Are the favorable outcomes of splenectomy predictable inpatients with idiopathic thrombocytopenic purpura (ITP)?

BACKGROUND: Historically, splenectomy has been an accepted procedure in the management of immune thrombocytopenic purpura (ITP). However, it is also true that the response to splenectomy in patients with ITP seems to be unpredictable. Therefore, the purpose of this study was to identify clinical variables that might predict a favorable response to splenectomy in patients with ITP. METHODS: Data were collected retrospectively for 40 adult patients with ITP who underwent laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between 1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease duration, comorbidities (ASA > 2), previous response to steroids and/or other medications, and preoperative platelet count were analyzed by univariate (t-test, Fisher's exact test) and multivariate statistical methods. RESULTS: Of the 20 patients in each group, improved platelet counts were noted in 18 patients (90%) in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3 months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84% and 87.5% sustained response rates, respectively. After univariate analysis, two variables (age and disease duration) were found to be significantly related to the outcome of splenectomy (p

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients.

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.

The role of tissue expansion in abdominal wall reconstruction.

Abdominal wall reconstruction of ventral hernia defects with loss of visceral domain and inadequate soft-tissue coverage presents a surgical challenge. Four patients with large, skin grafted ventral hernia defects were treated by staged abdominal wall reconstruction. During the initial stage, tissue expanders were placed under the skin and subcutaneous tissue lateral to the defects. After adequate interval expansion, the second stage was performed. The expanders were removed, the visceral contents reduced easily, and the fascia reapproximated with polypropylene mesh. The expanded skin was closed easily over the fascial repair. All four patients were reconstructed successfully without complications. Tissue expansion can restore abdominal domain and allow soft-tissue closure in complicated ventral hernia defects.

Management of pancreatic pseudocysts.

BACKGROUND: Operative internal drainage has been standard treatment for chronic unresolved pancreatic pseudocysts (PPs). Recently, percutaneous external drainage (PED) has become the primary mode of treatment at many medical centers. STUDY DESIGN: A retrospective chart review was performed of 96 patients with PPs who were managed between 1987 and 1996. Longterm followup information was obtained by telephone and mail questionnaire. RESULTS: Twenty-seven patients underwent computed tomographic (CT)-guided PED. PP resolution occurred in 17 patients. Clinical deterioration or secondary infection mandated urgent pancreatic debridement in 7 (26%) patients and cystgastrostomy in 2 (7%) patients. There was one hospital death in this group. Thirty-two patients underwent cystgastrostomy or cystjejunostomy (n = 21), distal pancreatectomy (n = 8), pancreatic debridement and external drainage (n = 2), or cystectomy (n = 1). Two (6%) patients required postoperative pancreatic debridement for failure of resolution and peritonitis and two patients underwent PED of abscess. There was one hospital death in the expectantly managed group of 37 patients. Median followup of 3 years (range, 0.5-9.3 years) in 66 patients revealed that 6, 3, and 4 patients of PED, surgery, and expectantly managed groups, respectively, had radiologic evidence of recurrent PPs. CONCLUSIONS: Operative management for PPs appears to be superior to CT-guided PED. Although the later was often successful, it required major salvage procedures in one third of the patients. An expectant management protocol may be suitable for selected patients.

Conversion of failed transjugular intrahepatic portosystemic shunt to distal splenorenal shunt in patients with Child A or B cirrhosis.

OBJECTIVE: The authors demonstrate the feasibility of converting failed transjugular intrahepatic portosystemic shunt (TIPS) to distal splenorenal shunt (DSRS) in patients with good hepatic reserve for long-term control of variceal bleeding. SUMMARY BACKGROUND DATA: TIPS is an effective method for decompressing the portal venous system and controlling bleeding from esophageal and gastric varices. TIPS insufficiency is, however, a common problem, and treatment alternatives in patients with an occluded TIPS are limited because most have already failed endoscopic therapy. METHODS: The records of five patients who underwent conversion from TIPS to DSRS because of TIPS failure or complication in the past 36 months were reviewed. RESULTS: Four patients had ethanol-induced cirrhosis and one patient had hepatitis C virus cirrhosis. Three patients were Child-Pugh class A and two were class B. All patients had excellent liver function, with galactose elimination capacities ranging from 388 to 540 mg/min (normal 500 +/- 100 mg/min). The patients had TIPS placed for acute (2) or sclerotherapy-resistant (3) variceal hemorrhage. All five TIPS stenosed 3 to 23 months after placement, with recurrent variceal hemorrhage and failed TIPS revision. One patient had stent migration to the superior mesenteric vein that was removed at the time of DSRS. All five patients underwent successful DSRS, and none have had recurrent hemorrhage 18 to 36 months after surgery. CONCLUSIONS: TIPS provides inadequate long-term therapy for some Child-Pugh A or B patients with recurrent variceal hemorrhage. TIPS failure in patients with good liver function can be salvaged by DSRS in many cases.

Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans.

The pharmacokinetics and utilization (flavocoenzyme synthesis) of orally and intravenously administered riboflavin in healthy humans were assessed. After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females (control period), each of these subjects received three different oral riboflavin doses (20, 40, and 60 mg) and one intravenous bolus injection of riboflavin (11.6 mg). Vitamins were administered in a randomized, cross-over design with 2 wk between each administration. Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration. Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma; riboflavin was assayed in urine. During the control period, a small circadian variation was observed: plasma concentrations and urinary excretion of riboflavin were low during the afternoon (P < 0.05). Pharmacokinetics were calculated using a two-compartment open model. The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult. Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration (P < 0.01). Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations. 7 alpha-Hydroxyriboflavin was identified in plasma. Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma. No sex differences were observed for any of the pharmacokinetic variables (P > 0.05).

The identification and kinetics of 7 alpha-hydroxyriboflavin (7-hydroxymethylriboflavin) in blood plasma from humans following oral administration of riboflavin supplements.

Following the administration of different oral (20, 40, 60 mg) and intravenous (11.6 mg) doses of riboflavin to healthy humans and female patients with liver cirrhosis (oral 40-mg dose), 7 alpha-hydroxyriboflavin (7-hydroxymethylriboflavin) was identified in blood plasma by fluorescence after high-performance liquid and thin-layer chromatographies, and by its absorbance spectrum. The apparent first-order absorption rate constant of 7 alpha-hydroxyriboflavin was 1.2 per hour in healthy subjects. Plasma peak concentrations of 40 nmol/l in males and 20 nmol/l in females (p < 0.01) were achieved within two hours. Peak concentrations and areas under the plasma curves (smaller in females, p < 0.01) of 7 alpha-hydroxyriboflavin were 5 to 16% of those observed for riboflavin. Healthy females showed an approximately 2.5-fold faster disposition of 7 alpha-hydroxyriboflavin from plasma than males (p < 0.01). Correction of peak concentrations and areas under the plasma curves by the rate constants of disposition led to the finding of approximately equal amounts of 7 alpha-hydroxyriboflavin released into plasma by both sexes (p > 0.05). No significant influence of different oral riboflavin doses on 7 alpha-hydroxyriboflavin kinetics was found (p > 0.05). Liver cirrhosis had no significant effect on the amount of 7 alpha-hydroxyriboflavin released into blood plasma (p > 0.05). However, the failure to detect this metabolite following intravenous riboflavin administration indicates a substantial influence of gastrointestinal- or liver-passage.

The metabolism of riboflavin in female patients with liver cirrhosis.

The metabolism of vitamin B2 was studied in five female patients with liver cirrhosis of varying etiology. Following the oral administration of 40 mg (106.3 mumol) riboflavin, plasma concentrations of riboflavin and flavo-coenzymes as well as urinary riboflavin excretion were analyzed over a period of 48 h. Results were compared to data obtained for healthy controls (Zempleni J. et al, Am. J. Clin. Nutr., 1996 [15]). About 18% of the administered vitamin was recovered from patients' urine, indicating an absorption similar to healthy subjects (p > 0.05). The area under the riboflavin plasma concentration vs time curve was 1.2-fold larger among patients than controls, but the difference was not significant (p > 0.05). Riboflavin peak concentrations in plasma (315.6 nmol/l) and times when those concentrations were achieved (3.0 h) were similar to those found for healthy subjects (p > 0.05). Flavocoenzyme peak plasma concentrations were increased 1.4-fold above their baseline levels in cirrhotics which was equal to controls (p > 0.05). 7 alpha-Hydroxyriboflavin was detected in the plasma of patients. Distribution and elimination kinetics of riboflavin were analyzed by using a two-compartment open model; the riboflavin plasma disposition rate constants of the patients (k alpha = 0.7232 h-1; k beta = 0.0627 h-1) were not different from controls (p > 0.05). No differences between both groups were found regarding renal excretion (renal clearance, first-order rate constants for renal excretion; p > 0.05). In conclusion, patients with liver cirrhosis of varying etiology and varying medical treatment did not show alterations of riboflavin turnover.

Salvage of colon interposition by antethoracic free jejunal transfer.

Intrathoracic disruption of an esophagocolonic anastomosis after colon interposition can be a fatal complication. A case is presented in which an antethoracic free jejunal transfer achieved successful salvage. The patient returned to oral alimentation with no functional impairment.

