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1.  High risk of acute pancreatitis after endoscopic ultrasound-guided fine needle aspiration of side branch intraductal papillary mucinous neoplasms 
Endoscopic Ultrasound  2015;4(2):109-114.
Background and Objectives:
Data on the risk of acute pancreatitis following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions are limited. The aim of our study was to evaluate the frequency of acute pancreatitis after EUS-FNA of pancreatic cysts and solid lesions, and determine whether there was a difference in pancreatitis risk in patients with side branch intraductal papillary mucinous neoplasms (SB-IPMN).
Patients and Methods:
A retrospective review of patients who underwent EUS-FNA of pancreatic cysts and solid lesions was performed. The primary outcome measure was development of acute pancreatitis after EUS-FNA. Factors associated with acute pancreatitis were examined by statistical analysis to determine independent predictors of acute pancreatitis. Statistical significance was determined at a P ≤ 0.05.
We identified 186 patients with pancreatic cystic lesions and 557 with solid lesions in which EUS-FNA was performed. The median size of the cysts was 19 mm (range: 10-66 mm). There were 37 IPMNs, 33 mucinous cystic neoplasms, 58 serous cysts and 46 pseudocysts and 12 solid-cystic ductal carcinomas. The majority of patients (75%) with solid lesions were diagnosed with adenocarcinoma. Patients with pancreatic cysts had a statistically greater frequency of developing pancreatitis after EUS-FNA when compared to those with solid lesions (2.6% vs. 0.36% respectively; P = 0.13). In patients with cysts, there were no statistically significant differences between the two groups (with and without pancreatitis) with regard to a cyst location, size of the cyst, and number of needle passes or trainee involvement. Patients with SB-IPMN had a statistically higher frequency of pancreatitis after EUS-FNA compared to those with other cyst types (8% vs. 1.3% respectively; odds ratio = 6.4, 95% confidence intervals = 1.0-40.3, P = 0.05).
Patients with SB-IPMN are at a higher risk of developing acute pancreatitis after a EUS-FNA. Alternative means of diagnosis such as magnetic resonance cholangiopancreatogram might be necessary to avoid risk of EUS-FNA.
PMCID: PMC4445167  PMID: 26020044
Acute pancreatitis; endosonography; fine-needle aspiration; intraductal papillary; mucinous neoplasm
2.  Objective assessment of an algorithmic approach to EUS-guided FNA and interventions 
Gastrointestinal endoscopy  2013;77(5):739-744.
Despite an increasing number of procedures being performed, there is no consensus on an optimal approach to EUS-guided FNA (EUS-FNA) or interventions.
Validate an algorithmic approach to EUS-FNA/interventions with the objective of improving technical outcomes and resource use.
Prospective study.
Tertiary-care referral center.
Consecutive patients undergoing EUS-FNA and/or interventions.
Phase I was a retrospective analysis of EUS-FNA/interventions performed in 548 patients. The 19-gauge needle was used for interventions, and the 22- or 25–gauge needle was used interchangeably for performing FNAs. At phase I, the technical failure rate was 11.5%. Based on these observations, an algorithm was proposed by which all transduodenal FNAs were performed by using a 25-gauge needle and other FNAs with a 22-gauge needle. All transduodenal interventions were performed with a Flexible 19-gauge needle and others with a standard 19-gauge needle. This algorithm was tested prospectively in phase II on 500 patients.
Main Outcome Measurements
Compare technical failure, diagnostic adequacy, procedural complications, and average needle costs between both phases.
The technical failure rate was significantly less in phase II compared with that of phase I (1.6% vs 11.5%; P < .001) for both FNA (1.8% vs 10.9%; P < .001) and therapeutic interventions (0% vs 16.4%; P = .001). Although there was no difference in diagnostic adequacy (97.1% vs 98.4%; P =.191) or complications (0.4% vs 0.2%; P = 1.0) between phases I and II, the average cost per case was significantly less in phase II ($199.59 vs $188.30; P =.008).
Single-center study.
An algorithmic approach to EUS-FNA/interventions yielded better technical outcomes and cost savings without compromising diagnostic adequacy.
