William J. Millikan

Nutritional consequences of total gastrectomy.

Nutritional status was investigated in 10 patients who had previously undergone total gastrectomy without evidence of malignancy. The ability of these patients to ingest and absorb adequate amounts of nutrients was examined. Metabolic balance studies were also performed to discover how effectively these patients could accumulate and use the absorbed nutrients. In the controlled hospital situation, the amount of food ingested was greater than the amount required for maintenance of Ideal Body Weight. Although mild malabsorption of fat and nitrogen was documented, weight gain and positive nitrogen balance occurred. In direct contrast, food intake significantly decreased when the patients returned to their home environment. While severe malabsorption may contribute to malnutrition in the individual patient, the most common mechanism responsible for postoperative malnutrition was inadequate intake. In the occasional patient with severe malabsorption, the universal demonstration of jejunal anaerobic bacterial overgrowth offers important therapeutic implications. The relative importance of pancreatico-biliary insufficiency in promoting malabsorption remains to be determined. Construction of a Hunt-Lawrence jejunal pouch was not found to favorably affect caloric intake, weight gain, degree of malabsorption, or dumping symptoms. Although some degree of malnutrition does result from total gastric resection, in most cases it is mild and potentially correctable. Avoidance of indicated total gastrectomy due to fears of progressive postoperative malnutrition is unwarranted.

Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Preliminary report of a prospective, randomized trial.

This paper reports the preliminary results of a prospective randomized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt (DSRS) in the management of patients with cirrhosis and variceal bleeding. Seventy-one patients have been entered; 36 have received sclerosis and 35 DSRS. Randomization of the study population was stratified on Childs A/B (56%) and Childs C (44%). Sixty-one per cent had alcoholic and 39% nonalcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p < 0.05) more frequently in patients in the sclerosis group (19 of 36: 53%) compared to DSRS (1 of 35: 3%), but only 11 of 36 (31%) were not controlled by further sclerosis and failed that therapy. Patients in whom sclerosis failed underwent surgery. Survival was significantly (p < 0.01) improved in the sclerosis group (+ surgery in 31%), with an 84% 2-year survival compared to a 59% 2-year survival in the DSRS group. Portal perfusion was significantly (p < 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p < 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p < 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: (1) has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; (2) allows significant improvement in liver function when successful; and (3) gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

Ten Years Portal Hypertensive Surgery at Emory: Results and New Perspectives

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.

A randomized, controlled trial of the distal splenorenal shunt.

In 1971 a prospective, randomized trial was initiated to determine efficacy of the distal splenorenal shunt in the management of cirrhotic patients who had previously bled from esophageal varices. When entry into the trial was terminated in 1976, 26 patients had received the distal splenorenal shunt (selective) and 29 had undergone a nonselective shunting procedure (18 interposition mesorenal, six interposition mesocaval, and five other nonselective shunts). Three operative deaths occurred in each group. Early postoperative angiography revealed preservation of hepatic portal perfusion in 14 of 16 selective patients (88%), but in only one of 20 non-selective patients (5%; p <.001). Quantitative measures of hepatic function (maximal rate of urea synthesis or MRUS and Childs score) were similar to preoperative values in the selective group but were significantly decreased in nonselective patients on the first postoperative evaluation (p <.001 for MRUS; p <.05 for Childs score). Eighty-seven per cent of selective and 81% of nonselective patients have now been followed for three to six years since surgery. Late postoperative evaluation of 29 survivors (12 selective, 17 non-selective) still shows an advantage to the selective group with respect to MRUS, Childs score, and incidence of hepatopetal portal blood flow, but differences are no longer statistically significant. However, if the seven patients with portal flow (five selective; two nonselective) are compared to the 20 with absent portal flow (seven selective; 13 nonselective), the former group has significantly higher values for MRUS (p <.05) and Childs score (p <.025). No patient with continuing portal perfusion has developed encephalopathy as compared to a 45% incidence of this complication in individuals without portal flow (p <.05). No significant differences between selective and nonselective groups have appeared with respect to total cumulative mortality (ten selective; 38%; eight nonselective, 28%), shunt occlusion (two selective, 10%; five nonselective, 18%), or recurrent variceal hemorrhage (one selective, 4%; two nonselective, 8%). Overall, significantly fewer selective patients have developed postoperative encephalopathy (three selective, 12%; 15 non-selective, 52%; p <001). Therefore, we conclude that the distal splenorenal shunt, especially when its objective of maintaining hepatic portal perfusion is achieved, results in significantly less morbidity than nonselective shunting procedures.

The Emory prospective randomized trial: selective versus nonselective shunt to control variceal bleeding. Ten year follow-up.

