Peroral cholangioscopy with cholangioscopy-directed biopsies in the diagnosis of biliary malignancies: a systemic review and meta-analysis.

BACKGROUND AND AIM: Accurate diagnosis is essential in the appropriate management of biliary strictures. Our aim is to evaluate the efficacy of cholangioscopy-directed biopsies in differentiating biliary intraductal malignancies from benign lesions. MATERIALS AND METHODS: Articles were searched in Medline, PubMed, and Ovid journals. Pooling was performed by both fixed-effects and random-effects models. Only studies from which a 2×2 table could be constructed for true-positive, false-negative, false-positive, and true-negative values were included. RESULTS: Initial search identified 2110 reference articles for peroral cholangioscopy; of these, 160 relevant articles were selected and reviewed. Data were extracted from 15 studies (N=539) that fulfilled the inclusion criteria. Pooled sensitivity of cholangioscopy-directed biopsies in diagnosing malignancy was 71.9% [95% confidence interval (CI): 66.1-77.1] and pooled specificity was 99.1% (95% CI: 96.9-99.9). The positive likelihood ratio of cholangioscopy-directed biopsies was 18.1 (95% CI: 9.1-35.8), whereas the negative likelihood ratio was 0.3 (95% CI: 0.2-0.4). The pooled diagnostic odds ratio was 71.6 (95% CI: 32.8-156.4). All the pooled estimates calculated by fixed-effects and random-effect models were similar. Summary receiver operating characteristic curves showed an area under the curve of 0.98. The χ heterogeneity for all the pooled accuracy estimates was 5.62 (P=0.96). CONCLUSION: Peroral cholangioscopy with cholangioscopy-directed biopsies has a high specificity in differentiating intraductal malignancies from benign lesions. Cholangioscopy-directed biopsies should be strongly considered for biliary stricture evaluation.

Seroconverting nonresponder of high-dose intramuscular HBV vaccine with intradermal HBV vaccine: A case report.

INTRODUCTION: Liver disease is a leading cause of death among human immunodeficiency virus (HIV)-infected patients in the United States. Patients with HIV and hepatitis B virus (HBV) coinfection have accelerated liver disease, higher rates of cirrhosis, and liver cancer, and markedly increased liver-related mortality. The CDC and US Advisory Committee on Immunization Practices recommend hepatitis B vaccination for all HIV-infected individuals. Unfortunately, HIV-infected patients have a worse response rate after standard HBV vaccination. Intradermal (ID) vaccination continues to emerge as an important modality in such difficult to vaccinate individuals and should be considered whenever permissible. Herein, we report a case of a 46-year-old male with HIV who failed to mount an immune response to standard intramuscular vaccine, standard booster dose, and repeat high-dose booster vaccine but subsequently mounted an immune response to the ID vaccine which was sustained at 3 months postvaccination. CONCLUSION: ID vaccination continues to emerge as an important modality in difficult to vaccinate individuals and should be considered in all applicable cases.

Treatment of orofacial granulomatosis: a case report.

BACKGROUND: Orofacial granulomatosis is a relatively recent term coined by Wiesenfield et al. in 1985 to define granulomatous lesions of oral mucosa without intestinal involvement. When it presents in a triad encompassing facial nerve palsy, lip swelling, and fissured or furrowed tongue it is called Melkersson-Rosenthal syndrome while monosymptomatic or oligosymptomatic forms are referred to as granulomatous cheilitis. It is an uncommon clinicopathologic entity which is distinct from classic Crohn's disease. The NOD2 variant which is commonly associated with Crohn's has not been shown to have any association with orofacial granulomatosis. CASE PRESENTATION: We present a case of a 31-year-old white man who had painful swelling of the lip with oral ulcers and difficulty eating for 2 to 3 years. He was diagnosed as having granulomatous cheilitis based on characteristic biopsy findings. There was serologic evidence of Crohn's disease with anti-Saccharomyces cerevisiae antibodies. However, he was not found to have any gastrointestinal involvement based on computed tomography enterography, and upper and lower endoscopies. He failed to respond to nonsteroidal anti-inflammatory drugs, steroids, and dapsone therapy but responded well to high doses of infliximab. CONCLUSIONS: Our case questions whether granulomatous cheilitis really exists or is it simply a variant of Crohn's disease with only oral presentation. Our patient did not have symptoms of Crohn's disease; moreover, endoscopic studies and computed tomography enterography were unremarkable for evidence of intestinal involvement. Our case is also the first reported case where high-dose infliximab alone has been used with sustained response for approximately 8 months. In conclusion, more research is needed to assess the underlying pathology as well as ideal treatment options for patients with orofacial granulomatosis. We propose that high-dose infliximab should be considered in patients who do not respond to traditional therapies.

Pancreas herniation into the mediastinum: a case report.

