Current approaches to the diagnosis and management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, and incidence rates in Western countries are on the rise. Despite many options, no ideal treatment yet exists for this highly malignant tumour, and management strategies have varied accordingly. This review summarises current strategies for the diagnosis and management of HCC.

The effect of a computer assisted instructional program on physical therapy students.

The purpose of this study was to assess the efficacy and efficiency of CAI for students learning evaluation and treatment skills for carpal tunnel syndrome (CTS). Ten volunteer physical therapy students were randomly assigned into either CAI or interactive lecture instructional groups. Each student completed a 36-item pretest on CTS. The CAI group used the Physical Therapy Patient Simulator CAI and the instructional group participated in lecture/discussion to complete the case studies. Following completion of instruction, an identical 36 item posttest was administered to all students. Individual start and finish times for the two groups were recorded by the instructor. A 2 x 2 ANOVA revealed no significant difference in pretest/posttest scores between CAI and interactive lecture. A t-test determined the CAI group completed the case assignment 30 minutes (24% faster than the interactive group. The findings suggest that using a CAI simulation program may be as effective and more efficient than traditional methods of instruction.

Thoracic spinal fractures and aortic rupture: a significant and fatal association.

We analyzed the frequency of occurrence of traumatic aortic rupture (TAR) in patients with and without thoracic spinal fractures. Among 4,676 blunt chest trauma victims admitted to the hospital between 1972 and 1988, 148 (3.2%) suffered one or more thoracic vertebral fractures. There were 73 patients with one or more fractures of the first eight thoracic vertebrae (T1 to T8); of these 73, 4 also suffered TAR (5.5%). There were 4,603 patients without fractures of T1 to T8, and 64 of these patients also suffered TAR (1.4%). This difference was significant by the chi2 and Fisher exact tests, p = 0.00378 and p = 0.021003, respectively. Additionally, all 5 patients with TAR and thoracic vertebral fractures died. We conclude that patients with one or more fractures of T1 to T8 have a statistically significant increase in the incidence of TAR.

Blunt trauma in adults and children: a comparative analysis.

Trauma remains the major cause of death in children and young adults. Adult and pediatric patients differ significantly in both mechanism of and physiologic response to injury. We reviewed the records of all consecutive adult and pediatric blunt trauma patients admitted to a major metropolitan trauma center for a 10-year period. An extensive computerized database has been maintained for all patients since 1977. A comparative statistical analysis of mechanism of injury, specific organ injury, and clinical outcome was performed. Altogether, 1,722 adults and 289 children were treated during the study period. Blunt trauma accounted for 82.8% of adult and 94.3% of pediatric injury (p = 0.00005), and only these patients were considered for analysis. Diagnostic peritoneal lavage was performed in 249 children and 1,464 adults, with a respective accuracy of 99.6% and 97.2%. Mechanism of injury was comparable for both groups, although children were far more likely to be injured by falls, bicycle accidents, or struck by an automobile. Comparative analysis of specific injuries demonstrated significantly fewer pediatric chest (p = 0.001), spine (p = 0.03), and pelvic (p = 0.003) injuries. Central nervous system (CNS) injury in children was a strong determinant of outcome: serious pediatric CNS trauma was associated with a tenfold increase in mortality. Mortality for children in the absence of CNS injury was less than 3%. Spinal injury also appeared to be a predictor of poor outcome in the pediatric population, with an associated mortality of greater than 50%. Overall, survival was age independent (82.5% of adults and 85.8% of children were survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Does sternal fracture increase the risk for aortic rupture?

We retrospectively reviewed the records of 99 patients who suffered sternal fractures between 1968 and 1987. Patients ranged in age from 5 to 86 years. The most common cause of injury was a motor vehicle accident. The 99 patients were compared with a concurrent series of 2,106 patients with chest injuries and no sternal fractures. Traumatic aortic rupture occurred in 2 of 99 patients with sternal fractures (2%) and in 75 of 2,106 patients without sternal fracture (3.6%). This difference was not statistically significant by the Fisher exact test (p = 0.326). We conclude that traumatic aortic rupture does not occur more commonly in patients with sternal fracture when compared with other patients with blunt chest injuries.

Splenic reticuloendothelial function after splenectomy, spleen repair, and spleen autotransplantation.

