Phillip S. Ge

The changing role of beta-blocker therapy in patients with cirrhosis

Cirrhosis is a leading cause of death in the United States and worldwide. Beta-blockers have been established in numerous studies as part of the cornerstone of the medical management of cirrhosis, particularly in the primary and secondary prevention of variceal hemorrhage. However, new evidence has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites. In this article, we review the beneficial effects of beta-blocker therapy, the potential harms of aggressive beta-blocker therapy, and provide suggestions regarding the appropriate use of this class of medications in patients with cirrhosis.

Treatment of Patients with Cirrhosis.

This guide to the practical treatment of patients with cirrhosis summarizes recent developments. It includes advice on medical management, invasive procedures, nutrition, prevention, and strategies to protect the cirrhotic liver from harm.

The Use of Human Acellular Dermal Matrix for Chest Wall Reconstruction

BACKGROUND Reconstruction of chest wall defects has evolved, but challenges remain. This is particularly true when defects are large or contamination is present. Although numerous materials are available for reconstruction, acellular dermal matrix has the advantage of becoming vascularized and incorporated autologously. By its resistance to infection and lack of adhesion formation, it is a promising although expensive alternative to synthetic materials in some circumstances. This report examines our experience with human acellular dermal matrix (HADM) in reconstruction of major chest wall and diaphragmatic defects. METHODS A retrospective study was conducted of all patients who underwent thoracic reconstruction using HADM between March 2007 and March 2010 at Harbor-University of California-Los Angeles Medical Center. Data acquisition included demographics, surgical indications, operative details, complications, and follow-up evaluation. RESULTS Ten patients were identified. Indications included thoracic tumor resection in 5, Clagett procedure modification for postpneumonectomy empyema in 2, resection of chest wall osteomyelitis in 2, and pneumonectomy for multiple aspergillomata in 1. Complications occurred in 4 patients and included respiratory failure, pneumonia, and wound seromas. All wounds healed without need to remove or revise the HADM, and sound chest wall closure was achieved in every case. CONCLUSIONS HADM is an effective but expensive alternative to synthetic mesh in reconstruction of chest wall and diaphragmatic defects. It is particularly attractive for use under conditions of potential or overt contamination.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipples procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

Serum Ammonia Level for the Evaluation of Hepatic Encephalopathy

A 31-year-old Asian man with hepatitis C cirrhosis complicated by variceal hemorrhage and ascites underwent an inpatient evaluation for orthotopic liver transplantation. He was a graduate student who was doing well until he developed decompensated cirrhosis with variceal hemorrhage. When he first presented, he had hypovolemic shock from acute blood loss related to variceal hemorrhage that was treated with many blood transfusions and variceal banding procedures. When he was transferred to the liver unit on hospital day 25, his liver test abnormalities had mostly recovered and he had no further gastrointestinal bleeding. He had a serum ammonia level measured as part of the routine liver transplant evaluation. He did not have any confusion, insomnia, or decreased mental alertness. Jaundice was noted on the physical examination but he was alert and oriented with normal cognitive function. No tenderness was noted onhisabdominalexaminationandhehadmildascites.Duringtheinpatientlivertransplantevaluation, his cognitive capacity and mental status remained stable and he had no symptoms of encephalopathy. He received oral diuretics for the management of his ascites. The Table lists results of laboratory analyses performed at admission and on hospital days 25 and 38.

Iatrogenic Pseudoaneurysm of the Superior Gluteal Artery Presenting as Pelvic Mass With Foot Drop and Sciatica: Case Report and Review of Literature

We report an unusual case of a pseudoaneurysm of the superior gluteal artery as a complication of bone marrow biopsy. A 51-year-old man presented with sciatic pain and foot drop after undergoing bone marrow biopsy and was initially diagnosed as having degenerative disc disease based on his past medical history. Pelvic magnetic resonance imaging (MRI) revealed a large heterogeneous mass suggestive of a neurogenic tumor, but pulsatile blood was instead encountered during computed tomography (CT)-guided needle biopsy. Subsequent workup established the diagnosis of a superior gluteal artery pseudoaneurysm, which was treated with coil embolization, followed by surgical evacuation of the hematoma, which relieved his sciatic pain. However, the patient continues to have a persistent foot drop. Gluteal artery pseudoaneurysms are exceedingly uncommon but should be considered in the workup of a patient with gluteal pain or sciatic nerve palsy following trauma or medical procedures in the gluteal region.

