Achyut K Bhattacharyya

Interests

No activities entered.

Courses

Scholarly Contributions

Journals/Publications

• Goulet, A., Einsphar, J. G., Alberts, D. S., Beas, A., Burk, C., Bhattacharyya, A., Bangert, J., Harmon, J. M., Fujiwara, H., Koki, A., & Nelson, M. A. (2016). Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression. Cancer biology & therapy, 2(6), 713-8.
  More info

  Cyclooxygenase 2 (COX-2) is an inducible enzyme involved in the production of prostaglandins and thromboxanes during inflammation. There are now several lines of evidence indicating that increased expression of COX-2 plays a functional role in the development and progression of malignant epithelial cancers. However, there is only limited data regarding the role of COX-2 in melanoma pathogenesis. In the present work, we retrospectively examined lesions through out the development of melanoma and metastatic disease (dysplastic nevi n = 10, melanoma in situ n = 4, stage II melanoma n = 10, stage III n = 4, stage IV n = 3, stage V n = 2, melanoma metastasis lymph nodes n = 13 metastasis to other sites n = 3). COX-2 was consistently observed in keratinocytes, dermal fibroblasts, and inflammatory cells in regions adjacent to benign evi and primary cutaneous melanomas. However, no COX-2 staining was detected in the nevi nor in the primary skin melanoma cells. In addition, COX-2 was undetected in all vertical and radial growth phase cases Interestingly, 13 out of 13 of the lymph node metastasis expressed extremely high levels of COX-2 in overlying epithelium and inflammatory cells, and COX-2 was strongly detected in the metastatic cancer cells per se. For additional information on the expression of COX-2 in malignant melanoma, we determined the expression of COX-2 protein in several different melanoma cell lines. We found that 3We found that 5 out of 7 of the melanoma cells over expressed COX-2 compared to normal melanocytes. Collectively, these data suggest that COX-2 may play a functional role in metastases of melanoma, and treatment with COX-2 inhibitors may be efficacious for malignant melanoma.
• Braunhut, B. L., Graham, A. R., Lian, F., Webster, P. D., Krupinski, E. A., Bhattacharyya, A. K., & Weinstein, R. S. (2014). Subspecialty surgical pathologist's performances as triage pathologists on a telepathology-enabled quality assurance surgical pathology service: A human factors study. Journal of pathology informatics, 5, 18.
  More info

  The case triage practice workflow model was used to manage incoming cases on a telepathology-enabled surgical pathology quality assurance (QA) service. Maximizing efficiency of workflow and the use of pathologist time requires detailed information on factors that influence telepathologists' decision-making on a surgical pathology QA service, which was gathered and analyzed in this study.
• Pugh, J. L., Jie, T., Bhattacharyya, A. K., Pugh, J. L., Jie, T., & Bhattacharyya, A. K. (2013). Pedunculated gastrointestinal stromal tumor (GIST) of the stomach presenting as pancreatic mucinous cystadenocarcinoma: A Case Report. Journal of Clinical and Experimental Pathology, 3(1), 135.
• Chandramouli, A., Onyeagucha, B. C., Mercado-Pimentel, M. E., Stankova, L., Shahin, N. A., LaFleur, B. J., Heimark, R. L., Bhattacharyya, A. K., & Nelson, M. A. (2012). MicroRNA-101 (miR-101) post-transcriptionally regulates the expression of EP4 receptor in colon cancers. Cancer biology & therapy, 13(3), 175-83.
  More info

  Expression of the PGE2 receptor, EP4, is up-regulated during colorectal carcinogenesis. However the mechanism leading to deregulation of the EP4 receptor is not known. The present study was conducted to investigate the regulation of EP4 receptor by miRNAs.
• Weinstein, R. S., Graham, A. R., Lian, F., Braunhut, B. L., Barker, G. R., Krupinski, E. A., & Bhattacharyya, A. K. (2012). Reconciliation of diverse telepathology system designs. Historic issues and implications for emerging markets and new applications. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 120(4), 256-75.
  More info

  Telepathology, the distant service component of digital pathology, is a growth industry. The word "telepathology" was introduced into the English Language in 1986. Initially, two different, competing imaging modalities were used for telepathology. These were dynamic (real time) robotic telepathology and static image (store-and-forward) telepathology. In 1989, a hybrid dynamic robotic/static image telepathology system was developed in Norway. This hybrid imaging system bundled these two primary pathology imaging modalities into a single multi-modality pathology imaging system. Similar hybrid systems were subsequently developed and marketed in other countries as well. It is noteworthy that hybrid dynamic robotic/static image telepathology systems provided the infrastructure for the first truly sustainable telepathology services. Since then, impressive progress has been made in developing another telepathology technology, so-called "virtual microscopy" telepathology (also called "whole slide image" telepathology or "WSI" telepathology). Over the past decade, WSI has appeared to be emerging as the preferred digital telepathology digital imaging modality. However, recently, there has been a re-emergence of interest in dynamic-robotic telepathology driven, in part, by concerns over the lack of a means for up-and-down focusing (i.e., Z-axis focusing) using early WSI processors. In 2010, the initial two U.S. patents for robotic telepathology (issued in 1993 and 1994) expired enabling many digital pathology equipment companies to incorporate dynamic-robotic telepathology modules into their WSI products for the first time. The dynamic-robotic telepathology module provided a solution to the up-and-down focusing issue. WSI and dynamic robotic telepathology are now, rapidly, being bundled into a new class of telepathology/digital pathology imaging system, the "WSI-enhanced dynamic robotic telepathology system". To date, six major WSI processor equipment companies have embraced the approach and developed WSI-enhanced dynamic-robotic digital telepathology systems, marketed under a variety of labels. Successful commercialization of such systems could help overcome the current resistance of some pathologists to incorporate digital pathology, and telepathology, into their routine and esoteric laboratory services. Also, WSI-enhanced dynamic robotic telepathology could be useful for providing general pathology and subspecialty pathology services to many of the world's underserved populations in the decades ahead. This could become an important enabler for the delivery of patient-centered healthcare in the future.
• Bernstein, C., Holubec, H., Bhattacharyya, A. K., Nguyen, H., Payne, C. M., Zaitlin, B., & Bernstein, H. (2011). Carcinogenicity of deoxycholate, a secondary bile acid. Archives of toxicology, 85(8), 863-71.
  More info

  High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8-10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.
• Rial, N. S., Gilchrist, K. B., Henderson, J. T., Bhattacharyya, A. K., Boyer, T. D., Nadir, A., & Cunningham, J. T. (2011). Endoscopic ultrasound with biopsy of omental mass for cholangiocarcinoma diagnosis in cirrhosis. World journal of gastrointestinal endoscopy, 3(6), 124-8.
  More info

  In this report, a patient had a previous diagnosis of cholangiocarcinoma with an extended cholecystectomy. Three years later, he was evaluated for recurrent ascites. The patient had several large volume paracentesis, without evidence of malignant cells. Subsequently, endoscopic ultrasound (EUS) with fine needle aspiration (FNA) of both lymph and omental nodules was utilized. While the lymph nodes were negative for malignancy, the omental nodule was interrogated with multiple antibodies and was found to be positive for neoplasia. EUS with FNA can safely be used in patients with cirrhosis to spare the patient invasive evaluation such as exploratory laparotomy (ex-lap) for diagnosis and staging of cholangiocarcinoma.
• Bartley, A. N., Thompson, P. A., Buckmeier, J. A., Kepler, C. Y., Hsu, C., Snyder, M. S., Lance, P., Bhattacharyya, A., & Hamilton, S. R. (2010). Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 23(2), 169-76.
  More info

  Serrated polyps of the colorectal mucosa represent a heterogeneous and controversial taxonomic category with variation in histopathological, molecular, and immunohistochemical characteristics and with an incomplete understanding of pathogenesis. A previous study reported that the expression of gastric pyloric-type mucin, MUC6, characterized sessile serrated adenomas. We therefore evaluated the expression of MUC6 in serrated polyps identified among 2502 participants in a Phase III chemoprevention trial within the Arizona Cancer Center Colorectal Cancer Prevention Trials Program and characterized the associated histopathological features and location. We carried out immunohistochemistry for MUC6 on 146 serrated lesions and 87 conventional tubular adenomas, and assessed the percentage of cells with expression and the grade of staining intensity. In all 92 hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional serrated adenomas were included. Polyps ranged in size from 1-150 mm. The association of MUC6 staining with serrated polyp category was evaluated using classification and regression tree (CART) analysis and two-sided Fisher's exact test. A total of 53% of sessile serrated adenomas (n=23), 17% of hyperplastic polyps (n=16), and 18% of traditional serrated adenomas (n=2), but none of 87 tubular adenomas, expressed MUC6. Expression was limited to the lower crypts in all serrated polyps. The extent of positive staining ranged from 2-100% of crypt cells and was independent of the histopathological type. MUC6 expression had relatively high specificity for sessile serrated adenoma (82%) but low sensitivity (54%). In CART analysis, proximal location was found to be the best partitioning factor for MUC6, followed by classification as sessile serrated adenoma. We conclude that MUC6 expression is strongly associated with proximal location of serrated polyps, but only has modest utility as a tissue biomarker for sessile serrated adenoma.
• Chandramouli, A., Mercado-Pimentel, M. E., Hutchinson, A., Gibadulinová, A., Olson, E. R., Dickinson, S., Shañas, R., Davenport, J., Owens, J., Bhattacharyya, A. K., Regan, J. W., Pastorekova, S., Arumugam, T., Logsdon, C. D., & Nelson, M. A. (2010). The induction of S100p expression by the Prostaglandin E₂ (PGE₂)/EP4 receptor signaling pathway in colon cancer cells. Cancer biology & therapy, 10(10), 1056-66.
  More info

