Perioperative factors and outcome associated with massive blood loss during major liver resections.

BACKGROUND: Mortality and morbidity rates from major liver resections have decreased sharply over the past 25 years. This improvement is due to a better understanding of liver anatomy and the introduction of new operative techniques, but also to improved anesthetic perioperative support. Certain cases are still associated with voluminous blood loss. These patients may be at higher risk for postoperative problems and increased length of stay (LOS) in hospital. METHODS: We have retrospectively reviewed 115 patients undergoing major hepatic resections (three or more anatomic segments) with respect to operative blood loss (EBL). Those with an EBL >or=5000 ml (group 1; n = 39) were compared to those with an EBL or=70 years), tumor size, mortality, morbidity, and hospital LOS were examined. Operative reports were examined for any explanation for excessive blood loss. Anesthetic support often entailed the use of a rapid infusion system. RESULTS: The EBL was 7692+/-3848 ml for group 1 and 1359+/-514 ml for group 2. Primary liver tumors were resected in 20 patients in group 1 and in 18 patients in group 2. The remaining resections were for metastatic tumors, primarily colorectal in origin. In group 1, 13/39 patients had a left hepatectomy compared to 10/42 patients in group 2 (p=0.34). The overall mortality was 5/1 15. Four deaths occurred in group 1 and one in group 2 (p=0.16). Two deaths in group 1 were intra-operative (hemorrhage, air embolism). There was no difference in the number of patients with complications, 12/ 39 in group 1 and 8/42 in group 2 (p=0.22). Two patients in group 1 required re-operation for bleeding; there were none in group 2. Largest tumor size did not differ between the two groups (p=0.08), nor did the proportion of patients aged 70 years or older (p=0.06). There was no difference in hospital LOS (10.54+/-6.1 vs 8.90+/-4.7 days, p=0.2l). Review of operative notes in group 1 indicated no unusual problems in 13/39, large tumors or proximity to the inferior vena cava in 10/39, and bleeding from the middle hepatic vein in 7/39. Three patients in group 1 required total vascular exclusion for tumor removal; there were none in group 2. DISCUSSION: Massive EBL during major liver resection seems to be provoked by tumors near the inferior vena cava or major hepatic veins, or injury to the middle hepatic vein during operation, and not by patient age, tumor size alone, or type of hepatectomy. However, by avoiding prolonged hypotension and hypothermia with the use of rapid infusion devices, the perioperative course of these patients does not differ from those with much less EBL.

Military, civilian, and rural application of the damage control philosophy.

Damage control surgery is a useful salvage strategy for the most critically injured patients. Conceptually, this approach to individual patients can be extrapolated to situations such as military field surgery, civilian mass casualty events, and long-range transfers from rural areas. The logistic realities of Army forward surgery teams are addressed with regard to typical damage control maneuvers and evacuation. Specific areas requiring improvement through directed research are identified. Initial civilian mass casualty strategies are discussed, and a plan to prevent transfer delays of rural trauma patients is presented. By transferring the lessons learned from individual damage control patients to military, civilian mass casualty, and rural casualty events, resource utilization is optimized. The concept of minimal acceptable care rather than optimal trauma care can be applied to these three seemingly different situations.

Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft.

BACKGROUND: Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). METHODS: We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. RESULTS: By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001). CONCLUSION: Longer CIT induces a humorally more immunogenic kidney.

IgM antibodies identified by a DTT-ameliorated positive crossmatch do not influence renal graft outcome but the strength of the IgM lymphocytotoxicity is associated with DR phenotype.

A positive crossmatch that is rendered negative by treating the serum with the IgM-reducing agent dithiothreitol (DTT) is generally reported not to influence short-term renal graft outcome. Its effect on long-term (> or = 3 years) cadaveric and live-donor transplant function, however, is less clear. We evaluated the effect of IgM antibodies in a DTT-ameliorated positive crossmatch (DTT-APXM) on long-term renal graft outcome in 1,290 consecutive cadaveric renal transplants (8-year survival) and 384 live-donor renal transplants (7-year survival) from patients transplanted between 1990 and 1999. The data show that 1- and 8-year graft survival for cadaveric renal transplants in patients with IgM antibodies (n=72) (DWFG censored = 91% and 65%; DWFG not censored = 90% and 60%) was not significantly different from the group without IgM antibodies (n = 1,218) (DWFG censored = 92% and 71%; DWFG not censored = 87% and 55%) (log-rank = 0.25 for DWFG censored, log-rank = 0.92 for DWFG not censored). The one- and seven-year graft survival for live-donor renal transplants in patients with IgM antibodies seen in a DTT-APXM (n = 22) (DWFG censored = 95% and 83%; DWFG not censored = 95% and 66%) was not significantly different from the group without IgM antibodies (n = 362) (DWFG censored = 94% and 81%; DWFG not censored = 92% and 73%) (log-rank = 0.61 for DWFG censored, log-rank = 0.89 for DWFG not censored). DR phenotype was found to be associated with the strong (>40% cell death) IgM reactivity in both black and white patients. In white patients, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) than in molecularly typed controls (28.5%) (P < 0.03) and concomitant with that DR increase, DR4 was decreased in white patients (6.8%) compared with controls (25.5%) (P < 0.02). In black patients with strong IgM reactivity, DR6 was increased in patients (46.1%) compared with controls (20.5%) (P = 0.07) and concomitant with that DR6 increase, DR5 was decreased in frequency in black patients (7.6%) compared with controls (41%) (P < 0.03). These data show that long-term graft survival in renal transplantation is not negatively influenced by the presence of donor-reactive lymphocytotoxic antibodies in the crossmatch ameliorated by serum DTT treatment. They also suggest that the strength of the IgM antibody response is regulated in part by certain gene (s) of the DR region.

Realistic expectations for cryoablation of liver tumors.

While cryoablation has been shown to be an effective method of destruction of primary and metastatic liver tumors, there is a disturbingly high incidence of recurrence at the cryoablated site and there are conflicting reports concerning long-term survival. For this reason, resection remains the preferred surgical treatment of liver tumors. However, there is a population of patients who, because of age, pre-existing liver disease, or likely systemic dissemination, present a higher risk for major resection, and for whom cryoablation may be favored. This study examined the safety and effectiveness of cryoablation in patients thought to be at higher risk for conventional hepatic resection, or in whom resection would not eradicate all known disease. Twenty-eight consecutive patients underwent cryoablation, with or without resection, of 39 hepatic tumors for primary (n = 9) or metastatic (n = 19) disease. Their postoperative course and long-term follow-up were examined for complications, survivability, and recurrence of disease. With the use of cryoablation, a major hepatic resection was avoided in 20 patients, 11 of whom were 70 years or older, 4 who likely had disseminated cancer even though the liver was the only site of detectable disease, 2 who were cirrhotic, and 2 with bilobar disease. An additional 7 patients had recurrence of disease in a previously resected liver, for whom additional resection would be hazardous. There was one operative death from an exaggerated systemic inflammatory response syndrome. Seven patients developed complications, including 2 patients with cryoablation-induced coagulopathy. Excluding 2 patients (including the postoperative death) the average hospital length of stay was 6.7 +/- 2.8 days. Seven patients required some intensive care unit (ICU) care. Three patients with primary liver cancer are alive 29 to 47 months after cryoablation. Two patients with metastatic disease are alive without recurrence at 12 and 16 months, and 9 are alive with disease from 13 to 58 months after cryoablation. Fifteen patients developed liver recurrence, 5/27 (19%) at the cryoablated site. Cryoablation appears to be a safe treatment modality for primary and metastatic liver cancer. It is particularly appealing in those patients who may be at higher risk for major hepatectomy because of age, pre-existing liver disease, type of metastatic disease, previous resection, or bilobar tumors. Most disturbing is the high incidence of recurrence at the cryoablated site, which may reflect problems with ultrasound localization or proximity of tumors to major vasculature. Disease-free survival is low. From this standpoint the procedure should be considered palliative, even though all hepatic tumors can be eradicated. However, these limitations should not deter the use of cryoablation in selected patients. There is the potential for long-term survival, just as there is with resection.

Hepatic apoptotic activity following transient normothermic inflow occlusion and reperfusion in the swine model.

