Ian Schreibman

The hamartomatous polyposis syndromes: a clinical and molecular review.

Inherited forms of gastrointestinal cancer have been a major focus of study and advancement over the past decade. Familial adenomatous polyposis and hereditary nonpolyposis colon cancer are the two most common heritable colon cancer syndromes. Inherited polyposis syndromes are characterized by the dominant type of polyp (whether adenomatous or hamartomatous) present and by the polyps location within the gastrointestinal tract. The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. They represent a small but appreciable number of the gastrointestinal inherited cancer predisposition syndromes; it is now known that many of these syndromes carry a substantial risk for developing colon cancer as well as other gastrointestinal and pancreatic cancers. Patients afflicted with these syndromes are also at significant risk for extraintestinal malignancies. Seven inherited hamartomatous polyposis syndromes have been described: familial juvenile polyposis syndrome, Cowdens syndrome, Bannayan-Ruvalcaba-Riley syndrome, Peutz-Jeghers syndrome, basal cell nevus syndrome, neurofibromatosis 1, and multiple endocrine neoplasia syndrome 2B. Hereditary mixed polyposis syndrome is a variant of juvenile polyposis characterized by both hamartomatous and adenomatous polyps. The hamartomatous syndromes occur at approximately 1/10th the frequency of the adenomatous syndromes and account for <1% of colorectal cancer in Northern America. While the diagnosis of these inherited syndromes is primarily clinical, genetic testing is now available for all six syndromes. However, there are a significant number of spontaneous mutations seen in each of the syndromes. The management of these patients necessitates a coordinated multidisciplinary approach. The purpose of this review is to characterize the clinical and pathological features of these syndromes and to review the targets of cancer surveillance. The molecular alterations responsible for the inherited hamartomatous polyposis syndromes will also be discussed.

Outcomes after orthotopic liver transplantation in 15 HIV-infected patients

Background. Human immunodeficiency virus (HIV) infection has been associated with poor outcomes after orthotopic liver transplantation (OLT). Highly active antiretroviral therapy (HAART) has led to an increasing number of successful OLTs. The aim of this study was to examine survival and cause-specific mortality in HIV-infected patients after OLT at our institution. Methods. A retrospective analysis of all HIV patients that underwent OLT was compared to all non-HIV patients undergoing OLT during the same period. Cumulative patient and cause-specific survival were calculated using Kaplan-Meier methods; the log-rank test was used to compare the two cohorts. Fifteen HIV-infected patients and 857 non-HIV patients underwent OLT between June 1, 1999 and May 1, 2006. Results. The actuarial 1-, 2-, and 3-year survival rates posttransplant (±standard error) were 73.3% (±11.4%) for the HIV group (unchanged from 1 to 3 years) versus 86.9% (±1.2%), 82.0% (±1.4%), and 79.4% (±1.5%) for the non-HIV group. Cumulative survival among HIV-infected recipients was not different from the non-HIV population (P=0.20). A difference was observed between the two groups in mortality rates due to infectious causes: the percentage of HIV patients dying from infection was 26.7% (4 of 15) vs. 8.2% (70 of 857) in the non-HIV group (P=0.006). Conclusions. PostOLT survival was comparable in HIV and non-HIV recipients; however, HIV patients had significantly higher mortality from infectious complications. This difference occurred despite adequate control of HIV postOLT. These findings suggest that OLT can be safely performed for HIV-infected patients; however, these patients are at higher risk of mortality from infectious complications.

Prevention and treatment of recurrent Hepatitis B after liver transplantation: the current role of nucleoside and nucleotide analogues

The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic liver disease in humans. Approximately 350–400 million people are affected worldwide and up to one million deaths occur annually from cirrhosis and hepatocellular carcinoma. When cirrhosis and liver failure develop, the definitive treatment of choice remains orthotopic liver transplantation (OLT). In the past, an unacceptable HBV recurrence rate with a high rate of graft loss was noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved patient and graft survival rates. The addition of the nucleoside analog Lamivudine (LAM) to HBIG has improved these survival curves to an even greater degree. Prolonged use of LAM will almost invariably lead to the development of viral mutations resistant to the drug. There are now several other nucleoside and nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for the clinician to utilize against these resistant strains. It should be possible to prevent recurrence in most, if not all, post-transplant patients and also to significantly reduce viral loads with normalization of transaminases in those who have developed recurrent infection. The antiviral regimen should be robust and minimize the risk of breakthrough mutations. A prudent approach may be the implication of combination antiviral therapy. This review summarizes the efficacy of previous regimens utilized to prevent and treat recurrent HBV following OLT. Particular attention will be paid to the newer nucleoside and nucleotide analogs and the direction for future strategies to treat HBV in the post transplant setting.