  Prostaglandin E₂ (PGE₂) levels are frequently elevated in colorectal carcinomas. PGE₂ is perceived via four transmembrane G protein coupled receptors (EP1-4), among which the EP4 receptor is most relevant. PGE₂/EP4-receptor interaction activates CREB via the ERK/MEK pathway. However, the downstream target genes activated by this pathway remained to be investigated.
• Rial, N. S., Henderson, J. T., Bhattacharyya, A. K., Nadir, A., & Cunningham, J. T. (2010). Use of endoscopic ultrasound for diagnosis of cholangiocarcinoma in auto-immune hepatitis. World journal of gastrointestinal endoscopy, 2(12), 404-7.
  More info

  In this report, a patient was exposed to an herbal remedy for hypercholesterolemia. She became acutely jaundiced while taking the remedy and presented for medical care. Endoscopic ultrasound was utilized, and found a distal common bile duct mass. Endoscopic retrograde cholangiopancreatography guided bile duct biopsies revealed that the mass was cholangiocarcinoma (CCA). This case highlights a unique association between autoimmune hepatitis and CCA. It also highlights that EUS can be safely used in patients with cirrhosis to spare invasive evaluation such as exploratory laporotomy for diagnosis and staging of cholangiocarcinoma.
• Wen, F., Shen, A., Shanas, R., Bhattacharyya, A., Lian, F., Hostetter, G., & Shi, J. (2010). Higher expression of the heterogeneous nuclear ribonucleoprotein k in melanoma. Annals of surgical oncology, 17(10), 2619-27.
  More info

  The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. Oncogenes c-Src, c-myc, and eIF4E are regulated by hnRNP K. We have shown an increased cytoplasmic hnRNP K in pancreatic cancer. In the present study, we investigated the altered expression of hnRNP K protein and its correlation with p-ERK in melanoma using human melanoma cell lines and tissue microarray.
• Zhou, R., Shanas, R., Nelson, M. A., Bhattacharyya, A., & Shi, J. (2010). Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53. International journal of cancer. Journal international du cancer, 126(2), 395-404.
  More info

  The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. In this study, we investigated the altered protein expression and the subcellular distribution of the hnRNP K protein using tissue microarrays in pancreatic cancer. We showed an increased cytoplasmic hnRNP K in pancreatic cancer. This increase in hnRNP K protein occurs at the posttranscriptional level. We postulate that the cytoplasmic accumulation of hnRNP K will lead to silenced mRNA translation of tumor suppressor genes and thus contributes to pancreatic cancer development. We also demonstrated that knocking down of hnRNP K expression by siRNA inhibited pancreatic cancer cell growth and colony formation. hnRNP K was identified as a member of the p53/HDM2 pathway. Whether hnRNP K interacts with the mutant p53 is not known. Using two different pancreatic cancer cell lines, we can demonstrate that hnRNP K interacts with the mutant p53. The subcellular distribution and function of the mutant p53 and the interaction of hnRNP K/mutant p53 were affected by the Ras/MEK/ERK pathway, growth factors and the specific p53 mutations in pancreatic cancer cells. Since Kras is activated and p53 is mutated in most pancreatic cancers, these data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis.
• Graham, A. R., Bhattacharyya, A. K., Scott, K. M., Lian, F., Grasso, L. L., Richter, L. C., Carpenter, J. B., Chiang, S., Henderson, J. T., Lopez, A. M., Barker, G. P., & Weinstein, R. S. (2009). Virtual slide telepathology for an academic teaching hospital surgical pathology quality assurance program. Human pathology, 40(8), 1129-36.
  More info

  Virtual slide telepathology is an important potential tool for providing re-review of surgical pathology cases as part of a quality assurance program. The University of Arizona pathology faculty has implemented a quality assurance program between 2 university hospitals located 6 miles apart. The flagship hospital, University Medical Center (UMC), in Tucson, AZ, handles approximately 20 000 surgical pathology specimens per year. University Physicians Healthcare Hospital (UPHH) at Kino Campus has one tenth the volume of surgical pathology cases. Whereas UMC is staffed by 10 surgical pathologists, UPHH is staffed daily by a single part-time pathologist on a rotating basis. To provide same-day quality assurance re-reviews of cases, a DMetrix DX-40 ultrarapid virtual slide scanner (DMetrix, Inc, Tucson, AZ) was installed at the UPHH in 2005. Since then, glass slides of new cases of cancer and other difficult cases have been scanned the same day the slides are produced by the UPHH histology laboratory. The pathologist at UPHH generates a provisional written report based on light microscopic examination of the glass slides. At 2:00 pm each day, completed cases from UPHH are re-reviewed by staff pathologists, pathology residents, and medical students at the UMC using the DMetrix Iris virtual slide viewer. The virtual slides are viewed on a 50-in plasma monitor. Results are communicated with the UPHH laboratory by fax. We have analyzed the results of the first 329 consecutive quality assurance cases. There was complete concordance with the original UPHH diagnosis in 302 (91.8%) cases. There were 5 (1.5%) major discrepancies, which would have resulted in different therapy and/or management, and 10 (3.0%) minor discrepancies. In 6 cases (1.8%), the diagnosis was deferred for examination of the glass slides by the reviewing pathologists at UMC, and the diagnosis of another 6 (1.8%) cases were deferred pending additional testing, usually immunohistochemistry. Thus, the quality assurance program found a small number of significant diagnostic discrepancies. We also found that implementation of a virtual slide telepathology quality assurance service improved the job satisfaction of academic subspecialty pathologists assigned to cover on-site surgical pathology services at a small, affiliated university hospital on a rotating part-time basis. These findings should be applicable to some community hospital group practices as well.
• Jin, Z., Cheng, Y., Gu, W., Zheng, Y., Sato, F., Mori, Y., Olaru, A. V., Paun, B. C., Yang, J., Kan, T., Ito, T., Hamilton, J. P., Selaru, F. M., Agarwal, R., David, S., Abraham, J. M., Wolfsen, H. C., Wallace, M. B., Shaheen, N. J., , Washington, K., et al. (2009). A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus. Cancer research, 69(10), 4112-5.
  More info

  Esophageal adenocarcinoma risk in Barrett's esophagus (BE) is increased 30- to 125-fold versus the general population. Among all BE patients, however, neoplastic progression occurs only once per 200 patient-years. Molecular biomarkers are therefore needed to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression. We therefore performed a retrospective, multicenter, double-blinded validation study of eight BE progression prediction methylation biomarkers. Progression or nonprogression were determined at 2 years (tier 1) and 4 years (tier 2). Methylation was assayed in 145 nonprogressors and 50 progressors using real-time quantitative methylation-specific PCR. Progressors were significantly older than nonprogressors (70.6 versus 62.5 years; P < 0.001). We evaluated a linear combination of the eight markers, using coefficients from a multivariate logistic regression analysis. Areas under the ROC curve (AUC) were high in the 2-year, 4-year, and combined data models (0.843, 0.829, and 0.840; P < 0.001,
• López, A. M., Graham, A. R., Barker, G. P., Richter, L. C., Krupinski, E. A., Lian, F., Grasso, L. L., Miller, A., Kreykes, L. N., Henderson, J. T., Bhattacharyya, A. K., & Weinstein, R. S. (2009). Virtual slide telepathology enables an innovative telehealth rapid breast care clinic. Human pathology, 40(8), 1082-91.
  More info

  An innovative telemedicine-enabled rapid breast care service is described that bundles telemammography, telepathology, and teleoncology services into a single day process. The service is called the UltraClinics Process. Because the core services are at 4 different physical locations, a challenge has been to obtain stat second opinion readouts on newly diagnosed breast cancer cases. To provide same day quality assurance rereview of breast surgical pathology cases, a DMetrix DX-40 ultrarapid virtual slide scanner (DMetrix Inc, Tucson, AZ) was installed at the participating laboratory. Glass slides of breast cancer and breast hyperplasia cases were scanned the same day the slides were produced by the University Physicians Healthcare Hospital histology laboratory. Virtual slide telepathology was used for stat quality assurance readouts at University Medical Center, 6 miles away. There was complete concurrence with the primary diagnosis in 139 (90.3%) of cases. There were 4 (2.3%) major discrepancies, which would have resulted in a different therapy and 3 (1.9%) minor discrepancies. Three cases (1.9%) were deferred for immunohistochemistry. In 2 cases (1.3%), the case was deferred for examination of the glass slides by the reviewing pathologists at University Medical Center. We conclude that the virtual slide telepathology quality assurance program found a small number of significant diagnostic discrepancies. The virtual slide telepathology program service increased the job satisfaction of subspecialty pathologists without special training in breast pathology, assigned to cover the general surgical pathology service at a small satellite university hospital.
• López, A. M., Graham, A. R., Barker, G. P., Richter, L. C., Krupinski, E. A., Lian, F., Grasso, L. L., Miller, A., Kreykes, L. N., Henderson, J. T., Bhattacharyya, A. K., & Weinstein, R. S. (2009). Virtual slide telepathology enables an innovative telehealth rapid breast care clinic. Seminars in diagnostic pathology, 26(4), 177-86.
  More info