Pediatric liver transplantation in Georgia: a paradigm for the health care crisis in the United States?

The United States health care system, felt by many to be the most technologically advanced program in the world, has many critics. Two indisputable facts that drive such criticism are 1) inequitable access and 2) rising costs out of proportion to other countries. Although Georgia is a poor state and ranks nationally near the bottom in most measures of child and adolescent care, we decided to start a pediatric liver transplant program at Egleston Children's Hospital at Emory, Atlanta. Over the past 2 1/2 years, 18 transplants have been performed in 14 patients; 10 children are presently surviving. Looking carefully at the expenses of the first 10 patients, the average cost of orthotopic liver transplantation for the eight survivors was $206,375. The hospital costs for providing care to these 10 children were over $2 million. In a state that ranks 49th out of 50 states in infant mortality and with nearly one-third of its pre-school children not immunized against preventable diseases, is this a fair and equitable distribution of our resources?

The effect of propranolol on portal perfusion in patients with alcoholic cirrhosis having distal splenorenal shunt.

This study tested the hypothesis that reduction in the hyperdynamic systemic circulation with propranolol in patients with alcoholic cirrhosis and distal splenorenal shunt would lead to improved maintenance of portal perfusion. After standard distal splenorenal shunt, 50-75% of patients with alcoholic cirrhosis lose portal flow in 6-12 months: this is associated with an increased hyperdynamic systemic circulation. Twelve patients with alcoholic cirrhosis with distal splenorenal shunt received propranolol in a dose sufficient to provide beta blockade. Pulse was reduced by 25%, cardiac output reduced by 32% and hepatic venous pressure gradient reduced by 15% (p < 0.05). These significant hemodynamic changes with propranolol did not lead to any improvement in the maintenance of portal perfusion: overall, 66% of patients lost prograde portal flow within 1 year. We conclude that the hyperdynamic systemic circulation is not the primary mediator of loss of portal perfusion in this group of patients. Rather, it appears that differences in either intrahepatic resistance or collateral pathway (portal vein to shunt) resistance must account for the different patterns or maintenance of portal perfusion after distal splenorenal shunt.

Malignant hepatic tumors: safety of high-dose percutaneous ethanol ablation therapy.

The authors retrospectively analyzed clinical records to determine the safety and complication rate of percutaneous ethanol ablation therapy with more than 10 mL of ethanol administered per session for treatment of malignant hepatic tumors. Ten patients underwent a total of 35 sessions with 10 mL or more of ethanol, and four underwent 18 sessions with 10 mL or less. No serious complications occurred with any dose. Pain and fever were the most common complications at all doses, and the higher frequency of these at larger ethanol volumes may be related to the greater degree of tumor necrosis induced by the larger volume.

Hemodynamics during liver transplantation: the interactions between cardiac output and portal venous and hepatic arterial flows.

Liver blood flow and systemic hemodynamics were measured intraoperatively in 34 patients after liver transplantation. Ultrasound transit-time flow probes measured hepatic arterial and portal venous flow over 10 to 75 min 1 to 3 hr after reperfusion. Cardiac output was measured by thermodilution. Mean cardiac output was 9.5 +/- 2.8 L/min; the mean total liver blood flow of 2,091 +/- 932 ml/min was 23% +/- 11% of cardiac output. Mean portal flow of 1,808 +/- 929 ml/min was disproportionately high at 85% +/- 10% of total liver blood flow. Correlation analysis showed a significant (p less than 0.01; r = 0.42) correlation between cardiac output and portal venous flow and a trend toward negative correlation (p = 0.087) between cardiac output and hepatic arterial flow. These data show that increased flow in the newly transplanted liver is predominantly portal venous flow and is associated with high cardiac output and reduced hepatic arterial flow. In the last 13 patients studied, portal flow was reduced by 50% and the hepatic artery response was measured. We saw a significant (p less than 0.05) increase in hepatic artery flow from 322 +/- 228 to 419 +/- 271 ml/min, indicating an intact hepatic arterial buffer response. The hepatic artery response also showed that it is a reversible rather than a fixed resistance that contributes to the low hepatic artery flow in these patients.

Selective shunt in the management of variceal bleeding in the era of liver transplantation.

