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Biomedical subjects

Nirag C Jhala

Publications and source records attributed to Nirag C Jhala.

At least 19 recordsLinked to original sources

Fine-needle aspiration biopsy of hepatic lesions: computerized tomographic-guided versus endoscopic ultrasound-guided FNA.

BACKGROUND: Computerized tomographic (CT)-guided fine-needle aspiration (FNA) cytology is a well-established tool in the diagnosis of hepatic lesions. Endoscopic ultrasound-guided FNA (EUS-FNA), developed recently and used predominantly in evaluating mediastinal and pancreatic lesions, provides access to a significant portion of the liver and to perihepatic structures not readily accessible by a percutaneous approach. METHODS: A recent experience (1997-2002) with CT-guided FNA of liver lesions at the University of Alabama Birmingham (UAB) was compared with the first 2.5 years of EUS-FNA experience (2000-2002). Cases were identified using a SNOMED search and all reports and cytologic slides were retrieved for review. RESULTS: In 6 years, 34 percutaneous CT-FNA liver biopsies were performed at UAB; in approximately 2.5 years, 16 EUS-FNA liver biopsies were done. In both groups the primary clinical indication was suspected metastatic carcinoma (CT, 41% of cases vs. EUS, 56%). The 2 techniques yielded a similar range of benign, atypical, and malignant diagnoses (CT: 26%, 18%, and 56% vs. EUS: 19%, 25%, and 56%). Because of the clinical setting in which EUS-FNA is usually performed, a much narrower range of neoplasms was sampled by EUS-FNA. Benign gastrointestinal epithelial cells were identified in 60% of the EUS-FNA specimens. CONCLUSIONS: Early experience suggests EUS-FNA is comparable to CT-FNA in terms of diagnostic utility for hepatic lesions. Anatomy limits EUS-FNA to only a fraction of the hepatic parenchyma, but that fraction includes the hilum and left lobe of the liver and the proximal biliary tract. The gallbladder, extrahepatic biliary system, and perihilar lymph nodes are readily accessible. Proximate high-resolution ultrasound imaging and cytopathologist involvement in the EUS-FNA process are further advantages. Awareness of artifacts inherent in EUS-FNA sampling (i.e., gut epithelial cells) can minimize a potential diagnostic pitfall.

Adenocarcinoma↗

Probabilistic reporting of EUS-FNA cytology: Toward improved communication and better clinical decisions.

BACKGROUND: The objectives of this study were to determine threshold probabilities needed to perform endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and those needed to treat patients suspected of having malignancy and then to compare these thresholds to the pre- and posttest probabilities of malignancy associated with benign, atypical, suspicious, and malignant diagnoses. The goal was to aid endoscopists in making appropriate clinical decisions based on both quantitative and qualitative approaches. METHODS: The study included 633 consecutive patients. A decision tree was constructed to estimate the "treatment" threshold. Using treatment threshold and likelihood ratios, the authors determined the "no-test-test" and "test-treatment" thresholds. Pretest probability was compared with no-test-test and test-treatment thresholds, and the post-EUS-FNA probability of malignancy for each diagnostic category with the treatment threshold. Results were stratified by lesion site, lesion size, and cytopathologist. RESULTS: EUS-FNA has a wide range of pretest probabilities within which it could be performed (0.06-0.98). The posttest probabilities for malignancy, 0.99 (95% confidence interval [CI], 0.967-0.996) and 0.09 (95% CI, 0.057-0.126), after a positive or a negative result, respectively, were significantly different from the treatment threshold but not those of suspicious, 0.92 (95% CI, 0.767-0.994) diagnosis. The posttest probability of atypical diagnosis, 0.60 (95% CI, 0.407-0.772), was not significantly different from that of pretest probability. Results did not vary by lesion size, organ site, or cytopathologist. CONCLUSION: The authors demonstrated the uncertainty associated with EUS-FNA diagnostic categories and used the threshold approach to qualify quantitatively the decision to perform EUS-FNA and the decision to treat patients suspected of having malignancy.

Antineoplastic Protocols↗

Non-Hodgkin's lymphoma of the breast: a review of 18 primary and secondary cases.

We evaluated the clinical features, morphology, and incidence of 18 cases of breast lymphoma over 10 years at the University of Alabama at Birmingham. Fine needle aspiration was performed in 7 of 18 patients, and tissue biopsy/resection was available for all 18 cases. Patients were 33 to 91 years old (median, 61); 17 were women and 1 was a man. Fine needle aspiration was consistent with the tissue diagnosis in 6 of the 7 cases (86%). One case was diagnosed by fine needle aspiration as atypical cells, favor benign; the biopsy revealed diffuse large B-cell lymphoma. Tissue diagnoses revealed that 11 cases (61%) represented diffuse large B-cell lymphoma and 3 (17%) were follicular lymphomas. The remaining 4 cases (22%) were plasma cell neoplasm, T-cell neoplasm, Burkitt's lymphoma, and precursor B-cell lymphoblastic lymphoma. Flow cytometry and/or gene rearrangement supported the diagnosis of lymphoma in 8 cases. Although rare, lymphoma should be considered in the differential diagnosis of a breast mass. Fine needle aspiration can facilitate appropriate triage of patients for further management.

Adult↗

Diagnosis of deep-seated lymphoma and leukemia by endoscopic ultrasound-guided fine-needle aspiration biopsy.

We retrospectively studied the use of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) as a tool for the diagnosis of deep-seated lymphoma. An on-site assessment at the time of EUS-FNAB was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou stains were performed on EUS-FNAB smears, immunohistochemical stains were performed on cell blocks, and additional samples were sent for flow cytometric analysis. Final cytologic diagnosis was correlated with surgical pathology and/or clinical follow-up. We evaluated EUS-FNAB specimens of deep-seated lymph nodes, spleen, stomach, and pancreas, and 1 EUS-guided needle core biopsy specimen of a lymph node. Thirteen cases of deep-seated lymphoma were diagnosed, including non-Hodgkin lymphomas and Hodgkin lymphoma. One case of hairy cell leukemia was diagnosed. EUS-FNAB is a minimally invasive, cost-effective, and useful tool for the primary diagnosis or staging of deep-seated lymphomas.

Adolescent↗

Interobserver agreement in hepatitis C grading and staging and in the Banff grading schema for acute cellular rejection: the "hepatitis C 3" multi-institutional trial experience.

CONTEXT: Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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). CONCLUSIONS: An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.

Acute Disease↗

SCF(beta-TrCP1) controls Smad4 protein stability in pancreatic cancer cells.

Smad4, also known as deleted in pancreatic carcinoma locus 4 (DPC4), is a critical co-factor in signal transduction pathways activated by transforming growth factor (TGF)-beta-related ligands that regulate cell growth and differentiation. Mutations in Smad4/DPC4 have been identified in approximately 50% of pancreatic adenocarcinomas. Here we report that SCF(beta-TrCP1), a ubiquitin (E3) ligase, is a critical determinant for Smad4 protein degradation in pancreatic cancer cells. We found that F-box protein beta-TrCP1 in this E3 ligase interacted with Smad4 and that SCF(beta-TrCP1) inhibited TGF-beta biological activity in pancreatic cancer cells by decreasing Smad4 stability. Very low Smad4 protein levels in human pancreatic ductal adenocarcinoma cells were observed by immunohistochemistry. By analyzing pancreatic tumor-derived Smad4 mutants, we found that most point-mutated Smad4 proteins, except those within or very close to a mutation cluster region, exhibited higher interaction affinity with beta-TrCP1 and significantly elevated protein ubiquitination by SCF(beta-TrCP1). Furthermore, AsPC-1 and Caco-2, two cancer cell lines harboring Smad4 point mutations, exhibited rapid Smad4 protein degradation due to the effect of SCF(beta-TrCP1). Both Smad4 levels and TGF-beta signaling were elevated by retrovirus-delivered beta-TrCP1 siRNA in pancreatic cancer cells. Therefore, inhibition of Smad4-specific E3 ligase might be a target for therapeutic intervention in pancreatic cancer.

