Portal vein thrombosis, a cause of obstructive jaundice

March 2004

SELECTED SUMMARIES

tion and continuous treatment with PPIs eliminate HGD and, by comparison with historical data, may reduce the expected frequency of carcinoma (Gastrointest Endosc 2003;58:183–188). Fennerty has provided a critical outlook assessment in an accompanying editorial (Gastrointest Endosc 2003;58:246 –249). From the clinician investigator’s evidence-based medicine point of view, the comments in the editorial seem appropriate. I urge you to read that terse editorial. However, looking through the upside of bifocals provides a different perspective. There are several conclusions from this article. First, it is inspiring to see this master piece report from a private practice setting, a rare phenomenon in today’s world. Second, the authors should be congratulated for their labor of love to advance the art and science of endoscopic therapy of Barrett’s esophagus for over a decade, where every single patient was treated with compassion and prayer before the PDT therapy (reported by a patient of mine who was one of subjects in this report). Without such dedication, one cannot give an account of every single patient as Overholt did—not an easy task to preach and practice! Third, long-term observational studies of this kind have immense value; they reveal the real life, true story as it is. One thing is very clear from Overholt’s study: only 4.6% of patients with HGD developed cancer during 50 months of follow-up. Irrespective of how we slice it (or slash it), this is an impressive result, substantially better than the lowest reported cancer incidence (9%) in other studies, something that simply cannot be ignored. However, evidence-based medicine purists insist on having the real evidence— where is the control (Gastrointest Endosc 2003;58:246 –249)? There is no peer-reviewed, controlled trial in publication yet, but preliminary results of an international, multicenter, partially blinded randomized study of PDT plus omeprazole (n ⫽ 138) versus omeprazole (n ⫽ 70) with a 24-month follow-up have shown that PDT decreased progression to cancer (13% vs. 28% in the control group) (Gastroenterology 2003;124:A151). Although these results are encouraging, current endoscopic therapies are far from reaching a clean sweep of the entire Barrett’s esophagus in one stroke, leaving no trace behind, either on the surface or beneath it. If Overholt’s personal observations were proven in a randomized controlled trial, can every patient with Barrett’s esophagus and HGD expect excellent outcome with PDT, irrespective of where they are treated. I doubt it! A decade of Overholt’s experience with PDT is hard to match, and the effects of adjuvant spiritual therapy (prayer before PDT) are hard to reproduce. In summary, this report truly reflects the results of labor of love in clinical medicine and a passion for life-long learning. Much can be learned from such Oslerian descriptions of disease and its natural history tinkered by man and machine. I am sure we all agree that Overholt has lived by the Oslerian Principles in his life course on endoscopic therapy of Barrett’s esophagus. The hardest conviction to get into the mind of a beginner is that the education upon which he is engaged is not a college course, not a medical course, but a life course. —Sir William Osler, 1900 GOTTUMUKKALA S. RAJU, M.D.

PORTAL VEIN THROMBOSIS, A CAUSE OF OBSTRUCTIVE JAUNDICE Condat B, Vilgrain V, Asselah T, O’Toole D, Rufat P, Zappa M, Moreau R, Valla D (Service d’Hepatologie and INSERM Unite 481, Federation Medico-chirurgicale d’Hepatogastroenreterologie, Service de

