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Soheila Korourian

Publications and source records attributed to Soheila Korourian.

At least 19 recordsLinked to original sources

Hematoma-directed ultrasound-guided (HUG) breast lumpectomy.

BACKGROUND: Needle localization breast biopsy (NLBB) is presently the primary means of localizing non-palpable lesions. Disadvantages of NLBB include vasovagal episodes, patient discomfort, and miss rates. Because hematomas naturally fill the cavity after vacuum-assisted breast biopsies (VABB), we hypothesized that ultrasound (US) could be used to find and accurately excise the actual biopsy site of non-palpable breast lesions without a needle. METHODS: This is a retrospective study from January 2000 to July 2005. Electronic chart review identified patients with non-palpable breast lesions detected by means of mammogram who then underwent lumpectomy via NLBB or the hematoma-directed ultrasound-guided technique (HUG). HUG involved localizing the hematoma with a 7.5-MHz US probe and using the "line of sight" technique straight down toward the chest wall. A block of tissue encompassing the hematoma was then excised. RESULTS: Localization procedures were performed in 186 patients-63 (34%) via needle localization and 123 (66%) via HUG. The previous VABB site in 100% of patients was successfully excised using HUG, 65 of 123 (53%) were benign and 58 of 123 (47%) were malignant; margins were positive in 13 of these 58 (22%). NLBB was successful in 100% of patients, 44 of 63 (70%) were benign and 19 of 63 (30%) were malignant; margins were positive in 14 of these 19 (73%). Margin positivity was significantly higher for NLBB than HUG (P = 0.0001, Fisher Exact). CONCLUSIONS: This study suggests that HUG is more accurate in localizing non-palpable lesions than NLBB. By eliminating the additional procedure needed for NLBB, HUG may also be more time- and cost efficient. HUG makes VABB not only a less invasive diagnostic procedure, but also a localization procedure.

Adult↗

eRFA: excision followed by RFA-a new technique to improve local control in breast cancer.

INTRODUCTION: Excision followed by RFA (eRFA) may allow improved cosmesis while ensuring negative margins in patients with breast cancer. This technique utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA will decrease the need for re-excision of inadequate margins. METHODS: Between July 2002 and January 2005, we conducted a multiphase trial of RFA of prophylactic mastectomy specimens and of women desiring lumpectomy. In both models, a lumpectomy was performed, the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 min. Whole mount slides were used to measure the zone of ablation for ex vivo specimens. Hematoxylin and eosin staining of in vivo lumpectomy margins < 3 mm was considered inadequate. RESULTS: Nineteen prophylactic mastectomy ablations revealed a consistent perimeter of ablation. Forty-one patients (mean age 63 +/- 14 years) had an average tumor size of 1.6 +/- 1.5 cm underwent in vivo eRFA, and 25% had inadequate margins: one focally positive, one < 2 mm, eight < 1 mm and one grossly positive. Only the grossly positive margin was re-excised. Overall complication rate of in vivo ablations was 7.5%. Twenty-four of 41 patients did not have post-eRFA XRT. No in-site local recurrences have occurred during a median follow-up of 24 months (12-45 months). Two patients have occurred elsewhere. CONCLUSIONS: The ex vivo ablation model reliably created a 5-10 mm perimeter of ablation. In vivo, this zone reduced the need for re-excision for inadequate margins by 91% (10/11). Short-term follow-up suggests that eRFA could reduce re-excision surgery and local recurrence.

Adult↗

The receptor expression pattern in ductal carcinoma in situ predicts recurrence.

