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HIV coinfection does not compromise liver histological response to interferon therapy in patients with chronic hepatitis C.

OBJECTIVE: Although discrepancies between histological and virological responses to anti-hepatitis C virus (HCV) therapy are well-established in HIV-negative patients, the liver histological outcome has never been assessed in HIV-HCV co-infected patients receiving anti-HCV therapy. We compared histological responses to interferon (IFN) alpha therapy between HIV-positive and HIV-negative injecting drug users (IDU) and determined factors associated with histological response. DESIGN: Retrospective cohort study. SETTING: Hepatology unit of a tertiary referral hospital. PATIENTS/INTERVENTIONS: Seventy-nine HCV-infected IDU (32 HIV-positive) receiving a 6-month course of IFN-alpha2b therapy, 3 x 106 U three times a week. PRIMARY OUTCOME MEASURE: Histological response, defined by a > or =2 point decrease in total Knodell score measured on paired liver biopsies over a 2-year follow-up period. RESULTS: The sustained response rate to IFN therapy was lower in HIV-positive patients than in HIV-negative patients (6.2% versus 29.8%;P = 0.012). Conversely, the rates of histological response (40.6% versus 36.2%) were not different between HIV-positive and HIV-negative patients. Independent factors associated with histological response were first total Knodell score (P = 0.0007) and sustained response to IFN therapy (odds ratio, 12.34; P = 0.005). Histological response was observed in 25% of IFN non-responders whatever their HIV status. In HIV-positive patients, the CD4 cell count did not influence the histological response. CONCLUSIONS: in HIV-HCV co-infected patients treated with IFN, liver histological improvement is frequently observed, similarly to that observed in HIV-negative patients. Such beneficial effect of interferon therapy supports early treatment of chronic hepatitis C in HIV-infected patients.

Adult↗

Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies.

UNLABELLED: Protocol biopsies were performed to define the histologic response to tacrolimus therapy in patients with refractory acute renal allograft rejection. Renal allograft biopsies were performed at defined intervals after initiation of tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1-week biopsy did not show rejection reversal, repeat protocol biopsies were obtained at 1- to 2-week intervals, until histologic reversal was observed. Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation of tacrolimus therapy. Indicated biopsies were also performed to evaluate increases in serum creatinine. A total of 92 biopsies were performed in 23 patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated mild acute rejection in 64% of patients and moderate acute rejection in 36%. One week after initiation of tacrolimus therapy, protocol biopsies revealed the following: no rejection (60%), improvement (13%), no change (20%), and worsening rejection (7%). Histologic changes at 1 week did not correlate with changes in renal function, as 63% of patients that showed histologic improvement or reversal during the first 2 weeks of therapy did not show improvement in serum creatinine. A lack of histologic improvement (or worsening) at 1 week was demonstrated in a significant proportion of patients (27%); increased tacrolimus dosing provided rejection reversal or improvement in 1-2 weeks in each of these patients. Recurrent rejection was diagnosed on eight biopsies in seven patients, however six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of an elevation in serum creatinine). Delayed improvement in renal function, despite histologic reversal, was likely due to physiologic effects of tacrolimus (i.e., afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus toxicity was not observed during the first 2 weeks of therapy. Histologic evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60 days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not correlate with development of clinically silent or clinically evident nephrotoxicity. IN CONCLUSION: 1) protocol biopsies provide information that allows individualization of tacrolimus rejection therapy, 2) histologic resolution of rejection often precedes biochemical improvement, 3) histologic evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of therapy, and 4) clinically silent recurrent rejection and clinically silent tacrolimus nephrotoxicity are observed with significant frequency during tacrolimus therapy for refractory renal allograft rejection.

Acute Disease↗

Histological evolution of chronic hepatitis C. Factors related to progression.

