William C. Palmer

Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma

BACKGROUND & AIMS Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. METHODS We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. RESULTS Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. CONCLUSIONS Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.

Update on the Diagnosis and Treatment of Cholangiocarcinoma.

Purpose of ReviewCholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates.Recent FindingsCholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease.SummaryThis article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease.

Cardiac tamponade due to low-volume effusive constrictive pericarditis in a patient with uncontrolled type II autoimmune polyglandular syndrome

Abstract Type II autoimmune polyglandular syndrome (APS), a relatively common endocrine disorder, includes primary adrenal insufficiency coupled with type 1 diabetes mellitus and/or autoimmune primary hypothyroidism. Autoimmune serositis, an associated disease, may present as symptomatic pericardial effusion. We present a case of a 54-year old male with APS who developed pericarditis leading to cardiac tamponade with a subacute loculated effusion. After urgent pericardiocentesis intrapericardial pressure dropped to 0, while central venous pressures remain elevated, consistent with acute effusive constrictive pericarditis. Contrast computerized tomography confirmed increased pericardial contrast enhancement. The patient recovered after prolonged inotropic support and glucocorticoid administration. He re-accumulated the effusion 16 days later, requiring repeat pericardiocentesis. Effusive–constrictive pericarditis, an uncommon pericardial syndrome, is characterized by simultaneous pericardial inflammation and tamponade. Prior cases of APS associated with cardiac tamponade despite low volumes of effusion have been reported, albeit without good demonstration of hemodynamic findings. We report a case of APS with recurrent pericardial effusion due to pericarditis and marked hypotension with comprehensive clinical and hemodynamic assessment. These patients may require aggressive support with pericardiocentesis, inotropes, and hormone replacement therapy. They should be followed closely for recurrent tamponade.

Patent foramen ovale in liver transplant recipients does not negatively impact short-term outcomes

Patent foramen ovale (PFO) is a common atrial septal defect that is largely asymptomatic and often undiagnosed. The impact of a PFO in patients undergoing liver transplantation (LT) is unknown.

Colonoscopy Bowel Preparation Quality Improvement for Patients with Decompensated Cirrhosis Undergoing Evaluation for Liver Transplantation.

Inadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education.

Rare Incidence of Ventricular Tachycardia and Torsades de Pointes in Hospitalized Patients With Prolonged QT Who Later Received Levofloxacin: A Retrospective Study

OBJECTIVE To determine the incidence of ventricular tachycardia and ventricular fibrillation in patients with prolonged corrected QT interval (QTc) who received levofloxacin through retrospective chart review at a tertiary care teaching hospital in the United States. PATIENTS AND METHODS We selected 1004 consecutive hospitalized patients with prolonged QTc (>450 ms) between October 9, 2009 and June 12, 2012 at our institution. Levofloxacin was administered orally and/or intravenously and adjusted to renal function in the inpatient setting. The primary outcome measure was sustained ventricular tachycardia recorded electrocardiographically. RESULTS With a median time from the start of levofloxacin use to hospital discharge (or death) of 4 days (range, 1-94 days), only 2 patients (0.2%; 95% CI, 0.0%-0.7%) experienced the primary outcome of sustained ventricular tachycardia after the initiation of levofloxacin use. CONCLUSION In this study, the short-term risk for sustained ventricular tachycardia in patients with a prolonged QTc who subsequently received levofloxacin was very rare. These results suggest that levofloxacin may be a safe option in patients with prolonged QTc; however, studies with longer follow-up are needed.

Association of Intraductal Papillary Mucinous Neoplasm (IPMN) With Extra-Pancreatic Cystic Lesions: Is there a Systemic Cystic Disorder?

Association of Intraductal Papillary Mucinous Neoplasm (IPMN) With Extra-Pancreatic Cystic Lesions: Is there a Systemic Cystic Disorder?

Management of high grade dysplasia in Barrett's oesophagus with underlying oesophageal varices: A retrospective study

BACKGROUND Endoscopic treatment of Barretts oesophagus leading to high grade dysplasia with oesophageal varices may lead to bleeding complications. AIMS Estimate effectiveness of endoscopic band-ligation in oesophageal varices patients treated for high grade dysplasia, and compare to endoscopically treated non-oesophageal varices high grade dysplasia patients. METHODS Retrospective comparative study. All 8 high grade dysplasia patients with varices who were treated initially with band-ligation at Mayo Clinic between 8/1/1999 and 2/28/2014 were compared with reference group of 52 high grade dysplasia patients treated endoscopically. RESULTS One high grade dysplasia patients patient with oesophageal varices (12.5%) achieved complete remission of intestinal metaplasia defined by at least one followup endoscopy with normal biopsies, and 3 (37.5%) achieved complete remission of dysplasia defined by at least one followup endoscopy with non-dysplastic biopsies. 39 (75.0%) endomucosal resection/radiofrequency ablation patients experienced at least one followup endoscopy with normal biopsies, and 49 (94.2%) experienced non-dysplastic biopsies. Both of these endpoints occurred significantly more often in the endomucosal resection/radiofrequency ablation group compared to the high grade dysplasia with oesophageal varices group (p=0.016 and p=0.025, respectively). CONCLUSIONS High grade dysplastic Barretts can be safely managed with band-ligation. However, resolution of Barretts epithelium is rarely achieved with banding alone.

