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ABSTRACT: Inadvertent transplantation of an α-1 antitrypsin-deficient liver into an adult man provided a unique opportunity to follow the natural history of morphological changes in serial liver biopsies. After doing well initially, the patient developed liver function test abnormalities 6 years posttransplant, but biopsies at that time and 2 years later revealed only chronic hepatitis with no specific features. It was only upon repeat biopsy 10 years posttransplant that characteristic cytoplasmic inclusions appeared. Genotypic and phenotypic testing of pretransplant and posttransplant specimens confirmed α-1 antitrypsin deficiency in the transplanted liver. Serologic tests for viral hepatitis and autoimmune disease were negative throughout the pretransplant and posttransplant period. The case suggests that patients with chronic hepatitis of unknown etiology should be tested for the possibility of α-1 antitrypsin deficiency and illustrates the prolonged course that may precede the development of typical cytoplasmic inclusions in the liver.
Human pathology 12/2011; 43(5):753-6. · 3.03 Impact Factor
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ABSTRACT: Macrovesicular steatosis may be used to exclude potential donor livers from use in transplantation. Livers with more than 50% macrovesicular steatosis are believed to be at risk for delayed graft function and primary graft nonfunction. However, the significance of even extensive microsteatosis is uncertain. The hematoxylin and eosin-stained slides of postperfusion donor liver biopsies from 161 transplants were examined. The type of steatosis (macrovesicular, low-grade microvesicular, and high-grade microvesicular ) was determined, and the extent of each type was semiquantitated into 3 groups (none, ≤50%, and >50%). These were analyzed in conjunction with the donor and recipient age and the recipient's sex and MELD score against postoperative outcome parameters, including serial measures of serum lactate, days in the intensive care unit and overall in hospital, and death less than 3 months posttransplant. High-grade microsteatosis usually coexisted with macrosteatosis and infrequently with low-grade microsteatosis. There was no significant association between the extent of either macrosteatosis or low-grade microsteatosis (even when >50%) and any of the outcome parameters. In contrast, the presence of high-grade microsteatosis was significantly associated with delayed hepatic function, but not with the other outcome parameters. Donor age greater than 60 years was associated with late postoperative rise in serum lactate, and higher recipient MELD score was associated with extended stay in the intensive care unit and in the hospital. In this patient population, the association of steatosis with adverse outcomes was largely restricted to delay in postoperative hepatic function, and was due to the subgroup that displayed high-grade microsteatosis.
Human pathology 03/2011; 42(9):1337-42. · 3.03 Impact Factor
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ABSTRACT: Pathology training programs typically retain teaching files of classic and unusual diagnostic cases. Since diagnostic criteria and terminology are mutable, we reviewed a surgical pathology teaching archive to determine if the materials continued to be acceptable for educational purposes. Each case (from 2001-2003) consisted of 1 to 3 slides and a 3 x 5 card with clinical information and the diagnosis. Cases were reviewed at a daily faculty consensus conference and categorized as follows: no diagnostic change; diagnosis added; or changed diagnosis. Slides were entirely missing from 79 (35.0%) of the 226 cases reviewed. Of the remaining 147 cases, 28 (19.0%) required additional clinical information and/or slides. The final disposition of the 147 cases was as follows: diagnosis unchanged, 126 (85.7%); diagnosis added, 15 (10.2%); and diagnosis changed, 6 (4.1%). Teaching files should be subject to prospective and retrospective controls to preserve the quality of the educational experience.
American Journal of Clinical Pathology 08/2010; 134(2):332-4. · 2.60 Impact Factor
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Histopathology 10/2009; 55(4):487-8. · 3.08 Impact Factor
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ABSTRACT: Morphologic differentiation of recurrent Hepatitis C from transplant rejection is a major problem in posttransplant liver biopsies. Although biopsies of the native livers from patients with Hepatitis C are known to display bile duct damage, other morphologic features similar to those seen in rejection, such as endotheliitis, portal eosinophils, and pericentral fibrosis, are not generally acknowledged. To determine the frequency with which features morphologically similar to rejection might be present, we examined 50 cases of core-needle biopsy from the native livers of patients with Hepatitis C for the presence of the following: bile duct damage, portal eosinophils, portal or central vein endotheliitis, ductopenia, vascular obliteration, pericentral fibrosis, and pericentral mononuclear cell infiltrate. Biopsy specimens with other concurrent disease processes were excluded. The frequency of each morphologic feature was as follows: bile duct damage (30%), portal eosinophils (42%), portal endotheliitis (20%), central vein endotheliitis (0%), pericentral mononuclear cell infiltrate (14%), ductopenia (2%), atrophic-looking bile ducts (2%), vascular obliteration (0%), and pericentral fibrosis (10%). Bile duct damage and portal endotheliitis were both more common with higher grade hepatitis (Fisher exact test, P = .001). None of the morphologic parameters correlated with biopsy stage, viral genotype, or liver function tests. We conclude that features similar to those found in acute rejection are common in Hepatitis C, whereas features resembling chronic rejection are less frequent. This study provides quantitative data that supports the need to interpret these features with great caution in posttransplant liver biopsies from patients with recurrent Hepatitis C who are suspected of rejection.
