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PubMed1997

The effect of interferon on the liver in chronic hepatitis C: a quantitative evaluation of histology by meta-analysis.

BACKGROUND/AIMS: Several randomized clinical trials of interferon in chronic hepatitis C have examined the histological changes in paired biopsy specimens. We have attempted a quantitative evaluation by meta-analysis. METHODS: Randomized Clinical Trials found by MEDLINE search were included if: a) they compared different IFN regimens with non-active treatment or with each other, b) they obtained biopsies before starting and at the time of stopping IFN in a sizable proportion of the treated and control patients, and c) they assessed the biopsy-specimens semi-quantitatively according to Scheuer's numerical scoring system or Knodell's Histological Activity Index, with quantitation of fibrosis and of lobular, portal and periportal necroinflammation. RESULTS: Seventeen trials were identified, in which 1223 adult patients had been studied. All trials homogeneously pointed towards a favorable interferon effect. The pooled data show a statistically significant histological improvement in treated patients as compared with controls for each of the four Histological Activity Index components and for the total Histological Activity Index score (overall improvement was -0.82 in favor of interferon, p<0.0001, 95% Confidence Interval -1.25 to -0.40). In the ten trials reporting histological changes separately in biochemical responders (primary and sustained responders) and non-responders, histological improvement was confined to the subset of biochemical responders. No change or very little change occurred in non-responders. CONCLUSIONS: Interferon treatment in chronic hepatitis C significantly improves liver histology. The effect of interferon is closely related to biochemical response. Studies assessing histological outcome 1 year or more after interferon treatment in long-term responders and comparatively in non-responders or relapsers would be important to confirm the regression of the necroinflammatory process in the former, as suggested by the normal serum alanine aminotransferase levels.

Adult↗
PubMedDate not supplied

Detection and characterization of vascular lesions by intravascular ultrasound: an in vitro study correlated with histology.

High-frequency intravascular ultrasound (30 and 40 MHz) was applied to study 112 human vascular specimens. The ultrasound images were compared with histologic cross-sections. In 44 out of 58 of the histologically classified muscular arteries, a hypoechoic middle layer was seen in the vessel wall, giving it a three-layered appearance. In 10 arteries, fibrous degeneration of the muscular media resulted in a homogeneous appearance of the vessel walls, whereas atherosclerotic plaque precluded the visualization of the arterial media in four of the arteries. A three-layered appearance was seen in seven of nine histologically classified transitional arteries, and a homogeneous arterial wall was seen in two of the nine. None of the 33 elastic arteries, veins, venous bypass, and Goretex conduits showed a hypoechoic medial layer. Histologically proved fibrous intimal thickening was echographically detected in 32 of 48 specimens (67%). It was noted that these intimal lesions were easier to detect with 40 MHz than with 30 MHz transducers. Hypoechoic areas of lipid deposition were detected in 32 of 36 specimens (89%) and could be distinguished from fibrous plaques. Histologically evident calcium deposits were detected with intravascular ultrasound in 35 of 36 specimens (97%). Measurement of plaque area was only possible in cross sections with a three-layered appearance. Quantitative analysis showed a significantly larger lumen area measured from ultrasonic images (26.3 +/- 21.3 mm2) than from histologic cross-sections (21.8 +/- 16.6 mm2, p less than 0.001), probably because of tissue shrinkage during processing for histology. A significant correlation (r = 0.96, p less than 0.001) between ultrasonic and histologic measurements of lumen areas was observed, with and a negligible interobserver and intraobserver variability. Plaque area and medial thickness correlated well with histology (r = 0.87, p less than 0.001 and r = 0.93, p less than 0.001, respectively). It appears from this in vitro study that intravascular ultrasound is an accurate technique for detection and characterization of atherosclerotic lesions. Vessel lumen area can be measured in most instances, whereas plaque area and medial thickness can only be reliably assessed in muscular arteries in which the hypoechoic media serves as a reference, and shadowing by calcium or attenuation by fibrous plaque components is absent.

Adolescent↗
PubMed2002

Lung tumors with mixed histologic pattern. Clinico-pathologic characteristics and prognostic significance.

