PubMed Health⌕ Search

Biomedical subjects

David C Chhieng

Publications and source records attributed to David C Chhieng.

At least 19 recordsLinked to original sources
PubMed2006

Dynamic telecytopathology of on site rapid cytology diagnoses for pancreatic carcinoma.

BACKGROUND: Diagnosis of pancreatic lesions can be accurately performed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) with onsite cytopathologists to assess specimen adequacy and to determine a preliminary diagnosis. Considerable time is needed to perform on-site assessments. This takes away work time of cytopathologists and prohibits them from serving remote locations. It is therefore logical to ask if real-time telecytopathology could be used to assess specimen adequacy and if telecytopathology diagnosis has the same level of agreement to the final diagnosis as that of onsite evaluation. In this study, we compare agreement between cytodiagnoses rendered using telecytopathology with onsite and final interpretations. METHOD: 40 Diff-Quik-stained EUS-FNA were re-evaluated retrospectively (patient ages 31-62, 19:21 male:female, 15 non-malignant lesions, 25 malignant lesions as classified by final diagnosis). Each previously assessed by a cytopathologist and finally reviewed by the same or different cytopathologist. Blinded to the final diagnosis, a resident pathologist re-screened all slides for each case, selected a slide and marked the diagnostic cells most representative of the lesion. Blinded to the diagnosis, one cytopathologist assessed the marked cells through a real time remotely operated telecytopathology system (MedMicroscopy). Diagnosis and time spent were recorded. Kappa statistic was used to compare agreements between telecytopathology vs. original onsite vs. final diagnoses. RESULTS: Time spent for prescreening ranged from 1 to 5 minutes (mean 2.6 +/- 1.3 minutes) and time spent for telecytopathology diagnosis ranged from 2-20 minutes (mean 7.5 +/- 4.5 minutes). Kappa statistics, K, was as follows: telecytopathology versus onsite diagnosis K, 95% CI = 0.65, 0.41-0.88, for telecytopathology versus final K, 95% CI = 0.61, 0.37-0.85 and for onsite diagnosis versus final K, 95% CI = 0.79, 0.61-0.98. There is no significant difference in agreement between onsite and telecytopathology diagnoses. Kappa values for telecytopathology were less than onsite evaluation when compared to the final diagnosis; however, the difference was not statistically significant. CONCLUSION: This retrospective study demonstrates the potential use of telecytopathology as a valid substitute for onsite evaluation of pancreatic carcinoma by EUS-FNA.

Journal Article↗
PubMed2006

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↗
PubMed2006

Increased expression of thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10) and survivin is associated with poor survival in glioblastoma multiforme (GBM).

BACKGROUND: The limited success of empirically designed treatment paradigms for patients diagnosed with glioblastoma multiforme (GBM) emphasizes the need for rationally designed treatment strategies based on the molecular profile of tumor samples and their correlation to clinical parameters. METHODS: In the current study, we utilize a novel real-time quantitative low density array (RTQ-LDA) to identify differentially expressed genes in de novo GBM tissues obtained from patients with distinctly different clinical outcomes. Total RNA was isolated from a cohort of 21 GBM specimens obtained from patients with either good (long-term survival (LTS) >36 months post surgery, n = 8) or poor (died of the disease (DOD) <24 months post surgery, n = 13) prognosis. Non-neoplastic brain tissue (n = 5) was obtained from patients who underwent surgery for refractory epilepsy. Demographic data was assessed for correlation with survival using Cox proportional hazards models. Sufficient RNA was available to use RTQ-LDA to quantify the expression of 93 independent genes in 5 LTS, 4 DOD, and 5 non-neoplastic brain samples. The eight differentially expressed genes identified by RTQ-LDA in LTS versus DOD (P <or= 0.050) were subsequently quantified in all 21 GBM samples by real-time quantitative PCR (RTQ). RESULTS: A correlation between younger patients and good prognosis was demonstrated (P <or= 0.05). The combination of RTQ-LDA and RTQ identified thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10), and survivin as significantly over-expressed (P <or= 0.050) in DOD compared to LTS patients. Ribonucleotide reductase subunit M2 (RRM2) was identified as tumor-specific, but not associated with survival. CONCLUSIONS: Taken collectively, TS, USP10, survivin and RRM2 may be useful as prognostic indicators and/or in the development of rationally designed treatment protocols.

