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Physiological Basis for Surgery in Portal Hypertension
• Physiological Basis for Surgery In Portal Hypertension HAROLD LAUFMAN, M.D. *
HYPERTENSION of the portal venous system has been brought to the attention of surgeons because of two serious complications: massive bleeding from esophageal varices and wasting ascites. In the majority of cases portal hypertension is itself a complication of the distortion in liver architecture pursuant to portal cirrhosis. In other instances, the portal hypertension follows one of several types of extrahepatic blocks, either in the portal or splenic veins. Authoritative data reveals that death from cirrhosis per se occurs in only about 15 per cent of patients with cirrhosis. Intercurrent infection, especially pneumonia, is usually the actual cause of death. When death is due directly to cirrhosis, about one-third of such patients die of hemorrhage and two-thirds die of progressive liver failure. However, the incidence of hemorrhage, fatal and nonfatal, is 34 per cent. Thus of 100 patients with cirrhosis, 34 will bleed at some time or another, the disease will cause death in 15, five of these deaths will have been due to hemorrhage from esophageal varices and 10 will have been the result of cholemia. Clinically demonstrable ascites occurs in about three-fourths of all patients with cirrhosis. There is no argument with the premise that the treatment of cirrhosis is primarily medical. The surgeon is called for therapeutic aid after medical means fail, in order that he might correct or prevent, in some mechanical manner, an exsanguinating hemorrhage from esophageal veins or the debilitating accumulation of ascitic fluid, or both. The early, prophylactic employment of surgery in cases of cirrhosis is a highly controversial matter. Esophageal varices may disappear under medical management. This indicates that fluctuations in portal hypertension are not always dependent upon surgery and therefore the benefits from early surgery are difficult to evaluate. In recent years several new surgical approaches to the problem have been made. However, as the number of reports in the surgical literature multiplies, the confusion keeps apace, particularly regarding which procedure to use, when to use it and what to expect from it. One reason for
* Associate
Professor of Surgery, Northwestern University MedicaZ School. 113
Harold Laufman
114
this situation is that not enough time has elapsed, nor have individual series been large enough to warrant unequivocal conclusions. However, I believe that if a fuller understanding of the physiological basis for the various procedures is known, some of the confusion may be dissipated. BLEEDING ESOPHAGEAL VARICES
The question as to why esophageal varices bleed is still not completely answered. For many years it was deduced that the trauma of food passing over a superficial varix might easily erode it and cause hemorrhage. This concept cannot be denied, and may be true in some instances. Yet, the actual time of onset of hematemesis from esophageal varices most usually has no relationship to the ingestion of food. Sudden increases in pressure due to physical straining with closed epiglottis can conceivably cause bleeding of superficial thin-walled varices. In the experimental animal, portal pressure may rise twofold under these conditions. Wangensteen has held for many years that peptic erosion of esophageal mucosa overlying varices is responsible for the hemorrhage, and recent microscopic examination of eroded areas in these patients has shown definite evidence of peptic erosion in 19 of 44 specimens examined. It should also be remembered that in a patient with liver disease, the level of circulating prothrombin may be low, so that the natural hemostatic mechanisms are not available. In fact, the opinion has been expressed that other hemorrhagic phenomena, such as epistaxis in cirrhotic patients, may stem from this cause. It is also known that thrombocytopenia occurs frequently in cirrhosis, and may contribute to excess bleeding. Therapy of bleeding esophageal varices must be divided into two parts: therapy during the phase of active bleeding, and therapy designed to prevent recurrence of bleeding by an attempt to lower portal pressure. Therapy During Active Hemorrhage It is during the stage of active hemorrhage that much of the controversy regarding therapy has arisen and the poorest results have been obtained. Although some surgeons have reported success in the treatment of actively bleeding varices by transesophagealligation, resection of the lower esophagus and cardia and other maj or procedures, it is becoming more and more evident that such procedures are successful only in the early cases, perhaps within 24 to 48 hours after the onset of bleeding. However, in early cases one cannot be sure that a much more conservative approach might not have been successful, or that the bleeding might have stopped spontaneously. The most widely used therapy for massive bleeding esophageal varices consists of use of the Sengstaken-Blakemore balloon or the Patton-
Physiological Basis for Surgery in Portal Hypertension
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Johnston tube for tamponage, while liberal but accurate replacement of lost blood is made by transfusions. Large doses of vitamin K are in order despite probable disorders in liver function. In the experience of most surgeons, any kind of definitive surgery on cirrhotic patients shortly after their blood volume has been replaced several times is hazardous despite the return of laboratory blood values to normal ranges. If surgery must be performed as a desperate measure in the face of exsanguinating hemorrhage, transesophageal suture-ligation is probably the procedure of choice. Any additional surgery at this stage is to be avoided because of the inability of the patient to withstand it even in the presence of continuous transfusion. It is certainly established that portacaval shunt procedures have no place in the presence of active bleeding nor should one feel justified in proceeding with hepatic arterial ligations under these circumstances. Therapy After HeulOrrhage Has Ceased
Attempts to lower portal pressure during the quiescent period have run a long gamut of surgical procedures. Their purpose, in patients with a history of bleeding, is to prevent the recurrence of bleeding. When ascites is present, their purpose is to stop or decelerate the formation of ascites. There is evidence that there are four contributory factors occurring in a cirrhotic liver which playa role in the production and maintenance of increased portal pressure: 1. Partial occlusion of the portal venous branches within the liver resulting from distortions in lobular architecture caused by contraction of scar and the regeneration of new, malformed lobules. 2. Intrahepatic venovenous shunts between the portal and hepatic venous collecting system. These may be enlarged counterparts of a normally occurring series of collateral veins, and/or may represent newly formed vessels in the presence of advanced portal cirrhosis. 3. Intrahepatic arteriovenous shunts between the portal venous and hepatic arterial branches. 4. Intrahepatic arteriovenous shunts between the hepatic venous and hepatic arterial branches. The sinusoids may serve as intermediary channels in the latter three categories. There has been a great deal of convincing evidence from work spread over many years to support the view that any or all of these alterations in vascular dynamics may occur. It is obvious that all these alterations need not contribute equally or simultaneously to the increased portal pressure. To illustrate the concept of the dynamic nature of portal hypertension in cirrhosis. one might visualize one small portal vein within the liver.
