Hemanth Gavini
University of Arizona
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Gastroenterology | 2011
Sachin Wani; Gary W. Falk; Jane Post; Lisa Yerian; Matthew Hall; Amy Wang; Neil Gupta; Srinivas Gaddam; Mandeep Singh; Vikas Singh; Keng–Yu Chuang; Vikram Boolchand; Hemanth Gavini; John Kuczynski; Priti Sud; Ajay Bansal; Amit Rastogi; Sharad C. Mathur; Patrick Young; Brooks D. Cash; John R. Goldblum; David A. Lieberman; Richard E. Sampliner; Prateek Sharma
BACKGROUND & AIMS Data vary on the progression of low-grade dysplasia (LGD) in patients with Barretts esophagus (BE); in patients with LGD, we investigated the incidence of high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) and compared progression in patients with different forms of LGD (prevalent vs incident and multifocal vs unifocal). We assessed the effects of consensus diagnosis of LGD on progression rates to HGD and EAC among expert pathologists. METHODS In a multicenter outcomes project, 210 patients with BE and LGD (classified as incident, prevalent, or persistent) were included. Patients were followed up for an average of 6.2 years (959.6 patient-years). Persistent LGD was defined as detection of LGD on ≥2 consecutive occasions during the follow-up period and extent as either unifocal (LGD at one level of BE segment) or multifocal (>1 level). Histology specimens were reviewed by 2 blinded pathologists. RESULTS Six patients developed EAC (incidence of 0.44%/year), and 21 developed HGD (incidence of 1.6%/year). The incidence of the combination of HGD and EAC was 1.83%/year. There were no associations between presence of prevalent, incident, or persistent LGD and the extent of LGD with progression rates. Based on consensus diagnosis of 88 reviewed specimens, there was no difference in the progression of LGD to either EAC (the incidence based on analyses by the local pathologist was 0.18%/year, the incidence when there was agreement between the local and one central pathologist was 0.21%/year, and the incidence when all 3 pathologists were in agreement was 0.39%/year) or combined HGD and EAC (0.94%/year, 0.87%/year, and 0.84%/year, respectively). CONCLUSIONS Overall, patients with BE and LGD have a low annual incidence of EAC, similar to nondysplastic BE. There are no risk factors for progression and there is significant interobserver variation in diagnosis, even among expert pathologists.
Clinical Gastroenterology and Hepatology | 2011
Sachin Wani; Gary W. Falk; Matthew Hall; Srinivas Gaddam; Amy Wang; Neil Gupta; Mandeep Singh; Vikas Singh; Keng–Yu Chuang; Vikram Boolchand; Hemanth Gavini; John Kuczynski; Priti Sud; Savio Reddymasu; Ajay Bansal; Amit Rastogi; Sharad C. Mathur; Patrick Young; Brooks D. Cash; David A. Lieberman; Richard E. Sampliner; Prateek Sharma
BACKGROUND & AIMS The risks of dysplasia and esophageal adenocarcinoma (EAC) are not clear for patients with nondysplastic Barretts esophagus (NDBE); the rate of progression has been overestimated in previous studies. We studied the incidences of dysplasia and EAC and investigated factors associated with progression of BE. METHODS The BE study is a multicenter outcomes project of a large cohort of patients with BE. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Patients followed up for at least 1 year after the index endoscopy examination were included, whereas those diagnosed with dysplasia and EAC within 1 year of diagnosis with BE (prevalent cases) were excluded. Of 3334 patients with BE, 1204 met the inclusion criteria (93.7% Caucasian; 88% male; mean age, 59.3 y) and were followed up for a mean of 5.52 years (6644.5 patient-years). RESULTS Eighteen patients developed EAC (incidence, 0.27%/y; 95% confidence interval [CI], 0.17-0.43) and 32 developed HGD (incidence, 0.48%/y; 95% CI, 0.34-0.68). The incidence of HGD and EAC was 0.63%/y (95% CI, 0.47-0.86). There were 217 cases of low-grade dysplasia (incidence, 3.6%/y; 95% CI, 3.2-4.1). Five and 10 years after diagnosis, 98.6% (n = 540) and 97.1% (n = 155) of patients with NDBE were cancer free, respectively. The length of the BE was associated significantly with progression (EAC <6 cm, 0.09%/y vs EAC ≥ 6 cm, 0.65%/y; P = 0.001). CONCLUSIONS There is a lower incidence of dysplasia and EAC among patients with NDBE than previously reported. Because most patients are cancer free after a long-term follow-up period, surveillance intervals might be lengthened, especially for patients with shorter segments of BE.
