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Editorials Why Should Every Physician Know About Hemobilia? HEMORRHAGE THROUGH THE BILIARY TRACT long remained obscure and was regarded as a medical curiosity but is now steadily rising in importance. Although there were occasional case reports, the first one by Glisson in 1654, the syndrome was practically unknown until about 50 years ago when it received its current name, hemobilia-a linguistic bastard of Greek and Latin. Whereas hematuria, its sister condition, was introduced in the Index Medicus from the beginning, more than a century ago, hemobilia does not appear until 1980. With about 25 references annually, it still has only a third of those on hematuria. One reason for the difference might be that tumors in the liver seldom bleed into the ducts, while those in the urinary tract are the main cause of hematuria. The rise in frequency can be explained partly by a growing knowledge, with fewer cases being overlooked, but it is mainly due to a real increase in occurrence. With more traffic accidents, there are more cases of liver trauma causing central liver ruptures, often a concealed source of hemobilia that is easily missed. Trauma is the most common cause of the pathologic vascular-biliary connection. It is a serious memento to physicians that the incidence of iatrogenic trauma from invasive diagnostic and therapeutic procedures such as percutaneous liver punctures for biopsy, transhepatic cholangiography, and lithotomy is increasing more rapidly than trauma from traffic accidents. A bleeding source that recently has attracted attention despite its rarity is the pancreatic one, causing what has been called "hemosuccus pancreaticus." In chronic pancreatitis, the lysing effect of extravasating pancreatic juice may cause not only pseudocysts but also pseudoaneurysms of the neighboring splenic artery. When these rupture into the duct of Wirsung, severe colicky pain and gastrointestinal hemorrhage through hemobilia ensue. There are two main reasons why physicians should be informed of the syndrome. The first concerns major profuse hemobilia. Whereas exsanguinating hemobilia is rare, it must be suspected and promptly recognized because lifesaving procedures might be urgently necessary. An uninformed surgeon may well be mistaken about the bleeding source and perform an inappropriate operation such as "blind gastric resection." The other reason why knowledge is necessary is that minor hemobilia, with the formation of coagula in the bile ducts, occurs often. The clots are easily mistaken for gallstones and are tempting to be treated aggressively with surgical or endoscoping measures. They will, however, usually resolve spontaneously through the fibrinolytic activity of bile, making operative treatment unnecessary. If a physician, confronted with the cardinal symptoms of gastrointestinal hemorrhage, biliary colic, and possibly jaundice, suspects hemobilia, he or she has excellent diagnostic means to confirm the diagnosis. Endoscopy will exclude other possible bleeding sources and may demonstrate blood extruding from the papilla of Vater. Selective arteriography is the foremost measure and will generally localize the source of the bleeding, which is essential for treatment. This
can be undertaken in direct connection with the diagnostic maneuver by employing the catheter to embolize the responsible bleeding vessel. Embolization is nowadays the primary therapeutic procedure, making operative ligature or liver resection unnecessary. Most physicians will encounter only a few cases of hemobilia in their career and will thus have to learn about it not through experience but through the literature. The article by Merrell and Schneider elsewhere in this issue presents that information in a most attractive way.1 With an excellent account of the pathophysiology, they give an accurate description of modern diagnostic and therapeutic methods. "The light which experience gives us," says Coleridge, "is a lantern on the stern which shines only on the waves behind us." The authors have provided us with an enlightening lantern on the bow. PHILIP SANDBLOM, MD Past President, University ofLund, Sweden Professor Emeritus of Surgery Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland REFERENCE 1. Merrell SW, Schneider PD: Hemobilia-Evolution of current diagnosis and Dec; 155:621-625
treatment. West J Med 1991
Dietary Folate-The Digestible Vitamin FOLIC ACID, a vitamin essential as a cofactor in the synthesis of cellular DNA, is particularly important for the support of tissues such as the bone marrow, intestine, and colon, where cell turnover is brisk. Although the ingestion of supplemental folic acid in its monoglutamate form (pteroylglutamic acid [PteGlu]) is common in young children and during pregnancy, most of us obtain adequate amounts of this vitamin in food as the complexed polyglutamate form (pteroylpolyglutamate [PteGlun, where the n subscript, denoting the number of peptide-linked glutamic acid units, is 2 to 7]).1 These glutamate residues of the pteroylpeptide are removed sequentially by cleavage from the end of the peptide chain, a reaction catalyzed by folate hydrolase (formerly called folate conjugase), an integral enzyme of the enterocyte brush-border membrane that is available to polyglutamates at the intestinal lumen-cell interface. This is an example of surface digestion by enterocytes that we now know to be an essential digestive step before transport of the final monoglutamate product. Although there are no other known instances of brush-border digestion of a vitamin, intestinal surface digestion of macronutrients at the brush-border membrane surface before entry into the enterocyte was identified many years ago. The brushborder oligosaccharidases2 (commonly called disaccharidases) cleave lactase, sucrase, and the oligosaccharide products from starch breakdown to monosaccharides; peptidases such as the amino-oligopeptidase3 (aminopeptidase N) and dipeptidylpeptidase4 remove amino acids from nutrient oligopeptides in preparation for the intestinal transport of dipeptides and amino acids. In these instances of nutrient surface hydrolysis by enterocytes, the oligomeric substrate, not being suitable for transport, must first be cleaved to trans-
portable products. When both digestion and transport are required by the enterocyte, questions arise concerning their relative rates and
