Vaibhav Mehendiratta

Identification of Cholangiocarcinoma by Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection

BACKGROUND & AIMS It is a challenge to collect samples from bile duct strictures to diagnose patients with cholangiocarcinoma. We investigated the utility of the Spyglass Spyscope, a single-operator endoscope that is used to perform cholangiopancreatoscopy, to identify extrahepatic cholangiocarcinoma in patients who were not diagnosed with this disorder by endoscopic retrograde cholangiopancreatography (ERCP) cytology or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) analyses. METHODS We conducted a retrospective analysis of data from 30 patients (median age, 67 years; 67% male) with indeterminate extrahepatic biliary strictures who were ultimately diagnosed with cholangiocarcinoma but had inconclusive results from initial biliary ductal brush cytology and EUS-FNA analyses. Patients then underwent cholangioscopy by using the Spyglass Spyscope and intraductal biopsy analysis. None of the patients had a definitive mass in abdominal imaging or EUS analyses. RESULTS The biliary stricture was located in the common bile duct in 13 patients and in the common hepatic duct in 17 patients. The Spyglass Spyscope system had 77% accuracy (23 of 30) in the diagnosis of malignancies that were inconclusive on the basis of ERCP-guided brush or EUS-FNA analyses. CONCLUSIONS The Spyglass Spyscope for cholangioscopy and biopsy collection identified malignancies with 77% accuracy in patients with suspected cholangiocarcinoma.

Serologic Markers Do Not Predict Histologic Severity or Response to Treatment in Patients With Autoimmune Hepatitis

BACKGROUND & AIMS Autoimmune hepatitis (AIH) is characterized by the presence of circulating autoantibodies, hypergammaglobulinemia, necroinflammatory histology, and a response to immunosuppressive drugs. The goal of this retrospective study was to determine whether the presence of antinuclear antibodies (ANAs) or anti-smooth muscle antibodies (ASMAs) in patients with AIH correlated with clinical presentation, histologic findings, or response to immunosuppressive therapy. METHODS Fifty-two patients diagnosed with AIH, on the basis of the revised scoring system of International Autoimmune Hepatitis group, were reviewed. Data on age, gender, aminotransferase levels, autoantibody titers, treatment regimens, and response to treatment were recorded. Seropositivity was defined as ANA >1:40 or ASMA >1:40. Percutaneous liver biopsies obtained at the initial presentation were reviewed. RESULTS Forty-two patients with AIH (81%) were seropositive, and 10 (19%) were seronegative. Both groups were similar with respect to demographics, treatment regimens, and response to therapy. Histologic parameters were similar among the 2 groups, including portal and lobular inflammation, piecemeal necrosis, and centrilobular necrosis. There were no significant differences in aminotransferase levels at diagnosis or after treatment. CONCLUSIONS The prevalence of ANAs or ASMAs did not correlate with the clinical or histologic severity of AIH at diagnosis. Furthermore, there was no correlation between antibody status and response to immunosuppressive therapy. Therefore, patients who meet the diagnosis of AIH on the basis of the revised scoring system of International Autoimmune Hepatitis Group should be given immunosuppressive therapy, regardless of antibody status.

Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells

Systemic sclerosis (SSc) IgGs affecting the M(3)-muscarinic receptor (M(3)-R) have been proposed to be responsible for the gastrointestinal (GI) dysmotility in this disease. However, the effect of SSc IgGs on smooth muscle cell (SMC) function has not been studied. We determined the effect of SSc IgGs on the muscarinic receptor activation by bethanechol (BeCh; methyl derivate of carbachol) in SMC and smooth muscle strips from rat internal anal sphincter. IgGs were purified from GI-symptomatic SSc patients and normal volunteers, with protein G-Sepharose columns. SMC lengths were determined via computerized digital micrometry. The presence of M(3)-R and IgG-M(3)-R complex was determined by Western blot. IgGs from SSc patients but not from normal volunteers caused significant and concentration-dependent inhibition of BeCh response (P < 0.05). The maximal shortening of 22.2 +/- 1.2% caused by 10(-4) M BeCh was significantly attenuated to 8.3 +/- 1.2% by 1 mg/ml of SSc IgGs (P < 0.05). Experiments performed in smooth muscle strips revealed a similar effect of SSc IgG that was fully reversible. In contrast to the effect on BeCh, the SSc IgGs caused no significant effect (P > 0.05) on K(+) depolarization and alpha(1)-adrenoceptor activation by phenylephrine. Western blot studies revealed the specific presence of SSc IgG-M(3)-R complex. SSc IgGs attenuated M(3)-R activation, which was reversible with antibody removal. These data suggest that SSc GI dysmotility may be caused by autoantibodies that inhibit the muscarinic neurotransmission. Future treatment of SSc patients may be directed at the removal or neutralization of these antibodies.

Fully Covered Self-expandable Metal Stents are Effective and Safe to Treat Distal Malignant Biliary Strictures, Irrespective of Surgical Resectability Status

Aim We report a retrospective analysis of patients with malignant biliary obstruction in whom a newly released fully silicon-covered, WallFlex, self-expandable metal stent (CSEMS) was placed for biliary decompression. Patients and Methods Between March, 2009 and March, 2010, all patients with obstructive jaundice secondary to pancreatic cancer underwent placement of a CSEMS, regardless of resectability. A CSEMS was placed across the malignant stricture. These patients were then staged for their cancer by computed tomography, magnetic resonance imaging, and/or endoscopic ultrasound-guided fine-needle aspiration. Patient found to have resectable cancer were offered a pancreaticoduodenectomy. Results We identified 88 patients with pancreatic cancer who received a CSEMS. Forty patients were deemed resectable and underwent surgery. Pancreaticoduodenectomy was performed in 34 of 40 patients. The CSEMS was easily removed at the time of surgical resection without any complications. The 44 unresected patients with covered SEMS were followed for a mean of 4.2 months (range, 1 to 13). The patency rate for stents was 97% at 12 months. Immediate procedural complications included post-endoscopic retrograde cholangiopancreatography pancreatitis (n=9) and duodenal perforation (n=2). Four patients (5%) had migration and 3 (3%) had stent occlusion. There were no cases of cholecystitis during the follow-up. The patients who presented with stent migration or occlusion underwent stent revision. Conclusions Placement of the newly available CSEMS can be used to effectively and safely treat biliary obstructions from pancreatic carcinoma. We recommend that the CSEMS be used as an initial intervention to relieve malignant biliary obstruction, even in patients whose surgical resectability status is uncertain.

Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function.

BACKGROUND & AIMS Patients with systemic sclerosis (SSc) have impairments in gastrointestinal smooth muscle function. The disorder has been associated with circulating antibodies to cholinergic muscarinic the type-3 receptor (M(3)-R). We investigated whether it is possible to neutralize these antibodies with pooled human IgGs (pooledhIgG). METHODS We studied the effects of IgGs purified from patients with SSc (SScIgGs) on cholinergic nerve stimulation in rat colon tissues. We also examined the effects of SScIgGs on M(3)-R activation by bethanechol (BeCh), M(3)-R occupancy, and receptor binding using immunofluorescence, immunoblot, and enzyme-linked immunosorbent analyses of human internal anal sphincter (IAS) smooth muscle cells, before and after administration of pooledhIgG. Functional displacement of M(3)-R occupancy by the SScIgGs was compared with that of other IgGs during the sustained phase of BeCh-induced contraction of intact smooth muscles from rats. RESULTS SScIgG significantly attenuated neurally mediated contraction and acetylcholine release in rat colon as well as BeCh-induced sustained contraction of the IAS smooth muscle. In immunofluorescence analysis, SScIgG co-localized with M(3)-R. In immunoblot and enzyme-linked immunosorbent analyses, M(3)-R loop-2 peptide and human IAS SMC membrane lysates bound significant amounts of SScIgG, compared with IgGs from healthy individuals and pooledhIgG. Binding was attenuated significantly by application of pooledhIgG, which by itself had no significant effect. Incubation of samples with pooledhIgG, or mixing pooledhIgG with SScIgG before administration to tissues, significantly reduced binding of SScIgG, indicating that pooledhIgG prevents SScIgG blockade of M(3)-R. CONCLUSIONS In studies of rat and human tissues, pooled human IgG prevent and reverses the cholinergic dysfunction associated with the progressive gastrointestinal manifestations of SSc by neutralizing functional M(3)-R antibodies present in the circulation of patients with SSc.