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) is based on size and pathologic morphology. We hypothesized that as with invasive breast cancer, receptor expression in DCIS is important for predicting recurrence. METHODS: Retrospective review from 1990 through 2002 identified 94 DCIS patients who had documented estrogen receptor (ER), progesterone receptor (PR), p53, Her-2/neu (HER), tumor characteristics, type of surgery, use of radiation or tamoxifen, and site of recurrence. RESULTS: Median age and tumor size was 57.5 years and 2.0 cm, respectively. Median follow-up was 4 years. Overall recurrence rate was 6%. The ER-positive/PR-negative/HER-positive receptor pattern represented 50% (3 of 6) of total recurrences (P = .01). The length of disease-free-survival in the ER-positive/PR-negative/HER-positive receptor pattern was significantly shorter than in the rest of the patients (P = .0011). COMMENTS: Receptor expression may be important in DCIS for predicting recurrence. HER positivity, even with ER positivity, is significantly associated with a higher risk of recurrence.

Aged↗

Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer.

Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly into the blood. We investigated the relative role of sLe(x) oligosaccharide in the dissemination of breast carcinoma, employing a spontaneous murine metastasis model. An sLe(x) deficient subpopulation of the 4T1 mammary carcinoma cell line was produced by negative selection using the sLe(x)-reactive KM93 MAb. This subpopulation was negative for E-selectin binding but retained P-selectin binding. Both sLe(x)-negative and -positive cells grew at the same rate; however, sLe(x)-negative cells spread more efficiently on plates and had greater motility in wound-scratch assays. Mice inoculated in the mammary fat pad with sLe(x)-negative and -positive variants produced lung metastases. However, the number of lung metastases was significantly increased in the group inoculated with the sLe(x)-negative variant (p = 0.0031), indicating that negative selection for the sLe(x) epitope resulted in enrichment for a subpopulation of cells with a high metastatic phenotype. Cell variants demonstrated significant differences in cellular morphology and pattern of tumor growth in primary and secondary tumor sites. These results strongly suggest that loss of sLe(x) may facilitate the metastatic process by contributing to escape from the primary tumor mass.

Animals↗

Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats.

INTRODUCTION: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. METHOD: Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. RESULTS: The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. CONCLUSION: Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Reduction of spontaneous metastases through induction of carbohydrate cross-reactive apoptotic antibodies.

The selective targeting of tumor-associated carbohydrate Ags by the induction of serum Abs that trigger apoptosis of tumor cells as a means to reduce circulating tumor cells and micrometastases would be an advantage in cancer vaccine development. Some plant lectins like Griffonia simplicifolia lectin I and wheat germ agglutinin mediate the apoptosis of tumor cells. We investigated the possibility of using these lectins as templates to select peptide mimotopes of tumor-associated carbohydrate Ags as immunogens to generate cross-reactive Abs capable of mediating apoptosis of tumor cells. In this study, we show that immunization with a mimotope selected based on its reactivity with Griffonia simplicifolia lectin I and wheat germ agglutinin induced serum IgM Abs in mice that mediated the apoptosis of murine 4T1 and human MCF7 cell lines in vitro, paralleling the apoptotic activity of the lectins. Vaccine-induced anti-carbohydrate Abs reduced the outgrowth of micrometastases in the 4T1 spontaneous tumor model, significantly increasing survival time of tumor-bearing animals. This finding parallels suggestions that carbohydrate-reactive IgM with apoptotic activity may have merit in the adjuvant setting if the right carbohydrate-associated targets are identified.

Amino Acid Sequence↗

Correlation of magnetic resonance imaging and pathologic size of infiltrating lobular carcinoma of the breast.

BACKGROUND: Determining the extent of infiltrating lobular carcinoma (ILCA) in the breast is difficult. This study was designed to determine if the size of ILCA on magnetic resonance imaging (MRI) correlated with final pathology. METHODS: Retrospective study of patients between 1998 and 2004, who were evaluated for extent of ILCA prior to definitive treatment, was conducted. Demographic data and radiology and pathology results were obtained. Spearman correlation coefficient was used. RESULTS: Twenty-nine patients (median age 62 years) had MRI of breast. Fourteen patients (48%) had contralateral MRIs; 13 (45%) normal; 1 (8%) prompted core biopsy; 6 of 13 patients underwent contralateral mastectomies, which were benign. The distribution of tumor size was: T1 = 15 (52%); T2 = 7 (24%); T3 = 5 (17%); T4 = 2 (7%). Spearman correlation coefficient between tumor size on ultrasound and MRI with pathology was .19 (P = .5) and .88 (P < .001), respectively. CONCLUSION: MRI provided superior correlation between tumor size and pathology.