OBJECTIVE: To analyze and compare clinico-pathologic characteristics and survival between lung tumors with mixed histologic pattern and our population of resected lung tumors with single histology in the same period. METHODS: From January 1993 to December 1999, 1158 patients received resection for lung tumors. Of these, 59 (5.1%) presented a mixed histologic pattern on the surgical specimen. There were 48 men and 11 women (mean age 64 years, range 43-79). Three groups of tumors were identified: adenosquamous carcinoma, combined neuroendocrine + non-neuroendocrine carcinoma (NNEC) and biphasic tumors (epithelial + mesenchymal malignant components) represented by carcinosarcoma and blastoma. The combined neuroendocrine tumors were further divided in small cell lung carcinoma (SCLC) + large cell neuroendocrine carcinoma (LCNEC)/NNEC and other neuroendocrine tumors/NNEC. Clinico-pathologic characteristics, pTNM and survival were analyzed and compared to our population of resected lung tumors with single histology. RESULTS: There were 33 adenosquamous carcinomas, 19 combined SCLC+LCNEC/NNEC, two other neuroendocrine tumors/NNEC and five biphasic tumors (three carcinosarcomas and two blastomas). Among adenosquamous carcinomas, high cell grading (G2 or G3), advanced stage (IIIa or higher) and intratumoral perineural invasion were significantly more evident than in the single histology population. Among combined neuroendocrine/NNEC, high cell grading (G3) and intratumoral vascular invasion were significantly more evident than in the single histology population. Among biphasic tumors, all were at early stages and showed high cell grading (G3). Three-year survival rates were 46% in the single histology group, 28% in the adenosquamous group and 21% in the combined SCLC + LCNEC/NNEC. The difference among the three groups was significant (P = 0.013). Median survival of biphasic tumors was 19 months (range 8-37). CONCLUSIONS: Lung tumors with mixed histologic pattern are rare tumors. Adenosquamous carcinoma and combined SCLC + LCNEC/NNEC present a more aggressive clinico-pathologic behaviour and reduced survival as compared to the single histology population of resected lung tumors.

Adult↗
PubMed1996

Immunohistochemical expression of p53 proteins in Wilms' tumour: a possible association with the histological prognostic parameter of anaplasia.

Wilms' tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms' tumour was carried out. Thirty-eight cases were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms' Tumour Study criteria. Archival formalin-fixed, paraffin-embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase-labelled streptavidin biotin kit (Dako). 'Cure' (disease-free survival of 60 months or longer) was documented in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demonstrating immunopositivity in > 75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours.

Anaplasia↗
PubMed2003

[Micrographic controlled surgery (3D-histology) in cutaneous melanoma].

Frederic E. Mohs was the first to apply micrographic surgery in cutaneous surgery. As a result in the English literature, micrographic surgery (3D-histology) is usually called Mohs micrographic surgery (MMS). Techniques of 3D-histology have been applied in various skin tumours. The method is most suitable for tumours with continuous spread. Excisions with 3D-histology can be performed with smaller initial safety margins. Thus less normal tissue is excised and often better cosmetic results can be obtained. Techniques of 3D-histology such as the Mohs technique (MMS) and the "Tuebingen Cake" technique are compared with routine histopathology. In addition, the current status of 3D-histology in cutaneous melanoma is assessed. Prospective randomized studies on 3D-histology in cutaneous melanoma are not available. Nevertheless, 3D-histology should usually be employed for lentigo maligna melanoma. In functionally and cosmetically important areas (face, hand, foot) 3D-histology may allow reduced safety margins in other histological types of cutaneous melanoma.

Humans↗
PubMed2004

[Bronchological bioptic diagnosis of lung cancer -- cytology and/or histology?].