PMCID: PMC4158618  PMID: 23369651
4.  Challenging the dogma: a randomized trial of standard vs. half-dose concomitant nonbismuth quadruple therapy for Helicobacter pylori infection 
Current treatment of Helicobacter pylori consists of three or four drugs for 7–14 days with important associated cost and adverse events.
This study compared efficacy and safety of standard dose vs. half-dose concomitant nonbismuth quadruple therapy (NBQT) for 7 days. The standard dose consisted of twice daily rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg.
This was a prospective randomized trial. 14C-urea breath test was performed ≥4 weeks after treatment and ≥2 weeks off acid suppressive therapy. Compliance and adverse events were monitored during treatment.
A total of 200 consecutive treatment-naïve patients were enrolled. Baseline characteristics were similar between groups, with 15.5% of subjects reporting prior macrolide use. Eradication occurred in 78% (95% CI 68.6–85.7%) in both groups on intention-to-treat analysis. Per-protocol rates were 82.1 vs. 83.9% for standard-dose patients vs. half-dose patients, respectively (p = NS). Adverse events (only mild) were reported in 57 vs. 41% of standard-dose patients vs. half-dose patients (p = 0.024), with metallic taste and nausea notably less frequent in the latter (36 vs. 12% and 18 vs. 7%, respectively; p < 0.05 for both). Overall, eradication failed in 38.7% of prior macrolide users vs. 18.9% without such exposure (p = 0.019). On multivariate logistic regression, prior macrolide exposure was the only factor associated with failed eradication (OR 2.60, 95% CI 1.06–6.39; p = 0.038). Treatment was cheaper with the half-dose regimen.
A 50% reduction in antibiotic dosage does not diminish efficacy of concomitant nonbismuth quadruple therapy but leads to significant reduction in cost and adverse events. Seven-day concomitant NBQT is suboptimal for H. pylori independent of prior macrolide exposure.
PMCID: PMC4212457  PMID: 25360301
Adverse events; dyspepsia; eradication; gastritis; pylori
5.  Endoscopic ultrasound, the one-stop shop for abdominal pain? 
The Endosonography for Right Sided and Acute Upper Intestinal Misery (EFRAIM) study indicates that the yield of endoscopic ultrasound (EUS) is equivalent if not superior to upper endoscopy combined with transabdominal ultrasound in patients presenting with acute discomfort. Furthermore, this strategy may be more cost effective as EUS simultaneously enables assessment of intraluminal disease as well as extra intestinal pathology. These results are in sync with prior studies demonstrating the hegemony of EUS in the assessment of pancreaticobiliary disease and its role in the assessment of enigmatic chronic abdominal pain. Nevertheless, EUS does not permit assessment for appendicitis or genitourinary catastrophe. Thus a careful history and physical examination to localize pain to the right upper quadrant and epigastrium is essential.
PMCID: PMC4040775  PMID: 24917979
Endoscopic ultrasonography; abdominal pain; cholecystitis; pancreatitis; acute; gallstones
6.  Diagnosis of Hydatid Cyto-Biliary Disease by Intraductal Ultrasound (With Video) 
Endoscopic Ultrasound  2013;2(4):225-227.
Hydatid disease is one of the relatively common infections in the Middle Eastern countries. It is seen in areas where dogs are used to raise livestock. In humans, the majority of Echinococcus cysts tends to develop in the liver (70%) and is asymptomatic. The two most common complications of hydatid cysts are abscess formation and rupture. Furthermore, in 5-25% of patients, rupture occurs into the biliary tract and patients may present with cholangitis, jaundice, abscess, or bilio-cutaneous fistula after surgery. Intraductal ultrasound (IDUS) is reportedly superior to conventional endoscopic ultrasound for the depiction of bile duct obstruction owing to its additional capability of providing higher resolution images due to the use of higher frequency transducers. Unfortunately IDUS is rarely used, possibly due to the limited availability of appropriate IDUS equipment, cost of the procedure and interventional endoscopists trained in its interpretation. IDUS with wire-guided, thin-caliber, high-frequency probes is a promising imaging modality, yet no previous reports discuss its usefulness in hydatid disease investigation. We hereby present the first report of biliary hydatid disease being diagnosed by IDUS.