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Harold Laufman
Mter the death of some liver cells, with the ensuing scar tissue, the wellknown ability of the liver to regenerate comes into play, and eventually the scar shrinkage plus the asymmetrical growth of liver regeneration results in a distorted parenchymal architecture, particularly in the area of the portal venules. This distortion may cause enough partial occlusion of the intrahepatic portal branches to act as a partial occlusion to the flow of portal blood cephalad through the liver. The direct consequence of this is the "backing up" or retrograde increase in hydrostatic pressure in the intrahepatic portal vein. The constantly elevated venous pressure acts as it does in other venous systems, such as the leg, and seeks compensation by distribution over a wider bed. The extrahepatic distribution of this compensatory mechanism is well known. The hypertrophy of existing channels and new formation of collateral channels results in esophageal varices by way of the coronary vein, the caput medusae by way of the veins of the round ligament, and hemorrhoidal varicosities by way of the inferior mesenteric veins. Carried one step further, actual or potential channels become established between these extensions of the portal system and branches of the caval system, again in an attempt to equalize and distribute the pressure. Thus, the esophageal veins make new connections and enlarge old connections with the azygos veins; the varicosities of the abdominal wall make connections with the superior and inferior superficial epigastric veins j the hemorrhoidal veins do likewise with the inferior hemorrhoidal branches of the pudendal veins. Since it is known that the pressure in the portal and caval systems are reciprocal, the pressure in the new connections between the two systems may be maintained at a relatively high level from both sides. When the portal pressure is high, the collateral channel pressures are maintained from that side. During straining or other maneuvers, both the caval pressure and the portal pressure rise, and the collateral channel pressures are elevated from both sides. The intrahepatic distribution of the compensatory mechanism is less well known. The increased portal pressure within the liver sooner or later seeks new pathways of distribution within the actual liver substance. Venovenous shunts and arteriovenous shunts are created either from hypertrophy of previously existing connections or from new collaterals or both, the hepatic sinusoids serving an intermediary function. Thus, in portal cirrhosis, what has been created is a rather rigid reservoir of vascular short-circuits. It is known that the connections between the hepatic arterial tree and portal vein branches are more direct in cirrhosis than a normal liver, allowing pressure to be transmitted more directly from the hepatic artery to the portal vein. Thus, it would appear that the compensatory development of new channels actually serves as the beginning of a vicious cycle in which the new channels transmit a portion of the intrahepatic arterial pressures into the portal system. The
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new portal-hepatic venous collaterals are thereby enhanced, and pressure in the hepatic vein rises as the cirrhosis progresses. Furthermore, the great pressure differentials between the hepatic arterial branches and the hepatic venous collecting branches encourage the development of hepatic arteriovenous short-circuits, and this also contributes to elevated pressures in the hepatic vein. The elevated hepatic vein pressures then serve as a retrograde contribution to elevate portal pressure by way of the portal-hepatic vein shunts, and the vicious cycle is complete. Employing this concept, the question of whether ascites or bleeding varices, or both, will result from the lesion, is dependent on whether passive congestion created by blockage of the venous flow or pressure distribution created by the shunts is the major feature, OPERATIONS DESIGNED TO HAVE A DELAYED EFFECT
Attelllpts to Prolllote the Developlllent of Collateral Circulation
The Talma-Morison omentopexy has proved to be a disappointment to most surgeons who have employed it. Recently pqcking gauze about the esophagus through a mediastinotomy has been recommended, but this procedure may not prevent recurrence of bleeding from esophageal varices. Close scrutiny of such procedures reveals that actually one should not expect that the encouragement of a few more collateral channels would add noticeably to the already established massive connections between the portal and caval systems incident to portal hypertension. It is possible that what benefits may be temporarily derived from the mediastinal packing operation are due to cutting off anastomotic channels from the azygos system rather than producing them. OPERATIONS DESIGNED TO HAVE AN IMMEDIATE EFFECT
Attelllpts to Interrupt the Coronary-Esophageal Venous Systeni
I I
British surgeons who have advocated excision of the coronary vein have not reported actual follow-up studies on its results. It is difficult to see how such a limited procedure could be of lasting benefit, especially since the increased pressure in the esophageal veins is not all transmitted directly through the coronary vein from the portal system. The large anastomotic channels between the esophageal varices and the azygos system allow caval blood to circulate through the thin-walled esophageal varices, allowing the direct transmission of increases in pressure incident to straining. Banti suggested ligation of the splenic and short gastric arteries with splenectomy and Flerow advanced the cause for ligation of the left gastric and the right and left gastroepiploic arteries, in addition to the accompany-
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ing veins. These procedures, in addition to interrupting the venous channels, allowed less arterial blood to flow into the stomach capillaries, hence permitting less blood to be picked up by the collecting venous system. None of these procedures has produced results of any lasting quality, probably because of the re-establishment of new venous channels. Wangensteen, in ~945, carried devascularization of the stomach to its ultimate and suggested total gastrectomy. Thus far, no information appears to be available on results in a series of cases with follow-up. Gastrectomy would appear to have no great advantage over the extensive devascularization procedures except, perhaps, that recanalization would occur more slowly. Furthermore, all of the physiological ill-effects pursuant to total gastrectomy can be expected. In 1947, Phemister and Humphreys reported resection of the lower esophagus and cardiac end of the stomach. Unquestionably, this procedure is a direct and radical attack upon the area of bleeding. However, it is an operation of some magnitude and carries a significant mortality and morbidity. Crile believes that this procedure is too radical for the purpose, and likens it to the performance of an abdominoperineal resection for a case of bleeding hemorrhoids. Crile's operation of transesophageal suture-ligation of the bleeding varices is a direct, yet not too formidable operation, which he used during a quiescent period in seven patients with extrahepatic blocks in the portal system. Most of these patients had had previous surgery for bleeding varices, including devascularization of the stomach and splenectomy. Shunt procedures could not be done in his cases because of the extrahepatic location of the portal block. Results were apparently gratifying up to the time of the report with follow-up of over a year in some cases. Attempts to Reduce Venous Inflow to the Portal System
