Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation

A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated.     

Erysipelothrix rhusiopathiae Peritonitis in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis

Erysipelothrix rhusiopathiae is known as a pathogen of occupational diseases or a zoonosis. We report a case of E. rhusiopathiae peritonitis in a 50-yr-old male undergoing continuous ambulatory peritoneal dialysis (CAPD). He was suffered from mild abdominal pain with a distinctive erysipeloid skin lesion. E. rhusiopathiae was considered to be introduced through a lacerated wound on his hand when he was exposed to contaminated materials. He was treated successfully with a first generation cephalosporin. To our knowledge, CAPD peritonitis due to E. rhusiopathiae is very rare, and this is a report of the first case in Asia.     

Bilateral hyperexcitability of thalamic VPL neurons following unilateral spinal injury in rats

In the present study, we have examined whether spinal hemisection injury induces changes in the electrophysiological properties of thalamic ventral posteriorlateral (VPL) neurons in rats. Male Sprague–Dawley rats were subjected to unilateral spinal cord injury by transverse hemisection at the T13 spinal segment. Four weeks after the T13 spinal hemisection, the injured rats displayed robust allodynic behaviors on both sides of hindpaws compared to sham controls (P < 0.05). Extracellular recordings taken 4 weeks after the hemisection revealed that wide dynamic range (WDR) neurons had significantly increased spontaneous and brush-, pressure-, and pinch-evoked activities, respectively, on both sides of the thalamic VPL regions (P < 0.05). In contrast, low threshold (LT) neurons showed only an increase in the brush-evoked activity compared to sham controls (P < 0.05). However, afterdischarge activity in both types of neurons showed no changes. In addition, both sides of the thalamic VPL regions showed higher incidences of WDR neurons. In conclusion, our data demonstrate that spinal unilateral injury induces bilaterally increased evoked activity in thalamic VPL neurons.     

Case Report: Intracerebral Hemorrhage After γ-Knife Surgery for Metastatic Brain Tumor

The authors report a case of a 69-year-old man with metastatic brain tumors who died of spontaneous intracerebral hemorrhage 3 days after -knife surgery. He had been suffering from lung cancer with multiple systemic metastasis. Preoperative magnetic resonance images showed two well-defined round lesions with intratumoral hemorrhage in the left frontal and right occipital lobe. There was no bleeding tendency in the hematological examination and the patient was normotensive. -Knife surgery was performed on both lesions in a single session. However, the patient died of massive intracerebral hemorrhage from the left frontal lesion 3 days after the surgery. There have been no previous reports of mortality resulting from spontaneous intracerebral hemorrhage after -knife surgery in metastatic brain tumors documented in the literature. It is likely that the two events, -knife surgery and spontaneous intracerebral hemorrhage, occurred separately and were not associated. However, it is worth noting that there is a possibility of bleeding after -knife surgery, especially in a metastatic brain tumor with preexisting intratumoral hemorrhage as in our case.     

Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas

Purpose: Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. Methods: Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. Results: Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. Conclusions: This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients. Grant Support: supported by grant No. 03-2005-024 from the Seoul National University Hospital Research Fund.     

Arsenic trioxide sensitizes CD95/Fas-induced apoptosis through ROS-mediated upregulation of CD95/Fas by NF-kappaB activation

CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As2O3) sensitized CD95/Fas-induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As2O3-mediated increase in the expression of the CD95/Fas. N-acetyl-L-cysteine, a specific scavenger of reactive oxygen species, abrogated As2O3-induced upregulation of CD95/Fas and enhancement of CD95/Fas-mediated apoptosis. Furthermore, inhibition of NF-kappaB by transient transfection of IkappaBalpha supersurppessor blocked the increase of CD95/Fas expression following As2O2 treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As2O3-sensitized CD95/Fas-induced apoptosis, demonstrating the specificity of CD95/Fas-binding ligands in the As2O3-sensitized CD95/Fas-induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas-mediated apoptosis by As2O3 can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF-kappaB activation.     

Long-term outcome of trigeminal neurinomas with modified classification focusing on petrous erosion

BACKGROUND: The authors present a retrospective analysis of 29 consecutive patients with trigeminal neurinomas. Modified classification based on the tumor distribution over petrous ridge is suggested to select the optimal surgical approach and to predict the outcome. METHODS: Preoperative computed tomography (CT) or magnetic resonance (MR) images were analyzed to measure a long diameter of tumor axis (LD), which divided into middle and posterior fossa and a width of the petrous erosion (PW) by the tumor on axial image. The tumors were classified into four groups (M, tumor confined to middle fossa; Mp, tumor mainly in middle fossa; M = P, tumor equally distributed into both middle and posterior fossa; Pm, tumor mainly in cisternal space of posterior fossa with slender, rarely round extension into Meckel's cave), and extent of removal was compared between the groups. Long-term outcomes were based on recurrence-free survival. RESULTS: Total removal was achieved in 16 patients including stage operation (55%). Excluding three tumors, which underwent gamma knife for residual tumor, 8 of 10 subtotally removed tumors recurred at 50 months on average. The LD and PW are significantly different among the tumor types. The M = P type is the largest in both parameter, while the M type is the smallest in LD; Pm type is the smallest in PW, respectively. The tumors with equal or lager posterior fossa component (M = P and Pm type) were more difficult to remove totally by single attempt than those with smaller or nil posterior fossa mass (Mp and M type). Also, the corrected PW (PW over the tumor diameter of minor portion) shows a tendency to influence the extent of removal as the relatively narrow PW hindered the total removal. CONCLUSIONS: Aggressive attempt for total removal using skull base approach is recommended, especially for those having dominant posterior fossa component and for those having relatively narrow PW.     

Analgesic effects of intra-nasal enkephalins

The analgesic effects of intranasal delivery of leucine enkephalin (Leu-Enk) and its synthetic analogue [D-ala(2)]-leucine enkephalinamide (YAGFL) with or without enzyme inhibitors and/or absorption enhancers were investigated using the acetic acid-induced writhing test in mice. The analgesic activity was significantly affected by the time delay after the administration of Leu-Enk; the inhibition rates for the groups administered with acetic acid 5 min and 30 min after the administration of Leu-Enk were 56.40 +/- 8.54 and 17.98 +/- 7.07%, respectively. The addition of enzyme inhibitors and absorption enhancers markedly increased the inhibition rate of Leu-Enk and YAGFL; their inhibition rates were about four times and twice those without any enzyme inhibitor or absorption enhancer, respectively. The enzyme inhibitors and absorption enhancers that produced the highest inhibition rates of Leu-Enk and YAGFL were azelaic acid (1%), thimerosal (0.5 mM, TM), ethylenediamine-tetraacetic acid (5 mM, EDTA) and L-alpha-lysophosphatidylcholine (0.5%, LPC), and TM (0.5 mM), EDTA (5 mM), LPC (0.5%) and povidone (5%), respectively. The ED50 value of both enkephalins was also determined and found to be about 13 microg kg(-1), which is 850 and 60 times more potent than literature values for ketoprofen and morphine, respectively. Based on these results it was concluded that Leu-Enk or YAGFL could exert very high analgesic activity when administered nasally with a combination of inhibitors and absorption enhancers as compared with other analgesics.