Robert C. Lim

Functional analysis of grafts from living donors. Implications for the treatment of older recipients.

OBJECTIVE Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy. SUMMARY BACKGROUND DATA The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors. METHODS Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology. RESULTS In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks. CONCLUSIONS Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.

Technical result of carotid endarterectomy: Arteriographic assessment

Abstract To evaluate the technical results of operative treatment of stenosis of the internal carotid artery, arteriographic assessment was used in one hundred consecutive procedures. Operative arteriograms were taken routinely at the completion of the endarterectomy and again two to eight weeks later. Late follow-up assessment was obtained by repeating the arteriograms whenever symptoms recurred or when the five-year follow-up period was reached. One fourth of the hundred arteriograms taken at the completion of operation revealed an unsuspected defect in the repair. In all but one of these patients immediate revision was carried out. The end point of the operation was a widely patent vessel as demonstrated by angiography. Follow-up arteriography at the time of discharge from the hospital revealed the only technical failure in the hundred operations, which was in the one patient in whom revision was not performed. Late follow-up examination revealed continued patency at the five year period in all but one instance, an asymptomatic occlusion which was found in a patient who had died of myocardial infarction. Since 25 per cent of the patients had unsuspected intraluminal defects or thrombosis, it is obvious that routine operative arteriograms will increase the technical success of carotid endarterectomy. When the operative arteriogram demonstrates a good result, long-term patency of the artery after endarterectomy is assured.

The Role of Packing and Planned Reoperation in Severe Hepatic Trauma

Liver lacerations are the most common intra-abdominal injury that leads to death, and control of hemorrhage remains the primary problem in lowering mortality from severe hepatic trauma. We retrospectively reviewed operative trauma cases in which liver packing and planned reoperation were used as temporizing measures in hemodynamically unstable patients. These cases were compared to patients closely matched for age, sex, type of trauma, and associated injuries but who did not undergo liver packing and planned reoperation. Preliminary data support our contention that liver packing and planned reoperation is a valuable adjunct for the management of hemorrhage from severe hepatic injury without incurring increased morbidity or mortality. This technique is useful for the experienced trauma surgeon to arrest hemorrhage and gain hemodynamic stability before attempting definitive care and for the community hospital surgeons who after gaining hemodynamic control would like to transfer the patient to a tertiary care facility.

Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial

PURPOSE This double-blind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, safety, and patient-reported outcomes. The correlation between genotype and clinical outcomes was also analyzed. RESULTS In all, 768 patients were randomly assigned to sunitinib plus FOLFIRI (n = 386) or placebo plus FOLFIRI (n = 382). Following a second prespecified interim analysis, the study was stopped because of potential futility of sunitinib plus FOLFIRI. Final results are reported. The PFS hazard ratio was 1.095 (95% CI, 0.892 to 1.344; one-sided stratified log-rank P = .807), indicating a lack of superiority for sunitinib plus FOLFIRI. Median PFS for the sunitinib arm was 7.8 months (95% CI, 7.1 to 8.4 months) versus 8.4 months (95% CI, 7.6 to 9.2 months) for the placebo arm. Sunitinib plus FOLFIRI was associated with more grade ≥ 3 adverse events and laboratory abnormalities than placebo (especially diarrhea, stomatitis/oral syndromes, fatigue, hand-foot syndrome, neutropenia, thrombocytopenia, anemia, and febrile neutropenia). More deaths as a result of toxicity (12 v four) and significantly more dose delays, dose reductions, and treatment discontinuations occurred in the sunitinib arm. CONCLUSION Sunitinib 37.5 mg per day (schedule 4/2) plus FOLFIRI is not superior to FOLFIRI alone and has a poorer safety profile. This combination regimen is not recommended for previously untreated mCRC.

Failure patterns of cryopreserved vein grafts in liver transplantation

Reports of early success with cryopreserved saphenous veins (CSV) as arterial conduits led us to develop cryopreserved iliac veins (CIV) as interposition grafts for portal vein reconstruction in living-related liver transplantation (LRLT). Despite encouraging short-term results, retrospective analysis of long-term cryopreserved vein graft performance in LRLT at our institution has revealed a high rate of late graft failures. Between July 1992 and JUly 1994, interposition grafts (CIV for portal vein interposition n=4, CSV for portal vein interposition n=3, and CSV for hepatic artery interposition n=2) were utilized in 7 LRLT. (Two transplanted organs had both CIV and CSV grafts.) Recipients included 5 children and two small adults (median: 3.5 years, range: 0.5--59 years). Posttransplant follow-up in excess of 36 months revealed portal vein (PV) and hepatic artery (HA) complications of cryopreserved grafts in each patient. PV complications included aneurysm (n=4) diagnosed at 28, 24, 18, and 1.5 mo, stricture (n=1) diagnosed at 11 mo, and thrombosis (n=1) diagnosed at 18 mo posttransplantation. All portal vein complications have been managed without retransplantation, but one (PV thrombosis) necessitated surgical shunt therapy. Each CSV hepatic artery interposition graft has been complicated by thrombosis (diagnosed at 11 days and 24 mo posttransplant) necessitating retransplantation. Based on these observations, we have adopted alternative strategies for HA and PV reconstruction. At present, 11 LRLT have been performed without cryopreserved vein conduits over 17 mo with no vascular complications. While this study does not permit statistical analysis, these results discourage the use cryopreserved iliac veins for portal interposition and cryopreserved saphenous veins for arterial interposition in liver transplantation.

