J. Michael Henderson

Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases

Objective:To examine recurrence and survival rates for patients treated with hepatic resection only, radiofrequency ablation (RFA) plus resection or RFA only for colorectal liver metastases. Summary Background Data:Thermal destruction techniques, particularly RFA, have been rapidly accepted into surgical practice in the last 5 years. Long-term survival data following treatment of colorectal liver metastasis using RFA with or without hepatic resection are lacking. Methods:Data from 358 consecutive patients with colorectal liver metastases treated for cure with hepatic resection ± RFA and 70 patients found at laparotomy to have liver-only disease but not to be candidates for potentially curative treatment were compared (1992–2002). Results:Of 418 patients treated, 190 (45%) underwent resection only, 101 RFA + resection (24%), 57 RFA only (14%), and 70 laparotomy with biopsy only or arterial infusion pump placement (“chemotherapy only,” 17%). RFA was used in operative candidates who could not undergo complete resection of disease. Overall recurrence was most common after RFA (84% vs. 64% RFA + resection vs. 52% resection only, P < 0.001). Liver-only recurrence after RFA was fourfold the rate after resection (44% vs. 11% of patients, P < 0.001), and true local recurrence was most common after RFA (9% of patients vs. 5% RFA + resection vs. 2% resection only, P = 0.02). Overall survival rate was highest after resection (58% at 5 years); 4-year survival after resection, RFA + resection and RFA only were 65%, 36%, and 22%, respectively (P < 0.0001). Survival for “unresectable” patients treated with RFA + resection or RFA only was greater than chemotherapy only (P = 0.0017). Conclusions:Hepatic resection is the treatment of choice for colorectal liver metastases. RFA alone or in combination with resection for unresectable patients does not provide survival comparable to resection, and provides survival only slightly superior to nonsurgical treatment.

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.

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

STUDY OBJECTIVEnTo define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis.nnnDESIGNnA prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months.nnnSETTINGnA private, tertiary-referral university hospital.nnnPATIENTSnSeventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval.nnnTREATMENTSnEndoscopic variceal sclerosis or distal splenorenal shunt.nnnMEASUREMENTS AND MAIN RESULTSnSurvival 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).nnnCONCLUSIONSnEndoscopic 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.

Surgical Versus Nonsurgical Management of Pancreatic Pseudocysts

Goals Compare patient characteristics and outcome and also physician referral patterns between surgically and nonsurgically managed patients with pancreatic pseudocysts. Background Treatment of pancreatic pseudocysts can be accomplished by surgical, endoscopic, or percutaneous procedures. The ideal treatment method has not yet been defined. Patients All patients treated for pancreatic pseudocyst between 1999 and 2005 were identified in our health services database. Patients were treated with surgical, endoscopic, and percutaneous drainage procedures at the discretion of the treating physician. Main outcome measures included complications, pseudocyst resolution, and treatment modality as a function of the treating physicians specialty. Results Thirty patients (49%) were treated surgically, 24 endoscopically (39%), and 7 (11%) with percutaneous drainage. The most common indications for treatment were symptoms of pain, and biliary or gastric outlet obstruction (81%). Patients treated surgically and endoscopically were similar in terms of age (49 vs. 52u2009y), mean cyst diameter (9.1 vs. 9.5u2009cm, P=0.74), incidence of chronic pancreatitis (50% vs. 32%, P=0.26) and complicated pancreaticobiliary disease (69% vs. 60%). There were no differences in complications (20% vs. 21%) or pseudocyst resolution (93.3% vs. 87.5%, P=0.39) between the surgical and endoscopic groups. There was no significant difference in the rate of surgical versus nonsurgical treatment in patients initially evaluated by surgeons versus nonsurgeons. Conclusions Surgical and endoscopic interventions for pancreatic pseudocysts are equally safe and effective with percutaneous drainage playing a less important role. Endoscopic drainage should be considered for initial therapy in appropriate patients.

Reversal of hepatic encephalopathy after occlusion of total portasystemic shunts

Abstract In conclusion, therefore, we recommend selective distal splenorenal shunt for patients with hepatopetal flow and nonselective total portasystemic shunt for most patients with hepatofugal flow in order to minimize the incidence of postshunt encephalopathy. Patients with hepatopetal flow who are treated by a nonselective shunt and develop chronic, refractory encephalopathy are candidates for shunt ligation if they have good liver function.

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.

Hepatic abscess after liver transplantation: 1990-2000.