INTRODUCTION: Bronchial carcinomas are commonly diagnosed through histological analysis of forceps biopsies. The use of flexible bronchoscopic biopsy techniques has led to an increase in the number of cytological investigations. The present study has the aim to assess the diagnostic efficiency of histology, cytology and their combined use. METHOD: In a retrospective analysis, 3630 cytological and/or histological samples that had been obtained bronchoscopically between 1/97 and 12/03 prior to surgery in 1436 patients, who were operated due to bronchial carcinoma, were compared to corresponding histological findings in the resected material. RESULTS: In 1888 preoperatively analysed areas the resected material ultimately allowed the detection of malignant lesions. Among these cases, histologic analysis of forceps biopsies yielded 399, cytological analysis 728, and their combined use 801 correct diagnoses prior to surgery. The combination of both procedures led to an increase of sensitivity by 16 % and 13.0 % compared to histology and cytology, respectively, as separate procedures. Histologically there were 149 cases, cytologically 1061 cases, and in combination 1040 cases that were falsely diagnosed as negative prior to surgery. The use of histology and/or cytology allowed to correctly detect 1250 areas of the resected material as free of malignant lesions. Specificity was 99.8 % for both methods. CONCLUSION: Currently bronchial carcinomas are often diagnosed preoperatively by minimally invasive cytological procedures. The present results demonstrate cytology and histology to be procedures that are complementary to each other. Their combined use offered the greatest diagnostic yield and therefore should be considered standard in the diagnosis of bronchial carcinoma.

Biopsy↗
PubMed2002

Accuracy of high resolution CT in assessing idiopathic pulmonary fibrosis histology by objective morphometric index.

To determine the accuracy of HRCT in assessing histology by objective morphometric index, twenty-five biopsy specimen-proved UIP were correlated with high-resolution CT (HRCT) by morphometric analysis. The scans were evaluated for the presence and extent of normal parenchyma, ground-glass attenuation, linear opacities, consolidation, honeycombing, vessels and bronchiectasis, and overall extent of histology involvement for normal parenchyma, honeycombing, alveolar septal inflammation, fibrosis, vessels, and bronchiectasis/bronchiolectasis. The comparison between morphometric measurements showed a strong correlation between HRCT and histologic parameters for extension (%) of normal tissue (p = 5 x 10(-5)), honeycombing (p = 6 x 10(-5)), and vessels (p = 0.0047). HRCT consolidation strongly correlated with alveolar septal inflammation (p = 0.015), whereas HRCT linear opacities had the highest correlation with histology for bronchiectasis or bronchiolectasis (p = 0.03). These associations also demonstrated that there was considerable residual scatter about the linear relationships found. By contrast, neither the ground glass patterns nor the bronchioectatic patterns determined by CT were associated with any histologic observation (p < 0.1). There was a borderline negative relationship between vessels determined by CT and histologic fibrosis (p = 0.069), i.e., the percentage of vessel patterns determined by CT was found to be lower when fibrosis was prominent histologically. Our results showed that HRCT patterns, usually employed to provide information about activity (ground glass) and fibrosis (consolidation) in IPF, failed to correlate with histology. On the other hand, chronic cystic lesions had a good correlation with histology. This finding suggests that in patients without a diffuse honeycomb pattern on HRCT, a lung biopsy may provide additional information. The more important limitation of our study was the lack of correlation related to the proximity of the biopsy site to the HRCT location evaluated by morphometry.

Lung↗
PubMed1992

Histological examination of first trimester spontaneous abortions: the impact of materno-embryonic interface features.

Cytogenetic findings and placental histological features of 319 consecutive first trimester spontaneous abortions were retrospectively investigated. Correlation of cell culture results and microscopic examination based on conventional villous histological criteria showed an overall sensitivity of 45.1% for histology in detecting chromosomal anomalies. Discrepant cases, i.e. normal histology with unequivocal chromosomal anomaly and abnormal histological features suggesting a chromosomal anomaly according to the classical criteria but with a normal karyotype, were reviewed by two independent observers using extended histological criteria including features of the materno-embryonic interface. There was a significant (P < 0.001) increase of the sensitivity of histology to 66.4% for both observers after the second histological examination. Macerated specimens or incomplete specimens made of chorion laeve or maternal decidua only are difficult to evaluate, and represent the main cause of discrepancy between cytogenetics and morphology. The results of this study indicate that the sensitivity and specificity of microscopic examination in cases of early spontaneous abortion may be improved by adding features of the materno-embryonic interface to classical villous histological criteria.

Abortion, Spontaneous↗
PubMed1994

Integrated decision support system/image archive for histological typing of breast cancer using a relation oriented inference system.

