Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

Diagnosis of dihydropyrimidinase deficiency in a Chinese boy with dihydropyrimidinuria.

Dihydropyrimidinase deficiency is an autosomal recessive inborn error of metabolism characterised by the presence of dihydropyrimidinuria. Its clinical presentation is variable and has also been reported in asymptomatic subjects. We report the first case of dihydropyrimidinase deficiency in Hong Kong, which is also the first reported in a Chinese subject. The patient was a 32-month-old boy who presented with language development delay. Biochemical analysis confirmed markedly increased urinary excretion of dihydrouracil and dihydrothymine, whilst DNA testing confirmed that the patient was compound heterozygous for two missense mutations, one known (p.R302Q) and the other was novel (p.N16K).

Benign childhood epilepsy with centrotemporal spikes: a study of 50 Chinese children.

In order to collect local data for children with Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS), we conducted a retrospective study of 50 Chinese children (32 males and 18 females) with BECTS diagnosed in two regional hospitals in Hong Kong from 1995 to 1998. Their peak age of onset was 7 years (range 3-13 years) and a male predominance was observed. Seven patients (14%) had a past history of febrile convulsions and five cases (10%) had a family history of epilepsy. The presentation was protean, but most of them had infrequent, short, nocturnal generalised seizures. The EEG spike foci were most frequently found in mid-temporal regions, followed by centrotemporal regions. Fourteen percent of children did not require anti-epileptic drug treatment. For those who were treated, they were easily controlled on a low dose of carbamazepine (median dosage of 12.75 mg/kg per day) or sodium valproate (median dosage of 20 mg/kg per day). Our study suggested a generally good prognosis for BECTS. No risk factors of frequent seizure recurrence could be identified.

High levels of hepatitis C virus RNA in native livers correlate with the development of cholestatic hepatitis in liver allografts and a poor outcome.

A subset of hepatitis C virus (HCV)-positive liver transplant recipients develop cholestatic hepatitis (CH). We investigated the role of pretransplantation disease activity (estimated by Knodell score and HCV RNA quantitation) in the native liver explant on the development of CH and graft and patient outcome. Eight patients with CH were identified among HCV-positive liver transplants and were compared with 20 consecutive patients with recurrent HCV hepatitis of noncholestatic type in liver transplants. We evaluated all 28 explanted native livers histologically using the Knodell scoring system. HCV viral load was measured in the native explant and 5 allograft explants from the CH group using Amplicor HCV RNA Monitor test. Six of 8 patients with CH had HCV RNA levels of 5,000 copies/microg of DNA or greater in the native liver explant, whereas only 1 of the control group had viral loads greater than this level. Greater HCV RNA levels correlated with worse graft and patient survival (P <.001). The 3-year survival rate in the CH group was 18% compared with 77% in the control group (P <.001). There was no difference in the primary immunosuppressive regimens used in the 2 groups. We conclude that (1) CH has a uniformly poor prognosis, (2) type of immunosuppressive therapy appears to have little influence on the development of CH, (3) high pretransplantation HCV RNA levels in the native explant may predict the development of CH, and (4) patients with high HCV RNA levels in the explanted native liver may be appropriate candidates for antiviral therapy to prevent the development of CH.

Optimal production of polyhydroxyalkanoates in activated sludge biomass.

Polyhydroxyalkanoates (PHAs) have been recognized as good candidates for biodegradable plastics, but their high price compared with conventional plastics has limited their use. In this study, activated sludge microorganisms from a conventional wastewater treatment process were induced, by controlling the carbon:nitrogen (C:N) ratio in the reactor liquor, to accumulate PHAs. In addition, an intermittent nitrogen feeding program was established to optimize the volumetric PHA productivity in a wastewater treatment process. The optimal overall polymer production yield of 0.111 g of polymer/g of carbonaceous substrate consumed was achieved under a C:N ratio of 96:1 by feeding nitrogen in the reactor liquor once every four cycles. At the same time, the amount of excess sludge generated from the wastewater treatment process was reduced by 22.9%.

Retrorectal cystic hamartoma: report of 5 cases with malignancy arising in 2.