Analysis of 425 consecutive trauma fatalities: An autopsy study

Four hundred and twenty-five trauma deaths were reviewed. This series confirms that the young productive age group is most at risk for accidental death. In this series, 44.9% of the deaths were due to brain injury, subdural or epidural hematomas. Thirty-five percent of the deaths were due to hemorrhage and probably represent the most potentially salvageable group. Eight patients had preventable deaths, and eleven patients had possible preventable deaths. Prevention of these deaths is dependent upon adequate ambulance personnel, physician judgment, quality of assessment and aggressive resuscitation and treatment. Regionalization of trauma centers may aid in the reduction of mortality from accidental death.

A step‐wise logistic regression analysis of hepatocellular carcinoma an aspiration biopsy study

Fine needle aspiration biopsy (FNAB) has become a popular method to diagnose mass lesions of the liver. Although several reports have listed FNAB criteria to be used to diagnose both primary and metastatic tumors of the liver, none have separated key cytologic criteria from secondary criteria. We reviewed the FNAB smears from 35 patients with proven hepatocellular carcinoma and 74 patients with proven metastatic tumors in the liver. All specimens were coded as to the presence or absence of the following variables: polygonal cells with centrally placed nuclei; well‐defined, granular cytoplasm; large nucleoli; small cytoplasmic vacuoles; large cytoplasmic vacuoles; bile; polymorphonuclear leukocytes; malignant cells separated by sinusoidal vessels; endothelial cells surrounding tumor cell clusters; multi‐nucleated tumor giant cells; basophilic intracytoplasmic inclusions; eosinophilic intracytoplasmic inclusions; and intranuclear cytoplasmic inclusions. A step‐wise logistic regression analysis was performed on the data to determine the variables predictive of hepatocellular carcinoma. The statistical analysis selected polygonal cells with centrally placed nuclei, malignant cells separated by sinusoidal capillaries, and bile as the key cytologic criteria for hepatocellular carcinoma. Endothelial cells surrounding tumor cell clusters and intranuclear cytoplasmic inclusions were selected as secondary criteria by this analysis.

Injuries sustained from high velocity impact with water: an experience from the Golden Gate Bridge.

Over 720 persons are reported to have died jumping from the Golden Gate Bridge. A review of 100 consecutive autopsies showed that, in the majority of cases, massive pulmonary contusion, pneumothorax, laceration or perforation of the heart, great vessels, or lungs by displaced ribs were the causes of immediate death. Irreparable fractures of the liver or spleen were the most common abdominal injuries. The persons fatally injured appeared to have entered the water in a horizontal position, experiencing maximal deceleration. In contrast, six survivors entered the water feet first with more gradual deceleration. These survivors remained conscious but sustained similar injuries of lesser degree; only one sustained rib fractures. Fifty per cent had fractures of the liver or spleen requiring operative therapy. Fifty per cent sustained lung contusions and subsequent pneumothoraces. Suspicion of underlying injuries to the liver, spleen, and lungs is essential during resuscitation of those who survive impact with water.

Surgical Anatomy of the Left Lateral Segment as Applied to Living-Donor and Split-Liver Transplantation: A Clinicopathologic Study

ObjectiveTo evaluate intrahepatic vascular and biliary anatomy of the left lateral segment (LLS) as applied to living-donor and split-liver transplantation. Summary Background DataLiving-donor and split-liver transplantation are innovative surgical techniques that have expanded the donor pool. Fundamental to the application of these techniques is an understanding of intrahepatic vascular and biliary anatomy. MethodsPathologic data obtained from cadaveric liver corrosion casts and liver dissections were clinically correlated with the anatomical findings obtained during split-liver, living-donor, and reduced-liver transplants. ResultsThe anatomical relation of the left bile duct system with respect to the left portal venous system was constant, with the left bile duct superior to the extrahepatic transverse portion of the left portal vein. Four specific patterns of left biliary anatomy and three patterns of left hepatic venous drainage were identified and described. ConclusionsAlthough highly variable, the biliary and hepatic venous anatomy of the LLS can be broadly categorized into distinct patterns. The identification of the LLS duct origin lateral to the umbilical fissure in segment 4 in 50% of cast specimens is significant in the performance of split-liver and living-donor transplantation, because dissection of the graft pedicle at the level of the round ligament will result in separate ducts from segments 2 and 3 in most patients, with the further possibility of an anterior segment 4 duct. A connective tissue bile duct plate, which can be clinically identified, is described to guide dissection of the segment 2 and 3 biliary radicles.

Continuous monitoring of tissue gas tensions and pH in hemorrhagic shock

Tissue and blood gases and pH were measured before and during hemorrhagic shock and after the infusion of dextran 40. Tissue changes were profound in contrast to blood values which changed little. Hypoxia occurred first, and was followed closely by an increase in PCO 2 and a decrease in pH. Liver surface pH changed more than did muscle surface pH.