We have evaluated the histological progression of liver disease in 29 untreated patients with chronic hepatitis C. All patients were positive to antibodies to hepatitis C virus by ELISA2 and RIBA2. Two liver biopsies were carried out for each patient, with an interval ranging between 12 and 126 months (mean 50.2 +/- 30.7). In all cases the usual histological classification was applied and the histological activity index scoring system according to Knodell et al. was determined. Fifteen cases worsened (51.7%), 12 cases showed no histological changes (41.4%) and two patients improved (6.9%). Cirrhosis was found in five patients (18.5%) in the second liver biopsy. Epidemiological, clinical, biochemical and histological progression and the group with impairment in liver histology. Factors related to histological worsening were: more advanced age (p = 0.002), high levels of aspartate aminotransferase (p = 0.04), high global histological activity index (p = 0.03) and piecemeal necrosis and bridging necrosis scores (p = 0.02) at first biopsy. The histological activity index can be applied to assess the natural history of chronic viral hepatitis, and is a good tool to evaluate the prognosis. Thus chronic hepatitis C virus infection is a histologically progressive disease in at least half the cases.

Adult↗

Comparison of results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage fluid, and histologic evaluation of lung specimens in dogs with respiratory tract disease: 16 cases (1996-2000).

OBJECTIVE: To compare results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and histologic evaluation of biopsy and necropsy specimens in dogs with respiratory tract disease and to determine whether histologic evaluation provides important diagnostic information not attainable by the other methods. DESIGN: Retrospective study. ANIMALS: 16 dogs. PROCEDURE: BAL fluid was classified as normal, neutrophilic, eosinophilic, mononuclear, mixed, neoplastic, or nondiagnostic. Radiographic abnormalities were classified as interstitial, bronchial, bronchointerstitial, or alveolar. Histologic lesions were classified as inflammatory, fibrotic, or neoplastic, and the predominant site of histologic lesions was classified as the alveoli, interstitium, or airway. RESULTS: The predominant radiographic location of lesions correlated with the histologic location in 8 dogs. Of 11 dogs with histologic evidence of inflammatory disease, 8 had inflammatory BAL fluid. Of the 2 dogs with histologic evidence of neoplasia, 1 had BAL fluid suggestive of neoplasia, and the other had BAL fluid consistent with septic purulent inflammation. Two dogs without any histologic abnormalities had mononuclear or nondiagnostic BAL fluid. Two dogs with histologic evidence of fibrosis had mononuclear or mixed inflammatory BAL fluid. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that although thoracic radiography, cytologic evaluation of BAL fluid, and histologic evaluation of lung specimens are complementary, each method has limitations in regard to how well results reflect the underlying disease process in dogs with respiratory tract disease. Lung biopsy should be considered in cases where results of radiography and cytology are nondiagnostic.

Animals↗

Significance of histologic criteria for the management of patients with malignant colorectal polyps and polypectomy.

BACKGROUND: The management of invasive cancer in colorectal polyps (malignant polyps) is controversial, particularly with regard to the different sets of histologic criteria for deciding whether malignant colorectal polyps should be treated by polypectomy alone or be followed by surgical resection. We report on the outcome of patients in accordance with the histologic assessment of their malignant polyps. METHODS: Malignant polyps were defined as having favourable histology (free margin, grade I or II, and no angiolymphatic invasion) or unfavorable histology (no free margin, grade III, or angiolymphatic invasion). Malignant polyps with favourable histology were treated by endoscopic polypectomy alone, whereas further therapy was recommended for malignant polyps with unfavourable histology. Residual cancer in a resection specimen and local or metastatic recurrence during the follow-up period (mean, 60 months; range, 12 - 120) were defined as adverse outcome. RESULTS: Thirty-seven malignant polyps were detected in 35 (0.5%) of 6605 patients. Five of these 35 patients were treated by primary bowel resection and analysed separately. In the other 30 patients the following unfavourable histologic signs were detected in 20 (62.5%) of 32 malignant polyps; no free margin in 16, grade III in 1, and angiolymphatic invasion in 3 polyps. Twelve polyps with favourable histology had no adverse outcome; in contrast, 5 of 20 polyps with unfavourable histology had an average outcome (P < 0.05). CONCLUSIONS: Locally excised malignant polyps without unfavourable histologic signs may not need further surgical treatment; for all other malignant polyps an ensuing bowel resection is recommended.