  An innovative telemedicine-enabled rapid breast care service is described that bundles telemammography, telepathology, and teleoncology services into a single day process. The service is called the UltraClinics Process. Since the core services are at four different physical locations a challenge has been to obtain STAT second opinion readouts on newly diagnosed breast cancer cases. In order to provide same day QA re-review of breast surgical pathology cases, a DMetrix DX-40 ultrarapid virtual slide scanner (DMetrix, Inc., Tucson, AZ) was installed at the participating laboratory. Glass slides of breast cancer and breast hyperplasia cases were scanned the same day the slides were produced by the University Physicians Healthcare Hospital histology laboratory. Virtual slide telepathology was used for STAT quality assurance readouts at University Medical Center, 6 miles away. There was complete concurrence with the primary diagnosis in 139 (90.3%) of cases. There were 4 (2.3%) major discrepancies, which would have resulted in a different therapy and 3 (1.9%) minor discrepancies. Three cases (1.9%) were deferred for immunohistochemistry. In 2 cases (1.3%), the case was deferred for examination of the glass slides by the reviewing pathologists at University Medical Center. We conclude that the virtual slide telepathology QA program found a small number of significant diagnostic discrepancies. The virtual slide telepathology program service increased the job satisfaction of subspecialty pathologists without special training in breast pathology, assigned to cover the general surgical pathology service at a small satellite university hospital.
• Nguyen, D. M., El-Serag, H. B., Henderson, L., Stein, D., Bhattacharyya, A., & Sampliner, R. E. (2009). Medication usage and the risk of neoplasia in patients with Barrett's esophagus. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 7(12), 1299-304.
  More info

  Experimental evidence indicates that proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin, and statins can protect patients with Barrett's esophagus (BE) from developing neoplasias. However, only limited data are available on chemoprevention in patients with BE.
• Weinstein, R. S., Graham, A. R., Richter, L. C., Barker, G. P., Krupinski, E. A., Lopez, A. M., Erps, K. A., Bhattacharyya, A. K., Yagi, Y., & Gilbertson, J. R. (2009). Overview of telepathology, virtual microscopy, and whole slide imaging: prospects for the future. Human pathology, 40(8), 1057-69.
  More info

  Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. Today, fourth-generation telepathology systems, so-called virtual slide telepathology systems, are being used for education applications. Both conventional and innovative surgical pathology diagnostic services are being designed and implemented as well. The technology has been commercialized by more than 30 companies in Asia, the United States, and Europe. Early adopters of telepathology have been laboratories with special challenges in providing anatomic pathology services, ranging from the need to provide anatomic pathology services at great distances to the use of the technology to increase efficiency of services between hospitals less than a mile apart. As to what often happens in medicine, early adopters of new technologies are professionals who create model programs that are successful and then stimulate the creation of infrastructure (ie, reimbursement, telecommunications, information technologies, and so on) that forms the platforms for entry of later, mainstream, adopters. The trend at medical schools, in the United States, is to go entirely digital for their pathology courses, discarding their student light microscopes, and building virtual slide laboratories. This may create a generation of pathology trainees who prefer digital pathology imaging over the traditional hands-on light microscopy. The creation of standards for virtual slide telepathology is early in its development but accelerating. The field of telepathology has now reached a tipping point at which major corporations now investing in the technology will insist that standards be created for pathology digital imaging as a value added business proposition. A key to success in teleradiology, already a growth industry, has been the implementation of standards for digital radiology imaging. Telepathology is already the enabling technology for new, innovative laboratory services. Examples include STAT QA surgical pathology second opinions at a distance and a telehealth-enabled rapid breast care service. The innovative bundling of telemammography, telepathology, and teleoncology services may represent a new paradigm in breast care that helps address the serious issue of fragmentation of breast cancer care in the United States and elsewhere. Legal and regulatory issues in telepathology are being addressed and are regarded as a potential catalyst for the next wave of telepathology advances, applications, and implementations.
• A-Kader, H. H., Henderson, J., Vanhoesen, K., Ghishan, F., & Bhattacharyya, A. (2008). Nonalcoholic fatty liver disease in children: a single center experience. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 6(7), 799-802.
  More info

  Nonalcoholic fatty liver disease (NAFLD) is the most common disorder seen in pediatric hepatology practice. However, little is known about the clinical, biochemical, and histologic features of the disorder. In addition, there have been no reports of the natural history of NAFLD in the pediatric age group.
• Doldan, A., Chandramouli, A., Shanas, R., Bhattacharyya, A., Cunningham, J. T., Nelson, M. A., & Shi, J. (2008). Loss of the eukaryotic initiation factor 3f in pancreatic cancer. Molecular carcinogenesis, 47(3), 235-44.
  More info

  Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in pancreatic cancer. Overexpression of eIF3f induces apoptosis in pancreatic cancer cells. The eIF3f gene is located at chromosome band region 11p15.4. Loss of 11p15.4 is a common event in many tumors including pancreatic cancer. In order to investigate the molecular mechanism of the decreased expression of eIF3f in pancreatic cancer, we performed loss of heterozygosity (LOH) analysis in 32 pancreatic cancer specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 71% to 93%. We also performed eIF3f gene copy number analysis using quantitative real time PCR to further confirm the specific allelic loss of eIF3f gene in pancreatic cancer. We demonstrated a statistically significant decrease of eIF3f gene copy number in pancreatic tumors compared with normal tissues with a tumor/normal ratio of 0.24. Furthermore, RNA in situ hybridization and tissue microarray immunohistochemistry analysis demonstrated that eIF3f expression is significantly decreased in human pancreatic adenocarcinoma tissues compared to normal pancreatic tissues. These data provides new insight into the understanding of the molecular pathogenesis of eIF3f during pancreatic tumorigenesis.
• Doldan, A., Chandramouli, A., Shanas, R., Bhattacharyya, A., Leong, S. P., Nelson, M. A., & Shi, J. (2008). Loss of the eukaryotic initiation factor 3f in melanoma. Molecular carcinogenesis, 47(10), 806-13.
  More info

  Aberrant regulation of the translation initiation is known to contribute to tumorigenesis. eIF3 plays an important role in translation initiation. eIF3f is the p47 subunit of the eIF3 complex whose function in cancer is not clear. Initial studies from our group indicated that eIF3f expression is decreased in melanoma. Overexpression of eIF3f inhibits translation and induces apoptosis in melanoma cells. The eIF3f gene is located at chromosome region 11p15.4. Loss of 11p15.4 is a common event in many tumors including melanoma. In order to investigate the molecular mechanism of the decreased expression of eIF3f in melanoma, we performed loss of heterozygosity (LOH) analysis in 24 melanoma specimens using three microsatellite markers encompassing the eIF3f gene. We showed that the prevalence of LOH ranged from 75% to 92% in melanoma. We also performed eIF3f gene copy number analysis using quantitative real-time PCR to further confirm the specific allelic loss of the eIF3f gene in melanoma. We demonstrated a statistically significant decrease of the eIF3f gene copy number in melanoma compared with normal tissues with a tumor/normal ratio of 0.52. To further elucidate the somatic genetic alterations, we carried out mutation analysis covering the entire coding region and 5'UTR of the eIF3f gene in melanoma tissues and cell lines. Despite some polymorphisms, we did not find any mutations. Furthermore, immunohistochemistry analysis demonstrated that eIF3f protein expression is decreased in melanoma compared to benign nevi. These data provide new insight into the understanding of the molecular pathogenesis of eIF3f during melanoma tumorigenesis.
• Chandramouli, A., Shi, J., Feng, Y., Holubec, H., Shanas, R. M., Bhattacharyya, A. K., Zheng, W., & Nelson, M. A. (2007). Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice. Carcinogenesis, 28(9), 2028-35.
  More info

  The Cdc2L gene encodes for the cyclin-dependent kinase 11 (CDK11) protein. Loss of one allele of Cdc2L and reduced CDK11 expression has been observed in several cancers, implicating its association with carcinogenesis. To directly investigate the role of CDK11 in carcinogenesis, we first generated cdc2l haploinsufficient mice by gene trap technology and then studied the susceptibility of these gene-trapped (cdc2l(GT)) mice to chemical-mediated skin carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis model. Wild-type and cdc2l(GT) mice were subjected to a single topical application of initiation by DMBA and promotion twice a week for 19 weeks with TPA. At 19 weeks, 70% of the cdc2l(GT) mice and 60% of the cdc2l+/+ mice developed benign papillomas. However, there was an overall 3-fold increase in the average number of tumors per mouse observed in cdc2l(GT) mice as compared with cdc2l+/+ mice. There was also an increased frequency of larger papillomas in cdc2l(GT) mice. By using the polymerase chain reaction-restriction fragment length polymorphism assay, we found A to T transversion mutations at the 61st codon of H-ras gene in the papilloma tissue of both cdc2l(GT) mice and cdc2l+/+ mice. Ki-67 staining revealed increased proliferation in the papillomas of cdc2l(GT) (77.75%) as compared with cdc2l+/+ (30.84%) tumors. These studies are the first to show that loss of one allele of cdc2l gene, encoding CDK11, facilitates DMBA/TPA-induced skin carcinogenesis in vivo.
• Guy, N. C., Garewal, H., Holubec, H., Bernstein, H., Payne, C. M., Bernstein, C., Bhattacharyya, A. K., & Dvorak, K. (2007). A novel dietary-related model of esophagitis and Barrett's esophagus, a premalignant lesion. Nutrition and cancer, 59(2), 217-27.
  More info

