Steven Keilin

Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma

Objectives: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. Methods: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. Results: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. Conclusions: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.

Cholesterol Ester Storage Disease (CESD) Diagnosed in an Asymptomatic Adult

Cholesterol ester storage disease (CESD) is a rare, autosomal-recessive, lysosomal storage disorder. It is characterized by deficiency of lysosomal acid lipase (LAL) enzyme, which is responsible for intracellular hydrolysis of triaclyglycerols and cholesteryl esters. The deficiency state of LAL can be expressed in two major phenotypic variants: Wolman’s disease, which is the severe infantile form, uniformly fatal within 1–2 years of life, and the more benign CESD, which is associated with some residual LAL activity [1–4]. Patients with CESD often present in the first or second decade of life with hepatosplenomegaly and elevated cholesterol levels. Hepatomegaly caused by hepatic steatosis and fibrosis can lead to micro-nodular cirrhosis. Hypercholesterolemia as a result of upregulation of hepatic very low density lipoprotein B-100 synthesis [5] and low plasma levels of high density lipoproteins (HDL) [6] may lead to premature atherosclerosis and vascular complications. In this paper, we report a completely asymptomatic 43-year-old male, who was found to have CESD incidentally while undergoing workup for chronic hepatitis C infection.

Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis. For steroid-dependent disease, azathioprine has been used for maintenance of remission. Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however, there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis. A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil, which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production. Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patients energy level and blood glucose control and was not associated with any adverse events. The patient was managed without a biliary stent. However, there was a return of symptoms, jaundice, increase in transaminases, and hyperbilirubinemia when the prednisone dose reached 11 mg per day. In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis, the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events, but it did not enable discontinuation of the steroids. Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

Diagnosis and management of Barrett’s esophagus for the endoscopist

In Barrett’s esophagus, the stratified squamous epithelium lining the esophagus is replaced by specialized intestinal-type columnar epithelium. The prevalence of Barrett’s esophagus has ranged from 0.9% to 4.5%. The rate of progression from Barrett’s esophagus to esophageal adenocarcinoma is 0.5% per patient-year. Proton-pump inhibitors are the mainstay of symptom control in Barrett’s patients. Nondysplastic Barrett’s and Barrett’s with low-grade dysplasia (LGD) are typically managed by periodic surveillance. Radiofrequency ablation is being evaluated as a modality for managing nondysplastic Barrett’s and Barrett’s with LGD. The options for the management of Barrett’s patients with high-grade dysplasia (HGD) include endoscopic therapy, surgery, and intensive surveillance until biopsy reveals adenocarcinoma. Endoscopic therapy involves endoscopic mucosal resection (EMR) and ablation. More aggressive techniques such as endoscopic submucosal dissection and larger segment endoscopic mucosal resection are under study. In this review, we discuss the diagnosis and management of Barrett’s esophagus. The recommendations from the major gastroenterologic societies and the current and investigational endoscopic modalities for the management of Barrett’s esophagus with and without dysplasia are reviewed.

Treatment allocation in patients with early-stage esophageal adenocarcinoma: Prevalence and predictors of lymph node involvement

In considering treatment allocation for patients with early esophageal adenocarcinoma, the incidence of lymph node metastasis is a critical determinant; however, this has not been well defined or stratified by the relevant clinical predictors of lymph node spread.

Is prior cholecystectomy associated with decreased survival in patients with resectable pancreatic adenocarcinoma following pancreaticoduodenectomy

BACKGROUND Patients with pancreatic cancer who present with biliary symptoms may undergo cholecystectomy and thus delay cancer diagnosis. We hypothesized that prior cholecystectomy leads to decreased overall survival in patients with pancreatic adenocarcinoma. METHODS Retrospective study of hepatobiliary database. RESULTS Three hundred sixty-five patients with a diagnosis of resectable periampullary pancreatic adenocarcinoma were identified. Eighty-seven patients underwent prior cholecystectomy. Median age (P = .48), body mass index (BMI) (P = .8), diabetes status (P = .06), American Society of Anesthesiologists (ASA) class (P = .22), stent placement (P = .13), operative time (P = .76), estimated blood loss (EBL) (P = .24), intraoperative transfusion (P = .91), portal vein resection (P = .25), LOS (P = .09) adjuvant therapy (P = .2), tumor size (P = .89), differentiation (P = .67), angiolymphatic invasion (P = .69), perineural invasion (P = 54), nodal metastasis (P = .43), complication rate (P = .75), and 30-day mortality (P = .58) were not statistically different between patients with previous cholecystectomy and those without. Median survival was 14 months for patients with a history of cholecystectomy and 16 months for those without (P = .25). Previous cholecystectomy was not a predictor of survival on Cox regression analysis. CONCLUSION There was no difference in overall survival in patients with pancreatic cancer with prior cholecystectomy versus those without.

