Spontaneous Portal-Systemic Shunting Without Varices
Massive Marvin J.
Wexler, MD, Lloyd D. MacLean,
MD
Using umbilical vein portal phlebography, a group of patients, often with previously unsuspected liver disease or portal hypertension, have been identified with massive spontaneous portal\x=req-\ systemic shunts. In all cases, the collateral circulation was a single large vessel. The splenoadrenorenal, umbilical vein, or inferior mesenteric vein routes were the common pathways. These natural shunts were functional and effective in the alleviation of portal hypertension without evidence of esophageal varices or other collaterals. Portal flow was usually retrograde, perhaps contributing to the small atrophic liver seen in all patients. Six such patients were seen in the last 40 studied. This phenomenon may be more common than suspected in the cirrhotic population and account in part for differences in natural history, complications, and results of surgical therapy.
Spontaneous shunting
between the portal and systemic circulations is a frequent occurrence in pa¬ tients with both liver disease and portal hypertension. It is generally believed and taught that extrahepatic portalsystemic collaterals are numerous and small and cannot be clinically effective in reducing portal pressure or pre¬ venting the formation of gastroesophageal varices and 1
venous
hemorrhage. With the application of newer diagnostic techniques, a tremendous variability in vascular patterns and hemody¬ namics is now being appreciated, and different spontane¬ ous portal-systemic shunts are being increasingly recog¬ nized. Recently, we identified a group of patients with massive spontaneous shunts. In these patients, the collat¬ eral circulation was a single large vessel resulting in "relief" of portal hypertension and absence of esoph¬ agogastric varices and the usual clinical appearance of liver disease.
Accepted for publication March 25, 1975. From the Department of Surgery, Royal Victoria Hospital and McGill University, Montreal. Read before the 32nd annual meeting of the Central Surgical Association, Chicago, Feb 28, 1975. Reprint requests to the Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, H3A 1A1, Canada (Dr. Wexler).
CLINICAL POPULATION AND METHODS Since 1970, a series of 40 patients have been studied by means of umbilical vein portography as part of a sequence of diagnostic procedures performed at a single session called "minilap."'2 This procedure was performed on patients who were difficult diagnostic problems or who had an atypical presentation of liver disease of undiagnosed cause. After performing umbilical vein catheter¬ ization using local anesthesia, the catheter is guided under fluo¬ roscopic control into the splenic vein. Pressures and rapid se¬ quence portography is performed with low and high pressure injections of contrast material at various sites along the extra¬
hepatic portal tree. Six patients, ranging in ages from 24 to 60 years, were dis¬ covered to have totally unsuspected massive spontaneous portalsystemic shunts. In two patients, the shunt was between the splenic and left renal vein, while in another it was between the coronary and left renal veins. In two patients, a spontaneously re¬ opened and patent umbilical vein served as a massive conduit anastomosing with the iliac system. Im one patient, the shunt was via the inferior mesenteric vein to the hemorrhoidal plexus. None of these patients had esophageal varices and all except one were free of gastrointestinal bleeding. The spectrum of clinical mani¬ festations varied greatly. Two totally asymptomatic patients were being investigated for splenomegaly while a third was being in¬ vestigated for epigastric pain. None were known to have liver dis¬ ease. One young man had severe encephalopathy, while a young girl with well-established asymptomatic liver disease since child¬ hood was admitted with upper gastrointestinal bleeding of obscure cause. Five of the six patients clearly demonstrated hepatofugal portal flow, while the sixth showed noticeable reduc¬ tion of the portal fraction of total hepatic blood flow. All patients had small, shrunken livers, enlarged spleens, and demonstrated a striking absence of the plethora of collateral veins usually seen on venous portography in patients with portal hypertension. The spontaneous shunt in each instance was of usually large caliber and resembled in magnitude, and perhaps in volume of flow, sur¬ gically constructed portal-systemic anastomoses. A liver biopsy specimen showed Laennec cirrhosis in two patients, postnecrotic cirrhosis in two, and chronic aggressive hepatitis with cirrhosis in two. The following are selected case reports. REPORT OF CASES Case 1.—A
46-year old wrestler was first admitted
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to
our
hospi-
tal in 1971. He had been in excellent health all his life. Family screening, done because two nephews were ill with aplastic ane¬ mia, disclosed thrombocytopenia and splenomegaly. He drank sev¬ eral quarts of beer daily. On physical examination, there was a huge smooth spleen, nonpalpable liver, and no stigmata of liver disease. Laboratory studies showed thrombocytopenia of 42,000 platelets per cubic millimeter, leukopenia, and evidence of hemoly¬ sis. Liver enzyme values were normal including serum glutamic oxaloacetic transaminase (SGOT), bilirubin, alkaline phosphatase, albumin, and prothrombin time. Results of an upper gastrointesti¬ nal series were normal. At his wish, all additional investigations and treatment were stopped. Two years later, he reappeared with a painful swollen ankle. Physical examination again disclosed only massive splenomegaly. An x-ray film showed osteomyelitis of the left ankle and Staphylo¬ coccus aureus was cultured. Preliminary laboratory studies again showed thrombocytopenia and leukopenia, however, the alkaline phosphatase level was now 23.1 units (N 3 to 13), albumin was 2.9 gm/100 ml (N 3.5 to 5.0), and indirect bilirubin was elevated to 1.3 mg/100 ml. Attention was focused on the massive spleno¬ megaly and he underwent one month of intensive hématologie and immunologie investigations. All the results of these studies were normal except for a decreased red blood cell survival due to trap¬ ping in the spleen. A "minilap" for diagnosis was performed. Through a 3-cm epigastric incision, a massively dilated patent umbilical vein was immediately seen (Fig 1). A catheter was in¬ serted, manipulated into the splenic vein, and portography per¬ formed. The proximal part of the splenic vein was thrombosed. Just proximal to this thrombosis, the inferior mesenteric vein filled retrograde and descended to the left lower quadrant. Good filling of the intrahepatic portal system occurred and a small shrunken liver was outlined. The coronary vein was seen and did not give rise to varices. The majority of the flow from the portal vein was hepatofugal into the huge umbilical vein, which acted as a large collateral shunt. It coursed inferiorly in a very tortuous manner to the pelvis to anastomose with the iliac system, and thence to the inferior vena cava. No other collaterals were seen (Fig 2). With the catheter tip at the portal bifurcation, low pres¬ sure infusion of contrast failed to outline the liver, all of the flow being retrograde through the umbilical shunt. In this position, pressure measured 28 cm of H20, decreasing as the catheter was withdrawn into the umbilical vein. A liver biopsy specimen from the atrophie liver demonstrated micronodular cirrhosis. The um¬ bilical vein puncture site was carefully closed, preserving the shunt. He has remained well. An almost identical situation was seen in a 60-year-old patient being investigated for epigastric pain. =
=
Case 2.-A healthy, active 22-year-old man was first hospitalized in March 1967 with swelling of his legs. Results of a physical ex¬ amination were normal except for moderate pitting edema of the legs. Laboratory investigations showed the following values: he¬ moglobin, 9 gm/100 ml; total bilirubin, 2.2 mg/100 ml; SGOT, 170 units (N 8 to 40); and total protein, 4.86 gm/100 ml. Renal func¬ tion was normal and results of the Paul Bunnell test were nega¬ tive. Two attempts at percutaneous liver biopsy were unsuccessful and the patient was discharged. He remained well until September 1969, when he was read¬ mitted with a one-month history of progressive abdominal dis¬ tention and leg edema. Severe ascites was noted. The following laboratory values were obtained: hemoglobin, 8.9 gm/100 ml; pro¬ thrombin activity, 91%; platelet count, 115,000/cu mm; total bili¬ rubin, 3.4 mg/100 ml; SGOT, 210 units; blood ammonia, 134µg/100 ml (N less than 100); and total protein, 5.7 gm/100 ml. He re¬ sponded rapidly to diuretic therapy with a weight loss of 15 kg (33 =
=
Fig 1.—Massive patent dilated umbilical "minilap" incision (case 1).
