Abhijeet Waghray

Hepatocellular carcinoma: From diagnosis to treatment.

Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments. Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.

Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation.

Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) carries a poor prognosis. The aim of our study was to assess the safety and efficacy of sorafenib in patients with recurrent HCC following LT.

Falsely Low Parathyroid Hormone Secondary to Biotin Interference: A Case Series

OBJECTIVE To present a case series on biotin interference in parathyroid hormone (PTH) level measurement. METHODS We review the presentation and management of patients at our institution evaluated for unexpectedly low PTH levels while taking biotin supplements in the setting of high or normal serum calcium. RESULTS Two patients presented with surprising low parathyroid levels--one during preoperative evaluation for hyperparathyroidism and another during postoperative follow-up after subtotal parathyroidectomy. The patients were found to be taking 1,500 mcg and 5,000 mcg of biotin per day, respectively. The role of biotin interference was confirmed in one of the patients when she was retested off biotin, and PTH levels responded appropriately. Biotin supplements remain as unbound molecules in the serum, thus interfering with PTH enzyme-linked immunosorbent assay (ELISA) results and falsely depressing the PTH level. CONCLUSION Biotin supplement use has expanded over the years, ranging from medically endorsed therapies to home remedies. Review of the 2 ELISA systems used at our institution demonstrates that free biotin mimics the biotinylated antibody used in the detection process. Screening for biotin use prior to PTH measurement and automatic biotin levels for clinically aberrant PTH levels provide the clinician with a true PTH level--lowering the disease burden of untreated hyperparathyroidism while avoiding unnecessary work-ups for other processes.

Cryopreservation of Parathyroid Tissue: An Illustrated Technique Using the Cleveland Clinic Protocol

Received June 21, 2012; Revised September 17, 2012; Acce 18, 2012. From the Andrology Laboratory and Sperm Bank, Glickm and Kidney Institute (Agarwal, Sharma, Gupta), Departmen Surgery, Endocrinology and Metabolism Institute (Wagh Clinic, Cleveland, OH, and Department of Surgery, Oreg Sciences University, Portland, OR (Milas). Correspondence address: Ashok Agarwal, PhD, Andrology Sperm Bank, Glickman Urological and Kidney Institute, C 9500 Euclid Ave, Cleveland, OH 44196. email: agarwaa@

Vaccinating Adult Patients with Cirrhosis: Trends over a Decade in the United States.

Introduction. The progression of chronic liver disease to cirrhosis involves both innate and adaptive immune system dysfunction resulting in increased risk of infectious complications. Vaccinations against pneumococcus, hepatitis A virus (HAV), and hepatitis B virus (HBV) are well tolerated and effective in disease prevention and reduction in morbidity and mortality. Prior studies assessing vaccination rates in patients with cirrhosis have specific limitations and to date no study has provided a comprehensive evaluation of vaccination rates in patients with cirrhosis in the United States. Aim. This study assessed vaccination rates for pneumococcus, HAV, and HBV in patients with cirrhosis. Results. Overall 59.7% of patients with cirrhosis received at least 1 vaccination during the study period. Vaccination rates within the same or following year of cirrhosis diagnosis were 19.9%, 7.7%, and 11.0% against pneumococcus, HAV, and HBV, respectively. Trend analysis revealed significant increases in vaccination rates for pneumococcus in all patients with cirrhosis and within subgroups based on age, gender, and presence of concomitant diabetes. Conclusion. The study demonstrated that vaccination rates in patients with cirrhosis remain suboptimal. Ultimately, the use of electronic medical record (EMR) reminders improved communication between healthcare professionals and public health programs to increase awareness are fundamental to reducing morbidity, mortality, and health-care related costs of vaccine preventable diseases in patients with cirrhosis.

Severe hemorrhagic gastritis after percutaneous endoscopic gastrostomy tube placement

1. Mansoor H, Masood MA, Yusuf MA. Complications of percutaneous endoscopic gastrostomy tube insertion in cancer patients: a retrospective study. J Gastrointest Cancer 2014;45:452-459. 2. Schurink CA, Tuynman H, Scholten P, et al. Percutaneous endoscopic gastrostomy: complications and suggestions to avoid them. Eur J Gastroenterol Hepatol 2001;13:819-823. 3. Nishiwaki S, Araki H, Takada J, et al. Clinical investigation of upper gastrointestinal hemorrhage aft er percutaneous endoscopic gastrostomy. Dig Endosc 2010;22:180-185. Departments of aMedicine (Abhijeet Waghray); bGastroenterology (Amy Michel-Calderon, Annette Kyprianou, Nisheet Waghray), MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH, USA