Overwhelming infection after splenectomy remains a problem despite the introduction of vaccine and antimicrobial prophylaxis. To evaluate prospectively various procedures proposed for salvage of the spleen, we measured reticuloendothelial function for two to five years in 51 patients who had initially presented with abdominal trauma and suspected splenic rupture. The mean percentage of pocked erythrocytes and the clearance of antibody-coated autologous erythrocytes in 8 patients who had splenic repair and in 6 who had partial splenectomy were the same as in 11 controls with intraabdominal injury that did not involve the spleen. The mean percentage of pocked erythrocytes remained significantly elevated in 19 patients who had undergone total splenectomy without autotransplantation of splenic tissue. One of seven patients who underwent splenic autotransplantation had a normal level of pocked erythrocytes 18 months after surgery, and a second patient had only a slight elevation at 24 months. The mean (+/- SEM) half-time clearance of labeled erythrocytes was significantly longer in the group that had total splenectomy without autotransplantation (421.1 +/- 74.5 hours) than in the autotransplantation group (91.6 +/- 20.0) or in the controls (5.4 +/- 2.0). We conclude that reticuloendothelial function was better preserved after partial splenectomy and splenic repair than after splenic autotransplantation, but that autotransplantation was superior to total splenectomy and appeared to be safe. Splenic autotransplantation deserves further study in patients who have had splenic trauma when other surgical maneuvers to save the spleen are not possible.

Renal failure and mortality after nephrectomy for severe trauma in multiply-injured patient: no inordinate risk.

It was recently reported that renal loss by partial or total nephrectomy for renal trauma increases the rates of acute renal failure and death in the multiply-injured patient. Because our preference has been for immediate surgical intervention in such patients, a retrospective review was performed to ascertain the effect of partial or total nephrectomy. Eighty-eight patients met the criteria of multiple injuries including severe renal injuries (laceration, rupture, or pedicle injury) and availability of renal function data. Partial or total nephrectomy had been performed in 50 patients, renorrhaphy in 23, and 15 were managed without renal operation. In patients with renal lacerations, the numbers of associated injuries (including intra-abdominal injuries) were similar to those managed conservatively or by operation, and the rates of acute renal failure and mortality were the same with conservative management, renorrhaphy, or nephrectomy. Patients with renal pedicle injuries who had a nephrectomy did have a higher rate of acute renal failure than those managed conservatively (75% vs 0%; p less than 0.05), but they also had more associated injuries (2.8 vs. 1.6/patient; p less than 0.04) and they were older. These two factors, rather than the nephrectomy, probably accounted for the greater rates of acute renal failure and death.

Development and characterization of an automated assay of effective heparin activity in plasma.

We describe a fully automated assay for determining effective heparin activity in plasma, based on heparin-catalyzed inhibition of Factor Xa (EC 3.4.21.6) by antithrombin III (AT III). Residual Factor Xa is determined kinetically by the Du Pont aca discrete clinical analyzer with a chromogenic substrate and is inversely related to heparin activity. Because the test plasma is the sole source of AT III, the assay result is dependent on AT III activity and reflects effective rather than total heparin activity. The assay range is 20-1200 USP units/L, and the assay shows equivalent sensitivity to standard and low-molecular-mass heparins. Within-run reproducibility (CV) is 1.6% at 390 units/L. There was no interference from common blood components or drugs. Results agreed well with those by the Coatest heparin kit (Kabi) adapted to the Cobas-Bio analyzer (r = 0.85, n = 122).

Brachial plexus injuries from blunt trauma--a harbinger of vascular and thoracic injury.

We reviewed the records of 59 patients who suffered brachial plexus injuries following blunt trauma between the years 1974 and 1984. The age of the patients ranged from 2 to 84 years, with a mean of 35.3 years. Forty-five were male patients. The majority of injuries (53%) were caused by motor vehicle accidents. Direct trauma was the mechanism of injury for 33 patients, traction for 18, shoulder dislocation for six, and acromioclavicular separation for two. The injuries occurred on the left side in 33 (56%); the right side in 23 (39%), and bilaterally in three (5%). Eight patients (14%) suffered complete brachial plexus palsies, and 51 (86%) incurred partial palsies. Nine patients (15.2%) presented in shock. Severe associated injuries occurred in this group of patients and included multiple rib fractures, hemopneumothorax, pulmonary contusion, head injuries, and upper extremity fractures. Subclavian artery injuries occurred in three patients, axillary artery in two patients, and an internal carotid injury in one patient. Complete resolution of the palsy occurred in 25 patients, partial resolution occurred in 17 cases, and the brachial plexus palsy remained permanent in nine. Eight patients were lost to follow-up. Brachial plexus injuries frequently occur in association with severe trauma, are usually partial palsies, and resolve partially or completely in two-thirds of cases. In addition, 10% of these patients suffered major vascular injuries and 10% incurred significant chest trauma.