  Barrett's esophagus (BE) is a premalignant lesion in which columnar epithelium (containing goblet cells) replaces esophageal squamous cells. Previous evidence suggested that hydrophobic bile acids and zinc deficiency each play a role in BE development. We fed wild-type C57BL/6 mice a zinc-deficient diet containing the hydrophobic bile acid, deoxycholic acid for various times up to 152 days. All mice fed this diet developed esophagitis by 69 days on the diet and 63% of the mice on this diet for 88 to 152 days also developed a BE-like lesion. Esophageal tissues showed thickened mucosa, increased proliferation, and increased expression of markers associated with oxidative and nitrosative stress. The newly formed BE-like lesions expressed Mucin-2, a marker of columnar differentiation. They also showed translocation of the p65 subunit of nuclear factor-kappaB and beta -catenin to the nucleus and typical histological changes associated with BE lesions. This mouse model of esophagitis and BE is expected to contribute to a deeper understanding of BE pathogenesis and to strategies for prevention of BE progression to cancer.
• Watts, G. S., Tran, N. L., Berens, M. E., Bhattacharyya, A. K., Nelson, M. A., Montgomery, E. A., & Sampliner, R. E. (2007). Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. International journal of cancer. Journal international du cancer, 121(10), 2132-9.
  More info

  Given the poor survival rate and efficacy of current therapy for esophageal adenocarcinoma (EAC), there is a need to identify and develop new therapeutic targets for treatment. Microarray analysis (Affymetrix U133A GeneChips, Robust Multi-Chip Analysis) was used to expression profile 11 normal squamous and 18 Barrett's esophagus biopsies, 7 surgically resected EACs and 3 EAC cell lines. Two hundred transcripts representing potential therapeutic targets were identified using the following criteria: significant overexpression in EAC by analysis of variance (p = 0.05, Benjamini Hochberg false discovery rate); 3-fold increase in EAC relative to normal and Barrett's esophagus and expression in at least 2 of the 3 EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor, for further validation based on its reported role in tumor cell survival and potential as a target for therapy. Fn14 protein expression was confirmed in SEG-1 and BIC-1 cell lines, but Fn14 was not found to affect tumor cell survival after exposure to chemotherapeutics as expected. Instead, a novel role in EAC was discovered in transwell assays, in which modulating Fn14 expression affected tumor cell invasion. Fn14's potential as a therapeutic target was further supported by immunohistochemistry on a tissue microarray of patient samples that showed that Fn14 protein expression increased with disease progression in EAC.
• Krupinski, E. A., Tillack, A. A., Richter, L., Henderson, J. T., Bhattacharyya, A. K., Scott, K. M., Graham, A. R., Descour, M. R., Davis, J. R., & Weinstein, R. S. (2006). Eye-movement study and human performance using telepathology virtual slides: implications for medical education and differences with experience. Human pathology, 37(12), 1543-56.
  More info

  A core skill in diagnostic pathology is light microscopy. Remarkably little is known about human factors that affect the proficiency of pathologists as light microscopists. The cognitive skills of pathologists have received relatively little attention in comparison with the large literature on human performance studies in radiology. One reason for this lack of formal visual search studies in pathology has been the physical restrictions imposed by the close positioning of a microscope operator's head to the microscope's eyepieces. This blocks access to the operator's eyes and precludes assessment of the microscopist's eye movements. Virtual slide microscopy now removes this barrier and opens the door for studies on human factors and visual search strategies in light microscopy. The aim of this study was to assess eye movements of medical students, pathology residents, and practicing pathologists examining virtual slides on a digital display monitor. Whole histopathology glass slide digital images, so-called virtual slides, of 20 consecutive breast core biopsy cases were used in a retrospective study. These high-quality virtual slides were produced with an array-microscope equipped DMetrix DX-40 ultrarapid virtual slide processor (DMetrix, Tucson, Ariz). Using an eye-tracking device, we demonstrated for the first time that when a virtual slide reader initially looks at a virtual slide his or her eyes are very quickly attracted to regions of interest (ROIs) within the slide and that these ROIs are likely to contain diagnostic information. In a matter of seconds, critical decisions are made on the selection of ROIs for further examination at higher magnification. We recorded: (1) the time virtual slide readers spent fixating on self-selected locations on the video monitor; (2) the characteristics of the ways the eyes jumped between fixation locations; and (3) x and y coordinates for each virtual slide marking the sites the virtual slide readers manually selected for zooming to higher ROI magnifications. We correlated the locations of the visually selected fixation locations and the manually selected ROIs. Viewing profiles were identified for each group. Fully trained pathologists spent significantly less time (mean, 4.471 seconds) scanning virtual slides when compared to pathology residents (mean, 7.148 seconds) or medical students (mean, 11.861 seconds), but had relatively prolonged saccadic eye movements (P < .0001). Saccadic eye movements are defined as eye movements between fixation locations. On the other hand, the pathologists spent significantly more time than trainees dwelling on the 3 locations they subsequently chose for zooming. Unlike either the medical students or the residents, the pathologists frequently choose areas for viewing at higher magnification outside of areas of foveal (central) vision. Eye movement studies of scanning pathways (scan paths) may be useful for developing eye movement profiles for individuals and for understanding the difference in performances between novices and experts. They may also be useful for developing new visual search strategies for rendering diagnoses on telepathology virtual slides.
• Erickson, R. P., Bhattacharyya, A., Hunter, R. J., Heidenreich, R. A., & Cherrington, N. J. (2005). Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet. American journal of physiology. Gastrointestinal and liver physiology, 289(2), G300-7.
  More info

  Cholestatic hepatitis is frequently found in Niemann-Pick C (NPC) disease. We studied the influence of diet and the low density lipoprotein receptor (LDLR, Ldlr in mice, known to be the source of most of the stored cholesterol) on liver disease in the mouse model of NPC. Npc1-/- mice of both sexes, with or without the Ldlr knockout, were fed a 18% fat, 1% cholesterol ("high-fat") diet and were evaluated by chemical and histological methods. Bile acid transporters [multidrug resistance protein (Mrps) 1-5; Ntcp, Bsep, and OatP1, 2, and 4] were quantitated by real-time RT-PCR. Many mice died prematurely (within 6 wk) with hepatomegaly. Histopathology showed an increase in macrophage and hepatocyte lipids independent of Ldlr genotype. Non-zone-dependent diffuse fibrosis was found in the surviving mice. Serum alanine aminotransferase was elevated in Npc1-/- mice on the regular diet and frequently became markedly elevated with the high-fat diet. Serum cholesterol was increased in the controls but not the Npc1-/- mice on the high-fat diet; it was massively increased in the Ldlr-/- mice. Esterified cholesterol was greatly increased by the high-fat diet, independent of Ldlr genotype. gamma-Glutamyltransferase was also elevated in Npc1-/- mice, more so on the high-fat diet. Mrps 1-5 were elevated in Npc1-/- liver and became more elevated with the high-fat diet; Ntcp, Bsep, and OatP2 were elevated in Npc1-/- liver and were suppressed by the high-fat diet. In conclusion, Npc1-/- mice on a high-fat diet provide an animal model of NPC cholestatic hepatitis and indicate a role for altered bile acid transport in its pathogenesis.
• El-Serag, H. B., Aguirre, T. V., Davis, S., Kuebeler, M., Bhattacharyya, A., & Sampliner, R. E. (2004). Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett's esophagus. The American journal of gastroenterology, 99(10), 1877-83.
  More info

  Esophageal acid exposure is important in the pathogenesis of Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and carcinoma. The aim of this study is to compare the development of dysplasia in BE patients treated with or without proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA).
• Mustacich, D., Wagner, A., Williams, R., Bair, W., Barbercheck, L., Stratton, S. P., Bhattacharyya, A. K., & Powis, G. (2004). Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse. Carcinogenesis, 25(10), 1983-9.
  More info

  Thioredoxin-1 is a low molecular weight redox protein that protects cells against oxidant damage. Thioredoxin-1 levels are increased in the epidermal layer of sun-damaged human skin. Thioredoxin-1 levels are also increased in several human primary tumors where its expression is associated with increased tumor cell proliferation, decreased apoptosis and aggressive tumor growth. We have investigated whether increased thioredoxin-1 levels in skin can lead to increased tumor formation using transgenic mice with mouse thioredoxin-1 expressed in keratinocytes under the control of the keratinocyte-14 (K14) promoter. Thioredoxin-1 protein expression was increased 2-fold in the keratinocyte layer of the transgenic mice. The skin was macroscopically and histologically normal but in the two-stage model of carcinogenesis using topical dimethylbenzanthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoting agent, there was a 6-fold increase in the number of papillomas per mouse and a 3-fold increase in papilloma size in the K14 thioredoxin-1 transgenic mice compared with non-transgenic littermates. Thus, increased thioredoxin-1 in keratinocytes acts as an enhancer of carcinogenesis in the DMBA/TPA two-stage model of skin carcinogenesis in mice.
• Weinstein, R. S., Descour, M. R., Liang, C., Barker, G., Scott, K. M., Richter, L., Krupinski, E. A., Bhattacharyya, A. K., Davis, J. R., Graham, A. R., Rennels, M., Russum, W. C., Goodall, J. F., Zhou, P., Olszak, A. G., Williams, B. H., Wyant, J. C., & Bartels, P. H. (2004). An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study. Human pathology, 35(11), 1303-14.
  More info