Sa1213 An Analysis of Crohn's Disease Over the Past Decade in the United States Related to Cost of Hospitalization, Outcome, Length of Stay and Demographics

maintenance infusion and 10.1% of patients received maintenance infusions on average more than one week late. A patient would be expected to accrue a dropped infliximab maintenance dose every 13.9 infusions (112.0 weeks) based on the standard maintenance regimen of infliximab 5mg/kg every eight weeks. However, among the 20 patients experiencing a mean delay in administration of infliximab of over 7 days, a dropped infliximab maintenance dose would be accrued every 33.3 weeks. As a percentage of time on maintenance infliximab, mean cumulative non-adherence was 6.1% (± 5.6%). In multivariate logistic regression analysis, only male gender (OR 1.77 [95% CI 1.01-3.11]) was predictive of non-adherence. Conclusions: While three quarters of patients are adherent with infliximab induction therapy, less than one third remain closely adherent to their maintenance infliximab infusion schedule. This non-adherence may have significant clinical implications for maintenance of remission and eventual secondary loss of response. Table 1: Baseline Patient Demographics and Adherence to Infliximab Therapy

Hepatocellular carcinoma complicating recurrent hepatitis C after liver transplantation

A 49-year-old male underwent orthotopic liver transplantation (LT) for hepatitis C (HCV) cirrhosis in October 2006. Pretransplant alpha fetoprotein (AFP) was 39.7 ng/mL (reference range: 1.0-10.0 ng/ mL) and computed tomography (CT) scan demonstrated changes consistent with cirrhosis without mass lesions. Explant pathology was consistent with HCV cirrhosis and showed no evidence of hepatocellular carcinoma (HCC). Posttransplant immunosuppression for this patient consisted of tacrolimus and mycofenolate mofetil, after initially starting prednisone and OKT3. Six months posttransplant, a liver biopsy showed recurrent HCV and the patient started pegylated interferon and ribavirin. Unable to tolerate the side effects, therapy was discontinued after 1 week. A 12-month posttransplant liver biopsy showed HCV progression with bridging fibrosis. He developed hepatic hydrothorax requiring transjugular intrahepatic portosystemic stent (TIPS) placement in March of 2008. In subsequent years the patient was admitted several times for hepatic encephalopathy. In June 2011 a routine ultrasound showed a new 1-cm hypoechoic mass in the dome of the liver which was indeterminate on contrast CT scan. The alphafetoprotein level was 117.5 ng/mL. The lesion grew to 1.9 3 1.4 3 1.7 cm in March 2012 on ultrasonography. On contrast CT the lesion was hypervascular but indeterminate, as it measured less than 1 cm (Fig. 1A,B). The AFP was 107.6 ng/mL in October 2011 but was 4.3 ng/mL in May 2012 (Fig. 1C). Due to the increasing size of the lesion an ultrasound-guided biopsy of the liver mass was performed in April 2012 and reviewed by three pathologists who concurred that there was evidence of welldifferentiated HCC on a background of HCV cirrhosis (Fig. 2). The patient was scheduled for radiofrequency ablation (RFA) therapy and relisted for LT, but died from complications of liver failure while waiting. HCV accounts for nearly half of all LT done in the U.S. and Europe. Unfortunately, viremia persists in over 95% of patients posttransplant and cirrhosis can occur within 5 years of HCV recurrence in transplant patients, resulting in liver failure and death. HCV is a well-established risk factor for HCC in patients with cirrhosis, but to our knowledge no case has been reported of a patient with recurrent HCV developing HCC posttransplant. The rapid development of HCC in our patient was likely multifactorial and related to the development of recurrent HCV. Immunosuppression affects the natural history of recurrent HCV and accelerates the development of cirrhosis. Mechanistically, CD8 T cells are responsible for lysis of tumor and virus-infected cells by way of antigen presentation with up-regulation of cytokines by CD4 T cells. Thus, the T-cell response to HCV is critical in achieving longterm control of the virus and prolonging the time between viremia and the presence of tumor. Immunosuppressive medications decrease immune-mediated viral elimination and suppress the immune tumor surveillance system. Consequently, transplant recipients have a 2-4 times greater risk of de novo malignancy compared to transplant-na€ıve patients. Specifically, posttransplant immunosuppression may also promote tumorigenesis. Tacrolimus has been shown to accelerate the doubling time for recurrent HCC from 273 to 37 days and may have accelerated the doubling time of this patient’s cancer. The role of surveillance for HCC is still unclear. AFP levels may be elevated in patients with HCV and this may account for the discordance seen in our patient (Fig. 1D). In conclusion, cirrhosis from recurrent HCV after OLT can be associated with de novo HCC. The incidence and role of surveillance have yet to be defined and need further study. Abbreviations: AFP, alpha fetoprotein; CT, computed tomography; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LT, liver transplantation. From the Department of Gastroenterology and Hepatology, Digestive Disease Institute (DDI), and Pathology, Cleveland Clinic, Cleveland, OH. Received November 10, 2012; accepted May 2, 2013. Address reprint requests to: Dr. K.V. Narayanan Menon, M.D., Cleveland Clinic A51, 9500 Euclid Ave., Cleveland, OH 44196. E-mail: menonk@ccf.org; fax: 216-445-5477. Copyright VC 2013 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.26548 Potential conflict of interest: Nothing to report.