This study reports the Emory experience with 147 distal splenorenal shunts (DSRS) and 110 orthotopic liver transplants (OLT) between January 1987 and December 1991. The purpose was to clarify which patients with variceal bleeding should be treated by DSRS versus OLT. Distal splenorenal shunts were selected for patients with adequate or good liver function. Orthotopic liver transplant was offered to patients with end-stage liver disease who fulfilled other selection criteria. The DSRS group comprised 71 Child's A, 70 Child's B, and 6 Child's C patients. The mean galactose elimination capacity for all DSRS patients was 330 +/- 98 mg/minute, which was significantly (p less than 0.01) above the galactose elimination capacity of 237 +/- 82 mg/minute in the OLT group. Survival analysis for the DSRS group showed 91% 1-year and 77% 3-year survival, which was better than the 74% 1-year and 60% 3-year survivals in the OLT group. Variceal bleeding as a major component of end-stage disease leading to OLT had significantly (p less than 0.05) poorer survival (50%) at 1 year compared with patients without variceal bleeding (80%). Hepatic function was maintained after DSRS, as measured by serum albumin and prothrombin time, but galactose elimination capacity decreased significantly (p less than 0.05) to 298 +/- 97 mg/minute. Quality of life, measured by a self-assessment questionnaire, was not significantly different in the DSRS and OLT groups. Hospital charges were significantly higher for OLT (median, $113,733) compared with DSRS ($32,674). These data support a role for selective shunt in the management of patients with variceal bleeding who require surgery and have good hepatic function. Transplantation should be reserved for patients with end-stage liver disease. A thorough evaluation, including tests of liver function, help in selection of the most appropriate therapeutic approach.

High cardiac output of advanced liver disease persists after orthotopic liver transplantation.

This study measured cardiac output before and 1 or 2 yr after orthotopic liver transplantation in 23 patients. Cardiac output was measured by thermodilution before transplantation and by first-pass radionuclide angiocardiography at follow-up. Study patients were selected as those doing well clinically and by standard laboratory tests at 1-yr and 2-yr reevaluations with no evidence of rejection: six had mild recurrent hepatitis shown on biopsy samples. Hepatocyte function was normal at the time of the study as shown by galactose elimination capacity of 442 +/- 90 mg/min. Medications were cyclosporine and prednisone in all patients, azathioprine in 10 patients and a combination of antihypertensive therapy to maintain diastolic blood pressure less than 90 mm Hg in 20 patients. Mean (+/- S.D.) pretransplantation cardiac output was 9.1 +/- 3.1 L/min and remained elevated at 8.3 +/- 2.1 L/min 1 yr, and 9.6 +/- 2.6 L/min (n = 13) 2 yr after transplantation. A significant (p less than 0.001) correlation was found between pretransplant and follow-up cardiac output. End diastolic, end systolic and stroke volumes are all increased in a pattern similar to that seen in end-stage cirrhosis. These data show that the high cardiac output of the hyperdynamic state of advanced liver disease persists after liver transplantation. The mechanisms and consequences of this require further study.

Selective splenocaval shunt. Report of 26 cases and review of the literature.

Splenocaval shunting was performed in 26 patients for the treatment of variceal bleeding. The indications for this alternative selective shunt were congenital anomalies of the left renal vein, inadequate outflow from the left renal vein on preoperative venography, or an anatomic relationship of the splenic vein favoring direct splenocaval rather than splenorenal anastomosis. Technical considerations in which splenocaval shunts differ from distal splenorenal shunting relate to exposure of the vena cava. Operative mortality was 7.7% (2/26). Immediate shunt patency was documented in 23 of 24 patients studied, and all 14 shunts studied at 13 to 57 months were patent. Portal perfusion was maintained in 95% (20/21) of the patients when studied at 7 to 10 days after shunting and in 57% (8/14) at late follow-up. This experience with distal splenocaval shunting has reaffirmed its place as an alternative technique to selective distal splenorenal shunts, particularly when the left renal vein is abnormal.

The role of continued drinking in loss of portal perfusion after distal splenorenal shunt.

Fifty percent of patients with alcoholic cirrhosis who undergo distal splenorenal shunting for variceal bleeding lose portal perfusion within 1 year. Although it was previously considered that this loss of portal flow was irrevocable, the present study shows that with resolution of alcoholic hepatitis, portal perfusion can be restored. A 34-year-old patient with alcoholic liver disease and a distal splenorenal shunt lost portal perfusion 1 year after the operation. He had continued to drink alcohol and had high sinusoidal pressure. Following forced abstinence over the next 2 years, his sinusoidal pressure fell, liver volume decreased, results of liver biopsy improved, and portal perfusion was restored. Shunt patency was documented, and the same collaterals from the portal vein to the shunt could still be visualized as had been seen when portal flow was absent. Restoration of portal perfusion was attributed to decreased intrahepatic resistance secondary to abstinence from alcohol. A return to drinking in the next 9 months led to alcoholic hepatitis and once again loss of portal perfusion. This study places emphasis on increased intrahepatic resistance rather than the development of portal-to-shunt collaterals as important in the loss of portal flow in such patients.