Histological typing of invasive breast cancer according to the World Health Organisation criteria is prognostically relevant, because some histological subtypes have a markedly better prognosis. However, reproducibility of histological typing is not high because of the absence of strict typing criteria, variations in the application of the typing criteria and the usually limited illustration of the relevant criteria. The aim of this study was to develop an expert system based on highly structured histological typing criteria, integrated with high-quality microscope images to illustrate the typing criteria. This system should be useful as a decision support system in the diagnosis of breast cancers and should increase the reproducibility of histological typing. Criteria for typing were extracted from textbooks and, based on experience, these criteria were structured and implemented in the Relation Oriented Inference System (ROIS), in which information can be structured by defining relations. Illustrative black and white images were digitized and integrated into the shell. The performance of the resulting decision support system was evaluated by a group of six pathologists using a set of slides covering the spectrum of the most frequently occurring histological types of invasive breast cancer. The pathologists first assessed histological type according to standard morphological procedures. The cases were then reassessed with the decision support system available for consultation. The use of the decision support system appeared to influence the previously assessed histological type in about half of the cases. Using the decision support system, histological typing was more uniform and more in accord with a 'gold standard' set by two experts.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗
PubMed1996

Histological grade in invasive ductal carcinoma of breast correlates with the proliferative activity evaluated by BrdU: an immunohistochemical study including correlations with p53, c-erbB-2 and estrogen receptor status.

Thirty cases of invasive ductal carcinoma of the breast were classified to histological subtype according to the General Rules for Clinical and Pathological Recording of Breast Cancer of the Japanese Breast Cancer Society and histologically graded using the Nottingham method and the correlation of histology with proliferative activity was investigated using bromodeoxyuridine (BrdU). In addition, the overexpression of p53 protein, c-erbB-2 oncoprotein and estrogen receptor (ER) were immunohistochemically examined in order to discuss the relationship with histological subtype and histological grade. Histological grade correlated positively to the BrdU labeling index (LI) and overexpression of p53. High grade carcinoma demonstrated c-erbB-2 more frequently and exhibited a low incidence of ER. However, no significant relationship was found between BrdU LI, overexpression of p53 and c-erbB-2 and histological subtype. These results suggest that the histological grade does represent the proliferative activity of tumor cells and that adding the histological grade to the pathological diagnosis in invasive ductal breast carcinoma may be useful from the clinicopathological aspect concerning tumor behavior.

Adult↗
PubMed1979

Significance of abnormal rabbit ileal histology in the pathogenesis of diarrhea.

In spite of several macroscopic criteria for predicting the presence of histological abnormalities in rabbit ileum, microscopic ileal abnormalities still can escape detection. The effect of histologically abnormal rabbit ileum was evaluated on basal intestinal absorption, on basal absorption, on basal adenylate cyclase activity, and on cholera toxin-induced secretion and cholera toxin-induced stimulation of adenylate cyclase activity. Compared to histologically normal rabbit ileum, the presence of histological abnormalities was associated with decreased basal intestinal water, Na, Cl, and glucose absorption, absent glucose-dependent water absorption, and elevated basal adenylate cyclase activities. However, histologically abnormal rabbit ileum responded to inoculation of purified cholera toxin with stimulation of intestinal water secretion and adenylate cyclase activity similar to that in histologically normal ileum. These data have implications concerning the design of experiments that attempt to study the pathogenesis of diarrheal diseases by correlating changes in ileal transport with changes in ileal mucosal adenylate cyclase activity. In spite of abnormal ileal histology, studies of intestinal secretory states which attempt to define the role of adenylate cyclase in secretory processes can be performed provided animals are used as their own controls. However, when groups of animals are compared, the presence of an histologically abnormal ileum can cause changes in basal and intestinal secretagogue-stimulated ileal water and electrolyte transport and in basal and intestinal secretagogue-stimulated mucosal adenylate cyclase activity which can lead to erroneous conclusions if the presence of the abnormal ileal histology is not considered.

Adenylyl Cyclases↗
PubMed2002

Histology predicts cirrhotic evolution of post transplant hepatitis C.

