Perianal Paget's disease: case report and review of the literature.

Cutaneous Paget's disease (PD) is a rare entity, predominantly involving the breasts. Anal involvement is rather exceptional, and can be associated with underlying malignancies, among which prostate and rectal adenocarcinoma. We report the case of a 71-year-old man suffering from a long history of anal itching, associated with an erythematosquamous lesion of the right buttock extending up to the anus. The diagnosis of perianal PD (PAPD) was confirmed by histopathological demonstration of Paget's cells from a biopsy performed after ineffective topical treatment. Radiological and further clinical inspections allowed us to exclude any synchronous malignancy. A first-step surgery consisted in coelioscopic diverting sigmoid colostomy, along with multiple perianal, anal and rectal biopsies revealing an anal canal involvement. Coelioscopic abdominoperineal surgery and a wide cutaneous excision were then performed. Histopathological analysis revealed positive posterior margin, requiring further excision. No adjuvant therapy was prescribed, and to this day, after a one-year and a half follow-up, the patient remains disease-free. Our case report and review of PAPD stress that appropriate management is required to improve the poor prognosis of this rare affection.

Ploidy and chromatin pattern analysis as an aid for cervical smear diagnosis.

In the present study we used computer-assisted microscopy to analyze the morphology of Feulgen-stained cell nuclei in cell populations obtained at the same time as routinely performed cervical smears and in the same way. We investigated in a series of 110 cases whether the quantitative morphonuclear description of cytological cervical samples is able to aid pathologists to distinguish between benign and more suspect premalignant lesions. For this task nuclear DNA content, nuclear morphometry (size and anisonucleosis level) and chromatin pattern-related parameters were compiled for each specimen enrolled in the database. A set of 32 normal and 17 high-grade squamous intraepithelial lesion (HSIL) specimens (with diagnostic confirmations) were selected as references and used to establish a discriminant model on the basis of cytometry-generated variables. This model was then used to score the remaining 61 cases in our series (including cases exhibiting benign cellular changes, squamous cells of undetermined significance, low-grade SIL and cancers). The results show that a model discriminating efficiently between normal and HSIL groups can be obtained by combining 5 quantitative features (1 DNA ploidy-related, 2 morphometrical and 2 chromatin texture features). A 97% specificity and an 88% sensitivity characterized the boundary so established. When applied to new cases, the model was in fact able to correct diagnoses for cases which had been down- or up-graded on the basis of the Bethesda system, and provided scores in accordance with histological control.

Severe acute pancreatitis associated with peliosis hepatis in a patient with systemic lupus erythematosus.

Acute pancreatitis is an unusual complication of systemic lupus erythematosus but can also stem from immunosuppressive therapy. Although abnormal liver tests are commonly seen in SLE, peliosis hepatis is very rarely described. We report here the first case of SLE associating a severe acute pancreatitis with peliosis hepatis who responded well to the immunosuppressive therapy. As suggested by the favourable outcome in this case, the presence of peliosis hepatis in SLE cannot not be held as a strong argument against an aggressive immunosuppressive therapy.

Breast sensation after superior pedicle versus inferior pedicle mammaplasty: anatomical and histological evaluation.

Despite contradictory information about the course and distribution of the nerves supplying the breast, surgical techniques using an inferior pedicle have been recommended over those using a superior pedicle for preserving the nipple-areolar sensation after surgery. This anatomical study was designed to quantify the nerve branches preserved in inferior and superior pedicles after reduction mammaplasty performed on cadavers. Reduction mammaplasty was done on four fresh cadavers (within 48h of death) using a superior pedicle on the right and an inferior pedicle on the left in a standard way. The pedicle was cut at its base and then fixed in formalin. The base was divided in biopsy specimens and embedded in paraffin. The nerves were quantified and located in each pedicle with haematoxylin-eosin stain and light-microscopic evaluation. Histological evaluation of the pedicles showed the presence of a variable number of nerves (between one and seven) within two superior pedicles and three inferior pedicles. The nerves were located in fibrous tissue and accompanied by vessels in most cases. The nerves were always found superficially and were most likely to be located in the central part of the pedicle. Our results showed that including the nerves within the pedicle is technically uncertain regardless of the mammaplasty technique used. The final recovery of sensation in the breast after mammaplasty seems to result from the regeneration of severed cutaneous nerve branches or the remaining cutaneous innervation rather than the preserved adjacent cutaneous branches.

Use of image cytometry to classify biliary and ampullary adenocarcinomas.

OBJECTIVE: To create an objective classification system to perform TNM classification of ampullary adenocarcinoma and cholangiocarcinoma using image cytometric data derived from Feulgen-stained tumor nuclei. STUDY DESIGN: Surgically resected cases of ampullary adenocarcinoma and cholangiocarcinoma with established TNM classifications were selected on the basis of available formalin-fixed, paraffin-embedded tissue. Fifteen numerical variables related to morphometric, densitometric and textural features of each tumor nucleus were recorded. We employed a methodology based on multivariate statistical tools to characterize the association of morphonuclear variables with TNM classification. The first step consisted of identifying and selecting representative nuclei of each T class. From this "purified" data set an objective classification system was created. The classification system was assessed using internal and external validation. RESULTS: Employing ANOVA, all 15 variables were significantly associated with T classification, 11 of 15 with N and 4 with M. Multivariate analysis was employed to distinguish between T1, T2 and T3 lesions. Our methodology correctly classified 76% of T1 nuclei, 47% of T2 nuclei and 84% of T3 nuclei. Heterogeneity within an individual tumor was defined in 61% of cases included in the training set. Complete concordance between pathologic classification and the classification system was observed in 71% of an independent validation.

