Biomedical subjects

R Kiss

Publications and source records attributed to R Kiss.

At least 163 records · Page 9Linked to original sources

PubMed1995

Influence of dihydrotestosterone, epidermal growth factor, and basic fibroblast growth factor on the cell kinetics of the PC3, DU145, and LNCaP prostatic cancer cell lines: relationship with DNA ploidy level.

The cell kinetics (percentage of cells in the S+G2 phases of the cell cycle) and the DNA ploidy levels (nuclear DNA content) were determined in 108 samples each of the PC3, DU145, and LNCaP prostate cancer models. This was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. Two to three hundred cell nuclei were analyzed for each of the 324 samples under study. The three cell lines were submitted to experimental conditions including the addition of dihydrotestosterone (DHT), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), either alone or in combination, to the culture media. The results show that under the present culture conditions, the PC3 cell line was DHT-, EGF- and bFGF-insensitive. In contrast to what is generally reported in the literature, the DU145 cell line was DHT- and EGF-sensitive under the present culture conditions, but bFGF-insensitive. The LNCaP cell line was DHT-sensitive, but EGF- and bFGF-insensitive. While mainly tetraploid, the three cell lines nevertheless exhibited a significant level of heterogeneity in their nuclear DNA content distributions. Indeed, the proportions of non-tetraploid (diploid, hyperdiploid, triploid, hypertriploid, hypertetraploid, polymorphic) DNA histograms were 14% in the PC3, 16% in the DU145, and 29% in the LNCaP cell lines. These results suggest that the DNA ploidy level would not influence the hormone sensitivity level in the cell lines since they had significantly distinct hormone sensitivity profiles while remaining mainly tetraploid.

Cell Division↗

PubMed1995

Morphonuclear characterization of drug resistance by means of digital cell-image analysis: an in vitro assessment.

The prediction of tumor resistance to antineoplastic drugs remains an important challenge in cancer chemotherapy. Several methods have been proposed in this connection, but they present a number of problems such as clinical relevance and applicability. In the present work we put forward an original methodology to assess the drug sensitivity of cancer cells. For this purpose we submitted chemosensitive and chemoresistant cell lines to different anticancer drugs and monitored the cell growth and the drug-induced morphonuclear effects by means of digital cell-image analysis of Feulgen-stained nuclei. The results showed that drug-induced effects at the morphonuclear level correlated statistically with the effects produced at the cell proliferation level. For example, the mean nuclear size value increased as a function of the drugs' efficiency recorded at the cell proliferation level. In the same way, the frequency of large dense chromatin clumps also increased in accordance with the drugs' efficiency. The present work thus demonstrates that digital cell-image analysis can be applied to monitor the efficiency of chemotherapeutic treatment carried out on cell lines in vitro. The present methodology could possibly be used on solid tumors, from which biological material can be obtained serially by means of fine-needle aspiration. As evidence of this, the present methodology can also be applied to hematological cancers.

Animals↗

PubMed1995

Characterization of chemotherapy-induced morphonuclear modifications in the P388 leukaemia and the MXT mammary tumour models of the mouse.

Chemotherapy-induced morphonuclear modifications were monitored in vivo by means of the digital cell image analysis of Feulgen-stained nuclei. Two experimental models were used, i.e. the P388 mouse leukaemia and the MXT mouse mammary carcinoma. The drugs used were doxorubicin, etoposide and cyclophosphamide. The results indicate that the chemotherapy induced a significant decrease in the MXT tumour growth and a significant increase in the survival of the P388 leukaemic mice. These effects were accompanied at the morphonuclear level by an increase in the nuclear area, by modifications in the DNA content in accordance with the effects of the drugs on the cell cycle and by several modifications in the chromatin texture in accordance with the model or the drugs studied. While there were neither homogeneous morphonuclear changes in all treatment groups nor clearcut correlations between the morphonuclear changes and tumour growth or the survival of the animals, the present study nevertheless shows that it is possible, at least partly, to monitor in vivo certain chemotherapy-induced effects occurring at the morphonuclear level, and subsequently to obtain information on the mode of action of the drugs.