A number of operations have been suggested or carried out over the past 75 years in which the goal is to reduce the blood flow into the portal vein, rather than to interrupt the portal-esophageal vein circuit. Splenectomy was first suggested by Banti in 1874 as one part of a combination attack, the other part consisting of ligation of the vessels of the stomach. The rationale of splenectomy in the reduction of portal pressure is based upon the fact that the venous drainage from the spleen enters the portal vein directly and contributes appreciably to its pressure. In the same sense, ligation of the splenic artery in poor risk cases without removal of spleen aims at this goal. Neither splenectomy nor ligation of the splenic artery has been found to give a lasting effect in most instances of cirrhosis. The reason for this failure is based upon the fact that in cirrhosis the block to the portal
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system is intrahepatic. The increased pressure in the portal vein is partially the result of a retrograde increase in hydrostatic pressure. Consequently, although some reduction in venous inflow will temporarily reduce the pressure within the portal system, the pressure will again rise as the intrahepatic causes for the high pressure progress. Infrahepatic blocks to the portal system lend themselves more logically to this procedure. Another method of reducing venous inflow to the portal system is massive intestinal resection. This procedure has been used in only one patient with ascites, and resulted in a marked deceleration in the rate of ascites formation. Extensive experimental studies on this procedure have been carried out in our laboratory on ascitic dogs. We found that extensive resection of the small intestine, with or without splenectomy, either retarded or prevented the reaccumulation of ascites. In addition to the imposed diminution in the volume of the extrahepatic portal (mesenteric venous) bed, the procedure results in a high fecal sodium excretion. It is our impression that both these factors are important. The question remains, however, as to the advisability of imposing such a great alteration in gastrointestinal physiology upon a patient with cirrhosis. It is possible that this easily executed procedure, consisting of resection of the middle 50 per cent of the small intestine, might be of value in a poor risk patient with ascites and in whom other procedures are not feasible. To date, probably the most popular surgical method of reducing venous inflow to the portal bed has been the portacaval shunt. This term has been employed to include any type of surgical anastomosis that joins the portal and caval systems of veins. The direct Eck fistula (anastomosis of portal vein to vena cava) became feasible in the human being only after present day advances in surgery, anesthesia and postoperative management permitted its clinical use. Variations of the operation consist of (1) direct side-to-side anastomosis of the portal vein to vena cava; (2) splenectomy and end-to-side anastomosis of the splenic vein to left renal vein; (3) end-to-side anastomosis of umbilical vein to vena cava; (4) anastomosis of portal vein to right renal vein; (5) anastomosis of inferior or superior mesenteric vein to vena cava. Since it is clear that the greatest shunt effect from the high pressure portal system to the low pressure caval system is obtained close to the liver, and between the largest vessels, any anastomosis other than a direct portal vein-vena cava anastomosis is a compromise, to be carried out only when the direct operation is not technically feasible. It is known that a large proportion of the splenorenal shunts close spontaneously, probably due to their small caliber and the lesser pressure differential. In Blakemore's series published in 1951, a history of bleeding was the
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major indication for surgery in 61 patients. In the 38 instances in which the portal vein was anastomosed to the vena cava, but one case had a recurrent hemorrhage, and this was in a patient with partial thrombosis of the portal vein at time of surgery. Of 38 splenorenal shunts, the shunt had closed in at least five instances proved at postmortem one to five years after surgery. Although results with splenorenal shunts are less impressive, Blakemore believes that the rapid rise in platelet count following splenectomy and a splenorenal shunt is important, and that results with this procedure can be improved. Although a substantial rise in circulating platelets follows a direct portacaval shunt, it is a slow response commensurate with gradual shrinkage of the spleen, and only occasionally does the number reach a low normal. Although varying amounts of ascites had been present in about twothirds of his cases, it was the major indication for surgery in only nine. Seven survivors were all apparently relieved of their ascites, one patient having been followed for five years. Linton has found that portacaval shunt is particularly difficult to perform in patients with ascites, because of the heavy lymphatic channels and edematous tissue surrounding a rather delicately walled portal vein. When he performs the procedure for ascites he prefers to do it in two stages. Welsh has stated that the operation is indicated primarily in patients who have had hemorrhage, and that ascites is not best treated by this method. The over-all operative mortality of shunt procedures in Blakemore's hands is 16.2 per cent, with a follow-up mortality of an additional 11 per cent. The follow-up mortality rate for the portal vein-vena cava group was 8 per cent while that for the splenorenal group was 23.7 per cent. Other surgeons have not been so successful, either in the results obtained or in their mortality rates. Attelllpts to Reduce Intrahepatic Portal Pressure
It is known that vasomotor influences are an important factor in the tonus of the liver vasculature, and hence in the regulation of vascular pressures in the liver. Stimulation of the hepatic sympathetic nerve plexus is known to cause an appreciable rise in portal pressure. It occurred to us, therefore, that sympathectomy of ihe appropriatejibers might serve to lower portal pressure by releasing some of the tonus in the portal venous tree. We found, however, that the effect was negligible, particularly in animals with a vena cava band-induced portal hypertension. This result would tend to support Berman's contention that vasomotor influences are greatly reduced in the cirrhotic. The increased resistance in linear flow is due more to the blockage than it is to vascular tone, and the former so far outbalances the latter that the release of tone is inconsequential. Reinhoff and Berman have independentlY explored the feasibility of
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ligation of the hepatic artery as a means of reducing intrahepatic pressure in the portal vein. Reinhoff ligates the hepatic artery distal to the gastroduodenal artery in addition to ligation of the splenic artery. Berman prefers to ligate the hepatic artery proximal to the gastroduodenal artery in addition to the splenic and left gastric arteries. He believes that ligation distal to the gastroduodenal artery may be more prone to produce necrosis. This operation, although not always technically easy, is a great deal less exacting than the performance of a shunt, and therefore stands to become more popular, provided its results compare favorably. Since the use of antibiotics has made hepatic artery ligations a relatively safe procedure, the maneuver became available as a therapeutic possibility. Its physiological rationale in cases of portal hypertension is based upon the knowledge that hepatic arterial pressure contributes appreciably to portal pressure under these circumstances, as described above. Therefore; if the arterial contribution could be largely eliminated, part of the vicious cycle might be restrained. Furthermore, the hepatic arterial-portal venous reflux could be ameliorated, and the hepatic venous pressure could be reduced, thereby permitting more portal blood to enter the liver under a lower pressure. Reinhoff and Berman agree that the greatest benefit from ligation of the common hepatic and splenic arteries occurs in patients with intractable ascites only. Addition of ligation of the left gastric artery to the procedure to prevent further bleeding from esophageal varices gave only equivocal results in the control of recurrent hemorrhage. There is no proof that the drop in portal pressure incident to hepatic and splenic arterial ligations is sustained over any length of time. Our laboratory work indicates that portal pressures resume preoperative levels even in the absence of recurrent ascites. Reinhoff believes that, for the patient with ascites alone, ligation of the hepatic and splenic arteries is the operation of choice. His results following ligation in patients with bleeding esophageal varices were not as successful as in those with portacaval shunts. Confirmatory reports of good results in patients with ascites have come from many quarters. However, there have been some failures and even some deaths from liver necrosis following hepatic arterial ligation. We believe our experiments with ascitic dogs, and the anatomical studies of Michels, explain this apparent discrepancy. The unpredictable amount of arterial collateral blood supply to the liver appears to be the deciding factor between the two extremes of failure of the liver to maintain viability, on the one hand, and sufficient collateral blood supply to permit the reaccumulation of ascites, on the other. Somewhere between these two extremes are the cases which fall within the therapeutic range of hepatic artery ligation by virtue of an optimum collateral blood supply.
Harold Laufman
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Although one cannot predict, on an anatomical basis, which patients with ascites will do well and which ones will not, Berman has stated several definite contraindications to hepatic artery ligation on the basis of his experience. These include: (1) patients who are actively bleeding from varices; (2) persistent severe jaundice; (3) severe hypertension; (4) cardiac decompensation. Poor liver function, as determined by the various laboratory tests, is not in itself a contraindication. Following hepatic artery ligation there is a temporary rise in alkaline phosphatase levels both in experimental animals and in some patients. Occasional elevations in serum bilirubin have also been observed. Berman's mortality rate consists of an immediate mortality of 25 per cent and an over-all mortality of 41.6 per cent, all operations having been performed on poor risk patients who did not respond to medical management, including use of cation-anion resins. Reinhoff's figures are almost the same, consisting of 26 per cent immediate mortality and 30.4 per cent over-all mortality. In patients with ascites as the main indication the mortality rate was only 16 per cent and all survivors were improved. SUMMARY
From the welter of claims and counterclaims, some clear principles appear to be arising regarding the surgical care of patients with portal hypertension. There is no perfect operation to cope with this problem. Nonetheless, a better understanding of the physiological basis for surgery and the accumulating experiences of bold, exacting surgeons have led to certain principles which appear to be justified at this time. 1. Massive, active bleeding from esophageal varices is best controlled by the use of a tamponading balloon while blood replacement is carried out. Surgery is to be avoided during this stage, if possible. If bleeding continues at an alarming rate, despite good therapy, creating the need for drastic measures, probably the best surgical procedure is the transesophageal suture-ligation technique of Crile. This procedure is also valuable in patients who have undergone other types of surgery for their bleeding, but who have had recurrent hemorrhages. 2. The portacaval shunt procedure of Blakemore is best suited to the quiescent period, when the patient is in good condition. Its best results follow the side-to-side portal vein-vena cava anastomosis, and the operation appears to be best suited for cirrhotic patients whose main symptom is repeated episodes of bleeding from esophageal varices. 3. Ligation of the hepatic artery together with ligation of the splenic artery and perhaps the left gastric artery, either as carried out by Reinhoff or by Berman, appears to be best suited to the cirrhotic patient whose main symptom is ascites. 25 E. Washington Street Chicago 2, Illinois