Adenocarcinoma↗

Cytologic grade independently predicts survival of patients with pancreatic adenocarcinoma.

Our objectives were to devise a cytologic grading system and determine whether it would predict survival of patients with solid-type pancreatic adenocarcinoma. We evaluated 116 consecutive patients from July 2000 to November 2002; they were followed up until September 2003. We scored the following features on rapid Romanowsky-stained endoscopic ultrasound-guided fine-needle aspiration smears: cell group architecture, single cells, nuclear grade, mucus, bizarre cells, and necrosis. A cytologic grade (low vs high) was assigned. The Kaplan-Meier estimate of 6-month survival was 76% (SE, 7%) for patients with low-grade tumors vs 50% (SE, 6%) for patients with high-grade carcinoma. The median survival for patients with low-grade vs high-grade tumors was 1 year vs 6 months, respectively (chi2 = 4.45; P = .035). Cox proportional hazards regression showed tumor stage, cancer-specific treatment, and cytologic grade to be independent predictors of survival (P = .001). No other factors (age, mass location, placement of stent, presence of concomitant chronic pancreatitis, race, sex) predicted survival. We devised a grading system that independently predicted survival in patients with pancreatic adenocarcinoma.

Adenocarcinoma↗

Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma.

Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55-9.77) but not with Stage III CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47-2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens.

Adenocarcinoma↗

Regulators of apoptosis in cholangiocarcinoma.

CONTEXT: Dysregulation of mediators of apoptosis is associated with carcinogenesis. For biliary duct cancers, p53 gene mutation is an important contributor to carcinogenesis. Mutations in the p53 gene affect transcription of the Fas gene, resulting in lack of Fas expression on cell membrane. It has been previously shown that cloned Fas-negative but not Fas-positive human cholangiocarcinoma cells are resistant to anti-Fas-mediated apoptosis and develop tumors in nude mice. In addition, interferon gamma induces Fas expression in Fas-negative cholangiocarcinoma cells and makes them susceptible to apoptosis. Therefore, it becomes important to characterize immunophenotypic expression of p53 and Fas in normal and neoplastic human tissues of the biliary tract to further understand the pathogenesis of the disease. To date, human studies to characterize differences in immunophenotypic expression of the Fas protein between intrahepatic and extrahepatic biliary duct cancers and in their precursor lesions have not been performed. OBJECTIVE: To report the immunophenotypic expression of p53 and Fas expression in various stages in the development of bile duct cancers (intrahepatic and extrahepatic tumor location) and their association with tumor differentiation. DESIGN: Thirty bile duct cancer samples (13 intrahepatic and 17 extrahepatic) from 18 men and 12 women who ranged in age from 44 to 77 years (mean age, 65.6 years) were retrieved from the surgical pathology files. Hematoxylin-eosin-stained slides were evaluated for the type and grade of tumor and dysplastic changes in the biliary tract epithelium. Additional slides were immunohistochemically stained with p53 and anti-Fas mouse monoclonal antibody. The pattern of Fas distribution and percentage of cells positive for p53 and Fas expression were determined. RESULTS: The percentage of Fas-expressing cells is significantly (P = .01) more frequently noted in extrahepatic tumors compared with intrahepatic tumors. Furthermore, Fas expression decreased from dysplastic epithelium to cholangiocarcinoma (P = .01), and this decreasing trend continued from well to poorly differentiated tumors. Nuclear p53 expression was not identified in normal and dysplastic epithelium but was noted in 30% of carcinomas (P = .02). CONCLUSION: Fas expression is an early event in pathogenesis of bile duct cancers. Immunophenotypic expression of Fas is associated with well to moderately differentiated tumors but not with poor tumor differentiation.

