A tree grows in the liver, and now we can see it


  • Potential conflict of interest: Nothing to report.

I think that I shall never see

A poem lovely as a tree…?

With these familiar opening lines of his brief poem Trees,1 the somewhat less familiar First World War American poet Joyce Kilmer (1886-1918), who died on a French battlefield, expresses frugally yet so elegantly the sentiments of love, fascination and reverence that most people and peoples have for trees. Trees are one of earth's oldest life forms, and were once the dominant plant over much of its land surface, as tropical, sub-tropical and temperate forests at one time covered a considerable part of the Americas, Africa, western Europe, China, Japan, Oceania and southern Australia. The 50 million years that our evolving ancestors spent in trees before returning to the ground, seems to have imprinted humans with a special relationship to trees. Aside from the importance of wood for fire, agriculture, building, printing, transport and music, trees have had a powerful emotional and spiritual influence and held an important place in religion, myth and lore. It is fabled that the prehistoric Ginko biloba tree, the oldest living tree species on the planet, was saved from extinction after the Ice Age by ancient Chinese monks who used it for temple plantings. People still believe that an extract of the leaf of this living fossil (the largest plantation of which is here in South Carolina) has brain-enhancing properties, a notion that is surely contradicted by the fact that they continue to ingest it. Trees have been worshiped as gods and as the dwelling place of spirits; groves have become sacred places. Yggdrasil, the legendary ash tree of Scandinavia, is the basis of Norse mythology. There is the Tree of Knowledge with its attendant serpent in the Jewish Torah, the Christian Bible and the Muslim Koran. The Buddhists have their Bodhi tree, and for Hindus trees are homes to spirits. The Romans had their Rowan, the Greeks had nymphs in oak, walnut, cherry, mulberry and fig. And in many countries it has been a tradition from antiquity to hold an annual tree or forest festival. The modern Arbor Day, first observed in 1872 in Nebraska and conceived by J. S. Morton as an idea to promote replanting following deforestation, has spread to more than 50 countries where it is variously celebrated. There is Arbor Day in Australia, the “Tree-loving Week” of Korea, “The Reforestation Week” of former Yugoslavia, “The Students' Afforestration Day of Iceland”, “The National Festival of Tree Planting” in India, and the “New Year's Day for Trees” in Israel. But perhaps nowhere are trees more revered than in Japan where Jomon culture was also a tree culture that can be traced back 12,000 years to the Japanese Neolithic period. O-Hanami, the popular flower viewing of the cherry tree blossom that has been a Japanese custom since the 7th Century heralds the arrival of spring, and Bonsai, the cultivation of miniaturized trees in containers, has flourished since it was first introduced there from China during the Kamakura period of the 14th Century. Perhaps it was the Japanese affection for trees that subconsciously stimulated and inspired the late Kunio Okuda (1921-2003), his colleagues and his trainees to perfect the art of safely visualizing the liver's own Tree of Life, the Biliary Tree.2, 3