Human pathology 10/2008; 40(1):92-7. · 3.03 Impact Factor
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ABSTRACT: Multiple "step-sections" are prepared for many diagnostic biopsies, but tissue is usually left in the block for possible additional studies. We sought to determine the frequency with which sampling the remaining tissue with additional step-sections would reveal pathologic abnormality in a series of colorectal biopsies originally diagnosed as normal. Slides of 232 cases were reviewed and classified into 7 standard diagnostic categories. Review of the original 3 slides showed pathologic abnormality to actually be present in 9 cases (3.9%). The additional step-sections revealed pathologic abnormality in 4 (1.7%) other cases, as follows: tubular adenoma, 3 cases; lymphocytic colitis, 1 case. Neither previous nor concurrent clinical or pathological information related to colorectal disease identified the cases that were more likely to yield diagnostic abnormality in the additional step-sections. However, there was a statistically nonsignificant trend for specimens with a clinical diagnosis of "polyp" to display tubular adenoma in the deeper sections. Because examination of remaining tissue yielded new diagnostic information less frequently than the observed rate of diagnostic error, reduction in interobserver error may be a more fruitful strategy for obtaining a correct diagnosis than would complete histologic sampling.
Human Pathlogy 05/2008; 39(4):579-83. · 2.88 Impact Factor
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George J Netto,
David L Watkins,
James W Williams,
Thomas V Colby,
Giovanni dePetris, Francis E Sharkey,
Christopher L Corless,
David Lewin,
Lydia Petrovic,
Shobha Sharma,
Gary Kanel,
Neil Theise,
A Brian West,
Alison Koehler,
Nirag C Jhala,
Jay Lefkowitch,
Julia Lezzoni,
Linda W Jennings,
G Weldon Tillery,
Goran B Klintmalm
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ABSTRACT: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials.
To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the "Hepatitis C 3" trial.
The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin-stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs.
Statistically significant agreement was found among all participating pathologists (P < .001). On kappa analysis, the degree of agreement was rated "moderate" for HCV grade and stage and ACR global grading (kappa = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (kappa = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (kappa = 0.76 "almost perfect" for HCV and 0.62 "substantial" for ACR).
An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.
Archives of pathology & laboratory medicine 08/2006; 130(8):1157-62. · 2.58 Impact Factor
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ABSTRACT: While colorectal cancer (CRC) incidence and mortality rates have declined slightly over the past decade, there remain marked differences by ethnicity. Our aim was to investigate ethnic differences in occurrence, clinical presentation and outcome of CRC at a tertiary university center that serves a predominantly Hispanic population.
Prospectively collected data from the tumor registry on patients diagnosed with colorectal cancer from 1985 through 2001 was examined. Age at diagnosis, mode of presentation, sex, tumor location, ethnicity, TNM stage, and survivals were assessed and ethnic differences were sought.
Records from 453 patients with CRC were reviewed. There were 296 (65%) patients that were Hispanics, 112 (25%) non-Hispanic Whites, 37 (8%) African Americans, and 8 (2%) of other or unknown ethnicity. Compared with non-Hispanic Whites, Hispanics presented at a younger age (58.5 +/- 14 versus 53.6 +/- 12.73, respectively; P < 0.01), with a significantly greater incidence of stage IV disease (19% versus 32%, respectively; P = 0.02). They had significantly poorer age-adjusted survival (median survival of 92 months for <55 years and 77 months for >55 years versus 48 months for <55 years and 48 months for >55 years, respectively; adjusted log rank P = 0.045). There were no differences in tumor location, mode of presentation or adjuvant treatment received.
Hispanic patients with CRC in our catchment area present at a younger age with more metastatic disease and have a poorer survival than non-Hispanic Whites. Modification of screening criteria and treatment paradigms may be required for Hispanics.
American journal of clinical oncology 05/2006; 29(2):123-6. · 2.21 Impact Factor
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ABSTRACT: The anatomic definitions for anal cancer (canal versus margin) are made based on the relationship of the tumor to the anal verge. This method had led to confusion for some providers. A modification in the terminology is proposed that includes intra-anal, perianal, and skin as categories. The cause of anal carcinoma remains to be fully elucidated, and HPV seems to play a central role in this process. The incidence of anal cancers has increased, which is related to the evolution of HIV and AIDS, and their treatment. The accurate pathologic analysis of anal tumors is complex and is significantly aided by close communication between clinician and pathologist.