  This paper describes the design and fabrication of a novel array microscope for the first ultrarapid virtual slide processor (DMetrix DX-40 digital slide scanner). The array microscope optics consists of a stack of three 80-element 10 x 8-lenslet arrays, constituting a "lenslet array ensemble." The lenslet array ensemble is positioned over a glass slide. Uniquely shaped lenses in each of the lenslet arrays, arranged perpendicular to the glass slide constitute a single "miniaturized microscope." A high-pixel-density image sensor is attached to the top of the lenslet array ensemble. In operation, the lenslet array ensemble is transported by a motorized mechanism relative to the long axis of a glass slide. Each of the 80 miniaturized microscopes has a lateral field of view of 250 microns. The microscopes of each row of the array are offset from the microscopes in other rows. Scanning a glass slide with the array microscope produces seamless two-dimensional image data of the entire slide, that is, a virtual slide. The optical system has a numerical aperture of N.A.= 0.65, scans slides at a rate of 3 mm per second, and accrues up to 3,000 images per second from each of the 80 miniaturized microscopes. In the ultrarapid virtual slide processing cycle, the time for image acquisition takes 58 seconds for a 2.25 cm2 tissue section. An automatic slide loader enables the scanner to process up to 40 slides per hour without operator intervention. Slide scanning and image processing are done concurrently so that post-scan processing is eliminated. A virtual slide can be viewed over the Internet immediately after the scanning is complete. A validation study compared the diagnostic accuracy of pathologist case readers using array microscopy (with images viewed as virtual slides) and conventional light microscopy. Four senior pathologists diagnosed 30 breast surgical pathology cases each using both imaging modes, but on separate occasions. Of 120 case reads by array microscopy, there were 3 incorrect diagnoses, all of which were made on difficult cases with equivocal diagnoses by light microscopy. There was a strong correlation between array microscopy vs. "truth" diagnoses based on surgical pathology reports. The kappa statistic for the array microscopy vs. truth was 0.96, which is highly significant (z=10.33, p 0.05). Array microscopy and light microscopy did not differ significantly with respect to the number/percent of correct decisions rendered (t=0.552, p=0.6376) or equivocal decisions rendered (t=2.449, p=0.0917). Pathologists rated 95.8% of array microscopy virtual slide images as good or excellent. None were rated as poor. The mean viewing time for a DMetrix virtual slide was 1.16 minutes. The DMetrix virtual slide processor has been found to reduce the virtual slide processing cycle more than 10 fold, as compared with other virtual slide systems reported to date. The virtual slide images are of high quality and suitable for diagnostic pathology, second opinions, expert opinions, clinical trials, education, and research.
• Einspahr, J. G., Krouse, R. S., Yochim, J. M., Danenberg, P. V., Danenberg, K. D., Bhattacharyya, A. K., Martínez, M. E., & Alberts, D. S. (2003). Association between Cyclooxygenase expression and colorectal adenoma characteristics. Cancer research, 63(14), 3891-3.
  More info

  The cyclooxygenase (COX) pathway is important in colorectal carcinogenesis with the majority of cancers overexpressing COX-2; however, the role of COX-2 in the development of colorectal adenomas is less well defined. Accordingly, we analyzed 108 colorectal adenomas for COX-1 and COX-2 transcription in archival formalin-fixed, paraffin-embedded tissue using by real-time PCR and normalized to beta-actin. Neither COX-1 nor COX-2 mRNA expression differed with regard to age or gender of the subject. COX-2 mRNA expression was significantly higher in distal adenomas (2.2 +/- 1.9) compared with proximal (0.7 +/- 0.5) adenomas (P < 0.0001) and in larger (>/=7 mm) compared with smaller (
• Romagnolo, D. F., Chirnomas, R. B., Ku, J., Jeffy, B. D., Payne, C. M., Holubec, H., Ramsey, L., Bernstein, H., Bernstein, C., Kunke, K., Bhattacharyya, A., Warneke, J., & Garewal, H. (2003). Deoxycholate, an endogenous tumor promoter and DNA damaging agent, modulates BRCA-1 expression in apoptosis-sensitive epithelial cells: loss of BRCA-1 expression in colonic adenocarcinomas. Nutrition and cancer, 46(1), 82-92.
  More info

  Deoxycholate, a bile salt present at high levels in the colonic lumen of individuals on a high-fat diet, is a promoter of colon cancer. Deoxycholate also causes DNA damage. BRCA-1 functions in repair of DNA and in induction of apoptosis. We show that, when cultured cells of colonic origin are exposed to deoxycholate at different concentrations, BRCA-1 expression is induced at a low noncytotoxic concentration (10 microM) but is strongly inhibited at higher cytotoxic concentrations ( > or =100 microM). Indication of phosphorylation of BRCA-1 by deoxycholate (100 microM) at a lower dose was seen by Western blot analysis, whereas, at a higher dose, deoxycholate (200 and 300 microM) caused a complete loss of BRCA-1 expression. We show that BRCA-1 is substantially lower in colon adenocarcinomas from five patients compared with associated non-neoplastic colon tissue from the same patients, suggesting that the loss of BRCA-1 expression contributes to the malignant phenotype. In the non-neoplastic colon tissue, BRCA-1 was localized to the nongoblet cells. Our results imply that reduced expression of BRCA-1 may be associated with carcinoma of the colon.
• Maltzman, T., Knoll, K., Martinez, M. E., Byers, T., Stevens, B. R., Marshall, J. R., Reid, M. E., Einspahr, J., Hart, N., Bhattacharyya, A. K., Kramer, C. B., Sampliner, R., Alberts, D. S., & Ahnen, D. J. (2001). Ki-ras proto-oncogene mutations in sporadic colorectal adenomas: relationship to histologic and clinical characteristics. Gastroenterology, 121(2), 302-9.
  More info

  [corrected] The goal of this study was to examine the relationship between Ki-ras mutations in colorectal adenomas and characteristics of both the subject (age, gender, and family/personal history of colonic neoplasia) and the adenoma (multiplicity, size, location, and histologic features).
• Weinstein, R. S., Descour, M. R., Liang, C., Bhattacharyya, A. K., Graham, A. R., Davis, J. R., Scott, K. M., Richter, L., Krupinski, E. A., Szymus, J., Kayser, K., & Dunn, B. E. (2001). Telepathology overview: from concept to implementation. Human pathology, 32(12), 1283-99.
  More info

  Telepathology is the practice of pathology at a distance by using video imaging and telecommunications. Significant progress has been made in telepathology. To date, 12 classes of telepathology systems have been engineered. Rapid and ultrarapid virtual slide processors may further expand the range of telepathology applications. Next-generation digital imaging light microscopes, such as miniaturized microscope arrays (MMA), may make virtual slide processing a routine laboratory tool. Diagnostic accuracy of telepathology is comparable with that of conventional light microscopy for most diagnoses. Current telepathology applications include intraoperative frozen sections services, routine surgical pathology services, second opinions, and subspecialty consultations. Three telepathology practice models are discussed: the subspecialty practice (SSP) model; the case triage practice (CTP) model; and the virtual group practice (VGP) model. Human factors influence performance with telepathology. Experience with 500 telepathology cases from multiple organs significantly reduces the video viewing time per case (P < .01). Many technology innovations can be represented as S-curves. After long incubation periods, technology use and/or efficiency may accelerate. Telepathology appears to be following an S-curve for a technical innovation.
• Baines, A. T., Holubec, H., Basye, J. L., Thorne, P., Bhattacharyya, A. K., Spallholz, J., Shriver, B., Cui, H., Roe, D., Clark, L. C., Earnest, D. L., & Nelson, M. A. (2000). The effects of dietary selenomethionine on polyamines and azoxymethane-induced aberrant crypts. Cancer letters, 160(2), 193-8.
  More info

  We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.
• Morales, T. G., Camargo, E., Bhattacharyya, A., & Sampliner, R. E. (2000). Long-term follow-up of intestinal metaplasia of the gastric cardia. The American journal of gastroenterology, 95(7), 1677-80.
  More info

  Recent studies have found a relatively high prevalence of gastric cardia intestinal metaplasia in individuals presenting for elective upper endoscopy. It has been hypothesized that this lesion may be a precursor of gastric cardia cancer. Our objective was to identify the incidence of dysplasia in patients with gastric cardia intestinal metaplasia.
• Sharma, P., Bhattacharyya, A., Garewal, H. S., & Sampliner, R. E. (1999). Durability of new squamous epithelium after endoscopic reversal of Barrett's esophagus. Gastrointestinal endoscopy, 50(2), 159-64.
  More info

  Endoscopic reversal of Barrett's esophagus with multipolar electrocoagulation and high-dose omeprazole has been previously described but long-term results are not available. The aim of this study was to follow patients after endoscopic reversal and to perform a detailed analysis of the "new" squamous mucosa.
• Sharma, P., Jaffe, P. E., Bhattacharyya, A., & Sampliner, R. E. (1999). Laser and multipolar electrocoagulation ablation of early Barrett's adenocarcinoma: long-term follow-up. Gastrointestinal endoscopy, 49(4 Pt 1), 442-6.
  More info

  Endoscopic ablation of Barrett's esophagus, including associated dysplasia and adenocarcinoma, can be achieved by various techniques, but few long-term results are available. The aim of our study was ablation of intramucosal adenocarcinoma with a combination of Nd:YAG laser plus multipolar electrocoagulation.
• Sharma, P., Morales, T. G., Bhattacharyya, A., Garewal, H. S., & Sampliner, R. E. (1998). Squamous islands in Barrett's esophagus: what lies underneath?. The American journal of gastroenterology, 93(3), 332-5.
  More info