vein
bulging
from
lb). Results of a barium swallow disclosed a normal esophagus without varices. Two additional attempts at liver biopsy were unsuccessful. He was admitted to the Royal Victoria Hospital for the first time in April 1971. He had been well until four days prior to ad¬ mission when he became drowsy, experienced dizziness, and felt himself "going into coma." On admission, he had normal vital signs but was disoriented and had gross "liver flap." He rapidly became unresponsive. Only the spleen was palpable, 3 cm below the left costal margin. There was no collateral abdominal wall cir¬ culation and stool specimens were negative for occult blood. As¬ cites and leg edema were not present. Investigations showed evi¬ dence of pancytopenia. The total bilirubin value was 2 mg/100 ml and SGOT 113 units. Serum electrolyte, calcium, glucose, blood urea nitrogen, creatinine, and blood gas levels were all normal. Arterial blood ammonia levels were 400^g/100 ml to 450/¿g/100 ml. An electoencephalogram was compatible with systemic metabolic disease. He was treated with protein restriction, intravenously ad¬ ministered fluids, purgatives, and orally given neomycin sulfate, and two days later he felt considerably better with corresponding improvement shown on EEG, although his fasting arterial blood ammonia level was still severely elevated. He denied recent alco¬ hol ingestion, drug use, infection, or major bleeding, and no past history of hepatitis was obtained. Details of previous hospitalizations were not immediately available. A liver biopsy was at¬ tempted unsuccessfully on four occasions and additional attempts were abandoned when the platelet count decreased to 22,000/cu mm. He underwent umbilical vein catheterization with local anes¬ thesia. The contrast medium was injected slowly with the catheter tip in the splenic vein. It was seen to flow retrograde to the hilus of the spleen and inferiorly through a large spontaneous shunt to the left renal vein (Fig 3). No contrast medium entered the main por¬ tal vein. The catheter was withdrawn to a position within the liver and the injection was repeated. Initially, this achieved good filling of the portal system in the liver; however, the predominant flow was retrograde down the portal vein, again demonstrating the splenorenal shunt. A large tortuous coronary vein was seen that coursed across the midline to enter the hilus of the spleen. There were no esophageal varices or other collaterals (Fig 4). The liver was substantially shrunken. The main portal vein pressure mea¬ sured 20 cm H,0 and was slightly greater than in the splenic vein. Free and wedged hepatic vein phlebograms and pressures were
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Fig 2.—Proximal splenic vein is thrombosed. Top left, Inferior mesenteric vein fills retrograde proximal to thrombosis (arrows). Top right, Coronary vein gives rise to no varices (arrows). Bot¬ tom, Majority of flow from well-filled portal vein goes into dilated umbilical vein, coursing to pelvis as single tortuous conduit (ar¬ rows) (case 1).
through the basilic vein in the arm. These showed the changes characteristic of severe cirrhosis with retrograde filling of intrahepatic portal radicles (Fig 5). However, the corrected he¬ patic vein pressure was only 10 cm H,0. Results of a liver biopsy, later accomplished under fluoroscopy using a posterior approach, disclosed postnecrotic cirrhosis but no active cellular necrosis. Case 3.—An 18-year-old student was admitted to the hospital in September 1972 with massive hematemesis. At age 9 she was diagnosed as having "plasma cell" hepatitis as shown by means of a liver biopsy. For the latter three years, the patient was treated with azathioprine and prednisone. She remained well and asymp¬ tomatic until three days prior to admission when she began vomit¬ ing blood and was admitted to her local hospital. Eleven units of blood were administered over the subsequent 24 hours. A bleeding site could not be found and she was transferred to the Royal Vic¬ toria Hospital. Examination on admission showed a comfortable, alert, mildly jaundiced young woman. The spleen was palpable 6 cm below the left costal margin but there was no evidence of hepatomegaly. Liver enzymes were noticeably deranged. Laboratory studies dis¬ closed the following values: SGOT, 501 units; lactic dehy¬ drogenase, 1,020 units; alkaline phosphatase, 20 units; bilirubin, 5.8 mg/100 ml; prothrombin time, 66%; and arterial ammonia, 170µg/ 100 ml. Emergency endoscopy demonstrated a normal esophagus, stomach, and duodenum, and results of an upper gastrointestinal tract series were normal. Despite intermittent episodes of bleed¬ ing, two additional endoscopies and upper gastrointestinal tract obtained
series showed
no
abnormalities. It
was
believed that the blood
was
coming from the fundus of the stomach but no bleeding site was seen. During this period, severe ascites developed, prothrombin time increased, and platelet levels decreased to 35,000/cu mm. There was no evidence of intravascular coagulation. Treatment consisted of fresh blood, platelets, and plasma and after two days the bleeding stopped. Liver scans disclosed noticeable splenomeg¬ aly with a small cirrhotic liver and abnormal clearances compat-
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ible with chronic hepatitis. There were no space-occupying lesions. Within three weeks, the ascites disappeared and liver enzymes improved dramatically, the SGOT level falling to 66 units, and bil¬ irubin to 1.68 mg/100 ml. "Minilap" was performed. An umbilical vein portogram demonstrated a small fibrotic liver and splenomegaly. While substantial hepatopedal portal flow was maintained, much of the extrahepatic portal flow was directed through a large tortuous, variceal coronary vein that had devel¬ oped a massive spontaneous shunt to the left renal vein (Fig 6). Esophageal varices were absent, and no other collaterals were demonstrated. With use of a right hepatic vein catheter, xenon Xe 133 blood flow studies were performed.3 Total hepatic blood flow measured 1,350 ml/minute with a portal fraction of 55%. A liver biopsy specimen showed chronic aggressive hepatitis. She continued to do well and was discharged only to be read¬ mitted 15 days later with recurrent bleeding. She underwent sple¬ nectomy and end-to-side splenorenal shunt. The huge coronary left renal vein shunt was identified and preserved (Fig 7). The pa¬ tient has remained well since. Although effective in preventing the development of esophageal varices, bleeding did occur, presum¬ ably from a gastric varix in the coronary vein itself, in combina¬ tion with disordered coagulation from hypersplenism and perhaps
drug therapy. COMMENT
The relationship of hepatic function to the prognosis and treatment of patients with hepatic cirrhosis is well ac¬ cepted. Less well appreciated are the complex, widely variable alterations in hepatic and splanchnic vascular physiology that occur. The advent of splenoportography has facilitated the understanding of these altered vascu¬ lar hemodynamics by showing that large, previously un¬ recognized portal-systemic shunts may develop spontane¬
ously.
In an extensive study of over 135 consecutive cirrhotic patients, Rousselot and associates4 found in 97% of those with portal hypertension, diversion of portal blood from the liver occurred by back flow and reversed circulation in the valveless, normally present veins of the extrahepat¬ ic portal system. The effect of this diversion was not re¬ flected in lowered portal pressure. On the contrary, the ex¬ tent of collateralization through these veins increased and correlated directly with progressively higher values in portal pressure. The final systemic communications in these cases is accomplished by multiple fine vessels. On the basis of Poiseuille law, with collateral vessels of half the radius of the normal portal vein, 16 such veins would be necessary to carry the portal blood without an increase in pressure. This may explain the ineffective decompressive effect obtained. However, in 28 patients, diversion was also by circulation through large reopened embryonic channels connecting the portal and systemic venous circu¬ lations. Twenty eight percent were into the left renal vein and 41% were via umbilical or paraumbilical veins to the deep epigastric and iliac veins. These reopened channels provided a larger and more direct connection with the sys¬ temic circulation, often acquiring unusual size. Nonethe¬ less, these investigators observed that even these shunts were not associated with reductions in portal pressure and did not prevent circulation of portal blood through varices (85%) nor did they prevent severe hemorrhage from rup-
tured varices (70.8%). This is contrary to the experience herein reported and is difficult to explain on the basis of Poiseuille law. Isolated observations by a number of inves¬ tigators suggest that our findings are not unique. Summerskill et al5 described 17 patients who had inter¬ mittent neuropsychiatrie disturbances. In 15 patients, extensive portal-systemic collateral circulation was dem¬ onstrated by percutaneous transsplenic phlebography. Usually, the collateral circulation was extensive and con¬ sisted of multiple small channels diverted through the left gastric and paraesophageal veins without a single major vessel. However, in two patients, the inferior mesenteric vein was distended to form a single large retrograde channel, while in another two, the umbilical vein was the sole patent functioning channel. These investigators found that when the collateral circulation was sufficiently great, the intrasplenic pressures were normal. Such pa¬ tients usually had only the one large collateral vein. They had constructed natural portacaval shunts of sufficient caliber to lower the portal pressure and did not develop esophageal varices. The diversion of portal blood into the collateral was occasionally so great that the portal vein did not visualize on splenic phlebogram. In 126 splenic phlebograms performed in 109 patients, with cirrhosis or portal hypertension, Turner and col¬ leagues6 described a wide variety of portal-collateral cir¬ cuits. The predominant route was through the gastric and esophageal vessels. However, four patients had abnormal collaterals between the splenic and renal veins. In six pa¬ tients, no contrast medium entered the portal vein after intrasplenic injection. Five of these six patients presented with encephalopathy. In three, all the injected contrast material entered the interior mesenteric vein, while in two it passed through massive collaterals from the splenic to the renal vein and then to the inferior vena cava. Var¬ ices were absent. Hemodynamic data were obtained in 13 cirrhotic pa¬ tients with portal hypertension undergoing combined he¬ patic vein, umbilicoportal vein, and superior mesenteric artery catheterization by Huet et al.7 The portal fraction of total hepatic blood flow was calculated after injection of red blood cells labeled with radioactive chromium (r>1Cr) into the superior mesenteric artery. In three patients, the portal fraction was 0%. In these three cases, portography and arteriography disclosed large spontaneous portacaval shunting with reverse or stagnant circulation in the portal vein, or both. In one, the shunt was a portosplenorenal, while in two there was reverse circulation into the inferior mesenteric veins with large hemorrhoidal shunts and no opacification of the portal vein seen on umbilicopor-
tography.