Detection of Helicobacter pylori infection in children with a standardized and simplified 13C-urea breath test.

BACKGROUND: The 13C-urea breath test, a reliable noninvasive method of detection of Helicobacter pylori in adults, needs validation in children. METHODS: In order to evaluate the diagnostic accuracy of 13C-urea breath test in children, the results of this test performed in 144 children were correlated with the histology and culture of contemporaneous gastric (antral and fundic) biopsy specimens. The test was performed with 2 mg/kg body weight 13C-Urea (maximum, 100 mg) ingested after a fat-rich test meal. Samples of expired breath taken at 0, 5, 10, 20, and 30 minutes were assayed with mass spectrometry. Results were considered positive when the curve of excretion of labeled carbon dioxide in the expired breath increased by 5%O or more above the baseline. RESULTS: Discrepancies in H. pylori status were observed in 14 children. To improve and simplify the test, the results were reanalyzed using different cutoff values for each sampling time. The best results, with sensitivity of 95.7% and specificity of 95.2%, were obtained with a cutoff of 3.5%O at 20 minutes. CONCLUSIONS: The 13C-urea breath test is a reliable method for the noninvasive detection of H. pylori infection in children. The test can be simplified and its accuracy improved using only the 0- and 20-minute breath samples and a cutoff of 3.5%O instead of the classical 5%O used in adults. The need for modification of the cutoff value may reflect the higher production of endogenous CO2 in children.

[Severity of ingestion of caustic substance in children]. / Gravité des ingestions de produits caustiques chez l'enfant.

BACKGROUND: Caustic ingestion is frequent in children, sometimes leading to esophageal stricture. PATIENTS AND METHODS: Between 1988 and 1994, esogastroscopy was performed in 65 children after caustic ingestion. The children were classified in three groups: no lesion (group A), minimal lesions (group B) and severe lesions (group C). Nature of the caustic substance, clinical signs and evolution were compared in the three groups. RESULTS: Median age was 2 years for the 65 children (24 girls, 41 boys). Ingestion occurred at home (94%) during meal periods. Substances were dishwater detergents (n = 14), oven cleaner (n = 10), bleach (n = 9), washing powder (n = 4), others (n = 20), more often in a liquid form (n = 37) than solid (n = 28). Children had no symptoms (57%), presented emesis (n = 20) or abdominal pain (n = 10) not correlated to endoscopic findings, and hematemesis (n = 3) or respiratory distress (n = 4), both symptoms seen only in group C. Buccal lesions (41%) were not correlated to endoscopic findings. After endoscopy, 28 children (43%) were classified into group A and 20 children (31%) in group B. Among the 17 children (26%) of the group C, eight developed an esophageal stricture: seven long strictures requiring replacement of the esophagus, one short stricture requiring repeated dilations. CONCLUSION: Esophageal stricture is still a severe complication after caustic ingestion. These data stress the interest of controlled studies to confirm the preventive role of high dose corticosteroids, and the importance of the prevention of accidental caustic ingestions in children.

Characterization by means of Delaunay triangulation and Voronoi paving of the influence of anti-hormone and/or anti-growth factor antibodies on the in vitro cell growth of human colorectal neoplastic cell lines.

A new tool is described which makes it possible to evaluate directly the influence of various growth factors on in vitro neoplastic cell growth on the one hand and to look at a concept of differentiation in terms of population dynamics, on the other. This tool relies upon the digital cell image analyses of Feulgen-stained nuclei and the mathematical method of Voronoi paving. This technique enabled us to characterize the influence on the proliferation and the differentiation of the HCT-15 and LoVo colorectal cell lines of anti-gastrin (G), anti-estradiol (E(2)), anti-epidermal growth factor (EGF), anti-luteinizing hormone-releasing hormone (LHRH), and anti-transforming growth factor alpha (TGF alpha) and beta (TGF beta) antibodies. Two variants were set up with respect to each of the two cell lines, i.e, one growing in culture medium supplemented with 5% fetal calf serum (FCS) and another supplemented with 1% FCS+10 nM G+10 nM E(2). The data show that it is possible to characterize the cell clone structure and to assess growth rate concomitantly by direct cell counts. It further appears that while the anti-hormone and/or anti-growth factor antibody-induced effects on growth were relatively similar, these effects were in sharp contrast at the level of cell clone architecture.

Multiple clonal chromosome aberrations in a case of childhood focal nodular hyperplasia of the liver.