Changes in efficiency and resource utilization after increasing experience with double balloon enteroscopy

AIM To investigate changes in efficiency and resource utilization as a single endoscopists experience increased with each subsequent 100 double balloon enteroscopy (DBE) procedures. METHODS We reviewed consecutive DBE procedures performed by a single endoscopist at our center over 4 years. DBE was employed when the clinician deemed the procedure was needed for disease management. The approach (oral, anal or both) was chosen based on suspected location of the target lesion. All DBE was performed in a standard endoscopy room with a portable fluoroscopy unit. Fluoroscopy was used to aid in shortening the small intestine and reducing bowel loops. For oral DBE, measurements were taken from the incisors. For anal DBE, measurements were taken from the anal verge. Enteroscopy continued until the target lesion was reached, until the entire small intestine was examined, or until no further progress was deemed possible. The length of small intestine examined (cm), procedure duration (min), and fluoroscopy time (s) were analyzed for sequential groups of 100 DBE. Sub-groups of diagnostic and therapeutic procedures were analyzed using multivariable linear regression. RESULTS 802 consecutive DBE procedures were analyzed. For oral DBE, median [interquartile range (IQR)] length of small bowel examined was 230.8 cm (range: 210-248 cm) and for anal DBE was 143.5 cm (range: 100-180 cm). No significant increase in length examined was noted for either the oral or anal approach with advancing position in series. In terms of duration of procedure, the median (IQR) for oral DBE was 86 min (range: 71-105 min) and for anal DBE was 81.3 min (range: 67-105 min). When comparing by the position in series, there was a significant (P value < 0.001) decrease in procedure duration for both upper and lower procedures with increasing experience. Median (IQR) time of exposure to fluoroscopy for oral DBE was 190 s (114-275) compared to anal DBE which was 196.4 s (312-128). This represented a significant (P value < 0.001) decrease in the amount of fluoroscopy used with increasing position in series. For both oral and anal DBE, fluoroscopy time was reduced by greater than 50% over the course of 802 total procedures performed. Sub-group analysis was conducted on therapeutic and diagnostic groups. Out of 802 procedures, a total of 434 were considered therapeutic. Argon plasma coagulation was by far the most common therapeutic intervention performed. There was no evidence of a difference in length examined or fluoroscopy exposure among oral DBE for diagnostic and therapeutic procedures, P = 0.91 and P = 0.32 respectively. The median (IQR) for length was 235 cm (range: 178-280 cm) for diagnostic vs 230 cm (range: 180-275 cm) for therapeutic procedures; additionally, fluoroscopy time median (IQR) was 180 s (range: 110-295 s) and 162 s (range: 102-263 s) for no intervention and intervention. However, there was a significant difference in procedure duration among oral DBE (P < 0.001). The median (IQR) was 80 min (range: 60-97 min) and 94 min (range: 77-110 min) for diagnostic and therapeutic interventions respectively. CONCLUSION For a single endoscopist, increased DBE experience with number of performed procedures is associated with increased efficiency and decreased resource utilization.

Lack of an association between autoimmune pancreatitis and Varicella Zoster Virus.

Autoimmune pancreatitis is a form of chronic pancreatitis that was first described by Sarles et al. in 1961, and later coined in 1995 by Yoshida et al. [1, 2]. Subsequently, two types of autoimmune pancreatitis have been described. Autoimmune pancreatitis type 1 fits the classic description of the disease and is associated with a lymphoplasmacytic sclerosing pancreatitis and an elevated level of immunoglobulin G4 subclass of IgG. Autoimmune pancreatitis type 2 is characterized by a distinct neutrophilic obliterating lesion of the ductal epithelium [3]. Although the histopathological findings of autoimmune pancreatitis are well studied, the risk factors, pathogenesis, and treatments are still not well understood. There have been many hypotheses to the etiology of autoimmune pancreatitis, which are still being studied. One proposed theory is that of microbial mimicry leading to an autoimmune disorder. Several studies have been conducted to evaluate for a link with autoimmune pancreatitis and infectious causes, such as Helicobacter Pylori, without identifying a clear relationship [4]. Additionally, there has been a reported link between viral infections and acute pancreatitis, such as Coxackievirus [5]. Beginning several months ago, some of the physicians of our Department of Gastroenterology noticed a general pattern of newly diagnosed autoimmune pancreatitis with recent shingles outbreak or Zoster vaccine administration. To further study the possible association, we conducted a pilot study to examine the incidence of autoimmune pancreatitis with concomitant Varicella Zoster Virus. We identified four patients from the Mayo Clinic Medical Data Trust who had undergone core biopsy or surgical resection of the pancreas and had been diagnosed with autoimmune pancreatitis. All cases of autoimmune pancreatitis were associated with an elevated (more than 1.5 x upper reference limit) IgG4 level as well as histologic changes consistent with the diagnosis. With these four cases of autoimmune pancreatitis identified, we identified two cases for controls with normal pancreatic tissue. Both of these groups of tissue samples had already been collected and were accessed from the Mayo Medical Laboratory. Once the six tissue samples were obtained, we conducted in-situ hybridization assays for Varicella Zoster Virus. We used this technique because it enables localization of the viral DNA in the tissues if present. Finally, we calculated the incidence of Varicella Zoster Virus antibodies in normal pancreatic tissue and in autoimmune pancreatitis tissue samples. Out of the four cases of confirmed autoimmune pancreatitis, zero tissue samples showed evidence of concomitant Varicella