Biomedical subjects
Publications and source records attributed to W D Warren.
These preliminary results of a new approach for the control of pain in chronic pancreatitis are presented with the hope that others experienced in this field will test this concept.
Portasystemic decompression remains the most definitive procedure in the control of portal hypertension (PHT) and bleeding gastroesophageal varices (BGEV). However, controversy prevails regarding shunt timing, type, and even propriety, especially in alcoholics. Analysis of a recent portal hypertension questionnaire submitted to 75 university-affiliated Veterans Administration Medical Centers (VAMC) reflected optimism regarding portasystemic shunts for the management of bleeding varices; disappointingly, however, on the average, only 20 to 25 per cent of variceal bleeders underwent definitive surgical management of any type. Ending in January 1980, a 14-year experience at the Atlanta VAMC with 72 portasystemic shunts was reviewed and demonstrates that shunt procedures may be extended to the veteran, predominantly alcoholic, population. Criteria for successful patient selection and operation are presented. While elective variceal decompression, preferably by the distal splenorenal shunt operation, may be performed with minimal morbidity and mortality, more efficient control of alcoholism is essential to prevent late deaths from hepatic failure.
Operative ligation of total portasystemic shunts is effective in reversing hepatic encephalopathy but is associated with significant mortality. In the case reported, invasive radiographic techniques were used to occlude a mesorenal shunt and reverse recurrent, disabling encephalopathy in a 72-yr-old woman. Occlusion of the shunt, coupled with coronary vein embolization, improved angiographic portal perfusion from grade IV to grade I, increased nutrient liver blood flow from 577 ml/min to 848 ml/min, and increased the hepatic fraction of cardiac output from 8.8% to 24.9%. Improved hepatocyte function was measured by an increase in galactose elimination capacity from 123 mg/min to 166 mg/min and a decrease in fasting ammonia from 107 micrograms/dl to 33 micrograms/dl. A 10-mo follow-up showed that there has been no recurrence of encephalopathy or variceal hemorrhage. Based on this experience, we conclude that (a) in selected cases total portasystemic shunts can be occluded by invasive radiographic techniques, and (b) restoration of portal perfusion can reverse hepatic encephalopathy and improve liver function.
The selective shunt concept has been validated both physiologically and clinically for the nonemergent patient with variceal bleeding. The patency rate of the shunt has been good and long-term control of gastroesophageal bleeding excellent. Furthermore, the transsplenic decompression of the upper stomach and lower esophagus has effectively prevented the problems related to gastritis and gastric varices seen with nonshunt procedures. Continued portal perfusion of the liver has been sustained for more than 9 years in some patients, and 9 of 11 patients have portal perfusion exceeding 7 years. The metabolic problems of the portaprival syndrome have been greatly ameliorated, and long-term survival with clinical well-being has been achieved. For the actively bleeding patient, acute renal vein hypertension needs to be prevented to provide effective control of hemorrhage. Selective splenocaval shunts have been successful in this regard in a small number of patients.
Can normal nutritional status, as indicated by albumin, transferrin and lean body mass values, be maintained during a 100 lb weight loss after gastric partitioning? Fifteen morbidly obese patients with normal nutritional status were fed three diets before (diet A) and after (diets B and C) gastric partitioning, and changes in albumin, transferrin, and lean body mass were monitored. Diets A and C were compositionally equal and contained 40 to 60 g of protein and 600 to 900 calories administered in six to eight equally divided portions per day. Diet B contained 20 to 40 g of protein and 600 to 800 calories per day and was given through a gastrostomy tube for three months after surgery while oral input was limited to noncaloric liquids. Results showed that weight loss was more rapid before surgery with diet A, than after surgery with diet B or C (diet A versus diet B, p less than 0.05; diet A versus diet C, p less than 0.05). Lean body mass was maintained with each diet, but transferrin (p less than 0.01) and albumin (p less than 0.05) decreased while patients were fed diet B. When gastrostomy tube feedings were discontinued, diet C restored albumin and transferrin to preoperative values (diet C versus diet B, p less than 0.05, diet C versus diet A, p greater than 0.1). Total postoperative weight loss averaged 106 +/- 20 lb after 2 years. These data show that in carefully selected patients with morbid obesity who demonstrate compliance to diet A before surgery, a 100 lb weight loss may be achieved while nutritional competence is maintained.