Adult↗

Isolation and characterization of human malignant glioma cells from histologically normal brain.

Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines derived from gross tumor and histologically normal brain were usually histologically identical and demonstrated equivalent motility, but had different growth rates.

Aged↗

Design-Dependent Variations in Coronary Stent Stenosis Measured as Precisely by Angiography as by Histology.

BACKGROUND: Coronary stent restenosis is a growing clinical concern which, because restenosis may vary with stent design, requires a validated, accurate, and sensitive method of evaluation as new stents are developed. Histologic analysis of arterial cross sections, a highly accurate tool in animal models, has limited applicability in humans. Quantitative coronary angiography, while commonly used in the clinical evaluation of coronary interventions, has a controversial role as an adequate measure of restenosis, and few studies have validated quantitative angiography in diseased arteries. We tested the hypothesis that in-stent stenosis could be assessed as accurately by pre-mortem angiography as by post-mortem histology, allowing angiographic discrimination of variable late luminal loss provoked by stents of different designs. METHODS AND RESULTS: Stent stenosis in porcine coronary arteries was assessed by quantitative coronary angiography and histology at 3, 28 and 56 days. Four stainless steel stent designs were studied: a slotted tube configuration with or without a polymer wrap and a corrugated ring configuration with or without a polymer coating. Although acute luminal gain (mean stent:artery ratio 1.07 +/- 0.01) and stent recoil (mean stent diameter at follow-up 2.65 +/- 0.02 mm) were similar for all designs and time points, significant differences in late luminal loss were observed and were detected as accurately by angiography as by histology. At 28 days, the polymer wrapped slotted tube design resulted in a nearly two-fold greater late loss than its bare metal counterpart (1.40 +/- 0.09 mm vs. 0.80 +/- 0.12 mm, p <.001 by angiography; 1.33 +/- 0.10 mm vs. 0.67 +/- 0.06 mm, p <.0001 by histology), while there was no significant difference in 28 day late loss between the polymer coated and bare metal corrugated ring designs (p = NS by angiography or histology). Time point differences were also observed both angiographically and histologically, with marked progression of lumen loss between 3 and 28 days and slower but persistent progression between 28 and 56 days. Overall comparison of individual lumen diameter measurements for all stented arteries independent of design or duration of follow-up demonstrated a precise correlation between angiography and histology (y = 0.96x +0.25, p <.0001, r2 = 0.82). CONCLUSIONS: Coronary stents of varied designs provoke markedly different degrees of late luminal loss, and these differences can be measured as accurately by quantitative angiography as by histologic analysis of arterial cross sections. This may be due to optimization of angiographic measurements by the concentric nature of intimal thickening in stented arteries, and to structural rigidity imparted by the stent, preserving arterial lumen size for histologic analysis. Quantitative angiography, therefore, may represent an adequate endpoint in clinical trials comparing stent designs.

Journal Article↗

Design-Dependent Variations in Coronary Stent Stenosis Measured as Precisely by Angiography as by Histology.