Accelerated hepatic apoptosis was first described in portal vein-ligated livers but has since been reported in a variety of liver injuries. Because porto-prival states can induce apoptosis we sought to determine whether transient ischemic periods followed by reperfusion would trigger such cell death. The cytokines TNF-alpha and TGF-beta are known to facilitate apoptosis and are released in response to a number of stimuli including ischemia. We also investigated alterations in plasma and tissue levels of these cytokines which might lend support to their role in increased apoptotic activity following ischemia/reperfusion. Female pigs were used as the experimental model. Inflow occlusion of portal and hepatic arterial blood was performed to a portion of the swine liver directing the entire splanchnic flow to the remaining hepatic lobes for a period of 2 h. The livers were then reperfused and plasma and tissue samples taken for determination of apoptotic activity utilizing cell death immunoperoxidase staining of 3'-OH DNA ends generated by fragmentation and ELISA assay of histone-associated DNA fragments. Plasma and tissue levels of TNF-alpha and plasma levels of TGF-beta were determined by ELISA assay. An increase in apoptotic activity following reperfusion was seen at Day 2 and Day 4 compared to preischemic values by the cell death stain. The ELISA cell death assay showed an increase in apoptotic activity at 60 min, Day 2, and Day 4. Moreover, the ELISA cell death assay showed enhanced apoptotic activity in "hyperperfused" hepatic lobes compared to preischemic, or resting, liver. This was also observed when compared to sham-operated animals. Surprisingly, there was no detectable increase in plasma TNF-alpha or TGF-beta levels following ischemia/reperfusion, although homogenized liver TNF-alpha levels were increased at 60 min and Day 2 following reperfusion. We conclude that transient hepatic inflow occlusion followed by reperfusion can induce increased apoptotic activity in the swine model. Furthermore, increased apoptotic activity also occurs in the hyperperfused liver raising the possibility of a locally active factor or global hepatic expression of receptor activity in response to ischemia/reperfusion. This period of ischemia/reperfusion did not produce a detectable increase in circulating cytokine levels, and accelerated apoptosis could not be linked to heightened TNF-alpha or TGF-beta plasma activity. Higher tissue levels of TNF-alpha could reflect enhanced binding to TNF cell surface receptors or amplified receptor expression.

Low falls: an underappreciated mechanism of injury.

OBJECTIVE: This is a retrospective study designed to evaluate the pattern and severity of injuries that result from low falls, defined as falls from less than 20 ft, subsequent mortality, and requirements of hospital resources. Our hypothesis is that many of these injuries, even without cardiopulmonary instability, are worthy of trauma center care. METHODS: The records of all patients entered into the hospital trauma registry at an urban Level I trauma center during the years 1991 through 1997 who suffered low falls and who either died after admission or were hospitalized for at least 3 days were reviewed. Patients suffering isolated hip fractures were excluded. One hundred seventy-six patients constituted the study population. This group accounts for about 2% of all admissions for falls at our institution. Patterns of injury were examined. Age, mechanism of injury, Injury Severity Score (ISS), and cardiopulmonary or neurologic instability on admission were documented. Mortality, length of intensive care unit and hospital stays, as well as billed hospital charges, were reviewed. RESULTS: The majority of patients (62%) were younger than 50 years. Sixty patients had ISS >15 and 116 patients had ISS >9. Sixty patients had multisystem injuries requiring specialty care. Head injuries were found in 81 patients (35%), and vertebral fractures or spinal cord injuries were found in 49 patients (22%), including 9 quadriplegics and 5 paraplegics. There were seven patients with intra-abdominal injuries (five spleen and two bowel injuries). There was one patient with a rupture of the thoracic aorta. Seventeen patients had deteriorating neurologic or pulmonary function on arrival, but the majority (90%) were stable. Of the 159 "stable" patients, 48 suffered head injuries, 7 were quadriplegic, and 3 were paraplegic. All intra-abdominal injuries were in this group. Overall, 14 of 176 patients (8%) died. Seven deaths were in patients older than 60 years, and seven deaths were in younger patients (p = 0.04). The majority of deaths (9 of 14) were from head trauma. Care in the intensive care unit was required in 92 of 176 patients. Nine patients had billed charges exceeding $100,000. CONCLUSION: Low falls can cause significant injuries, most commonly to the head and spine. Based on mechanism of injury alone, patients injured in low falls might not be taken to trauma centers. We have found, however, that many of these patients sustain serious multisystem injuries, even though they are stable initially. Although these patients represent only a fraction of those who fall, our study would support adjustment of triage guidelines to recommend transport of such patients, particularly elderly patients, to trauma centers.

In Flanders fields: the Great War, Antoine Depage, and the resurgence of débridement.