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Radiologie, Service de Gastroenterologie, and Cellule MSI, Hopital Beaujon, AP-HP, Paris, France). Portal cavernoma-associated cholangiopathy: a clinical and MR cholangiography coupled with MR portography imaging study. Hepatology 2003;37:1302–1308. Twenty-five consecutive adults with portal cavernoma secondary to portal vein thrombosis, without cancer or cirrhosis, were studied with MR cholangiography coupled with MR portography. Seven patients presented with clinical manifestations of biliary disease. Twenty-one patients were found, on MR cholangiography, to have biliary stenosis, with displacement in 13, and upstream dilatation in 16. MR cholangiography, coupled with MR portography, showed that the biliary abnormalities were caused by a mass effect of a portal cavernoma exerting pressure on the biliary system. The main conclusion from this study is that portal vein thrombosis must now be considered in the differential diagnosis of extrahepatic cholestasis. Comment. Cavernous transformation of the portal vein, portal cavernoma, occurs as the result of extrahepatic portal vein obstruction. Classically, in contrast to acute portal vein thrombosis, the patient has a silent clinical presentation at the time of thrombosis (Hepatology 2000;32:466 – 470). The reason for the silent presentation is thought to be a combination of two major factors. Immediately there is dilatation of the hepatic arterial system, as part of the so-called reciprocal hepatic vascular response, in which a decrease in portal venous blood flow stimulates an increase in hepatic arterial blood flow (Can J Physiol Pharmacol 1980;58:105–123). Following this, secondary to the presence of extrahepatic or presinusoidal portal hypertension, there is the rapid development of multiple collateral veins around the obstructed portion of the portal vein, forming the cavernoma, as well as in the walls of adjacent structures resulting in varices (J Hepatol 2000;32:865– 871). Indeed, it is these varices that are usually the initial presentation of portal vein thrombosis as a result of gastrointestinal bleeding. In these patients, the bleeding commonly results in morbidity but uncommonly in mortality (Gut 2001;49: 720 –724), in contrast to variceal bleeding secondary to cirrhosis. Patients can develop portal vein thrombosis as a result of local factors, especially inflammation, effecting the portal vein, or as part of a systemic hypercoagulopathy caused by either single or multiple thrombophilic disorders (Hepatology 2000;31:345–348), or to both local and inflammatory factors (Gut 2001;49:720 –724). Radiographic biliary tract abnormalities associated with extrahepatic portal vein thrombosis (EPVT) are well described (Hepatology 1993;17:807– 813, Acta Radiol 2000;41:612– 615). Indeed, the biliary radiographic appearances can vary from bile duct stenosis with or without stones (Dig Dis Sci 1988;33:1626 –1628, Hepatology 1993; 17:586 –592, Gastrointest Endosc 1995;42:178 –181, J Hepatol 1996;25:58 – 63). The stenoses can be single or multiple. But the cholangiographic appearances can also mimic bile duct cancer, with the cavernoma appearing as a solid tumor, the so-called “pseudocholangiocarcinoma sign” (Am J Gastroenterol 1995;90:2015–2019), or sclerosing cholangitis (Gut 1992;33:272–276). In the present report of Condat et al., MR portography revealed the presence of the intra- and extrahepatic cavernomas in close proximity to the biliary system. The authors indicated that the difference in the radiographic findings of the presence or absence of bile duct stenosis was associated with the size of the cavernoma. All these variants can present differently clinically and biochemically. Therefore, it is surprising that in

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a recent extensive review of one of the largest series of 172 patients with EPVT, there was no mention of any biliary complications, or results of the cholestatic enzymes (Gut 2001;49:720 –724). In contrast in the present report, the number of biliary presentations was about half of the number of patients who presented with variceal bleeding. The most common clinical presentations were those of an acute cholecystitis-like syndrome, with elevated alanine transaminases levels, with or without gallstones, and of cholestatic jaundice with or without pruritus, with or without cholangitis. In one case, the patient had 5 previous episodes of ascending cholangitis (during 1 episode, pigment stones had been extracted endoscopically) before the patient finally presented with acalculous cholecystitis, and the diagnosis of cavernoma cholangiopathy had been made. The prevalence of EPVT-associated cholangiography has been suggested in the literature to more than 70% (Hepatology 1993;17:807– 813). In the present series, it was more than 90%, but this may be due to patient selection because the majority of patients were followed up at Hopital Beaujon, where there is a known special interest in vascular disorders of the liver. The literature suggests that between 20% and 35% of patients with EPVT may present with biliary symptoms (Acta Radiol 2000;41:612– 615, Hepatology 1993;17:807– 813). In the present series, it was more than 50%. The authors provide impressive evidence that the major cause of this syndrome is the presence of a cavernoma, because previously, they have not found this syndrome in patients with EPVT in the absence of a cavernoma (Hepatology 2000;32:466 – 470). By the same argument, since cavernoma is a later manifestation of EPVT, the associated cholangiography will likely also be a later manifestation and may explain the predominant literature from the Indian subcontinent and Southeast Asia. Nevertheless, alternative theories have been presented for the development of EPVT-associated cholangiopathy, which include ischemia (Gastrointest Endosc 1999;50:646 – 652). In the present study, the authors found no evidence to support this possibility. An alternative theory is obstruction by biliary varices (Endoscopy 2000;32:520 –524). The different theories on pathogenesis impact methods of treatment. In the present series, the patients presenting with bile duct stones were treated with ursodeoxycholate alone, even though the patients had bile duct stenosis, associated with pigment stones in the dilated proximal part of the duct. Three of the 4 patients had no recurrence of symptoms on the medication. In contrast, the standard therapeutic approach would be endoscopic sphincterotomy and dilatation of the stricture, extraction of any bile duct stones, with or without placement of a stent (Endoscopy 1993;25:423– 425, Gastrointest Endosc 1995;42:178 –181). This approach has been reported to be very effective in relieving biliary symptoms in these cases. The alternative approach is based on the theory that the underlying pathogenesis is related to portal hypertension, secondary to EPVT. Surgical shunting, such as meso caval anastomosis, has been tried and reported to be successful in alleviating symptoms (J Hepatol 1995; 23:629 – 630, Br J Surg 1998;85:326 –329). However, shunting can be difficult or impossible in these patients because of an absence of suitable veins for the anastomosis. For this reason, there are case reports of transjugular intrahepatic portovenous shunting (TIPS) having been used successfully in such patients (Am J Gastroenterol 1996;91:150 –154). In the present series, TIPS was chosen as therapy for 1 patient, but was unsuccessful. An alternative approach might be to use portal hypotensive medical therapy, such as beta blockade. In summary, improvement in the management of variceal bleeding, and recognition and treatment of underlying coagulopathies preventing recurrent thromboses, may result in the biliary complications of EPVT becoming increasingly clinically relevant. Further-