Animals↗

PubMed1995

The use of the digital cell image analysis of Feulgen-stained nuclei to detect apoptosis.

Cell death is an essential event in the functioning of multicellular organisms. It plays a role opposite to that of mitosis in the regulation of cell populations. In the present work, we describe an original methodology which permits the easy detection and count of apoptotic cells in a given tissue. This methodology is based on the digital cell image analysis of Feulgen-stained nuclei, which also permits the calculation of the proliferation index, i.e. the percentage of cells in the S phase of the cell cycle. This percentage of cells in the S phase is strongly related to the mitotic index. Our methodology, which involves the multivariate analysis of 14 morphonuclear parameters computed by means of the digitized cell image analysis of Feulgen-stained nuclei, was applied here to a well-known biological apoptosis model, namely glucocorticoid-treated rat thymocytes. The parameters that permitted the detection of apoptotic cells were the integrated optical density, a parameter that describes the nuclear DNA content, and the run length percentage and long run length parameters which are related to the pattern of chromatin condensation. This determination can be carried out on a relatively small number of cells.

Animals↗

PubMed1995

Chemotherapy-induced nuclear alterations of morphologic and genomic characteristics in a human colon cancer grafted onto nude mice.

PURPOSE: A human Dukes B colonic adenocarcinoma was grafted onto 40 nude mice. The mice were divided into four groups, one control and three representing experimental conditions. Animals in the three experimental groups received either adriamycin (ADR), 5-fluorouracil (5-FU), or camptothecin (CPT) over a 25-day period beginning 34 days after grafting. Control animals received saline on an identical schedule. Animals were killed 105 days after grafting. METHODS: The effect of therapy was assessed by three techniques: 1) tumor size was periodically measured during the life of the animals, 2) modifications of APC, Ki-ras, and p53 genes were studied by polymerase chain reaction, dot-blot analysis, restriction analysis, and DNA sequencing, and 3) image cytometry of Feulgen-stained material was used to characterize 15 parameters describing morphometric, densitometric, and textural features of tumor nuclei. RESULTS: When compared with controls, tumor growth (size) was maximally suppressed by treatment with CPT (P < or = 0.001). Growth was inhibited significantly by treatment with 5-FU (P < or = 0.01); no statistical difference in tumor size was observed between controls and animals treated with ADR. Modifications of APC, Ki-ras, and p53 genes were not observed; however, treatment did inhibit amplification of APC and p53 genes. CONCLUSIONS: The 15 morphonuclear parameters were assessed to define populations of cell nuclei altered by chemotherapy. Although CPT maximally suppressed growth, it did not alter nuclear morphology when compared with controls. Treatment with either 5-FU or ADR resulted in nuclear morphologic alterations defined as distinct populations using multivariate analysis. Nonsupervised linear discriminant analysis was used to quantify the relative proportions of these populations. Four morphonuclear parameters were identified, which discriminated nuclei exposed to either ADR or 5-FU from controls.

Adenocarcinoma↗

PubMed1995

Image cytometry determination of ploidy level, proliferative activity, and nuclear size in a series of 314 transitional bladder cell carcinomas.

Image cytometry was carried out on 281 superficial (Ta and T1) and 33 invasive (T2 to T4) bladder cancers. The parameters used to characterize these bladder tumors were: (1) histopathological grading, (2) clinical staging, (3) tumor size, (4) deoxyribonucleic acid (DNA) index (DI), (5) DNA histogram type (DHT), (6) percentage of euploid (diploid plus tetraploid) cells, (7) percentage of polyploid cells (> 5C DNA content), (8) proliferative activity (S phase fraction value), and (9) nuclear area (NA). The proliferative activity of the tumors was not related to either histopathological grade or to clinical stage, but it was related to the DHT parameter, which made it possible to identify diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic tumors. The hypertriploid tumors exhibited a significantly lower proliferative activity than the nonhypertriploid ones. Although both the DI and the NA values correlated significantly with histopathological grading, only the NA values correlated significantly with clinical staging. We further observed that some grade III bladder tumors were definitely diploid, whereas some grade I tumors were highly aneuploid. We thus hypothesize that the ploidy level of a given tumor reflects its age directly and its aggressiveness only very indirectly. In our opinion aneuploidy is only an indirect marker of aggressiveness because it reflects the fact that a malignant tumor is old, ie, has been present in a patient over a long period of time and has had ample time to express its malignancy at the clinical level. A significant relationship was accordingly obtained between tumor size and ploidy level with the highest proportion of aneuploid tumors and the highest percentage of polyploid cell nuclei being observed among the largest bladder tumors.

