Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis, quality of life, and potentially survival. We compared survival in patients with unresectable cholangiocarcinoma undergoing endoscopic retrograde cholangiopancreatography (ERCP) with PDT and stent placement with a group undergoing ERCP with stent placement alone. METHODS:Forty-eight patients were palliated for unresectable cholangiocarcinoma during a 5-year period. Nineteen were treated with PDT and stents; 29 patients treated with biliary stents alone served as a control group. Multivariate analysis was performed by using Model for End-Stage Liver Disease score, age, treatment by chemotherapy or radiation, and number of ERCP procedures and PDT sessions to detect predictors of survival. RESULTS:Kaplan-Meier analysis demonstrated improved survival in the PDT group compared with the stent only group (16.2 vs 7.4 months, P<.004). Mortality in the PDT group at 3, 6, and 12 months was 0%, 16%, and 56%, respectively. The corresponding mortality in the stent group was 28%, 52%, and 82%, respectively. The difference between the 2 groups was significant at 3 months and 6 months but not at 12 months. Only the number of ERCP procedures and number of PDT sessions were significant on multivariate analysis. Adverse events specific to PDT included 3 patients with skin phototoxicity requiring topical therapy only. CONCLUSIONS:ERCP with PDT seems to increase survival in patients with unresectable cholangiocarcinoma when compared with ERCP alone. It remains to be proved whether this effect is attributable to PDT or the number of ERCP sessions. A prospective randomized multicenter study is required to confirm these data.

PURPOSE/OBJECTIVE:There is no algorithm for the initial staging of esophageal cancer that is considered standard of care. This prospective blinded study analyzes the utility of FDG-PET as an adjunct to EUS and CT for the management of patients with esophageal cancer. METHODS:Between December 2003 and October 2006, patients diagnosed with esophageal carcinoma underwent EUS, CT, and FDG-PET at their initial evaluation. Two thoracic surgeons were given staging EUS results and CT scan reports. They were asked if the patient needed surgical resection, neoadjuvant chemotherapy followed by resection, or palliation. With each case, one surgeon was unblinded to the FDG-PET results. The treatment decisions of each surgeon were compared to determine if PET altered clinical management. RESULTS:A total of 50 patients (45 male, 5 female) were enrolled and data were prospectively collected. Forty-three (86%) had adenocarcinoma and 7 (14%) had squamous cell carcinoma. EUS was completed in 88% (44) of cases while 6 (12%) were incomplete secondary to tight stenosis. Nineteen were treated with surgery, 25 with neoadjuvant chemotherapy and surgery, and 6 with palliative chemoradiation. In 49 of 50 patients, the surgeons came to identical management decisions independent of PET results. In the one case that the treatment decision differed, the EUS was incomplete. The agreement on treatment strategy was 98% (kappa= 0.97, 95% CI 0.93-0.99). CONCLUSION/CONCLUSIONS:This study shows that the addition of FDG-PET to EUS and CT offers little information to the initial treatment stratification of patients with esophageal cancer. However, in patients with incomplete EUS, FDG-PET may have some clinical utility.

BACKGROUND:A 39-year-old man presented with a 2-month history of abdominal pain, jaundice, non-bloody diarrhea, weakness, and weight loss. Initial evaluation revealed intrahepatic ductopenia consistent with vanishing bile duct syndrome and IBD, type unclassified. Although treatment with budesonide improved his symptoms, they worsened several months later. On repeat evaluation, he was found to have extensive lymphadenopathy and an elevated white blood cell count. INVESTIGATIONS/METHODS:Physical examination, laboratory investigations, abdominal ultrasound, CT scans, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, colonoscopies with biopsies, hepatic biopsy, axillary lymph node biopsy. DIAGNOSIS/METHODS:Hodgkin's lymphoma with secondary vanishing bile duct syndrome and IBD, type unclassified. MANAGEMENT/RESULTS:The initial symptoms were managed with budesonide, but following recurrence, the patient's underlying lymphoma was treated with nitrogen mustard and dexamethasone.

Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time--INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation.

BACKGROUND & AIMS/OBJECTIVE:Wilson's disease is a genetic autosomal-recessive copper deposition disorder often presenting with neurologic or hepatic symptoms. In cases of hepatic presentation, treatment usually is initiated with potentially toxic copper chelators, such as D-penicillamine or trientine. Although multiple studies have introduced zinc as a low-toxicity and low-cost Wilson's disease treatment, its use has been limited to adjunctive or single-agent maintenance options. In this report, we describe the use of zinc monotherapy in a patient with severe hepatic presentation of Wilson's disease. METHODS:Zinc has not been evaluated as a single-agent treatment option for active hepatic Wilson's disease. Zinc monotherapy was initiated for a single patient with fulminant hepatic failure caused by Wilson's disease while awaiting liver transplantation. RESULTS:Over a 1-year period with zinc monotherapy, this patient experienced normalization of hepatic synthetic function and resolution of hypoalbuminemia and coagulopathy. Clinical stabilization of variceal bleeds, ascites, and lower-extremity edema also were observed. The patient is no longer a transplant candidate as a result of clinical recovery and improvement of Model for End-stage Liver Disease and Child-Turcotte-Pugh scores. CONCLUSIONS:This case highlights the potential use of zinc as a low-toxicity and low-cost single-agent treatment in severely decompensated hepatic Wilson's disease. Despite promising results in this case, further clinical evaluation will be necessary to assess fully the clinical efficacy of zinc monotherapy.

OBJECTIVE:Despite the endogenous coagulopathy of cirrhosis, some patients with cirrhosis experience thrombophilic states. This study aims to determine the incidence and predictors of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism, in hospitalized patients with cirrhosis. METHODS:A retrospective case-control study was performed in a tertiary-care teaching hospital over an 8-yr period. A total of 113 hospitalized patients with cirrhosis with a documented new VTE were compared to controls. Risk factors for VTE were determined using univariate and multivariate statistical analyses. RESULTS:Approximately 0.5% of all hospitalized patients with cirrhosis had a VTE. Traditional markers of coagulation such as INR and platelet count were not predictive of VTE. In the univariate analysis, serum albumin level was significantly lower in cases than controls (2.85 vs. 3.10 g/dL, respectively, p = 0.01). In the multivariate analysis, serum albumin remained independently predictive of VTE, with an odds ratio of 0.25 (95% CI 0.10-0.56). CONCLUSIONS:Approximately 0.5% of admissions involving cirrhosis patients resulted in a new thromboembolic event. Low serum albumin was strongly predictive of increased risk for developing VTE, independent of international normalized ratio or platelet count. Serum albumin deficiency may indicate low levels of endogenous anticoagulants.