The studies of Burchell and coworkers8 suggest that the splenorenal pathway is probably a more important and readily available area of shunting than has been clinically appreciated. Splenoportograms were performed in 735 pa¬ tients with cirrhosis and portal hypertension. In 45 pa¬ tients, technically successful splenic portograms failed to visualize the portal vein. Additional studies confirmed the complete patency of this vessel. In approximately half of
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patients, the primary route of hepatic bypass splenoadrenorenal "natural shunt" to the infe¬
these latter was over a
rior vena cava. Even before the advent of portography, Learmonth,9 on the basis of anatomic and pathologic considerations, emphasized the clinical importance of natural portalsystemic anastomoses in the neighborhood of the spleen
where veins pass from the splenic vein to veins in the dia¬ phragm, pancreas, and adrenal. The ultimate systemic-col¬ lecting vessels for all these small veins predisposes to natural splenorenal shunts in portal hypertension. The pancreatic and diaphragmatic veins reach the left renal vein by forming connections with the ascending lumbar vein, which is connected caudally to the left renal vein.
Fig 3—Umbilical catheter situated in main splenic vein (case 2). Contrast medium flows to hilus of spleen (left) and through large spontaneous splenorenal shunt to inferior vena cava (right). No dye enters main portal vein. Fig 4.—Catheter withdrawn to intrahepatic portal vein. Predominant flow is retrograde down portal vein (left), nal shunt (right). Large coronary vein courses across midline to enter spleen without formation of varices.
then
interiorly
demonstrating splenore¬
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The presence of direct communication between the splenic vein and the left adrenal vein often results in ballooning of the adrenal from the increased portal pressure. The left adrenal vein in turn empties into the left renal vein, thus providing another of nature's indirect splenorenal anasto¬ moses. The frequent nonvisualization of the portal and splenic veins on splenoportography noted by many au-
Fig 5.—Wedged hepatic vein angiogram outlines hetero¬ geneous sinusoidal bed with numerous small filling defects. Ret¬ rograde filling of portal radicles in liver occurs (arrow) (case 2).
thors when a splenorenal-caval bypass existed, emphasizes the potential functional ability of this "natural shunt" in the presence of portal hypertension. This was seen in two of our patients. Portal
Hypertension
A recent review of the St. Vincent's Hospital experience with splenic portograms in almost 1,000 patients with por¬ tal hypertension"' demonstrated a spontaneously re¬ opened and patent functioning umbilical vein in 9%. As recognized by the authors, many more patients with por¬ tal hypertension may have such a spontaneously available outflow tract than would be suggested by conventional portography done with the patient in the supine position. With the use of splenoportography with the patient in the prone position, Moskowitz et al11 have demonstrated a large patent and spontaneously functioning umbilical vein in a patient in whom this vessel had not been demon¬ strated in the supine position, where contrast medium flows preferentially to the right lobe due to gravitational forces. The hemodynamic importance and potential effi¬ cacy of this patent shunt in sinusoidal decompression is evidenced by the fact that the pressure in the hepatic limb of the occluded portal vein (sinusoidal pressure) was sub¬ stantially lower in patients with a functioning umbilical collateral than in patients without such a collateral. The pressure increment on the splanchnic side of an occluding portal vein clamp was noticeably greater in these patients supporting an element of splanchnic decompression as well. However, this hepatofugal collateral was clinically ineffective in preventing varices or variceal hemorrhage in this series, contrary to the experience with our two pa¬ tients with a similar shunt. This may be due to differences
Fig 6.—Left, tortuous coronary vein (CV), caliber of splenic (SV), and main portal veins (PV), developed massive shunt to left renal vein (RV) with rapid appearance of contrast material in inferior vena cava (IVC) (right). No esophageal varices or other collaterals seen (case 31. Riaht atrium indicated bv RA.
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Fig 7.—Pancreas and splenic vein (SV) retracted to left after splenectomy. Note large spontaneous shunt to renal vein (RV) (case 3). Surgical shunt constructed to left of this spontaneous shunt.
in the type of patients studied. Neither of our patients was known to have either cirrhosis or portal hypertension prior to study, which was initiated for other complaints. This again suggests that this phenomenom may be much more common than suspected—perhaps in a population of unknown and asymptomatic cirrhotic patients who re¬ main so because of their ability to develop spontaneously such shunts. Substantial preoperative ascites was present in only 8% of patients with a patent umbilical vein. In a comparable group without a patent vein, 28% had ascites.1" After a single decompressive shunt, ascites occurred in only one patient with preservation of the preexisting functioning vein but in 21% of patients with a nonvisualized vein or operative ligation of patent vein. This role as an outflow tract thus assumes particular importance in as¬ saying the factors that may influence the development of ascites. In case 2, ascites was absent at the time the shunt was demonstrated, whereas it had been a problem in pre¬ vious years, perhaps while this shunt was in formation. The nonvisualization of the portal vein on splenic por¬ tography raises several hemodynamic possibilities that have considerable importance. It may occur as a result of the simple interposition of a large bypass collateral vessel be¬ tween the spleen and the liver through which the contrast medium is directed. On the other hand, there may be no portal hepatic flow due to occlusion of the vein. Alterna¬ tively, the contrast medium may not be able to enter the portal vein because of true reverse flow of hepatic blood down the portal vein, spontaneously decompressing the liver. On the basis of intrahepatic parenchymal deposition of contrast medium, and direct determination of direction and rate of portal flow, Burchell and coworkers8 concluded that it was the result of the drastic reduction in portal flow and corresponding hepatic bypass of splanchnic flow. There was no instance in which reverse flow in the portal vein could be observed. Moreno et al12 reported a series of 85 cirrhotic patients in whom portal flow was measured with use of an electromagnetic flow meter. They failed to show any patients with retrograde flow in the portal vein. Smith et al,13 in an extensive study of hepatic vein phle-
bography, observed only one of 84 cirrhotic patients with reversal of flow on the angiogram, and this was not sub¬ stantiated by direct operative measurement. At the opposite extreme, Warren and colleagues have long postulated that this phenomenon could occur based on manometric studies obtained prior to and at the time of performing portacaval shunts.14 The pressure available to perfuse the portal venous bed was obtained by sub¬ tracting the hepatic occluded portal pressure from the splanchnic occluded portal pressure. A negative result pre¬ sumably meant reversal of portal flow. In a subsequent study of 80 cirrhotic patients, wedged hepatic vein an¬ giograms, splenoportography, and hepatic arteriography were performed as well as pressure measurements. Six pa¬ tients were shown to have spontaneous reversal of portal venous blood flow, thp portal vein acting as an outflow tract from the livCi. When hepatic vein phlebography was performed, the contrast material left the liver by way of the portal vein. In such instances, the portal vein was not opacified on the splenoportogram. In these six patients, only one required surgery for bleeding. They character¬ istically had developed extensive caudally directed collat¬ erals sparing the coronary-azygous system.15 Indeed, the initial idea of the distal splenorenal shunt stemmed from such a patient.16 The existence of reversed portal vein flow was clearly shown in five of our six cases, by serial low- and high-pres¬ sure injections at various points within the portal system. It is additionally supported by the strikingly small size of the liver seen in all patients, as might be expected with absent portal flow. The relatively low corrected hepatic vein wedge pressure in case 2, in the face of almost com¬ plete obliteration of the hepatic venous system (Fig 5), is probably due to sinusoidal decompression by the hepatofugal "portal flow." Those patients who in the face of portal hypertension have the ability to reopen large embryonic channels or "natural shunts," as demonstrated in our pa¬ tients, might be expected to show this phenomenon of re¬
flow. As the outflow obstruction increases in the cirrhotic liver, intrahepatic pressure increases and trans¬ hepatic flow decreases. More blood bypasses the liver. The ability to open a single large "natural" portosystemic shunt would presumably lower the free portal venous pressure below that of the hepatic sinusoids. When this happens, the direction of flow changes and blood passes from the sinusoids to the portal vein. This would explain the high association of a nonvisualized portal vein on splenoportography when such shunts are present. The sparing of the coronary-azygous system with resultant ab¬ sence of esophagogastric varices, bleeding, and perhaps ascites is also consistent with this concept. It is possible that this phenomenon is far more common than has been recognized in the total population of patients with liver disease. Many may go undetected by the clinician during this period because of their ability to construct such effec¬ tive natural shunts. Umbilical vein portography is a supe¬ rior method to demonstrate these changes. It should be performed early in all patients with suspected hepatic disease. verse
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References 1. Strack PR, Newman HK, Lerner AG, et al: An integrated procedure for the rapid diagnosis of biliary obstruction, portal hypertension and liver disease of uncertain etiology. N Engl J Med 285:1225-1231, 1971. 2. Wexler MJ, McLean AP, Skinner GB, et al: "Minilap": An accurate, rapid and safe approach to the diagnosis of liver disease and jaundice. Ann Surg 178:736-744, 1973. 3. Shizgal HM, Goldstein M: Measurement of portal and total hepatic blood flow by the intestinal xenon-technique. Surgery 72:83-90, 1972. 4. Rousselot LM, Moreno AH, Panke WF: The clinical and physio-patho-
logic significance of self-established (non-surgical) portal systemic venous shunts. Ann Surg 150:384-410, 1959. 5. Summerskill WHJ, Davidson EA, Sherlock S, et al: Neuropsychiatric syndrome associated with hepatic cirrhosis and an extensive portal collateral circulation. Q J Med 25:245-266, 1956. 6. Turner MD, Sherlock S, Steiner RE: Splenic venography and intrasplenic pressure measurement in the clinical investigation of the portal venous
system. Am J Med 23:846-859, 1957. 7. Huet PM, et al: Combined hepatic vein umbilicoportal vein and superior mesenteric artery catheterization in portal hypertension. Yale J Biol Med, to be published.
AR, Moreno AH, Panke WF, et al: Some limitations of I. Incidence, hemodynamics and surgical implications of the non-visualized portal vein. Ann Surg 162:981-995, 1965. 9. Learmonth J: On certain aspects of portal hypertension. Edinb Med J 58:1-16, 1951. 10. Burchell AR, Panke WF, Moreno AH, et al: The patent umbilical vein in portal hypertension. Surg Gynecol Obstet 130:77-86, 1970. 11. Moskowitz H, Chait A, Margulies M, et al: Prone splenoportography. Radiology 90:1132-1135, 1968. 12. Moreno AH, Burchell AR, Rousselot LM, et al: Portal blood flow in cirrhosis of the liver. J Clin Invest 46:436-445, 1967. 13. Smith GW, Westgaard T, Bjorn-Hansen R: Hepatic venous angiography in the evaluation of cirrhosis of the liver. Ann Surg 173:469-480,1971. 14. Warren WD, Fomon JJ, Viamonte M, et al: Preoperative assessment of portal hypertension. Ann Surg 165:999-1012, 1967. 15. Warren WD, Fomon JJ, Viamonte M, et al: Spontaneous reversal of portal venous blood flow in cirrhosis. Surg Gynecol Obstet 126:315-323,1968. 16. Warren WD, Zeppa R, Foman JJ: Selective trans-splenic decompres8. Burchell
splenic portography:
sion of
gastroesophageal
varices
by
distal
spenorenal
shunt. Ann
Surg
166:437-455, 1967.
Discussion Jeremiah G. Turcotte, MD, Ann Arbor, Mich: I agree with the thesis that the spontaneous shunts are probably more common than generally appreciated. Perhaps the authors have provided us with an explanation for some well-known statistics concerning cir¬ rhotic patients. Only about 50% of cirrhotic patients will develop varices, and only about one third of individuals with varices will ever bleed from them. So, the question is, why don't all cirrhotic patients develop varices, and why don't all varices bleed? Perhaps the answer is that many of them have these natural shunts to ex¬ plain the lack of variceal hemorrhage in many patients with cir¬ rhosis. I would like to call your attention to two groups of patients with portal hypertension in whom I think the natural shunts are of particular importance. One group is children with extrahepatic portal hypertension, and the other group is adults (ie, aged 55 to 60 years) who for reasons we don't understand well at this point have thrombosed their portal venous systems. Dr. Fonkalsrud and the group at UCLA recently pointed out that many children with extrahepatic portal hypertension will out¬ grow their disease-that is, with time the recurrent variceal hem¬ orrhage will cease. They have recommended that we only selec¬ tively apply surgical portal decompression to this group of pa¬ tients. Probably, natural shunts form with time and explain this sequence of events. The other group of patients is adults with extrahepatic portal hypertension. We recently looked up a number of cases in our series and, somewhat to our surprise, found that even though we were not able to surgically construct a shunt, either these patients never rebled or rebled infrequently, and they all remained alive if they survived the immediate postoperative period. Again, proba¬ bly the development of natural shunts explains this history. I would like to inject a word of caution in interpreting some of the studies presented as indicating that retrograde portal blood flow is present. Any time you inject the portal venous system directly, you change the hemodynamics of the system sufficiently so that you may see some phenomena not present normally. The error introduced by different methods of measuring flow may ex¬ plain the great discrepancy in the literature concerning the inci¬ dence of retrograde portal flow. Some authors state that only a few percent of cirrhotic patients have reversal of flow in the por¬ tal vein, while others claim that as many as 25% have retrograde flow. A good way to check for the presence of retrograde flow is to study the venous phase of superior mesenteric artery arterio¬ gram. Since in this study there is no direct injection into the por¬ tal venous system, portal hemodynamics are minimally disturbed.
I wonder if mesenteric arteriograms were done in the cases de¬ scribed? Francis Jackson, MD, Lubbock, Tex: Eleven years ago we pre¬ sented at the annual meeting the first 200 of some 600 percu¬ taneous splenoportagrams done at the Veterans Administration Hospital in Pittsburgh over a period of years. Four general venographic patterns were described that we called "differential flow patterns." Dr. Wexler has indicated at least two of these pat¬ terns. We pointed out at that time the importance of the coronary vein and its relationship to the appearance of varices and, ulti¬ mately, hemorrhage. We also had a substantial number of pa¬ tients with varices but without opacification of the coronary vein, using the splenic injection technique. I would like to point out that some 15 repeated studies were per¬ formed and we were surprised to note that the patterns changed. Therefore, the static studies may not always represent all of the naturally existing portosomatic shunts available. Therefore, it is possible that similar studies performed through the umbilical vein may not be the pattern that might be seen a few weeks from to¬ day or even a year from today. I believe the flow characteristics as we see on a single set of phlebograms are affected by a number of variables, such as the existing portal flow dynamics, including the resistance in the col¬ lateral system vs intrahepatic resistance, the amount of dye we inject, the specific physical characteristics of the dye (ie, specific gravity), the supine position of the patient, and the extent of venovenogenesis or hypertrophie changes that go on in the devel¬ opment of the intrahepatic collateral circulation as they change over a period of time. I would urge the authors to follow up these patients very care¬ fully. At the Veterans Administration Hospital, we have been able to follow up cirrhotic populations for years because it seems that eventually they end up on our wards. We have been struck, there¬ fore, by the fact that with large collateral flow patterns, as you saw here, ultimately these people do bleed from their varices, de¬ spite the seeming effectiveness of their natural shunts. So, I ask the authors: Have they followed up their patients long enough to be sure, in their own minds, that these static anatomical characteristics are truly persistent, or is this only a temporary demonstration of the portosystemic flow? Do they feel comfort¬ able that these patients will never bleed from varices? Raymond C. Read, MD,: One of the main points about this re¬ port is that these patients developed large abdominal shunts and yet they had no varices in the esophagus. I would like to point out that in the mechanism of getting esophageal varices, I think ob-
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struction of the vena cava by the liver is an important point. In other words, these shunts were in the abdominal vena cava. Why didn't they develop any varices going into the superior vena cava? As Dr. Gliedman has pointed out, in a large number of patients with portal hypertension and bleeding varices, they do have a pressure difference between the abdominal vena cava and the su¬ perior vena cava at the liver. In some patients, Dr. McDermott has recently drawn attention to this in his book, and in some of these people, if a portacaval shunt is performed on them, they may have so much obstruction in the vena cava by the liver that their vari¬ ces remain. So, I think esophageal varices not only decompress the portal vein into the superior vena cava but also may decompress the ab¬ dominal vena cava into the right atrium or into the chest. I would like to ask Dr. Wexler whether or not in any of these patients they measured intra-vena cavai pressures, and whether these were ele¬ vated? Dr. Wexler: We have dealt a little with the controversy of ret¬ rograde portal flow in the report, however, I did not have time to present it. We are not really certain ourselves about this phenom¬ enon. With our catheters initially in the extrahepatic portal sys¬ tem, we were able to draw them back into an intrahepatic position and repeatedly do contrast injections under low and high pres¬ sure. All of these patients were studied while under local anesthe¬ sia, so there was nothing to change things other than the tiny inci¬ sion and a tiny catheter in the vessel. We did observe that when we withdrew the catheter back into the intrahepatic portal posi¬ tion, the dye flowed retrograde down the portal vein and the pres¬ sures at this site were usually higher than pressures lower down in the extrahepatic portal system. We thus conclude that it must be retrograde flow. We did not do venous phase arteriography, but for several patients we did hepatic vein catheterizations, and we saw filling of portal radicals in the liver when the dye was injected
into the hepatic vein, again suggesting that there is in fact true retrograde flow stemming from the sinusoidal bed in the liver. One of the reasons we believed this technique was of great ad¬
vantage is that when others have met situations such as these with large spontaneous shunts, it was usually just these patients
who on conventional splenoportography did not opacif y the portal vein. In every large series that is reported in the literature where large groups of cirrhotic patients have had splenoportography, there is always a small group of patients in whom you get no opacification of the portal vein. You then get into a controversy: Is it occlusion of the vein? Is it retrograde flow? Is it stagnant flow? In all of these cases we believed we had shown this was retrograde flow. We have not had the opportunity to repeat these dye studies on any of the patients. We have followed up all of them. Of the six patients we have had with massive shunts, only one has bled. That was the young girl I described who had the shunt from her coro¬ nary vein to the renal vein, and she in fact came to the hospital with gastrointestinal bleeding of undetermined site. She even¬ tually had a splenorenal shunt, and it was assumed she had bled from varices within the coronary vein itself, which had shunted into the renal vein. We did not measure pressures in the inferior vena cava. In at¬ tempting to explain this phenomenon, we believe there probably exists a population who have the ability to open up preferentially these "embryonic channels," as Dr. Rousselot referred to them. If they have the ability to do that, then they are in fact creating what we would do surgically, one big massive shunt, and these pa¬ tients do not form esophageal varices. In fact, it is a patient such as this that led Dr. Dean Warren to devise his operation of distal splenorenal shunt. It was a patient with a single massive sponta¬ neous shunt to the renal vein, in whom he noticed that the azygous
system
was
totally decompressed.
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Massive Marvin J.
Wexler, MD, Lloyd D. MacLean,
MD
Using umbilical vein portal phlebography, a group of patients, often with previously unsuspected liver disease or portal hypertension, have been identified with massive spontaneous portal\x=req-\ systemic shunts. In all cases, the collateral circulation was a single large vessel. The splenoadrenorenal, umbilical vein, or inferior mesenteric vein routes were the common pathways. These natural shunts were functional and effective in the alleviation of portal hypertension without evidence of esophageal varices or other collaterals. Portal flow was usually retrograde, perhaps contributing to the small atrophic liver seen in all patients. Six such patients were seen in the last 40 studied. This phenomenon may be more common than suspected in the cirrhotic population and account in part for differences in natural history, complications, and results of surgical therapy.
Spontaneous shunting
between the portal and systemic circulations is a frequent occurrence in pa¬ tients with both liver disease and portal hypertension. It is generally believed and taught that extrahepatic portalsystemic collaterals are numerous and small and cannot be clinically effective in reducing portal pressure or pre¬ venting the formation of gastroesophageal varices and 1
venous
hemorrhage. With the application of newer diagnostic techniques, a tremendous variability in vascular patterns and hemody¬ namics is now being appreciated, and different spontane¬ ous portal-systemic shunts are being increasingly recog¬ nized. Recently, we identified a group of patients with massive spontaneous shunts. In these patients, the collat¬ eral circulation was a single large vessel resulting in "relief" of portal hypertension and absence of esoph¬ agogastric varices and the usual clinical appearance of liver disease.
Accepted for publication March 25, 1975. From the Department of Surgery, Royal Victoria Hospital and McGill University, Montreal. Read before the 32nd annual meeting of the Central Surgical Association, Chicago, Feb 28, 1975. Reprint requests to the Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, H3A 1A1, Canada (Dr. Wexler).
CLINICAL POPULATION AND METHODS Since 1970, a series of 40 patients have been studied by means of umbilical vein portography as part of a sequence of diagnostic procedures performed at a single session called "minilap."'2 This procedure was performed on patients who were difficult diagnostic problems or who had an atypical presentation of liver disease of undiagnosed cause. After performing umbilical vein catheter¬ ization using local anesthesia, the catheter is guided under fluo¬ roscopic control into the splenic vein. Pressures and rapid se¬ quence portography is performed with low and high pressure injections of contrast material at various sites along the extra¬
hepatic portal tree. Six patients, ranging in ages from 24 to 60 years, were dis¬ covered to have totally unsuspected massive spontaneous portalsystemic shunts. In two patients, the shunt was between the splenic and left renal vein, while in another it was between the coronary and left renal veins. In two patients, a spontaneously re¬ opened and patent umbilical vein served as a massive conduit anastomosing with the iliac system. Im one patient, the shunt was via the inferior mesenteric vein to the hemorrhoidal plexus. None of these patients had esophageal varices and all except one were free of gastrointestinal bleeding. The spectrum of clinical mani¬ festations varied greatly. Two totally asymptomatic patients were being investigated for splenomegaly while a third was being in¬ vestigated for epigastric pain. None were known to have liver dis¬ ease. One young man had severe encephalopathy, while a young girl with well-established asymptomatic liver disease since child¬ hood was admitted with upper gastrointestinal bleeding of obscure cause. Five of the six patients clearly demonstrated hepatofugal portal flow, while the sixth showed noticeable reduc¬ tion of the portal fraction of total hepatic blood flow. All patients had small, shrunken livers, enlarged spleens, and demonstrated a striking absence of the plethora of collateral veins usually seen on venous portography in patients with portal hypertension. The spontaneous shunt in each instance was of usually large caliber and resembled in magnitude, and perhaps in volume of flow, sur¬ gically constructed portal-systemic anastomoses. A liver biopsy specimen showed Laennec cirrhosis in two patients, postnecrotic cirrhosis in two, and chronic aggressive hepatitis with cirrhosis in two. The following are selected case reports. REPORT OF CASES Case 1.—A
46-year old wrestler was first admitted
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to
our
hospi-
tal in 1971. He had been in excellent health all his life. Family screening, done because two nephews were ill with aplastic ane¬ mia, disclosed thrombocytopenia and splenomegaly. He drank sev¬ eral quarts of beer daily. On physical examination, there was a huge smooth spleen, nonpalpable liver, and no stigmata of liver disease. Laboratory studies showed thrombocytopenia of 42,000 platelets per cubic millimeter, leukopenia, and evidence of hemoly¬ sis. Liver enzyme values were normal including serum glutamic oxaloacetic transaminase (SGOT), bilirubin, alkaline phosphatase, albumin, and prothrombin time. Results of an upper gastrointesti¬ nal series were normal. At his wish, all additional investigations and treatment were stopped. Two years later, he reappeared with a painful swollen ankle. Physical examination again disclosed only massive splenomegaly. An x-ray film showed osteomyelitis of the left ankle and Staphylo¬ coccus aureus was cultured. Preliminary laboratory studies again showed thrombocytopenia and leukopenia, however, the alkaline phosphatase level was now 23.1 units (N 3 to 13), albumin was 2.9 gm/100 ml (N 3.5 to 5.0), and indirect bilirubin was elevated to 1.3 mg/100 ml. Attention was focused on the massive spleno¬ megaly and he underwent one month of intensive hématologie and immunologie investigations. All the results of these studies were normal except for a decreased red blood cell survival due to trap¬ ping in the spleen. A "minilap" for diagnosis was performed. Through a 3-cm epigastric incision, a massively dilated patent umbilical vein was immediately seen (Fig 1). A catheter was in¬ serted, manipulated into the splenic vein, and portography per¬ formed. The proximal part of the splenic vein was thrombosed. Just proximal to this thrombosis, the inferior mesenteric vein filled retrograde and descended to the left lower quadrant. Good filling of the intrahepatic portal system occurred and a small shrunken liver was outlined. The coronary vein was seen and did not give rise to varices. The majority of the flow from the portal vein was hepatofugal into the huge umbilical vein, which acted as a large collateral shunt. It coursed inferiorly in a very tortuous manner to the pelvis to anastomose with the iliac system, and thence to the inferior vena cava. No other collaterals were seen (Fig 2). With the catheter tip at the portal bifurcation, low pres¬ sure infusion of contrast failed to outline the liver, all of the flow being retrograde through the umbilical shunt. In this position, pressure measured 28 cm of H20, decreasing as the catheter was withdrawn into the umbilical vein. A liver biopsy specimen from the atrophie liver demonstrated micronodular cirrhosis. The um¬ bilical vein puncture site was carefully closed, preserving the shunt. He has remained well. An almost identical situation was seen in a 60-year-old patient being investigated for epigastric pain. =
=
Case 2.-A healthy, active 22-year-old man was first hospitalized in March 1967 with swelling of his legs. Results of a physical ex¬ amination were normal except for moderate pitting edema of the legs. Laboratory investigations showed the following values: he¬ moglobin, 9 gm/100 ml; total bilirubin, 2.2 mg/100 ml; SGOT, 170 units (N 8 to 40); and total protein, 4.86 gm/100 ml. Renal func¬ tion was normal and results of the Paul Bunnell test were nega¬ tive. Two attempts at percutaneous liver biopsy were unsuccessful and the patient was discharged. He remained well until September 1969, when he was read¬ mitted with a one-month history of progressive abdominal dis¬ tention and leg edema. Severe ascites was noted. The following laboratory values were obtained: hemoglobin, 8.9 gm/100 ml; pro¬ thrombin activity, 91%; platelet count, 115,000/cu mm; total bili¬ rubin, 3.4 mg/100 ml; SGOT, 210 units; blood ammonia, 134µg/100 ml (N less than 100); and total protein, 5.7 gm/100 ml. He re¬ sponded rapidly to diuretic therapy with a weight loss of 15 kg (33 =
=
Fig 1.—Massive patent dilated umbilical "minilap" incision (case 1).