  Squamous islands are frequently visualized at the time of upper endoscopy in patients with Barrett's esophagus, especially those on proton pump inhibitor therapy (PPI). The significance of these islands is not clearly understood. The aim of this study was to systematically biopsy macroscopic squamous islands and to examine their histologic characteristics.
• Basu, A., Sanyal, S., Bhattacharyya, A., Bhattacharyya, S., & Dasgupta, S. (1997). A comparative study of silver binding nucleolar organiser regions (AgNORs) of breast lesions in histological sections and fine needle aspiration smears. Journal of the Indian Medical Association, 95(8), 443-7.
  More info

  The study presents a comparative profile of AgNOR dot counting in different types of breast lesions in histopathological (HP) sections and fine needle aspiration cytology (FNAC) smears. The breast lesions chosen were non-neoplastic lesion like fibroadenosis, benign neoplastic lesion like fibroadenoma and malignant neoplastic lesion like infiltrating duct carcinoma-grade 2. The AgNOR counts of non-neoplastic lesion were significantly less in number than the neoplastic lesions--both benign and malignant, in both the HP section and FNAC smear. But the counts did not show significant difference in the two neoplastic lesions eg, fibroadenoma and infiltrating duct carcinoma-grade 2, in both the HP section and FNAC smear. The appearance of the dots, as felt by the observers, were more discriminating between the three lesions, eg, uniform small compact centrally placed in fibroadenosis; mostly uniform small compact but occasional large irregular in fibroadenoma and large irregular marginally located in infiltrating duct carcinoma. Counting was easier and the appearance of the dots more easily discernible in FNAC smear than the HP section as the smear was monolayer and the malignant cells were easily detected from macrophages and stromal cells. But the tissue fluid or secretions or blood when present in the smear gave the smear a dirty background which was disturbing to the observers. Thus this AgNOR technique, when applied in HP section or FNAC smear, appears cost ineffective, lengthy and tedious procedure; did not offer absolute histochemical discriminant for malignancy from benignancy. But the shape and size distribution and appearance of the dots showing much variability in FNAC smear than the HP section, might be of some help in the diagnosis of malignancy and discriminating from benignancy.
• Bhattacheryya, A., Roy, M., Sanyal, S., Dasgupta, S., Basak, S. D., & Sinha, S. (1997). Study of myopathies by histological and histochemical methods with special reference to staining for desmin expression. Indian journal of pathology & microbiology, 40(3), 339-43.
  More info

  An attempt was made to study the histological and histochemical changes as well as immunohistochemical changes in desmin expression occurring in four types of clinical myopathies e.g. Chronic ischaemic myopathy due to Buerger's disease (Group I), Carcinomatous myopathy (Group II), Metabolic myopathy (Group III) and Muscular dystrophy (Group IV). The number of cases studied were 16 cases, 15 cases, 4 cases and 5 cases respectively. The study revealed: (i) a combination of normal, degenerated, necrotic and regenerating fibres in different proportions in all the four groups having maximum number of degenerated fibres in Group I and Group IV, relatively more number of regenerating fibres in groups III and absence of necrotic fibres in Group I. (ii) Altered tinctorial property in most of the fibres indicating degenerated and regenerating fibres in all the groups with Masson's trichrome staining against inconstant staining with PTAH appear to be a good indicator for myopathy. (iii) The Desmin expression was week and irregular in most of the cases with most of the fibres probably due to reduction of desmin content probably indicating degenerated fibres, appear to be a good indicator for myopathy. (iv) Chronic ischaemic myopathy showed close resemblance with muscular dystrophy though no typical or distinct distinguishing feature could be identified in these four groups.
• Halliday, B. E., Bhattacharyya, A. K., Graham, A. R., Davis, J. R., Leavitt, S. A., Nagle, R. B., McLaughlin, W. J., Rivas, R. A., Martinez, R., Krupinski, E. A., & Weinstein, R. S. (1997). Diagnostic accuracy of an international static-imaging telepathology consultation service. Human pathology, 28(1), 17-21.
  More info

  Static-image and dynamic- (real-time) image telepathology are competing technologies. Although some studies suggest that the diagnostic accuracy of the dynamic-image telepathology approaches the accuracy of light microscopy, few reports have documented the diagnostic accuracy of static-image telepathology as used in the setting of an actual surgical pathology consultation practice. We report the results of an analysis of 171 telepathology consultation cases submitted to the Arizona-International Telemedicine Network (AITN). Digital images were submitted by pathologists from six participating institutions in Arizona, Mexico, and China. Telepathologists could render a telepathology diagnosis (TP) or defer rendering a diagnosis to obtain additional video images, glass slides for detailed analysis, or to obtain tissue blocks for special studies such as immunohistochemistry. The telepathologists rendered diagnoses for 144 cases and deferred 27 cases. Two pathologists retrospectively evaluated-glass slides from each case and rendered a consensus glass slide (GS) "truth" diagnosis. There was 88.2% concordance between TP and GS diagnoses (127 of 144 diagnoses). Concordance of 96.5% was achieved for clinically important diagnoses (139 of 144 diagnoses). Telepathologists deferred making a diagnosis to obtain glass slides for conventional light microscopy in 14 cases (8.1%) and for results of immunohistochemistry studies in 13 cases (7.6%). Thus, correct diagnoses were rendered by static-image telepathology in 127 of 171 cases (74.3%) at the time of telepathology diagnostic sessions. Inappropriate field selection and sampling biases of referring pathologists, as well as a tendency of static-image telepathologists to underestimate the complexity of some cases, may reduce the value of consultations based on the viewing of static images.
• Morales, T. G., Bhattacharyya, A., Johnson, C., & Sampliner, R. E. (1997). Is Barrett's esophagus associated with intestinal metaplasia of the gastric cardia?. The American journal of gastroenterology, 92(10), 1818-22.
  More info

  Barrett's esophagus has been associated with adenocarcinoma of the esophagogastric junction and gastric cardia. The purpose of this study was to determine whether patients with Barrett's esophagus have a higher prevalence of intestinal metaplasia involving the gastric cardia than those without Barrett's esophagus.
• Morales, T. G., Sampliner, R. E., & Bhattacharyya, A. (1997). Intestinal metaplasia of the gastric cardia. The American journal of gastroenterology, 92(3), 414-8.
  More info

  Although the incidence of gastric adenocarcinoma in the U. S. is declining, the incidence of cancer localized to the gastric cardia has risen dramatically. It is not yet clear whether cancer of the gastric cardia arises from a premalignant lesion such as intestinal metaplasia (IM). The purpose of this study was to determine the prevalence of IM involving the cardia in patients presenting for elective EGD, and evaluate potential associated factors.
• Sharma, P., Morales, T. G., Bhattacharyya, A., Garewal, H. S., & Sampliner, R. E. (1997). Dysplasia in short-segment Barrett's esophagus: a prospective 3-year follow-up. The American journal of gastroenterology, 92(11), 2012-6.
  More info

  Short segments of intestinal metaplasia in the distal esophagus are being recognized with increasing frequency. Both long and short segments of Barrett's esophagus can progress to dysplasia and cancer. However, the risk of short-segment Barrett's esophagus (SSBE) for the development of dysplasia and adenocarcinoma of the esophagus is not yet known. Our purpose, therefore, was to determine the frequency with which dysplasia occurs in patients with SSBE.
• Weinstein, R. S., Bhattacharyya, A. K., Graham, A. R., & Davis, J. R. (1997). Telepathology: a ten-year progress report. Human pathology, 28(1), 1-7.
• Bhattacharyya, A. K., Davis, J. R., Halliday, B. E., Graham, A. R., Leavitt, S. A., Martinez, R., Rivas, R. A., & Weinstein, R. S. (1995). Case triage model for the practice of telepathology. Telemedicine journal : the official journal of the American Telemedicine Association, 1(1), 9-17.
  More info

  To implement and evaluate a practice model for telepathology.
• Morales, T. G., Sampliner, R. E., Bhattacharyya, A., & Alter, M. J. (1995). Liver histology in anti-HCV-positive persons with normal or minimally elevated aminotransferases. Journal of clinical gastroenterology, 21(4), 301-5.
  More info

  The significance of a positive hepatitis C virus (HCV) screening test in asymptomatic blood donors with normal or near normal aminotransferases was studied along with the usefulness of HCV RNA polymerase chain reaction (PCR) testing for predicting chronic hepatitis in these individuals. One hundred and thirty-nine volunteer blood donors who were found positive by second generation ELISA for antibodies to HCV agreed to participate in the study. Thirty-one of them were supplemental test positive, had ALT values less than twice normal, and were followed over a minimum of 12 months. Thirteen consented to percutaneous liver biopsy and also had HCV RNA determination by PCR. Ten of the 13 subjects were positive for HCV RNA by PCR. Of the nine who were positive for HCV RNA and had adequate tissue for evaluation, seven had evidence of chronic hepatitis, three with limiting plate necrosis. Lobular inflammation was similar in severity to that found in the portal region. In addition, two had periportal fibrosis, and one had bridging fibrosis. Of the three subjects who were negative for HCV RNA, only one had portal inflammation which was limited to the portal region. None of these three had lobular changes, or periportal or bridging fibrosis. Of the three normal biopsies, two were from subjects who were negative for HCV RNA. The sensitivity and specificity of HCV RNA testing for chronic hepatitis was 87.5% and 50%, respectively, yielding an overall accuracy of 75%. We conclude that asymptomatic blood donors with antibodies to HCV, normal or mildly elevated liver tests, and HCV RNA may have abnormal liver histology indicating the potential for progressive liver disease. HCV RNA testing by PCR may be clinically useful as a noninvasive means to discriminate between those with and without chronic liver disease.
• Roy, M., Bhattacharyya, A., Sanyal, S., & Dasgupta, S. (1995). Study of benign superficial cysts by fine needle aspiration cytology. Journal of the Indian Medical Association, 93(1), 8-9, 13.
  More info