BACKGROUND: Retrorectal cystic hamartomas, or tailgut cysts, are rare congenital lesions that typically present as presacral masses. These lesions are frequently clinically unrecognized and misdiagnosed. Malignant change is extremely rare. Only 10 additional cases with associated malignancy were recovered from the literature. We describe the clinicopathologic features of 5 cases, including 2 cases with malignant transformation. RESULTS: All patients were women (age range, 36-69 years). The most common symptoms were pain with defecation and rectal bleeding. One patient was asymptomatic. All lesions presented as multicystic presacral masses and all were surgically resected. The lesions varied in size from approximately 2 to 12 cm (average, 9.5 cm) and overall had similar histology composed of a variety of epithelial linings (stratified squamous, transitional, and simple or ciliated pseudostratified columnar). Skin adnexa, neural elements, and heterologous mesenchymal tissue, discriminators between retrorectal cystic hamartoma and teratoma, were not identified. Arising in association with the cysts was a focus of adenocarcinoma in one case and a neuroendocrine carcinoma in another. CONCLUSIONS: The clinical diagnoses in our cases were often delayed, which in part may be due to unfamiliarity with this entity. The main diagnostic difficulty is distinction from presacral mature cystic teratomas and rectal duplication cysts. Tailgut cysts require complete surgical excisions to prevent future recurrences and to preclude possible malignant transformation. Meticulous gross examination and adequate sampling are important to document the exact nature of these cysts and to rule out possible coexisting malignancies, which may be focal.

Tissue quantification of hepatitis C virus RNA with morphologic correlation in the diagnosis of recurrent hepatitis C virus in human liver transplants.

BACKGROUND: Histologic findings and liver enzymes in liver transplants are often non-diagnostic of recurrent hepatitis C virus (HCV) disease. In addition, the relationship between HCV replication and the presence of recurrent HCV hepatitis after liver transplantation remains unclear. We studied liver transplant recipients to determine if quantitation of HCV RNA in liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) correlates with histopathologic disease and/or liver enzymes. METHODS: Twenty-six patients who received liver transplants for HCV infection were evaluated. Four sequential biopsies were analyzed for each patient. HCV RNA was extracted and quantified using the Amplicor HCV Monitor Test. Histologic examination and RNA quantitation were blinded. All available liver enzymes on the day of liver biopsy were analyzed. RESULTS: HCV RNA quantity in liver tissue was significantly increased at the time of clinically-suspected recurrence (P < .0001). HCV RNA levels were highest in biopsies with lobular hepatitis and nonspecific inflammation, followed by biopsies with cytomegalovirus infection, chronic hepatitis, and acute cellular rejection. HCV RNA quantity had a significant correlation with increasing portal inflammation (P = .0002), decreasing amount of interface hepatitis (P = .0333), and presence of acidophilic bodies (P = .0316). Increasing HCV RNA levels significantly correlated with decreasing number of episodes of treated rejection. HCV RNA quantity did not correlate with other histologic features or liver enzymes. CONCLUSIONS: HCV RNA levels are highest at the time of active hepatocellular destruction. Elevated HCV RNA indicates recurrence. HCV RNA quantitation may be a useful diagnostic test for determining recurrent disease and distinguishing it from other causes of inflammation, such as rejection.

Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients.

OBJECTIVES: It is currently recommend to perform a liver biopsy for patients with chronically elevated liver function tests (LFT) of unknown etiology (marker negative). The necessity and benefits of these recommendations are unknown. The aims of this study were to determine the prevalence of marker-negative LFT in patients referred for evaluation of chronically elevated LFT; to determine the prevalence of diseases that may be associated with marker-negative abnormal LFT; and to assess whether a liver biopsy alters the management of such patients. METHODS: We conducted a prospective observational study of 1124 adults referred for evaluation of chronically elevated LFT. Patients who consented to a liver biopsy were eligible. Marker-negative abnormal LFT was defined as the absence of accepted serum markers for infectious, metabolic, autoimmune, or hereditary liver disease, the absence of a history of alcohol or hepatotoxic drug use, and the absence of signs of chronic liver disease. RESULTS: Eighty-one of 1124 eligible patients were marker-negative. Liver biopsies in the 81 marker-negative patients revealed: normal histology (eight), steatosis (41), steatohepatitis (26), fibrosis (four), and cirrhosis (two). All 73 abnormal liver biopsies had some degree of steatosis. There were no significant associations between histological findings and the presence of obesity (p = 0.13), hyperlipidemia (p = 0.4), or diabetes (p = 0.9). There were no significant associations when classifying patients by gender or by symptoms. CONCLUSION: In the setting of marker-negative elevated LFT, the most likely histological diagnosis is fatty metamorphosis of the liver with occasional associated fibrosis.