The ancients, preoccupied with deciding how many lobes the liver had and the whence and the whither of its complex venous connections, paid relatively little heed to the overall structure and functional anatomy of the bile secretory apparatus per se, even though they were deeply invested in describing the origin, properties and fate of bile. As far back as 2,000-3,000 BCE, the Babylonians had mapped the gross and surface anatomy of livers of sheep and other animals for divination purposes, describing the lobes, grooves, fissures and channels in intricate detail.4 They recognized the “bitter part”, the gall bladder, and correctly inferred that it emptied into the cystic duct and common bile duct, but erroneously reasoned that there was also retrograde flow into the hepatic ducts. The Babylonians were not concerned with function but rather with prognostication, of both public events and private affairs, from the disposition of the organ. If the gallbladder was swollen on the right, the strength of the King's army would increase, but swelling on the left meant that the enemy would prosper. If the gallbladder were tightly embedded in the gallbladder groove, then the King's army would be in the firm grasp of the enemy. If the biliary duct was long, it pointed to long life; if the hepatic duct was well enclosed in the porta hepatis, the gate of the liver, it meant success in battle, and so on. Virtually unmodified, the Babylonian vision of the extrahepatic biliary tree remained secure through the Greco-Roman period and far beyond, but there was little progress if any in understanding the structure of its intrahepatic portion until well into the 17th Century. Galen and his followers for 1,500 years, believed that yellow bile, the light bitter component of digested food, was separated by the liver after digestion of intestinal contents, and then was somehow sucked or attracted by force into the bile ducts and stored in the gallbladder for excretion into the intestine when necessary.5 The opposing view that bile forms in the gallbladder, championed by Franciscus Sylvius (also known as Franz de le Boë), whose discovery of the lateral cerebral fissure has proven more durable, was debunked experimentally by Marcello Malpighi.6 Malpighi, of hepatic lobule fame,7 performed a cholecystectomy in a cat and found that bile still flowed from the liver. Francis Glisson, Regius Professor of Physic at Cambridge, showed quite elegantly in a digested liver specimen that branches of the hepatic artery, portal vein and bile duct lie in a common sheath that is an extension of his eponymous covering liver capsule.8 Kiernan, early in the 19th Century, using a hand lens and a simple quicksilver injection technique, identified and defined the portal tract that included a bile duct along with an hepatic arteriole and portal venule.9 And to complete the pathway from hepatocyte canaliculus to bile ductule, some 30 years later, Karl Ewald Konstantin Hering discovered the canals that bear his name,10 which are partially lined by hepatocytes and partly by small cuboidal or pyramidal cells that may be the hepatic stem cells.11 In recent years, the art of anatomical preparation by injection and corrosion that was perfected in the 17th and 18th centuries by masters like Frederick Ruysch (1638-1731), Professor of Anatomy in Amsterdam, has been resurrected to show not only the unique intimate arterial supply of the bile duct,12 but also its capillary network using scanning electron microscopy of resin casts.13 Finally, this brief romp through the history of biliary anatomy would not be complete without mentioning the two men who described the biliary exit apparatus, namely Abraham Vater (1684-1751)14 and Ruggero Oddi (1864-1913).15 Whereas Vater's life and career were stellar but staid, Oddi's meteoric professional life ended in torment, scandal and ignominy. Vater, the son of an eminent professor of anatomy in Wittenberg, studied at the most prominent medical institutions of his period after graduating in medicine from the University of Leipzig. He then rose through the ranks to become “Professor Primus” at the University in his native city. His anatomical discoveries included the duodenal structure through which bile and pancreatic juice jointly enter the duodenum, which incidentally he called neither papilla nor ampula but diverticulum,16 and the large subcutaneous sensory receptor that is now known as the Vater-Pacinian corpuscle. He was elected to both the Royal Society in London and the Prussian Academy of Sciences and died, ironically enough, of jaundice.

Oddi discovered the sphincter that brought him fame when he was only 23 years old and still a 4th year medical student in Perugia, in Umbria Italy, where he was born. His discovery was not fortuitous but stemmed from the results of careful work on dogs that suggested the presence of a special mechanism at the distal end of the bile duct that regulates bile flow into the duodenum. Oddi proved the existence of the sphincter with extensive histologic examinations in many species, including humans, and with physiological measurements of sphincter resistance that he conducted the following year at the University of Bologna, including neural studies. Oddi's achievement crowned the previous work of luminaries Vesalius, Glisson, Vater and Cage. At age 29, he was promoted to the Chair of Physiology at the University of Genoa, where his laboratory was ultimately ruined financially by the drug-addicted cultist, Stefano Capranica, head of physiological chemistry teaching, under whose spell he had fallen, and who may also have been responsible for the disappearance of his wife. Abandoning his academic career, Oddi intended to work lucratively as a contract doctor in the Free State of the Congo but he became profoundly depressed while in Brussels. There, he was cured of his mental illness by a homeopathic Belgian doctor, who also converted him to Indian mysticism. Oddi's stay in the Congo was cut short by a serious illness and his unlimited use of narcotics. After a brief sojourn in Spain and 6 years of practising homeopathic medicine in his home town, prescribing the same homeopathic concoction of glycerin, sodium borate, ammonium chloride and alcohol (called Gatchkowski's Vitaline) that had cured him of depression, he was accused of abusive use of medical products and involuntary manslaughter. He died mysteriously a couple of years later in Tunisia, and the whereabouts of his grave are unknown.

