Marshall J. Orloff

A 27-year experience with surgical treatment of Budd-Chiari syndrome.

ObjectiveTo determine the effects of surgical portal decompression in Budd-Chiari syndrome (BCS) on survival, quality of life, shunt patency, liver function, portal hemodynamics, and hepatic morphology during periods ranging from 3.5 to 27 years. Summary Background DataExperiments in the authors’ laboratory showed that surgical portal decompression reversed the deleterious effects of BCS on the liver. This study was aimed at determining whether similar benefit could be obtained in patients with BCS. MethodsFrom 1972 to 1999, the authors conducted prospective studies of the treatment of 60 patients with BCS who were divided into three groups: the first had occlusion confined to the hepatic veins treated by direct side-to-side portacaval shunt (SSPCS); the second had occlusion involving the inferior vena cava (IVC) treated by a portal decompressive procedure that bypassed the obstructed IVC; and the third group, who had advanced cirrhosis and hepatic decompensation and were referred too late for treatment by portal decompression, required orthotopic liver transplantation. ResultsIn the 32 patients with BCS resulting from hepatic vein occlusion alone, SSPCS had a surgical death rate of 3%, and 94% of the patients were alive 3.5 to 27 years after surgery. All 31 survivors remained free of ascites and almost all had normal liver function. No patient with a patent shunt had encephalopathy. The SSPCS remained patent in all but one patient. Liver biopsies showed no evidence of congestion or necrosis, and 48% of the biopsies were diagnosed as normal. Mesoatrial shunt was performed in eight patients with BCS caused by IVC thrombosis. All patients survived surgery, but five subsequently developed thrombosis of the synthetic graft and died. Because of the poor results, mesoatrial shunt was abandoned. Instead, a high-flow combination shunt was introduced, consisting of SSPCS combined with a cavoatrial shunt (CAS) through a Gore-Tex graft. There were no surgical or long-term deaths among 10 patients who underwent combined SSPCS and CAS, and the shunts functioned effectively during 4 to 16 years of follow-up. Ten patients with advanced cirrhosis were referred too late to benefit from surgical portal decompression, and they were approved and listed for orthotopic liver transplantation. Three patients died of liver failure while awaiting a transplant, and four patients died after the transplant. The 1- and 5-year survival rates were 40% and 30%, respectively. ConclusionsSSPCS in BCS with hepatic vein occlusion alone results in reversal of liver damage, correction of hemodynamic disturbances, prolonged survival, and good quality of life when performed early in the course of BCS. Similarly good results are obtained with combined SSPCS and CAS in patients with BCS resulting from IVC occlusion. In contrast, mesoatrial shunt has been discontinued in the authors’ program because of an unacceptable incidence of graft thrombosis and death. In patients with advanced cirrhosis from long-standing, untreated BCS, orthotopic liver transplantation is the only hope of relief and results in the salvage of some patients. The key to long survival in BCS is prompt diagnosis and treatment by portal decompression.

Pancreaticoduodenal transplantation in the rat.

SUMMARY A technique for pancreaticoduodenal (PD) transplantation in the rat is presented. The rejection reaction in pancreatic grafts in inbred strains of rats is described. The major complication, acute hemorrhagic pancreatitis, can be partially prevented by carefully ligating tributaries in the vicinity of the pancreas, reducing the is chemic time, perfusing with cold saline, and using a no-touch technique.

A TECHNIQUE FOR ORTHOTOPIC LIVER TRANSPLANTATION IN THE RAT

This report describes in detail the technique of orthotopic liver transplantation in syngeneic rats which are relatively inexpensive and readily available. We also report the long-term survival and function of these grafts. The technique involves the use of a miniaturized extracorporeal portal to jugular shunt. The donor liver is perfused and cooled. Implantation is accomplished using standard microvascular suture techniques. Successful orthotopic liver transplants were performed in 47 of 64 rats. Long-term survival up to 14 months was achieved in seven animals. Liver function was measured by serial determination of bilirubin, serum glutamic oxaloacetic transaminase (SGOT), and alkaline phosphatase. Elevations in bilirubin and SGOT in the immediate postoperative period returned to normal by the second postoperative week. Marked variations were seen in alkaline phosphatase values, and there was slow return to normal levels. Open liver biopsies were performed on long-term survivors at 3, 5, and 7 months and revealed essentially normal liver parenchyma, with slight mononuclear infiltration of the portal spaces and some sinusoidal dilatation. The practicability of the transplant and organ preservation, and the advantages of using the inbred rat as the experimental animal are discussed.