Increased Incidence of Benign Pancreatic Pathology following Pancreaticoduodenectomy for Presumed Malignancy over 10 Years despite Increased Use of Endoscopic Ultrasound.

Despite using imaging studies, tissue sampling, and serologic tests about 5–10% of surgeries done for presumed pancreatic malignancies will have benign findings on final pathology. Endoscopic ultrasound (EUS) is used with increasing frequency to study pancreatic masses. The aim of this study is to examine the effect of EUS on prevalence of benign diseases undergoing Whipple over the last decade. Patients who underwent Whipple procedure for presumed malignancy at Emory University Hospital from 1998 to 2011 were selected. Demographic data, history of smoking and drinking, history of diabetes and pancreatitis, imaging data, pathology reports, and tumor markers were extracted. 878 patients were found. 95 (10.82%) patients had benign disease. Prevalence of benign finding had increased over the recent years despite using more EUS. Logistic regression models showed that abdominal pain (OR: 5.829, 95% CI 2.681–12.674, P ≤ 0.001) and alcohol abuse (OR: 3.221, CI 95%: 1.362–7.261, P: 0.002) were predictors of benign diseases. Jaundice (OR: 0.221, 95% CI: 0.084–0.58, P: 0.002), mass (OR: 0.145, 95% CI: 0.043–0.485, P: 0.008), and ductal dilation (OR: 0.297, 95% CI 0.134–0.657, P: 0.003) were associated with malignancy. Use of imaging studies, ERCP, and EUS has not decreased the percentage of benign findings after surgery for presumed pancreatic malignancy.

Giant cell tumor of the common bile duct.

C 60-year-old man with diabetes and atrial fibrillation was incidentally found to have a common bile duct mass on computed omography of the chest during a work-up for pneumonia. The atient was asymptomatic. Physical exam revealed no jaundice, scleral cterus, abdominal pain, masses, or hepatosplenomegaly. Alkaline hosphatase was 175 U/L, -glutamyl transpeptidase 230 IU/L, asartate aminotransferase 63 U/L, and alanine aminotransferase 64 /L. Total bilirubin, viral hepatitis serologies, human immunodefiiency virus, and tumor markers (including alpha-fetoprotein, carcioembryonic antigen, CA 19-9, and CA-125) were normal. A comuted tomography scan of the abdomen revealed a dilated common ile duct of 2.3 cm, with a 1.7-cm mass projecting into the lumen of he distal common bile duct from the right lateral wall at the level of he head of the pancreas (Figure A). The patient underwent endocopic retrograde cholangiopancreatography, which demonstrated a ilated common bile duct of 2.2 cm, with a 2 3 cm intraluminal lling defect attached to the right wall of the distal common bile duct Figure B). A sphincterotomy and basket sweeps were performed to btain soft tissue samples. Pathology revealed multinucleated giant ells in a background of mononuclear cells, with a reactive process avored over neoplastic. The patient subsequently underwent surgical esection with a Whipple procedure. Postoperative gross pathology evealed a 1.5-cm polypoid lesion in the common bile duct (Figure C), ith histology showing multinucleated osteoclast-like giant cells and any mononuclear cells (Supplementary Figure A), yielding a diagosis of a giant cell tumor of the common bile duct. Immunohistohemical staining of the multinucleated giant cells was positive for D68, whereas the mononuclear cells were positive for CD163, vientin, and epithelial membrane antigen. All cells were cytokeratinegative. The patient was alive and disease-free 16 months postopertively. Tumors containing osteoclast-like giant cells are rarely found outide of bone. Those involving the hepatobiliary tree are especially rare, ith only 12 cases reported in the literature. Of these, 4 have been lassified as benign giant cell tumors, whereas the others have been escribed as malignant or existing in the setting of malignant cells.1 he benign cases presented predominantly in men in the sixth decade f life. The patients experienced jaundice, abdominal pain, or were symptomatic. All tumors invaded the ductal wall and consisted istologically of osteoclast-like giant cells and mononuclear cells withut atypical features. These patients had a benign course, whereas hose patients with malignant tumors pursued a variable course and ad significant differences in long-term survival.2 Controversy has existed over the malignant potential of these giant ell tumors. In those described as malignant, the multinucleated giant ells are thought to be benign cells that exist in a bed of neoplastic onocytes that exhibit atypical features, including variations in size nd shape, and abnormal mitoses.3 Neoplastic spindle cells, necrosis, nd/or portions of frank adenocarcinoma might be present. In conrast, in the benign giant cell tumors, the mononuclear cells have ore uniform characteristics with fewer mitoses and no bizarre feaures, necrosis, spindle cells, or carcinomatous components. Also faoring the argument for a benign classification are the patients’ linical courses, which included long-term disease-free survival. This ase illustrates the benign potential of osteoclast-like giant cell tumors f the biliary system and the need for accurate histologic evaluation in roperly diagnosing and managing such patients.

