Shivakumar Vignesh

Endoscopic diagnosis and treatment of pancreatic cysts.

Pancreatic cystic neoplasms have emerged as an important new opportunity for many disciplines to participate in the diagnosis and management of early pancreatic neoplasia. With an increase in an understanding of these lesions and their potential for malignant transformation, there has been a dramatic increase in the frequency of diagnosis. We critically examined the literature on diagnostic methods for pancreatic cystic lesions over the past 5 years. The methods of endoscopic pancreatic pseudocyst drainage and clinical outcomes are also discussed. Morphologic studies of cystic lesions using cross-sectional imaging or endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of diagnosis. The management of cystic lesions is heavily dependent on the type of cyst, the neoplastic potential, and the risk of surgery. The traditional therapy is pancreatic resection and not cyst enucleation. In contrast to cystic neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic cystic neoplasms. The fluid collections arise from chronic pancreatitis and ductal leaks. Because pseudocysts have no neoplastic potential, they can be drained rather than resected. Drainage can be safely accomplished with external catheters or endoscopically with internal catheters. As we learn more about the pathophysiology of the various cystic lesions, treatment will be tailored to the specific cyst lesion. Endoscopic ultrasound has an important role in the characterization of pancreatic cystic lesions and helps in selection of the optimal treatment modality.

Stability of endoscopic ultrasound-guided fiducial marker placement for esophageal cancer target delineation and image-guided radiation therapy

PURPOSE Fiducial markers have been integrated into the management of multiple malignancies to guide more precise delivery of radiation therapy (RT). Fiducials placed at the margins of esophageal tumors are potentially useful to facilitate both RT target delineation and image-guided RT (IGRT). In this study, we report on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for esophageal cancers and utilization for radiation treatment planning and IGRT. METHODS An institutional review board-approved database was queried for patients treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in the analysis had a diagnosis of esophageal cancer, were referred for treatment with CRT, and had fiducials placed under EUS guidance. Images acquired at time of radiation treatment planning, daily IGRT imaging, post-treatment restaging, and surveillance scans were analyzed to determine the stability of implanted markers. RESULTS We identified 60 patients who underwent EUS-guided fiducial marker placement near the margins of their esophageal tumors in preparation for RT treatment planning. A total of 105 fiducial markers were placed. At time of CT simulation, 99 markers were visualized. Fifty-seven patients had post-treatment imaging available for review. Of the 100 implanted fiducials in these 57 patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%) fiducials were still present post-treatment imaging at a median of 107 days (range, 33-471 days) after implantation. CONCLUSIONS EUS-guided fiducial marker placement for esophageal cancer aids in target delineation for radiation planning and daily IGRT. Fiducial stability is reproducible and facilitates conformal treatment with image-guided RT techniques.

A MicroRNA-Based Test Improves Endoscopic Ultrasound–Guided Cytologic Diagnosis of Pancreatic Cancer

BACKGROUND & AIMS Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false-negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC. METHODS Levels of miRNAs were analyzed in a centralized clinical laboratory by relative quantitative polymerase chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland. RESULTS We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or nondiagnostic by cytology. Cytology and miRNA test results each were associated significantly with PDAC (P < .001), with positive predictive values greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS We developed and validated a 5-miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.

Cell-surface markers for colon adenoma and adenocarcinoma

Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

Endoscopic therapy of neoplasia related to Barrett's esophagus and endoscopic palliation of esophageal cancer.

BACKGROUND Barretts esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma. METHODS This article reviews the current endoscopic therapies for BE with high-grade dysplasia and intramucosal cancer and briefly discusses the endoscopic palliation of advanced esophageal cancer. RESULTS The diagnosis of low-grade or high-grade dysplasia (HGD) is based on several cytologic criteria that suggest neoplastic transformation of the columnar epithelium. HGD and carcinoma in situ are regarded as equivalent. The presence of dysplasia, particularly HGD, is also a risk factor for synchronous and metachronous adenocarcinoma. Dysplasia is a marker of adenocarcinoma and also has been shown to be the preinvasive lesion. Esophagectomy has been the conventional treatment for T1 esophageal cancer and, although debated, is an appropriate option in some patients with HGD due to the presence of occult cancer in over one-third of patients. CONCLUSIONS Endoscopic ablative modalities (eg, photodynamic therapy and cryoablation) and endoscopic resection techniques (eg, endoscopic mucosal resection) have demonstrated promising results. The significant morbidity and mortality of esophagectomy makes endoscopic treatment an attractive potential option.

