiology
      Chicago, Illinois, United States
  • 1988-1989
    • University of New Mexico
      • Division of Hospital Medicine
      Albuquerque, New Mexico, United States
  • 1982
    • Loma Linda University
      Loma Linda, California, United States
  • 1980
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1979
    • University of Illinois at Chicago
      • Section of Cardiology
      Chicago, Illinois, United States
    • Boston Children's Hospital
      • Department of Neurology
      Boston, Massachusetts, United States
  • 1974
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan