David W. Victor

Hepatocellular carcinoma: a review

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT) or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an aggressive cancer that occurs in the setting of cirrhosis and commonly presents in advanced stages. HCC can be prevented if there are appropriate measures taken, including hepatitis B virus vaccination, universal screening of blood products, use of safe injection practices, treatment and education of alcoholics and intravenous drug users, and initiation of antiviral therapy. Continued improvement in both surgical and nonsurgical approaches has demonstrated significant benefits in overall survival. While OLT remains the only curative surgical procedure, the shortage of available organs precludes this therapy for many patients with HCC.

Crohn Disease of the Esophagus : A Review of the Literature

Esophageal Crohn disease is a difficult disease both to diagnose and treat. The diagnosis is made in patients with other extraintestinal manifestations of Crohn disease in whom other esophageal pathology has been ruled out. This often requires integration of clinical, endoscopic, radiographic, and histologic findings. Despite its relative rarity, it does cause severe symptoms that are difficult to treat. Treatment requires careful integration of medical, endoscopic, and surgical techniques. This review aims to discuss the significant literature regarding diagnosis and treatment of this important manifestation of inflammatory bowel disease. There is additional discussion of the literature regarding the efficacy of newer medical and endoscopic therapies, including biologic agents and removable polymer stents.

Current endoscopic approach to indeterminate biliary strictures

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patients outcome. Early and accurate diagnosis of malignancy impacts not only a patients candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

Chief complaints, diagnoses, and medications prescribed seven weeks post-Katrina in New Orleans.

BACKGROUND In the aftermath of Hurricane Katrina, widespread flooding devastated the New Orleans healthcare system. Prior studies of post-hurricane healthcare do not consistently offer evidence-based recommendations for re-establishing patient care post-disaster. The primary objective of this study is to examine associations between patient characteristics, chief complaints, final diagnoses, and medications prescribed at a post-Katrina clinic to better inform strategic planning for post-disaster healthcare delivery (e.g., charitable donations of medications and medical supplies). METHODS This study is a retrospective chart review of 465 patient visits from 02 September 2005 to 22 October 2005 at a post-Katrina clinic in New Orleans, Louisiana that was open for seven weeks, providing urgent care services in the central business district. Using logistic regression, the relationships between patient characteristics (date of visit, gender, age, evacuation status), type of chief complaint, final diagnosis, and type of medication prescribed was examined. RESULTS Of 465 patients, 49.2% were middle-aged, 62.4% were men, 35% were relief workers, and 33.3% were evacuees; 35% of visits occurred in week five. Of 580 chief complaints, 71% were illnesses, 21% were medication refill requests, and 8.5% were injuries. Among 410 illness complaints, 25% were ears, nose, and throat (ENT)/dental, 17% were dermatologic, and 11% were cardiovascular. Most requested classes of medication refills for chronic medical conditions (n = 121) were cardiovascular (52%) and endocrine (24%). Most illness-related diagnoses (n = 400) were ENT/dental (18.2%), dermatologic (14.8%), cardiovascular (10.2%), and pulmonary (10.2%). Thirty-six percent of these diagnoses were infectious. Among 667 medications prescribed, 21% were cardiac agents, 13% pulmonary, 13% neurologic/musculoskeletal/pain, 11% antibiotics, 10% endocrine, and 9.3% anti-allergy. The likelihood of certain chief complaints, diagnoses, and medications prescribed varied with patient characteristics. CONCLUSIONS Donations of certain classes of medications were more useful than others. Prevalence of select co-morbidities, the nature of patient involvement in recovery activities in the disaster area, and post-disaster health hazards may explain variations in chief complaints, diagnoses, and medications prescribed by patient characteristics.

Liver transplant patients have a risk of progression similar to that of sporadic patients with branch duct intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can progress from low‐ to high‐grade dysplasia to invasive adenocarcinoma. The management of patients with IPMNs is dependent on their risk of malignant progression, with surgical resection recommended for patients with branch‐duct IPMN (BD‐IPMN) who develop high‐risk features. There is increasing evidence that liver transplant (LT) patients are at increased risk of extrahepatic malignancy. However, there are few data regarding the risk of progression of BD‐IPMNs in LT recipients. The aim of this study was to determine whether LT recipients with BD‐IPMNs are at higher risk of developing high‐risk features than patients with BD‐IPMNs who did not receive a transplant. Consecutive patients who underwent an LT with BD‐IPMNs were included. Patients with BD‐IPMNs with no history of immunosuppression were used as controls. Progression of the BD‐IPMNs was defined as development of a high‐risk feature (jaundice, dilated main pancreatic duct, mural nodule, cytology suspicious or diagnostic for malignancy, cyst diameter ≥3 cm). Twenty‐three LT patients with BD‐IPMN were compared with 274 control patients. The median length of follow‐up was 53.7 and 24.0 months in LT and control groups, respectively. Four (17.4%) LT patients and 45 (16.4%) controls developed high‐risk features (P = 0.99). In multivariate analysis, progression of BD‐IPMNs was associated with age at diagnosis but not with LT. There was no statistically significant difference in the risk of developing high‐risk features between the LT and the control groups. Liver Transpl 20:1462‐1467, 2014.

Efficacy and cost‐effectiveness of voriconazole prophylaxis for prevention of invasive aspergillosis in high‐risk liver transplant recipients

Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high‐risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high‐risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End‐Stage Liver Disease score at the time of LT was 33 (range, 18‐49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was

Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis

5324 or 5.6% of the predicted cost associated with post‐LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost‐effective in high‐risk LT recipients. Liver Transpl 22:163–170, 2016.

Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series

Context An optimal therapeutic strategy has not yet been identified for the pharmacological treatment of intrahepatic cholestasis of pregnancy (ICP). The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) and S-adenosylmethionine (SAMe) in the treatment of ICP, both individually and in combination. Evidence Acquisition A meta-analysis of all randomized controlled trials (RCTs) comparing UDCA, SAMe, and combination therapy was performed. We carried out a literature search using pubmed, embase, the cochrane register of controlled trials, and the science citation index of web of science. The maternal clinical and biochemical responses, including pruritus scores, total bilirubin, total bile acids, alanine aminotransferase, and aspartate transaminase, were evaluated. Safety assessments, including preterm delivery, cesarean section, and meconium-stained amniotic fluid, were also analyzed. Results Five RCTs including 311 patients were evaluated. In comparison to SAMe, UDCA significantly reduced the pruritus score (OR = -0.45, 95% confidence interval [CI]: -0.66 to -0.25, P < 0.0001) and improved the levels of total bile acids (TBAs; OR = -0.59, 95% CI: -0.99 to –0.30, P < 0.0001) and alanine aminotransferase (ALT; OR = -0.38, 95% CI: -0.66 to -0.09, P = 0.01). UDCA was associated with significantly lower preterm delivery rates than SAMe (RR = 0.48, 95% CI: 0.32–0.72, P = 0.0004). Interestingly, combination therapy significantly reduced total bilirubin (TB; vs. SAMe, OR = -0.41, 95% CI, -0.74 to -0.08, P = 0.02), aspartate transaminase (AST; vs. UDCA, OR = -0.40, 95% CI, -0.74 to –0.06, P = 0.02), and the rate of preterm delivery (vs. SAMe, OR = 0.62, 95% CI, 0.42 - 0.91, P = 0.02), in comparison with either drug administered alone. Conclusions UDCA decreased the pruritus score, TBA, and ALT levels more effectively than SAMe, reducing the rate of preterm delivery for ICP.

Hepatocellular carcinoma: the rising tide from east to west—a review of epidemiology, screening and tumor markers

BACKGROUND At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING None.

The Microbiome and the Liver: The Basics

Hepatocellular carcinoma (HCC) is no longer a disease of the Eastern hemisphere. HCC incidence has tripled in the United States in the past two decades. It is the fastest rising cause of cancer mortality in the U.S. and in parts of Western Europe. In the past the HCC epidemic was fueled by the Hepatitis B virus (HBV) seen mainly in Asia via horizontal transmission. In this decade, we are experiencing a rising tide due to the maturation of the Hepatitis C epidemic related to contaminated blood products and, more importantly, intravenous drug experimentation. As the obesity epidemic sweeps across the west the incidence of nonalcoholic fatty liver disease (NAFLD) and its inflammatory component nonalcoholic steatohepatitis (NASH) are becoming the harbinger of HCC yet to come. Worldwide, the incidence of HCC equals the mortality. Five year survival is at best 12%. These grim statistics underscore the need for earlier detection through screening resulting in initiation of early treatment that has the greatest impact on survival. An understanding of the epidemiology, risk factors and screening techniques is an essential first step in achieving this goal.