HYPERTENSION of the portal venous system has been brought to the attention of surgeons because of two serious complications: massive bleeding from esophageal varices and wasting ascites. In the majority of cases portal hypertension is itself a complication of the distortion in liver architecture pursuant to portal cirrhosis. In other instances, the portal hypertension follows one of several types of extrahepatic blocks, either in the portal or splenic veins. Authoritative data reveals that death from cirrhosis per se occurs in only about 15 per cent of patients with cirrhosis. Intercurrent infection, especially pneumonia, is usually the actual cause of death. When death is due directly to cirrhosis, about one-third of such patients die of hemorrhage and two-thirds die of progressive liver failure. However, the incidence of hemorrhage, fatal and nonfatal, is 34 per cent. Thus of 100 patients with cirrhosis, 34 will bleed at some time or another, the disease will cause death in 15, five of these deaths will have been due to hemorrhage from esophageal varices and 10 will have been the result of cholemia. Clinically demonstrable ascites occurs in about three-fourths of all patients with cirrhosis. There is no argument with the premise that the treatment of cirrhosis is primarily medical. The surgeon is called for therapeutic aid after medical means fail, in order that he might correct or prevent, in some mechanical manner, an exsanguinating hemorrhage from esophageal veins or the debilitating accumulation of ascitic fluid, or both. The early, prophylactic employment of surgery in cases of cirrhosis is a highly controversial matter. Esophageal varices may disappear under medical management. This indicates that fluctuations in portal hypertension are not always dependent upon surgery and therefore the benefits from early surgery are difficult to evaluate. In recent years several new surgical approaches to the problem have been made. However, as the number of reports in the surgical literature multiplies, the confusion keeps apace, particularly regarding which procedure to use, when to use it and what to expect from it. One reason for
* Associate
Professor of Surgery, Northwestern University MedicaZ School. 113
Harold Laufman
114
this situation is that not enough time has elapsed, nor have individual series been large enough to warrant unequivocal conclusions. However, I believe that if a fuller understanding of the physiological basis for the various procedures is known, some of the confusion may be dissipated. BLEEDING ESOPHAGEAL VARICES
The question as to why esophageal varices bleed is still not completely answered. For many years it was deduced that the trauma of food passing over a superficial varix might easily erode it and cause hemorrhage. This concept cannot be denied, and may be true in some instances. Yet, the actual time of onset of hematemesis from esophageal varices most usually has no relationship to the ingestion of food. Sudden increases in pressure due to physical straining with closed epiglottis can conceivably cause bleeding of superficial thin-walled varices. In the experimental animal, portal pressure may rise twofold under these conditions. Wangensteen has held for many years that peptic erosion of esophageal mucosa overlying varices is responsible for the hemorrhage, and recent microscopic examination of eroded areas in these patients has shown definite evidence of peptic erosion in 19 of 44 specimens examined. It should also be remembered that in a patient with liver disease, the level of circulating prothrombin may be low, so that the natural hemostatic mechanisms are not available. In fact, the opinion has been expressed that other hemorrhagic phenomena, such as epistaxis in cirrhotic patients, may stem from this cause. It is also known that thrombocytopenia occurs frequently in cirrhosis, and may contribute to excess bleeding. Therapy of bleeding esophageal varices must be divided into two parts: therapy during the phase of active bleeding, and therapy designed to prevent recurrence of bleeding by an attempt to lower portal pressure. Therapy During Active Hemorrhage It is during the stage of active hemorrhage that much of the controversy regarding therapy has arisen and the poorest results have been obtained. Although some surgeons have reported success in the treatment of actively bleeding varices by transesophagealligation, resection of the lower esophagus and cardia and other maj or procedures, it is becoming more and more evident that such procedures are successful only in the early cases, perhaps within 24 to 48 hours after the onset of bleeding. However, in early cases one cannot be sure that a much more conservative approach might not have been successful, or that the bleeding might have stopped spontaneously. The most widely used therapy for massive bleeding esophageal varices consists of use of the Sengstaken-Blakemore balloon or the Patton-
Physiological Basis for Surgery in Portal Hypertension
115
Johnston tube for tamponage, while liberal but accurate replacement of lost blood is made by transfusions. Large doses of vitamin K are in order despite probable disorders in liver function. In the experience of most surgeons, any kind of definitive surgery on cirrhotic patients shortly after their blood volume has been replaced several times is hazardous despite the return of laboratory blood values to normal ranges. If surgery must be performed as a desperate measure in the face of exsanguinating hemorrhage, transesophageal suture-ligation is probably the procedure of choice. Any additional surgery at this stage is to be avoided because of the inability of the patient to withstand it even in the presence of continuous transfusion. It is certainly established that portacaval shunt procedures have no place in the presence of active bleeding nor should one feel justified in proceeding with hepatic arterial ligations under these circumstances. Therapy After HeulOrrhage Has Ceased
Attempts to lower portal pressure during the quiescent period have run a long gamut of surgical procedures. Their purpose, in patients with a history of bleeding, is to prevent the recurrence of bleeding. When ascites is present, their purpose is to stop or decelerate the formation of ascites. There is evidence that there are four contributory factors occurring in a cirrhotic liver which playa role in the production and maintenance of increased portal pressure: 1. Partial occlusion of the portal venous branches within the liver resulting from distortions in lobular architecture caused by contraction of scar and the regeneration of new, malformed lobules. 2. Intrahepatic venovenous shunts between the portal and hepatic venous collecting system. These may be enlarged counterparts of a normally occurring series of collateral veins, and/or may represent newly formed vessels in the presence of advanced portal cirrhosis. 3. Intrahepatic arteriovenous shunts between the portal venous and hepatic arterial branches. 4. Intrahepatic arteriovenous shunts between the hepatic venous and hepatic arterial branches. The sinusoids may serve as intermediary channels in the latter three categories. There has been a great deal of convincing evidence from work spread over many years to support the view that any or all of these alterations in vascular dynamics may occur. It is obvious that all these alterations need not contribute equally or simultaneously to the increased portal pressure. To illustrate the concept of the dynamic nature of portal hypertension in cirrhosis. one might visualize one small portal vein within the liver.
