Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report.

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.

Rapidly increasing liver progenitor cell numbers in human regenerating liver after portal vein ligation and liver partition.

BACKGROUND: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitor cells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells. Although liver progenitor cell proliferation during the regenerative process has been observed in animal models of severe liver injury, it has never been observed in vivo in humans because it is unethical to take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitor cells and the roles they play in liver regeneration. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy so that major hepatectomy can be performed safely. This staged procedure allows for liver biopsy specimens to be taken before and after the liver begins to regenerate. CASE PRESENTATION: The liver progenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatic tumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number of liver progenitor cell under high magnification examination by stain of immunomarkers. This is the first in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.

Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis.

Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1ß (IL-1ß) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

PURPOSE: Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. METHODS: In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. RESULTS: Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. CONCLUSION: Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts.

HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E

Prediction of microvascular invasion of hepatocellular carcinoma by pre-operative CT imaging.

OBJECTIVE: The aim of this study was to diagnose microvascular invasion in patients with solitary hepatocellular carcinoma (HCC) from pre-operative CT imaging. METHODS: 102 patients with solitary HCC who underwent curative hepatectomy were retrospectively included in our study. The pre-operative 3-phase CT imaging and laboratory data for the 102 patients were reviewed. Tumour size, tumour margin, peritumoral enhancement and α-fetoprotein level were assessed. Surgical pathology was reviewed; tumour differentiation, liver fibrosis score and microvascular invasion were recorded. RESULTS: The histopathological results revealed that 50 HCCs were positive and the other 52 were negative for microvascular invasion. Univariate analysis revealed that tumour size (p = 0.036), higher Edmondson-Steiner grade (p = 0.047) and non-smooth tumour margin (p < 0.001) showed statistically significant associations with microvascular invasion. Multivariate logistic regression analysis showed that non-smooth tumour margin had a statistically significant association with microvascular invasion only (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the non-smooth tumour margin in the prediction of microvascular invasion were 66%, 86.5%, 82.5% and 72.6%, respectively. CONCLUSION: Non-smooth tumour margin in pre-operative CT had a statistically significant association with microvascular invasion. More aggressive treatment should be considered in HCC patients with suspected positive microvascular invasion.

[The evaluation of the anti-shivering effect of tramadol during epidural anesthesia].

60 patients (except parturients) suffering from shivering after receiving epidural anesthesia were randomly divided into 2 equal groups. In order to evaluate the effect of Tramadol on the shivering, i.v. Tramadol (1 mg/Kg), in contrast to distilled water (20 ml) for the control group, was administered to the patients in the experimental group. We compared the arrest time between the two groups in addition to systolic blood pressure, diastolic blood pressure, heart rate, arterial O2 saturation, respiratory rate and body surface temperature. Furthermore, the degree of shivering was also compared sequentially. The systolic pressure of the control group declined significantly in the first 30 minutes (P < 0.05). The other data, including the diastolic pressure, heart rate, arterial O2 saturation, respiratory rate and body surface temperature, showed no significant difference (P > 0.05). The arrest time in the experimental group was 179 +/- 71.25 seconds in contrast to 2790 +/- 440.23 seconds in the control group, a large significant difference (P < 0.001). 10% of the patients in the experimental group experienced nausea or vomiting and 6.67% of the patients showed sedation which did not disturb consciousness level of psychomotor status. Since the exact mechanism of shivering during epidural anesthesia is not established, we sincerely hope more information about the effect to Tramadol on shivering can be uncovered.

["Walkman music" during epidural anesthesia].

The sedating effect and influence of walkman music on 120 patients, that were randomly divided into a music and non-music group, who had received epidural anesthesia were investigated. It was found that significantly fewer patients in the music group felt anxious during surgery (P = 0.049). Meanwhile, heart rate and mean arterial pressure of the non-music group remained at a higher level, resulting in higher heart loading. Furthermore, patients listening to music had a significantly smaller need of sedatives (P = 0.001). With the purpose of reducing the consumption of sedatives, and offering a better anesthetic environment, we recommend the use of music during regional anesthesia.