Journal of Biomedical Optics | 2013
Timothy Renkoski; Bhaskar Banerjee; Logan R. Graves; Nathaniel S. Rial; Sirandon Ah Reid; Vassiliki L. Tsikitis; Valentine N. Nfonsam; Piyush Tiwari; Hemanth Gavini; Urs Utzinger
Abstract. The accepted screening technique for colon cancer is white light endoscopy. While most abnormal growths (lesions) are detected by this method, a significant number are missed during colonoscopy, potentially resulting in advanced disease. Missed lesions are often flat and inconspicuous in color. A prototype ultraviolet spectral imager measuring autofluorescence (AF) and reflectance has been developed and applied in a study of 21 fresh human colon surgical specimens. Six excitation wavelengths from 280 to 440 nm and formulaic ratio imaging were utilized to increase lesion contrast and cause neoplasms to appear bright compared to normal tissue. It was found that in the subset of lesions which were most difficult to visualize in standard color photographs [low contrast lesions, (LCLs)] a ratio image (F340/F440) of AF images excited at 340 and 440 nm produced extraordinary images and was effective in about 70% of these difficult cases. Contrast may be due to increased levels of reduced nicotinamide adenine dinucleotide, increased hemoglobin absorption, and reduced signal from submucosal collagen. A second successful ratio image (R480/R555) combined two reflectance images to produce exceptional images especially in particular LCLs where F340/F440 was ineffective. The newly discovered ratio images can potentially improve detection rate in screening with a novel AF colonoscope.
Gastroenterology | 2010
Srinivas Gaddam; Patrick E. Young; Amy Wang; Ajay Bansal; Neil Gupta; Sachin Wani; Mandeep Singh; Vikas Singh; Keng-Yu Chuang; Vikram Boolchand; Hemanth Gavini; Priti Sud; John Kuczynski; April D. Higbee; Amit Rastogi; Sharad C. Mathur; Brooks D. Cash; Gary W. Falk; Richard E. Sampliner; Prateek Sharma
Predicting High-Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients With Non-Dysplastic Barretts Esophagus (BE): Results From a Large, Multicenter Cohort Study Srinivas Gaddam, Patrick E. Young, Amy Wang, Ajay Bansal, Neil Gupta, Sachin B. Wani, Mandeep Singh, Vikas Singh, Keng-Yu Chuang, Vikram Boolchand, Hemanth Gavini, Priti Sud, John Kuczynski, April D. Higbee, Amit Rastogi, Sharad C. Mathur, Brooks D. Cash, Gary W. Falk, Richard E. Sampliner, Prateek Sharma
Gastroenterology | 2010
Sachin Wani; Gary W. Falk; Matthew Hall; Amy Wang; Neil Gupta; Mandeep Singh; Srinivas Gaddam; Vikas Singh; Keng-Yu Chuang; Vikram Boolchand; Hemanth Gavini; John Kuczynski; Priti Sud; Savio Reddymasu; Ajay Bansal; Amit Rastogi; Sharad C. Mathur; Patrick E. Young; Brooks D. Cash; David A. Lieberman; Richard E. Sampliner; Prateek Sharma
Background: Pregnancy-related gastroesophageal reflux (GERD) is a common condition, afflicting 40-85% of all expectant women. Thus, PPI have been prescribed to an increasing number of pregnant women for GERD1. However, the safety of PPI therapy in pregnancy is unclear; while previous observational studies failed to find a significant association between maternal PPI use and birth defects, all were under-powered or uncontrolled. Nevertheless, the proportion of cardiac defects observed in PPI-exposed pregnancies was unusually high in the two largest studies2,3. Hence, we conducted a large population-based study to determine if PPI exposure in utero is associated with increased risk for cardiac birth defects in newborns. Methods: Data from the The Health Improvement Network (THIN) database, a UK general practitioner (GP) electronic medical record system (2000-2008), were used to identify 208,951 pregnancies in which babies could be clearly linked to mothers who were followed by a GP for at least 1y prior to delivery. Within this source cohort, we then performed a nested case-control analysis in which all babies with a coded diagnosis for cardiac birth defect were identified. Up to 10 controls were identified per case matching for maternal age, GP location, delivery site, date of birth, and sex. Odds ratios (OR) for cardiac birth defects were calculated based on PPI exposure during the pregnancy. Conditional logistic regression was performed to adjust for potential confounders including BMI, cardiac malformation in the mother, smoking status, number of pregnancy GP visits, alcohol use, and use of medications associated with cardiac defects in published reports. To confirm the specificity of our analysis, case-control analyses were performed to determine if