Accumulation of biopolymers in activated sludge biomass.

In this study, activated sludge bacteria from a conventional wastewater treatment process were induced to accumulate polyhydroxyalkanoates (PHAs) under different carbon-nitrogen (C:N) ratios. As the C:N ratio increased from 20 to 140, specific polymer yield increased to a maximum of 0.38 g of polymer/g of dry cell mass while specific growth yield decreased. The highest overall polymer production yield of 0.11 g of polymer/g of carbonaceous substrate consumed was achieved using a C:N ratio of 100. Moreover, the composition of polymer accumulated was dependent on the valeric acid content in the feed. Copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] was produced in the presence of valeric acid. The 3-hydroxyvalerate (3HV) mole fraction in the copolymer was linearly related to valeric content in the feed, which reached a maximum of 54% when valeric acid was used as sole carbon source. When the 3HV U in the polymer increased from 0-54 mol%, the melting temperature decreased from 178 degrees to 99 degrees C. Thus, the composition, and hence the mechanical properties, of the copolymer produced from activated sludge can be controlled by adjusting the mole fraction of valeric acid in the feed medium.

Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells.

Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the scrotum, one from the penis, and one from the nose) and one histologic "simulant" (from skin of the nose) were studied. The lesions were solitary, raised, or polypoid with cup-shaped craters filled with parakeratotic cells that blended into keratinocytes of an acanthotic and papillomatous epidermis. There was a neutrophilic infiltrate of varying intensity between plump parakeratotic cells and keratinocytes, near the surface of the epidermis. Aggregates of foam cells were present in the papillary dermis, which was highly vascular. A plasma cell predominant infiltrate was seen at the base in a bandlike fashion. Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case. The foam cells were weakly positive for cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac 387 immunostain showed focal weak staining in foam cells. We postulate that a cascade of events pursue after initial keratinocytic damage attracting neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by dermal dendrocytes, eventually leading to the ultimate manifestation of the lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on our findings, we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated squamoproliferative lesion and that the foam cells, a histologic hallmark of the lesion, are most likely derived from dermal dendritic cells.

Small intestinal stromal tumors: a clinicopathologic study of 20 cases with immunohistochemical assessment of cell differentiation and the prognostic role of proliferation antigens.

Small intestinal stromal tumors (SISTs), similar to their gastric counterpart, are complex because of their divergent cellular differentiation and because of the difficulty in accurately predicting their clinical outcome. We studied a series of 22 SISTs from 20 patients to characterize lineage and investigate prognostic morphologic parameters and possible histologic and immunohistochemical differences from gastric stromal tumors (GSTs) and to determine the potential prognostic value of proliferation markers. Cases were categorized into the three following groups based on mitotic count (MC) per 50 high-power fields and tumor size: (1) benign, n = 6 (< 5 MC, < 5 cm); (2) borderline, n = 6 (< 5 MC, > or = 5 cm); and (3) malignant, n = 10 (> or = 5 MC, any size). For the formalin-fixed, paraffin-embedded tissue sections, an immunohistochemical panel was used to characterize differentiation toward myogenic cells (pan-muscle specific actin [HHF-35], alpha-smooth muscle actin, and desmin), Schwann cells (S-100 protein), enteric glial (glial fibrillary acidic protein), and nerve cells (neurofilament). Cellular proliferative activity was assessed immunohistochemically using monoclonal antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67 antigen (MIB-1) and a tumor proliferation index (TPI) was obtained as the percentage of positive-staining tumor nuclei. Clinical follow-up revealed that none of the benign tumors progressed (mean follow-up, 96 months). Half of the patients with borderline tumors were dead of disease (mean, 50.7 months), while 8 of 9 patients with a malignant tumor died of disease (mean, 24.6 months). By Cox Proportional Hazard Regression analysis, mitotic count, tumor size, and cellularity significantly predicted survival. PCNA, MIB-1, tumor necrosis, and atypia were not significant predictors of survival. All tumors stained with vimentin; 17 (77%) and 13 (59%) of the tumors showed immunoreactivity with muscle-specific actin markers (HHF-35) and alpha-smooth muscle actin, respectively. Only 1 tumor stained with desmin, and none stained with S-100 protein, neurofilament, or glial fibrillary acidic protein. Immunophenotypic characteristics did not differ among the 3 groups. The TPI for PCNA and MIB-1 significantly differed between benign and malignant tumors and between borderline and malignant tumors, but it failed to separate the benign and borderline groups. Compared with 52 cases of GST previously reported by us using the same criteria and antibody panel, these tumors were histologically and immunohistochemically indistinguishable. However, none of the 18 borderline GSTs progressed, while 3 of 6 patients with a borderline SIST died of the disease. Based on this series of 22 SISTs, we conclude the following: (1) MC, size, and cellularity are the best predictors of clinical outcome in SIST. (2) The majority of SISTs show smooth muscle differentiation based on their immunoreactivity with HHF-35 and alpha-smooth muscle actin). (3) The TPI for PCNA and MIB-1 correlated with MC but failed to predict survival for individual cases. (4) SISTs and GSTs are morphologically and immunohistochemically similar; however, SISTs seem to have greater malignant potential than GSTs of similar size.