Adult↗

Endoscopic ultrasound-guided fine-needle aspiration biopsy of the adrenal glands: analysis of 24 patients.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy allows the detailed imaging and FNA not only of both intramural and extramural structures and lesions of the gastrointestinal (GI) tract but also of various intraabdominal organs. Thus, EUS-FNA biopsy offers a novel opportunity to evaluate and obtain cytology samples from adrenal gland lesions. The objective of the current study was to determine the utility of EUS-FNA in the diagnosis of adrenal lesions. METHODS: The authors conducted a prospective evaluation of 24 consecutive EUS-FNA biopsy specimens obtained from patients with adrenal lesions. An attending cytopathologist was present on site to assess specimen adequacy and to provide rapid interpretation of air-dried material that had been stained with Diff-Quik (Baxter Scientific Products, McGraw Park, IL). Additional samples were obtained for ThinPrep (Cytyc Corporation, Boxborough, MA) preparation, and cell blocks subsequently were prepared. Appropriate immunohistochemical staining was performed as indicated. The cytologic diagnosis was then analyzed for correlations with the final diagnosis, which was based on relevant correlative cytologic or histologic examination of biopsied/resected pathology materials and/or final clinical follow-up. RESULTS: In total, 24 EUS-FNA biopsy specimens (from 18 males and 6 females) were obtained from adrenal glands. The mean patient age was 62.2 years (range, 48-81 years). Adequate cellularity was noted in all 24 samples. Seven of 24 samples (29%) were reported to be positive for carcinoma. All samples that were diagnosed as metastatic carcinoma were confirmed on subsequent follow-up. EUS-FNA performed simultaneously with adrenal gland aspiration either from the primary site (n = 1) or from metastases to lymph nodes (n = 3) supported diagnoses of metastatic carcinoma. Six of seven samples were metastatic from the lung, and one specimen was a direct extension of a transitional renal cell carcinoma. EUS-FNA biopsy of the right adrenal gland in one patient revealed myelolipoma. In 16 patients, benign adrenal gland cells were noted on EUS-FNA biopsy specimens from enlarged adrenal glands. In 5 samples (31%), signs of adenoma were evident. Morphology alone could not distinguish between adrenal adenoma and adrenal hyperplasia. No significant complications were reported after EUS-FNA biopsy of adrenal glands. CONCLUSIONS: EUS-FNA biopsy is a highly specific and safe technique for confirming the diagnosis of carcinoma metastatic to the adrenal glands. Along with cytologic evaluation, EUS imaging is needed to support the diagnosis of adrenal adenoma.

Adenoma↗

Endoscopic ultrasound-guided fine-needle aspiration biopsy: a powerful tool to obtain samples from small lesions.

BACKGROUND: Endoscopic ultrasound (EUS) is a powerful imaging modality to identify and determine the extent of a lesion. In addition, EUS is superior to a computed tomography scan in detecting lesions < 3 cm. The objective of the current study was to determine whether small lesions (< or = 25 mm) affected the specimen adequacy and the diagnostic accuracy for lesions aspirated under EUS guidance. METHODS: In the current study, 209 consecutive EUS-guided fine-needle aspiration biopsy (EUS-FNAB) samples < or = 25 mm (100 samples) or > 25 mm (109 samples) as determined by EUS were obtained from 151 patients with a mean age of 62 years (range, 39-94 years). A cytopathologist present in the endoscopy suite determined specimen adequacy. Yield of adequate samples for diagnosis, number of passes, and operating characteristics of EUS-FNAB for small (< or = 25 mm) and large lesions (>25 mm) were compared. RESULTS: The overall yield of obtaining adequate samples for diagnosis was 96% (201 of 209). There was no difference noted with regard to the yield of obtaining samples (96% vs. 96%) from small or large lesions. A mean of 2.5 passes (range, 1-9 passes) was needed to obtain adequate samples from lesions < or = 25 mm, whereas a mean of 4.5 passes (range, 1-11 passes) was needed to obtain adequate samples from lesions > 25 mm. The sensitivity (96% vs. 96%), specificity (100% vs. 100%), and diagnostic accuracy (98% vs. 97%) for EUS-FNAB were comparable whether the lesion was < or = 25 mm or > 25 mm. CONCLUSIONS: EUS-FNAB was a highly effective technique to obtain samples from small (< or = 25 mm) and large (> 25 mm) lesions without affecting the sensitivity, specificity, or diagnostic accuracy.

Adult↗

Prognostic significance of p27(kip-1) expression in colorectal adenocarcinomas is associated with tumor stage.

