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ABSTRACT: BACKGROUND: Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstruction. OBJECTIVE: To compare outcomes between covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) in malignant biliary obstruction. DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center. PATIENTS: Patients with malignant biliary obstruction. INTERVENTIONS: Placement of CSEMS or USEMS. MAIN OUTCOME MEASUREMENTS: Time to recurrent biliary obstruction (TRO), overall survival (OS), and adverse events. RESULTS: From January 2000 to June 2011, 749 patients received SEMSs: 171 CSEMSs and 578 USEMSs. At 1 year, there was no significant difference in the percentage of patients with recurrent obstruction (CSEMSs, 35% vs USEMSs, 38%) and survival (CSEMSs, 45% vs USEMSs, 49%). There was no significant difference in the median OS (CSEMSs, 10.4 months vs USEMSs, 11.8 months; P = .84) and the median TRO (CSEMSs, 15.4 months vs USEMSs, 26.3 months; P = .61). The adverse event rate was 27.5% for the CSEMS group and 27.7% for the USEMS group. Although tumor ingrowth with recurrent obstruction was more common in the USEMS group (76% vs 9%, P < .001), stent migration (36% vs 2%, P < .001) and acute pancreatitis (6% vs 1%, P < .001) were more common in the CSEMS group. LIMITATIONS: Retrospective study. CONCLUSIONS: There was no significant difference in the patency rate or overall survival between CSEMSs and USEMSs for malignant distal biliary strictures. The CSEMS group had a significantly higher rate of migration and pancreatitis than the USEMS group. No significant SEMS-related adverse events were observed in patients undergoing neoadjuvant chemoradiation or surgical resection.
Gastrointestinal endoscopy 04/2013; · 6.71 Impact Factor
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Wei Wang,
Alexander Shpaner,
Somashekar G Krishna,
William A Ross,
Manoop S Bhutani,
Eric P Tamm, Gottumukkala S Raju,
Lianchun Xiao,
Robert A Wolff,
Jason B Fleming,
Jeffrey H Lee
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ABSTRACT: BACKGROUND: Diagnosis of pancreatic neoplasm is challenging in patients with inconclusive findings on pancreatic multidetector row CT (MDCT). OBJECTIVE: To determine the diagnostic accuracy and to identify predictors of pancreatic neoplasm by EUS with FNA in this setting. DESIGN: Retrospective chart review during the study period of January 2002 to December 2010. SETTING: Tertiary referral center. PATIENTS: Of the 1046 patients who underwent pancreatic EUS, 116 patients were selected because their clinical presentation was suspicious for pancreatic malignancy, but their MDCT findings were inconclusive. INTERVENTION: EUS with FNA. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of malignancy and significance of clinical variables. RESULTS: When surgical pathology or subsequent clinical course was used as the criterion standard, EUS with FNA had a sensitivity, specificity, positive predictive value, and accuracy of 87.3%, 98.3%, 98.5%, and 92.1%, respectively, in diagnosing a pancreatic neoplasm that was indeterminate on MDCT. Factors significantly associated with EUS detection of pancreatic ductal adenocarcinoma were total bilirubin level greater than 2 mg/dL (P < .001), CT finding of pancreatic duct dilation (P < .001), bile duct stricture (P < .001), and tumor size 1.5 cm or larger detected by EUS (P = .004). Among them, pancreatic duct dilation on CT (odds ratio 4.10; 95% confidence interval, 1.52-11.05), and tumor size 1.5 cm or larger detected by EUS (odds ratio 8.46; 95% confidence interval, 2.02-35.45) were independent risk factors. LIMITATIONS: Retrospective design and patient referral bias. CONCLUSIONS: When MDCT is indeterminate, EUS is a highly sensitive and accurate modality for the detection of pancreatic neoplasm, especially when the tumor is smaller than 2.0 cm.
