The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined. in a 5 1/2-year study, we randomly assigned 299 men with alcoholic cirrhosis, who had persistent or recurrent severe ascites despite a standard medical regimen, to receive either intensive medical treatment or peritoneovenous (LeVeen) shunting. We identified three risk groups: Group 1 had normal or mildly abnormal results on liver-function tests, Group 2 had more severe liver dysfunction or previous complications, and Group 3 had severe prerenal azotemia without kidney disease. For the patients who received the medical treatment and those who received the surgical treatment combined, the median survival times were 1093 days in Group 1, 222 days in Group 2, and 37 days in Group 3 (P less than or equal to 0.01) for all comparisons). For all the groups combined, the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients (P less than 0.01). Within each risk group, mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment. However, the median time to the recurrence of ascites in Group 1 was 4 months in medical patients, as compared with 18 months in surgical patients (P = 0.01); in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients (P = 0.04). The median duration of hospitalization was longer in medical patients than in surgical patients (6.1 vs. 2.4 weeks in Group 1 [P less than 0.001] and 5.0 vs. 3.1 weeks in Group 2 [P less than 0.01]). Group 3 was too small to permit a meaningful comparison. During the initial hospitalization, the incidence of infections, gastrointestinal bleeding, and encephalopathy was similar among the medical and surgical patients. We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management. However, survival was closely related to the severity of the illness at the time of randomization and was not altered by shunting.

Background & Aims Following radiofrequency ablation (RFA), patients may experience recurrence of Barrett’s esophagus (BE) after complete eradication of intestinal metaplasia (CEIM). Rates and predictors of recurrence after successful eradication are poorly described. Methods We used the U.S. RFA Registry, a nationwide registry of BE patients receiving RFA, to determine rates and factors that predicted recurrence of IM. We assessed recurrence by Kaplan-Meier analysis for the overall cohort and by worst pretreatment histology. Characteristics associated with recurrence were included in a logistic regression model to identify independent predictors. Results Among 5521 patients, 3728 had biopsies ≥12 months after initiation of RFA. Of these, 3169 (85%) achieved CEIM, and 1634 (30%) met inclusion criteria. Average follow-up was 2.4 years after CEIM. IM recurred in 334 (20%), and was non-dysplastic or indefinite for dysplasia in 86% (287/334); the average length of recurrent BE was 0.6 cm. In Kaplan-Meier analysis, more advanced pretreatment histology was associated with an increased yearly recurrence rate. Compared to patients without recurrence, patients with recurrence were more likely, based on bi-variate analysis, to be older, have longer BE segments, be non-Caucasian, have dysplastic BE before treatment, and require more treatment sessions. In multivariate analysis, likelihood for recurrence was associated with increasing age and BE length, and non-Caucasian race. Conclusion BE recurred in 20% of patients followed for an average of 2.4 years after CEIM. Most recurrences were short segments and were non-dysplastic or indefinite for dysplasia. Older age, non-Caucasian race, and increasing length of BE length were all risk factors. These risk factors should be considered when planning post-RFA surveillance intervals.

Background & Aims Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, predictors of EAC, and EAC-specific and all-cause mortality rates. Methods We assessed outcomes in a multicenter study of RFA for BE. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (both all-cause and EAC-specific) rates were calculated, and adjusted all-cause mortality rates were assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. Results Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years (PY)), and 9 (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in non-dysplastic BE (NDBE) was 0.5/1000 PY. Overall, 157 (3%) patients died during follow-up (all-cause mortality 11.2/1000 PY). On multivariate logistic regression, baseline BE length (OR 1.1 per cm) and baseline histology (ORs of 5.8 and 50.3 for low grade dysplasia and high grade dysplasia (HGD) respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extra-esophageal cancers (15%). No deaths were associated with RFA. Conclusion In this multicenter registry of RFA for BE, death from EAC was rare. The incidence of EAC was markedly lower than natural history studies, with the greatest absolute benefit seen in HGD.

Methylprednisolone pharmacokinetics and its directly suppressive effects on plasma cortisol, blood histamine (basophils), and circulating helper T cells were evaluated in six obese (at least 35% above ideal body weight) men and six nonobese male volunteers. Methylprednisolone doses of 0.6 mg/kg total body weight were administered as the 21-succinate sodium salt. Absolute clearance (in liters per hour) of methylprednisolone was 40% less in the obese subjects. Total volume of distribution (Vss) of methylprednisolone was unchanged (about 120 L), but when normalized for total body weight, Vss per kilogram was less in obesity. The patterns of cortisol, blood histamine, and helper T cell responses after methylprednisolone administration were similar in both groups, but more profound effects were observed in the obese subjects. Pharmacodynamic models were applied for these immediate effects of methylprednisolone based on the premise that receptor interactions of steroids are followed by rapid suppression of the circadian rhythm of cortisol and recirculation of basophils and helper T cells, which persist until inhibitory concentrations (IC50) of methylprednisolone disappear. Similar IC50 values for the three effects were obtained in both groups, indicating no intrinsic pharmacodynamic differences in sensitivity to these methylprednisolone effects in obesity. However, methylprednisolone should be administered on the basis of ideal body weight, and the dosing interval should be potentially lengthened because of decreased methylprednisolone clearance in obesity.