vein
bulging
from
lb). Results of a barium swallow disclosed a normal esophagus without varices. Two additional attempts at liver biopsy were unsuccessful. He was admitted to the Royal Victoria Hospital for the first time in April 1971. He had been well until four days prior to ad¬ mission when he became drowsy, experienced dizziness, and felt himself "going into coma." On admission, he had normal vital signs but was disoriented and had gross "liver flap." He rapidly became unresponsive. Only the spleen was palpable, 3 cm below the left costal margin. There was no collateral abdominal wall cir¬ culation and stool specimens were negative for occult blood. As¬ cites and leg edema were not present. Investigations showed evi¬ dence of pancytopenia. The total bilirubin value was 2 mg/100 ml and SGOT 113 units. Serum electrolyte, calcium, glucose, blood urea nitrogen, creatinine, and blood gas levels were all normal. Arterial blood ammonia levels were 400^g/100 ml to 450/¿g/100 ml. An electoencephalogram was compatible with systemic metabolic disease. He was treated with protein restriction, intravenously ad¬ ministered fluids, purgatives, and orally given neomycin sulfate, and two days later he felt considerably better with corresponding improvement shown on EEG, although his fasting arterial blood ammonia level was still severely elevated. He denied recent alco¬ hol ingestion, drug use, infection, or major bleeding, and no past history of hepatitis was obtained. Details of previous hospitalizations were not immediately available. A liver biopsy was at¬ tempted unsuccessfully on four occasions and additional attempts were abandoned when the platelet count decreased to 22,000/cu mm. He underwent umbilical vein catheterization with local anes¬ thesia. The contrast medium was injected slowly with the catheter tip in the splenic vein. It was seen to flow retrograde to the hilus of the spleen and inferiorly through a large spontaneous shunt to the left renal vein (Fig 3). No contrast medium entered the main por¬ tal vein. The catheter was withdrawn to a position within the liver and the injection was repeated. Initially, this achieved good filling of the portal system in the liver; however, the predominant flow was retrograde down the portal vein, again demonstrating the splenorenal shunt. A large tortuous coronary vein was seen that coursed across the midline to enter the hilus of the spleen. There were no esophageal varices or other collaterals (Fig 4). The liver was substantially shrunken. The main portal vein pressure mea¬ sured 20 cm H,0 and was slightly greater than in the splenic vein. Free and wedged hepatic vein phlebograms and pressures were
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Fig 2.—Proximal splenic vein is thrombosed. Top left, Inferior mesenteric vein fills retrograde proximal to thrombosis (arrows). Top right, Coronary vein gives rise to no varices (arrows). Bot¬ tom, Majority of flow from well-filled portal vein goes into dilated umbilical vein, coursing to pelvis as single tortuous conduit (ar¬ rows) (case 1).
through the basilic vein in the arm. These showed the changes characteristic of severe cirrhosis with retrograde filling of intrahepatic portal radicles (Fig 5). However, the corrected he¬ patic vein pressure was only 10 cm H,0. Results of a liver biopsy, later accomplished under fluoroscopy using a posterior approach, disclosed postnecrotic cirrhosis but no active cellular necrosis. Case 3.—An 18-year-old student was admitted to the hospital in September 1972 with massive hematemesis. At age 9 she was diagnosed as having "plasma cell" hepatitis as shown by means of a liver biopsy. For the latter three years, the patient was treated with azathioprine and prednisone. She remained well and asymp¬ tomatic until three days prior to admission when she began vomit¬ ing blood and was admitted to her local hospital. Eleven units of blood were administered over the subsequent 24 hours. A bleeding site could not be found and she was transferred to the Royal Vic¬ toria Hospital. Examination on admission showed a comfortable, alert, mildly jaundiced young woman. The spleen was palpable 6 cm below the left costal margin but there was no evidence of hepatomegaly. Liver enzymes were noticeably deranged. Laboratory studies dis¬ closed the following values: SGOT, 501 units; lactic dehy¬ drogenase, 1,020 units; alkaline phosphatase, 20 units; bilirubin, 5.8 mg/100 ml; prothrombin time, 66%; and arterial ammonia, 170µg/ 100 ml. Emergency endoscopy demonstrated a normal esophagus, stomach, and duodenum, and results of an upper gastrointestinal tract series were normal. Despite intermittent episodes of bleed¬ ing, two additional endoscopies and upper gastrointestinal tract obtained
series showed
no
abnormalities. It
was
believed that the blood
was
coming from the fundus of the stomach but no bleeding site was seen. During this period, severe ascites developed, prothrombin time increased, and platelet levels decreased to 35,000/cu mm. There was no evidence of intravascular coagulation. Treatment consisted of fresh blood, platelets, and plasma and after two days the bleeding stopped. Liver scans disclosed noticeable splenomeg¬ aly with a small cirrhotic liver and abnormal clearances compat-
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ible with chronic hepatitis. There were no space-occupying lesions. Within three weeks, the ascites disappeared and liver enzymes improved dramatically, the SGOT level falling to 66 units, and bil¬ irubin to 1.68 mg/100 ml. "Minilap" was performed. An umbilical vein portogram demonstrated a small fibrotic liver and splenomegaly. While substantial hepatopedal portal flow was maintained, much of the extrahepatic portal flow was directed through a large tortuous, variceal coronary vein that had devel¬ oped a massive spontaneous shunt to the left renal vein (Fig 6). Esophageal varices were absent, and no other collaterals were demonstrated. With use of a right hepatic vein catheter, xenon Xe 133 blood flow studies were performed.3 Total hepatic blood flow measured 1,350 ml/minute with a portal fraction of 55%. A liver biopsy specimen showed chronic aggressive hepatitis. She continued to do well and was discharged only to be read¬ mitted 15 days later with recurrent bleeding. She underwent sple¬ nectomy and end-to-side splenorenal shunt. The huge coronary left renal vein shunt was identified and preserved (Fig 7). The pa¬ tient has remained well since. Although effective in preventing the development of esophageal varices, bleeding did occur, presum¬ ably from a gastric varix in the coronary vein itself, in combina¬ tion with disordered coagulation from hypersplenism and perhaps
drug therapy. COMMENT
The relationship of hepatic function to the prognosis and treatment of patients with hepatic cirrhosis is well ac¬ cepted. Less well appreciated are the complex, widely variable alterations in hepatic and splanchnic vascular physiology that occur. The advent of splenoportography has facilitated the understanding of these altered vascu¬ lar hemodynamics by showing that large, previously un¬ recognized portal-systemic shunts may develop spontane¬
ously.
In an extensive study of over 135 consecutive cirrhotic patients, Rousselot and associates4 found in 97% of those with portal hypertension, diversion of portal blood from the liver occurred by back flow and reversed circulation in the valveless, normally present veins of the extrahepat¬ ic portal system. The effect of this diversion was not re¬ flected in lowered portal pressure. On the contrary, the ex¬ tent of collateralization through these veins increased and correlated directly with progressively higher values in portal pressure. The final systemic communications in these cases is accomplished by multiple fine vessels. On the basis of Poiseuille law, with collateral vessels of half the radius of the normal portal vein, 16 such veins would be necessary to carry the portal blood without an increase in pressure. This may explain the ineffective decompressive effect obtained. However, in 28 patients, diversion was also by circulation through large reopened embryonic channels connecting the portal and systemic venous circu¬ lations. Twenty eight percent were into the left renal vein and 41% were via umbilical or paraumbilical veins to the deep epigastric and iliac veins. These reopened channels provided a larger and more direct connection with the sys¬ temic circulation, often acquiring unusual size. Nonethe¬ less, these investigators observed that even these shunts were not associated with reductions in portal pressure and did not prevent circulation of portal blood through varices (85%) nor did they prevent severe hemorrhage from rup-
tured varices (70.8%). This is contrary to the experience herein reported and is difficult to explain on the basis of Poiseuille law. Isolated observations by a number of inves¬ tigators suggest that our findings are not unique. Summerskill et al5 described 17 patients who had inter¬ mittent neuropsychiatrie disturbances. In 15 patients, extensive portal-systemic collateral circulation was dem¬ onstrated by percutaneous transsplenic phlebography. Usually, the collateral circulation was extensive and con¬ sisted of multiple small channels diverted through the left gastric and paraesophageal veins without a single major vessel. However, in two patients, the inferior mesenteric vein was distended to form a single large retrograde channel, while in another two, the umbilical vein was the sole patent functioning channel. These investigators found that when the collateral circulation was sufficiently great, the intrasplenic pressures were normal. Such pa¬ tients usually had only the one large collateral vein. They had constructed natural portacaval shunts of sufficient caliber to lower the portal pressure and did not develop esophageal varices. The diversion of portal blood into the collateral was occasionally so great that the portal vein did not visualize on splenic phlebogram. In 126 splenic phlebograms performed in 109 patients, with cirrhosis or portal hypertension, Turner and col¬ leagues6 described a wide variety of portal-collateral cir¬ cuits. The predominant route was through the gastric and esophageal vessels. However, four patients had abnormal collaterals between the splenic and renal veins. In six pa¬ tients, no contrast medium entered the portal vein after intrasplenic injection. Five of these six patients presented with encephalopathy. In three, all the injected contrast material entered the interior mesenteric vein, while in two it passed through massive collaterals from the splenic to the renal vein and then to the inferior vena cava. Var¬ ices were absent. Hemodynamic data were obtained in 13 cirrhotic pa¬ tients with portal hypertension undergoing combined he¬ patic vein, umbilicoportal vein, and superior mesenteric artery catheterization by Huet et al.7 The portal fraction of total hepatic blood flow was calculated after injection of red blood cells labeled with radioactive chromium (r>1Cr) into the superior mesenteric artery. In three patients, the portal fraction was 0%. In these three cases, portography and arteriography disclosed large spontaneous portacaval shunting with reverse or stagnant circulation in the portal vein, or both. In one, the shunt was a portosplenorenal, while in two there was reverse circulation into the inferior mesenteric veins with large hemorrhoidal shunts and no opacification of the portal vein seen on umbilicopor-
tography.