Risk factors for the development of renal failure following the surgical treatment of traumatic aortic rupture.

A retrospective study of 44 patients who were treated surgically for traumatic aortic rupture was undertaken to determine risk factors for the development of postoperative renal failure. Renal failure occurred in 11 of 41 patients (27%) eligible for analysis. The Pearson product-moment correlation showed no significant relationship between the occurrence of renal failure and the patient's age, injury severity score, initial blood pressure, or the interval between accident and thoracotomy. Renal failure was significantly correlated with cross-clamping only (r = .2751, p = .043). There was no relationship between renal failure and total cross-clamp times. The mortality rate was significantly higher for patients with renal failure.

Risk factors for survival following surgical treatment of traumatic aortic rupture.

Linear discriminate analysis was used to determine the effects of age and Injury Severity Score on survival in 37 consecutive patients treated surgically for traumatic rupture of the thoracic aorta. Pearson product moment correlations were calculated between associated injuries and survival. The age of the injured patients was the only variable that correlated statistically with survival: the lower the patient's age, the greater the chance of survival (r = 0.3535; p = 0.016). The severity of the injury, as represented by the Injury Severity Score, showed a tendency toward decreased survival with increasing Injury Severity Score (r = -0.2523; p = 0.066). Specific types of associated injuries did not correlate with survival. Survival rates were not statistically different for patients who underwent cardiopulmonary bypass compared with those in whom a temporary plastic shunt was used (chi-square = 1.72; p = 0.19). We conclude that age is the most significant factor in predicting survival in patients who undergo surgical repair of traumatic aortic rupture.

Significance of symptoms and signs in patients with traumatic aortic rupture.

The records of 50 patients with traumatic aortic rupture (Group I) and 50 patients with blunt chest trauma but negative aortograms (Group II) were reviewed retrospectively. Symptoms and signs referable to the chest and thoracic aorta were recorded and compared in Group I and Group II patients. Each patient's chart was evaluated for chest pain, respiratory distress, thoracic back pain, hypotension, hypertension, and decreased femoral pulses. None of the symptoms or signs attained statistical significance between Group I and Group II patients. The only significant difference between Group I and Group II patients was in the injury severity score (ISS). The mean ISS for aortic rupture patients was 42.1 +/- 11.6 (SD), but was only 19.9 +/- 11.4 (SD) (P less than .001) for patients without aortic rupture. We conclude that the diagnosis of aortic rupture in patients sustaining blunt chest trauma cannot be accurately predicted or excluded on the basis of the patients' presenting complaints or physical findings.

The management of subclavian artery injuries following blunt thoracic trauma.

The records of 15 patients who sustained blunt rupture of the subclavian artery were reviewed. The findings on physical examination included arterial hypotension, unilateral absence of the radial pulse, brachial plexus palsy, and supraclavicular hematoma. The chest roentgenographic findings included wide mediastinums, apical pleural hematomas, and first rib fractures. Fourteen patients survived to undergo angiography and operation. Arterial continuity was restored by primary anastomosis, synthetic grafts, and venous interposition grafts. Ligation of a pseudoaneurysm was carried out in 1 patient with a complete brachial plexus palsy. Amputation of an upper extremity was required in 1 patient. Two patients died postoperatively. We conclude that blunt subclavian artery injuries may be suspected clinically. Absent upper extremity pulses, a wide mediastinum, unrelenting thoracic hemorrhage, and persistent hypotension dictate the necessity for aortography. Relative indications for angiography include brachial plexus palsy, apical pleural hematoma, and a fractured first rib.

Injuries associated with fractures of the transverse processes of the thoracic and lumbar vertebrae.

The records of 92 patients who sustained fractures of the transverse processes of thoracic or lumbar vertebrae between 1976 and mid-1982 were reviewed. The majority were injured in motor vehicle accidents. Trauma to abdominal viscera occurred in 19 patients including hepatic injuries in six, splenic injuries in 12, and colonic injuries in five. Hematuria was present in 51 patients and five of 51 had urinary tract injury requiring operative treatment. None of 34 patients without hematuria incurred anatomic disruption of the urinary tract. Thirty-two patients suffered other associated injuries, including thoracic, orthopedic, maxillofacial, and cerebral trauma. Fifteen patients incurred other spinal injuries. The overall mortality was 11% (ten patients). The mean Injury Severity Score in the 92 patients was 13.9. The frequency of abdominal visceral trauma with this bony injury (19/92-21%) suggests great energy expenditure and should alert physicians to seek other severe injuries.