From 1971 to 1975, 55 patients with variceal bleeding secondary to cirrhosis were entered into a prospective randomized trial comparing distal splenorenal (selective) and H-graft interposition (nonselective) shunt. This 10-year follow-up documents that selective shunt is better (p less than 0.05) in four of the five variables monitored. Control of bleeding: selective shunt prevented variceal bleeding better than interposition shunt due to the higher (0.05 less than p less than 0.1) occlusion rate (30%) of interposition shunt. Selective shunt maintained postoperative portal perfusion better (p less than 0.01) than patent interposition shunt. Seventy-five per cent of selective shunt survivors have portal perfusion at 10 years: no patient with a patent nonselective shunt perfuses the liver. Quantitative liver function was better preserved (p less than 0.01) 10 years after selective shunt than nonselective shunt. Postoperative encephalopathy occurred in fewer (p less than 0.01) selective (27%) than nonselective (75%) shunt patients over the 10 years. Survival: in the randomized population, the improved survival in the selective shunt subgroup did not reach statistical significance. However, improved survival was confirmed in nonalcoholics. Five of eight nonalcoholics operated with selective shunt are alive at 10 years with patent shunts. No nonalcoholic, of seven total, operated with nonselective shunt survived 10 years with a patent shunt. These data show that selective shunt was superior to nonselective shunt. There was less rebleeding and encephalopathy after distal splenorenal shunt; postoperative portal perfusion and hepatic function were maintained.

Endoscopic Variceal Sclerosis Compared with Distal Splenorenal Shunt To Prevent Recurrent Variceal Bleeding in Cirrhosis: A Prospective, Randomized Trial

STUDY OBJECTIVE To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. DESIGN A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. SETTING A private, tertiary-referral university hospital. PATIENTS Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. TREATMENTS Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS AND MAIN RESULTS Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). CONCLUSIONS Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Surgical options, hematologic evaluation, and pathologic changes in Budd-Chiari syndrome

This article presents a scheme of management for Budd-Chiari syndrome based on experience with 33 patients. Therapy in acute Budd-Chiari syndrome is dictated by the liver biopsy, with hepatocyte necrosis indicating the need for placement of a decompressive shunt. The type of shunt was determined by intrahepatic vena cava obstruction; a higher morbidity rate was associated with the mesoatrial shunt in 11 patients than with a portacaval shunt in 10 patients. Successful shunt placement allowed stabilization of the liver biopsy and maintenance of good hepatocyte function [galactose elimination capacity (preoperative: 349 +/- 40 mg/minute; 20 months: 344 +/- 60 mg/minute)]. Severe fibrosis and reduced galactose elimination capacity (264 +/- 43 mg/minute) indicated advanced disease--chronic Budd-Chiari syndrome--and were indications for liver transplant. Hematologic evaluation documented a myeloproliferative disorder in 8 of the last 13 patients evaluated; perioperative and late anticoagulation and/or chemotherapy reduced recurrent thrombosis. We conclude that the Budd-Chiari syndrome requires different therapies depending on the stage of disease. If no hepatocyte injury is present on biopsy, therapy may not be needed. Acute, reversible injury can be managed by placement of a decompressive shunt. Irreversible damage requires transplantation. Selection of the right therapy requires a complete evaluation.

Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients.

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Aid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (±SD) nitrogen balance on the Casein diet at 1.5 ± 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 ± 1.2 g/day. Plasma amino acid profiles showed a significant fall (p < 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p < 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p < 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.

Hemodynamic Differences Between Alcoholic and Nonalcoholic Cirrhotics Following Distal Splenorenal Shunt—effect on Survival?

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.

Management of variceal bleeding in patients with noncirrhotic portal vein thrombosis

Since 1971, 70 patients have been seen at Emory University Hospital with gastroesophageal varices secondary to extrahepatic portal vein thrombosis (PVT). Thirty-seven of these patients had had prior major operative therapy. In only three patients (8%) was shunt surgery successful, and there was a high incidence of rebleeding, other morbidity, and mortality. Of especial note are the serious consequences of simple splenectomy; splenomegaly and thrombycytopenia should rarely, if ever, be used as indication for splenectomy in portal hypertension. In 1977, the use of selective distal splenorenal shunt (DSRS) was begun at Emory in this population and a selective shunt has been possible in 24 of 29 patients (83%) who had had no prior operative therapy. Results have been excellent with a greater than 90% patency rate, long-term portal perfusion in all, no encephalopathy, and late rebleeding in one patient. Quantitative studies at 3–6 years show stability of liver function, significant decrease in spleen size, and rise in platelet count. However, long-term follow-up (>15 years) is required in PVT patients before definitive assessment can be obtained. A specific problem of the PVT patient is late shunt stenosis which requires close observation; dilatation of the shunt was performed in six of the 24 patients with a patent shunt. Poor results with non-shunt operative procedures in PVT were again documented. The proper role of endoscopie variceal sclerotherapy is not yet clear, but appears to be an excellent addition to the therapeutic options. In conclusion, for patients with a patent splenic vein, initial therapy should be a selective shunt; for patients without a patent splenic venous system, endoscopie sclerotherapy is the procedure of choice.