BACKGROUND: Coronary stent restenosis is a growing clinical concern which, because restenosis may vary with stent design, requires a validated, accurate and sensitive method of evaluation as new stents are developed. Histologic analysis of arterial cross sections, a highly accurate tool in animal models, has limited applicability in humans. Quantitative coronary angiography, while commonly used in the clinical evaluation of coronary interventions, has a controversial role as an adequate measure of restenosis, and few studies have validated quantitative angiography in diseased arteries. We tested the hypothesis that in-stent restenosis could be assessed as accurately by pre-mortem angiography as by post-mortem histology, allowing angiographic discrimination of variable late luminal loss provoked by stents of different designs. METHODS AND RESULTS: Stent stenosis in porcine coronary arteries was assessed by quantitative coronary angiography and histology at 3, 28 and 56 days. Four stainless steel stent designs were studied: a slotted tube configuration with or without a polymer wrap and a corrugated ring configuration with or without a polymer coating. Although acute luminal gain (mean stent:artery ratio of 1.07 +/- 0.01) and stent recoil (mean stent diameter at follow-up 2.65 +/- 0.02 mm) were similar for all designs and time points, significant differences in late luminal loss were observed and were detected as accurately by angiography as by histology. At 28 days, the polymer wrapped slotted tube design resulted in a nearly two-fold greater late loss than its bare metal counterpart (1.40 +/- 0.09 mm vs. 0.80 +/- 0.12 mm, p <.001 by angiography; 1.33 +/- 0.10 mm vs. 0.67 +/- 0.06 mm, p <.0001 by histology), while there was no significant difference in 28 day late loss between the polymer coated and bare metal corrugated ring designs (p = NS by angiography or histology). Time point differences were also observed both angiographically and histologically, with marked progression of lumen loss between 3 and 28 days and slower but persistent progression between 28 and 56 days. Overall comparison of individual lumen diameter measurements for all stented arteries independent of design or duration of follow-up demonstrated a precise correlation between angiography and histology (y = 0.96x +0.25, p <.0001, r2 = 0.82). CONCLUSIONS: Coronary stents of varied designs provoke markedly different degrees of late luminal loss, and these differences can be measured as accurately by quantitative angiography as by histologic analysis of arterial cross sections. This may be due to optimization of angiographic measurements by the concentric nature of intimal thickening in stented arteries, and to structural rigidity imparted by the stent, preserving arterial lumen size for histologic analysis. Quantitative angiography, therefore, may represent an adequate endpoint in clinical trials comparing stent designs.

Journal Article↗

Treatment of low grade gastric mucosa-associated lymphoid tissue lymphoma in stage I with Helicobacter pylori eradication. Long-term results after sequential histologic and molecular follow-up.

BACKGROUND AND OBJECTIVES: Most cases of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma are associated with H. pylori. In localized disease (stage I), eradication of H. pylori can result in histologic regression of the lymphoma in 50% to 100% of the patients. Moreover, in half of the apparently cured patients a monoclonal rearrangement of the IgH gene can be demonstrated. However, data on the long-term outcome of the patients are scarce. We report the evolution of a series of patients followed-up since 1994 in order to evaluate the long-term outcome of the apparently cured lymphoma. DESIGN AND METHODS: From January 1994 to July 2000, 19 consecutive patients with stage I gastric low grade MALT lymphoma were sequentially studied in our hospital. They had all been diagnosed by endoscopy and had had a complete staging (including CT-scan, contrast X-ray of the small bowel, bone marrow biopsies, immunophenotyping of bone marrow and peripheral blood and, in the later years, endoscopic ultrasonography). Diagnosis required established histologic criteria for low grade MALT lymphoma in the samples obtained by endoscopy. The investigation of H. pylori status included histologic search, serology and breath test urea-(13)C. Only patients in stage I disease associated with H. pylori were included in the study. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed every 2-3 months in the first year, every 6 months in the second year and then yearly. Post-treatment biopsies were obtained by endoscopy for histologic studies, H. pylori cultures and molecular studies. The criteria of Wotherspoon et al. were used for the histological evaluation. Molecular studies were performed with a polymerase chain reaction analysis of the IgH gene using semi-nested procedures with consensus primers for the V(H) (Fr3A/Fr2A) and J(H) (LJH and VLJH) regions. RESULTS: After the eradication treatment, 18 of the 19 patients (94.7%) achieved histologic regression of the MALT lymphoma that occurred after a mean of 4.6 months (range 2-19). In 11 of the 18 histologically cured patients (61%) a monoclonal rearrangement of the IgH gene was demonstrated. In 2 patients the monoclonality disappeared completely, but 9 of the 11 patients (82%) had either persistent (3 patients) or intermittently persistent (5 patients) monoclonality for as long as 64 months. None of the patients who achieved a histologic remission (either with or without monoclonality) relapsed after a mean follow-up of 37 months (range 2-78). Two patients were lost to follow-up and another patient died of a gastric carcinoma; the remaining 15 patients are still in histologic remission after a mean period of 43 months (range 5-78). Ten patients studied between 1994 and the end of 1996 are in remission after a mean of 59 months (range 33-78). INTERPRETATIONS AND CONCLUSIONS: In most cases of gastric low-grade MALT lymphoma in stage I eradication of H. pylori can produce histologic regression of the lymphoma and this regression can be maintained for years. However, IgH gene monoclonality can be detected and persists in most cases. Although this persistent monoclonality seems to indicate the presence of a latent lymphoma population, over a period of 6 years it has not so far influenced the outcome. These findings indicate that in cases of localized gastric low-grade MALT lymphoma associated with H. pylori, the first step of treatment should be eradication of the H. pylori; however, a close and long follow-up is essential to determine the ultimate outcome of these patients and the possible significance of the persistent monoclonality.