Surgical Oncology Clinics of North America 05/2004; 13(2):263-75. · 1.12 Impact Factor
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ABSTRACT: The histologic diagnosis of acute hepatic allograft rejection is usually based upon the identification of characteristic portal tract features. In addition to these, centrilobular alterations such as central vein endothelialitis, zone 3 inflammation, and hepatocyte necrosis may also be seen during episodes of acute rejection. The purpose of this study was to identify any differences in the subsequent clinical course of patients with and without centrilobular alterations during their first biopsy-proven episode of acute rejection. Acute rejection was diagnosed at least once in 35 liver recipients who had undergone allograft biopsy. Of these, 15 (43%) had centrilobular alterations in their first posttransplant biopsy. These 15 patients developed ductopenia (60% vs. 30%) and subsequent episodes of acute rejection (53% vs. 25%) more often than did the 20 patients who lacked centrilobular alterations in their first posttransplant biopsy. Time to first episode of acute rejection and rates of subsequent recurrent hepatitis and death were similar between the 2 groups. Patients with centrilobular alterations during a first episode of acute rejection are more likely to have subsequent episodes of acute rejection and to develop features of chronic rejection than are patients without these changes. These patients may benefit from more vigilant clinical follow-up and/or higher levels of immunosuppression.
Liver Transplantation 04/2004; 10(3):369-73. · 3.39 Impact Factor
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ABSTRACT: Radiofrequency thermal ablation has been used as a treatment for several types of hepatic malignancies. Many of these lesions exist in the presence of cirrhosis. Limitations exist to the size of the ablations and, subsequently, the efficacy of treatment. Hepatic vascular inflow occlusion has been advocated as an adjunctive measure to increase the efficacy of the ablation. We present a model in the human cirrhotic liver that demonstrates the advantage of blood flow occlusion during radiofrequency ablation.
Five patients with advanced endstage liver disease scheduled to have orthotopic liver transplantation were enrolled in this study. After laparotomy and before hepatectomy, radiofrequency ablation was performed without and with hepatic blood flow occlusion. After hepatectomy, the liver was sectioned, the area of ablation was measured in three dimensions, and the volume of ablation calculated.
Three of the patients had had previously placed transjugular intrahepatic portosystemic shunt. The mean volume of the ablation without blood flow occlusion was 22.5 +/- 7.4 cm(3) and that with blood flow occlusion was 48.4 +/- 24.0 cm(3) (P =.05).
Ablation area is increased significantly with hepatic blood flow occlusion in the human cirrhotic liver. This result may have application in the treatment of larger (>3 cm) hepatic malignancies.
Annals of Surgical Oncology 09/2003; 10(7):773-7. · 4.17 Impact Factor
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ABSTRACT: Although atrial myxoma is the most common primary tumor of the heart, the synchronous occurrence of myxomas of the intestine and the heart has not been reported in the English literature. We report a case of a 47-year-old woman who presented with small bowel obstruction by a pedunculated mass that was found to be a myxoma after resection. A left atrial mass was found incidentally by a computed tomographic scan, and a diagnosis of atrial myxoma was confirmed after a second surgery. The cardiac myxoma showed classic histologic features, with tumor cells layered around vascular channels in an abundant myxoid matrix, while the small bowel lesion was less cellular. Immunohistochemical stains yielded identical results in both. No vascular involvement was noted at either site. This case supports the recommendation that a search for a cardiac lesion should be performed when a myxoma is identified at an unusual location.
Archives of pathology & laboratory medicine 05/2003; 127(4):481-4. · 2.58 Impact Factor
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Archives of pathology & laboratory medicine 04/2003; 127(3):e175-6. · 2.58 Impact Factor
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ABSTRACT: We present a case of histologic changes resembling acute cellular rejection in a liver transplant patient treated with terbinafine. Approximately 5 years after orthotopic liver transplantation, a 51-year-old Hispanic man developed elevated liver enzyme levels. A biopsy sample was interpreted as acute cellular rejection, and the patient was treated with increased immunosuppression. Review of medications showed that the patient had been started on terbinafine approximately 4 weeks earlier for onychomycosis, and it was discontinued. A follow-up visit 2 weeks later revealed progressive jaundice, malaise, and nausea, and evaluation of a second liver biopsy sample revealed marked centrilobular cholestasis and severe bile duct damage, consistent with terbinafine hepatotoxicity. Although these histologic changes have been described in treated patients with both normal and abnormal livers, the potential for confusion with acute rejection in patients with hepatic transplantation has not previously been reported.
Human Pathlogy 03/2003; 34(2):187-9. · 2.88 Impact Factor
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ABSTRACT: Three levels of histologic sections are routinely prepared for small biopsies in many surgical pathology laboratories. The first level is superficial and may not be representative of the entire biopsy, and may therefore represent wasted resources and time for technologists and pathologists alike.