  Fine needle aspiration cytology of 213 cases of different cystic lesions from various regions of body and different superficial organs was analysed in an attempt to present the experience of the authors in the diagnosis of such lesions. The predominant lesion diagnosed by fine needle aspiration cytology was adnexal cyst/sebaceous cyst (41 cases) followed by vascular hamartoma (40 cases) and thyroglossal cyst (9 cases). One hundred fifty-eight (74.2%) out 213 cases were confirmed histopathologically. There was false negative diagnosis in 14 cases (6.6%). The remaining 41 (19.2%) cases did not turn up for further treatment. The fallacies that have been recorded in the diagnosis of thyroid cysts, salivary gland cysts and breast cysts in respect of papillary cystic thyroid carcinoma, muco-epidermoid carcinoma of salivary gland and intraductal carcinoma with fibrocystic disease of breast respectively have been highlighted in the present study.
• Roy, M., Bhattacharyya, A., Sanyal, S., Roy, A., & Dasgupta, S. (1995). Fine needle aspiration cytology of bone and joint lesions: an assessment. Journal of the Indian Medical Association, 93(7), 259-61.
  More info

  Fine needle aspiration cytology and subsequent correlation with histology and therapeutic follow-up was done in 198 cases of bone and joint lesions. Overall accuracy was found to be 87.34%; false diagnosis was recorded in 4.5% of cases; 8.08% cases were excluded from correlation as they did not turn up for further treatment or follow-up after the diagnosis. False diagnosis was encountered mostly with inflammatory lesions and primary neoplasms, diagnosing osteosarcoma and Ewing's sarcoma as chronic inflammatory lesion, chondroma as chondrosarcoma and vice versa. The possible cause of default has been discussed. The benign cystic lesions could be diagnosed with almost 100% accuracy by fine needle aspiration cytology where 10% cases were excluded as they could not be followed up.
• Weinstein, R. S., Bhattacharyya, A., Yu, Y. P., Davis, J. R., Byers, J. M., Graham, A. R., & Martinez, R. (1995). Pathology consultation services via the Arizona-International Telemedicine Network. Archives d'anatomie et de cytologie pathologiques, 43(4), 219-26.
  More info

  The Arizona-International Telemedicine Network (AITN) links 4 cities in Arizona and two international sites in China and Mexico, into a telepathology diagnostic network. Established in 1993, the Network provides second opinions on surgical pathology and cytopathology cases. Workstations are 486 PC-based computers. Static images (1024 x 774 x 8 pixels) are grabbed with a variable resolution video camera and sent by 14,400 bit per second modems over ordinary telephone lines. Second opinions are either rendered directly by a general telepathologist or triaged to a specialist. Experience with the first 37 cases indicates a high level of success in providing useful information to referring pathologists over the Network.
• Earnest, D. L., Holubec, H., Wali, R. K., Jolley, C. S., Bissonette, M., Bhattacharyya, A. K., Roy, H., Khare, S., & Brasitus, T. A. (1994). Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer research, 54(19), 5071-4.
  More info

  The present studies were conducted at the Universities of Chicago and Arizona to examine and compare the effects of supplemental dietary ursodeoxycholic acid to cholic acid, a known tumor promoter, and to piroxicam, a known chemopreventive agent, in the azoxymethane (AOM) model of experimental colonic carcinogenesis. Male Fischer 344 rats were utilized in these experiments. All animals were fed a basal diet (AIN-76) supplemented with 0.2% or 0.4% cholic acid, 0.2% or 0.4% ursodeoxycholic acid, 0.2% ursodeoxycholic acid plus 0.2% cholic acid, or 75 ppm piroxicam. Rats were given s.c. injections once a week for 2 weeks with AOM (15 mg/kg body wt/week) or vehicle (saline) after being fed their respective diets for 2 weeks. The rats in each group were then maintained on their respective diets for approximately 28 weeks; after sacrifice, their colons were removed and examined macroscopically and microscopically for the presence of tumors. The results of these studies demonstrated that none of the control rats fed the various diets injected with AOM-vehicle developed tumors. In groups receiving AOM, the addition of cholic acid (0.4%) caused a significant increase in the incidence of tumors. In contrast, the addition of 0.2% ursodeoxycholic acid did not promote AOM-induced colonic tumors, and when it was added to a promoting dose of cholic acid (0.2%), 0.2% ursodeoxycholic acid prevented enhancement of tumor promotion. At higher doses (0.4%), supplemental dietary ursodeoxycholic acid significantly reduced the incidence of colon tumors and cancers. Moreover, the tumor suppressive effects of 0.4% ursodeoxycholic acid exceeded that of dietary piroxicam. Our results further emphasize the important role of bile salts in modulating colonic tumor development. These studies also demonstrate for the first time that supplemental dietary ursodeoxycholic acid is a chemopreventive agent in the AOM model of experimental colonic carcinogenesis.
• Thompson, F., Emerson, J., Dalton, W., Yang, J. M., McGee, D., Villar, H., Knox, S., Massey, K., Weinstein, R., & Bhattacharyya, A. (1993). Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease. Genes, chromosomes & cancer, 7(4), 185-93.
  More info

  Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were -17 and -19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes I (10/18-56%) and 6 (8/18-44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11-13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p.
• Foster, P. F., Bhattacharyya, A., Sankary, H. N., Coleman, J., Ashmann, M., & Williams, J. W. (1991). Eosinophil cationic protein's role in human hepatic allograft rejection. Hepatology (Baltimore, Md.), 13(6), 1117-25.
  More info

  Although it is known that eosinophils consistently infiltrate rejecting human liver allografts, their function is unknown. Infiltrating eosinophils can release a cytotoxic substance, eosinophil cationic protein. Furthermore, eosinophil cationic protein may be identified in biopsy specimens using immunoperoxidase staining of an eosinophil cationic protein-specific monoclonal antibody. To study a possible effector role of eosinophils in rejecting liver allografts, 38 serial allograft biopsy specimens from 12 patients with acute rejection, 54 biopsy specimens from 11 patients with allograft dysfunction caused by other causes and 22 biopsy specimens from 8 patients without allograft dysfunction were stained for extracellular eosinophil cationic protein. In addition, the absolute blood eosinophil counts and the portal tract eosinophil percent of the total number of portal tract inflammatory cells were tabulated in these patients until 30 days after transplantation. The blood absolute eosinophil count, portal tract eosinophil percent and incidence of positive extracellular eosinophil cationic protein staining were significantly increased in patients with rejection compared with patients with dysfunction from other causes (p less than 0.05 to 0.005, t test). Furthermore, each of these parameters predicted rejection with excellent sensitivity (75% to 92%) and specificity (91% to 100%). Of patients with rejection, 59% had significant elevation of all three parameters before or during rejection, and 92% had at least two parameters elevated. Conversely, of the patients with dysfunction from other causes, 0% had elevations of any parameter. The recognized cytotoxic properties of eosinophil cationic protein and its almost exclusive presence, along with eosinophils in the blood and allograft biopsy specimens of patients during acute rejection, support the role of the eosinophil as an effector cell in tissue injury during acute liver allograft rejection.
• Foster, P. F., Sankary, H. N., Williams, J. W., Bhattacharyya, A., Coleman, J., & Ashmann, M. (1991). Morphometric inflammatory cell analysis of human liver allograft biopsies. Transplantation, 51(4), 873-6.
  More info

  To quantitate the inflammatory cell response within the portal tracts of liver allografts during acute rejection, we retrospectively and in a blinded fashion reviewed 431 biweekly, protocol, core allograft biopsies in 58 consecutive adult recipients. Following the determination of the cross-sectional area of each portal tract, the number of eosinophils, neutrophils, and lymphocytes therein was tabulated. The average number, percentage, and density of each type of portal inflammatory cell were calculated for each biopsy. Each biopsy was prospectively and independently classified as either associated (REJ+) or not associated (REJ-) with acute rejection. Acute rejection consisted of simultaneous allograft dysfunction and qualitative pathologic findings of acute rejection. Biopsies obtained during periods of normal allograft function or during episodes of dysfunction due to other causes were classified as not associated with rejection (REJ-). Ninety biopsies were classified as associated with acute rejection (REJ+) while 241 biopsies were classified as not associated with acute rejection (REJ-). In general, the average portal-tract number, percentage, and density of all inflammatory cells were significantly increased in biopsies associated with acute rejection. In contrast, only the portal-tract eosinophil values were consistently predictive of acute rejection following receiver-operating characteristic curve analysis (sensitivity = 82-86%, specificity = 91-92%). This quantitative method of allograft assessment appears to improve the objectivity of the serial biopsy protocol. By using this method, we found the eosinophil's appearance within the portal tracts to be a dependable indicator of acute rejection.
• Koukoulis, G. K., Gould, V. E., Bhattacharyya, A., Gould, J. E., Howeedy, A. A., & Virtanen, I. (1991). Tenascin in normal, reactive, hyperplastic, and neoplastic tissues: biologic and pathologic implications. Human pathology, 22(7), 636-43.
• Sankary, H., Foster, P., Novich, K., Ashmann, M., Bhattacharyya, A., Coleman, J., & Williams, J. (1991). Quantitative analysis of portal tract infiltrate allows for accurate determination of hepatic allograft rejection. American journal of surgery, 161(1), 131-4; discussion 134-5.
  More info

  Changes in the qualitative character of the portal tract infiltrate of hepatic allografts can influence the diagnosis of acute rejection. Since qualitative data rely on subjective findings, the aim of this study was to perform a quantitative analysis of portal tract infiltrates to improve the accuracy of the diagnosis of acute rejection. A total of 431 serial hepatic biopsies in 58 consecutive adult patients were obtained. The average number of eosinophils, neutrophils, and lymphocytes in each portal tract were counted. The area of each portal tract was determined using an optical micrometer. Rejection was confirmed by an independent investigator using both clinical and histologic criteria. Using a backward stepwise logistic regression analysis, we found that eosinophils were the only variable predictive of rejection. Using this model, the probability of having rejection on a single biopsy can be determined with greater than 90% accuracy.