Use of radiofrequency ablation probe for eradication of residual adenoma after ampullectomy

required to detect a 9% difference in ADRs (a error 5%, b error level 20%). In the context of endoscopy performance, this article illustrates the potential pitfall of judging overall ADRs based on a brief “snapshot in time” that may capture only a single high point or low point and not reflect the overall trend. Observations should encompass a 12-month duration and comprise at least 30 endoscopists in each practice site.

A rare cause of dilated bile duct incidentally detected on imaging

Adenomas involving the extrahepatic bile ducts are rare benign tumours of the biliary tract. Given the asymptomatic nature of these tumours and the natural progression of biliary adenoma to carcinoma including cholangiocarcinoma, early detection is challenging. We present a case of an octogenarian woman with a remote history of gallstones who initially presented to the gastroenterology office for an incidental finding of biliary dilation, and whose subsequent imagings and biopsy suggested common bile adenoma. However, the patient was deemed a poor surgical candidate for pancreaticoduodenectomy, and unfortunately represented 5 months later with findings suggesting cholangiocarcinoma. This case provides a unique opportunity to study the natural progression of biliary adenoma to cholangiocarcinoma.

Adenomas involving the extrahepatic biliary tree are rare but have an aggressive clinical course

Biliary adenomas that are usually found in surgically removed gallbladders are rare, but can also occur in the extrahepatic biliary tree. We present a case series of extrahepatic bile duct adenomas at our institution, along with a review of the literature. All three patients with extrahepatic biliary adenomas (two in the common bile ducts, one in the hepatic duct) were female with a mean age of 74 years. On initial presentation, none of the patients had obstructive jaundice but two of the three patients had symptoms of biliary origin. Case 1 is an 85-year-old woman with an incidental biliary dilation seen on chest imaging; endoscopic ultrasound revealed a sessile adenomatous polyp in the distal bile duct. The patient refused surgery and presented with occlusive biliary stricture and jaundice 5 months after initial presentation, with cytology confirming malignant progression. Case 2 is a 78-year-old woman with a history of primary sclerosing cholangitis and who presented with cholangitis, and Gram-negative sepsis. A polypoid lesion was seen on imaging in the common hepatic duct and direct cholangioscopy with biopsies confirmed the presence of adenoma with high grade dysplasia. The patient underwent successful total bile duct resection and hepaticojejunostomy but represented 1 year later with diffuse metastatic disease to the bone, liver, and peritoneum. Case 3 is a 61-year-old woman who presented with symptoms suggestive of gallbladder pathology and was found to have a polypoid bile duct lesion on intraoperative cholangiogram. Endoscopic retrograde cholangioscopy showed an adenomatous polyp with high grade dysplasia involving the distal common bile duct. The patient underwent distal bile duct resection with choledochojejunostomy but presented with jaundice 4 years after surgery. She was found to have adenocarcinoma involving the small bowel in the Roux limb of jejunum and transverse colon. All three patients in our series presented with interval gastrointestinal malignancy and we therefore recommend aggressive surgical intervention and close postoperative surveillance when diagnosis of extrahepatic bile duct adenoma is made.