Peritoneal lavage for the diagnosis of abdominal visceral injury.

Peritoneal lavage has become standard for the diagnosis of abdominal visceral injury following trauma. Peritoneal lavage is indicated after blunt trauma when a patient presents with abdominal symptoms or signs and the integrity of the abdominal viscera is in doubt. Immediate laparotomy may be indicated following penetrating abdominal wounds when symptoms, signs, or hypotension are present. However, peritoneal lavage may be indicated if the patient is asymptomatic. Lavage is also indicated after penetrating extra-abdominal wounds when the path of the wounding agent suggests that the peritoneal cavity might have been entered. Peritoneal lavage is 98% accurate in determining the presence or absence of abdominal visceral injury following blunt trauma (100,000 red blood cells [RBCs]/mm3 or 500 white blood cells [WBCs]/mm3). The diagnostic accuracy of peritoneal lavage in penetrating abdominal injuries is more controversial than in blunt trauma, but recent retrospective data suggest that peritoneal lavage has the potential of giving 98% accurate results following penetrating abdominal injury when the threshold for a positive result of lavage is lowered to 50,000 RBCs/mm3 or 500 WBCs/mm3.

Coagulation testing with the Du Pont aca discrete clinical analyzer.

Methods for the measurement of the functional concentration of AT III, PLG, and FBG have been developed for the Du Pont aca discrete clinical analyzer. These methods are fully automated, provide excellent reproducibility, and compare favorably with existing methodologies. The availability of these and future coagulation assays on this automated analyzer will provide the hospital laboratory with a reliable means for evaluating hemostatic function. In addition, excellent method reproducibility and use of defined reference standards should significantly contribute to the standardization of coagulation methods.

Development and analytical performance of automated tests for antithrombin III and plasminogen on the Du Pont aca analyzer.

We describe assays for functional antithrombin III (AT III) and plasminogen in plasma with the Du Pont aca discrete clinical analyzer. Both are two-stage kinetic assays, based on synthetic substrate methodologies, and require 20-microL sample volumes. In the AT III assay the sample is incubated with excess thrombin and heparin to form the functionally inactive AT III-thrombin complex. Residual thrombin is measured through its rate of hydrolysis of a lysine thioester and is inversely related to analyte concentration. In the plasminogen assay excess streptokinase is reacted with the sample to form an enzymatically active complex. The substrate hydrolysis rate of this complex is measured, which is linearly related to the concentration of plasminogen in the sample. Reaction conditions for both assays were optimized by univariate and response surface techniques. The assay for AT III has a range of 0 to 150% of the value for normal human plasma (% NHP) with a CV of 3% at 80% NHP. The plasminogen assay is linear from 25 to 200% NHP with a CV of less than 2% at 80% NHP. No significant interferences with either method by common blood components or drugs were found.

Optimization of enzyme-based assays in coagulation testing.

Optimized assays for antithrombin III and plasminogen have been developed based on a study of the kinetic parameters Km and Kcat for four commercially available substrates: the p-nitroanilide derivatives of D-Phe-pipecolyl-Arg (S-2238), and toluenesulfonyl-Gly-Pro-Arg (Chromozym TH), which are thrombin substrates; D-Val-Leu-Lys (S-2251), a plasminogen/streptokinase substrate; and alpha-N-carbobenzoxy-L-lysine thiobenzyl ester, a substrate for both enzymes. We used a centrifugal analyzer system for rapid data acquisition and interactive analysis. Optimized conditions for assay of a particular enzyme are not constant for different substrates in the same buffering agent. For example, in 1,4-piperazine diethanesulfonic acid buffer at 37 degrees C, thrombin-catalyzed hydrolysis of Chromozym TH is optimal at 125 mmol/L buffer, 100 mmol/L NaCl, and pH 8.2, whereas substitution of S-2238, also a tripeptide p-nitroanilide, yields optimal hydrolysis at 85 mmol/L buffer, 300 mmol/L NaCl, and pH 7.2. We conclude that optimized assay conditions are best obtained by an extensive survey of available buffers and a detailed investigation of the effects of variation in pH and in the concentrations of the buffer and auxiliary reagents through use of both one-factor-at-a-time and multivariate response surface experimentation.