Liver transplantation for hepatocellular carcinoma

OBJECTIVE: To analyze patient and tumor characteristics that influence patient survival to select patients who would most benefit from liver transplantation. SUMMARY BACKGROUND DATA: The selection of patients with hepatocellular carcinoma (HCC) for liver transplantation remains controversial. METHODS: One hundred twelve patients with nonfibrolamellar HCC who underwent a liver transplant from 1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier method, with differences in outcome assessed using the log-rank procedure. Multivariate analysis was then performed using a Cox regression model. RESULTS: Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years, respectively. Patients infected with the hepatitis B virus had a worse 5-year survival than those who were not (43% vs. 64%), with most deaths being attributed to recurrent hepatitis B. However, patients with hepatitis B virus who underwent more recent transplants using antiviral therapy fared as well as those who were negative for the virus, showing a 5-year survival rate of 77%. Patients with vascular invasion by tumor had a worse 5-year survival than patients without vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm, and poorly differentiated tumor grade were predictors of tumor recurrence by univariate analysis; however, only vascular invasion remained significant on multivariate analysis: the rate of tumor recurrence at 5 years was 65% in patients with vascular invasion and only 4% for patients without vascular invasion. CONCLUSIONS: For well-selected patients with HCC, liver transplantation in the current era can achieve equivalent results to transplantation for nonmalignant indications. Vascular invasion is an indicator of high risk of tumor recurrence but is difficult to detect before transplantation.     

Assessment of Depth of Anesthesia and Postoperative Respiratory Recovery after Remifentanil-versus Alfentanil-based Total Intravenous Anesthesia in Patients Undergoing Ear-Nose-Throat Surgery

Background: The authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics.

Methods: Forty consenting patients (classified as American Society of Anesthesiologists physical status I-III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 [mu]g/kg; maintenance infusion, 0.25 [mu]g [middle dot] kg-1 [middle dot] min-1) or alfentanil (loading dose, 50 [mu]g/kg; maintenance infusion, 1 [mu]g [middle dot] kg-1 [middle dot] min-1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 [mu]g [middle dot] kg-1 [middle dot] min-1). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded.

Results: Demographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group.     

Favorable results of acetabular reconstruction with impacted morsellized bone grafts in patients younger than 50 years: A 10- to 18-year follow-up study of 34 cemented total hip arthroplasties

We report a long-term review of 41 acetabular reconstructions using impacted morsellized bone grafts and a cemented total hip arthroplasty (THA) in patients younger than 50 (22-49; average 38) years. Reconstruction was performed in 23 primary THA (19 patients) and 18 revision THA (17 patients). 3 patients were lost to follow-up and 3 (4 hips) died within 10 years of surgery; none had a revision. Thus, 34 hips (30 patients) were reviewed with an average follow-up of 13 (10-18) years. In 2 hips, a revision was performed for aseptic loosening of the acetabular component 7 and 11 years after surgery. One additional cup was revised after 12 years during a femoral stem revision due to wear and matching problems, but was well fixed. The survival rate of the acetabular reconstruction technique was 94% (95% CI: 90-98%).     

Perivenous support reduces early changes in human vein grafts: studies in whole blood perfused human vein segments

BACKGROUND: Patency of vein grafts in coronary artery bypass grafting procedures is generally less favorable than those of selected arterial grafts. However, vein grafts still are needed in cardiac operations. It would be desirable to find measures to improve the patency of vein grafts next to antithrombotic regimens. Animal studies demonstrated that arterial pressure induces overdistention of the thin-walled vein grafts and that prevention of this overdistention with extravascular support ameliorates the arterialization process with, subsequently, more favorable patency. To evaluate whether perivenous stenting of the rather muscular human vein grafts is also beneficial, we designed an in vitro model to study the early effects of perivenous support in human vein grafts. METHODS: Seven paired segments of human vein graft obtained during coronary artery bypass grafting procedures were placed in a perfusion circuit and perfused simultaneously with autologous whole blood, with a pressure of 60 mm Hg (nonpulsatile flow). After 30 minutes of perfusion, one segment, and after 60 minutes of perfusion, the remaining segment were taken for histologic and immunohistochemical examination. In the next experiments 7 segments of human vein graft were placed in the circuit and supported with a polytetrafluoroethylene graft to prevent overdistention with 7 unstented segments as controls. RESULTS: In unsupported vein grafts perfused with autologous blood under a pressure of 60 mm Hg, a complete de-endothelialization was shown after 1 hour of perfusion. In the study vein grafts, with a perivenous polytetrafluoroethylene graft preventing overdistention (n = 7), the endothelium remained intact. Electron microscopic investigation of the media showed severe damage in the circular smooth muscle layer in the unstented group, whereas in the stented group almost no injury was found. CONCLUSION: In our in vitro closed-loop model, reproducible vessel wall changes were observed in all human vein graft specimens studied. The beneficial effect of perivenous support could also be established for the human greater saphenous vein, providing a basis for clinical application.     