Aged↗

Determination of HER2/neu status in uterine serous papillary carcinoma: Comparative analysis of immunohistochemistry and fluorescence in situ hybridization.

OBJECTIVE: To evaluate and compare HER2/neu protein overexpression and gene amplification in uterine serous papillary endometrial cancer (USPC). STUDY DESIGN: Immunohistochemical (IHC) and fluorescent in situ hybridization (FISH) assays were used to analyze and compare HER2/neu protein expression and gene amplification, respectively, in paraffin blocks from 26 women harboring stage IA to IV USPC treated at the University of Arkansas for Medical Sciences from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. RESULTS: Moderate-to-strong expression of HER2/neu protein was noted in 16 (62%) of 26 USPC samples evaluated, with 7 (27%) samples showing moderate staining (2+) and 9 (35%) showing strong staining (3+) for HER2/neu. Amplification of the ERBB2 gene by FISH was observed in 11 of the 26 (42%) cases. Protein overexpression and gene amplification were found to correlate in 100% (9 of 9) of the 3+ positive tumors and 2 out of 7 (29%) of the 2+ positive tumors. Heterogeneity was noted in 3 cases in the amplification of the HER2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. None of the 10 USPC cases scored by IHC as 0 or 1+ was found positive for ERBB2 amplification by FISH. CONCLUSIONS: Amplification of the HER2/neu oncogene represents a common finding in USPC. FISH analysis should be used for confirmation of gene amplification in USPC showing 2+ expression of HER2/neu. Prior screening and selection of appropriate immunohistochemistry-positive areas may be beneficial in the selection of some USPC patients undergoing FISH analysis.

Aged↗

Lack of sexual dimorphism in alcohol-induced liver damage (ALD) in rats treated chronically with ethanol-containing low carbohydrate diets: The role of ethanol metabolism and endotoxin.

Evidence has been presented suggesting that females are significantly more susceptible to alcohol-induced liver damage (ALD) than males. In the current study, we examined sexual dimorphism in hepatic pathology, metabolism and cytokine profiles using two different rat models of ALD. Male and female Sprague-Dawley or Wistar rats were fed ethanol-containing low-carbohydrate liquid diets using oral or intragastric methods for 42 or 60 days. In both models, ethanol treatment produced similar significant liver hyperplasia accompanied by increases in plasma ALT, steatosis, inflammation and necrosis (p < 0.05). Greater pathology scores were observed in the intragastrically infused rats. Males did not differ significantly from females in serum ALT values or pathology despite greater elevations in TNFalpha and IL-1beta mRNAs in ethanol-treated female rat livers (p < 0.05). Furthermore, there was no sexual dimorphism in blood ethanol concentrations or CYP2E1-induction even though sexually dimorphic alterations in other hepatic cytochrome P450 enzymes were observed. These data do not support previous observations that female rats have a greater susceptibility to ethanol-induced hepatotoxicity than males.

Alanine Transaminase↗

A morphologic and statistical comparative study of small-cell carcinoma and non-Hodgkin's lymphoma in fine-needle aspiration biopsy material from lymph nodes.