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It has been proposed that hepatic encephalopathy and malnutrition in cirrhosis can be reversed by infusion of a protein formula (F080) enriched with branched-chain amino acids (valine, leucine, isoleucine) and containing decreased amounts of aromatic amino acids (phenylalanine, tyrosine, tryptophan). This hypothesis was tested by measuring changes in encephalopathy status, plasma ammonia, amino acid profile, and liver function during seven metabolic balance studies in three patients with cirrhosis and subclinical encephalopathy given increasing amounts (20-100 g/d) of F080. The results showed the following: 1) positive nitrogen balance was achieved only with 80 and 100 g F080/day; 2) plasma ammonia fell during negative, but increased during positive nitrogen balance; 3) plasma tyrosine and cystine fell significantly (p less than 0.05) with all intakes of F080; 4) the abnormal branched-chain to aromatic amino acid ratio was reversed; 5) extracellular volume was expanded in all patients; 6) albumin, bilirubin, prothrombin time became abnormal; and 7) encephalopathy did not significantly change from baseline. It is concluded that, in this population, F080 is an inadequate nutritional formula when given as the sole protein source because it produces hypotyrosinemia and hypocystinemia. The marked changes in the ratio of branched-chain to aromatic amino acids are not accompanied by improvement in encephalopathy.
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The distal splenorenal shunt significantly improves 5-year survival from variceal bleeding in nonalcoholic (70%) compared to alcoholic (45%) cirrhosis patients. This study quantitates hemodynamic differences occurring in the first year after DSRS in 16 alcoholic compared to eight nonalcoholic patients. Portal venous perfusion was retained significantly better (p less than .01) by the nonalcoholic (seven of eight) than by the alcoholic (four of sixteen) patients. Mean liver blood flow (p less than 0.07), flow/unit liver volume (p less than .05), and flow required to perform a specific hepatocyte function (p less than 0.05) all increased significantly in the alcoholic compared to nonalcoholic group. Cardiac output increased significantly in the alcoholic patients (p less than 0.05), but was unchanged in the nonalcoholic patients. The alcoholic patients divided into two subsets, 11 who showed increase in flow (1082 +/- 260 to 1496 +/- 388 ml/min) and five who did not (1246 +/- 269 to 994 +/- 159 ml/min). The former had significantly (p less than 0.05) poorer hepatocyte function and had a significant (p less than 0.05) increase in flow/unit volume and flow/unit function at 1 year, which may have helped to maintain hepatocyte integrity. The latter, in parallel with the nonalcoholic patients, showed no significant change in these parameters and maintained a good functional hepatocyte mass. These data lead us to hypothesize that: 1) alcoholic liver injury has an increased risk of leading to loss of portal perfusion after DSRS, 2) as hepatocyte function falls, there is initial increase in hepatic arterial flow in alcoholic patients, triggered by increase in cardiac output, and 3) progressive injury and/or failure of the compensatory hemodynamic mechanism leads to earlier mortality in alcoholic patients. In contrast, the nonalcoholic cirrhosis patients preserve portal perfusion and maintain liver blood flow, both quantitatively and qualitatively, with retained hepatocyte function and improved survival.
Stenosis of a distal splenorenal shunt may lead to inadequate variceal decompression with the risk of rebleeding. We report this complication in three patients at five, 16 and 17 months after DSRS, with successful management by balloon dilation. One patient had rebled from varices and the other two showed roentgenologic evidence of inadequate variceal decompression. All of the shunts were patent but showed a mean pressure gradient of 15 millimeters of mercury which was reduced to a mean of 7 millimeters of mercury by dilation. Angiography at 15 months showed no restenosis and sustained reduction of the pressure gradient in one patient. The other two patients await long term follow-up observation. Rebleeding or reappearance of varices are indications for repeat angiography after DSRS to determine the cause. The risk of dilating a venous anastomosis must be weighed against the risk of rebleeding; the results of this report demonstrate that this can be done with a satisfactory outcome.
Five hundred four Shunt procedures have been done at Emory University Hospitals between 1971 and 1981 to decompress bleeding esophageal varices. This paper reviews how far the experiences of a prospective randomized study (55 patients) of distal splenorenal shunts against total shunts is supported by the nonrandomized experience (449 patients), and outlines our current methods of management dictated by this experience. The overall operative mortality for 348 selective shunts is 4.1% and for 156 nonselective shunts, 14.1%. The five-year survival following Selective shunt is 59%, and following nonselective shunt is 49%: more than half the selective shunt patients are alive, in contrast to the median survival of 44.5 months for patients having nonselective shunts. Following Selective shunt, the survival in nonalcoholic patients is significantly better than the median survival of alcoholic patients of 57 months. Encephalopathy, reported at three years after surgery in the randomized patients was significantly (p < 0.001) lower after selective shunt (12%) compared to nonselective shunt (52%): in the same population at seven years, all patients with patent nonselective shunts have clinical or subclinical encephalopathy, but only 30% of the selective shunt patients have subclinical encephalopathy. Shunt patency, immediately after surgery, is 93% following selective shunt, with only two documented late thromboses: nine of nine patients, at a mean of seven years, retain patency in the randomized study. Shunt occlusion increases with time after interposition nonselective shunts: seven of 13 are occluded at a mean follow-up of seven years in the randomized study. Portal venous perfusion is retained in 93% of patients seven to ten days after selective shunt, but in no patient with a patent nonselective shunt. Late portal perfusion is maintained in nine of the eleven patients in the randomized group studied at a mean of seven years after selective shunt. Restoration of portal perfusion has led to clearing of encephalopathy and improvement in hepatic function in six patients. The following conclusions are made: (1) selective shunts can be done with low operative mortality, and long-term patency with excellent control of bleeding; (2) hepatic portal venous perfusion has been maintained after selective shunt for ten years, and this is vital for preventing encephalopathy and maintaining hepatic function; (3) long-term survival after selective shunt is better than any reported series for nonselective shunt; and (4) selective shunts are the operative procedure of choice for variceal decompression and nonselective shunts should rarely be performed for elective decompression.