PPI exposure were associatedwith defects in other organ systems.Results: 2,445 cases of cardiac malformations and 19,530 matched controls were identified. Maternal PPI use during pregnancy was associated with a significant increase in cardiac birth defects (OR=2.08 (95% CI: 1.33, 3.25; p<0.001); adjusted OR=2.14 (1.37, 3.35; p<0.001)). Further, PPI use was not associated with birth defects in other organ systems. Conclusions: In this large population-based cohort, PPI exposure in utero was associated with a significant increase in the risk for cardiac birth defects. Thus, these findings, if confirmed, may have direct clinical implications in the treatment of millions of women worldwide. 1. Richter, JE. Aliment Pharmacol Ther 2005;22:749-57 2. Nielsen GL, et al. Aliment Pharmacol Ther 1999;13:10859 3. Kallen B. Br J Obstet Gynaecol 1998;105:87781
Journal of Clinical Gastroenterology | 2015
Hemanth Gavini; Jeffrey H. Lee
Over the last 2 decades, endoscopic ultrasound (EUS) has evolved from a noninvasive diagnostic tool to a combined diagnostic and therapeutic modality. The use of EUS complementary to endoscopic retrograde cholangiopancreatography (ERCP) has made possible biliary and pancreatic drainage in situations where conventional ERCP is unsuccessful or unlikely to be feasible. The degree of proximity to the pancreas achieved during the procedure has enabled therapeutic interventions such as drainage of peripancreatic fluid collections, pancreatic cyst ablation, and pancreatic cancer therapy. Real-time visualization of flow in adjacent blood vessels using Doppler ultrasound has allowed endovascular therapy for ablation of gastric varices and feeding vessels. Furthermore, the role of EUS is evolving in a multitude of applications such as bilioenteric and enteroenteric anastomosis in a minimally invasive manner, potentially reducing the need for surgery. This article reviews the role of EUS as an alternative to surgery in selective situations and provides an overview of future directions and evolving uses of EUS.
Gastroenterology | 2010
Sachin Wani; Neil Gupta; Amy Wang; Patrick E. Young; Ajay Bansal; Keng-Yu Chuang; Vikram Boolchand; Hemanth Gavini; Priti Sud; John Kuczynski; Srinivas Gaddam; Vikas Singh; Mandeep Singh; Savio Reddymasu; Amit Rastogi; Brooks D. Cash; Sharad C. Mathur; April D. Higbee; Richard E. Sampliner; David A. Lieberman; Gary W. Falk; Prateek Sharma
represent potential therapeutic targets for the treatment of esophageal malignancies. Methods: Esophageal cell lines HET-1A(normal-squamous), QhTRT(metaplastic), GOhTRT(dysplastic) and SKGT4(adenocarcinoma) were utilized. Cell viability was assessed using the MTT proliferation assay. Preliminary experiments demonstrated that specific inhibition using siRNA to BCL-XL sensitized GOhTRTs to DCA(10hours@500μM) induced cell death, decreasing cell viability by ~45%(p-value <0.0001). siBCL-XL was incorporated as a positive control in the screening protocol. An automated siRNA transfection protocol was developed using the Matrix Hydra II and Matrix WellMate liquid handling robots. Results: A significant level of resistance to DCA-induced cell death was observed in the GOhTRTs when compared to Het-1As(normal-squamous). An siRNA screen targeting GPCRs identified a number of genes whose specific inhibition resulted in a sensitization of the GOhTRT cell line to DCA induced cell death (10hours @ 500μM). The top 25 targets that reduced cell viability by greater than 25% include FZD3, GPSM2, GPR27, CCL25 and IL8Rα. Validation and further investigations will assess how these molecules mediate resistance to DCA induced cell death. Discussion: IL8Rα is a high affinity receptor for IL8 and mediates its angiogenic effect in intestinal microvascular endothelial cells. This may be important in progression through the esophageal carcinogenic sequence from Barretts esophagus(BE) to adenocarcinoma. CCL25 is a chemokine ligand with chemotactic activity for dendritic cells, thymocytes and activated macrophages. Interestingly, the promoter region of CCL25 contains the binding site for the caudal-related homeobox(Cdx) transcription factors. This is significant as CDX2 is upregulated in BE and may drive an inflammatory response through CCL25. These findings have potential implications for pathogenesis and therapeutics of esophageal cancer. Future investigations will involve the implementation of this screening strategy with more comprehensive siRNA libraries to target a larger number of genes to potentially identify new therapeutic targets.