PURPOSE: Although the decreased expression of p27(kip-1), a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27(kip-1) expression varies with the tumor site, tumor stage and patient ethnicity. EXPERIMENTAL DESIGN: We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27(kip-1), and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods. RESULTS: Although, similar proportion of CRCs with decreased p27(kip-1) expression was observed in all stages (range, 26-36%), the decreased p27(kip-1) expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27(kip-1) was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs. CONCLUSIONS: No prognostic significance was found for p27(kip-1) expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27(kip-1) is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.

Adenocarcinoma↗

Endoscopic ultrasound-guided fine needle aspiration biopsy of suspected cholangiocarcinoma.

BACKGROUND AND AIMS: Despite advances in endoscopic techniques for sampling bile duct strictures, the diagnosis of cholangiocarcinoma remains a challenge. The purpose of this study was to evaluate the yield of EUS-FNA and its impact on patient management for patients with suspected cholangiocarcinoma. METHODS: All patients undergoing EUS for the evaluation of suspected malignant biliary strictures were prospectively evaluated over a 23-month period. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Reference standard for final diagnosis included surgery, death from disease, and clinical and/or imaging follow-up. RESULTS: Twenty-eight patients (mean age 67 years [SD +/- 11], 72% male) were evaluated. Most patients (91%) presented with obstructive jaundice, and all except 1 had nondiagnostic sampling of the biliary lesions either at ERCP (88%), percutaneous transhepatic cholangiogram (n = 2), and/or computed tomography-guided biopsy (n = 1). Sixty-seven percent (14/21) had no definitive mass seen on prior abdominal imaging studies. The mean tumor size by EUS was 19 mm x 16 mm with a median number of passes to diagnosis of 3 (range 1-7). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86%, 100%, 100%, 57%, and 88%, respectively. EUS-FNA had a positive impact on patient management in 84% of patients: preventing surgery for tissue diagnosis in patients with inoperable disease (n = 10), facilitating surgery in patients with unidentifiable cancer by other modalities (n = 8), and avoiding surgery in benign disease (n = 4). CONCLUSIONS: Given the apparent accuracy and safety of EUS with FNA for imaging bile duct mass lesions and for obtaining a tissue diagnosis in patients with suspected cholangiocarcinoma, this technology may represent a new approach to diagnosis especially when other methods fail. The ability to obtain a definite diagnosis has a significant impact on patient management.

Adult↗

Endoscopic ultrasound-guided fine-needle aspiration. A cytopathologist's perspective.

Endoscopic ultrasound (EUS) is used to detect and delineate the extent of lesions in the gastrointestinal tract, periluminal lymph nodes, pancreas and hepatobiliary tree, left kidney, spleen, and adrenal glands. EUS-guided fine-needle aspiration (FNA) has added a new dimension to the capabilities of EUS because it permits characterization of the lesion, thereby enabling triage of patients for more efficient and effective management. This review focuses on the advantages and limitations of EUS-FNA, including a discussion of potential pitfalls in the diagnosis of commonly aspirated deep-seated lesions, such as those of the pancreas and lymph nodes. It also addresses the practical considerations associated with establishing an effective service and the importance of an integrated approach in which the cytopathologist undertakes a key role, interacting extensively with the endoscopist and the patient management team. EUS-FNA is a sensitive modality that enables specific and accurate diagnosis of deep-seated lesions. Samples can be obtained effectively from small lesions (< 25 mm), irrespective of the organ site. On-site assessment permits a highly accurate preliminary diagnosis of malignancy for samples obtained by EUS-FNA and provides an opportunity to increase the diagnostic yield of samples.

Biopsy, Needle↗

Infiltration of Helicobacter pylori in the gastric mucosa.