Gastrointestinal endoscopy 03/2013; · 6.71 Impact Factor
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ABSTRACT: OBJECTIVES: Metastatic lesions to the pancreas pose diagnostic challenges with regards to their differentiation from primary pancreatic cancer. Data on the yield of endoscopic ultrasonography (EUS)-guided fine-needle aspiration in detection of these lesions are limited. METHODS: This is a retrospective review of 23 patients referred to a tertiary referral center for further evaluation of suspected pancreatic metastases. Main outcome measures were diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in evaluation of metastatic lesions to the pancreas. RESULTS: Of 644 patients, 23 (3.6%) undergoing EUS of the pancreas were diagnosed to have metastatic disease to the pancreas based on clinical, radiological, and cytological results. Mean (SD) age was 64.3 (11.7) years. Of the 23 patients, 18 (78.3%) were asymptomatic. Mean (SD) size of lesion on EUS was 39.1 (19.9) mm. A diagnosis of malignant lesion was made in 21 of 23 cases, with a diagnostic accuracy of 91.3%. CONCLUSIONS: Metastatic lesions to the pancreas present as incidental, solitary mass lesions on staging or surveillance imaging. Endoscopic ultrasonography-guided fine-needle aspiration is an important tool in the characterization and further differentiation of metastatic lesions to the pancreas from primary pancreatic cancer.
Pancreas 12/2012; · 2.39 Impact Factor
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ABSTRACT: After surviving an episode of acute necrotizing pancreatitis (ANP), a variety of late sequelae develop and require nonoperative or operative interventions. Persistent pancreatic fistula, fluid collections, recurrent pancreatitis, sepsis, pain, and intolerance of po intake are seen.
We have maintained records for all patients hospitalized from 1993 through 2010 with a diagnosis of ANP. Once discharged from hospital, patients were managed with routine clinic follow-up at close intervals and later at 6-month intervals. Using ERCP or magnetic resonance cholangiopancreatography, all patients' pancreatic ducts were classified as type I (normal), type II (stricture), or type III (disconnected). Patients were monitored for the complications mentioned. Operations performed >8 weeks after the initial episode of ANP were defined as late and evaluated for operative mortality, morbidity, success in resolving symptoms/collections, and length of stay.
One hundred and ninety-seven patients with ANP were included. Seventy-one late operations were performed (59 drainage procedures/12 resections). Operative mortality was 1%, morbidity was 19%, and mean length of stay was 6.3 ± 5.6 days. Poor po intake was seen in 80% of operated patients and total parenteral nutrition dependence in 42%. Duct type correlated with pancreatic debridement, persistent fluid collection/fistula, pain, po intake intolerance, and late operation. Late operation successfully resolved symptoms and/or fluid collections in 96%. Recurrent pancreatitis was improved in 87% and eliminated in 78%.
Patients who require late operation after surviving an episode of ANP are more likely to have sustained ductal injuries and are likely to require operation for either pain or for inability to tolerate po intake. Operation can be performed safely with a low mortality.
Journal of the American College of Surgeons 04/2012; 214(4):682-8; discussion 688-90. · 4.55 Impact Factor
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Pancreas 03/2012; 41(2):327-9. · 2.39 Impact Factor
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Gastrointestinal endoscopy 12/2011; 74(6):1380-8. · 6.71 Impact Factor
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Muslim Atiq,
Manoop S Bhutani,
Mehmet Bektas,
Jeffrey E Lee,
Yun Gong,
Eric P Tamm,
Chintan P Shah,
William A Ross,
James Yao, Gottumukkala S Raju,
Xuemei Wang,
Jeffrey H Lee
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ABSTRACT: Pancreatic neuroendocrine tumors (PNET) are fairly uncommon. Recent data highlight the importance of EUS in diagnosis of PNET. With this background, we decided to review our experience from a tertiary cancer center with regard to the presentation and clinical features of PNET and the diagnostic utility of EUS-FNA in this scenario.