Small-cell carcinoma (SmC) and high-grade non-Hodgkin's lymphoma (NHL) are aggressive neoplasms that require prompt diagnosis and treatment. An immediate diagnosis can be obtained using fine-needle aspiration biopsy (FNAB) material from lymph nodes (LNs), which are clinically or radiologically suspicious for tumor involvement. However, in aspirates from LNs, the cytologic distinction of SmC from NHL can be challenging. The purpose of this study was to evaluate the usefulness of various cytologic features that can be used during a rapid on-site evaluation to differentiate these two entities. Twenty-seven metastatic SmC and 50 NHLs cases diagnosed by FNAB of LNs were reviewed. All NHL diagnoses (neck, 29; abdomen, 9; axilla, 6; groin, 5; and parotid, 1) were confirmed with tissue sections, flow cytometry, or immunohistochemistry. These cases were classified as follicular, 21 (42%); diffuse large B cell, 13 (26%); small lymphocytic, 7 (14%); mantle cell, 4 (8%); anaplastic large cell, 2 (4%); and 1 each (2%), Burkitt, lymphoplasmacytic, and peripheral T-cell lymphomas. Immunochemistry confirmed the cytologic diagnoses of all SmC cases (neck, 16; mediastinum, 9; abdomen, 1; and axilla, 1) with either positive chromogranin or synaptophysin. All specimens were reviewed independently by three cytopathologists who were unaware of the original diagnoses. The presence and proportion of single (noncohesive) tumor cells, lymphoglandular bodies, nuclear fragments, paranuclear blue inclusions, nuclear molding, evenly dispersed fine-granular chromatin, crush artifact, and composition of cell clusters (monomorphic vs. polymorphic) were statistically evaluated. The presence of evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments was each statistically significant in differentiating SmC when compared with NHL (P < 0.01). The remaining features were not significant in distinguishing SmC from NHL in LN aspirates. The identification of distinct cytologic findings such as evenly dispersed fine-granular chromatin, paranuclear blue inclusions, and nuclear fragments can be a valuable aid to accurately diagnose and differentiate metastatic SmC from NHL in FNAB preparations from LNs.

Biopsy, Fine-Needle↗

Diagnostic value of GLUT-1 immunoreactivity to distinguish benign from malignant cystic squamous lesions of the head and neck in fine-needle aspiration biopsy material.

The distinction of cystic squamous-cell carcinoma (SCC) from benign cystic squamous lesions (BCSLs) of the head and neck can be problematic on fine-needle aspiration biopsy (FNAB) material, particularly when BCSLs display epithelial reactive atypia or when SCC is well differentiated. Glucose transporter 1 (GLUT-1), a facilitative cell surface glucose transport protein, is aberrantly expressed in many cancers including oral and hypopharyngeal SCC. We evaluated the expression of GLUT-1 by immunochemistry on FNAB material to determine its value in distinguishing cystic SCC from BCSL of the head and neck. A 5-yr retrospective review of all head and neck cystic squamous lesions having FNAB specimens with cell block material, radiological studies, and histological confirmation was performed at our institution. Cell block material from 24 cystic squamous lesions, including 8 (33%) BCSL (7 branchial cleft cysts and 1 thyroglossal duct cyst[TDC]) and 16 (67%) metastatic SCCs with cystic/liquefactive degeneration, was retrieved and immunostained with anti-GLUT-1. GLUT-1 expression was considered positive when at least 10% of squamous cells exhibited distinct cell membrane reactivity. Positive GLUT-1 immunostaining was detected in all 16 SCCs and in none of the 8 BCSLs. In the carcinoma cases, the majority of malignant cells exhibited GLUT-1 reactivity; only a minor population of well-differentiated SCC cells displaying keratinization and arranged as squamous pearls did not express GLUT-1. GLUT-1 expression in cell block material can help to distinguish cystic SCCs from BCSLs of the head and neck. In conjunction with clinical and radiological correlation, GLUT-1 immunoreactivity can be an important diagnostic aid when the cytological findings are ambiguous.

Adult↗

Dietary saturated fat reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and membrane composition.