Impact of geographic disparity on liver allocation for hepatocellular cancer in the United States

BACKGROUND & AIMS Liver allocation for hepatocellular cancer (HCC) is undergoing constant re-evaluation in the United States, but the impact of geographic differences in organ access has not been examined. METHODS From February 28th, 2002 until November 20th, 2009, 9730 adult patients with T2 HCC and 326 Beyond Milan HCC patients were studied using the UNOS database. Kaplan-Meier survival curves were generated and log-rank tests were used to test for differences in survival curves. RESULTS Length of waiting time and presence/absence of loco-regional therapy in T2 HCC patients did not significantly impact transplant recipient (p=0.65) and graft survival (p=0.74) (Fig. 1B). Regions with median waiting times >6 months performed more loco-regional therapy (Fig. 1D) and had significantly higher waiting list dropout rates (Regions 1: p=0.01; 5: p<0.001, and 9: p<0.001). T2 HCC post-transplant outcomes were not significantly different between UNOS regions (Fig. 2) or between T2 and Beyond Milan HCC patients (transplant recipient p=0.37, and graft p=0.72 survival) (Fig. 1C). The Beyond Milan cohort had significantly greater dropout/death (p=0.007) and a worse overall survival trend (p=0.11) (Fig. 1C). CONCLUSIONS Analysis of the UNOS database shows inhomogeneous access to liver transplantation in the United States. Regions with longer waiting times had significantly higher T2 HCC dropout rates (Table 2), and used more loco-regional therapy (Fig. 1D). Conversely, T2 HCC patients had uniform liver transplant outcomes despite geographic differences (Fig. 2). Beyond Milan HCC patients showed significantly greater dropout/death (p=0.007) and a worse overall survival trend in an intent-to-treat analysis (p=0.11) (Fig. 1C).

Immune functional assay for immunosuppressive management in post‐transplant malignancy

Uemura T, Riley TR, Khan A, Hollenbeak C, Schreibman I, Ghahramani N, Reeves B, Domen RE, Zander DS, Kadry Z. Immune functional assay for immunosuppressive management in post‐transplant malignancy.
Clin Transplant 2011: 25: E32–E37.

Hemorrhagic Complications of Paracentesis: A Systematic Review of the Literature

Introduction. Large volume paracentesis is considered a safe procedure carrying minimal risk of complications and rarely causing morbidity or mortality. The most common complications of the procedure are ascitic fluid leakage, hemorrhage, infection, and perforation. The purpose of this study was to evaluate all hemorrhagic complications and their outcomes and to identify any common variables. Methods. A literature search for all reported hemorrhagic complications following paracentesis was conducted. A total of 61 patients were identified. Data of interest were extracted and analyzed. The primary outcome of the study was 30-day mortality, with secondary endpoints being achievement of hemostasis after intervention and mortality based on type of intervention. Results. 90% of the patients undergoing paracentesis had underlying cirrhosis. Three types of hemorrhagic complications were identified: abdominal wall hematomas (52%), hemoperitoneum (41%), and pseudoaneurysm (7%). Forty percent of the patients underwent either a surgical (35%) or an IR guided intervention (65%). Patients undergoing a surgical intervention had a significantly higher rate of mortality at day 30 compared to those undergoing IR intervention. Conclusion. Abdominal wall hematomas and hemoperitoneum are the most common hemorrhagic complications of paracentesis. Transcatheter coiling and embolization appear to be superior to both open and laparoscopic surgery in treatment of these complications.

Current treatment of choice for chronic hepatitis C infection

More than three million Americans have chronic hepatitis C infection, and the disease remains one of the most common blood-borne infections in the US. Treatment is focused on the chronic form of the disease, because the acute one tends to be self-limiting. In this article, we review the recent literature regarding the most effective therapy against hepatitis C infection, to confirm the current treatment of choice for the disease. We conclude that combination therapy with pegylated interferon and ribavirin remains the initial treatment of choice. New research focusing on adjuvant therapies, such as protease and polymerase inhibitors, has yielded early data that appear to be promising.

Serotonin Syndrome in a Patient on Trazodone and Duloxetine Who Received Fentanyl following a Percutaneous Liver Biopsy

Serotonin syndrome is a rare but potentially life-threatening adverse drug reaction resulting from the use or overuse of serotonergic medications alone or in combination. Mild symptoms, overlapping features with similar conditions and clinician lack of awareness are the major reasons for an often missed diagnosis. Not surprisingly, this condition is significantly underreported as a potential complication of endoscopy if serotonergic medications are used periprocedurally for sedation and analgesia. Here we report the case of a patient with relapsed chronic hepatitis C on antidepressant medications who developed signs and symptoms of serotonin syndrome after a percutaneous liver biopsy. Review of the patients medication list suggested a possible interaction between her home antidepressants and the post-procedure use of fentanyl for abdominal pain. The patient required monitoring in the medical intensive care unit and stabilized after the administration of benzodiazepines and temporary discontinuation of her home medications. We propose that clinicians need to be aware of the increased risk of serotonin syndrome in the outpatient endoscopy setting, particularly with the wider use of serotonergic antidepressants now available and the repeated number of liver biopsies being performed for management of patients with chronic liver disease.

Portal Hypertension: An Underestimated Entity?

Objective:The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures. Background:Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension. Methods:From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (⩽15 vs >15) and compared with NEV patients. Results:One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients. Conclusions:Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

Background and aims: Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient’s clinical profile. Methods: A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. Results: A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. Conclusion: A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy.