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Biomedical subjects

W D Warren

Publications and source records attributed to W D Warren.

At least 55 records · Page 3Linked to original sources

Recent advances in the management of variceal bleeding.

A prospective randomized trial of selective distal splenorenal shunt (DSRS) versus H-graft interposition total shunt at Emory Hospital in 1971 showed DSRS to be superior to a total shunt in shunt patency, prevention of variceal bleeding, preserving hepatic cell function, preserving the quality of life and patient survival. These results were particularly evident in the non-alcoholic patients. In the alcoholic patients, there was a greater loss of hepatic portal perfusion. In a later phase of the study, it was found that pancreatic veins formed a pathway of collaterals to the shunt, that is a so-called pancreatic siphon. In order to prevent loss of portal and pancreatic flow through the siphon, a total spleno-pancreatic disconnection was developed, whereby the hormone diversion is expected to be diminished.

Esophageal and Gastric Varices↗

A method of measuring quantitative hepatic function and hemodynamics in cirrhosis: the changes following distal splenorenal shunt.

Quantitative measurement is required to define the severity of chronic liver disease and the effects of therapy on its complications. This paper presents a method of such assessment based on measurement of hepatocyte function, liver volume, functional liver blood flow, portal perfusion and cardiac output. Data are presented on 54 patients evaluated prior to, and one year after DSRS for variceal bleeding. Preoperative testing showed that alcoholics (n = 24) had significantly (p less than 0.05) larger liver and smaller spleen volumes than nonalcoholic cirrhotics (n = 22) and patients with portal vein thrombosis (n = 8), but that the other parameters were not significantly different by etiologies. At one year after DSRS: all groups showed a significant (p less than 0.01) reduction of 41 per cent in spleen size: liver volume was significantly (p less than 0.05) reduced in cirrhotics: there was a significantly (p less than 0.01) greater loss of portal perfusion in alcoholic cirrhosis: liver blood flow showed a significant (p less than 0.05) rise in alcoholics when compared to nonalcoholics and portal vein thrombosis patients: cardiac output rose in alcoholic cirrhosis: hepatocyte function was not significantly different in any group. This study shows that in patients all doing well clinically one year after DSRS, there are markedly different hemodynamic responses. Further studies on cirrhosis aimed at improving therapy for its complications should include some objective, quantitative assessment, first to define the study population, and second to measure the effect of the therapy.

Cardiac Output↗

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 Child's A/B (56%) and Child's C (44%). Sixty-one per cent had alcoholic and 39% non-alcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p less than 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 less than 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 less than 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p less than 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p less than 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; allows significant improvement in liver function when successful; and gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

Acute Disease↗

Denervated splenopancreatic flap for chronic pancreatitis.

Various surgical procedures have addressed the disabling pain of chronic pancreatitis. Pain control must be weighed against the surgical morbidity and metabolic consequences of operation. Although ductal drainage works well for patients with dilated ducts, a new procedure was devised to avoid the diabetic morbidity of near-total pancreatectomy or pancreaticoduodenectomy in patients with small duct pancreatitis. Five patients have undergone the splenopancreatic flap procedure. The head of the pancreas is resected in a manner similar to near-total pancreatectomy, while the body and tail are denervated by dissection from their bed, with retrograde perfusion from the splenic hilus. All patients are alive a mean of 9 months after operation, and none is diabetic. Only one patient requires narcotic analgesics. Although none is asymptomatic, all have shown significant weight gain, and four of five are vocationally rehabilitated. Flap viability and the absence of transgastric varices have been documented by angiography and CT scanning. Although the durability of pain relief and islet cell function is unknown, these results suggest that this procedure may offer an alternative to major resection in chronic pancreatitis.

Adult↗

Splenopancreatic disconnection. Improved selectivity of distal splenorenal shunt.

UNLABELLED: Distal splenorenal shunt (DSRS) improves survival from variceal bleeding in nonalcoholic cirrhotics but not in alcoholic subjects. The metabolic response after DSRS is also different in alcoholic and nonalcoholic cirrhotics. Portal perfusion, quality of blood perfusing the liver, cardiac output, and liver blood flow do not change in nonalcoholics. In alcoholics, portal perfusion is frequently lost (60%), quality of blood perfusing the liver decreases, and cardiac output and liver blood flow increase. It is proposed that portal flow is lost in alcoholics via pancreatic and colonic collaterals after surgery. Elimination of this sump by adding complete dissection of the splenic vein and division of the splenocolic ligament to DSRS (splenopancreatic disconnection, SPD) could preserve portal perfusion, decrease shunt loss of hepatotrophic factor, and improve survival in alcoholic cirrhotics. This report compares data 1 year after surgery in two groups of cirrhotics: group I (8 nonalcoholic; 16 alcoholic) had DSRS without SPD; group II (17 nonalcoholic; 11 alcoholic) received DSRS + SPD. METHODS: Portal perfusion grade, cardiac output (CO), liver blood flow (f), hepatic function (GEC), and hepatic volume (vol) were measured before and 1 year after surgery. Shunt loss of hepatotrophic factor was estimated by insulin response (change in plasma concentration over 10 minutes: AUC) after arginine stimulation. RESULTS: Groups I and II were similar before surgery. Metabolically, nonalcoholics remained stable after both DSRS and DSRS + SPD. After standard DSRS, alcoholics lost portal perfusion (75%, p less than 0.05), CO, and f increased (p less than 0.05), and quality of blood perfusing the liver was decreased (GEC/f: p less than 0.05). DSRS + SPD preserved portal perfusion better (p less than 0.05) in alcoholic cirrhotics than did DSRS alone. After DSRS + SPD, the metabolic response in alcoholics resembled that of nonalcoholics. CO, f, and GEC/f remained stable. These data show: DSRS + SPD preserves postoperative portal perfusion in alcoholic cirrhotics better than DSRS alone. Metabolic response to DSRS + SPD is similar in alcoholic and nonalcoholic cirrhotics. Because portal perfusion and metabolic integrity are preserved after DSRS + SPD, its use in alcoholic cirrhotics should improve survival.

Cardiac Output↗

Approach to the spectrum of Budd-Chiari syndrome: which patients require portal decompression?

Budd-Chiari syndrome (occlusion of the hepatic veins) represents a spectrum disorder. From 1974 to 1984, 20 patients with the syndrome were managed. Eleven required shunt surgery (Group 1) and 5 were managed with nonshunt therapy (Groups 2 and 3). Results have been good. Retrospective review of the liver biopsy specimens showed that Group 1 patients had a greater degree of zone 3 necrosis than Group 2 and 3 patients. We submit that presence of zone 3 necrosis on an initial liver biopsy specimen may define the failing liver of Budd-Chiari syndrome that requires conversion of the portal vein to an outflow tract by shunting.

Adult↗

Portaprival collaterals following distal splenorenal shunt. Incidence, magnitude and associated portal perfusion changes.

Collateral venous pathways develop between the high pressure portal vein and low pressure splenic vein following distal splenorenal shunt. This review of angiography in 50 patients with cirrhosis prior to and 1 year after DSRS shows that 98% developed collaterals: 72% transpancreatic, 48% transgastric, and 46% colonic. Multiple pathways developed in 64% of patients. Grading of the size of these collaterals showed that in 74% these exceeded the size of the portal and/or superior mesenteric vein. The effect of these collaterals on portal perfusion showed that 32% lost perfusion at 1 year, but significantly (P less than 0.05) more alcoholics (48%) lost perfusion than nonalcoholics (16%). The size, site and number of collaterals was not different between etiologies. Late follow-up in a subset of 32 of the patients showed no change in the site, and minimal increase in size of the collaterals at 3-11 years, with no further loss of portal perfusion. We conclude that virtually all patients develop collaterals after DSRS, these are along predictable pathways and are of significant size in the majority. However, development of collaterals per se does not equate to loss of portal venous flow, and a stable pattern is set in the first year after shunt. Characterization of these pathways will permit new approaches to minimizing their development.

Angiography↗

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.

Clinical Trials as Topic↗

Splenectomy is contraindicated for thrombocytopenia secondary to portal hypertension.

We believe that splenectomy is contraindicated in patients with portal hypertension and secondary hypersplenism. The greatest threat to life in this group of patients is variceal bleeding, and the primary consideration in the management of these patients should be to control this bleeding. Concomitant improvement in the hematologic indices of hypersplenism is achieved by DSRS.

Hematocrit↗

In vivo measurement of leucine metabolism with stable isotopes in normal subjects and in those with cirrhosis fed conventional and branched-chain amino acid-enriched diets.

Low plasma levels of branched-chain amino acids, leucine, isoleucine, and valine are postulated to play an etiologic role in hepatic encephalopathy. Supplementation is advocated to reverse encephalopathy and improve nutritional status and survival. We measured in vivo leucine metabolism in normal individuals (n = 5) and in two groups of patients with cirrhosis (n = 8) with a primed continuous infusion of L-[15N, 1-13C] leucine to quantitate the following parameters of leucine metabolism: nitrogen and carbon fluxes, oxidation, contribution to protein synthesis, breakdown of endogenous protein to leucine, deamination and reamination to/from ketoisocaproate. Studies were performed in the fasting and fed states with a conventional enteral diet (Propac) and a branched chain-enriched diet (one third Propac plus two thirds Hepatic-Aid). In vivo leucine metabolism was similar in the fasting and fed states in normal individuals in patients with cirrhosis and with both diets when studied at a protein intake of 0.6 gm/kg ideal body weight/day. When fed these diets, oxidation increased (p less than 0.05) and breakdown decreased (p less than 0.05). The Hepatic-Aid diet increased (p less than 0.05) nitrogen and carbon fluxes significantly more than did the standard diet. Four additional patients with cirrhosis on a diet with more protein were studied (0.75 gm/kg ideal body weight/day). Carbon and nitrogen fluxes, oxidation, synthesis, and deamination were increased (p less than 0.05) when patients with cirrhosis were fed the Propac diet compared with those who fasted. The Hepatic-Aid diet further increased (p less than 0.05) all parameters except synthesis and did not decrease protein breakdown. These data show that patients with cirrhosis metabolize leucine in vivo in a manner identical to that of normal subjects and that leucine-enriched formulas increase oxidation to CO2 without improving protein synthesis.