Presentations

• Abrams, A., Jie, T., Ong, E., Heimark, R. L., Bhattacharyya, A. K., & Patel, C. (2013, Feb/Spring). Characterization of Pancreatic Adenocarcinoma of Primary and Peritoneal Metastasis a Pilot Study Using Biomarkers for Metastasis (EMT). 2013 Americas Hepato-Pancreato-Biliary Association Meeting. Miami, FL.

Case Studies

• Das, T., Gupta, P., Bommaya, N., Roy, A. K., Basu, A., Bhattacharya, S., Sanyal, S., & Dasgupta, S. (1996. A case of splenic cyst(p. 321).
• Wolf, B. C., Khettry, U., Leonardi, H. K., Neptune, W. B., Bhattacharyya, A. K., & Legg, M. A. (1988. Benign lesions mimicking malignant tumors of the esophagus(pp 148-54).
  More info

  Three cases of benign lesions which mimicked malignant tumors of the esophagus are described. In all three cases, two inflammatory pseudotumors and one case of diffuse leiomyomatosis, the clinical presentations, radiologic features, and gross pathologic findings led to the mistaken diagnosis of carcinoma at thoracotomy. The benign nature of the processes was recognizable only on microscopic examination. Although most benign tumors of the esophagus are localized solitary lesions that are easily distinguished from carcinoma, occasionally benign conditions may present as infiltrative, ulcerated mass lesions. Inflammatory pseudotumor and diffuse leiomyomatosis should be included in the differential diagnosis of esophageal malignancies.
• Bhattacharyya, A. K., & Balogh, K. (1985. Retroperitoneal lymphangioleiomyomatosis. A 36-year benign course in a postmenopausal woman(pp 1144-6).
  More info

  An 89-year-old asymptomatic white woman was found to have a pelvic mass with retroperitoneal extension. Biopsy of the lesion demonstrated lymphangioleiomyomatosis. Review of her records revealed that 36 years ago a mass in the same location had been found incidentally and biopsy was performed during abdominoperineal resection for rectal carcinoma. Comparison of the old and recent biopsy specimens showed an identical histologic appearance. This case, therefore, represents a benign, localized form of lymphangioleiomyomatosis; the long survival without therapy may be related to the fact that this patient was postmenopausal.

Others

• Thompson, P., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Hamilton, S. R., Bhattacharyya, A., Green, S., Hsu, C., Chow, H. S., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Martinez, M. E., Jacobs, E., Ashbeck, E. L., Alberts, D. S., & Lance, P. (2012). Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention. Cancer prevention research (Philadelphia, Pa.).
  More info

  COX inhibitors reduce colorectal adenoma recurrence by up to 45% and selenium supplementation may prevent colorectal cancer. Following colonoscopic adenoma resection, 1,600 men and women, ages 40 to 80 years, were randomized to celecoxib (400 mg daily), a selective COX-2 inhibitor, and/or selenium (200 μg daily as selenized yeast), or double placebo. The trial was initiated in November 2001. The primary trial endpoint is adenoma recurrence in each intervention group compared with placebo, as determined by surveillance colonoscopy conducted three to five years after baseline. Randomization was stratified by use of low-dose aspirin (81 mg) and clinic site. Following reports of cardiovascular toxicity associated with COX-2 inhibitors, the celecoxib arm was discontinued in December 2004 when 824 participants had been randomized. Accrual continued with randomization to selenium alone or placebo. Randomization of the originally planned cohort (n = 1,621) was completed in November 2008. A further 200 patients with one or more advanced adenomas (denoting increased risk for colorectal cancer) were accrued to enhance statistical power for determining intervention efficacy in this higher-risk subgroup. Accrual of the total cohort (n = 1,824) was completed in January 2011. Baseline cohort characteristics include: mean age 62.9 years; 65% male; body mass index (BMI) 29.1 ± 5.1; 47% taking low-dose aspirin while on trial; 20% with three or more adenomas; and 38% with advanced adenomas. Intervention effects on adenoma recurrence will be determined, and their modification by genetic background and baseline selenium level. The effect of selenium supplementation on risk for type II diabetes will also be reported.
• Payne, C. M., Holubec, H., Bhattacharyya, A. K., Bernstein, C., & Bernstein, H. (2010). Exposure of mouse colon to dietary bile acid supplement induces sessile adenomas. Inflammatory bowel diseases.
• Einspahr, J. G., Martinez, M. E., Jiang, R., Hsu, C., Rashid, A., Bhattacharrya, A. K., Ahnen, D. J., Jacobs, E. T., Houlihan, P. S., Webb, C. R., Alberts, D. S., & Hamilton, S. R. (2006). Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
  More info

  In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is associated with late progression to carcinoma. We evaluated the relationship of demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene product overexpression in 1,093 baseline sporadic colorectal adenomas from 926 individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation was found in 14.7% of individuals and p53 overexpression was found in 7.0% of those tested. Multivariate analysis found older age, rectal location, and villous histology to be independently associated with Ki-ras mutation. Individuals with an advanced adenoma (>or=1 cm or high-grade dysplasia or villous histology) had a 4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95% confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G-to-A transition type were more frequent in older individuals, whereas G-to-T transversion was more frequent in rectal adenomas than in the colon. Multivariate analysis showed that previous history of a polyp (P = 0.03) was inversely associated with p53 overexpression. Large adenoma size (>or=1 cm), high-grade dysplasia, and villous histology were independently associated with p53 overexpression, with the strongest association for advanced adenomas (OR, 7.20; 95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P
• Alberts, D. S., Martínez, M. E., Hess, L. M., Einspahr, J. G., Green, S. B., Bhattacharyya, A. K., Guillen, J., Krutzsch, M., Batta, A. K., Salen, G., Fales, L., Koonce, K., Parish, D., Clouser, M., Roe, D., Lance, P., & , P. a. (2005). Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. Journal of the National Cancer Institute.
  More info

  Ursodeoxycholic acid (UDCA) treatment is associated with a reduced incidence of colonic neoplasia in preclinical models and in patients with conditions associated with an increased risk for colon cancer. We conducted a phase III, double-blind placebo-controlled trial of UDCA to evaluate its ability to prevent colorectal adenoma recurrence.
• Sharma, P., Weston, A. P., Topalovski, M., Cherian, R., Bhattacharyya, A., & Sampliner, R. E. (2003). Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus. Gut.
  More info

  The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett's mucosa would be helpful.
• Martínez, M. E., Sampliner, R., Marshall, J. R., Bhattacharyya, A. K., Reid, M. E., & Alberts, D. S. (2001). Adenoma characteristics as risk factors for recurrence of advanced adenomas. Gastroenterology.
  More info

  The link between adenoma characteristics at baseline colonoscopy and adenoma recurrence is poorly understood. We assessed whether the number, size, location, or histology of resected adenomas was related to the probability of recurrence of advanced lesions.
• Alberts, D. S., Martínez, M. E., Roe, D. J., Guillén-Rodríguez, J. M., Marshall, J. R., van Leeuwen, J. B., Reid, M. E., Ritenbaugh, C., Vargas, P. A., Bhattacharyya, A. B., Earnest, D. L., & Sampliner, R. E. (2000). Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. The New England journal of medicine.
  More info

  The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas.
• Roy, M., Bhattacharyya, A., Dasgupta, S., & Sanyal, S. (1994). Fallacies of the fine needle aspiration cytology of surgical lesions of liver. Journal of the Indian Medical Association.
  More info

  Seventy-six cases of surgical hepatomegaly were subjected to fine needle aspiration cytology (FNAC) for initial diagnosis. Primary malignancies, as suspected clinically with adjunction of other investigative procedures, were 29 cases of whom 25 were confirmed by biopsy or therapy. Secondary deposits in liver were 27 of whom 15 were confirmed by therapy. Inflammatory lesions were 9 of whom 6 were confirmed by therapeutic response with specific therapy. Benign lesions were 10 of whom 5 were confirmed by surgery. Diagnosis of malignancies of liver is rather easier than that of benign lesions like hydatid cysts of liver which were Casoni's test negative; and hepatocellular adenoma, as the aspirate in the former is clear fluid and that of the latter is only normal looking liver cells. Thus, in respect of benign lesions of liver, FNAC diagnosis may be clinched after due consideration to the clinical findings, radiological and ultrasonographic findings and ultimately confirmed by exploration. Thus the fallacy lies in aspiration of normal looking liver cells whereby the histology may prove it to be hepatocellular adenoma, well differentiated hepatocellular carcinoma and secondary deposits where the exact site has not been hit. Ultrasonogram (USG) guidance helps in these cases where the same facility is available. This fallacy can again be avoided, where USG guidance is not available, by imparting due importance to clinical findings, USG findings and also by repeat smear.