OBJECTIVE: The care of traumatic wounds has evolved over hundreds of years, largely as a result of armed conflicts. The lessons learned during World War I in the treatment of extensive soft-tissue injuries proved invaluable in reducing infection and preventing loss of limb and life. Foremost among these was the use of debridement. This report reviews the development of debridement as standard treatment of war wounds and highlights the surgeon largely responsible for its resurgence during one of this century's saddest chapters. SUMMARY BACKGROUND DATA: Before World War I, the care of wounds consisted of minimal exploration and liberal use of then-new antiseptics. For limited injuries, this approach appeared adequate. World War I saw the introduction of devastating weapons that produced injuries that caused extensive devitalization of tissue. Standard treatment of these patients proved woefully inadequate to prevent life-threatening infections. METHODS: This is a historical review of the conditions that occurred during World War I that prompted a change in wound management. One of those responsible for this change was the Belgian surgeon Antoine Depage. His life and contributions to the care of war wounds are profiled. Depage reintroduced the discarded French practice of wound incision and exploration (debridement) and combined it with excision of devitalized tissue. RESULTS: Through the use of debridement, excision, and delayed wound closure based on bacteriologic survey, Depage was able to reduce the incidence of infectious complications of soft-tissue injuries, particularly those involving fractures. CONCLUSIONS: Through his experiences in the Great War, Antoine Depage was able to formulate a treatment plan for wounds of war. All such injuries were assumed to be contaminated and, as such, they required early and careful debridement. Depage thought that wound closure should often be delayed and based his decision to close on the bacteriologic status of the wound. To him, we owe our current management of traumatic wounds.

Influence of the Rh (D) blood group system on graft survival in renal transplantation.

BACKGROUND: The Rh (D) blood group system has not traditionally been considered to be a clinically relevant histocompatibility barrier in transplantation since conflicting results of its clinical importance have been reported. METHODS: We analyzed 786 consecutive primary cadaveric renal transplants performed by transplant centers in our Organ Procurement Organization (OPO) between 1990 and 1997. We also analyzed United Network for Organ Sharing (UNOS) data on 26,469 kidney transplants done from April 1994 to June 1996. RESULTS: Multivariate analysis revealed that Rh identity between the recipient and donor was significantly related to better graft outcome (risk ratio, 0.43; 95% confidence interval, 0.30 to 0.61; P=0.0001). Multivariate analysis of the UNOS data revealed that the Rh -/- group may have a positive influence on graft survival with a risk ratio of 0.43 (P=0.14). CONCLUSION: Multivariate analysis of primary cadaveric renal allografts performed within the Midwest Organ Bank OPO indicates that Rh (D) is a clinically relevant histocompatibility barrier that influences 7-year graft survival.

Ten-year experience in transplantation of A2 kidneys into B and O recipients.

BACKGROUND: This article summarizes our 10-year multicenter experience with transplantation of 50 blood group A2 and A2B kidneys into B and O patients. METHODS: Since 1986, we have transplanted kidneys from 46 cadaver donors and 4 living donors who were blood group A2 (47 donors) or A2B (3 donors) into 19 B and 31 O patients. In 1991, we began allocating these kidneys preferentially to B and O recipients who were selected based on a history of low (< or =4) anti-A IgG isoagglutinin titers. Immunosuppression was no different from that used in ABO-compatible grafts. RESULTS: The 1-month function rate before thus selecting the patients was 68% (19/28), but is now 94% (17/18). Two-year cadaver-donor graft survival with this selection method is 94%, compared with 88% for 640 concurrent and consecutive ABO-compatible transplants (log-rank, 0.15). All four living-related transplants are still functioning, with a mean follow-up of 71 months. Since we began allocating A2 kidneys preferentially to B and O recipients, the percentage of the B patients who received A2 or A2B kidneys has increased from 29% (8/28) to 55% (10/18). CONCLUSIONS: Transplantation of A2 or A2B kidneys into B and O patients is clinically equivalent to that of ABO-compatible transplantation when recipients are selected by low pretransplant anti-A titer histories. This approach increases access of blood group B recipients to kidneys.

Transplantation rate of the blood group B waiting list is increased by using A2 and A2B kidneys.

BACKGROUND: We have increased the transplantation rate for blood group B cadaveric waiting list candidates by transplanting them with A2 and A2B kidneys. METHODS: Since 1991, five of the seven renal transplant programs in our organ procurement organization service area have preferentially transplanted blood group A2 and A2B cadaveric kidneys to B blood group waiting list candidates with histories of low anti-A isoagglutinin titers. RESULTS: Between 1991 and 1997, these five centers performed transplantations on 71 patients from the B cadaveric waiting list. Of those 71 patients, 29% (21 of 71) underwent transplantation with either A2 (n=18) or A2B (n=3) cadaveric kidneys. In 1997 alone, 48% (11 of 23) of the B patient transplant recipients received A2 or A2B kidneys. CONCLUSIONS: Transplantation of A2 and A2B kidneys into B waiting list patients has successfully increased access of B patients to kidneys. Such an allocation algorithm implemented nationally may similarly increase the transplantation rate of B waiting list candidates.

Long-term graft survival is improved in cadaveric renal retransplantation by flow cytometric crossmatching.