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more, liver biopsies in some of the patients in the present series showed the presence not only of cholestasis, but of marked bile duct proliferation and severe biliary fibrosis and septa formation. These histological abnormalities could progress to secondary biliary cirrhosis. It is, therefore, incumbent on physicians treating such patients to be aware of the entire spectrum of clinical problems associated with EPVT cholangiopathy and to develop suitable algorithms (J Gastroenterol Hepatol 2001;16:1086 –1092) derived from evidence-based medicine to optimize their treatment. LAURIE BLENDIS, M.D. FRED M. KONIKOFF, M.D.

IS BIGGER BETTER? RE-EXPLORING THE RELATIONSHIP BETWEEN HOSPITAL VOLUME AND SURGICAL OUTCOMES Goodney PP, Stukel TA, Lucas FL, Finlayson EVA, Birkmeyer JD (VA Outcomes Group, Department of Veterans’ Affairs Medical Center, White River Junction, Vermont; the Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; the Center for Outcomes Research and Evaluation, Maine Medical Center, Portland, Maine; and the Department of Surgery, University of California, San Francisco, San Francisco, California). Hospital volume, length of stay and readmission rates in high-risk surgery. Ann Surg 2003;238: 161–167. Little guidance is available for the patient (or third-party payer) who wishes to assess the quality of a provider or health care system. Although professional accolades, such as board certification or membership in medical societies, might attest to a physician’s standing in his or her field, they are far from perfect markers of quality care. Furthermore, they do not speak to the efficacy of the entire system— even a virtuoso surgeon might be hamstrung by poor nursing or inadequate ancillary services. Because of the increasingly competitive nature of medicine as a business, and given the increasing sophistication of the consumers, it is not surprising that patients and insurers seek surrogate markers of quality and value. Chief among these investigated markers is hospital volume for the procedure under consideration. In a previous seminal study, Birkmeyer and colleagues demonstrated that surgical mortality was improved in larger volume hospitals for each of 6 procedures that they studied using the Medicare database (N Engl J Med 2002;346:1128 –1137). This report joined multiple other studies describing superior outcomes in high-volume centers (JAMA 1998;280:1747–1751, J Surg Res 2003;114:50 –56, Stroke 2003;34:2200 –2207). Mortality is an attractive outcome to track for surgical procedures, given that it is not open to interpretation and is often available in administrative databases. Less is known about other surgical outcomes, such as length of stay in the hospital or the likelihood of readmission in the post-surgical period. These outcomes are of special interest to payers because they may serve as proxies for health care utilization and cost. On this background, Goodney et al. studied the effect of