Radioimmunotherapy in patients with head and neck squamous cell carcinoma: initial experience

BACKGROUND: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. METHODS: The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. RESULTS: Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. CONCLUSIONS: Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.     

Effect of interleukin-17 on nitric oxide production and osteoclastic bone resorption: is there dependency on nuclear factor-kappaB and receptor activator of nuclear factor kappaB (RANK)/RANK ligand signaling?

Interleukin-17 (IL-17) is a proinflammatory cytokine produced exclusively by activated memory T cells and has recently been found to stimulate osteoclastic resorption. Like other proinflammatory cytokines, IL-17 may affect osteoclastic bone resorption indirectly via osteoblasts, possibly by mechanisms previously reported for chondrocytes that respond in very similarly to osteoblasts. As in chondrocytes, but only in combination with tumor necrosis factor-alpha (TNF-alpha), IL-17 induced nitric oxide (NO) production in osteoblastic cells and fetal mouse metatarsals by a nuclear factor-kappaB (NF-kappaB)-dependent mechanism. This effect was associated with elevated mRNA levels of the NF-kappaB isoforms RelA and p50. In fetal mouse metatarsals, IL-17 stimulated osteoclastic bone resorption only in combination with TNF-alpha. The pathway by which the cytokine combination exerts this effect was examined using inhibitors of NO synthesis and NF-kappaB activation. Although both inhibitors used abolished NO production, they did not prevent the stimulatory effect of the cytokine combination on osteoclastic resorption. In contrast, the inhibitors slightly increased osteoclastic resorption, suggesting a suppressive rather than stimulatory effect of NO on cytokine-induced bone resorption. In addition, we showed that IL-17 + TNF-alpha stimulated osteoclastic resorption independent of NF-kappaB signaling. To further examine the pathway by which osteoclastic resorption was stimulated, we used osteoprotegerin, a specific inhibitor of the receptor activator of NF-kappaB (RANK)/receptor activator of the NF-kappaB ligand (RANKL) pathway. Osteoprotegerin partially inhibited IL-17 + TNF-alpha-stimulated osteoclastic resorption only at the high concentration of 1000 ng/mL, whereas it completely blocked parathyroid hormone-related peptide-stimulated resorption at 300 ng/mL. In conclusion, IL-17 stimulated NO production by an NF-kappaB-dependent pathway in osteoblastic cells and fetal mouse metatarsals only in combination with TNF-alpha. Neither NO production nor NF-kappaB signaling, and only partly the RANK/RANKL pathway, were involved in the stimulatory effect of the cytokine combination on osteoblastic bone resorption in these long bones, suggesting the existence of other pathways by which osteoclastic resorption can be stimulated.     

Naloxone improves functional recovery of myocardial stunning in conscious dogs through its action on the central nervous system

This study tests the hypothesis that naloxone, but not its quarternarysalt, naloxone methiodide (which does not enter the centralnervous system), improves recovery from myocardial stunningin conscious dogs. Twenty dogs were chronically instrumentedfor measurement of heart rate, left atrial, aortic and leftventricular pressure (LVP), LV dP•dt_max^–1 and myocardialwall thickening fraction (WTF). Regional myocardial blood flowwas determined with coloured microspheres. Occluder around theleft anterior descending artery (LAD) allowed induction of reversibleLAD ischaemia. Each of the 20 dogs underwent two LAD ischaemicchallenges. Experiments (performed on separate days, in crossoverfashion) were: (i) 10 min of LAD occlusion after applicationof naloxone 63 µg kg^–1 or naloxone methiodide 63µg kg^–1 and (ii) occlusion without naloxone or naloxonemethiodide. WTF was measured at baseline and until completerecovery occurred. LAD ischaemia significantly reduced LAD WTFwith (mean (SD) 54 (15)% lower than baseline) and without naloxone(55 (16)% lower than baseline), without significant haemodynamicdifferences. Between 1 to 30 min of reperfusion, WTF was significantlyhigher with naloxone (P<0.05). There was no difference inWTF with or without naloxone methiodide. We conclude that naloxoneimproved recovery from myocardial stunning in conscious dogs,and that this was centrally mediated. Br J Anaesth 2001; 86: 545–9     

Is a 1-cm margin necessary during nephron-sparing surgery for renal cell carcinoma?

