Uncovered Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites

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endoscopy. However, that possibility (along with other strategies) is the subject of the next report of the AGA Future Trends Committee—stay tuned. DAVID A. PEURA President American Gastroenterological Association Institute doi:10.1053/j.gastro.2006.02.053

Addenda and Corrections Concerning Friedrich Krukenberg Dear Sir: The biographical sketch about the person behind the “Krukenberg tumor” contains several inaccuracies. The accompanying picture shows obviously not Friedrich, but Peter Krukenberg (1787–1865), a famous physician in his time and the grandfather of Friedrich Krukenberg. Peter Krukenberg was the son-in-law of the also-mentioned Johann Christian Reil (1759 –1813). This would make Friedrich Krukenberg the great-grandson of Reil. To describe Reil as anatomist falls rather short of his role in history. He should be remembered as Goethe’s physician and as a pioneer of mental diseases.1,2 He is probably the first author, who coined the term “psychiatry” in 1808. I am not certain whether Friedrich Krukenberg really “had a lifelong interest in gynecologic pathology.” According to other sources, he continued his studies rather in the field of ophthalmology (together with T. Axenfeld). One of his publications, “What can schools do to fight short-sightedness?” from this period is available online3 as a facsimile. ULRICH S. SCHULER Department of Internal Medicine I Technical University Dresden, Germany 1. Haubrich WS. Krukenberg of the Krukenberg tumor. Gastroenterology 2005;6:1844. 2. Harms E. Johann Christian Reil, 1759 –1813. Am J Psychiatry 1960;116:1037–1039. 3. http://www.bbf.dipf.de/cgi-shl/digibert.pl?id⫽BBF0430593. doi:10.1053/j.gastro.2006.02.049

Uncovered Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites Dear Sir: We have read with interest the meta-analysis of D’Amico et al,1 which appeared in the October 2005 issue concerning TIPS in patients with refractory ascites. They found that TIPS enables better control of ascites than paracentesis, but that it increases the rate of encephalopathy. We had reached the same conclusions in our previous meta-analysis published in January 2005.2 However, we are most concerned about their conclusions suggesting that TIPS may improve survival. Data related to mortality are heterogeneous in the 5 analyzed studies. In fact, only 3 of the 5 studies were well designed. Two of them did not find any survival difference between the 2 groups,3,4 while a survival advantage for patients treated by TIPS was observed in the third.5 The design of the other 2 studies may have introduced potential biases. In the fourth study, the sample size initially planned

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was not attained, because interim analysis disclosed a higher rate of death in the TIPS group; as a result, the number of included patients was insufficient for drawing definitive conclusions.6 The last study showing a tendency toward lower mortality in the TIPS group7 penalized the paracentesis group because albumin infusion was not systematically performed, but was restricted to patients with ascites of over 4 liters or “when clinically indicated.” In their meta-analysis, D’Amico et al postulated that “the trend toward improved survival might become a significant benefit when more studies are added.”1 This conclusion is not accurate, since they cannot predict that future studies will have a positive impact on survival. It is important to note that a third meta-analysis on TIPS, like ours, concluded that there was an absence of survival benefits.8 The absence of significance in the meta-analysis of D’Amico was not affected by inclusion or exclusion of the study of Lebrec.6 The most pertinent question is whether or not it is possible to identify ideal candidates for TIPS. Only meta-analysis of individual data can attain this objective. Unfortunately, none of the published meta-analyses can answer it. Therefore, the only take-home message for patients with refractory ascites is that there is no evidence that TIPS improves survival. Currently, the main issue involves assessing the benefits provided by covered TIPS rather than performing further studies with uncovered TIPS, as suggested by a recent randomized controlled trial.9 Indeed, only an improvement in the TIPS procedure, such as that provided by covered TIPS, is likely to change the conclusions concerning the absence of survival benefits. PIERRE DELTENRE*† DIDIER LEBREC‡ PHILIPPE MATHURIN*§ *Service d’Hépato-Gastroentérologie Hôpital Huriez CHRU Lille, France † Service d’Hépato-Gastroentérologie Hôpital de Jolimont Haine-Saint-Paul Belgium ‡ INSERM U 481 and Service d’Hépatologie Hopital Beaujon Clichy, France § Equipe INSERM EPI 0114 CHRU Lille, France 1. D’Amico G, Luca A, Morabito A, Miraglia R, D’Amico M. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. Gastroenterology 2005;129:1282–1293. 2. Deltenre P, Mathurin P, Dharancy S, Moreau R, Bulois P, Henrion J, et al. Transjugular intrahepatic portosystemic shunt in refractory ascites: a meta-analysis. Liver Int 2005;25:349 –356. 3. Gines P, Uriz J, Calahorra B, Garcia-Tsao G, Kamath PS, Del Arbol LR, et al. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology 2002;123:1839 –1847. 4. Sanyal AJ, Genning C, Reddy KR, Wong F, Kowdley KV, Benner K, et al. The North American Study for the Treatment of Refractory Ascites. Gastroenterology 2003;124:634 – 641. 5. Salerno F, Merli M, Riggio O, Cazzaniga M, Valeriano V, Pozzi M, et al. Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites. Hepatology 2004;40: 629 – 635. 6. Lebrec D, Giuily N, Hadengue A, Vilgrain V, Moreau R, Poynard T, et al. Transjugular intrahepatic portosystemic shunts: comparison