Rats fed a saturated fat diet are protected from experimentally induced alcoholic liver disease, but the molecular mechanisms underlying this phenomenon remain in dispute. We fed male Sprague-Dawley rats intragastrically by total enteral nutrition using diets with or without ethanol. In 1 control and 1 ethanol group, the dietary fat was corn oil at a level of 45% of total energy. In other groups, saturated fat [18:82 ratio of beef tallow:medium-chain triglyceride (MCT) oil] was substituted for corn oil at levels of 10, 20, and 30% of total energy, while keeping the total energy from fat at 45%. After 70 d, liver pathology, serum alanine aminotransferase (ALT), biochemical markers of oxidative stress, liver fatty acid composition, cytochrome P450 2E1 (CYP2E1) expression and activity and cytochrome P450 4A (CYP4A) expression were assessed. In rats fed the corn oil plus ethanol diet, hepatotoxicity was accompanied by oxidative stress. As dietary saturated fat content increased, all measures of hepatic pathology and oxidative stress were progressively reduced, including steatosis (P < 0.05). Thus, saturated fat protected rats from alcoholic liver disease in a dose-responsive fashion. Changes in dietary fat composition did not alter ethanol metabolism or CYP2E1 induction, but hepatic CYP4A levels increased markedly in rats fed the saturated fat diet. Dietary saturated fat also decreased liver triglyceride, PUFA, and total FFA concentrations (P < 0.05). Increases in dietary saturated fat increased liver membrane resistance to oxidative stress. In addition, reduced alcoholic steatosis was associated with reduced fatty acid synthesis in combination with increased CYP4A-catalyzed fatty acid oxidation and effects on lipid export. These findings may be important in the nutritional management and treatment of alcoholic liver disease.

Alanine Transaminase↗

Intraoperative subareolar radioisotope injection for immediate sentinel lymph node biopsy.

OBJECTIVE: To determine the identification of sentinel lymph node biopsy (SLNB) in breast cancer patients after intraoperative injection of unfiltered technetium-99m sulfur colloid (Tc-99) and blue dye. BACKGROUND: SLNB guided by a combination of radioisotope and blue dye injection yields the best identification rates in breast cancer patients. Radioisotope is given preoperatively, without local anesthesia, whereas blue dye is given intraoperatively. We hypothesized that, because of the rapid drainage noted with the subareolar injection technique of radioisotope, intraoperative injection would be feasible and less painful for SLN localization in breast cancer patients. METHODS: Intraoperative injection of Tc-99 and confirmation blue dye was performed using the subareolar technique for SLNB in patients with operable breast cancer. The time lapse between injection and axillary incision, the background count, the preincision and ex vivo counts of the hot nodes, and the axillary bed counts were documented. The identification rate was recorded. RESULTS: Ninety-six SLNB procedures were done in 88 patients with breast cancer employing intraoperative subareolar injection technique for both radioisotope (all 96 procedures) and blue dye (93 procedures) injections. Ninety-three (97%) procedures had successful identification; all SLNs were hot; 91 (of 93 procedures with blue dye) were blue and hot. The mean time from radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with failure of localization had previous excisional biopsies: 1 circumareolar and 2 upper outer quadrant incisions that may have disrupted the lymphatic flow. CONCLUSION: Intraoperative subareolar injection of radioisotope rapidly drains to the SLNs and allows immediate staging of the axilla, avoiding the need to coordinate diagnostic services and a painful preoperative procedure.

Aged↗

Routine syndecan-1 immunohistochemistry aids in the diagnosis of chronic endometritis.