We identified patients who underwent EUS at our institution between January 1st 2001 and December 31st 2009 for a suspected PNET. Data on clinical features, cross-sectional imaging findings, EUS findings, and cytology results were collected.
A total of 81 patients were referred for EUS-FNA for a suspected PNET. Mean age was 58.1 years. There were 41 (50.6%) males. PNET was found incidentally in 38 (46.9%) patients. Computed tomography scanning identified a pancreatic mass in 72 out of 79 (91.1%) cases. Mean diameter of the largest lesion seen on EUS was 27.5 mm (range: 6.9-80 mm). The most common site (34; 42%) was the head of the pancreas. EUS-FNA correctly confirmed a PNET in 73 out of 81 cases with diagnostic accuracy of 90.1%. Seven (8.6%) out of 81 patients had functional lesions, including three gastrinomas and four insulinomas. Liver metastases were found in 31 out of 81 (38.3%) cases. Of the 31 patients with liver metastasis, the mean diameter of lesions on EUS was 33.9 mm compared with 23.5 mm in patients without liver metastasis (P = 0.005).
EUS-FNA is a reliable modality for further characterization of suspected lesions and for establishing a tissue diagnosis. The occurrence of complications of EUS-FNA in this setting is low. Non-functional PNET are more frequently encountered than functional PNET.
Digestive Diseases and Sciences 10/2011; 57(3):791-800. · 2.12 Impact Factor
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ABSTRACT: Duodenal lesions (DLS) are common in patients with familial adenomatosis polyposis (FAP), and screening for duodenal adenocarcinoma (DA) is currently recommended. Endoscopic treatment of DLS is controversial.
To report management and outcomes of endoscopic therapy for DLS in patients with FAP.
The records of patients with FAP who underwent endoscopic surveillance or therapy for DLS over a 15-year period were reviewed. Endoscopic intervention included endoscopic surveillance with biopsies, argon plasma coagulation (APC), endoscopic mucosal resection (EMR), EMR with APC, and ampullectomy. Main outcome measurements were recurrence and histology of DLS after endoscopic therapy, complications of endoscopic therapy, and need for duodenectomy.
Seventy-one patients with FAP and DLS were identified from our endoscopy database as undergoing upper endoscopy for screening and/or surveillance (1995-2009). Mean follow up was 4.5 years (1-15 years). Seventy of the seventy-one (98.5%) patients had multiple flat DLS. Most of the patients were followed with yearly biopsies. APC was performed in 17 patients and EMR was performed in eight patients; in five of the eight EMR patients, APC was also performed to treat the edges of EMR site. During the follow up, 17/55 (31%) patients had histological progression (HP). HP was seen in 5/16 (31%) patients who underwent APC (one was lost to follow-up) and 12/40 (30%) patients followed with biopsies alone. Recurrence of lesions was noted in all patients. Two patients underwent duodenectomy. None of the patients developed DA during follow up.
Endoscopic surveillance with directed endotherapy for DLS in FAP is feasible and safe when diligently performed.
Digestive Diseases and Sciences 09/2011; 57(3):732-7. · 2.12 Impact Factor
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ABSTRACT: Regulatory T (Treg) cells (CD4+ CD25high FoxP3+) regulate mucosal tolerance; their adoptive transfer prevents or reduces symptoms of colitis in mouse models of inflammatory bowel disease. Colonic CD90+ mesenchymal myofibroblasts and fibroblasts (CMFs) are abundant, nonprofessional antigen-presenting cells in the normal human colonic mucosa that suppress proliferation of activated CD4+ effector T cells. We studied CMF suppressive capacity and evaluated the ability of CMF to induce Treg cells.
Allogeneic cocultures of CD4+ T cells and CMFs, derived from normal mucosa of patients undergoing colectomy for colon cancer or inflamed colonic tissues from patients with ulcerative colitis or Crohn's disease, were used to assess activation of the Treg cells.