EUS-Guided Pancreatic Diagnosis and Beyond

The therapeutic ability of endoscopic ultrasound has expanded, especially in assisting with radiation planning for image guided radiation techniques such as stereotactic body radiation therapy. Endoscopic ultrasound enables precise placement of fiducial markers into pancreatic cancers to accurately delineate the position of the target lesion as it moves with respiration. The authors summarize the data presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, including Abstracts #302, #327, #176, #182, and #349. Image: Dose painting of pancreas protocol CT scan (detail).

Survival benefits in colorectal adenocarcinoma with the use of metformin among a black diabetic inner city population

We assessed the association of metformin use with survival in colorectal cancer in a population consists mostly of African-American and Afro-Caribbean patients. We identified 585 colorectal cancer patients, 167 (28.6%) and 418 (71.5%) were as diabetic (DM) and nondiabetic, respectively. The diagnosis of diabetes did not impact cancer survival or extent of disease. Overall, DMs with metformin use (D+M+) have better overall survival than both DMs without metformin use (D+M∼) and nondiabetics (D∼M∼), with a mean survival of 109.9 months compared with 95.7 and 106.1 months, respectively (log-rank p < 0.05). The use of metformin shows significant reduction of risk of mortality compared with nonusers (hazard ratio: 0.34; 95% CI: 0.15-0.81; p = 0.01). Use of insulin and status of diabetes did not have a significant impact on overall cancer survival.

The Utility of Endoscopic Ultrasound–Guided Brachytherapy in Liver Metastasis: A Case Report and Review of the Literature

Endoscopic ultrasound guided brachytherapy (EGBT) has been reported to be useful in certain malignancies including esophageal and pancreatic cancers. Percutaneous or surgical placement of radioactive seeds into the liver secondaries (brachytherapy) has been done successfully, however, the utility of EGBT in liver metastasis remains largely unclear. In this case report, we demonstrate the safety, efficacy and feasibility of EUS guided brachytherapy (EGBT) in liver metastasis secondary to leiomyosarcoma.

Design of Cost Effective Home Automation System

Abstract: The rapidly advancing mobile communication technology and the decrease in costs make it possible to incorporate mobile technology into home automation systems. We propose a mobile-based home automation system that consists of a mobile phone with Java capabilities, a cellular modem, and a home server. The home appliances are controlled by the home server, which operates according to the user commands received from the mobile phone via the cellular modem. In our proposed system the home server is built upon an SMS/GPRS (short message service/general packet radio service) mobile cell module and a microcontroller, allowing a user to control and monitor any variables related to the home by using any Java capable cell phone.

Effect of neoadjuvant dose-painted IMRT to 56 Gy for locally advanced esophageal cancer on outcomes.

144 Background: Standard of care chemoradiation doses of 50.4 Gy for locally advanced (T3, T4, and/or node positive) esophageal cancer is associated with a pathologic complete response (pCR) rate of 40% at our institution. We evaluated whether pCR would be increased with 4D CT planning scans, intensity-modulated radiation therapy (IMRT) delivery with motion management, and dose painting to 56 Gy in 28 fractions. METHODS This retrospective review of 9 patients who have undergone esophagogastrectomy (7 adenocarcinoma, 2 squamous cell) evaluates our initial experience with neoadjuvant dose painted IMRT to 56 Gy. Pre-treatment workup included PET scan, chest and abdomen CT scans, endoscopic ultrasound (EUS), and EUS-guided fiducial marker placement. Fiducial markers were placed superior and inferior to the gross endoscopic tumor volume to facilitate analysis of tumor motion with 4D CT simulation. Internal target volumes (ITVs) of gross disease were generated to account for motion. Once the GITV was generated, a clinical target volume (CTV) encompassing a 3-4 cm superior margin and 3-4 cm distal margin was contoured. Two planning target volumes (PTVs) were created for dose painting: PTV 50.4 and PTV 56 Gy in 28 fractions. IMRT was utilized for all patients with either a weight belt or with compensators. Concurrent cisplatin and continuous infusion 5-FU were delivered with radiotherapy and patients were restaged 3-6 weeks after completion for response evaluation. RESULTS Treatment was well tolerated without any grade 3 acute morbidity. Surgical complications were not increased in this group overall. However, there was 1 patient with a chyle leak and radiation pneumonitis, but her case was complicated by having a remote history of radiotherapy. Six of the 9 treated patients were found to have a pCR (4 adenocarcinoma, 2 squamous cell). Two had a near CR with < 5 mm of residual disease. One additional patient with an initial bulky T4N1 tumor had 9 mm of viable tumor. CONCLUSIONS With motion management, dose painted IMRT to 56 Gy is feasible and may be associated with improved rates of pathologic complete or near complete response. No significant financial relationships to disclose.