Adult↗

[Application of transbronchial brushing for histological diagnosis of lung cancer].

In order to improve the preoperative diagnostic rate of lung cancer, histological examination was performed by transbronchial brushing in 35 cases, and diagnostic contribution of brushing specimen was compared with that of transbronchial forceps biopsy (TBFB). Histological structures were well preserved in the histology section of brushing specimens, especially in cases of small cell lung cancer. The positive rate of brushing histology was 46%, which was the same as that of TBFB. The total histological diagnostic rate was 66% with simultaneous examination of bronchial brushing and TBFB specimens. Consequently, the use of brushing specimens for histologic evaluation made an additional contribution to the correct positive histology diagnostic rate. Brushing histology is indicated for all types of lung cancer, because in most TBFB-negative cases, biopsies were performed from inappropriate sites of tumors or their materials wer crushed by forceps. It was suggested that concomitant application of brushing specimen for histology examination, contributed to more accurate preoperative histology diagnosis for lung cancer.

Adenocarcinoma↗

[Value of the light-test histological study in photodermatoses].

Clinic and histologic analysis of 92 phototests of various photodermatosis (14 benign summer light eruption (BSLE), 47 polymorphous light eruption (PMLE) 20 persistent light reactor photodermatitis (PLRP), 11 drug induced photodermatitis (DIP) has been performed. Clinically, a phototoxic aspect was observed in 30 cases, it was photoallergic in 36 cases and uncertain in 26 cases. Histologically, a phototoxic picture was present in 32 cases, a photoallergic one in 48 cases, and 12 cases exhibited unclassified aspect. Only one case of BSLE was associated with photoallergic aspect, clinically and histologically. Photoallergic type was observed in 70 p. 100 of iterative exposure phototest (IEP) of PMLE; clinical and histological aspects were concordant; in contrast phototoxic aspects were constantly observed when single exposure phototest (SEP) were used. In PLRP histological aspect of IEP was constantly of photoallergic type; whereas clinical aspect was uncertain in 50 p. 100 of the cases; 7 of the 10 biopsies of SEP exhibited a photoallergic picture. In DIP histological aspect of IEP was constantly photoallergic, whereas 5 of the 6 cases exhibited uncertain clinical aspect; only one of the 5 SEP gave a photoallergic reaction both clinically and histologically. Comparison of histological features revealed a more typical photoallergic picture in PLRP than in PMLE. We conclude that: the reproducibility of clinical and histological lesions is better with the iterative exposure phototest than with single exposure phototest; histologic examination is more reliable than clinical findings in persistent light reactor photodermatitis and drug induced photodermatitis.