116
Harold Laufman
Mter the death of some liver cells, with the ensuing scar tissue, the wellknown ability of the liver to regenerate comes into play, and eventually the scar shrinkage plus the asymmetrical growth of liver regeneration results in a distorted parenchymal architecture, particularly in the area of the portal venules. This distortion may cause enough partial occlusion of the intrahepatic portal branches to act as a partial occlusion to the flow of portal blood cephalad through the liver. The direct consequence of this is the "backing up" or retrograde increase in hydrostatic pressure in the intrahepatic portal vein. The constantly elevated venous pressure acts as it does in other venous systems, such as the leg, and seeks compensation by distribution over a wider bed. The extrahepatic distribution of this compensatory mechanism is well known. The hypertrophy of existing channels and new formation of collateral channels results in esophageal varices by way of the coronary vein, the caput medusae by way of the veins of the round ligament, and hemorrhoidal varicosities by way of the inferior mesenteric veins. Carried one step further, actual or potential channels become established between these extensions of the portal system and branches of the caval system, again in an attempt to equalize and distribute the pressure. Thus, the esophageal veins make new connections and enlarge old connections with the azygos veins; the varicosities of the abdominal wall make connections with the superior and inferior superficial epigastric veins j the hemorrhoidal veins do likewise with the inferior hemorrhoidal branches of the pudendal veins. Since it is known that the pressure in the portal and caval systems are reciprocal, the pressure in the new connections between the two systems may be maintained at a relatively high level from both sides. When the portal pressure is high, the collateral channel pressures are maintained from that side. During straining or other maneuvers, both the caval pressure and the portal pressure rise, and the collateral channel pressures are elevated from both sides. The intrahepatic distribution of the compensatory mechanism is less well known. The increased portal pressure within the liver sooner or later seeks new pathways of distribution within the actual liver substance. Venovenous shunts and arteriovenous shunts are created either from hypertrophy of previously existing connections or from new collaterals or both, the hepatic sinusoids serving an intermediary function. Thus, in portal cirrhosis, what has been created is a rather rigid reservoir of vascular short-circuits. It is known that the connections between the hepatic arterial tree and portal vein branches are more direct in cirrhosis than a normal liver, allowing pressure to be transmitted more directly from the hepatic artery to the portal vein. Thus, it would appear that the compensatory development of new channels actually serves as the beginning of a vicious cycle in which the new channels transmit a portion of the intrahepatic arterial pressures into the portal system. The
Physiological Basis for Surgery in Portal Hypertension
117
new portal-hepatic venous collaterals are thereby enhanced, and pressure in the hepatic vein rises as the cirrhosis progresses. Furthermore, the great pressure differentials between the hepatic arterial branches and the hepatic venous collecting branches encourage the development of hepatic arteriovenous short-circuits, and this also contributes to elevated pressures in the hepatic vein. The elevated hepatic vein pressures then serve as a retrograde contribution to elevate portal pressure by way of the portal-hepatic vein shunts, and the vicious cycle is complete. Employing this concept, the question of whether ascites or bleeding varices, or both, will result from the lesion, is dependent on whether passive congestion created by blockage of the venous flow or pressure distribution created by the shunts is the major feature, OPERATIONS DESIGNED TO HAVE A DELAYED EFFECT
Attelllpts to Prolllote the Developlllent of Collateral Circulation
The Talma-Morison omentopexy has proved to be a disappointment to most surgeons who have employed it. Recently pqcking gauze about the esophagus through a mediastinotomy has been recommended, but this procedure may not prevent recurrence of bleeding from esophageal varices. Close scrutiny of such procedures reveals that actually one should not expect that the encouragement of a few more collateral channels would add noticeably to the already established massive connections between the portal and caval systems incident to portal hypertension. It is possible that what benefits may be temporarily derived from the mediastinal packing operation are due to cutting off anastomotic channels from the azygos system rather than producing them. OPERATIONS DESIGNED TO HAVE AN IMMEDIATE EFFECT
Attelllpts to Interrupt the Coronary-Esophageal Venous Systeni
I I
British surgeons who have advocated excision of the coronary vein have not reported actual follow-up studies on its results. It is difficult to see how such a limited procedure could be of lasting benefit, especially since the increased pressure in the esophageal veins is not all transmitted directly through the coronary vein from the portal system. The large anastomotic channels between the esophageal varices and the azygos system allow caval blood to circulate through the thin-walled esophageal varices, allowing the direct transmission of increases in pressure incident to straining. Banti suggested ligation of the splenic and short gastric arteries with splenectomy and Flerow advanced the cause for ligation of the left gastric and the right and left gastroepiploic arteries, in addition to the accompany-
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ing veins. These procedures, in addition to interrupting the venous channels, allowed less arterial blood to flow into the stomach capillaries, hence permitting less blood to be picked up by the collecting venous system. None of these procedures has produced results of any lasting quality, probably because of the re-establishment of new venous channels. Wangensteen, in ~945, carried devascularization of the stomach to its ultimate and suggested total gastrectomy. Thus far, no information appears to be available on results in a series of cases with follow-up. Gastrectomy would appear to have no great advantage over the extensive devascularization procedures except, perhaps, that recanalization would occur more slowly. Furthermore, all of the physiological ill-effects pursuant to total gastrectomy can be expected. In 1947, Phemister and Humphreys reported resection of the lower esophagus and cardiac end of the stomach. Unquestionably, this procedure is a direct and radical attack upon the area of bleeding. However, it is an operation of some magnitude and carries a significant mortality and morbidity. Crile believes that this procedure is too radical for the purpose, and likens it to the performance of an abdominoperineal resection for a case of bleeding hemorrhoids. Crile's operation of transesophageal suture-ligation of the bleeding varices is a direct, yet not too formidable operation, which he used during a quiescent period in seven patients with extrahepatic blocks in the portal system. Most of these patients had had previous surgery for bleeding varices, including devascularization of the stomach and splenectomy. Shunt procedures could not be done in his cases because of the extrahepatic location of the portal block. Results were apparently gratifying up to the time of the report with follow-up of over a year in some cases. Attempts to Reduce Venous Inflow to the Portal System