Adult↗

PubMed1995

Combination of computerized morphonuclear and multivariate analyses to characterize in vitro the antineoplastic effect of alkylating agents.

The influence of 13 anticancer alkylating agents on cell proliferation, cell cycle parameters, and morphonuclear characteristics was monitored in vitro on three neoplastic cell lines. This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. This computer-assisted microscope analysis of chromatin texture made it possible to assess 15 morphonuclear parameters. These 15 parameters were submitted to multivariate analyses, that is, principal-components analyses followed by the canonical transformation of the data. The 13 alkylating agents included four nitrogen mustards (chlormethine, chlorambucil, melphalan, and cyclophosphamide), two nitrosoureas (carmustine and lomustine), two platinum analogues (cisplatine and carboplatine), two ethyleneimine derivatives (thiotepa and investigational PE1001), one antibiotic (mitomycin C), one alkylsulfonate (busulfan), and one triazene (dacarbazine). The mouse MXT mammary and the human J82 and T24 bladder tumor cell lines were used in this study. The results show that these alkylating agents induced specific modifications to the chromatin pattern according to the subclass to which they belong. In other words, the multivariate statistical analyses of the 15 parameters made it possible to identify, at least partly, distinct subclasses of alkylating agents according to their mechanisms of action. As a validation of the methodology, the results also show that most of the alkylating agents induced an increase in the percentage of cells in the G2 phase, while some sometimes induced an increase in the percentage of cells in the S phase of the cell cycle.

Adenocarcinoma↗

PubMed1995

Characterization of alkylating versus intercalating anticancer drug-induced effects on cell survival, cell cycle kinetic and morphonuclear pattern of three neoplastic cells lines growing in vitro.

PURPOSE: The influence of three alkylating and three intercalating anticancer drugs on cell survival, cell cycle kinetics and chromatin patterns was monitored in vitro on three neoplastic cell lines. METHODS: This monitoring was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. RESULTS: Results show that in term of cytotoxicity, the intercalating drugs were more potent than the alkylating ones. As for the cell kinetics assessment, most of the experimental conditions led to a blockage of the cells in the G2 phase of the cell cycle. A study of chromatin patterns by means of digital cell image analysis enabled us to describe 15 morphonuclear parameters. The results show that the drugs tested induced specific morphonuclear modifications, e.g. an increase in nuclear size. The 15 morphonuclear parameters were submitted to multivariate analyses, i.e. principal-components analyses followed by the canonical transformation of the data. The results of these multivariate analyses enabled us to discriminate between the alkylating and the intercalating drugs. CONCLUSIONS: We conclude that it would be possible to "diagnose" the mechanism of action of DNA interacting agents (alkylating or intercalating drugs) by means of the combination of digital cell image and multivariate analysis.

Adenocarcinoma↗

PubMed1995

Relationship between DNA ploidy level, nuclear size, and survival in large cell lymphoma.

Intermediate and high grade subtypes of non-Hodgkin's large cell (LCL) and immunoblastic lymphomas exhibit considerable variability, and histologic morphology alone may not adequately characterize those features important for prognosis. The relationship between nuclear morphology and survival was assessed in a series of 50 cases of large cell lymphomas in which ploidy, proliferation, and nuclear area (NA) were measured. Ploidy was calculated by both DNA index (DI) and DNA histogram type (DHT). Proliferation was calculated from the proportion of S phase (SPF) cells present in the DHT. These four parameters were measured using image cytometry of Feulgen-stained nuclei from fine-needle aspirations. To characterize the relationship with survival, these parameters were associated with the clinical follow-up of the patients. The results show that of the 50 LCL cases, only 5 were clearly aneuploid, whereas the remaining 45 were either diploid (29 cases), tetraploid/hypotetraploid (13 cases), or weakly aneuploid (hyperdiploid, 3 cases). Of the 34 patients who died from their disease, both smaller NA and DI correlated with longer survival in an equivalent fashion; neither conferred greater sensitivity when combined with the other. The SPF did not correlate with survival. In LCL, aneuploidy seems to be a relatively uncommon event, but when present ploidy measurement appears useful to define prognosis.