Coculture of normal CMF with resting or naïve CD4+ T cells led to development of cells with a Treg phenotype; it also induced proliferation of a CD25+ CD127- FoxP3+ T cells, which expressed CTLA-4, interleukin-10, and transforming growth factor-β and had suppressive activities. In contrast to dendritic cells, normal CMFs required exogenous interleukin-2 to induce proliferation of naturally occurring Treg cells. Induction of Treg cells by normal CMFs required major histocompatibility complex class II and prostaglandin E2. CMFs from patients with inflammatory bowel diseases had reduced capacity to induce active Treg cells and increased capacity to transiently generate CD4+CD25+/- CD127+ T cells that express low levels of FoxP3.
CMFs suppress the immune response in normal colon tissue and might therefore help maintain colonic mucosal tolerance. Alterations in CMF-mediated induction of Treg cells might promote pathogenesis of inflammatory bowel diseases.
Gastroenterology 03/2011; 140(7):2019-30. · 11.68 Impact Factor
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ABSTRACT: Endoscopic retrograde biliary drainage (ERBD) with plastic or self-expanding metal stents (SEMS) is often performed for palliative care for cholangiocarcinoma.
The objective was to compare the clinical effectiveness, including stent patency, complication rate, and need for salvage percutaneous transhepatic biliary drainage, of SEMS and plastic stents.
A total of 100 patients with inoperable cholangiocarcinoma were identified from an endoscopic database from 1/1/01 to 9/30/06 at a tertiary cancer hospital and their clinical history was retrospectively reviewed. All patients were followed to death, re-intervention, or for at least one year. Stent patency and patient survival were estimated by Kaplan-Meier analysis, supplemented by the log-rank test for comparisons between groups.
Forty-eight patients had SEMS placed and 52 patients had plastic stents placed. ERBD was successful in 46 (95.8%) in the SEMS group and 49 (94.2%) in the plastic group (P = 0.67). Median patency times were 1.86 months in the plastic group and 5.56 months in the SEMS group (P < 0.0001). A mean of 1.53 and 4.60 re-interventions were performed in the SEMS and plastic groups, respectively (P < 0.05). Complications occurred in 4/48 (8.3%) in the SEMS group and 4/52 (7.7%) in the plastic group (P = 0.79). Median survival was 9.08 and 8.22 months in the SEMS and plastic stent groups, respectively (P = 0.50).
Metallic stent patency was superior to that of plastic stents in all Bismuth-Corlette classifications of hilar cholangiocarcinoma with similar complication rates. SEMS seem to be cost-effective and, when feasible, should be considered as an initial intervention in patients with inoperable hilar cholangiocarcinoma.
Digestive Diseases and Sciences 01/2011; 56(5):1557-64. · 2.12 Impact Factor
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Gastrointestinal endoscopy 10/2009; 70(3):552-3; discussion 553. · 6.71 Impact Factor
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ABSTRACT: Colonoscopic full-thickness resection (CFTR) of the colon may obviate the need for surgical resection of benign lesions.
To develop an animal model for CFTR of the colon followed by endoscopic suture closure with through-the-endoscope devices.
Pilot study.
University medical center.
Twenty pigs.
A 2-cm circular area was resected on the antimesenteric side of the colon (phase 1, n = 10) and on the mesenteric side (phase 2, n = 10) by using an insulated tip knife cut followed by the use of a grasping forceps and a snare to resect and retrieve the specimen. The tissue apposition system was used to close the defect.
Resection and closure times were recorded. The animals were euthanized at 2 weeks and examined for peritonitis, adhesions, wound healing, and T-tag injury to adjacent viscera.
The CFTR was successful in all 20 attempts. The median resection time was 6 minutes (range 2.5-35 minutes). Suture closure was successful in 19 animals. It took a median time of 41 minutes (range 21-125 minutes) and 4 sutures to close the defect. Eighteen animals survived without clinical signs of distress; there was a well-healed scar without peritonitis or distant adhesions on necropsy at 2 weeks. One animal failed to thrive, and necropsy revealed mild peritonitis, small abscesses, distant adhesions, and a 2-mm hole at the suture site. Two of the 132 T-tags were inserted in the adjacent viscera.