Long-term Results of Emergency Portacaval Shunt for Bleeding Esophageal Varices in Unselected Patients with Alcoholic Cirrhosis

A prospective evaluation of emergency protacaval shunt has been conducted in 180 unselected, consecutive patients with cirrhosis and bleeding varices who were operated on between 1963 and 1978. An extensive diagnostic work-up was completed within three to seven hours of admission to the emergency department, and the shunt operation was undertaken within a mean of 7.81 hours. A program of lifelong follow-up was conducted such that the current status of 97% of the patients is known. On each patient, 220 categories of data were collected and entered into a computer program for analysis. On admission, 49% of the patients had jaundice, 53% had ascites, 19% had encephalopathy, 30% had severe muscle wasting and 100% had abnormal BSP retention. Administration of a bolus dose of vasopressin by the systemic intravenous route temporarily controlled the varix hemorrhage in 95% of patients, and emergency shunt permanently controlled the bleeding in 98%. Maximum perfusion pressure in the portal vein prior to shunt did riot correlate with survival rate or incidence of encephalopathy after shunt. The operative survival rate was 58%, the five-year actuarial survival rate is 38% and the 12-year actuarial survival rate is 30%. Encephalopathy was observed in 31.5% of the patients, but was severe enough to require chronic dietary protein restriction in only 7%. The portacaval shunt remained patent in 99% of patients. Of the survivors, 48% abstained from alcohol, 60% resumed gainful employment or housekeeping, and two-thirds were judged to be in excellent or good condition after one and five years. Preoperative factors that adversely influenced survival rate were ascites, SGOT ≤ 100 units, BSP retention < 50%, hypokalemic alkalosis, blood transfusion requirement ≤ 5 L, and consumption of alcohol within seven days of admission. In comparison with our previous prospective studies, emergency portacaval shunt produced a significantly greater long-term survival rate than either emergency medical therapy or emergency varix ligation, followed by elective shunt. During the past four years, 80% of 49 unselected patients have survived emergency shunt, and the four year actuarial survival rate is 69%.

Bleeding esophagogastric varices from extrahepatic portal hypertension: 40 Years' experience with portal-systemic shunt

BACKGROUND This article discusses the largest and longest experience reported to date of the use of portal-systemic shunt (PSS) to treat recurrent bleeding from esophagogastric varices caused by extrahepatic portal hypertension associated with portal vein thrombosis (PVT). STUDY DESIGN Two hundred consecutive children and adults with extrahepatic portal hypertension caused by PVT who were referred between 1958 and 1998 after recovering from at least two episodes of bleeding esophagogastric varices requiring blood transfusions were managed according to a well-defined and uniformly applied protocol. All but 14 of the 200 patients were eligible for and received 5 or more years of regular followup (93%); 166 were eligible for and received 10 or more years of regular followup (83%). RESULTS The etiology of PVT was unknown in 65% of patients. Identifiable causes of PVT were neonatal omphalitis in 30 patients (15%), umbilical vein catheterization in 14 patients (7%), and peritonitis in 14 patients (7%). The mean number of bleeding episodes before PSS was 5.4 (range 2 to 18). Liver biopsies showed normal morphology in all patients. The site of PVT was the portal vein alone in 134 patients (76%), the portal vein and adjacent superior mesenteric vein in 10 patients (5%), and the portal and splenic veins in 56 patients (28%). Postoperative survival to leave the hospital was 100%. Actuarial 5-year, 10-year, and 15-year survival rates were 99%, 97%, and 95%, respectively. Five patients (2.5%), all with central end-to-side splenorenal shunts, developed thrombosis of the PSS, and these were the only patients who had recurrent variceal bleeding. During 10 or more years of followup, 97% of the eligible patients were shown to have a patent shunt and were free of bleeding. No patient developed portal-systemic encephalopathy, liver function tests remained normal, liver biopsies in 100 patients showed normal architecture, hypersplenism was corrected. CONCLUSION PSS is the only consistently effective therapy for bleeding esophagogastric varices from PVT and extrahepatic portal hypertension, resulting in many years of survival, freedom from recurrent bleeding, normal liver function, and no encephalopathy.