BACKGROUND: Hepatitis C recurring after orthotopic liver transplantation varies in severity and some patients rapidly develop fully established liver cirrhosis. Neither clinical nor biological markers of such rapid cirrhotic evolution are available. AIM: To assess the value of histology in identifying patients who will develop cirrhosis shortly after liver transplantation. PATIENTS AND METHODS: Only cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive serum and liver changes consistent with hepatitis, with no other causes of allograft injury, were considered. A total of 128 liver biopsies were scored from 29 consecutive patients with a mean follow up of 48 (13.97) months. The histological activity index was evaluated according to Ishak et al. The time of the first histological diagnosis of recurrent hepatitis C in the absence of rejection was defined as time of histological recurrence (RHC-T). RESULTS: First histological diagnosis of recurrent hepatitis with no features of rejection was obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18-60)). The remainder (mean follow up 46 (13.40) months (24-72)) showed a spectrum of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T significantly correlated with rapid development of cirrhosis. At the RHC-T biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median value of the histological activity index was 11 (mean 11.11 (1.76) (range 9-14)) in patients who developed cirrhosis and four (mean 4 (1.78) (range 1-8)) in the others (p<0.0001). A histological activity index > or =9 was associated with rapid development of cirrhosis in 100% of cases. CONCLUSIONS: After liver transplantation, the histological activity of recurrent hepatitis C predicts the risk of development of cirrhosis. By adopting Ishak's scoring system, a histological activity index > or =9 was 100% sensitive/specific in identifying subjects who rapidly developed cirrhosis.

Acute Disease↗
PubMed1996

Comparison of histological and biochemical hepatic iron indexes in the diagnosis of genetic haemochromatosis.

AIMS: To compare a histological hepatic iron index with a biochemical hepatic iron index, derived from atomic absorption spectroscopy measurements of hepatic iron content, for the diagnosis of genetic haemochromatosis (GH). METHODS: Histological sections of liver biopsy specimens from 70 subjects, who had previously had their biochemical hepatic iron index measured, were examined. The iron stores were scored to derive a histological hepatic iron index and were also graded from 0 to 4 by a standard grading system. The case history of each patient was then reviewed to establish a definitive clinical diagnosis and patients were classified as GH, non-GH or indeterminate. RESULTS: There were 26 cases of GH, 40 cases of non-GH and four indeterminate cases in whom a definite clinical diagnosis was not established. Using a biochemical hepatic iron index cut off level of 2.0, two cases were misclassified, with one case of GH having a biochemical hepatic iron index of 1.8 and one non-GH case having a biochemical hepatic iron index of 3.1. This could not have been improved by altering the cut off level. Using the recommended cut off level of 0.15, the histological hepatic iron index was raised in all cases of GH, but was also increased in 11 of the 40 non-GH patients. The specificity of this histological index can be improved by increasing the cut off level to 0.30. A histological iron grade of > or = 3 is more specific than the histological index but has a lower sensitivity, which particularly affects the diagnosis of younger patients with GH. CONCLUSIONS: The biochemical hepatic iron index is a reliable method for establishing a diagnosis of homozygous GH. In contrast, the histological hepatic iron index as originally described is non-specific and does not reliably distinguish patients with GH from others with a raised hepatic iron index due to other causes. The specificity of this index can be improved by increasing the cut off level used, but the discrimination provided by the histological index is still inferior to that provided by the biochemical hepatic iron index.

Adult↗
PubMed2002

Prognostic value of histologic stage and proliferative activity in canine malignant mammary tumors.