The incidence of thrombus formation in the portal vein following distal splenorenal shunt was 4% occlusive and 14% nonocclusive from 1974 to 1977, and 6% occlusive and 22% nonocclusive in 1980. The increased incidence was probably due to more aggressive ligation of collaterals on the portal vein. Ten patients with this complication were evaluated prospectively with clinical and biochemical parameters, angiography, and nutrient hepatic perfusion. In this group, one thrombus was occlusive immediately after operation, and nine were nonocclusive: eight of the latter resolved by six months, but one progressed to total thrombosis. There were no demonstrable adverse clinical or biochemical sequelae. Angiography showed continuing portal perfusion in the face of nonocclusive thrombus, but at six months there was increased collateral formation and significant (p less than 0.05) reduction in portal vein diameter, from 20 +/- 4 mm to 14 +/- 5 mm. Nutrient hepatic perfusion at six months, 896 +/- 257 ml/min, was not significantly different from that seen prior to operation, 848 +/- 92 ml/min. It is concluded that the natural history of nonocclusive portal vein thrombus after distal splenorenal shunt is resolution, and management should be expectant.
The aim of the emergency management of bleeding varices is to stop the hemorrhage nonoperatively if possible, avoiding emergency shunt surgery, an operation that has a higher mortality than elective shunt surgery. Patients with an upper gastrointestinal hemorrhage should undergo endoscopy immediately to verify the diagnosis of bleeding varices. They can then be categorized according to whether they stop bleeding spontaneously (group 1), continue to bleed slowly (group 2) or continue to bleed rapidly (group 3). Group 1 patients are discussed in the second part of this two-part series. Group 2 patients are initially treated with vasopressin given intravenously; those who fail to respond should undergo emergency angiography and receive vasopressin intra-arterially. If this fails, patients at low surgical risk should undergo urgent shunt surgery; those at high risk do better with endoscopic sclerotherapy. Group 3 patients are also given an intravenous infusion of vasopressin. Patients at low surgical risk who continue to bleed then receive tamponade with a Sengstaken--Blakemore tube. If this fails, they undergo emergency creation of an H-shaped mesocaval shunt. Patients at high surgical risk who fail to respond to vasopressin given intravenously are next treated intra-arterially. If this fails they are given either endoscopic or transhepatic sclerotherapy.
Patients who have previously bled from esophageal varices should have their hepatic function, neurologic status and nutritional status evaluated and should be examined for ascites before elective variceal decompression is done to prevent recurrent variceal hemorrhage. The two most important procedures used for this evaluation are liver biopsy and visceral angiography. If the liver biopsy reveals little or no necroinflammatory activity, shunt surgery is indicated. For patients with moderate or severe necroinflammatory activity, surgery is delayed until the inflammation subsides. The central aim of visceral angiography is to determine whether the patient has hepatopetal or hepatofugal portal venous flow. Patients with hepatopetal flow are treated with a selective distal splenorenal shunt. Those with hepatofugal flow are managed with a total shunt, such as an interposition H-graft portacaval or mesocaval shunt.
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Radioactivity verus time curves were generated for the first pass of technetium-99m pertechnetate through the left ventricle, kidneys, spleen and liver, after a 20 mCi peripheral intravenous bolus injection. The rate of change of radioactivity in these organs before recirculation is proportional to blood flow through the organ. The hepatic perfusion index, defined as the ratio of portal flow to total hepatic blood flow, was correlated with the angiographic grade of portal perfusion. The hepatic perfusion index in seven normal subjects was 66.0 +/- 3.4 percent (mean +/- standard error of the mean), and in 22 cirrhotic patients with decreasing angiographic perfusion of grades 1 to 4 the index was 54 +/- 4.6, 37 +/- 2.6, 17 +/- 4.7 and 3 +/- 1.1 percent, respectively. The correlation between the calculated perfusion index and the angiographic grade of portal flow was highly significant (p less than 0.001). The passage of radionuclide through the spleen differed before and after shunt surgery in patients with portal hypertension. The slope to height ratio, based on the downslope of the splenic curve, was significantly greater (p less than 0.01) in the shunted patients and provided a simple index for assessing shunt patency.
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