Prognostic significance of DNA ploidy and proliferation in 309 colorectal carcinomas as determined by two-color multiparametric DNA flow cytometry.

BACKGROUND: Although DNA flow cytometry has been shown to be of independent value in determining the prognosis of colorectal carcinoma, a number of well-designed studies with contradictory findings have left unresolved the clinical significance of DNA ploidy and proliferation in biologically meaningful subsets of colorectal carcinoma cases. METHODS: To evaluate the prognostic significance of DNA ploidy and proliferation as determined by flow cytometry in a prospective series of 309 human colorectal carcinomas with 4-6 years of follow-up, fresh tumors were mechanically dissociated into whole cell suspensions and dual fluorescence-labeled to allow gated analysis of subpopulations with phenotypic markers. Software programs with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell cycle quantitation. Data were analyzed according to recommendations of the 1992 DNA Flow Cytometry Consensus Conference. RESULTS: None of the clinical, site, or staging parameters, including TNM stage variables, correlated with any flow cytometric DNA ploidy or proliferation measurement. Tumors classified as DNA aneuploid or tetraploid, by any definition, did not differ in prognosis or correlate with stage or any pathologic parameter. Univariate Kaplan-Meier survival analysis showed prognostic significance of the following: Dukes staging, individual components of TNM stage (tumor depth, lymph node status, and metastasis), vascular invasion, histologic pattern of tumor infiltration, and peritumoral lymphocytic inflammation. DNA ploidy status and proliferation measurements were not predictive of survival for the overall group or within any particular stage. Only Dukes Stage D (metastasis), vascular invasion, and depth of invasion (T classification) were significant independent predictors of survival in multivariate Cox regression models. CONCLUSIONS: In this analysis, DNA ploidy and proliferation measurements were not predictive of survival in any stage of colorectal carcinoma. However, clinical and pathologic documentation of staging and select histopathologic observations were significant predictors of survival in univariate and multivariate analyses.

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection.

BACKGROUND & AIMS: Multiple tests are available for determining Helicobacter pylori infection. Our aim was to compare the sensitivity, specificity, and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori. METHODS: A total of 268 patients (mean age, 53.7 +/- 15.8 years; 142 male and 126 female; 125 white and 143 nonwhite) was tested for H. pylori infection by [13C]urea breath test (UBT), measurement of serum immunoglobulin (Ig) G and IgA antibody levels, and antral biopsy specimens for CLO test, histology, and Warthin-Starry stain. No patient received specific treatment for H. pylori before testing. The infection status for each patient was established by a concordance of test results. RESULTS: Warthin-Starry staining had the best sensitivity and specificity, although CLO test, UBT, and IgG levels were not statistically different in determining the correct diagnosis. The absence of chronic antral inflammation was the best method to exclude infection. Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age. IgA was a better predictor in white patients. CONCLUSIONS: The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry.

Control of translation by mRNA secondary structure: the importance of the kinetics of structure formation.