Gastrointestinal: Incidentally detected gastric carcinoma in patient with common variable immunoglobulin deficiency: Education and Imaging

The patient is a 58 year old woman with medical history of common variable immune deficiency (CVID) presented with chronic, intermittent diarrhea and abdominal bloating. Laboratory studies, colonoscopy and upper GI-small bowel follow-through were unremarkable. Esophagogastroduodenoscopy (EGD) revealed a broadbased, multilobulated mass measuring 4 cm in the mid-gastric body (Figure 1) with endoscopic ultrasound representing a T1 N0 tumor. Subsequent endoscopic resection confirmed the diagnosis of adenocarcinoma, arising in a background of an adenoma with high grade dysplasia (Figure 2). There was also focal high grade dysplasia and intramucosal carcinoma at the pylorus, an endoscopically unremarkable area. The dysplasia was present in a background of chronic, focally active gastritis with intestinal metaplasia (Figure 3). Other biopsies showed chronic and focally active gastritis. Immunohistochemical studies for Helicobacter pylori were negative. The patient ultimately underwent total gastrectomy with Roux-en-Y esophagojejunostomy given no computed tomographic evidence of metastatic disease. This case is interesting in that it underscores the up to 47-fold increase in risk for gastric carcinoma in patients with CVID as reported in European populations. Gastric lesions are usually detected incidentally during endoscopy for non-specific dyspeptic symptoms and have been reported in patients as young as 11 years of age. A study found that Helicobacter pylori infection was detected in 41% of CVID patients and that Helicobacter pylori may play a role in the gastric carcinogenesis in CVID patients. Overexpression of p53 was also found in 18% of CVID patients. To date, there are no definitive society guidelines for screening for gastric malignancy in patients with CVID. Given the high incidence of dysplasia and increased risk of gastric malignancy in these patients, physicians should have a low threshold for diagnostic endoscopy, especially if gastrointestinal symptoms persist despite therapy.

Education and imaging. Gastrointestinal: Incidentally detected gastric carcinoma in patient with common variable immunoglobulin deficiency.

The patient is a 58 year old woman with medical history of common variable immune deficiency (CVID) presented with chronic, intermittent diarrhea and abdominal bloating. Laboratory studies, colonoscopy and upper GI-small bowel follow-through were unremarkable. Esophagogastroduodenoscopy (EGD) revealed a broadbased, multilobulated mass measuring 4 cm in the mid-gastric body (Figure 1) with endoscopic ultrasound representing a T1 N0 tumor. Subsequent endoscopic resection confirmed the diagnosis of adenocarcinoma, arising in a background of an adenoma with high grade dysplasia (Figure 2). There was also focal high grade dysplasia and intramucosal carcinoma at the pylorus, an endoscopically unremarkable area. The dysplasia was present in a background of chronic, focally active gastritis with intestinal metaplasia (Figure 3). Other biopsies showed chronic and focally active gastritis. Immunohistochemical studies for Helicobacter pylori were negative. The patient ultimately underwent total gastrectomy with Roux-en-Y esophagojejunostomy given no computed tomographic evidence of metastatic disease. This case is interesting in that it underscores the up to 47-fold increase in risk for gastric carcinoma in patients with CVID as reported in European populations. Gastric lesions are usually detected incidentally during endoscopy for non-specific dyspeptic symptoms and have been reported in patients as young as 11 years of age. A study found that Helicobacter pylori infection was detected in 41% of CVID patients and that Helicobacter pylori may play a role in the gastric carcinogenesis in CVID patients. Overexpression of p53 was also found in 18% of CVID patients. To date, there are no definitive society guidelines for screening for gastric malignancy in patients with CVID. Given the high incidence of dysplasia and increased risk of gastric malignancy in these patients, physicians should have a low threshold for diagnostic endoscopy, especially if gastrointestinal symptoms persist despite therapy.