The aim of this study was to investigate the correlation between the histologic invasiveness (histologic stage) and various cell proliferation activity assays (quantity of argyrophil proteins associated with nucleolar organizer regions [AgNORs], mitotic activity, MIB1 [Ki67] immunohistochemical detection) for predicting the biologic behavior of malignant canine mammary tumors. Sixty specimens from malignant canine mammary tumors with no distant metastases (M0) at surgery were selected, and follow-up data were collected over a 2-year period. The histologic invasiveness was graded by histologic stage (stage 0 = tumors without stromal invasion; stage I = tumors with stromal invasion; stage II = tumors with neoplastic emboli in vessels), and the proliferative indices were expressed as MIB1 index (the percentage of nuclear area immunohistochemically stained by MIB1 antibody), mitotic index (the number of mitoses per 1,000 neoplastic cells), and AgNOR index (the ratio between mean AgNOR area of tumor cells and the mean AgNOR area of fibroblasts/lymphocytes). The measures of proliferative activity were compared among groups with different histologic stages, and the influence of different prognostic variables (histologic stage, AgNOR index, mitotic index, MIB1 index) on survival time was evaluated. A significant difference in the proliferation patterns was recorded between the different histologic stages for the mitotic index (P = 0.0006) and MIB1 index (0.0013). Among the different parameters considered, histologic stage (P < 0.05), AgNOR index (P = 0.0291), and MIB1 index (P = 0.014) revealed a significant association with prognosis in univariate analysis. AgNOR index for 1-year survival and histologic stage for 2-year survival were the most significant parameters influencing survival, as determined by multiple nonlinear logistic regression.

Adenocarcinoma↗
PubMed1990

Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease.

Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome.

Adolescent↗
PubMed1997

Does histology influence outcome in childhood Hodgkin's disease? Results from the United Kingdom Children's Cancer Study Group.

PURPOSE: Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS: The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS: Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION: This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.

Actuarial Analysis↗
PubMed1997

The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria.

STUDY OBJECTIVE: To evaluate histologic, microbiological, and clinical criteria in the recognition of ventilator-associated pneumonia (VAP) in patients who died while mechanically ventilated. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. Postmortem fiberoptic bronchoscopy (FOB) and open lung biopsy were performed with collection of specimens initiated <1 h after death. The microbiological specimens included suction catheter aspirate of tracheal secretions, FOB-guided protected specimen brush (PSB) of tracheal secretions, blindly placed PSB in a distal airway, FOB-guided PSB in a distal airway, and FOB-guided BAL fluid (BALF) in a distal airway. Qualitative bacteriologic study was performed on all specimens, and quantitative bacteriologic study was performed on all but the suction catheter aspirate of the trachea. A biopsy specimen of peripheral lung parenchyma from the same region sampled by FOB was sent for quantitative culture and histologic analysis. The BALF was analyzed for cell population and percent of neutrophils containing intracellular organisms. The clinical criteria selected for comparison with histologic and microbiological results included a temperature > or =38.5 degrees C during the 48 h prior to death, a WBC count > or =15,000/mm3 in the 48 h prior to death, presence of a bacterial or fungal pathogen on the last sputum culture, radiographic worsening in the week prior to death, and worsening gas exchange defined as a 15% decrease in the PaO2/fraction of inspired oxygen ratio in the 72 h prior to death. RESULTS: None of the quantitative cultures had a reliable positive predictive value for histologic pneumonia. None of the five clinical criteria tested showed agreement with the presence or absence of histologic pneumonia. There was a significant correlation between qualitative and quantitative microbiological results from the distal airway/FOB-guided PSB, distal airway/BALF, and quantitative culture of the lung parenchyma. Also, suction catheter aspirate of the trachea had a sensitivity of 87% in recognizing the bacterial species simultaneously present in lung parenchyma. None of the patients with histologic pneumonia had <50% neutrophils in the BALF. CONCLUSIONS: Neither the bacterial, density from the four airway quantitative cultures, nor the bacterial density from quantitative culture of lung parenchyma accurately separated the histologic pneumonia and nonpneumonia groups. No clinical criteria or combination of clinical criteria correlated with the presence or absence of histologic pneumonia. A BALF with <50% neutrophils had a 100% negative predictive value for histologic pneumonia. A BALF quantitative culture had a sensitivity of 63%, specificity of 96%, and positive predictive value of 91% in recognizing sterile lung parenchyma. Thus, BALF may have a role in excluding pneumonia/infection in the ventilated patient. Antibiotic choice for the empiric therapy of VAP can be accurately guided by the microbial population recognized through culture of a tracheal suction catheter aspirate.

Aged↗
PubMed2005

Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver.

AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular nodules (106 HCC; 74 MRN; 32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA). RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale". Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool classified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepancies were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8 were assigned to the DN category by the classification tool. CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.

Carcinoma, Hepatocellular↗