The studies of Burchell and coworkers8 suggest that the splenorenal pathway is probably a more important and readily available area of shunting than has been clinically appreciated. Splenoportograms were performed in 735 pa¬ tients with cirrhosis and portal hypertension. In 45 pa¬ tients, technically successful splenic portograms failed to visualize the portal vein. Additional studies confirmed the complete patency of this vessel. In approximately half of
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patients, the primary route of hepatic bypass splenoadrenorenal "natural shunt" to the infe¬
these latter was over a
rior vena cava. Even before the advent of portography, Learmonth,9 on the basis of anatomic and pathologic considerations, emphasized the clinical importance of natural portalsystemic anastomoses in the neighborhood of the spleen
where veins pass from the splenic vein to veins in the dia¬ phragm, pancreas, and adrenal. The ultimate systemic-col¬ lecting vessels for all these small veins predisposes to natural splenorenal shunts in portal hypertension. The pancreatic and diaphragmatic veins reach the left renal vein by forming connections with the ascending lumbar vein, which is connected caudally to the left renal vein.
Fig 3—Umbilical catheter situated in main splenic vein (case 2). Contrast medium flows to hilus of spleen (left) and through large spontaneous splenorenal shunt to inferior vena cava (right). No dye enters main portal vein. Fig 4.—Catheter withdrawn to intrahepatic portal vein. Predominant flow is retrograde down portal vein (left), nal shunt (right). Large coronary vein courses across midline to enter spleen without formation of varices.
then
interiorly
demonstrating splenore¬
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The presence of direct communication between the splenic vein and the left adrenal vein often results in ballooning of the adrenal from the increased portal pressure. The left adrenal vein in turn empties into the left renal vein, thus providing another of nature's indirect splenorenal anasto¬ moses. The frequent nonvisualization of the portal and splenic veins on splenoportography noted by many au-
Fig 5.—Wedged hepatic vein angiogram outlines hetero¬ geneous sinusoidal bed with numerous small filling defects. Ret¬ rograde filling of portal radicles in liver occurs (arrow) (case 2).
thors when a splenorenal-caval bypass existed, emphasizes the potential functional ability of this "natural shunt" in the presence of portal hypertension. This was seen in two of our patients. Portal
Hypertension
A recent review of the St. Vincent's Hospital experience with splenic portograms in almost 1,000 patients with por¬ tal hypertension"' demonstrated a spontaneously re¬ opened and patent functioning umbilical vein in 9%. As recognized by the authors, many more patients with por¬ tal hypertension may have such a spontaneously available outflow tract than would be suggested by conventional portography done with the patient in the supine position. With the use of splenoportography with the patient in the prone position, Moskowitz et al11 have demonstrated a large patent and spontaneously functioning umbilical vein in a patient in whom this vessel had not been demon¬ strated in the supine position, where contrast medium flows preferentially to the right lobe due to gravitational forces. The hemodynamic importance and potential effi¬ cacy of this patent shunt in sinusoidal decompression is evidenced by the fact that the pressure in the hepatic limb of the occluded portal vein (sinusoidal pressure) was sub¬ stantially lower in patients with a functioning umbilical collateral than in patients without such a collateral. The pressure increment on the splanchnic side of an occluding portal vein clamp was noticeably greater in these patients supporting an element of splanchnic decompression as well. However, this hepatofugal collateral was clinically ineffective in preventing varices or variceal hemorrhage in this series, contrary to the experience with our two pa¬ tients with a similar shunt. This may be due to differences
Fig 6.—Left, tortuous coronary vein (CV), caliber of splenic (SV), and main portal veins (PV), developed massive shunt to left renal vein (RV) with rapid appearance of contrast material in inferior vena cava (IVC) (right). No esophageal varices or other collaterals seen (case 31. Riaht atrium indicated bv RA.
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Fig 7.—Pancreas and splenic vein (SV) retracted to left after splenectomy. Note large spontaneous shunt to renal vein (RV) (case 3). Surgical shunt constructed to left of this spontaneous shunt.
in the type of patients studied. Neither of our patients was known to have either cirrhosis or portal hypertension prior to study, which was initiated for other complaints. This again suggests that this phenomenom may be much more common than suspected—perhaps in a population of unknown and asymptomatic cirrhotic patients who re¬ main so because of their ability to develop spontaneously such shunts. Substantial preoperative ascites was present in only 8% of patients with a patent umbilical vein. In a comparable group without a patent vein, 28% had ascites.1" After a single decompressive shunt, ascites occurred in only one patient with preservation of the preexisting functioning vein but in 21% of patients with a nonvisualized vein or operative ligation of patent vein. This role as an outflow tract thus assumes particular importance in as¬ saying the factors that may influence the development of ascites. In case 2, ascites was absent at the time the shunt was demonstrated, whereas it had been a problem in pre¬ vious years, perhaps while this shunt was in formation. The nonvisualization of the portal vein on splenic por¬ tography raises several hemodynamic possibilities that have considerable importance. It may occur as a result of the simple interposition of a large bypass collateral vessel be¬ tween the spleen and the liver through which the contrast medium is directed. On the other hand, there may be no portal hepatic flow due to occlusion of the vein. Alterna¬ tively, the contrast medium may not be able to enter the portal vein because of true reverse flow of hepatic blood down the portal vein, spontaneously decompressing the liver. On the basis of intrahepatic parenchymal deposition of contrast medium, and direct determination of direction and rate of portal flow, Burchell and coworkers8 concluded that it was the result of the drastic reduction in portal flow and corresponding hepatic bypass of splanchnic flow. There was no instance in which reverse flow in the portal vein could be observed. Moreno et al12 reported a series of 85 cirrhotic patients in whom portal flow was measured with use of an electromagnetic flow meter. They failed to show any patients with retrograde flow in the portal vein. Smith et al,13 in an extensive study of hepatic vein phle-
bography, observed only one of 84 cirrhotic patients with reversal of flow on the angiogram, and this was not sub¬ stantiated by direct operative measurement. At the opposite extreme, Warren and colleagues have long postulated that this phenomenon could occur based on manometric studies obtained prior to and at the time of performing portacaval shunts.14 The pressure available to perfuse the portal venous bed was obtained by sub¬ tracting the hepatic occluded portal pressure from the splanchnic occluded portal pressure. A negative result pre¬ sumably meant reversal of portal flow. In a subsequent study of 80 cirrhotic patients, wedged hepatic vein an¬ giograms, splenoportography, and hepatic arteriography were performed as well as pressure measurements. Six pa¬ tients were shown to have spontaneous reversal of portal venous blood flow, thp portal vein acting as an outflow tract from the livCi. When hepatic vein phlebography was performed, the contrast material left the liver by way of the portal vein. In such instances, the portal vein was not opacified on the splenoportogram. In these six patients, only one required surgery for bleeding. They character¬ istically had developed extensive caudally directed collat¬ erals sparing the coronary-azygous system.15 Indeed, the initial idea of the distal splenorenal shunt stemmed from such a patient.16 The existence of reversed portal vein flow was clearly shown in five of our six cases, by serial low- and high-pres¬ sure injections at various points within the portal system. It is additionally supported by the strikingly small size of the liver seen in all patients, as might be expected with absent portal flow. The relatively low corrected hepatic vein wedge pressure in case 2, in the face of almost com¬ plete obliteration of the hepatic venous system (Fig 5), is probably due to sinusoidal decompression by the hepatofugal "portal flow." Those patients who in the face of portal hypertension have the ability to reopen large embryonic channels or "natural shunts," as demonstrated in our pa¬ tients, might be expected to show this phenomenon of re¬
flow. As the outflow obstruction increases in the cirrhotic liver, intrahepatic pressure increases and trans¬ hepatic flow decreases. More blood bypasses the liver. The ability to open a single large "natural" portosystemic shunt would presumably lower the free portal venous pressure below that of the hepatic sinusoids. When this happens, the direction of flow changes and blood passes from the sinusoids to the portal vein. This would explain the high association of a nonvisualized portal vein on splenoportography when such shunts are present. The sparing of the coronary-azygous system with resultant ab¬ sence of esophagogastric varices, bleeding, and perhaps ascites is also consistent with this concept. It is possible that this phenomenon is far more common than has been recognized in the total population of patients with liver disease. Many may go undetected by the clinician during this period because of their ability to construct such effec¬ tive natural shunts. Umbilical vein portography is a supe¬ rior method to demonstrate these changes. It should be performed early in all patients with suspected hepatic disease. verse
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References 1. Strack PR, Newman HK, Lerner AG, et al: An integrated procedure for the rapid diagnosis of biliary obstruction, portal hypertension and liver disease of uncertain etiology. N Engl J Med 285:1225-1231, 1971. 2. Wexler MJ, McLean AP, Skinner GB, et al: "Minilap": An accurate, rapid and safe approach to the diagnosis of liver disease and jaundice. Ann Surg 178:736-744, 1973. 3. Shizgal HM, Goldstein M: Measurement of portal and total hepatic blood flow by the intestinal xenon-technique. Surgery 72:83-90, 1972. 4. Rousselot LM, Moreno AH, Panke WF: The clinical and physio-patho-
logic significance of self-established (non-surgical) portal systemic venous shunts. Ann Surg 150:384-410, 1959. 5. Summerskill WHJ, Davidson EA, Sherlock S, et al: Neuropsychiatric syndrome associated with hepatic cirrhosis and an extensive portal collateral circulation. Q J Med 25:245-266, 1956. 6. Turner MD, Sherlock S, Steiner RE: Splenic venography and intrasplenic pressure measurement in the clinical investigation of the portal venous
system. Am J Med 23:846-859, 1957. 7. Huet PM, et al: Combined hepatic vein umbilicoportal vein and superior mesenteric artery catheterization in portal hypertension. Yale J Biol Med, to be published.