Humans↗

Differentiating histologic malignancy of primary brain tumors: pentavalent technetium-99m-DMSA.

UNLABELLED: This study assessed pentavalent 99mTc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. METHODS: SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq 99mTc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. RESULTS: Approximately 95% of both benign and malignant primary brain tumors were demonstrated by 99mTc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. The delayed uptake ratio, retention ratio and retention index were higher in the malignant tumors than the benign tumors. CONCLUSION: Technetium-99m(V)-DMSA washout from the tumor was highly dependent upon its histology and histologic malignancy. The delayed uptake ratio considerably reflected tumor histology and differentiated benign tumors from malignant tumors. The retention ratio and retention index significantly reflected tumor histology and histologic grade of primary brain tumors and clearly distinguished between benign and malignant tumors with statistically significant difference (p < 0.05). These results could suggest the clinical utility of 99mTc(V)-DMSA in imaging primary brain tumors and differentiating their histological malignancy grade noninvasively.

Adolescent↗

A new histological procedure for re-evaluation of the serological test for Helicobacter pylori.

To re-evaluate the accuracy of the serological test for Helicobacter pylori, fixation of biopsy specimens with Carnoy's solution (preserving the mucous layer in tissue preparations) followed by immunohistochemical staining (a new histological procedure) was used as the reference histological method instead of 10% formalin fixation followed by hematoxylin-eosin staining (the conventional histological procedure). Biopsy specimens (antrum and body) from 114 patients with gastritis (including non-ulcer dyspepsia) or gastric and/or duodenal ulcers were obtained by endoscopy and used for both bacteriological culture and histological examination. Serum samples were taken from all patients at the time of endoscopy. The serum levels of specific IgG and IgA antibodies for Helicobacter pylori were measured by commercial enzyme immunoassay kits. The reliability of the IgG and IgA measurements was evaluated by analyzing receiver operating characteristic curves obtained using the two histological procedures. With the conventional histological procedure as the reference, the sensitivity and specificity levels of the serological test were 87.2% and 82.1%, respectively. With the new histological procedure as reference, sensitivity and specificity were 94% and 96.7%, respectively. The insufficient accuracy reported for the serological test could be due to false-positive or false-negative results obtained when the conventional histological procedure is used as the reference. The new histological procedure used here revealed that the serological test for Helicobacter pylori is more reliable than previously thought.

Antibodies, Bacterial↗

Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging.

Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P = 0.013), MRI grade (P = 0.02) and radiological grade (P < 0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r = 0.3, P = 0.033). MRI correlated with overall histological grade (r = 0.41, P = 0.015, n = 34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50 years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MRI.

Aged↗

The creation of a brain atlas for image guided neurosurgery using serial histological data.

Digital and print brain atlases have been used with success to help in the planning of neurosurgical interventions. In this paper, a technique presented for the creation of a brain atlas of the basal ganglia and the thalamus derived from serial histological data. Photographs of coronal histological sections were digitized and anatomical structures were manually segmented. A slice-to-slice nonlinear registration technique was used to correct for spatial distortions introduced into the histological data set at the time of acquisition. Since the histological data were acquired without any anatomical reference (e.g., block-face imaging, post-mortem MRI), this registration technique was optimized to use an error metric which calculates a nonlinear transformation minimizing the mean distance between the segmented contours between adjacent pairs of slices in the data set. A voxel-by-voxel intensity correction field was also estimated for each slice to correct for lighting and staining inhomogeneity. The reconstructed three-dimensional (3D) histological volume can be viewed in transverse and sagittal directions in addition to the original coronal. Nonlinear transformations used to correct for spatial distortions of the histological data were applied to the segmented structure contours. These contours were then tessellated to create three-dimensional geometric objects representing the different anatomic regions in register with the histological volumes. This yields two alternate representations (one histological and one geometric) of the atlas. To register the atlas to a standard reference MR volume created from the average of 27 T1-weighted MR volumes, a pseudo-MRI was created by setting the intensity of each anatomical region defined in the geometric atlas to match the intensity of the corresponding region of the reference MR volume. This allowed the estimation of a 3D nonlinear transformation using a correlation based registration scheme to fit the atlas to the reference MRI. The result of this procedure is a contiguous 3D histological volume, a set of 3D objects defining the basal ganglia and thalamus, both of which are registered to a standard MRI data set, for use for neurosurgical planning.

