Rajan Kochar

Pulmonary Complications of Cirrhosis

Pulmonary vascular complications of liver disease comprise two distinct clinical entities: hepatopulmonary syndrome (HPS—microvascular dilatation and angiogenesis) and portopulmonary hypertension (POPH—vasoconstriction and remodeling in resistance vessels). These complications occur in similar pathophysiologic environments and may share pathogenic mechanisms. HPS is found in 15% to 30% of patients with cirrhosis and its presence increases mortality and the risks of liver transplantation, particularly when hypoxemia is present. Contrast echocardiography and arterial blood gas analysis are required to establish the diagnosis. No medical therapies are available, although liver transplantation is effective in reversing the syndrome. POPH is found in 4% to 8% of patients undergoing liver transplantation evaluation, and the presence of moderate to severe disease significantly increases perioperative transplant mortality. Transthoracic echocardiography is recommended for screening and right-heart catheterization is required to establish the diagnosis. Medical therapies are increasingly effective in improving pulmonary vascular hemodynamics in POPH and may result in better perioperative outcomes.

Pulmonary Diseases and the Liver

Chronic liver disease is associated with many pulmonary complications. Several, including hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax have been extensively reviewed. However, hepatobiliary manifestations of primary pulmonary diseases have received less attention. This review focuses on hepatobiliary complications of respiratory failure, cystic fibrosis, α-1 antitrypsin deficiency, sarcoidosis, and tuberculosis.

Diagnostic criteria for autoimmune hepatitis: what is the gold standard?

mitochondrial TMRM release and calcein uptake even after longer times of reperfusion, demonstrating directly that minocycline blocks the characteristic inner membrane permeabilization of the MPT (Fig. 1C). Thus, minocycline protects against mitochondrial dysfunction after both warm and cold ischemia-reperfusion by prevention of the MPT. These results under truly physiological conditions are simply incompatible with the proposal that the chief effects of minocycline are respiratory inhibition and MPT promotion. Rather, such mitochondrial dysfunction is likely the basis for loss of efficacy at higher nontherapeutic minocycline concentrations. Currently, we are screening a panel of tetracycline derivatives for compounds with a larger therapeutic window of efficacy. Minocycline is a well-characterized and cost-effective anitbiotic of proven safety in a broad spectrum of indications.6 In rare instances, hepatotoxicity after chronic use occurs, which is attributed to the metabolite 4-epiminocycline.7 However, such toxicity would be unlikely after one-time use to minimize storage-reperfusion injury to transplanted livers. To decrease infection, antibiotics are a standard peritransplant regimen, and use of minocycline in donors, recipients, and during graft storage might have added benefit, especially in marginal livers from higher risk donors or in livers subjected to longer periods of storage. Overall, we agree with Månsson et al. that the safety and efficacy of minocycline for use in clinical liver transplantation deserve further exploration.

Primary and secondary prophylaxis of gastric variceal bleeding

Gastric variceal bleeding is a common problem in patients with cirrhosis and is associated with increased morbidity and mortality. Management is complex and includes pharmacotherapy, endoscopic therapy, and shunt placement. Recent studies indicate that endoscopic therapy with tissue adhesives has similar hemostasis rates and outcomes in terms of mortality as shunt placement but has a lower complication rate and therefore could be considered the first line therapy for acute bleeding and secondary prophylaxis of gastric varices.

229 A Prospective, Randomized Trial of Adenoma Miss Rates At Colonoscopy Associated With 3-Minute vs. 6-Minute Withdrawal Time

Introduction: A minimum withdrawal time for screening colonoscopy of 6 minutes has been proposed, based on an observational study. The 6-minute withdrawal time remains controversial and has not been compared in a standardized fashion to alternate withdrawal times. Aim: To perform a prospective, randomized trial to compare adenoma miss rates (AMR) associated with withdrawal times of 6 minutes vs. 3 minutes. Methods: Consecutive patients undergoing colonoscopy at Stanford University and Palo Alto Veterans Administration Hospital were randomized to undergo either a 3-minute or 6-minute withdrawal (1st pass), followed immediately by a tandem 6-minute withdrawal (2nd pass). AMR was defined as the number of adenomas detected on the 2nd pass divided by total number of adenomas found. A chi-square statistic was used to directly compare AMR. A z-statistic was used to determine effect of polyp size/location on AMR. A mixed-effects logistic regression model was then created to compare AMR, controlling for endoscopist, size/location of adenoma, and patient. Finally, a Cochrane-Armitage test for trend was used to evaluate the trend of adenoma detection associated with increasing withdrawal time. Results: 200 subjects were enrolled (99 in the 3-minute group, 101 in the 6-minute group). Demographics and indications for colonoscopy were similar between the two groups (Table 1). AMR was significantly higher in the 3-minute withdrawal group compared to the 6-minute withdrawal group (48.5% vs 21.8%; p≤0.0001). Adenomas were significantly more likely to be missed in the 3-minute withdrawal group in all 3 locations of the colon (right, transverse and left colon). AMR was higher in the 3-minute withdrawal group among adenomas that were ≤5mm; there was no significant difference in AMR for adenomas that were 6-9mm or ≥10mm. After controlling for endoscopist, size/location of the polyp/adenoma, and the patient, AMR remained significantly higher in the 3-minute withdrawal group compared to the 6-minute withdrawal group (OR 2.92, 95% CI=1.54-5.55) (Table 1). Adenoma detection rate (ADR) was similar between both 3 and 6 minute withdrawal groups (38.4% vs 40.6%, p=0.75); however, this study was not powered to detect differences in ADR. There was a significant trend towards higher total number of adenomas detected as withdrawal time increased (52 at 3 minutes, 87 at 6 minutes, 101 at 9 minutes, and 111 at 12 minutes; p<0.001) (Figure 1). Conclusions: A 3-minute withdrawal time leads to an unacceptably high AMR. A 6minute withdrawal time is more appropriate for colorectal cancer screening. Location did not affect AMR; however, adenomas that were ≤5mm were more likely to be missed in the 3-minute withdrawal group. Further research into the optimal withdrawal time, including evaluation of withdrawal times longer than 6 minutes, is warranted.