Case Reports in Medicine | 2010
Vivek Nagaraja; Joel A. Terriquez; Hemanth Gavini; Lokesh Jha; Stephen A. Klotz
Recent studies have shown an increased risk of arterial and venous vascular diseases in HIV patients, pulmonary thromboembolism being one of them. HIV-infected individuals may have procoagulants predisposing them to thromboembolism. Patients with thromboembolism may have a clinical presentation mimicking common opportunistic infections. It is important to consider pulmonary embolism in the differential of HIV patients with fever, cough, and dyspnea, particularly in those with well-controlled HIV infection.
Gastroenterology | 2014
Hemanth Gavini; Winnie Sheu-Woc; Venkat Dirish Arukala; Patrick M. Lynch; Lopa Mishra; Jason B. Fleming; Selvi Thirumurthi; William A. Ross; Claudius Conrad; Brian Weston; Jeffrey H. Lee
Pancreatic stellate cells (PSCs) within the tumor microenvironment are important for cancer cell growth, migration and metastasis. We have shown previously that the lipid signaling molecule sphingosine 1-phosphate (S1P) activates PSCs to release paracrine factors including MMP9 to promote tumor cell migration and invasion in vitro through a S1P receptor-2 (SIP2)-c-abl-NFκB-MMP9 pathway. We therefore hypothesized that knockdown of S1P2 in PSCs might inhibit tumor growth in vivo. Methods: We used subcutaneous and orthotopic tumor cell/PSC co-implantation models in which PSC are known to stimulate tumor growth in vivo. In the subcutaneous model, L3.6 human pancreatic cancer cells were mixed with human PSCs transfected with control or S1P2 shRNA (1:1 ratio) and subcutaneously injected into the lower flank of nude mice. Tumor diameters were measured and tumor tissues were cryosectioned for immunofluorescence studies and mRNA was extracted for real time qPCR analyses. Orthotopic pancreatic implant models were done with ASPC1 cell mixed with PSC transfected with scramble or S1P2 shRNA PSC (1: 1 ratio) injected into the pancreatic tail of nude mice. Tumor size was monitored with in vivo Luciferase activity. Results: Tumor size was smaller in L3.6 derived tumors that were coimplanted with S1P2 shRNA PSC compared to scramble PSC (64 mg vs 145 mg, n=10, p<0.01). qPCR from tumor tissue from S1P2sh PSC and L3.6 co-implantation showed a 34% reduction of MMP9 and 26% reduction of CSF1r mRNA levels compared to control (n= 10, p<0.05). Staining for endothelial cell marker Von Willebrand factor indicated decreased angiogenesis in the tumor from co-implantation of S1P2sh PSC and L3.6 compare to control PSC and L3.6 co-implantation. Similar results were observed in the orthotopic model using ASPC1 cells. Conclusion: S1P2 in PSCs promotes cancer growth in vivo through activation of the tumor microenvironment including angiogenesis and macrophage infiltration.
Gastroenterology | 2014
Hemanth Gavini; Winnie Sheu-Woc; Jeffrey H. Lee
Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.