Adult↗

Peritoneovenous shunts. Lessons learned from an eight-year experience with 70 patients.

The peritoneovenous shunt (PVS) is preferred over other treatment modalities in the treatment of the cirrhotic patient who has intractable ascites. The favorable effects on nutrition, pulmonary, and renal function, in addition to prompt control of ascites, frequently overshadow potentially life-threatening complications. We summarized our experience with the PVS in 70 patients with portal hypertension at Emory University, Atlanta, and identified the perioperative complications and operative mortalities. Late complications of sepsis and variceal hemorrhage were frequent and often were fatal. Of the multiple preoperative clinical and laboratory determinants, only the serum bilirubin level (greater than or equal to 3 mg/dL) was predictive of the operative mortality and longevity of survivors. The PVS should be reserved for patients with disabling, truly refractory ascites.

Adolescent↗

Selective variceal decompression in portal vein thrombosis.

Thirty-two patients with congenital portal vein thrombosis have been managed for bleeding gastro-oesophageal varices. Fifteen had splenectomy and/or other therapy before referral: nine were managed by endoscopic sclerosis, four by devascularization and two by total shunt; six rebled. Seventeen had their spleen 'in situ' at referral and were evaluated for selective shunt: thirteen had distal splenorenal shunts (DSRS)--one transiently rebled despite a patent shunt and one had shunt thrombosis; four had no veins suitable for shunt, and were managed by splenectomy and devascularization, with two rebleeds. Detailed study of seven patients before, and 1 year after DSRS, showed a rise in platelet count, maintenance of hepatocyte function, portal perfusion, liver blood flow and liver size. The spleen showed a significant (P less than 0.025) reduction in size with trans-splenic decompression. We conclude that DSRS provides an excellent method for long-term control of bleeding in such patients, without alteration of liver function or haemodynamics. Patients managed by splenectomy and direct ablative procedures have a significantly (P less than 0.05) greater risk of rebleeding than patients receiving DSRS.

Adolescent↗

Emergency distal splenorenal shunts for variceal hemorrhage refractory to nonoperative control.

Two points are emphasized by this report. First, every attempt should be made to control acute variceal hemorrhage nonoperatively. Such control can be gained in about 80 percent of patients, allowing for a period of stabilization of liver disease, correction of coagulation defects, and nutritional repletion. Operative mortality then becomes equivalent to that in other elective candidates. Second, when necessary, because of ongoing hemorrhage in the face of maximal nonoperative therapy, selective shunting can be accomplished on an emergency basis. In our study, it resulted in a 70 percent survival rate and excellent protection against recurrent variceal hemorrhage with long-term maintenance of portal perfusion in 89 percent of the patients.

Adult↗

Selective variceal decompression after splenectomy or splenic vein thrombosis. With a note on splenopancreatic disconnection.

Eight patients have had selective variceal decompression after a splenectomy or splenic vein thrombosis with successful control of bleeding. The principle veins utilized in these patients, either alone or in combination, were: (a) the splenic remnant, (b) the coronary, (c) the gastroepiploic, and (d) an inferior mesenteric that joined the splenic. High quality preoperative angiography is essential but operative exploration is often required to assess fully the possible shunt options. Simple splenectomy for thrombocytopenia in portal hypertension is rarely justifiable and creates far more problems than it solves. Complete splenopancreatic disconnection extends the selective shunt concept.

Adolescent↗

Distal splenorenal shunt in treatment of bleeding esophageal varices in renal transplant recipients.

We conclude from this study that bleeding esophageal varices may occur as a late complication of liver disease associated with chronic renal failure and renal transplantation. In two of the three patients reported upon, the liver disease was probably determined on the basis of cirrhosis, secondary to chronic, active hepatitis from non-A, non-B hepatitis, while the third patient had hepatic fibrosis. Such bleeding is best controlled by selective variceal decompression with a DSRS. Finally, it is technically feasible to perform a DSRS upon some patients following a left nephrectomy, and the renal vein is of adequate caliber even in the presence of nonfunctioning kidneys.

Adult↗

Two stage surgical management of the Budd-Chiari syndrome associated with obstruction of the inferior vena cava.

A new, staged surgical approach to the treatment of Budd-Chiari syndrome complicated by inferior vena caval obstruction has been described. The first stage consists of a mesoatrial shunt. After an interval to allow hepatic decongestion, re-establishment of caval flow and overall improvement in the status of the patient, a portacaval shunt is established and the mesoatrial shunt removed. Such a staged procedure produced an excellent result in the patient reported upon in this study and represents a treatment option in similar patients with Budd-Chiari syndrome complicated by obstruction of the inferior vena cava.

Adult↗