Fluoroscopic gastric peroral endoscopic pyloromyotomy (G-POEM) in patients with a failed gastric electrical stimulator

Abstract Background Gastric electrical stimulators (GESs) have been used to treat refractory gastroparesis in patients who fail initial therapies such as dietary modifications, control of psychological stressors and pharmacologic treatment. More recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has emerged as a novel endoscopic technique to treat refractory gastroparesis. We present a case series of patients with refractory gastroparesis who failed treatment with an implanted GES that were safely treated with G-POEM performed under fluoroscopy as a salvage therapy. Methods Cases of G-POEM performed on patients with refractory gastroparesis who failed treatment with a GES were retrospectively reviewed. All G-POEM procedures were performed under fluoroscopic guidance with the GES still in place. Gastroparesis Cardinal Symptoms Index (GCSI) and gastric emptying scintigraphy were assessed before and after the procedure. Patients were followed up for up to 18 months post procedure. Results Five patients underwent G-POEM after failing treatment with a GES. Under fluoroscopy, the GES and their leads were visualized in different parts of the stomach. One GES lead was observed at the antrum near the myotomy site. All procedures were successfully completed without complications. Patients’ GCSI decreased by an average of 62% 1 month post procedure. Patients also had notable improvements in gastric emptying 2 months post procedure. Conclusion In patients with refractory gastroparesis who have failed treatment with a GES, G-POEM can be safe and effective without removing the GES. To visualize the GES and avoid cutting GES leads during myotomy, the procedure should be performed under fluoroscopy.

Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis

BACKGROUND & AIMS: Gastric peroral endoscopic pyloromyotomy (GPOEM) is becoming a promising treatment option for patients with refractory gastroparesis. We aimed to systematically assess the efficacy of GPOEM and its effects on health care use. METHODS: We performed a retrospective study on 30 patients with refractory gastroparesis who underwent GPOEM from June 2015 through July 2017 at a tertiary center. We compared outcomes with those of 7 patients with refractory gastroparesis who did not undergo the procedure (controls). The primary outcomes were patient‐reported reductions in symptoms, based on the gastroparesis cardinal symptom index (GCSI), and increases in 8 aspects of quality of life, based on Short Form 36 (SF‐36) scores. Data were collected on the day of the procedure (baseline) and at 1 month, 6 months, 12 months, and 18 months afterward. Secondary outcomes included visits to the emergency department or hospitalization for gastroparesis‐related symptoms. RESULTS: GPOEM was technically successful in all patients and significantly reduced GCSI scores in repeated‐measure analysis of variance (F2.044, 38.838 = 22.319; P < .0005). The mean score at baseline was 3.5 ± 0.6, at 1 month after GPOEM was 1.8 ± 1.0 (P < .0005), at 6 months after was 1.9 ± 1.2 (P < .0005), at 12 months after was 2.6 ± 1.5 (P < .026), and at 18 months after was 2.1 ± 1.3 (P < .016). GPOEM was associated with improved quality of life: 77.8%, 76.5%, and 70% of patients had significant increases in SF‐36 scores, compared with baseline, at 1 month, 6 months, and 12 months after GPOEM, respectively (F1.71,18.83 = 14.16; P < .0005). Compared with controls, patients who underwent GPOEM had significant reductions in GCSI, after we controlled for baseline score and duration of the disease (F1,31 = 9.001; P = .005). Patients who received GPOEM had significant reductions in number of emergency department visits (from 2.2 ± 3.1 times/mo at baseline to 0.3 ± 0.8 times/mo; P = .003) and hospitalizations (from 1.7 ± 2 times/mo at baseline to 0.2 ± 0.4 times/mo; P = .0002). CONCLUSIONS: In a retrospective study of patients who underwent GPOEM for refractory gastroparesis, we found the procedure significantly improved symptoms, increased quality of life, and reduced health care use related to gastroparesis.