To determine if disposing of the first of 3 standard levels materially affects the diagnosis of cervical biopsies.
We retrospectively reviewed levels 2 and 3 of 241 cervical biopsies and compared the review diagnosis with the original diagnosis, using 6 diagnostic categories: I, benign lesions; II, human papillomavirus-associated changes or low-grade dysplasia; III, high-grade dysplasia/carcinoma in situ; IV, invasive carcinoma; V, insufficient tissue for diagnosis; and VI, further workup needed. If there was a discrepancy between the original and review diagnostic categories, then we examined level 1 to determine if this would resolve the disagreement.
The surgical pathology laboratory.
Women undergoing cervical biopsy.
None.
The frequency with which level 1 information changed the diagnostic category determined with levels 2 and 3 only.
After review of levels 2 and 3, the diagnosis in 42 (17%) of 241 cases was in disagreement with the original diagnosis. Upon review of level 1, the review category was changed to that of the original diagnosis in only one case.
The first of 3 levels contributed little to reaching a diagnosis in these cervical biopsies. Control of interobserver variation would seem to be superior to preparation of additional levels as a strategy for reducing diagnostic error.
Archives of pathology & laboratory medicine 11/2002; 126(10):1205-8. · 2.58 Impact Factor
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John R Leyendecker,
Gerald D Dodd,
Glenn A Halff,
Victor A McCoy,
Dacia H Napier,
Linda G Hubbard,
Kedar N Chintapalli,
Shailendra Chopra,
W Kenneth Washburn,
Robert M Esterl,
Francisco G Cigarroa,
Ruth E Kohlmeier, Francis E Sharkey
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ABSTRACT: We performed a study to determine the correlation between the diameter of the echogenic response observed with intraoperative sonography during radiofrequency ablation of the cirrhotic liver and the mean diameter of tissue necrosis.
A total of 22 intraoperative radiofrequency ablations were created in 11 cirrhotic livers. The largest diameter of the sonographically observed echogenic response surrounding and perpendicular to the radiofrequency probe was measured. The subsequent zone of necrosis observed at pathology in the hepatectomy specimens after liver transplantation was measured in three planes and compared with the measured diameter of the echogenic response.
During all except three ablations, a hyperechoic region was visualized surrounding the radiofrequency probe. The diameter of the echogenic response correlated significantly with the mean diameter of necrosis (correlation coefficient, 0.84). However, the echogenic response overestimated the minimal diameter of necrosis (mean difference, 0.8 +/- 0.4 cm) in 18 of 22 ablations and underestimated the maximum diameter of necrosis (mean difference, 0.9 +/- 0.8 cm) in 16 of 22 ablations.
The diameter of the echogenic response observed with intraoperative sonography during radiofrequency ablation of the cirrhotic liver correlates closely with the mean diameter of the subsequent area of tissue necrosis. However, the solitary diameter of the echogenic response as measured in our study was often greater than the smallest diameter and less than the largest diameter of the area of tissue necrosis. Therefore, the echogenic response associated with radiofrequency ablation of the cirrhotic liver should be viewed only as a rough approximation of the area of induced tissue necrosis; the final assessment of the adequacy of ablation should be deferred to an alternative imaging technique.
American Journal of Roentgenology 06/2002; 178(5):1147-51. · 2.78 Impact Factor
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Alexander R Miller,
Virginia E Thomason,
I-Tien Yeh,
Amin Alrahwan, Francis E Sharkey,
Jay Stauffer,
Pamela M Otto,
Claire McKay,
Morton S Kahlenberg,
William T Phillips,
Anatolio B Cruz
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ABSTRACT: Sentinel lymph node mapping (SLNM) and neoadjuvant chemotherapy are becoming established components of therapy for selected patients with breast carcinoma. However, neoadjuvant therapy has been considered a relative contraindication to SLNM. In an effort to learn whether patients who have received preoperative chemotherapy can undergo accurate SLNM, we evaluated our experience with this technique.
From January 1997 to June 2000, SLNM and axillary lymph node dissection were concurrently performed in 35 patients who received preoperative chemotherapy. Mapping was performed with (99m)Tc sulfur colloid only in one patient and Lymphazurin dye only in 15 patients, and the two methods were combined in the remainder.
SLNM successfully identified a sentinel lymph node in 30 (86%) patients. Metastatic disease was identified in the sentinel lymph nodes of four patients during surgery. The intraoperative pathologic diagnosis proved to be correct in 19 (79%) of 24 patients. The final pathologic diagnosis of the sentinel lymph node reflected the status of the axillary contents in all patients in whom it was identified.
These results demonstrate that SLNM can be consistently performed in patients receiving preoperative chemotherapy for breast cancer, suggesting the utility of this technique in this patient population.
Annals of Surgical Oncology 05/2002; 9(3):243-7. · 4.17 Impact Factor