BACKGROUND: Pancreatic tissue found in the mediastinum (both true ectopic and herniated pancreas) is rare. It becomes even more challenging when there are complications associated with this entity. CASE PRESENTATION: We report an unusual case of pancreatic herniation into the mediastinum in a 90-year-old Caucasian female. This patient initially presented with nausea and vomiting associated with abdominal pain. Serum lipase and amylase both were elevated. Computed tomography scan of the chest, abdomen and pelvis revealed a large hiatal hernia with pancreas herniation into the mediastinum, with superimposed acute pancreatitis likely due to gallstone. Because of its unusual location, the patient also developed acute mediastinitis. The patient was management conservatively and did well. On the day of discharge; she was tolerating a diet, had no pain or nausea and was back to her baseline health. CONCLUSION: Acute pancreatitis can be managed conservatively even if it is in the mediastinum. Also, ectopic or herniated pancreatic tissue is extremely rare and leads to unique clinical presentations, along with diagnostic and therapeutic challenges. Clinicians should not only be vigilant to the presence of ectopic or herniated pancreatic tissue, but also be mindful of the resulting complications.

Treatment of HCV in Patients who Failed First-Generation PI Therapy: a Review of Current Literature.

The addition of the first direct-acting antiviral agents, the NS3 protease inhibitors boceprevir or telaprevir, to peg interferon and ribavirin was a major advance in the treatment of genotype 1 hepatitis C individuals with sustained virological response (SVR) rates of 63-75 %. Those who did not achieve SVR had high rates of resistance-associated variants against NS3 protease domain. Retreatment options for those who have failed first-generation protease inhibitors generally are guided by retreatment with direct-acting antiviral agents from other classes. Phase 2 and phase 3 data have demonstrated that retreatment with 12-24 weeks of a NS5B inhibitor (sofosbuvir) in combination with a NS5a inhibitor (daclatasvir or ledipasvir) with or without ribavirin can achieve SVR at high rates comparable to treatment-naive individuals.

New hepatitis C virus therapies: drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease.

PURPOSE OF REVIEW: This article will review the new direct acting antiviral agent (DAA) drug classes for the treatment of hepatitis C, how they are combined and the relevant drug-drug interactions in the postliver transplant setting. Treatment options for chronic hepatitis C in patients with decompensated cirrhosis and end-stage renal disease will also be discussed. RECENT FINDINGS: The availability of new drug classes has increased the treatment options in patients with hepatitis C in the post-transplant settings. Clinical trials have concluded that sofosbuvir (SOF) with ledipasvir (LDV) may be safely administered with calcineurin inhibitors (tacrolimus, cyclosporine) and rapamycin inhibitors (sirolimus, everolimus). Similarly, paritaprevir/ritonavir, ombitasvir, and dasabuvir may be administered with tacrolimus and cyclosporine though appropriate dose adjustments must be made to the calcineurin inhibitors. In those with decompensated Childs B/C cirrhosis, SOF, SOF and LDV, as well as daclatasvir may be given without dose adjustment. In renal impairment, all DAAs may be used safely down to a glomerular filteration rate (GFR) of 30 ml/min. Simeprevir, paritaprevir, ombitasvir, and dasabuvir may be given for those down to GFR of 15 ml/min. Finally, daclatasvir may be given without dose administration change. SUMMARY: In summary, DAAs have better tolerability and greater efficacy than interferon-based therapy post-transplant. Drug-drug interactions must be carefully assessed when these newer agents are used for therapy in the postliver transplant settings. Thus far, dose adjustments for DAAs have not been required in chronic kidney disease though data are incomplete in those with severe chronic kidney disease (CKD) or on dialysis. Hepatitis C treatment in those with decompensated cirrhosis results in impaired hepatic metabolism that may affect DAA levels, and clinicians should carefully choose treatment options for Childs B and C cirrhotic patients.

The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated with Diagnosis of Hepatocellular Carcinoma.

AIMS: To determine whether the presence of portal vein thrombosis (PVT) where venous flow within the liver may be altered may delay the diagnosis of HCC and be associated with more advanced disease. We characterized the incidence and imaging characteristics of patients diagnosed with hepatocellular carcinoma in a cohort of patients with PVT compared with those without PVT. METHODS: This is a single-center retrospective study of a subset of HCC patients who underwent dynamic imaging for HCC screening and were found to have PVT. Data abstracted included demographic data, TNM stage, number/type of scans, AFP level, MELD score, and time to diagnosis. RESULTS: Eighty-two patients newly diagnosed with HCC on screening were reviewed, of which 37 % (30/82) were found to have portal vein thrombosis. Patients with PVT had higher rates of atypical imaging associated with HCC compared with those without PVT (83 vs 56 %, p = 0.01) and had lower rates of portal venous washout (23 % vs 50 %, p = 0.018). Patients with PVT and HCC were also diagnosed at later TNM stage than those without PVT (70 vs 23 %, p < 0.001) and were significantly less likely to receive orthotopic liver transplant (3.6 vs 42 %, p < 0.001). Fourteen patients had preexisting PV clot without HCC; 16 developed PVT during screening or at diagnosis. Those with preexisting PVT were older (63. vs 55 years) and had higher rates of diagnosis of HCC using MRI (79 vs 21 % with CT, p = 0.01), compared with those without preexisting PVT. CONCLUSION: The presence of PVT found on dynamic imaging was associated with advanced stage of HCC at the time of diagnosis. Clinicians should have a high suspicion for HCC diagnosis in new liver lesions with atypical enhancement in the setting of PVT. In this setting, MRI was more frequently associated with HCC diagnosis.