PMCID: PMC4062277  PMID: 24949401
biliary disease; hydatid disease; intraductal ultrasound
7.  Propafenone Hepatotoxicity: Report of a New Case and Review of the Literature 
Propafenone is a class Ic antiarrhythmic drug. It is a beta-adrenergic blocker that causes bradycardia and bronchospasm. It is metabolized primarily in the liver. Its bioavailability and plasma concentration differ among patients under long-term therapy. They are genetically determined by the hepatic cytochrome P-450 2D6. Hepatic toxicity is highly uncommon. To date, only eight patients were reported in the reviewed world literature. In this article, one new case will be reported emphasizing the importance of medication history taking in patients presenting with new-onset liver enzymes abnormalities.
PMCID: PMC3793476  PMID: 24045598
Endoscopic ultrasound; jaundice; liver toxicity; liver biopsies; propafenone
8.  McKittrick–Wheelock syndrome presenting with dermatomyositis and rectal prolapsed 
McKittrick–Wheelock syndrome is a rare disease characterized by a large hypersecretory rectosigmoid villous adenoma resulting in persistent large volume diarrhea, electrolyte abnormalities, and renal dysfunction. We report an unusual presentation of this syndrome in a patient who developed persistent diarrhea along with dermatomyositis and rectal prolapse and was later discovered to have a large rectal villous adenoma along with a smaller sigmoid tubulovillous adenoma. In our literature review, we were able to find one case report of a dermatomyositis occurring in conjunction with a tubulovillous adenoma and few case reports of rectal prolapse in the setting of a secretory villous adenoma. However, there were no reports on both occurring in association with McKittrick–Wheelock syndrome. This report highlights the variable manifestations of colorectal adenomas and the importance of searching for an underlying neoplastic entity in patients with new onset dermatomyositis or rectal prolapse or both.
PMCID: PMC3697959  PMID: 23825927
villous adenoma; McKittrick–Wheelock syndrome; dermatomyositis; rectal prolapse; secretory adenoma; rectal polyps
9.  Role of Endoscopic Ultrasonography in the Evaluation of Extrahepatic Cholangiocarcinoma 
Endoscopic Ultrasound  2013;2(2):71-76.
Cholangiocarcinoma is a malignancy that arises from biliary epithelium and is associated with a poor prognosis. Accurate preopera-tive diagnosis and staging of cholangiocarcinoma continues to remain difficult. Endoscopic retrograde cholangiopancreatography (ERCP) is the most commonly performed procedure for cholangiocarcinoma and can provide a tissue diagnosis through brush cytology of the bile duct. However, the sensitivity of biliary brush cytology to diagnose cholangiocarcinoma may be as low as 30%. Endoscopic ultrasound (EUS) is a diagnostic modality which may overcome the limitations of other imaging and biopsy techniques in this setting. EUS can complement the role of ERCP and provide a tissue diagnosis through fine needle aspiration (FNA) and staging through ultrasound imaging. There is currently a paucity of data about the exact role of EUS for the diagnosis of cholan-giocarcinoma in patients with indeterminate extrahepatic biliary strictures. Although multiple studies have shown that EUS is more accurate than ERCP and radiologic imaging for identifying a biliary mass and diagnosing cholangiocarcinoma, the sensitivities are variable. More importantly, the incidence of false negative results is not negligible, though the specificity is close to 100%. There is also controversy regarding the role of EUS-FNA, since even though this may increase diagnosis, it can also lead to tumor seeding.
PMCID: PMC4062251  PMID: 24949368
cholangiocarcinoma; endosonography; fine needle aspiration
10.  Endoscopic ultrasound evaluation in the surgical treatment of duodenal and peri-ampullary adenomas 
AIM: To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection.
METHODS: Records of 111 patients seen at our institution from November 1999 to July 2011 with the post-operative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed.
RESULTS: Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included villous adenoma (n = 5), adenoma (n = 8), tubulovillous adenoma (n = 10), tubular adenoma (n = 20) and hyperplastic polyp (n = 2). Among the 47 patients who underwent resection, 8 (17%, 5 of which corresponded to surgical resection) developed post-procedural complications which included retroperitoneal hematoma, intra-abdominal abscess, wound infection, delayed gastric emptying and prolonged ileus. After median follow-up of 20 mo there were 6 local recurrences (13%, median follow-up = 20 mo) 4 of which were in patients with FAP.