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with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists. J Hepatol 1996;25:135–144. 7. Rossle M, Ochs A, Gulberg V, Siegerstetter V, Holl J, Deibert P, et al. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites. N Engl J Med 2000;342:1701–1707. 8. Albillos A, Banares R, Gonzalez M, Catalina MV, Molinero LM. A meta-analysis of transjugular intrahepatic portosystemic shunt versus paracentesis for refractory ascites. J Hepatol 2005;43:990 – 996. 9. Bureau C, Garcia-Pagan JC, Otal P, Pomier-Layrargues G, Chabbert V, Cortez C, et al. Improved clinical outcome using polytetrafluoroethylene-coated stents for TIPS: results of a randomized study. Gastroenterology 2004;126:469 – 475. doi:10.1053/j.gastro.2006.02.050

Reply. We are grateful to Dr. Deltenre et al for their comments on our meta-analysis of RCTs of TIPS for refractory ascites.1 We agree that the available studies were heterogeneous for the effect on mortality. According to our analysis, the ␹2 for heterogeneity was in fact 9.20, P ⫽ .056. To explore the reasons of the heterogeneity, we used a meta-regression analysis to investigate the relationships between several patient and trial characteristics and the treatment effect on mortality. The analysis showed that the effect on mortality was significantly associated with the mean bilirubin of patients included in the studies and with the number of successful TIPS performed in each study. Among the included studies, mean bilirubin had the highest value and successful TIPS the lowest one in the only study showing a nearly significant increase in mortality with TIPS.2 This study was also the very first published in this field, the one achieving the lowest portal pressure gradient reduction after TIPS, and the one achieving the lowest TIPS assisted patency rate. We therefore hypothesized that this study could almost entirely explain the heterogeneity for the TIPS effect on mortality. The hypothesis was supported by a sensitivity analysis by excluding that study: in this analysis, the ␹2 for heterogeneity was 5.27 (P ⫽ .15) and the pooled odds ratio for mortality was 0.74 (CI, 0.40 to 1.37). This is a nonsignificant trend toward a reduction in mortality, found after having explained heterogeneity. Therefore, since several studies have found significant predictors of encephalopathy and mortality after TIPS, we hypothesize that a better selection of patients according to these criteria may help to identify a subgroup of patients with refractory ascites who may benefit from TIPS also for mortality. This hypothesis should be tested in future studies. Of course, we agree that a meta-analysis based on individual patient data would provide more reliable information on criteria to select the best candidates for TIPS. Therefore, we agree with Dr. Deltenre et al that the available studies are heterogeneous for the effect on mortality. However, having found a reasonable explanation for this heterogeneity, we went beyond heterogeneity and suggested criteria for new studies, which we strongly recommend. We also agree with Dr. Deltenre et al that future studies should use covered stents as we stated in our article. GENNARO D’AMICO Unit of Gastroenterology Ospedale V.Cervello Palermo, Italy

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ANGELO LUCA Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (ISMETT) Palermo, Italy ALBERTO MORABITO Cattedra di Statistica Medica Dipartimento di Medicina e Chirurgia e Odontoiatria Università di Milano Milano, Italy ROBERTO MIRAGLIA Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (ISMETT) Palermo, Italy MARIO D’AMICO Unit of Gastroenterology Ospedale V Cervello Palermo, Italy 1. D’Amico G, Luca A, Morabito A, Miraglia R, D’Amico M. Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis. Gastroenterology 2005;129:1282–1293. 2. Lebrec D, Giuily N, Hadengue A, Vilgrain V, Moreau R, Poynard T, Gadano A, et al. Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. J Hepatol 1996;25:135–144. doi:10.1053/j.gastro.2006.02.051

Prevalence of Barrett’s Esophagus Dear Sir: Ronkainen et al1 recently reported the prevalence of Barrett’s esophagus in a randomly selected sample of 1000 Swedish subjects who were invited by mail to undergo endoscopy. The prevalence of any Barrett’s was 1.6%, and long-segment Barrett’s (ⱖ 2 cm in length) was 0.5%. These prevalences were lower than what we found (6.8% and 1.2%, respectively) in 961 colonoscopy patients age ⱖ 40 years, without prior upper endoscopy, who agreed to undergo screening upper endoscopy on the day of their colonoscopy.2 Ronkainen et al attributed the differences to a greater degree of selection bias in our study. We suggest that the differences between studies could be largely due to differences in the methodology of endoscopy. Methodologic features that may have contributed to the differences in Barrett’s include the efficiency of detecting intestinal metaplasia (IM) in columnar-lined esophagus (CLE) and the endoscopic interpretation of “tongues” of CLE. Thus, we identified 12 segments of CLE 3 cm or longer, and all 12 had IM identified. We found 7 segments of CLE 20 –29 mm in length, of which 5 had IM. Ronkainen et al found 12 segments of CLE ⱖ 20 mm of length, of which 5 had IM. The difference in detection of IM in segments ⱖ 20 mm in the 2 studies (17 of 19 versus 5/12; P ⫽ .004; ␹2 test) could reflect the number or size of biopsies taken or the pathologist’s interpretation of IM. We biopsied 157 segments of CLE ⱖ 5 mm in length but ⬍ 20 mm in length, of which 48 (30.5%) had IM. We biopsied segments ⱖ 5 mm, although endoscopic identification of segments 5–10 mm in length is undoubtedly subject to intra- and interobserver variation, and 33 of the Barrett’s segments we identified were 5–9 mm in length. Ronkainen et al did not specify a length of CLE required prior to biopsy of very short segments of CLE, but identified 91 segments of CLE ⬍ 20 mm in length, of which 12.1% had IM (P ⬍ .001 for percent of CLE segments ⬍ 20 mm with IM compared