Gastro-intestinal stromal tumor (GIST) complicating a colonic interposition: a novel case report.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a rare tumor comprising 0.1-0.3% of all gastrointestinal (GI) malignancies. Stomach followed by small intestine is the most common sites of involvement, implicated in 95% of the cases. We present a case of GIST complicating a colonic interposition. To the best of the author's knowledge, this is the first reported case of GIST complicating a colonic interposition. CASE PRESENTATION: A 47 year old African American male presented to the emergency department with intermittent, severe chest pain. Past medical history was significant for alkali (NaOH) ingestion during 1980 for which esophageal resection and a colonic pull-through was performed. A CXR revealed a widened mediastinum and CT scan chest revealed showed a large (11.4 × 8.3 × 12.1 cm) vascular mediastinal mass. At endoscopy, a large, ulcerated, cratered and friable mass was found at 29 cm extending to 36 cm at which point the lower anastomosis of the colonic pull through was present. Multiple endoscopic biopsies were obtained which showed that the tumor was immunoreactive with CD117, CD34 and DOG1 while markers of carcinoma, melanoma and lymphoma were negative. In light of the pathology report, the immunohistochemistry and the CT scans, the tumor was classified as a stage 4 GIST of colonic interposition. CONCLUSIONS: GIST can complicate unusual locations such as colonic interposition and should be kept in the differential diagnosis of such unusual presentations.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature.

BACKGROUND: Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions. METHODS: We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients". RESULTS: Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary. CONCLUSION: Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Complex partial non-convulsive status epilepticus masquerading as hepatic encephalopathy: a case report.

INTRODUCTION: Hepatic encephalopathy is usually suspected in patients who are cirrhotic with neuropsychiatric manifestations. We present a case of suspected hepatic encephalopathy that did not respond to standard empiric therapy and was eventually diagnosed as non-convulsive status epilepticus of complex partial type. Our patient responded dramatically to anti-convulsive therapy. CASE PRESENTATION: We report the case of a 45-year-old African-American man with hepatitis C virus cirrhosis and human immunodeficiency virus who presented to our facility with a one-day history of confusion and a variable mental status. Our patient's vital signs were stable and all his electrolytes were within normal range. A clinical diagnosis of hepatic encephalopathy was made and our patient was started on empiric therapy with lactulose and rifaximin. Our patient did not respond to therapy. After five days of treatment, alternative diagnoses were sought and a neurology consult was requested. An electroencephalogram was eventually performed which showed seizure activity in the right parietal lobe. A diagnosis of non-convulsive status epilepticus was made and our patient was started on oral levetiracetam. On day two of therapy, our patient was alert and oriented. He continues to do well on follow-up approximately one year after discharge. CONCLUSIONS: Non-convulsive status epilepticus should be considered in the differential diagnosis of patients with suspected hepatic encephalopathy who do not respond to empirical treatment. Further studies are needed to investigate the incidence of this entity in patients with persistent hepatic encephalopathy.

Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: a meta-analysis of randomized controlled trials.

BACKGROUND: Hepatocellular cancer is notorious for recurrence even after curative therapy. High recurrence determines the long term prognosis of the patients. Vitamin K2 has been tested in trials for its effect on prevention of recurrence and improving survival. The results are inconclusive from individual trials and in our knowledge no systematic review which entirely focuses on Vitamin K2 as a chemo preventive agent is available to date. This review is an attempt to pool all the existing trials together and update the existing knowledge on the topic. METHODS: Medline, Embase and Cochrane Register of Controlled trials were searched for randomized controlled trials where vitamin K2 or its analogues, in any dosage were compared to placebo or No vitamin K2, for participants of any age or sex. Reference lists and abstracts of conference proceedings were searched by hand. Additional papers were identified by a manual search of the references from the key articles. Attempt was made to contact the authors of primary studies for missing data and with the experts in the field.Trials were assessed for inclusion by two independent reviewers. Primary outcomes were recurrence rates and survival rates. There were no secondary outcomes. Data was synthesized using a random effects model and results presented as relative risk with 95% Confidence Intervals. RESULT: For recurrence of hepatocellular cancer after hepatic resection or local ablative therapy, compared with controls, participants receiving Vitamin K2, pooled relative risks for hepatocellular cancer were 0.60; 95% CI: 0.28-1.28, p = 0.64) at 1 yr 0.66; 95% CI: 0.47-0.91), p = 0.01) at 2 yr; 0.71; 95% CI: 0.58-0.85, p = 0.004) at 3 yr respectively. The results were combined using the random analysis model. CONCLUSION: Five RCTs evaluated the preventive efficacy of menatetrenone on HCC recurrence after hepatic resection or local ablative therapy. The meta-analysis of all five studies, failed to confirm significantly better tumor recurrence- free survival at 1 year. Improved tumor recurrence at 2nd and 3rd year may be just due to insufficient data. There was no beneficial effect on the overall survival. However, to confirm the beneficial effect or lack of it, large, higher quality randomized controlled trials are still required.