Adolescent↗
PubMed2006

Ovarian expression of markers associated with proliferation or apoptosis in women with diminished ovarian reserve.

OBJECTIVE: To determine DNA fragmentation and several molecules associated with apoptosis or proliferation in ovaries of patients with diminished ovarian reserve. DESIGN: Cross-sectional analysis. SETTING: Tertiary institutional hospital. PATIENT(S): Patients with benign uterine pathology who had undergone a hysterectomy and oophorectomy were categorized by the citrate clomiphene challenge test in diminished ovarian reserve or control group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Apoptosis was determined using TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end-labeling) assay and p53, p27, Bax, caspase-3, caspase-8, caspase-9, Fas-L, Bcl-2, GATA-4, Ki-67, proliferating-cell nuclear antigen (PCNA), estrogen receptor, P receptor, and androgen receptor expression by immunohistochemistry. RESULT(S): Fifteen patients were studied. DNA fragmentation and expression of Bax, caspase-3, caspase-8, caspase-9, Fas-L, Bcl-2, GATA-4, Ki-67, and PCNA were observed in the whole ovary in both groups. In the control group, the expression of caspase-3 and caspase-8 in the ovarian stroma was significantly higher. CONCLUSION(S): DNA fragmentation and the expression of several molecules that participate in ovarian proliferation or apoptosis are present in cycling ovaries, but these markers were not significantly different in patients with diminished ovarian reserve. Thus, the mechanism leading to diminished ovarian reserve does not involve an easily detectable dysregulation in apoptosis or proliferation of ovarian follicles.

Adult↗
PubMed2006

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↗
PubMed2006

Incidence and clinical significance of morphologically benign-appearing endometrial cells in patients age 40 years or older: the impact of the 2001 Bethesda System.

BACKGROUND: The 2001 Bethesda System (TBS 2001) introduced a new diagnostic category-normal endometrial cells in women age 40 years or older (EM >or= 40). The objective of the current study was to determine whether there was any significant increase in the frequency with which this diagnosis was reported after the implementation of TBS 2001 and the clinical significance of this diagnosis. METHODS: All women who had a Papanicolaou (Pap) test and a diagnosis of EM >or= 40 between January 1999 to December 2003 were identified. Follow-up included repeat Pap tests and/or surgical pathology. TBS 2001 was implemented on January 1, 2002. RESULTS: In total, 556 Pap tests with a diagnosis of EM >or= 40 were identified, accounting for 0.52% of the 106,204 Pap tests evaluated during the study period. The incidence of EM >or= 40 before and after implementation of the new TBS was 0.47% and 0.61%, respectively, and showed a statistically significant difference. One hundred four patients (19%) underwent endometrial tissue sampling, including 22 patients who underwent hysterectomy (4%) and 82 patients who underwent endometrial biopsy (15%). Overall, 1 patient (2%) had significant endometrial pathology, namely, complex endometrial hyperplasia without atypia. CONCLUSIONS: A significant increase in the incidence of EM >or= 40 was observed with the implementation of TBS 2001. However, there was no difference in the proportion of patients that underwent endometrial tissue sampling. In addition, the incidence of clinically significant endometrial lesions associated with such a diagnosis was very low. The authors recommend that women with benign endometrial cells on Pap tests in women age 40 years or older should undergo endometrial biopsy only when additional clinical indicators are identified.

Adult↗
PubMed2006

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↗
PubMed2006

Celecoxib inhibits cellular growth, decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines.