It is our hypothesis that if Helicobacter pylori could be demonstrated conclusively to have transgressed the mucosal surface into the lamina propria, this would help explain how H pylori recruits inflammatory cells. We report our immunohistochemical and electron microscopic findings that demonstrate that H pylori can be detected in the lamina propria of the stomach, offering evidence of its invasive potential. We stained 67 endoscopic gastric biopsy specimens with Warthin-Starry silver and immunoperoxidase stains for H pylori. In addition, transmission electron microscopy was performed on 1 case. The presence of surface H pylori was associated significantly with active (P < .0001) and chronic (P < .0001) inflammation. H pylori could not be identified in the lamina propria using the Warthin-Starry silver stain alone. Immunoreactivity for H pylori in the lamina propria was detected in 20 (30%) of 67 gastric biopsy specimens. Transmission electron microscopy confirmed the immunohistochemical findings. H pylori can infiltrate the lamina propria of the gastric mucosa, thereby proving morphologic evidence of its invasive capability.

Acute Disease↗

Pancreatic acinar cell metaplasia in autoimmune gastritis.

OBJECTIVE: To determine the frequency and significance of pancreatic acinar cells in the gastric oxyntic mucosa. DESIGN: One hundred gastric oxyntic mucosal biopsy specimens from patients with chronic active gastritis (n = 30), multifocal atrophic gastritis (n = 15), autoimmune gastritis (n = 18), and normal gastric oxyntic mucosa (n = 37) were evaluated for the presence of pancreatic acinar cells. Formalin-fixed, paraffin-embedded tissues were stained with hematoxylin-eosin, and those positive for pancreatic acinar cells were immunostained with antibodies against trypsin and pancreatic amylase. RESULTS: Eleven (11%) of 100 oxyntic mucosal tissue samples contained pancreatic acinar cells. These samples came from 9 of the 18 (50%) specimens of autoimmune gastritis, 1 of the 15 (6.6%) specimens of multifocal atrophic gastritis, and 1 of the 37 (2.7%) specimens of normal oxyntic mucosa. None of the samples with chronic active gastritis contained pancreatic acinar cells. CONCLUSIONS: Pancreatic acinar cells were found in the oxyntic mucosa of patients with autoimmune gastritis significantly more frequently (P <.001) than in individuals with multifocal atrophic gastritis, normal oxyntic mucosa, or chronic active gastritis. Our study supports a metaplastic origin for pancreatic acinar cells in the oxyntic mucosa. Furthermore, detection of pancreatic acinar cells in the oxyntic mucosa of patients with gastritis strongly suggests an autoimmune pathogenesis.

Autoimmune Diseases↗

Interobserver variability: comparison between liquid-based and conventional preparations in gynecologic cytology.

BACKGROUND: Studies have shown that the ThinPrep Papanicolaou test (TP) increases the detection of epithelial cell abnormalities compared with the conventional preparation. Little is known about the interobserver variability of reporting gynecologic cytology results using the TP preparation and its comparison with results obtained using the conventional method. METHODS: To compare the interobserver variability between the TP method and the conventional method for reporting the diagnoses of gynecologic cytology, 20 pairs of conventional and TP slides (total, 40 slides) that were prepared from split samples were evaluated blindly by 19 cytotechnologists from three different laboratories. Each reviewer was asked to categorize each slide into the following five categories: within normal limits, benign cellular changes, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). For both conventional and TP preparations, interobserver variability was analyzed using Spearman rank correlation coefficients. The mean correlation coefficients (weak, 0.0-0.4; fair, 0.4-0.7; and strong, 0.7-1.0) between the TP method and the conventional method were then compared. RESULTS: The overall interobserver agreement as well as interobserver agreement within each laboratory was good for both TP and conventional preparations. Based on the set of conventional cervical smears, only one slide that was diagnosed as HSIL had unanimous agreement; whereas, based on the set of TP slides, three slides, including two diagnosed as HSIL and one diagnosed as LSIL, had a unanimous diagnosis. The difference in the interobserver agreement between TP and conventional methods, based on comparing their mean +/- standard deviation correlation coefficients (TP method, 0.84 +/- 0.081; conventional method, 0.82 +/- 0.105; P < 0.001), was statistically significant. CONCLUSIONS: Interobserver agreement in reporting gynecologic cytology using the TP method is good, particularly for squamous intraepithelial lesions, and appears to be superior to the conventional method.

Carcinoma, Squamous Cell↗