A number of operations have been suggested or carried out over the past 75 years in which the goal is to reduce the blood flow into the portal vein, rather than to interrupt the portal-esophageal vein circuit. Splenectomy was first suggested by Banti in 1874 as one part of a combination attack, the other part consisting of ligation of the vessels of the stomach. The rationale of splenectomy in the reduction of portal pressure is based upon the fact that the venous drainage from the spleen enters the portal vein directly and contributes appreciably to its pressure. In the same sense, ligation of the splenic artery in poor risk cases without removal of spleen aims at this goal. Neither splenectomy nor ligation of the splenic artery has been found to give a lasting effect in most instances of cirrhosis. The reason for this failure is based upon the fact that in cirrhosis the block to the portal
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system is intrahepatic. The increased pressure in the portal vein is partially the result of a retrograde increase in hydrostatic pressure. Consequently, although some reduction in venous inflow will temporarily reduce the pressure within the portal system, the pressure will again rise as the intrahepatic causes for the high pressure progress. Infrahepatic blocks to the portal system lend themselves more logically to this procedure. Another method of reducing venous inflow to the portal system is massive intestinal resection. This procedure has been used in only one patient with ascites, and resulted in a marked deceleration in the rate of ascites formation. Extensive experimental studies on this procedure have been carried out in our laboratory on ascitic dogs. We found that extensive resection of the small intestine, with or without splenectomy, either retarded or prevented the reaccumulation of ascites. In addition to the imposed diminution in the volume of the extrahepatic portal (mesenteric venous) bed, the procedure results in a high fecal sodium excretion. It is our impression that both these factors are important. The question remains, however, as to the advisability of imposing such a great alteration in gastrointestinal physiology upon a patient with cirrhosis. It is possible that this easily executed procedure, consisting of resection of the middle 50 per cent of the small intestine, might be of value in a poor risk patient with ascites and in whom other procedures are not feasible. To date, probably the most popular surgical method of reducing venous inflow to the portal bed has been the portacaval shunt. This term has been employed to include any type of surgical anastomosis that joins the portal and caval systems of veins. The direct Eck fistula (anastomosis of portal vein to vena cava) became feasible in the human being only after present day advances in surgery, anesthesia and postoperative management permitted its clinical use. Variations of the operation consist of (1) direct side-to-side anastomosis of the portal vein to vena cava; (2) splenectomy and end-to-side anastomosis of the splenic vein to left renal vein; (3) end-to-side anastomosis of umbilical vein to vena cava; (4) anastomosis of portal vein to right renal vein; (5) anastomosis of inferior or superior mesenteric vein to vena cava. Since it is clear that the greatest shunt effect from the high pressure portal system to the low pressure caval system is obtained close to the liver, and between the largest vessels, any anastomosis other than a direct portal vein-vena cava anastomosis is a compromise, to be carried out only when the direct operation is not technically feasible. It is known that a large proportion of the splenorenal shunts close spontaneously, probably due to their small caliber and the lesser pressure differential. In Blakemore's series published in 1951, a history of bleeding was the
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major indication for surgery in 61 patients. In the 38 instances in which the portal vein was anastomosed to the vena cava, but one case had a recurrent hemorrhage, and this was in a patient with partial thrombosis of the portal vein at time of surgery. Of 38 splenorenal shunts, the shunt had closed in at least five instances proved at postmortem one to five years after surgery. Although results with splenorenal shunts are less impressive, Blakemore believes that the rapid rise in platelet count following splenectomy and a splenorenal shunt is important, and that results with this procedure can be improved. Although a substantial rise in circulating platelets follows a direct portacaval shunt, it is a slow response commensurate with gradual shrinkage of the spleen, and only occasionally does the number reach a low normal. Although varying amounts of ascites had been present in about twothirds of his cases, it was the major indication for surgery in only nine. Seven survivors were all apparently relieved of their ascites, one patient having been followed for five years. Linton has found that portacaval shunt is particularly difficult to perform in patients with ascites, because of the heavy lymphatic channels and edematous tissue surrounding a rather delicately walled portal vein. When he performs the procedure for ascites he prefers to do it in two stages. Welsh has stated that the operation is indicated primarily in patients who have had hemorrhage, and that ascites is not best treated by this method. The over-all operative mortality of shunt procedures in Blakemore's hands is 16.2 per cent, with a follow-up mortality of an additional 11 per cent. The follow-up mortality rate for the portal vein-vena cava group was 8 per cent while that for the splenorenal group was 23.7 per cent. Other surgeons have not been so successful, either in the results obtained or in their mortality rates. Attelllpts to Reduce Intrahepatic Portal Pressure