Colon resection in the proximal colon was not studied.
In this animal model, CFTR of the colon followed by suture closure can be accomplished successfully by using through-the-endoscope devices.
Gastrointestinal endoscopy 08/2009; 70(1):159-65. · 6.71 Impact Factor
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ABSTRACT: A prominent role for inhibitory molecules PD-L1 and PD-L2 in peripheral tolerance has been proposed. However, the phenotype and function of PD-L-expressing cells in human gut remains unclear. Recent studies suggest that colonic myofibroblasts (CMFs) and fibroblasts are important in the switch from acute inflammation to adaptive immunity. In the normal human colon, CMFs represent a distinct population of major histocompatibility complex class II(+) cells involved in the regulation of mucosal CD4(+) T-cell responses.
PD-L1 and PD-L2 expression on human CMFs was determined using Western blot, fluorescence-activated cell sorter analysis and confocal microscopy. Lymphoproliferation assays and cytokine enzyme-linked immunosorbent assays were used to evaluate the role of B7 costimulators expressed by CMFs with regard to the regulation of preactivated T-helper cell responses.
We demonstrate here the expression of PD-L1/2 molecules by normal human CMF and fibroblasts in situ and in culture. Both molecules support suppressive functions of CMFs in the regulation of activated CD4(+) T-helper cell proliferative responses; blocking this interaction reverses the suppressive effect of CMFs on T-cell proliferation and leads to increased production of the major T-cell growth factor, interleukin (IL)-2. PD-L1/2-mediated CMF suppressive functions are mainly due to the inhibition of IL-2 production, because supplementation of the coculture media with exogenous IL-2 led to partial recovery of activated T-cell proliferation.
Our data suggest that stromal myofibroblasts and fibroblasts may limit T-helper cell proliferative activity in the gut and, thus, might play a prominent role in mucosal intestinal tolerance.
Gastroenterology 08/2008; 135(4):1228-1237, 1237.e1-2. · 11.68 Impact Factor
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Gottumukkala S Raju,
Annette Fritscher-Ravens,
Richard I Rothstein,
Paul Swain,
Andres Gelrud,
Ijaz Ahmed,
Guillermo Gomez,
Markus Winny,
Thomas Sonnanstine,
Maria Bergström,
Per-Ola Park
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ABSTRACT: Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure.
The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study.
University hospitals in the United States and Europe.
After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication.
Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera.
This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans.
Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.
Gastrointestinal endoscopy 07/2008; 68(2):324-32. · 6.71 Impact Factor
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Gastrointestinal endoscopy 07/2008; 67(7):1175-6; discussion 1176. · 6.71 Impact Factor
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Gastrointestinal endoscopy 07/2008; 67(7):1207-8. · 6.71 Impact Factor
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Gastrointestinal endoscopy 04/2008; 68(3):602-4. · 6.71 Impact Factor
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ABSTRACT: This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute on "Evaluation and Management of Occult and Obscure Gastrointestinal Bleeding." It was approved by the Clinical Practice and Economics Committee on March 12, 2007, and by the AGA Institute Governing Board on May 19, 2007. This medical position statement is based upon the interpretation and assimilation of scientifically valid research, derived from a comprehensive review of published literature.
Gastroenterology 12/2007; 133(5):1694-6. · 11.68 Impact Factor
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ABSTRACT: This literature review and the recommendations therein were prepared for the AGA Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on March 12, 2007, and by the AGA Institute Governing Board on May 19, 2007.
Gastroenterology 12/2007; 133(5):1697-717. · 11.68 Impact Factor
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Gastrointestinal Endoscopy 11/2007; 66(4):774-85. · 4.88 Impact Factor