CONCLUSION: EUS accurately predicts the depth of mucosal invasion in suspected benign ampullary and duodenal adenomas. These patients can safely undergo endoscopic or local resection.
PMCID: PMC3558574  PMID: 23382629
Endoscopic ultrasound; Duodenal periampullary adenoma; Esophagogastroduodenoscopy; Cholangio-pancreatography
11.  Pancreatico-biliary endoscopic ultrasound: A systematic review of the levels of evidence, performance and outcomes 
Our aim was to record pancreaticobiliary endoscopic ultrasound (EUS) literature of the past 3 decades and evaluate its role based on a critical appraisal of published studies according to levels of evidence (LE). Original research articles (randomized controlled trials, prospective and retrospective studies), meta-analyses, reviews and surveys pertinent to gastrointestinal EUS were included. All articles published until September 2011 were retrieved from PubMed and classified according to specific disease entities, anatomical subdivisions and therapeutic applications of EUS. The North of England evidence-based guidelines were used to determine LE. A total of 1089 pertinent articles were reviewed. Published research focused primarily on solid pancreatic neoplasms, followed by disorders of the extrahepatic biliary tree, pancreatic cystic lesions, therapeutic-interventional EUS, chronic and acute pancreatitis. A uniform observation in all six categories of articles was the predominance of LE III studies followed by LE IV, IIb, IIa, Ib and Ia, in descending order. EUS remains the most accurate method for detecting small (< 3 cm) pancreatic tumors, ampullary neoplasms and small (< 4 mm) bile duct stones, and the best test to define vascular invasion in pancreatic and peri-ampullary neoplasms. Detailed EUS imaging, along with biochemical and molecular cyst fluid analysis, improve the differentiation of pancreatic cysts and help predict their malignant potential. Early diagnosis of chronic pancreatitis appears feasible and reliable. Novel imaging techniques (contrast-enhanced EUS, elastography) seem promising for the evaluation of pancreatic cancer and autoimmune pancreatitis. Therapeutic applications currently involve pancreaticobiliary drainage and targeted fine needle injection-guided antitumor therapy. Despite the ongoing development of extra-corporeal imaging modalities, such as computed tomography, magnetic resonance imaging, and positron emission tomography, EUS still holds a leading role in the investigation of the pancreaticobiliary area. The major challenge of EUS evolution is its expanding therapeutic potential towards an effective and minimally invasive management of complex pancreaticobiliary disorders.
PMCID: PMC3436039  PMID: 22969187
Endoscopic ultrasound; Fine needle aspiration; Contrast harmonic endoscopic ultrasound; Pancreatic tumors; Pancreatic cysts; Acute pancreatitis; Chronic pancreatitis; Bile duct stones; Duct drainage
12.  Lymph-node ratio is an independent prognostic factor in patients with stage III colorectal cancer: a retrospective study from the Middle East 
In this retrospective study, we evaluated the prognostic effect of positive lymph-node ratio (pLNR) on patients with stage III colorectal cancer (CRC). Our paper is the first analysis, to our knowledge, to deal with such data from the Middle East.
We analyzed the clinicopathological data of 535 patients diagnosed with colorectal cancer at our institution between 1983 and 2003. The 164 patients diagnosed with stage III disease were divided into two categories based on lymph-node ratio (LNR) being the ratio of positive lymph nodes over total lymph nodes dissected: LNR ≤0.4 and LNR >0.4. We used Kaplan-Meier and Cox proportional hazard models to evaluate the prognostic effect of pLNR.
The 10-year survival rate for the patients with stage IIIA, IIIB and IIIC cancers were 76%, 56% and 0% respectively (P = 0.014). Using pLNR of 0.4 as the cutoff point was found to yield clinically and significant results, with a significant difference in the outcomes of patients with pLNR ≤0.4 compared to those with pLNR >0.4 (hazard ratio = 5.25, 95% confidence interval = 1.2 to 22.1, P = 0.02).
