Type 1 Autoimmune Pancreatitis Unmasked by COVID-19 Vaccine.

Autoimmune pancreatitis is a rare fibro-inflammatory disease with 2 distinct subtypes of which each has their own clinical presentation, risk factors, and histopathological patterns. We present a case of newly diagnosed type 1 autoimmune pancreatitis in a symptomatic 54-year-old man with stable ulcerative colitis 1 month after COVID-19 vaccination. Previous reports have indicated that vaccinations can trigger autoimmune disease in predisposed individuals. This case discusses the occurrence of autoimmune pancreatitis triggered after COVID-19 vaccination.

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.

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.

Self-expanding metal stents (SEMS) for preoperative biliary decompression in patients with resectable and borderline-resectable pancreatic cancer: outcomes in 241 patients.

BACKGROUND AND AIM: Obstructive jaundice caused by distal biliary obstruction can present in up to 70 % of patients with localized cancer of the head of the pancreas. The aim of this study was to report our experience in using self-expanding metal stents (SEMS) for preoperative biliary decompression in patients with resectable and borderline resectable carcinoma of the pancreatic head. METHODS: We performed a retrospective study evaluating patients from two tertiary referral centers. Two-hundred and forty-one patients with resectable and borderline resectable pancreatic carcinoma underwent ERCP with metal biliary stent placement between September 2006 and August 2011. We assessed the effectiveness of SEMS to adequately decompress the biliary tree, procedural success, patient survival, stent patency, and stent-related complications. RESULTS: Two-hundred and forty-one patients were evaluated [123 male, mean age (± SD) 67.4 ± 9.8 years; resectable 174, borderline resectable 67]. Patients with borderline-resectable cancer underwent neoadjuvant therapy and restaging before possible curative surgery. Successful placement of a metal biliary stent was achieved in all patients and improved jaundice. Patients were followed for mean duration of 6.3 months. The overall survival was 49 % at 27 months. Fourteen (5.8 %) patients experienced stent occlusion; the mean time to stent occlusion was 6.6 (range 1-20) months. Immediate complications included: post-ERCP pancreatitis (n = 14), stent migration (n = 3), and duodenal perforation (n = 3). Long-term complications included stent migration (n = 9) and hepatic abscess (n = 1). A total of 144/174 patients deemed to have resectable cancer at time of diagnosis underwent curative surgery. Due to disease progression or the discovery of metastasis after neoadjuvant therapy, only 22/67 patients with borderline-resectable cancer underwent curative surgery. CONCLUSIONS: SEMS should be considered for patients with obstructive jaundice and resectable or borderline resectable pancreatic cancer, especially if surgery is not planned immediately as a result of preoperative chemoradiation. These stents appear to be safe and effective.

Boerhaave's syndrome as an initial presentation of eosinophilic esophagitis: a case series.

BACKGROUND: Prior studies report esophageal rupture following endoscopy or bolus impaction in eosinophilic esophagitis (EoE). The purpose of this study is to add new information to available evidence defining the clinical spectrum of spontaneous rupture (Boerhaave's syndrome) associated with vomiting in EoE. METHODS: A retrospective search of inpatient and outpatient records was conducted from January 2001 to January 2011. A faculty member in pathology blindly reviewed all esophageal biopsy specimens. EoE was defined as 15 or more eosinophils in at least 2 high-power fields (hpfs) or 25 or more eosinophils in any single HPF. RESULTS: In ten years, 447 patients were identified with a diagnosis of EoE. Of these, four patients presented with Boerhaave's syndrome in the setting of EoE. None of the patients had an established diagnosis of EoE prior to presentation. All cases presented with a triad of vomiting, chest pain and pneumomediastinum. In two patients, water-soluble contrast extravasation prompted surgical intervention (50%). Full thickness surgical specimen provides a unique opportunity to show eosinophils in the muscularis propria. Intraepithelial eosinophil infiltration was seen on all mucosal biopsies (>25/hpf) with significant improvement after steroid (topical or systemic) treatment. CONCLUSIONS: Spontaneous esophageal rupture is a rare (4/447, less than 1%) but critical presentation of EoE manifesting with vomiting, chest pain and pneumomediastinum. Surgery is required if extravasation is seen with water-soluble contrast. We suggest that EoE may be a transmural disease in some patients, thus making the esophageal wall susceptible to spontaneous rupture with vomiting (Boerhaave's syndrome).

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.

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.

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.

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.

Clinical utility of selective esophageal manometry in a tertiary care setting.

PURPOSE: To evaluate the utility of selective esophageal manometry in clinical practice. RESULTS: Retrospective data from 200 subjects was reviewed. Manometry was considered to be (1) high clinical utility when specific abnormality was identified resulting in therapeutic intervention, (2) low clinical utility when specific abnormality was identified without alteration of therapy, (3) limited clinical utility when manometry was normal. High, low, and limited clinical utility was noted in 47, 40, and 13% of instances. Manometry was of high utility in patients with dysphagia or non-cardiac chest pain (P < 0.05), and low utility in gastroesophageal reflux (P < 0.05). CONCLUSIONS: (1) Esophageal manometry has high clinical utility in dysphagia after exclusion of structural disorders; and non-cardiac chest pain after careful exclusion of reflux. (2) Ineffective motility disorder has high association with gastroesophageal reflux disease but low clinical utility except in preoperative assessment for fundoplication. (3) Esophageal manometry is of high utility in clinical practice when used in conjunction with other diagnostic exclusions.

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.

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.

OBJECTIVES: Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. METHODS: In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >or= 14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. RESULTS: Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). CONCLUSIONS: Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.

Computerized tomography (CT)-guided aspiration of abscesses: outcome of therapy at a tertiary care hospital.

OBJECTIVE: To review the experience with percutaneous aspiration of abscesses at a general, tertiary care hospital from 2000 to 2005. METHODS: Computerized medical records of 90 patients who underwent radiologically guided drainage of 92 fluid collections were reviewed for demographic data, co-morbid conditions, location, radiographic imaging characteristics and culture results and to determine the long-term outcome of the procedure. RESULTS: Sixty-seven of 92 (73%) abscesses were cured without the need for open surgical drainage; 44 were cured within 14 days, and 23 had delayed resolution requiring prolonged antibiotics and/or a second drainage. Of the abscesses 85% were drained using a catheter in situ, the remaining aspirated using a needle. Twenty-five (27%) of the 92 abscesses failed percutaneous drainage, requiring open surgical drainage or lead to sepsis and death. Neither co-morbid conditions nor the location of abscesses affected the outcome of drainage. Patients who had sterile cultures of aspirated material after receiving antibiotics prior to the procedure had a significantly higher cure rate than otherwise (P<0.05). Catheter drainage was associated with a significantly higher cure rate than was needle aspiration (P<0.05). CONCLUSION: Percutaneous drainage, along with appropriate antibiotics, is an effective approach to treat deep abscesses. Drainage, itself, is the major determinant of outcome, rather than the location, characteristics of the abscess or condition of the patient prior to the procedure.