BACKGROUND: There is controversy on the safety of inhibitors of cyclooxygenase administered at high doses; however, these drugs have been reported to be effective in the prevention of a variety of human cancers. To determine if celecoxib influences cellular growth, we evaluated several effects in ovarian carcinoma cell lines. METHODS: CAOV3, OVCAR3 and SKOV3 cell lines were exposed to different concentrations of celecoxib (0-100 microM) for 24-96 h. Cellular growth was assessed using a cell viability assay. Immunohistochemistry was performed to evaluate Ki-67 and cleaved caspase-3. Apoptosis was determined by a TUNEL assay, and Western blot was used to determine COX-2 protein expression. RESULTS: We observed a significant decrease in the cellular growth of all cell lines studied exposed to > or = 70 microM of celecoxib for 72 and 96 h (p < 0.02). All cells demonstrated pancytotoxicity at 100 microM of celecoxib. A significant decrease in Ki-67 expression in all cell lines exposed to > or = 30 microM of celecoxib (p < or = 0.05) for 72 h was observed. We observed significant changes in apoptosis and cleaved caspase-3 expression in SKOV3 cells exposed to 50 microM of celecoxib. Downregulation of COX-2 protein expression caused by celecoxib was observed in SKOV3 cells. CONCLUSIONS: We found that celecoxib inhibits cellular growth and proliferation in a dose-dependent manner in all cell lines studied. SKOV3 cells showed an increase in cleaved caspase-3 expression. Additional studies are in progress to evaluate the effects of celecoxib on other aspects of the control of the cell cycle in cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Use of mesothelin as a marker for mesothelial cells in cytologic specimens.

Immunocytochemistry is often employed for the distinction between mesothelial cells and adenocarcinoma. Mesothelin has recently been reported to be expressed in reactive mesothelial cells and epithelioid mesotheliomas. The objective of this study is to determine the utility of mesothelin as marker for mesothelial cells in cytologic preparations. Thirty cell blocks were retrieved from the archives and immunostained with monoclonal antibody directed against mesothelin and calretinin. Heat-induced epitope retrieval technique was employed, and the immunostaining was accomplished using an automated stainer. These tissue blocks were from 35 patients (17 females and 18 males) with a median age of 64 years. Nine were benign effusions, 11 mesotheliomas, and 18 metastatic adenocarcinomas. The presence of any immunoreactivity, irrespective of level of intensity or percentage of cells, was considered positive for mesothelin expression. Follow up included correlation with pathology materials obtained at surgery and review of medical records. Mesothelin staining was positive in 7/9 benign cases, 8/11 mesotheliomas, and 8/18 adenocarcinomas. The difference of mesothelin expression between mesothelial cells and adenocarcinoma was statistically significant. For calretinin, all cases, except 2 malignant mesotheliomas and 3 adenocarcinomas, showed positive staining with calretinin. As a marker for mesothelial cells, the sensitivity and specificity of mesothelin were 73% and 55%, respectively, and the sensitivity and specificity of calretinin were 95% and 86%, respectively. Therefore, mesothelin is not a sensitive or a specific marker for mesothelial cells in cytologic specimens when compared with calretinin.

Adenocarcinoma↗
PubMed2006

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↗
PubMed2006

Negative colposcopic biopsy after positive human papilloma virus (HPV) DNA testing: false-positive HPV results or false-negative histologic findings?

We studied histologic examination-related factors contributing to false-negative colposcopic biopsy results. Patients positive for high-risk human papillomavirus (HPV) DNA with negative cervical histologic findings were identified between January 2002 and December 2003. Three additional H&E-stained levels were obtained when the original diagnosis was confirmed on review. Patients with atypical squamous cells of undetermined significance (ASC) Papanicolaou test results, positive HPV DNA results, and negative cervical histologic findings accounted for 4.5% of all ASC smears submitted for HPV DNA testing. Slides and tissue blocks were available for 95 cases; 4% had focal HPV infection or mild dysplasia. When deeper levels were examined, 31% had clinically significant lesions: HPV infection or cervical intraepithelial neoplasia (CIN) 1, 19%; CIN 2/3, 8%; and dysplasia, not otherwise specified, 3%. Of the remaining patients, follow-up revealed squamous abnormalities in 25%. About 5% of patients with positive HPV DNA results had a negative follow-up biopsy result. "False-negative" biopsies accounted for one third of cases. Additional levels should be obtained for discrepant results. Close follow-up is crucial when the initial biopsy result is negative because a small number of patients will have squamous abnormalities in subsequent studies.

Biopsy↗
PubMed2005

Antitumor efficacy of capecitabine and celecoxib in irradiated and lead-shielded, contralateral human BxPC-3 pancreatic cancer xenografts: clinical implications of abscopal effects.