When Should the β-Blocker Window in Cirrhosis Close?

he b-blocker controversy continues. b Blockers are Twell-established in the primary and secondary prevention of variceal hemorrhage in patients with cirrhosis. Nonselective b blockers such as propranolol exert their influence via splanchnic vasoconstriction and the reduction of cardiac output, thereby reducing the hepatic venous pressure gradient. However, a series of recent studies from Sersté et al demonstrated reduced survival in patients with decompensated cirrhosis and refractory ascites who were treated with b blockers. Not surprisingly, these findings have ignited significant controversy among hepatologists, ranging from outright disbelief to calls for additional studies in the hopes that “better-designed” studies would refute these findings. In this issue of Gastroenterology, Mandorfer et al provide important new evidence demonstrating the detrimental effect of b blocker treatment after the development of spontaneous bacterial peritonitis (SBP). In this retrospective cohort study of 607 patients with cirrhosis, nonselective b blockers were shown to increase transplant-free survival in patients without SBP, with reduced hospitalization rates. However, with the first diagnosis of SBP, nonselective b blockers were associated with hemodynamic compromise and decreased blood pressures, reduced transplant-free survival, increased hospitalization rates, and increased incidence of the hepatorenal syndrome and acute kidney injury. Although the study was retrospective, it was well-designed and thorough; statistical models were adjusted for Child–Pugh stage and presence of varices in an attempt to avoid the limitations of the Sersté et al studies. Aside from a higher proportion of female patients in the b-blocker group at first paracentesis, and a higher bilirubin level in the b-blocker group at first SBP diagnosis, no other differences were noted between the study populations. Mandorfer et al conclude in this study that patients with cirrhosis and SBP should not receive nonselective b-blocker therapy. However, the impact and clinical implications of this study are far-reaching—it adds to the growing body of recent evidence documenting the harms of b-blocker therapy in patients with advanced cirrhosis. Together with the studies from Sersté et al, these studies directly support the recently described “window hypothesis” for b-blocker therapy, in which Krag et al propose that b blockers improve survival within only a narrow window in the natural history of cirrhosis. According to this hypothesis, b blockers are beneficial only during a certain “window” of clinical opportunity, and are either ineffective or harmful outside of this window. In early cirrhosis, b blockers have no effect on survival, increase adverse events and do not prevent the formation of varices. As cirrhosis progresses, portal pressures increase and the sympathetic nervous system becomes increasingly activated. Ascites and esophageal varices develop, and there is increased risk of variceal bleeding and bacterial translocation. Systemic hemodynamics remains relatively preserved, and blood pressure and cardiac output are maintained to deliver adequate end-organ perfusion. In this middle stage of cirrhosis, the b-blocker “window” opens for the primary and secondary prevention of gastrointestinal bleeding. However, in advanced cirrhosis with refractory ascites, the inability of the circulatory system to increase cardiac output via the b-adrenergic system during situations of increased physiologic stress results in decreased mean arterial pressures, decreased perfusion to vital organs, azotemia, and subsequently increased risk for the hepatorenal syndrome and end-organ damage. Exactly when the “window” closes is up for debate. Part of the reason why it is unclear when the “window” closes is that, until recently, the effects of b blockers in patients with cirrhosis and refractory ascites had never been studied. In the original study from Lebrec et al in 1981, which established the role of b blockers in prevention of variceal bleeding, patients with ascites were purposely excluded. Given that cirrhosis is a dynamic process, it makes sense that early studies only included the middle stages of cirrhosis, because the entire disease course is too heterogeneous. The recommendation to start and indefinitely continue b blockers, in essentially all patients with cirrhosis and medium-to-large varices regardless of blood pressure or ascites, was largely extrapolated rather than specifically studied. The role of cardiac output and blood pressure is central to understanding why b blockers are harmful in patients with advanced cirrhosis. As cirrhosis progresses, circulatory changes occur including the maximal up-regulation of the sympathetic nervous system and of the renin– angiotensin–aldosterone system. These changes, alongwith sodium and water retention and the formation of ascites, are aimed at maintaining adequate cardiac output and organ perfusion. Together, they reflect an adaptive response to the peripheral vasodilation, effective hypovolemia, and arterial hypotension that accompanies advanced cirrhosis. However, the cardiovascular system eventually loses its compensatory ability. It is at this stage that the maintenance of blood pressure and cardiac output is paramount, and the hemodynamic effects of b blockers in reducing blood pressure and cardiac output results in decreased survival. The correlation between blood pressure and survival in patients with cirrhosis was suggested by Llach et al in 1988. In their study, a mean arterial pressure of 82 mmHg was the single variable most strongly correlated with shortened survival; the survival probability rate of patients