RNA secondary structure is important in a wide variety of biological processes, but relatively little is known about the pathways and kinetics of RNA folding. When the IS10 transposase (tnp) gene is transcribed from a promoter outside the element, little increase in tnp expression is observed. This protection from outside transcription (pot) occurs at the translational level, presumably resulting from mRNA secondary structure proposed to sequester the tnp ribosome-binding site. Here, we confirm the pot RNA structure and show that it blocks 30S ribosomal subunit binding in vitro. Point mutations that abolish protection in vivo map to the pot structure. Surprisingly, these pot mutations do not severely alter the pot secondary structure or increase 30S subunit binding in vitro, except in one case. Using an oligonucleotide hybridization assay, we show that most of the pot mutations slow the kinetics of pot structure formation, with little or no effect on the inhibitory function of the final structure. Moreover, a suppressor mutation reverses this effect. We propose a pathway for pot mRNA folding that is consistent with the mutations and implicates the formation of important kinetic intermediates. The significance of these observations for the RNA folding problem in general is discussed.

Decrease in ornithine decarboxylase activity after eradication of Helicobacter pylori.

OBJECTIVE: Our aim was to determine whether gastric mucosal ODC activity is altered after successful eradication of HP. Recent reports have suggested that Helicobacter pylori (HP) infection of the stomach is associated with the development of gastric cancer. Gastrointestinal cancers usually do not arise de novo; a series of mucosal changes leading to neoplastic transformation and degrees of dysplasia are believed to precede the development of cancer. These conditions are associated with increased cellular proliferation. Ornithine decarboxylase (ODC) activity is induced by factors that stimulate cellular proliferation, and has been shown to be elevated in gastrointestinal neoplasia, including gastric cancer. METHODS: Gastric antral and body biopsies were obtained from 17 HP-positive patients at endoscopy, for ODC activity and histology (including Warthin Starry stain) before and 4-6 wk after successful triple therapy. RESULTS: Patients included 12 males and five females, with a mean age of 55 yr (27-73 yr). Mean ODC activity (in pmol CO2/mg protein/h) was significantly decreased after eradication of HP, compared with pretreatment levels in antral (147 +/- 26 vs. 80 +/- 15) and body mucosa (76 +/- 21 vs. 20 +/- 5) (p < 0.05). CONCLUSION: Successful eradication of HP decreases mucosal proliferative activity, as reflected by decreased ODC activity. We speculate that by decreasing mucosal proliferative activity, HP eradication may help decrease the subsequent risk of gastric cancer.

Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome.

Morphologic studies of gastric stromal tumors (GSTs) indicate that mitotic counts (MCs) and tumor size are major discriminants predictive of biologic behavior. The authors evaluated the tumor proliferation of GSTs with anti-proliferating cell nuclear antigen (PCNA; DAKO clone PC10, DAKO Corporation, Carpinteria, CA) for correlation with MCs, histologic cell type, and clinical outcome. Fifty-eight tumors ranging from 1.5 to 45 cm in size were selected for clinicopathologic assessment. Mitotic activity was counted per 50 high-power fields (MC). For this study, combined parameters of MC and tumor size were used to categorize tumors into three groups: (1) benign: MC less than 5, tumor smaller than 5 cm; (2) borderline: MC less than 5, tumor larger than 5 cm; and (3) malignant: MC greater than 5, tumor any size. The PCNA tumor proliferation index (TPI) was assessed from evaluation of 200 tumor cells per case and expressed as the percentage of cells with positive results. Clinical follow-up was available in 45 cases. None of the 19 benign or 16 borderline tumors recurred or metastasized, whereas 7 of 10 malignant tumors metastasized and 1 of 10 recurred. The mean PCNA TPI values among benign (11.2%), borderline (16%), and malignant (34.5%) tumors were significantly different (P = 0.0002, Kruskal-Wallis test). When the pathologic tumor categories were compared, the mean TPI of benign tumors was significantly different from that of borderline tumors (P = 0.0306, Kruskal-Wallis), and the TPI of borderline tumors was different from that of the malignant tumors (P = 0.0060, Kruskal-Wallis test). The Spearman rank correlation showed a significant relationship between the MC and PCNA TPI (P = 0.0003, r = 0.4543). Logistic regression analysis showed that the TPI, independent of MC and size, contributed significantly (P = 0.00295) to the prediction of outcome. In the malignant group, the mean TPI for malignant tumors with metastases (43.6%) was significantly different (P = 0.0411, Kruskal-Wallis test) from that of malignant tumors without metastases (including the case with probable recurrence) (11.83%). No correlation was found when PCNA TPIs for epithelioid GCTs were compared with those of spindle cell GSTs.(ABSTRACT TRUNCATED AT 400 WORDS)

Myenteric plexus destruction alters morphology of rat intestine.

BACKGROUND: It has been shown previously that myenteric plexus destruction by benzalkonium chloride (BAC) increased villus height, crypt depth, and muscle thickness, suggesting that these neurons influence intestinal morphology. A nonspecific trophic effect of BAC, intraluminal stasis, and inflammation resulting from the chemical treatment could also be causes for these changes. Our goals were to (1) show that the morphological sequelae of BAC treatment are caused by myenteric plexus removal and not the factors listed above, and (2) determine whether segmental myenteric plexus removal alters morphology elsewhere in the small intestine. METHODS: Six groups of rats were studied: control, chemical denervation (3 mmol/L BAC), surgical denervation, intraluminal stasis produced by partial obstruction, chemical inflammation (5% acetic acid), and surgical inflammation (serosa removal only). Tissue for histological study was taken from the treated segment, 15-20 cm proximal to the treated segment, and 5-10 cm distal to the treated segment 28 days after treatment. RESULTS: Chemical and surgical denervation reduced the number of myenteric neurons by 94% and 98%, respectively. Denervation had a direct effect on morphology; it increased villus height, crypt depth, and muscle thickness in the treated and proximal segments, but only muscle thickness was increased in the distal segment. The other treatments had minimal morphological sequelae. CONCLUSIONS: Segmental myenteric plexus removal alters the mucosa in the treated and proximal segments but influences muscle thickness throughout the intestine.

Signet ring variant of lobular carcinoma of the breast: a clinicopathologic and immunohistochemical study.

Signet ring carcinoma of the breast often metastasizes to gastrointestinal tract and female genital tract. We report clinicopathologic features of 10 breast carcinomas with signet ring features, five of which had unusual metastatic patterns. The primary breast tumor in all these cases was lobular carcinoma. Although signet ring cells were prominent in metastatic sites, the primary tumor lacked signet ring cells in two cases. A linitis plastica-like presentation and presence of signet ring cells in gastric metastases raised a strong possibility of primary gastric carcinoma in three cases. The monoclonal antibody to gross cystic disease fluid protein (GCDFP-15) was positive in signet ring cell-rich areas in the primary breast tumor (8/10) and/or in the metastases in all cases. For comparison we studied GCDFP-15 immunoreactivity in 10 infiltrating lobular and 10 infiltrating ductal breast carcinomas with no obvious signet ring cells, and in 14 signet ring carcinomas from other sites (10 gastric, 2 prostatic, 2 colonic). The gastric, colonic, and one prostatic signet ring carcinoma were nonreactive. One prostatic signet ring carcinoma exhibited focal but unequivocal positivity with GCDFP-15. The cases of this report reinforce the concept that signet ring carcinoma of the breast is usually a variant of lobular carcinoma and not a distinct entity. Signet ring cell predominance in metastases, even in the absence of signet ring cells in the primary tumor, attest to the morpho-functional heterogeneity of lobular carcinoma. GCDFP-15 is a sensitive marker for signet ring breast carcinoma and a very useful adjunct tool in the diagnosis of metastatic signet ring carcinoma of mammary origin.

Ki-67 and proliferating cell nuclear antigen tumor proliferative indices in DNA diploid colorectal adenocarcinomas. Correlation with histopathologic characteristics and cell cycle analysis with two-color DNA flow cytometry.

The prognostic significance of tumor proliferative activity (TPA) in colorectal adenocarcinomas (CA) determined by proliferating cell nuclear antigen (PCNA) and Ki-67 staining is not well defined. Previous investigations of TPA using Ki-67 immunohistologic studies and flow cytometric (FCM) analysis have found no correlation with conventional histopathologic parameters. To better define the relationship of these various TPA measurements in CA, the authors selected 46 tumors with diploid DNA content previously analyzed by two-color DNA FCM analysis of fresh specimens to more effectively assess actual S-phase fractions (SPFs) from cytokeratin-gated DNA histograms for comparison with the following: (1) immunohistologic Ki-67 and PCNA tumor proliferation indices (TPIs); and (2) conventional histopathologic observations of prognostic import. These data show no significant correlation coefficient between Ki-67 or PCNA TPIs and SPFs derived from FCM analysis; however, the DNA diploid tumor subset categorized as having a greater than median SPF value had a significantly higher mean Ki-67 but not PCNA proliferation index. There was no correlation of any measure of proliferation with any of the eight histopathologic features of known prognostic significance.