The earliest recorded radiological incursion into the human biliary tree of life, was accomplished in Germany in 1921 via gallbladder puncture.17 This was next achieved more safely under direct vision at peritoneoscopy, initially in Germany by Kalk18 but later in many other countries. An alternative “blind” percutaneous method for gallbladder puncture was being developed in two Japanese centers, at Tohoku University in Sendai in the Miyagi Prefecture, and at Chiba University to the east of Tokyo. In 1954 Suzuki, in the Department of Surgery in Sendai, accessed the gallbladder using a 0.7mm needle with a transhepatic approach19 that Sato, in the same department, later modified by shifting to a flank approach.20 At about the same time, from 1956 to 1970, surgeons in Chiba were successfully refining a similar tack21–24 using similar sized needles (0.5-0.9mm) and the same attention to anatomical detail and route of access. Ueno even succeeded in performing direct percutaneous transhepatic cholangiography percutaneously in 26 patients without a single bile leak.23 By this time, the fickle anatomy of the intrahepatic biliary tree had been well described.25 Meanwhile, in Hanoi, seemingly unaware of the earlier studies of cholangiography, Frenchman Pierre Huard and his Vietnamese colleague Colonel Do-Xuan-Hop entered and opacified the intrahepatic bile ducts with Lipiodol™ while attempting to visualize liver abscesses, thereby inadvertently performing the first percutaneous transhepatic cholangiogram.26 Not surprisingly their article in French, published in an obscure Indochinese medical-surgical bulletin,27 attracted little notice. Their technique was thus re-invented a few years later by two New York City surgeons, Carter and Saypol, who were undoubtedly ignorant of the Hanoi experience. Publication in a journal of wide readership28 meant that within a few years the procedure was performed and published in many parts of the world, especially South America, North America, Britain and Europe.29–36 The advent of fluoroscopy37, 38 and the use of the catheter needle technique, pioneered by Swede Sven-Ivar Seldinger (1921-1998),39 which permitted easy catheter placement, further advanced the field. Nonetheless, percutaneous cholangiography was still essentially a surgical procedure that was performed as an immediate prelude to an operation because of the risk of bile leak and bile peritonitis. The stage was set for a further leap forward, and one that would free the internist from dependency on surgical colleagues. The breakthrough in direct biliary imaging came at Chiba University, where Ohto, Tsuchiya and others of the First Department of Medicine perfected percutaneous cholangiography using a thin unsheathed needle, a right flank approach, horizontal needle direction and the injection of contrast medium under fluoroscopy instead of aspiration of bile to locate intrahepatic bile ducts.2, 3 In 1972, Tsuchiya reported his results in 554 patients, with only 13 minor complications.41

Dr. Kunio Okuda (Fig. 1) was appointed Professor and Chairman of the First Department of Medicine at Chiba University in 1971. Having graduated in medicine from Manchuria Medical College and on completion of a fellowship at Chiba University, Dr. Okuda spent 3 years as a fellow in Biochemistry and Medicine at Johns Hopkins University researching on vitamin B12, where he was also briefly an assistant professor. He then became Chairman of Medicine at Kurume University in Kyasyu Island. Next, at Chiba University, he established a world famous liver unit with special interests in idiopathic portal hypertension, hepatocellular carcinoma, intrahepatic lithiasis and imaging techniques in hepatobiliary disease, on which he published profusely. Although the development of what Dr. Okuda famously termed the “Chiba” needle was already in progress when he assumed the Chair, he played a pivotal, collaborative and permissive role in development of the technique and, of great importance, in introducing it to the medical world outside Japan. Dr. Okuda's command of English, about which he taught, published books and even committed to gramophone record, was key in exporting the Chiba needle technique to the rest of the world. In his landmark article,42 Okuda reported the results of “skinny needle cholangiography” on 314 patients gathered from his own experience and from colleagues and former trainees. Among patients with surgical hepatobiliary conditions, the success of the procedure for malignancies, gallstone disease and bile duct abnormalities was 100, 83, and 83%, respectively, of whom 25 patients or 8% had complications, such as fever, hypotension, bile leak, biliary peritonitis, bleeding or coughing. Of the 80 patients without surgical disease, the intrahepatic bile ducts were visualized in 54 (67.5%) and only one patient experienced an exacerbation of cough due to a preexisting hepatobronchial fistula. Even failure to opacify the bile ducts was deemed significant and suggested a non-surgical cause. In earlier reports, percutaneous cholangiography with fluoroscopy was never successful in patients without dilated bile ducts. Soon after this landmark paper was published, general interest was stimulated and there was publication of a supportive report from southern California43 followed by confirmatory reports from Boston,44 Miami,45 London,46 and Copenhagen.47 Percutaneous cholangiography compared favorably to endoscopic retrograde cholangiography in an early randomized trial that showed the strengths and weaknesses of each technique, and their complementary natures.48 Dissemination of percutaneous cholangiography paved the way for other comparable transhepatic techniques such as catheterization of the portal vein for obliteration of esophageal varices,49 and for obtaining portal hemodynamic measurements.50 These latter indications have now been superceded by the transjugular approach for intrahepatic stent placement and wedged hepatic venous pressure testing.