The ratio-based staging (pLNR) of CRC is a more accurate and clinically useful prognostic method than the number of positive LNs resected or the total number of LNs retrieved for predicting the course of patients with stage III CRC.
PMCID: PMC3420313  PMID: 22533518
Colorectal cancer; Stage III; Lymph node ratio; Prognosis
13.  Combined use of EUS-guided FNA and immunocytochemical stains discloses metastatic and unusual diseases in the evaluation of mediastinal lymphadenopathy of unknown etiology 
Annals of Thoracic Medicine  2012;7(2):84-91.
Mediastinal lymphadenopathy (ML) is a cause for concern, especially in patients with previous malignancy. We report our experience with the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunocytochemical stains in patients being evaluated for ML.
Retrospective analysis of patients with ML of unknown origin who underwent EUS-FNA. On-site evaluation was performed by experienced cytologist, and special immunocytochemical stains were requested as indicated.
A total of 116 patients were included, and a total of 136 mediastinal LN were sampled. Prior malignancy was present in 45%. The most common site of examined lymph node (LN) were subcarinal (76%, 103 LN). The median long and short axis diameters were 28 mm and 13 mm, respectively. FNA was read on-site as malignant, 21 (16%); benign, 100 (76.9%); suspicious, six (4%); atypical, 3 (2%); and inadequate sample, six (4%). Sixty-four LN were deferred for additional studies; 22 for immunocytochemical and 26 for Gimesa (GMS) stain and 21 for flow cytometry. Final FNA read was malignant in 28 (21%), benign in 103 (76%), suspicious in three (2%), and atypical in two (1%). Metastatic malignancies disclosed included Hodgkin's and Non-Hodgkin's lymphoma, melanoma, hepatoma, breast, lung, colon, renal, endometrial, Fallopian tube, and unknown carcinoma. The sensitivity, specificity, and accuracy of the final FNA read to predict malignancy were 100%.
EUS-guided FNA with additional ancillary studies is useful in disclosing metastatic ML from a variety of neoplasms. Due to its safety and accuracy profile, it should be considered the test of choice in evaluating abnormal ML in appropriately selected patients.
PMCID: PMC3339209  PMID: 22558013
Endoscopic ultrasound; fine needle aspiration; immunostains; lung cancer; metastatic disease
14.  Unusual, Metastatic, or Neuroendocrine Tumor of the Pancreas: A Diagnosis with Endoscopic Ultrasound–guided Fine-needle Aspiration and Immunohistochemistry 
To determine the yield of endoscopic ultrasound–guided fine-needle aspiration (EUS–FNA) in combination with immunostains in diagnosing unusual solid pancreatic masses (USPM) in comparison with pancreatic adenocarcinoma (ACP).
Patients and Methods:
All EUS–FNA of solid pancreatic masses performed with a 22-gauge needle were included. Data on clinical presentations, mass characteristics, presence of pancreatitis, yield of tissue, and final diagnosis were compared between the two groups. On site cytopathology was provided and additional passes were requested to perform immunostains.
Two hundred and twenty-nine cases with either adenocarcinoma or USPM were included. The median age of the cohort was 65 years. ACP (210/229, 92%) accounted for the majority of the cases. The USPM included neuroendocrine (NET) masses (n=13), metastatic renal carcinoma (n=3), metastatic melanoma (n=1), lymphoma (n=1), and malignant fibrous histiocytoma (n=1). Subjects with ACP were significantly more likely to present with loss of weight (P=0.02) or obstructive jaundice (P<0.001). Subjects with ACP were more likely to have suspicious/atypical FNA biopsy results as compared with USPM (10% vs 0%). The sensitivity of EUS–FNA with immunostains was 93% in ACP as compared with 100% in USPM. Diagnostic accuracy was higher in USPM as compared with ACP (100% vs 93%).
EUS–FNA using a 22-gauge needle with immunostains has excellent diagnostic yield in patients with USPMs, which is comparable if not superior to the yield in pancreatic adenocarcinoma.
PMCID: PMC3326984  PMID: 22421714
Cytology; endoscopic ultrasound; fine needle aspiration; immunostains; metastasis; neuroendocrine tumors; pancreas
15.  Serum Biomarker Panels for the Detection of Pancreatic Cancer 
Serum biomarker-based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.