It is known that vasomotor influences are an important factor in the tonus of the liver vasculature, and hence in the regulation of vascular pressures in the liver. Stimulation of the hepatic sympathetic nerve plexus is known to cause an appreciable rise in portal pressure. It occurred to us, therefore, that sympathectomy of ihe appropriatejibers might serve to lower portal pressure by releasing some of the tonus in the portal venous tree. We found, however, that the effect was negligible, particularly in animals with a vena cava band-induced portal hypertension. This result would tend to support Berman's contention that vasomotor influences are greatly reduced in the cirrhotic. The increased resistance in linear flow is due more to the blockage than it is to vascular tone, and the former so far outbalances the latter that the release of tone is inconsequential. Reinhoff and Berman have independentlY explored the feasibility of
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ligation of the hepatic artery as a means of reducing intrahepatic pressure in the portal vein. Reinhoff ligates the hepatic artery distal to the gastroduodenal artery in addition to ligation of the splenic artery. Berman prefers to ligate the hepatic artery proximal to the gastroduodenal artery in addition to the splenic and left gastric arteries. He believes that ligation distal to the gastroduodenal artery may be more prone to produce necrosis. This operation, although not always technically easy, is a great deal less exacting than the performance of a shunt, and therefore stands to become more popular, provided its results compare favorably. Since the use of antibiotics has made hepatic artery ligations a relatively safe procedure, the maneuver became available as a therapeutic possibility. Its physiological rationale in cases of portal hypertension is based upon the knowledge that hepatic arterial pressure contributes appreciably to portal pressure under these circumstances, as described above. Therefore; if the arterial contribution could be largely eliminated, part of the vicious cycle might be restrained. Furthermore, the hepatic arterial-portal venous reflux could be ameliorated, and the hepatic venous pressure could be reduced, thereby permitting more portal blood to enter the liver under a lower pressure. Reinhoff and Berman agree that the greatest benefit from ligation of the common hepatic and splenic arteries occurs in patients with intractable ascites only. Addition of ligation of the left gastric artery to the procedure to prevent further bleeding from esophageal varices gave only equivocal results in the control of recurrent hemorrhage. There is no proof that the drop in portal pressure incident to hepatic and splenic arterial ligations is sustained over any length of time. Our laboratory work indicates that portal pressures resume preoperative levels even in the absence of recurrent ascites. Reinhoff believes that, for the patient with ascites alone, ligation of the hepatic and splenic arteries is the operation of choice. His results following ligation in patients with bleeding esophageal varices were not as successful as in those with portacaval shunts. Confirmatory reports of good results in patients with ascites have come from many quarters. However, there have been some failures and even some deaths from liver necrosis following hepatic arterial ligation. We believe our experiments with ascitic dogs, and the anatomical studies of Michels, explain this apparent discrepancy. The unpredictable amount of arterial collateral blood supply to the liver appears to be the deciding factor between the two extremes of failure of the liver to maintain viability, on the one hand, and sufficient collateral blood supply to permit the reaccumulation of ascites, on the other. Somewhere between these two extremes are the cases which fall within the therapeutic range of hepatic artery ligation by virtue of an optimum collateral blood supply.
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Although one cannot predict, on an anatomical basis, which patients with ascites will do well and which ones will not, Berman has stated several definite contraindications to hepatic artery ligation on the basis of his experience. These include: (1) patients who are actively bleeding from varices; (2) persistent severe jaundice; (3) severe hypertension; (4) cardiac decompensation. Poor liver function, as determined by the various laboratory tests, is not in itself a contraindication. Following hepatic artery ligation there is a temporary rise in alkaline phosphatase levels both in experimental animals and in some patients. Occasional elevations in serum bilirubin have also been observed. Berman's mortality rate consists of an immediate mortality of 25 per cent and an over-all mortality of 41.6 per cent, all operations having been performed on poor risk patients who did not respond to medical management, including use of cation-anion resins. Reinhoff's figures are almost the same, consisting of 26 per cent immediate mortality and 30.4 per cent over-all mortality. In patients with ascites as the main indication the mortality rate was only 16 per cent and all survivors were improved. SUMMARY
From the welter of claims and counterclaims, some clear principles appear to be arising regarding the surgical care of patients with portal hypertension. There is no perfect operation to cope with this problem. Nonetheless, a better understanding of the physiological basis for surgery and the accumulating experiences of bold, exacting surgeons have led to certain principles which appear to be justified at this time. 1. Massive, active bleeding from esophageal varices is best controlled by the use of a tamponading balloon while blood replacement is carried out. Surgery is to be avoided during this stage, if possible. If bleeding continues at an alarming rate, despite good therapy, creating the need for drastic measures, probably the best surgical procedure is the transesophageal suture-ligation technique of Crile. This procedure is also valuable in patients who have undergone other types of surgery for their bleeding, but who have had recurrent hemorrhages. 2. The portacaval shunt procedure of Blakemore is best suited to the quiescent period, when the patient is in good condition. Its best results follow the side-to-side portal vein-vena cava anastomosis, and the operation appears to be best suited for cirrhotic patients whose main symptom is repeated episodes of bleeding from esophageal varices. 3. Ligation of the hepatic artery together with ligation of the splenic artery and perhaps the left gastric artery, either as carried out by Reinhoff or by Berman, appears to be best suited to the cirrhotic patient whose main symptom is ascites. 25 E. Washington Street Chicago 2, Illinois