Background. Infections following solid-organ transplants are a major cause of morbidity and mortality. Few studies have reported the complications of hepatic abscesses. Methods. This investigation consisted of a retrospective chart review of all solid-organ transplant recipients from 1990 to 2000. Criteria for diagnosis included parenchymal hepatic lesions, positive cultures from liver aspirates or blood cultures, or both, and a compatible clinical presentation. Results. Of 2175 recipients of all organ transplants (heart, lung, kidney, liver, pancreas), we identified 12 patients who had experienced 14 episodes of hepatic abscess, all in liver transplant recipients. Median time from transplant to hepatic abscess was 386 days (range 25–4198). The most common predisposing factor was hepatic artery thrombosis (HAT), which occurred in eight patients, and was diagnosed at an average of 249 days (range 33–3215) after transplantation. Clinical presentation of hepatic abscess was similar to that described in non-immunosuppressed patients. All but one patient showed hypoalbuminemia (<3.5 g/dL); those with HAT also had significantly elevated lactate dehydrogenase. Liver aspirates grew gram-positive aerobic bacteria (50% of isolates), gram-negative aerobic bacteria (30%), and anaerobes and yeasts (10% each). Patients received an average of 6 weeks of intravenous antibiotic therapy. Catheter drainage was successful in 70% of cases; and five patients required retransplantation. Altogether, five of the patients died, yielding a mortality rate of 42%. Conclusions. Hepatic abscess, a rare complication after liver transplantation, was frequently associated with hepatic artery thrombosis. Mortality was higher than in patients who had not undergone transplantation. Prolonged antibiotic therapy, drainage, and even retransplantation may be required to improve the outcome in these patients.

Vitamin B6 Metabolism by Human Livera

The B6 vitamers (pyridoxine, pyridoxamine, and pyridoxal) are primarily metabolized in liver to pyridoxal 5-phosphate (PLP) and the deadend catabolite 4-pyridoxic acid. We have built on the elegant early work of Snell and others to describe the activities of the human liver enzymes responsible for vitamin B6 metabolism and to develop a model of the relative rates of these interconversions in vivo. This model is consistent with changes in plasma B6 after a load, the clearance of different vitamers (e.g., pyridoxine versus pyridoxal), and with the low plasma PLP in patients with cirrhosis. Because cirrhotics were found to be capable of PLP synthesis, we have used oral supplementation with pyridoxine to restore plasma PLP to the normal range, and have evaluated the effects of this intervention on amino acid metabolism. No significant differences were observed in plasma or urinary clearance of methionine (or cystathionine) after an oral load, nor in amino acid clearance from circulation after a protein load for cirrhotic patients before and after restoration of normal plasma PLP. Hence, the abnormal metabolism of vitamin B6 does not appear to be an important factor in the deranged amino acid metabolism in this disease. Nonetheless, this approach may be generally useful in assessing the importance of PLP in other abnormalities.

Analysis of Twenty-three Plasma Proteins in Ascites The Depletion of Fibrinogen and Plasminogen

The concentrations of 23 plasma proteins were measured by radial immunodiffusion in the plasma and ascites of 17 patients with cirrhosis and four patients with intraperitoneal malignancies, to learn whether there is a selectivity in the movement of proteins from plasma into ascites, analogous to that of proteinuria. Additionally, since some of the proteins are involved in coagulation, we hoped to clarify the coagulopathy frequently seen following peritoneovenous shunting of ascites. Analysis was by groups: group 1 consisted of nine patients with cirrhosis with an ascites-total protein content less than 2.5 g/dl; group 2 consisted of eight patients with cirrhosis with ascites-total protein content greater than or equal to 2.5 g/dl; and group 3 consisted of four patients with malignant ascites. The ratio of the plasma concentration/ascites concentration ([P]/[A]) for each protein was calculated for each patient. In each group the median [P]/[A] for each protein was plotted against the natural logarithm of its molecular weight (In MW). For 21 of the 23 proteins, [P]/[A] showed a close linear relationship to In MW. Fibrogen and plasminogen showed significant (p < 0.0002) elevation above the regression line relating [P]/[A] to In MW. This indicates depletion of fibrinogen and plasminogen in ascites. The ascites in group 1 showed moderate selectivity, defined as the slope of the regression line (1.59), while groups 2 and 3 were essentialy nonselective (0.35 and 0.50). Fibrin-split products were elevated in all ascites but not in plasma, indicating either fibrinolysis or fibrinogenolysis within the ascites. A normal ratio for prothrombin suggests fibrinogenolysis may be the dominant mechanism. Thus the coagulopathy induced by LeVeen valve insertion may be in part secondary to the infusion of plasmin or a plasminogen activator into the circulation.