Treatment of Budd-Chiari syndrome by side-to-side portacaval shunt: experimental and clinical results.

The Budd-Chiari syndrome caused by occlusion of the major hepatic veins, often of unknown etiology, is typically characterized by massive ascites, hepatomegaly and abdominal pain due to intense congestion of the liver. The outcome has almost always been fatal. This report describes an evaluation of side-to-side portacaval shunt in dogs with experimental Budd-Chiari syndrome and in six patients with hepatic vein thrombosis. In the animal studies, side-to-side portacaval shunt was very effective in relieving massive ascites, hepatomegaly, hepatic congestion and portal hypertension produced by ligation of the hepatic veins. Only one of 24 dogs with side-to-side anastomosis reformed ascites, 67% of the animals survived until the study was concluded after one year, and liver biopsies showed reversal of the severe pathologic abnormalities. In contrast, all 20 control dogs subjected to a sham laparotomy, and all 20 dogs that underwent end-to-side portacaval shunt reformed massive ascites and died within six months with continued hepatic congestion and necrosis. All six patients with the Budd-Chiari syndrome due to hepatic vein occlusion had massive ascites (4.4-15.9 l), hepatomegaly, abdominal pain and disturbed liver function. In all six, angiography demonstrated occlusion of the hepatic veins with a patent inferior vena cava (IVC) and a normal IVC pressure, and liver biopsy showed intense centrilobular congestion and necrosis. The most valuable diagnostic study was angiography of the IVC and hepatic veins with pressure measurements. Side-to-side portacaval shunt was performed from four to 14 weeks after the onset of symptoms, and produced dramatic and sustained relief of ascites in five of the six patients during follow-up periods of from eight months to seven years. Liver function returned to normal, hepatosplenomegaly disappeared, none of the survivors developed portal-systemic encephalopathy, and follow-up liver biopsies showed disappearance of congestion and necrosis, but mild to moderate fibrosis. One patient died following an emergency IVC thrombectomy and portacaval shunt, which was undertaken when, during the course of his workup, his condition deteriorated suddenly because the thrombotic process extended from the hepatic veins into the IVC. The everpresent risk of this complication, and the dangers associated with delaying operation were emphasized by this case. It is concluded that side-to-side portacaval shunt, which decompresses the liver by converting the portal vein into an outflow tract, provides effective treatment of the Budd-Chiari syndrome when the occlusive process is confined to the hepatic veins.

Clonidine and lidamidine to inhibit watery diarrhea in a patient with lung cancer.

A patient with watery diarrhea syndrome secondary to bronchogenic carcinoma responded to treatment with clonidine and lidamidine. Stool weight decreased to 43% and 53% of control on two separate trials of clonidine. Stool weight decreased to 35% of control during a trial of lidamidine. Both clonidine and lidamidine increased sodium and chloride absorption in vitro in human intestine. Clonidine, lidamidine, or drugs that are structurally similar may become therapeutic choices for secretory diarrhea.

Simplified technic for orthotopic liver transplantation in the rat

A new surgical procedure has been developed to simplify the difficult, complex technic of orthotopic liver transplantation in the rat that we previously described. This procedure eliminates the hepatic artery anastomosis and specifically changes the sequence of anastomoses of the vena cava and portal vein to minimize splanchnic congestion and hepatic ischemia. This has simplified and shortened the operation and has eliminated the need for an extracorporeal portosystemic shunt. Seventy-two per cent operative survival was achieved in fifty-seven orthotopic liver transplantations. This simplified technic of orthotopic liver transplantation in the rat can be applied widely to studies of liver physiology, immunologic rejection, and liver preservation.