A case of focal nodular hyperplasia is described that was accompanied by intense reactive stromal changes giving rise to a pseudosarcomatous appearance. Cytogenetic study revealed complex karyotypic abnormalities including five partially identifiable clonal aberrations and one marker chromosome. The composite karyotype was interpreted as: 45-46,XY,add(4)(q21-25)[24], add(11)(p14)[24], add (19)(p13)[15], der(20)t(1;20)(q25;p12)[31], add(21) (q22)[13],-22[3], +mar[2][cp31]. In addition, quadriradial or complex figures, telomeric associations tas, unidentified ring chromosomes, chromosome breaks, and markers were seen in some cells. Such cytogenetic findings, although suggestive of malignancy, could most likely be related to a nonneoplastic condition, i.e., the unusual florid reactive changes associated with this focal nodular hyperplasia.

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.

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.

Severe hepatotoxicity related to benzarone: a report of three cases with two fatalities.

We report three cases of severe hepatotoxicity related to benzarone, a benzofuran derivative. Our cases include a 35-year-old woman with (sub)fulminant hepatitis, a 67-year-old woman with macronodular cirrhosis, and a 68-year-old man with severe chronic active hepatitis and cirrhosis, with positivity of anti-smooth muscle antibodies. Two patients died. We stress the potential of benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related to benzarone.

Listeria monocytogenes hepatitis in a liver transplant recipient: a case report and review of the literature.

Listeria is an uncommon cause of hepatitis in adults. We report the case of a liver transplant recipient who presented with a clinical picture of acute hepatitis, 8 months after grafting. Blood cultures yielded Listeria monocytogenes. The patient made a full clinical recovery after adequate antimicrobial therapy (ampicillin and gentamicin intravenously for 4 weeks). Hepatitis was attributed to the Listeria infection. We believe this is the first reported case of Listeria hepatitis in an organ transplant recipient.

Nuclear DNA content, proliferation index, and nuclear size determination in normal and cirrhotic liver, and in benign and malignant primary and metastatic hepatic tumors.

The distribution values of ploidy, of the proliferation index, of the percentages of diploid cells/case, of nuclear size, and DNA histogram type are described in a series of 92 liver samples from 87 patients. The 92 samples include normal (31 cases) and cirrhotic (14 cases) tissues, benign tumors (7 cases), well-differentiated hepatocellular carcinomas (HCCs, 13 cases), moderately and poorly differentiated HCCs (8 cases), and colorectal glandular metastatic tissues (19 cases). The samples are from either fine-needle aspiration biopsy (FNAB) or histologic imprint smears (HIS). Nuclear assessments were computed on Feulgen-stained nuclei by means of a cell image processor. The results show that the mean DNA index value, the mean nuclear area (NA) value, and the mean percentages of diploid cells per sample are significantly different in the three benign groups under study (normal and cirrhotic tissues and benign tumors) as compared with the mean parameter values from the three neoplastic liver groups (well-differentiated and poorly differentiated HCCs and colorectal metastases). None of these three parameters, however, makes it possible to discriminate clearly between these six histopathologic groups at the individual case level. The mean proliferation index values were significantly lower in the normal tissues and the benign tumors than in the four other histopathologic groups. Recognizing six DNA histogram types, ie, diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic, we observed that all the benign samples (the normal and cirrhotic tissues and the benign tumors) exhibited a diploid and/or tetraploid DNA histogram pattern, whereas the neoplastic samples exhibited the six DNA histogram patterns. The combination of the five computerized parameters into a cytologic score (CS) ranging from 5 to 15 permits clear-cut discrimination between nonneoplastic and neoplastic liver cases. The specificity and sensitivity, and the positive and negative predictive values relating to this score were as high as 100%, 95%, 100%, and 96%, respectively.

Heterogeneity of DNA ploidy, proliferation index and nuclear size in human colorectal carcinomas.

Measurements of DNA ploidy, proliferation index and nuclear area were performed on 210 samples taken from 15 human colorectal tissues. The tissues were divided into four groups labeled G1, G2, G3 and C. For each of the 15 tissues 9 samples were taken from the so-called unaffected--i.e., marginal--mucosa (G1-G3 groups) and 5 from the tumor (C group). The 9 samples from the unaffected mucosa of each tumor were obtained at a distance of 10 cm (3 samples/tissue, G1 group), 5 cm (3 samples/tissue, G2 group) and 1 cm (3 samples/tissue, G3 group) from the tumor. Computerized cell image analysis was carried out on Feulgen-stained cell suspensions obtained from paraffin-embedded, formalin-fixed tissues. The results revealed that four to five analyses are necessary to detect minor aneuploid cell nuclei populations in human colorectal tumors. A definite homogeneous diploid pattern was found in the G1-G3 samples. In contrast, proliferative activity varied widely between the normal and tumor samples, with such variations observed at both the sample-to-sample and tissue-to-tissue level. The nuclear area also varied markedly across the samples from a given tissue--i.e., both marginal and tumoral and across the tissues themselves. Finally, we observed that the diploid tumors, the nuclear sizes of which varied as widely as those of the aneuploid tumors, possessed a higher proportion of highly proliferating samples than did the aneuploid.