Editorials Why Should Every Physician Know About Hemobilia? HEMORRHAGE THROUGH THE BILIARY TRACT long remained obscure and was regarded as a medical curiosity but is now steadily rising in importance. Although there were occasional case reports, the first one by Glisson in 1654, the syndrome was practically unknown until about 50 years ago when it received its current name, hemobilia-a linguistic bastard of Greek and Latin. Whereas hematuria, its sister condition, was introduced in the Index Medicus from the beginning, more than a century ago, hemobilia does not appear until 1980. With about 25 references annually, it still has only a third of those on hematuria. One reason for the difference might be that tumors in the liver seldom bleed into the ducts, while those in the urinary tract are the main cause of hematuria. The rise in frequency can be explained partly by a growing knowledge, with fewer cases being overlooked, but it is mainly due to a real increase in occurrence. With more traffic accidents, there are more cases of liver trauma causing central liver ruptures, often a concealed source of hemobilia that is easily missed. Trauma is the most common cause of the pathologic vascular-biliary connection. It is a serious memento to physicians that the incidence of iatrogenic trauma from invasive diagnostic and therapeutic procedures such as percutaneous liver punctures for biopsy, transhepatic cholangiography, and lithotomy is increasing more rapidly than trauma from traffic accidents. A bleeding source that recently has attracted attention despite its rarity is the pancreatic one, causing what has been called "hemosuccus pancreaticus." In chronic pancreatitis, the lysing effect of extravasating pancreatic juice may cause not only pseudocysts but also pseudoaneurysms of the neighboring splenic artery. When these rupture into the duct of Wirsung, severe colicky pain and gastrointestinal hemorrhage through hemobilia ensue. There are two main reasons why physicians should be informed of the syndrome. The first concerns major profuse hemobilia. Whereas exsanguinating hemobilia is rare, it must be suspected and promptly recognized because lifesaving procedures might be urgently necessary. An uninformed surgeon may well be mistaken about the bleeding source and perform an inappropriate operation such as "blind gastric resection." The other reason why knowledge is necessary is that minor hemobilia, with the formation of coagula in the bile ducts, occurs often. The clots are easily mistaken for gallstones and are tempting to be treated aggressively with surgical or endoscoping measures. They will, however, usually resolve spontaneously through the fibrinolytic activity of bile, making operative treatment unnecessary. If a physician, confronted with the cardinal symptoms of gastrointestinal hemorrhage, biliary colic, and possibly jaundice, suspects hemobilia, he or she has excellent diagnostic means to confirm the diagnosis. Endoscopy will exclude other possible bleeding sources and may demonstrate blood extruding from the papilla of Vater. Selective arteriography is the foremost measure and will generally localize the source of the bleeding, which is essential for treatment. This
can be undertaken in direct connection with the diagnostic maneuver by employing the catheter to embolize the responsible bleeding vessel. Embolization is nowadays the primary therapeutic procedure, making operative ligature or liver resection unnecessary. Most physicians will encounter only a few cases of hemobilia in their career and will thus have to learn about it not through experience but through the literature. The article by Merrell and Schneider elsewhere in this issue presents that information in a most attractive way.1 With an excellent account of the pathophysiology, they give an accurate description of modern diagnostic and therapeutic methods. "The light which experience gives us," says Coleridge, "is a lantern on the stern which shines only on the waves behind us." The authors have provided us with an enlightening lantern on the bow. PHILIP SANDBLOM, MD Past President, University ofLund, Sweden Professor Emeritus of Surgery Centre Hospitalier Universitaire Vaudois Lausanne, Switzerland REFERENCE 1. Merrell SW, Schneider PD: Hemobilia-Evolution of current diagnosis and Dec; 155:621-625
treatment. West J Med 1991
Dietary Folate-The Digestible Vitamin FOLIC ACID, a vitamin essential as a cofactor in the synthesis of cellular DNA, is particularly important for the support of tissues such as the bone marrow, intestine, and colon, where cell turnover is brisk. Although the ingestion of supplemental folic acid in its monoglutamate form (pteroylglutamic acid [PteGlu]) is common in young children and during pregnancy, most of us obtain adequate amounts of this vitamin in food as the complexed polyglutamate form (pteroylpolyglutamate [PteGlun, where the n subscript, denoting the number of peptide-linked glutamic acid units, is 2 to 7]).1 These glutamate residues of the pteroylpeptide are removed sequentially by cleavage from the end of the peptide chain, a reaction catalyzed by folate hydrolase (formerly called folate conjugase), an integral enzyme of the enterocyte brush-border membrane that is available to polyglutamates at the intestinal lumen-cell interface. This is an example of surface digestion by enterocytes that we now know to be an essential digestive step before transport of the final monoglutamate product. Although there are no other known instances of brush-border digestion of a vitamin, intestinal surface digestion of macronutrients at the brush-border membrane surface before entry into the enterocyte was identified many years ago. The brushborder oligosaccharidases2 (commonly called disaccharidases) cleave lactase, sucrase, and the oligosaccharide products from starch breakdown to monosaccharides; peptidases such as the amino-oligopeptidase3 (aminopeptidase N) and dipeptidylpeptidase4 remove amino acids from nutrient oligopeptides in preparation for the intestinal transport of dipeptides and amino acids. In these instances of nutrient surface hydrolysis by enterocytes, the oligomeric substrate, not being suitable for transport, must first be cleaved to trans-
portable products. When both digestion and transport are required by the enterocyte, questions arise concerning their relative rates and