Experimental Design
Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) (n=333), benign pancreatic conditions (n=144), and healthy control individuals (n=227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n=33), lung (n=62), and breast (n=108) cancers.
Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In a training set (n=160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19-9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19-9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with a SN/SP of 76/90%. In an independent validation set (n=173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19-9, ICAM-1 and OPG demonstrated a SN/SP of 78/94 while the panel of CA19-9, CEA, and TIMP-1 demonstrated a SN/SP of 71/89%. The CA19-9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP=100%), lung (SP=97%), or colon (SP=97%) cancer.
The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations.
PMCID: PMC3075824  PMID: 21325298
Pancreatic Cancer; PDAC; Early Detection; Diagnosis; Serum Biomarkers; CA 19-9; Multimarker Panel
16.  Successful Closure of Pharyngo-cutaneous and Phayryngo-tracheal Fistulas using Removable Hypopharyngeal Stent after Laryngectomy for Laryngeal Carcinoma 
Placement of removable stents to close pharyngo-cutaneous and tracheo-pharyngeal fistulas after laryngectomy has not been reported before. This case presents the feasibility of removable esophageal stent in closing pharyngo-cutaneous and tracheo-pharyngeal fistulas after laryngectomy for laryngeal cancer. Consecutive patients who underwent placement of removable esophageal stent for closing pharyngo-cutaneous and tracheo-pharyngeal fistulas after laryngectomy for laryngeal cancer. Three patients underwent successful stent placement in the hypopharynx. The stents were well tolerated. Patient one had the stent for 14 months, leading to complete healing of the fistula. Removal was successful. The second patient was palliated but died 8 weeks after stent placement. The third patient has successful palliation of his tracheo-esophageal fistula and the stent is being exchanged every 3-4 months to palliate his fistula. Closure of pharyngo-cutaneous and tracheo-esophageal fistulas is feasible with esophageal removable stents. These stents provide alternative options when dealing with these challenging problems.
PMCID: PMC3271698  PMID: 22249096
Laryngeal cancer; leaks; removable esophageal stents; stricture
17.  Epidermal growth factor receptor (EGFR) intron 1 polymorphism and clinical outcome in pancreatic adenocarcinoma 
American journal of surgery  2010;200(3):398-405.
EGFR intron1 has a polymorphic region of CA-repeats which is believed to be associated with increased EGFR expression, tumor aggressiveness, and worse survival in cancer patients.
We investigated a large population of pancreatic adenocarcinoma patients to evaluate this polymorphism as a potential prognostic marker of clinical outcome. We included DNA obtained from 50 resected pancreatic adenocarcinomas and from 85 diagnostic EUS-FNA corresponding to patients with unresectable tumors. The correlation between CA-repeats length and EGFR mRNA levels was also examined.
Analysis of the 135 patients revealed no correlation between EGFR intron 1 CA repeats length and tumor stage. There was no difference in overall patient survival when stratified by allele length. A correlation between EGFR intron 1 length and EGFR transcript and protein levels could not be established.
The length of the EGFR intron1 CA repeats does not correlate with levels of EGFR expression and can not be employed as marker of clinical prognosis in pancreatic cancer patients.
PMCID: PMC2909357  PMID: 20409526
EGFR; pancreatic cancer; intron 1 polymorphism
18.  Predictors of malignancy in EUS-guided FNA for mediastinal lymphadenopathy in patients without history of lung cancer 
Annals of Thoracic Medicine  2011;6(3):126-130.
Mediastinal lymphadenopathy (ML) poses a great diagnostic challenge.
To investigate the predictors of malignancy in endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of ML in patients without known lung cancer.
Retrospective study.
Tertiary referral center.
One hundred eight patients without known lung cancer who underwent EUS guided-FNA for ML between 2000 and 2007. All subjects underwent EUS-guided FNA. Data was collected on patients′ demographics, and lymph node (LN) characteristics. Diagnosis of LN malignancy was based on FNA findings and clinical follow-up.