Objectives. To determine whether a 1-cm margin is necessary for cancer control during nephron-sparing surgery (NSS) for renal cell carcinoma (RCC).Methods. A retrospective review of 67 patients who underwent NSS for RCC between 1990 and 2000 was conducted. The data collected included patient demographics, tumor size and location, histologic type and grade, margin status (positive or negative), and the shortest distance of normal parenchyma (in millimeters) around the tumor in the final pathologic specimen. Recurrence was determined from the clinical follow-up, which included physical examination, ultrasonography or computed tomography, and various laboratory tests.Results. Fifty-five cases were performed open and 12 laparoscopically. The mean follow-up was 60 months (range 5 to 124). The mean tumor size was 3.0 cm (range 0.9 to 11.0). Seven patients were found to have a positive margin; 1 died of metastatic RCC, 1 was alive with systemic recurrence, and 5 had no evidence of disease. Of 11 patients with a negative margin distance of less than 1 mm, 9 were recurrence free, 1 had simultaneous local and pulmonary relapse, and the other had pulmonary recurrence only. The remainder of the study patients (n = 49) had negative margins greater than 1 mm, and all were alive without evidence of disease at the last follow-up.Conclusions. This review questions the necessity of a 1-cm margin to prevent recurrence after NSS for RCC. Additional studies to determine the optimal margin distance should be conducted.     

Brain death-related energetic failure of the donor heart becomes apparent only during storage and reperfusion: an ex vivo phosphorus-31 magnetic resonance spectroscopy study on the feline heart.

BACKGROUND AND OBJECTIVE: Recently, we have shown, by using localized in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) of the anterior left ventricular wall, that brain death (BD) is not associated with reduced myocardial energy status. In this study, we applied ex vivo 31P MRS of the entire heart to study the effects of BD on the energy status of the feline donor heart following explantation. METHODS: We used cats (6 BD and 6 controls [C]) in a 26-hour protocol. After 2 hours of preparation, we induced BD by filling an intracranial balloon at t = 0 hour. At t = 6 hours, the hearts were arrested with St. Thomas' Hospital cardioplegic solution, explanted, and stored in the same solution at 4 degrees C in a 4.7 Tesla magnet for 17 hours. Subsequently, the hearts were reperfused in the Langendorff mode at 38 degrees C for 1 hour. The first 5-minute 31P MRS spectrum was obtained 1 hour after crossclamping the aorta; we obtained subsequent spectra every hour during storage and every 5 minutes during reperfusion. At the end, the hearts were dried and weighed. Phosphocreatine (PCr), gamma-adenosine triphosphate (gamma-ATP), inorganic phosphate (Pi), and phosphomonoesters (PME), were expressed per g dry heart weight. The intracellular pH (pH(i)) and the PCr/ATP ratio were calculated. RESULTS: During storage, we identified a significant but similar decrease of pH(i), PCr/ATP ratio, and PCr in both groups. During reperfusion, pH(i) and PCr/ATP ratio recovered similarly in both groups, whereas the recovery of PCr in the BD group was significantly lower (p < 0.05). The Pi and PME increased in both groups during storage but to a lesser extent in the BD group (p < 0.05). This difference disappeared during reperfusion. The gamma-ATP was already significantly lower in the BD group at the onset of storage, and this remained so throughout storage and reperfusion (p < 0.05 vs C). Contractile capacity was lost in all hearts, except for 1 heart in the BD group. CONCLUSION: Brain death-related failure of the energetic integrity of the feline donor heart becomes apparent only when using 31P MRS during ischemic preservation and subsequent reperfusion.     

Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries

OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries to study the gene expression pattern between normal and osteoarthritic cartilage. METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular cartilage was isolated and used to prepare cDNA libraries. Approximately 5000 ESTs from each library were sequenced and analysed using bioinformatic tools. The expression of select genes was confirmed by Northern blot and in situ hybridization analysis. RESULTS: Multiple gene families including several classical cartilage matrix protein encoding genes were identified. Approximately 28-40% of the genes sequenced from these libraries were novel, while half of the genes encoded known proteins and 4-6% of the genes encoded novel homologs of known proteins. Several known genes, whose expression has not been reported previously in cartilage, were also identified. We have confirmed the cartilage expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ hybridization analysis. CONCLUSION: This is the first report of the preparation and sequencing of cDNA libraries from adult human normal and osteoarthritic articular cartilage. Further analysis of genes identified from these libraries may provide molecular targets for diagnosis and/or treatment of osteoarthritis (OA).