Evaluation of the 2015 AGA guidelines on pancreatic cystic neoplasms in a large surgically confirmed multicenter cohort

Absract Background and study aims The American Gastroenterological Association (AGA) recently published guidelines for the management of asymptomatic pancreatic cystic neoplasms (PCNs). We aimed to evaluate the diagnostic characteristics of the AGA guidelines in appropriately recommending surgery for malignant PCNs. Patients and methods A retrospective multicenter study was performed of patients who underwent endoscopic ultrasound (EUS) for evaluation of PCNs who ultimately underwent surgical resection from 2004 – 2014. Demographics, EUS characteristics, fine-needle aspiration (FNA) results, type of resection, and final pathologic diagnosis were recorded. Patients were categorized into 2 groups (surgery or surveillance) based on what the AGA guidelines would have recommended. Performance characteristics for the diagnosis of cancer or high-grade dysplasia (HGD) on surgical pathology were calculated. Results Three hundred patients underwent surgical resection for PCNs, of whom the AGA guidelines would have recommended surgery in 121 (40.3 %) and surveillance in 179 (59.7 %) patients. Among patients recommended for surgery, 45 (37.2 %) had cancer, whereas 76 (62.8 %) had no cancer/HGD. Among patients recommended for surveillance, 170 (95.0 %) had no cancer/HGD; however, 9 (5.0 %) patients had cancer that would have been missed. For the finding of cancer/HGD on surgical pathology, the AGA guidelines had 83.3 % sensitivity (95 % CI 70.7 – 92.1), 69.1 % specificity (95 % CI 62.9 – 74.8), 37.2 % positive predictive value (95 % CI 28.6 – 46.4), 95.0 % negative predictive value (95 % CI 90.7 – 97.7), and 71.7 % accuracy (95 % CI 67.4 – 74.6). Conclusions The 2015 AGA guidelines would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95 % of patients with asymptomatic PCNs. Future prospective studies are required to validate these guidelines. Meeting presentations: Presented in part at Digestive Diseases Week 2016

The Great Imitator: Ocular Syphilis Presenting as Posterior Uveitis

Patient: Female, 34 Final Diagnosis: Ocular syphilis Symptoms: Painful unilateral vision loss Medication: Benzylpenicillin Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases • Ophthalmology Objective: Rare disease Background: Syphilis is often known as the “Great Imitator”. The differential diagnosis of posterior uveitis is broad with ocular syphilis being particularly challenging to diagnose as it presents similarly to other ocular conditions such as acute retinal necrosis. Case Report: A 34-year-old woman with multiple sexual partners over the past few years presented with painful and progressively worsening unilateral vision loss for 2 weeks. Several months prior, she had reported non-specific symptoms of headache and diffuse skin rash. Despite treatment with oral acyclovir for 3 weeks, her vision progressively declined, and she was referred to the university ophthalmology clinic for further evaluation. On examination, there was concern for acute retinal necrosis and she was empirically treated with parenteral acyclovir while awaiting further infectious disease study results. Workup ultimately revealed ocular syphilis, and neurosyphilis was additionally confirmed with cerebrospinal fluid studies. Treatment with intravenous penicillin was promptly initiated with complete visual recovery. Conclusions: Ocular syphilis varies widely in presentation and should be considered in all patients with posterior uveitis, especially with a history of headache and skin rashes. However, given that acute retinal necrosis is a more common cause of posterior uveitis and can rapidly result in permanent vision loss, it should be empirically treated whenever it is suspected while simultaneous workup is conducted to evaluate for alternative diagnoses.

Preventing Future Infections in Cirrhosis: A Battle Cry for Stewardship

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