Adult↗

PubMed1995

Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.

Adolescent↗

PubMed1995

Prognostic evaluation of morphonuclear parameters in superficial and invasive bladder cancer.

OBJECTIVE: To assess the prognostic value of morphonuclear parameters determined by means of computerized image analysis in untreated bladder tumours. PATIENTS AND METHODS: Fifty patients had untreated bladder cancer; in 28 patients the tumours were superficial (7pT1G1; 14pT1G2; 7pT1G3) and in 22 they were invasive (6T2G2, 9T2G3, 2T3G2, 5T3G3). Feulgen-stained imprints were processed for morphonuclear analysis on a SAMBA 200 computerized image analysis system (T1TN, France), which measures optical density (integrated optical density, IOD; surface area, SURF; mean optical density, MOD), texture (long run length, LRL; short run length, SRL; run length distribution, RLD; run length percentage, RLP; grey level distribution, GLD) and contrast (contrast, C; energy, E). RESULTS: Morphonuclear parameters IOD, SURF, LRL, SRL and C were found to correlate with the risk of recurrence and progression of superficial bladder tumours (results for ANOVA respectively IOD P < 0.001; SURF P = 0.02; LRL P = 0.05; RLD P = 0.04; SRL P = 0.04; C P < 0.001). In invasive bladder cancer, parameters IOD and C only correlated with the risk of progression (ANOVA respectively IOD P < 0.001; C P < 0.001). On the other hand, progression-free curve analysis using the Kaplan Meier method showed that morphonuclear parameters may be useful in predicting the outcome for superficial tumours (Log/Rank test: SURF P < 0.001; RLD < 0.001; SRL = 0.003; LRL < 0.001; C < 0.001; IOD < 0.001). In the case of invasive tumours, only two parameters provided prognostic information (Logrank test: C < 0.001; IOD < 0.001). CONCLUSION: Nuclear morphometry assessed by image analysis is potentially useful in assessing the prognosis of bladder tumours; it provides objective and quantitative parameters. Further studies will determine whether morphonuclear analysis can be used to monitor the treatment of bladder cancer, particularly superficial tumours.

Analysis of Variance↗

PubMed1995

Cytotoxicity, cell cycle kinetics and morphonuclear-induced effects of Vinca alkaloid anticancer agents.

The effects of four Vinca alkaloids (vinblastine, vincristine, vindesine and vinorelbine) on three neoplastic cell lines (the MXT mouse mammary cell line and the T24 and J82 bladder cell lines) were studied at three biological levels, i.e. cell proliferation, cell cycle kinetics and morphonuclear characteristics. These effects were studied by means of digital cell image analysis on Feulgen-stained nuclei. The aim of the present work was to characterize the effects specifically induced by Vinca alkaloids as compared with those obtained previously with other pharmacological classes of anticancer drugs. The results show that Vinca alkaloids inhibit the cell proliferation of neoplastic cell lines at a concentration of 10(-8) M except in the case of the J82 cell line, for which only a slowing down of cell proliferation was observed. Concerning the cell cycle kinetics, the results show that the Vinca alkaloids induce an accumulation of cells in the mitosis phase. This accumulation of mitotic cells was maximal after 15 h incubation in the presence of the drugs. A study of the morphonuclear-induced effects of Vinca alkaloids showed that the variance of the optical density (VOD) is strongly influenced by these Vinca alkaloids. The development of the VOD was parallel with the development of the percentage of mitosis; thus, the VOD enabled the Vinca alkaloid-induced effects to be specifically characterized from a morphonuclear point of view. On the other hand, the results show that the mean value of the variance of the optical density was very highly correlated (P < 0.001) with the efficiency of the Vinca alkaloids in terms of cytotoxicity. In clinical studies, the analysis of the development of this parameter would make it possible to assess the response to chemotherapy in the case of patients treated with Vinca alkaloids.

Adenocarcinoma↗

PubMed1995

Characterisation of the influence of anti-gastrin, anti-epidermal growth factor, anti-oestradiol, and anti-luteinising hormone releasing hormone antibodies on the proliferation of 27 cell lines from the gastrointestinal tract.

Numerous data from published reports prove that the proliferation of gastrointestinal tumour cell lines are under the control of many hormones or growth factors, or both. Most of these publications report the influence on a very small number of cell lines of one or two such factors only. This work deals with the in vitro characterisation of the influence of the anti-gastrin, the anti-epidermal growth factor (EGF), the anti-oestradiol (E2), and the anti-luteinising hormone releasing hormone (LHRH) antibodies on the proliferation of a large series of gastrointestinal cell lines. Cell proliferation was assessed by means of the colorimetric MTT assay on a series of 27 gastrointestinal cell lines obtained from the American Type Culture Collection (ATCC). Of the 27 cell lines, the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH neutralising antibodies considerably influenced the proliferation of 13, 25, 12, and 16. No gastrointestinal cell line was unresponsive to the four antibodies simultaneously. The anti-gastrin and anti-EGF antibody induced effects on the 27 gastrointestinal cell line proliferation were significantly correlated, as was also the case for the anti-E2 and anti-LHRH antibody induced effects. Of the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH antibodies, it was the anti-EGF one that had the greatest influence, both quantitatively and qualitatively, on gastrointestinal cell proliferation. The correlation of the effects of definite anti-hormone antibodies is suggestive of a common mechanism of action for the corresponding hormones and casts some doubt on the efficiency of anti-hormone monotherapy.

Animals↗

PubMed1995

Aneuploidy occurrence in human tumours: a logical-automaton approach.

The search for new, reliable factors of prognosis in cancerology is sadly deficient at the present moment. Of these factors, the measurement of ploidy gives rise to considerable hope. Nevertheless, despite the impressive number of papers currently published, no general law seems to be emerging that associates the ploidy rate of a tumour with its clinical evolution in a patient. The purpose of the present work is firstly to use a logical automation to describe the cell cycle in terms of binary variables (the validation of the methodology), and secondly to demonstrate that a certain 'cancer logic' can be distilled, at least with respect to the genesis of DNA histograms among tumours.

Aneuploidy↗

PubMed1995

[Organ culture of human tissue as study model of hormonal and pharmacological regulation of benign prostatic hyperplasia and of prostatic cancer].

We have established organ cultures of human prostate in vitro analysis of the hormone responsiveness of prostatic carcinoma. The influence of dihydrotestosterone (DHT), the epidermal growth factor (EGF) and prolactin (PRL) was assessed on the proliferation rate of 30 benign human prostatic hyperplasias (BPH) maintained for 48 hours as short-term primary cultures. The influence exerted by the EGF, the DHT and the PRL on the BPH cell proliferation was characterized by adding these compounds alone or in combination to the culture media. The proliferation rate was assessed by means of histo-autoradiographical nuclear labeling with titriated thymidine. The results show that of the DHT, EGF and PRL, the first two induced a statistically significant increase in the cell proliferation rate in a proportion of BPH significantly higher than the proportion of BPHs whose cell proliferation was increased significantly by the PRL. Furthermore, the PRL was able to antagonize the EGF-induced stimulatory effect on the BPH glandular cell proliferation rate. Lastly, the EGF- and PRL-mediated effects on the BPH glandular cell proliferation correlated with each other, while the DHT-mediated did not correlate with either the PRL- or the EGF-mediated effects. This model of organ, culture provide a basis for developing a method for in vitro testing of the individual hormone and drug responsiveness of a prostatic carcinoma.

Aged↗

PubMed1995

In vitro digital cell image analysis of morphonuclear modifications induced by natural DNA-interacting anticancer drugs in three neoplastic cell lines.

The effects of seven natural anticancer drugs acting through interaction with DNA were characterized at three levels: cell proliferation, cell cycle kinetics and chromatin texture. These drug-induced effects were monitored in vitro by means of the digital cell image analysis which provides 15 morphonuclear parameters. In terms of cell proliferation, results show that the drug-induced effects ranged from 10(-11)M to 10(-6)M. With respect to the cell cycle kinetics, the results show that the drugs induced an accumulation of the cells in the G2 phase. Concerning the chromatin levels, the results show that it is possible to classify the drugs according to their mechanism of action on the basis of the multivariate analysis of the 15 parameters.

Animals↗

PubMed1995

Stereotactic biopsies from astrocytic tumors. Diagnostic information contributed by the quantitative chromatin pattern description.

OBJECTIVE: To reduce the problem of heterogeneity in astrocytic tumors by means of computer-assisted microscope analysis of Feulgen-stained nuclei. STUDY DESIGN: Thirty-eight glial tumors for which we obtained 227 stereotactic biopsies were subjected to digital cell image analysis of Feulgen-stained nuclei. This series of 38 glial tumors included 36 supratentorial astrocytic tumors (13 astrocytomas, 7 anaplastic astrocytomas and 16 glioblastoma multiformes) and 2 grade 3 astrocytic tumors of the cerebellum. RESULTS: The results suggest a new methodology, enabling the biologic characteristics of the brain parenchymal area surrounding a given glial tumor to be characterized. This methodology relies on the performance of three successive steps. The first is quantitative characterization of nuclear morphology and its chromatin pattern by means of 15 morphonuclear variables. This characterization is carried out by means of the computer-assisted microscope analysis of Feulgen-stained nuclei. The second step consists of setting up morphonuclear data banks, with each process giving the precise portrait of a given cell nuclear population. This process is carried out by means of multivariate analysis, taking into account the 15 variables mentioned above. Multivariate analysis includes principal components analysis followed by the canonical transformation of the data. The third step consists of testing unknown cases against these morphonuclear data banks. This is carried out by means of linear discriminant analysis, which enables the various cell nuclear types in the stereotactic biopsy to be quantified. CONCLUSION: The present methodology makes it possible to investigate whether infiltrating tumor cells are present in or absent from the parenchymal brain area surrounding a glial tumor. It can therefore contribute additional information to that contributed by computed tomography and/or magnetic resonance imaging with respect to the precise delineation of the volume of a brain tumor. This delineation must be as precise as possible to allow total surgical resection of the tumor and prevention of its recurrence.

Astrocytoma↗

PubMed1995

Multiparameter digital image analysis of biliary, ampullary, and pancreatic adenocarcinomas.

Periampullary adenocarcinomas arise from pancreatic, biliary, or ampullary ductal epithelium. Their origin is difficult or impossible to discern by routine light microscopy of cytologic or small biopsy specimens. We used image analysis to describe the morphologic features of Feulgen-stained nuclei of biliary and ampullary adenocarcinomas and to compare these findings with those of pancreatic ductal adenocarcinomas. Surgically resected cases of ampullary adenocarcinoma (n = 7) and cholangiocarcinoma (n = 26) were selected on the basis of available formalin-fixed, paraffin-embedded tissue and diagnostic clinical data. Disaggregated nuclei were stained by the Feulgen reaction and analyzed using a digital image processor. Data from 15 morphonuclear parameters were assessed and compared with the results from the morphonuclear analysis of 22 pancreatic ductal adenocarcinomas. Multivariate analysis with canonical transformation of the data defined the ampullary adenocarcinomas and cholangiocarcinomas as occupying similar factorial distributions, whereas the pancreatic carcinomas were separate and distinct. Monovariate analysis identified seven parameters distinguishing pancreatic carcinoma from both ampullary carcinoma and cholangiocarcinoma, with P values < or = 0.001 and two others having P values < or = 0.01. Adenocarcinomas of ampullary or bile duct origin possess similar morphonuclear features described by image analysis. Image analysis provides a mechanism to discriminate adenocarcinomas arising from the bile ducts or ampulla from those arising in the pancreas.

Adenocarcinoma↗