Figure 1.

Kunio Okuda (1921-2003), a life dedicated to medical science. Recipient of the highest honors in his native Japan (e.g., in 1996, the 3rd Order of the Rising Sun), and worldwide renowned medical scientist, ambassador, humanist and passionate piscator. Equally comfortable with the culture of the West, and serenely at ease amid the blooming cherries of his Chiba University home.

Although there are many aspects of Kunio Okuda's professional life that could have been selected to highlight as landmarks, for he published 553 articles in English alone, 208 of which appeared after he “retired” in 1987, as well as several monographs in English, and Japanese, and scores of articles in Japanese too, his article on percutaneous cholangiography exemplifies many facets of this great man. First and foremost, he was an ambassador for medical science and a highly effective communicator in both his native Japanese language and in English. His role as a facilitator and selfless consultant is readily apparent in this article42 and his historical review3 of the Chiba needle approach. Legions of medical scientists visited his unit in Chiba and, in turn, he was a frequent guest all over the world. He played leadership roles in many medical, clinical and scientific societies and worked tirelessly in editorial capacities. This did not prevent him from participating in family life and in many physical and extracurricular activities, including classical music, tennis, scuba, his passion for fishing, and even hang gliding. He received many awards and honors at home and abroad. The affection and esteem with which he was regarded cannot be exaggerated.

The field of percutaneous cholangiography has not been stationary since the publication of Okuda's landmark article, and now includes a panoply of therapeutic options. In the early days, overuse of the technique by inexperienced operators led to an increase in complications that soon became recognized,51 and steps were taken to correct the problem and put appropriate guidelines in place for quality control.52 The percutaneous transhepatic route was used early on for external drainage of obstructive lesions53 and for the placement of endoprostheses.54 Biliary ascariasis can be treated,55 endoscopic sphincterotomy can be done,56 intrahepatic stones can be cleared57 and strictures can be dilated by the transhepatic route.58 More recent developments have been the design of electrolytic stents that generate their own electrical current to inhibit tumor growth59 or self-destruct. Covered stents that are less likely to occlude are being tested.60 And finally, we can see the biliary tract in all its immaculate arborescence using computer-assisted reconstructions,61, 62 even at the microscopic level.61

In closing this discussion of a technological tour de force, it is as well to remember how we started, by considering the importance of trees and other natural phenomena to human well-being. As natural resources and the gifts of nature become eroded in our increasingly industrialized world, we are in danger of “not seeing the wood”, because there are no trees. Ogden Nash stigmatizes this risk from another perspective with his sardonic parody of Alfred Joyce Kilmer's Trees.

I think that I shall never see a billboard lovely as a tree Indeed, unless the billboards fall I'll never see a tree at all.63


The author thanks Dr. Alan F. Hofmann for introducing and loaning to him the illustrated autobiography of Kunio Okuda (from which the Figure derives). The author also appreciates all the help that Dr. Renan Uflacker, Chief of Interventional Radiology at the Medical University of South Carolina, has given him in preparing for this Landmark and for his incomparable skill in performing percutaneous transhepatic cholangiography and many other interventional procedures on his patients. The author thanks Margie Myers for continuing hard labor of literature retrieval and, for her manuscript skills.