Algorithms↗

Does ultrasound core breast biopsy predict histologic finding on excisional biopsy?

BACKGROUND: The purpose of this study was to determine whether ultrasound-guided core breast biopsy accurately predicts the histologic finding of a subsequent excisional procedure. METHODS: Data were collected prospectively from 1997 to 2001 for 832 ultrasound-guided core breast biopsies (USB) that were followed by excisional breast procedure (EP) within 1 year at our institution. The principal histologic finding obtained at USB and EP was identified for each procedure and the degree of agreement was assessed. RESULTS: The USB histology predicted EP histology in 90% (n = 746) of the procedures. The USB histology was more significant than EP histology in 3% (n = 22) of procedures; USB histology underdetermined EP histology in 7% (n = 64) of procedures. Overall, our results indicate moderate agreement between the principal histology identified at USB relative to that identified at EP. CONCLUSIONS: Ultrasound-guided core breast biopsy is an effective diagnostic method, but sampling limitations do exist.

Biopsy↗

Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors.

PURPOSE: Teratoma with malignant transformation refers to a form of germ cell tumor in which a somatic teratomatous component becomes morphologically malignant and develops aggressive growth. We evaluated the spectrum of histologies, chromosomal abnormalities and clinical outcome in patients with teratoma with malignant transformation. MATERIALS AND METHODS: We identified 46 patients with germ cell tumor meeting morphologic criteria for malignant transformation. Histology, disease extent and treatment were correlated with survival. Tumors in 12 patients were studied by conventional cytogenetics or molecular genetic techniques for the isochromosome 12p [i(12p)], a marker for germ cell tumor, as well as other chromosomal abnormalities. RESULTS: The site of first detection of malignant transformation occurred in the primary tumor of 21 cases (44%), at a metastatic site in 20 (43%) and in both sites in 5 (10%). Sarcoma was the most frequent histology, identified in 29 patients (63%) with rhabdomyosarcoma the most common subtype. Seventeen tumors (37%) contained a solid tumor histology other than sarcoma, with adenocarcinoma and primitive neuroectodermal tumor as the most common histologies. Four patients with mediastinal germ cell tumor containing sarcoma also had hematological malignancies, including a focus of nonHodgkin's lymphoma in the mediastinal primary tumor (1) and nonlymphocytic leukemia in spleen or bone marrow (3). Patients who had teratoma with malignant transformation components confined to the testis or retroperitoneum completely resected experienced a longer survival than those with distant metastases or incompletely resected tumors (p = 0.003). Chromosomal abnormalities associated with germ cell tumor (i[12p]) were identified in 11 of 12 tumors containing adenocarcinoma, primitive neuroectodermal tumor, sarcoma and leukemia. In addition to i (12p), chromosomal rearrangements characteristic of the transformed histology were detected in 4 tumors. CONCLUSIONS: A variety of nongerm cell histologies, including sarcoma, adenocarcinoma, primitive neuroectodermal tumor and leukemia, may occur in association with germ cell tumor. Chromosomal abnormalities in these tumors include i (12p), reflecting germ cell tumor clonality, as well as chromosomal abnormalities associated with the transformed histology. These tumors do not respond like germ cell tumor to cisplatin-containing chemotherapy regimens. Treatment should be tailored according to that used in standard management of the transformed histology, and surgical resection is the mainstay of therapy.

Adenocarcinoma↗

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.

OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. METHODS: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. RESULTS: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with 16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.

Anti-Inflammatory Agents↗