One hundred eight patients were analyzed; 58 (54%) were men and 87 (79%) were Caucasian. Mean age was 55 years. Prior malignancy was present in 48 (43%) patients. A total of 126 FNA samples from 126 distinct LNs were performed. Twenty-five (20%) LNs were positive for malignancy. Mean short and long-axis for LNs were 13 and 29 mms respectively. Round shape and sharp borders were found in 29 (15%) and 25 (22%) LNs, correspondingly. Independent predictors of a malignant FNA were: Prior cancer (OR 13.10; 95% CI 2.7-63.32; P = 0.001), short axis (OR 1.10; 95% CI 1.00-1.22; P = 0.041) and sharp LN borders (OR 5.47; 95% CI 1.01-29.51; P = 0.048). Age, race, gender, long axis, round shape were not associated with cancer in our cohort.
Retrospective design and lack of surgical gold standard.
Increased risk of malignancy was associated with prior history of cancer, larger LN short axis and presence of LN sharp borders. These predictors may help guide endoscopists perform FNA in malignant LNs, increasing the overall efficiency of EUS-FNA for ML.
PMCID: PMC3131754  PMID: 21760843
Endoscopic ultrasound; lung cancer; mediastinal lymphadenopathy; staging; fine needle aspiration
20.  Dynamic telecytopathology of on site rapid cytology diagnoses for pancreatic carcinoma 
CytoJournal  2006;3:27.
Diagnosis of pancreatic lesions can be accurately performed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) with onsite cytopathologists to assess specimen adequacy and to determine a preliminary diagnosis. Considerable time is needed to perform on-site assessments. This takes away work time of cytopathologists and prohibits them from serving remote locations. It is therefore logical to ask if real-time telecytopathology could be used to assess specimen adequacy and if telecytopathology diagnosis has the same level of agreement to the final diagnosis as that of onsite evaluation. In this study, we compare agreement between cytodiagnoses rendered using telecytopathology with onsite and final interpretations.
40 Diff-Quik-stained EUS-FNA were re-evaluated retrospectively (patient ages 31–62, 19:21 male:female, 15 non-malignant lesions, 25 malignant lesions as classified by final diagnosis). Each previously assessed by a cytopathologist and finally reviewed by the same or different cytopathologist. Blinded to the final diagnosis, a resident pathologist re-screened all slides for each case, selected a slide and marked the diagnostic cells most representative of the lesion. Blinded to the diagnosis, one cytopathologist assessed the marked cells through a real time remotely operated telecytopathology system (MedMicroscopy). Diagnosis and time spent were recorded. Kappa statistic was used to compare agreements between telecytopathology vs. original onsite vs. final diagnoses.
Time spent for prescreening ranged from 1 to 5 minutes (mean 2.6 +/- 1.3 minutes) and time spent for telecytopathology diagnosis ranged from 2–20 minutes (mean 7.5 +/- 4.5 minutes). Kappa statistics, K, was as follows: telecytopathology versus onsite diagnosis K, 95% CI = 0.65, 0.41–0.88, for telecytopathology versus final K, 95% CI = 0.61, 0.37–0.85 and for onsite diagnosis versus final K, 95% CI = 0.79, 0.61–0.98. There is no significant difference in agreement between onsite and telecytopathology diagnoses. Kappa values for telecytopathology were less than onsite evaluation when compared to the final diagnosis; however, the difference was not statistically significant.
This retrospective study demonstrates the potential use of telecytopathology as a valid substitute for onsite evaluation of pancreatic carcinoma by EUS-FNA.
PMCID: PMC1713251  PMID: 17156485
21.  Preoperative diagnosis of a mediastinal granular cell tumor by EUS-FNA: a case report and review of the literature 
CytoJournal  2005;2:8.
We report the first case of a posterior mediastinal granular cell tumor initially diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in a 51-year-old male with a prior history of colon cancer. Aspirates obtained were cellular and composed of polygonal cells with abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase stain performed on the cell block for antibodies to S-100 protein showed strong, diffuse staining of the cytoplasmic granules. Electron microscopy performed on the cell block revealed numerous cytoplasmic lysosomes. This is the first case report in the English literature of a definitive preoperative diagnosis of a mediastinal granular cell tumor utilizing material obtained via EUS-FNA.
PMCID: PMC1184093  PMID: 15943858
granular cell tumor; EUS-FNA; cytology; mediastinum

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