PURPOSE: X-ray therapy (XRT) remains one of the major modalities used to treat patients diagnosed with locally advanced pancreatic adenocarcinoma. However, the effect of XRT on metastatic tumors outside the field of irradiation (abscopal effect) remains largely unknown. In the current study, we examined the effect of XRT alone and in combination with capecitabine and/or celecoxib in both irradiated and lead-shielded contralateral BxPC-3 pancreatic cancer xenografts. This chemoradiation regimen was chosen based on our molecular analysis of pancreatic adenocarcinoma. EXPERIMENTAL DESIGN: Athymic mice were injected bilaterally with BxPC-3 cells and treatment was initiated 28 days postimplant. During XRT (2 Gy for 5 consecutive days, administered on days 0 and 24), one flank was irradiated whereas the rest of the body (including the contralateral tumor) was lead shielded. Capecitabine (350 mg/kg) was administered on days 0 to 13 and 24 to 37. Celecoxib was initiated in the diet at 100 ppm (equivalent to 20 mg/kg/d p.o.) and administered throughout the study. RESULTS: In irradiated xenografts, capecitabine and XRT showed synergistic anitiumor efficacy (P=0.008), which was further improved with the addition of celecoxib (P<0.001). In contralateral shielded xenografts, abscopal effects were observed. Whereas monotherapy with XRT showed significant reduction in tumor area in irradiated xenografts, growth was promoted by 23% (P<0.001) in contralateral lead-shielded tumors in the same animals relative to untreated tumors. Interestingly, synergistic antiproliferative efficacy occurred in these contralateral tumors when capecitabine was administered (P<0.001), despite being outside the irradiated field. The addition of celecoxib further inhibited tumor growth (P<0.001). This trimodal combination most effectively stabilized disease in both shielded and irradiated tumors; however, tumor eradication was not observed. There were no significant changes in thymidine phosphorylase, dihydropyrimidine dehydrogenase, or cyclooxygenase-2 mRNA levels in irradiated or lead-shielded tumors, suggesting that efficacy cannot be predicted solely from these previously identified indicators of response. Immunohistochemistry examining the proliferation marker Ki-67 showed concordance with tumor response in both irradiated and contralateral shielded xenografts. CONCLUSIONS: These results have implications in the rational design of treatment paradigms for pancreatic cancer where metastatic disease remains the primary cause of patient morbidity and abscopal effects in tumors outside the field of irradiation may affect tumor response.

5'-Nucleotidase↗
PubMed2005

Reflex human papilloma virus infection testing detects the same proportion of cervical intraepithelial neoplasia grade 2-3 in young versus elderly women.

BACKGROUND: The American Society for Colposcopy and Cervical Pathology recently recommended triage of women with atypical squamous cells of undetermined significance (ASCUS) through reflex human papilloma virus (HPV) infection testing. Because age is an important determinant of the incidence of both ASCUS and HPV infection, the current study was conducted to determine the impact of age on reflex HPV infection test performance. METHODS: The authors reviewed all liquid-based Papanicolaou tests submitted for reflex HPV infection testing to the University of Alabama Medical Center during the period from January 2002 to January 2004. To assess the impact of age on reflex HPV infection testing, women were divided into 6 age groups (<25, 25-34, 35-44, 45-54, 55-64, >64 years). Trend of different diagnostic categories with age was assessed using the chi-square test for linear trend. As a measure of test performance, the proportions of cervical intraepithelial neoplasia (CIN) lesions confirmed by biopsy through reflex testing (of the total CIN lesions detected in the study population) were then compared among different age groups. RESULTS: During the study period, 25,164 ThinPrep tests were performed during the study period, with 2672 (11%) cases of ASCUS and 1371 (5%) cases of squamous intraepithelial lesions (SILs). A total of 2309 (86%) ASCUS cases were tested for HPV infection, of which 789 (34%) were positive. Biopsy specimens were obtained from 831 patients with SILs and from 316 patients with HPV+ASCUS. Of 246 patients with CIN Grade 2-3 (CIN2-3) detected on biopsy, 36 (15%) were triaged through reflex HPV infection testing and the rest were triaged through cytologic diagnosis of SILs. Despite the trend in the prevalence of HPV+ASCUS and SILs with increasing age (P < 0.05), there was no significant difference in the proportion (range, 9-23%) of CIN2-3 detected through reflex HPV infection testing in different age groups. CONCLUSIONS: Reflex HPV infection testing performed similarly for women in different age groups, including perimenopausal and postmenopausal women.

Adult↗
PubMed2005

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↗