CONTEXT: Chronic endometritis is reportedly observed in 3% to 10% of women undergoing endometrial biopsy for abnormal uterine bleeding. The diagnosis of chronic endometritis rests on the identification of the plasma cells. Their identification may be obscured by a mononuclear cell infiltrate, plasmacytoid stromal cells, abundant stromal mitoses, a pronounced predecidual reaction in late secretory endometrium, menstrual features, or secondary changes due to exogenous progesterone treatment prior to the biopsy. Syndecan-1 is a proteoglycan that is found on the cell surface of plasma cells and keratinocytes. Immunohistochemistry stains for this antibody may facilitate diagnosis of chronic endometritis. OBJECTIVE: To determine whether or not routine syndecan-1 immunohistochemistry will aid in the diagnosis of chronic endometritis. DESIGN: Immunohistochemistry stains for syndecan-1 were performed on 3 levels of 47 endometrial biopsies from patients with abnormal uterine bleeding. None of the patients had endometrial hyperplasia or an underlying malignancy. Clinical correlation and follow-up was attempted in 20 cases that showed evidence of plasma cells by syndecan-1 by immunohistochemistry. RESULTS: Plasma cells were identified in 20 cases, 7 of which were initially diagnosed as chronic endometritis. The remaining 13 positive cases were diagnosed as tubal metaplasia (1), secretory endometrium (4), proliferative endometrium (4), menstrual endometrium (1), endometrial polyp (1), secretory endometrium with endometrial polyp (1), and endometrial polyp with exogenous hormone effect (1) based on the original hematoxylin-eosin section. CONCLUSIONS: Syndecan-1 may be a useful adjunct in the diagnosis of chronic endometritis. Approximately half of the cases of chronic endometritis responded to an antibiotic regime; thus, this diagnosis is important and may potentially obviate the need for surgical intervention.

Adult↗

Subareolar sentinel node biopsy for multiple breast cancers.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is deemed suitable only for unifocal breast cancers since multiple foci of cancers may drain to different nodes. We hypothesized that subareolar injection (SI) could identify the sentinel lymph nodes (SLN) accurately in patients with multiple cancers (MC) in the breast. METHODS: We prospectively employed SI of lymphazurin or technetium sulfur colloid, or both, for the identification of SLN in patients with MC in the breast. All patients underwent axillary dissection to compute the accuracy of SLNB. RESULTS: Forty patients presented with MC in the same breast between January 1996 and July 2002. Fifty-two percent (21 of 40) of patients had involvement of more than 1 quadrant; 18% (7 of 40) had more than 1 histologic type of cancers. SLNs were successfully identified in 100% of patients. Axillary disease was present in 63% (25 of 40) of patients. Sensitivity of SLNB was 100% and false negative rate was 0%. The SLN was the only node involved in 45% (18 of 40) of patients. CONCLUSIONS: SLNB using the SI technique may be an alternative to complete axillary dissection in patients with multiple breast cancers.

Adult↗

Touch preparation of breast core needle specimens is a new method for same-day diagnosis.

BACKGROUND: Touch preparation cytology (TPC) has proven to be a quick and accurate intraoperative diagnostic tool for excisional breast biopsy, margins and sentinel nodes. We hypothesized that TPC of core needle biopsy (CNB) specimens can provide a same-day diagnosis in the outpatient setting. METHODS: Outpatients presenting with breast lesions underwent TPC of biopsy cores performed by biopsy gun or vacuum-assisted CNB. The TPC results were compared with the final diagnosis of CNB specimens. RESULTS: In all, 199 CNB and TP were performed between August 1997 and October 2002. Twenty-nine percent of lesions were malignant. Touch preparation was deferred in 21% of cases. In the remaining 157 evaluable cases, TPC had an accuracy of 89% and a false negative rate of 26%. The sensitivity, specificity, positive predictive value and negative predictive value of TPC were 74%, 97%, 93%, and 86% respectively. CONCLUSIONS: Touch preparation cytology on CNB can be performed simply in the outpatient setting. Collaboration between the surgeon and pathologist allows TP to be an accurate means of same-day pathological determination.

Biopsy, Needle↗

Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury.

BACKGROUND: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. METHODS: Female Sprague Dawley(R) rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. RESULTS: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. CONCLUSIONS: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events.

Aldehydes↗