AR, Moreno AH, Panke WF, et al: Some limitations of I. Incidence, hemodynamics and surgical implications of the non-visualized portal vein. Ann Surg 162:981-995, 1965. 9. Learmonth J: On certain aspects of portal hypertension. Edinb Med J 58:1-16, 1951. 10. Burchell AR, Panke WF, Moreno AH, et al: The patent umbilical vein in portal hypertension. Surg Gynecol Obstet 130:77-86, 1970. 11. Moskowitz H, Chait A, Margulies M, et al: Prone splenoportography. Radiology 90:1132-1135, 1968. 12. Moreno AH, Burchell AR, Rousselot LM, et al: Portal blood flow in cirrhosis of the liver. J Clin Invest 46:436-445, 1967. 13. Smith GW, Westgaard T, Bjorn-Hansen R: Hepatic venous angiography in the evaluation of cirrhosis of the liver. Ann Surg 173:469-480,1971. 14. Warren WD, Fomon JJ, Viamonte M, et al: Preoperative assessment of portal hypertension. Ann Surg 165:999-1012, 1967. 15. Warren WD, Fomon JJ, Viamonte M, et al: Spontaneous reversal of portal venous blood flow in cirrhosis. Surg Gynecol Obstet 126:315-323,1968. 16. Warren WD, Zeppa R, Foman JJ: Selective trans-splenic decompres8. Burchell
splenic portography:
sion of
gastroesophageal
varices
by
distal
spenorenal
shunt. Ann
Surg
166:437-455, 1967.
Discussion Jeremiah G. Turcotte, MD, Ann Arbor, Mich: I agree with the thesis that the spontaneous shunts are probably more common than generally appreciated. Perhaps the authors have provided us with an explanation for some well-known statistics concerning cir¬ rhotic patients. Only about 50% of cirrhotic patients will develop varices, and only about one third of individuals with varices will ever bleed from them. So, the question is, why don't all cirrhotic patients develop varices, and why don't all varices bleed? Perhaps the answer is that many of them have these natural shunts to ex¬ plain the lack of variceal hemorrhage in many patients with cir¬ rhosis. I would like to call your attention to two groups of patients with portal hypertension in whom I think the natural shunts are of particular importance. One group is children with extrahepatic portal hypertension, and the other group is adults (ie, aged 55 to 60 years) who for reasons we don't understand well at this point have thrombosed their portal venous systems. Dr. Fonkalsrud and the group at UCLA recently pointed out that many children with extrahepatic portal hypertension will out¬ grow their disease-that is, with time the recurrent variceal hem¬ orrhage will cease. They have recommended that we only selec¬ tively apply surgical portal decompression to this group of pa¬ tients. Probably, natural shunts form with time and explain this sequence of events. The other group of patients is adults with extrahepatic portal hypertension. We recently looked up a number of cases in our series and, somewhat to our surprise, found that even though we were not able to surgically construct a shunt, either these patients never rebled or rebled infrequently, and they all remained alive if they survived the immediate postoperative period. Again, proba¬ bly the development of natural shunts explains this history. I would like to inject a word of caution in interpreting some of the studies presented as indicating that retrograde portal blood flow is present. Any time you inject the portal venous system directly, you change the hemodynamics of the system sufficiently so that you may see some phenomena not present normally. The error introduced by different methods of measuring flow may ex¬ plain the great discrepancy in the literature concerning the inci¬ dence of retrograde portal flow. Some authors state that only a few percent of cirrhotic patients have reversal of flow in the por¬ tal vein, while others claim that as many as 25% have retrograde flow. A good way to check for the presence of retrograde flow is to study the venous phase of superior mesenteric artery arterio¬ gram. Since in this study there is no direct injection into the por¬ tal venous system, portal hemodynamics are minimally disturbed.
I wonder if mesenteric arteriograms were done in the cases de¬ scribed? Francis Jackson, MD, Lubbock, Tex: Eleven years ago we pre¬ sented at the annual meeting the first 200 of some 600 percu¬ taneous splenoportagrams done at the Veterans Administration Hospital in Pittsburgh over a period of years. Four general venographic patterns were described that we called "differential flow patterns." Dr. Wexler has indicated at least two of these pat¬ terns. We pointed out at that time the importance of the coronary vein and its relationship to the appearance of varices and, ulti¬ mately, hemorrhage. We also had a substantial number of pa¬ tients with varices but without opacification of the coronary vein, using the splenic injection technique. I would like to point out that some 15 repeated studies were per¬ formed and we were surprised to note that the patterns changed. Therefore, the static studies may not always represent all of the naturally existing portosomatic shunts available. Therefore, it is possible that similar studies performed through the umbilical vein may not be the pattern that might be seen a few weeks from to¬ day or even a year from today. I believe the flow characteristics as we see on a single set of phlebograms are affected by a number of variables, such as the existing portal flow dynamics, including the resistance in the col¬ lateral system vs intrahepatic resistance, the amount of dye we inject, the specific physical characteristics of the dye (ie, specific gravity), the supine position of the patient, and the extent of venovenogenesis or hypertrophie changes that go on in the devel¬ opment of the intrahepatic collateral circulation as they change over a period of time. I would urge the authors to follow up these patients very care¬ fully. At the Veterans Administration Hospital, we have been able to follow up cirrhotic populations for years because it seems that eventually they end up on our wards. We have been struck, there¬ fore, by the fact that with large collateral flow patterns, as you saw here, ultimately these people do bleed from their varices, de¬ spite the seeming effectiveness of their natural shunts. So, I ask the authors: Have they followed up their patients long enough to be sure, in their own minds, that these static anatomical characteristics are truly persistent, or is this only a temporary demonstration of the portosystemic flow? Do they feel comfort¬ able that these patients will never bleed from varices? Raymond C. Read, MD,: One of the main points about this re¬ port is that these patients developed large abdominal shunts and yet they had no varices in the esophagus. I would like to point out that in the mechanism of getting esophageal varices, I think ob-
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struction of the vena cava by the liver is an important point. In other words, these shunts were in the abdominal vena cava. Why didn't they develop any varices going into the superior vena cava? As Dr. Gliedman has pointed out, in a large number of patients with portal hypertension and bleeding varices, they do have a pressure difference between the abdominal vena cava and the su¬ perior vena cava at the liver. In some patients, Dr. McDermott has recently drawn attention to this in his book, and in some of these people, if a portacaval shunt is performed on them, they may have so much obstruction in the vena cava by the liver that their vari¬ ces remain. So, I think esophageal varices not only decompress the portal vein into the superior vena cava but also may decompress the ab¬ dominal vena cava into the right atrium or into the chest. I would like to ask Dr. Wexler whether or not in any of these patients they measured intra-vena cavai pressures, and whether these were ele¬ vated? Dr. Wexler: We have dealt a little with the controversy of ret¬ rograde portal flow in the report, however, I did not have time to present it. We are not really certain ourselves about this phenom¬ enon. With our catheters initially in the extrahepatic portal sys¬ tem, we were able to draw them back into an intrahepatic position and repeatedly do contrast injections under low and high pres¬ sure. All of these patients were studied while under local anesthe¬ sia, so there was nothing to change things other than the tiny inci¬ sion and a tiny catheter in the vessel. We did observe that when we withdrew the catheter back into the intrahepatic portal posi¬ tion, the dye flowed retrograde down the portal vein and the pres¬ sures at this site were usually higher than pressures lower down in the extrahepatic portal system. We thus conclude that it must be retrograde flow. We did not do venous phase arteriography, but for several patients we did hepatic vein catheterizations, and we saw filling of portal radicals in the liver when the dye was injected
into the hepatic vein, again suggesting that there is in fact true retrograde flow stemming from the sinusoidal bed in the liver. One of the reasons we believed this technique was of great ad¬
vantage is that when others have met situations such as these with large spontaneous shunts, it was usually just these patients
who on conventional splenoportography did not opacif y the portal vein. In every large series that is reported in the literature where large groups of cirrhotic patients have had splenoportography, there is always a small group of patients in whom you get no opacification of the portal vein. You then get into a controversy: Is it occlusion of the vein? Is it retrograde flow? Is it stagnant flow? In all of these cases we believed we had shown this was retrograde flow. We have not had the opportunity to repeat these dye studies on any of the patients. We have followed up all of them. Of the six patients we have had with massive shunts, only one has bled. That was the young girl I described who had the shunt from her coro¬ nary vein to the renal vein, and she in fact came to the hospital with gastrointestinal bleeding of undetermined site. She even¬ tually had a splenorenal shunt, and it was assumed she had bled from varices within the coronary vein itself, which had shunted into the renal vein. We did not measure pressures in the inferior vena cava. In at¬ tempting to explain this phenomenon, we believe there probably exists a population who have the ability to open up preferentially these "embryonic channels," as Dr. Rousselot referred to them. If they have the ability to do that, then they are in fact creating what we would do surgically, one big massive shunt, and these pa¬ tients do not form esophageal varices. In fact, it is a patient such as this that led Dr. Dean Warren to devise his operation of distal splenorenal shunt. It was a patient with a single massive sponta¬ neous shunt to the renal vein, in whom he noticed that the azygous
system
was
totally decompressed.
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