Treatment of bleeding esophagogastric varices due to extrahepatic portal hypertension: Results of portal-systemic shunts during 35 years☆

From 1958 to 1990, elective therapeutic portal-systemic shunt (PSS) procedures were performed for recurrent bleeding esophagogastric varices in 162 children and adults with extrahepatic portal hypertension (EHPH) resulting from portal vein thrombosis (PVT). The onset of EHPH was in childhood for at least 74% of patients. Of the 162 patients, 147 were eligible for and received 5 years of follow-up (100%), and 117 were eligible for and received 10 years of follow-up (100%). The longest follow-up was 35 years. The cause of PVT was unknown in 68%, neonatal omphalitis in 12%, umbilical vein catheterization in 8%, peritonitis in 6%, trauma in 4%, and thrombotic coagulopathy in 2%. The number of variceal bleeding episodes ranged from 2 to 18 (mean, 5.6). None of the patients had clinical, biochemical, or liver biopsy evidence of liver disease. Esophageal varices were demonstrated by endoscopy, and/or contrast x-rays, and/or angiography in all patients. Visceral angiography was always used to demonstrate the extent of portal obstruction and the veins available for shunting. Before referral, the following procedures had failed: endoscopic sclerotherapy (68 patients), splenectomy alone (32 patients), central splenorenal shunt with splenectomy (10 patients), transesophageal varix ligation (12 patients). Three types of PSS were used: (1) central side-to-side splenorenal without splenectomy (75 patients, 46%); (2) central end-to-side splenorenal with splenectomy (34 patients, 21%); and (3) mesocaval (end-to-side cavomesenteric) (53 patients, 33%). PSS reduced the mean corrected portal pressure from 292 to 28 mm saline. All patients survived the procedure and left the hospital (100%). The actuarial survival rate for 5 years is 99%, and for 10 years is 96%. Three of the 6 deaths were unrelated to EHPH or PSS. Shunt patency for up to 35 years was demonstrated in 98% of patients by angiography and/or ultrasonography. In four patients (2%), all of whom had end-to-side splenorenal shunts, shunt thrombosis and rebleeding developed 3, 4, 4, and 6 years (respectively) after PSS. There were the only patients who experienced rebleeding. A diligent and repeated effort was made to detect portal-systemic encephalopathy (PSE), and no instance of PSE was found during 3 to 35 years of follow-up. Liver function and morphology remained normal, and hypersplenism was corrected in all patients. Quality of life was good in 98% of patients, and 5 years after PSS 96% were gainfully employed, engaged in full-time homemaking, or attending school.(ABSTRACT TRUNCATED AT 400 WORDS)

Randomized trial of emergency endoscopic sclerotherapy versus emergency portacaval shunt for acutely bleeding esophageal varices in cirrhosis.

BACKGROUND The mortality rate of bleeding esophageal varices in cirrhosis is highest during the period of acute bleeding. This is a report of a randomized trial that compared endoscopic sclerotherapy (EST) with emergency portacaval shunt (EPCS) in cirrhotic patients with acute variceal hemorrhage. STUDY DESIGN A total of 211 unselected consecutive patients with cirrhosis and acutely bleeding esophageal varices who required at least 2 U of blood transfusion were randomized to EST (n=106) or EPCS (n=105). Diagnostic workup was completed within 6 hours and EST or EPCS was initiated within 8 hours of initial contact. Longterm EST was performed according to a deliberate schedule. Ninety-six percent of patients underwent more than 10 years of followup, or until death. RESULTS The percent of patients in Childs risk classes were A, 27.5; B, 45.0; and C, 27.5. EST achieved permanent control of bleeding in only 20% of patients; EPCS permanently controlled bleeding in every patient (p< or =0.001). Requirement for blood transfusions was greater in the EST group than in the EPCS patients. Compared with EST, survival after EPCS was significantly higher at all time intervals and in all Childs classes (p< or =0.001). Recurrent episodes of portal-systemic encephalopathy developed in 35% of EST patients and 15% of EPCS patients (p< or =0.01). CONCLUSIONS EPCS permanently stopped variceal bleeding, rarely became occluded, was accomplished with a low incidence of portal-systemic encephalopathy, and compared with EST, produced greater longterm survival. The widespread practice of using surgical procedures mainly as salvage for failure of endoscopic therapy is not supported by the results of this trial (clinicaltrials.gov #NCT00690027).