BACKGROUND: Cadaveric renal retransplantation is associated with a higher risk of early graft failure than primary grafts. A large proportion of those graft losses is likely attributable to donor-directed HLA class I antibodies, detectable by flow cytometry cross-matching but not by conventional crossmatching techniques. METHODS: Long-term graft survival in a group of 106 recipients of consecutive cadaveric renal regrafts between 1990 and 1997, in whom a negative flow T-cell IgG crossmatch was required for transplantation, was compared with two other groups of cadaveric transplant recipients. The first group consisted of 174 cadaveric regrafts transplanted between 1985 and 1995 using only a negative anti-human globulin (AHG) T-cell IgG crossmatch. The second group was primary cadaveric transplants done concurrently with the flow group (1990 to 1997) using only the AHG T-cell IgG crossmatch. RESULTS: The long-term (7 year) graft survival rate of flow crossmatch-selected regraft recipients (68%; n= 106) was significantly improved over that of regraft recipients who were selected for transplantation by only the AHG crossmatch technique (45%; n=174; log-rank=0.001; censored for patients dying with a functioning graft). Graft outcome for the flow cross-matched regraft recipients was not significantly different from that of primary cadaveric patients (72%; n=889; log-rank=0.2; censored for patients dying with a functioning graft). Finally, a positive B-cell IgG flow cytometric crossmatch had no influence on long-term regraft outcome. CONCLUSIONS: The use of the flow T-cell IgG cross-match as the exclusion criterion for cadaveric renal retransplantation yields an improved long-term graft outcome over that obtained when only the AHG cross-match is used and has improved survival of regraft recipients to the level of our primary cadaveric renal transplant population.

Treatment of liver injuries at level I and level II centers in a multi-institutional metropolitan trauma system. The Midwest Trauma Society Liver Trauma Study Group.

OBJECTIVE: The development of trauma systems and trauma centers has had a major impact on the fate of the critically injured patient. However, some have suggested that care may be compromised if too many trauma centers are designated for a given area. As of 1987, the state of Missouri had designated six adult trauma centers, two Level I and four Level II, for the metropolitan Kansas City, Mo, area, serving a population of approximately 1 million people. To determine whether care was comparable between the Level I and II centers, we conducted a concurrent evaluation of the fate of patients with a sentinel injury, hepatic trauma, over a 6-year period (1987-1992) who were treated at these six trauma centers. METHODS: All patients during the 6-year study period who suffered liver trauma and who survived long enough to be evaluated by computerized tomography or celiotomy were entered into the study. Patients with central nervous system trauma were excluded from analysis. Information concerning mechanism of injury, RTS, Injury Severity Score (ISS), presence of shock, liver injury scoring, mode of treatment, mortality, and length of stay were recorded on abstract forms for analysis. Care was evaluated by mortality, time to the operating room (OR), and intensive care unit (ICU) and hospital length of stay. RESULTS: Over the 6-year period 300 patients with non-central nervous system liver trauma were seen. Level I centers cared for 195 patients and Level II centers cared for 105. There was no difference in mean ISS or ISS > 25 between Level I and II centers. Fifty-five (28%) patients arrived in shock at Level I centers and 24 (23%) at Level II centers. Forty-eight patients (16%) died. Thirty-two (16%) died at Level I centers, and 16 (15%) died at Level II centers. Twenty of 55 patients (36%) in shock died at Level I centers, and 11 of 24 (46%) died at Level II centers (p = 0.428). Forty-three patients (22%) had liver scaling scores of IV-VI at Level I centers, and 10 (10%) had similar scores at Level II centers (p < 0.01). With liver scores IV-VI, 22 of 43 (51%) died at Level I centers and 10 of 14 (71%) died at Level II centers (p = 0.184). There was no difference in mean time or in delays beyond 1 hour to the OR for those patients in shock between Level I and II centers. There was a longer ICU stay at Level II centers (5.0 +/- 8.3 vs. 2.8 +/- 8.4 days, p = 0.04). This difference was confined to penetrating injuries. There was no difference in hospital length of stay. CONCLUSIONS: In a metropolitan trauma system, when Level I and II centers were compared for their ability to care for victims of hepatic trauma, there was no discernible difference in care rendered with respect to severity of injury, mortality, delays to the OR, or hospital length of stay. It was observed that more severe liver injuries were seen at Level I centers, but this did not seem to significantly affect care at Level II centers. There was a longer ICU stay observed at Level II centers owing to penetrating injuries, possibly because there were fewer penetrating injuries treated at these facilities. Although the bulk of patients were seen at Level I centers, care throughout the system was equivalent.