Decorin expression is decreased in first trimester placental tissue from pregnancies with small for gestation age infants at birth.

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. FGR pregnancies are often associated with histological evidence of placental vascular thrombosis. The proteoglycans are important components and regulators of vascular homeostasis. Previous studies from our laboratory highlighted mRNA and protein expression differences in placental proteoglycan decorin (DCN), within a clinically well-characterised cohort of third-trimester idiopathic FGR compared with gestation-matched uncomplicated control pregnancies. We also showed that decorin contributes to abnormal angiogenesis and increased thrombin generation in vitro. These observations suggest that DCN gene expression may contribute to the etiology of FGR. Small for gestational age (SGA) is frequently used as a proxy for FGR and is defined as a birth weight below the 10th percentile of a birth weight curve. We therefore made use of a unique resource of first trimester tissues obtained via chorionic villus sampling during the first trimester to investigate the temporal relationship between altered DCN expression and any subsequent development of SGA. We hypothesized that placental DCN expression is decreased early in gestation in SGA pregnancies. Surplus chorionic villus specimens from 15 women subsequently diagnosed with FGR and 50 from women with uncomplicated pregnancies were collected. DCN mRNA and DCN protein were determined using real-time PCR and immunoblotting, respectively. Both DCN mRNA and protein were significantly decreased in placentae from first-trimester SGA-pregnancies compared with controls (p < 0.05). This is the first study to report a temporal relationship between altered placental DCN expression and subsequent development of SGA.

The effects of a Chinese medicinal suppository (Vitalliver) on insulin-like growth factor 1 and homocysteine in patients with hepatitis B infection.

The liver is the major organ for the metabolism of homocysteine (Hcy) and production of insulin-like growth factor 1 (IGF-1). Hcy metabolism and IGF-1 synthesis may be impaired in chronic liver diseases. The study investigated the regulatory effect of a Chinese herbal suppository, Vitalliver, on Hcy and IGF-1, as well as their relationship in patients with hepatitis B infection. Forty patients with chronic hepatitis B virus (HBV) infection without cirrhosis, 25 males and 15 females, were observed for changes in Hcy and IGF-1 after the administration of Vitalliver (one nightly) for a period of 3 months. Serum levels of Hcy, IGF-1 and IGFBP-3 were measured at baseline, and at 1 month and 3 months after treatment. Vitalliver reduced Hcy levels significantly (p = 0.001) from 9.7 +/- 2.8 to 9.0 +/- 2.1 micromol/L after treatment of 3 months. Furthermore, the IGF-1 levels increased significantly (p < 0.001) from 170.2 +/- 81.8 to 212.8 +/- 80.9 ng/mL at 1 month and 187.5 +/- 72.3 ng/mL at 3 months (p = 0.001) after treatment. In conclusion, it is speculated Vitalliver may have a self-regulatory effect on the release of IGF-1 in HBV patients without liver cirrhosis.

Complications of liver donation for living related liver transplantation.

Living related liver transplantation (LRLT) has gained popularity, especially in Asian countries as the primary mode of liver transplantation. LRLT, however, carries the inherent problem of potential donor harm. In view of reports of donor deaths and significant donor morbidity (as high as 67%), we examined donor complication rates in our LRLT program. All sixteen LRLT donors between February 2000 and January 2003 were retrospectively analyzed. The 16 donors (13 men, 3 women) of mean age 30 years (range, 18-49 years) included 5 donations from siblings, 2 from parents, and 9 from offsprings. The portion of liver donated was L hepatectomy (n = 4) R hepatectomy (n = 7), and Modified Extended R hepatectomy (n = 5) with the weight of resected liver being 618.9 g (range, 380-1000). The mean blood loss was 936 mL (range, 400-1900 mL), but only 2 donors required transfusion of banked blood. The mean intensive care unitstay was 1.06 days (range, 1-2 days) and the mean hospital stay was 9.12 days (range, 7-14 days). There was no case of reoperation and no mortality. There was no biliary or vascular complication. Four of 16 (25%) donors had a minor morbidity; 2 of 16 (12.5%) had a morbidity requiring intervention. In conclusion, with meticulous preoperative, intraoperative, and postoperative management, successful LRLT can be performed with minimal donor morbidities.

Critical graft size and functional recovery in living donor liver transplantation.

With a high prevalence of chronic hepatitis B and a low cadaveric organ donation rate, living donor liver transplantation (LDLT) remains the only option for many patients in Hong Kong. In such cases, the liver graft volume is smaller owing to a partial liver graft; therefore, a problem of small-for-size grafts often occurs. Between September 1999 and April 2003, 25 cadaveric, 16 living related, and 1 auto-LTs were performed at our center. The outcomes of LDLT were analyzed to assess the critical graft size and functional recovery. Among the 16 LDLT recipients (mean age, 44.4 +/- 14.4 years; mean weight, 61.9 +/- 11.4 kg), 1 patient received a graft from a donor left lobe (weight, 400 g) in an auxillary partial orthotopic LT (APOLT), 12 received right lobes, and 3 received left lobes. Besides the APOLT case, the overall graft/recipient weight ratio (GRWR) for the 15 LDLTs was 1.11 (0.76 to 1.75). The GRWR in the 25 cadaveric LTs was 1.92 (1.05 to 3.69) (P < .001). Among the 12 successful LDLTs, there were 5 (41.7%) cases of small-for-size graft syndrome: 3 of 3 (100%) in GRWR < or = 0.8%; 5 of 6 (83.3%) in GRWR < 1%; and 0 of 6 with GRWR > 1%. The initial post-LT graft function parameters were significantly higher among the LDLT group: International normalized ratio (INR), 1.42 vs 1.24, P = .03; alanine aminotransferase (ALT, 387 vs 201 IU/L, P = .005, and bilirubin, 170 vs 48 micromol/L, P < .001 as compared to the cadaveric transplant group). Small-for-size graft syndrome can be avoided if GRWR > 1%, but often occurs when GRWR < 0.8%. Graft function in LDLT recovers more slowly than in cadaveric liver transplant.

Multimodality tumor control and living donor transplantation for unresectable hepatocellular carcinoma.

Liver transplantation (LT) is an acceptable mode of treatment for selected patients with unresectable hepatocellular carcinoma (HCC). However, due to the scarcity of cadaveric donor organs, it is considered desirable for patients to opt for living donor liver transplantation (LDLT) or, for those not being transplanted soon, to have some form of tumor control therapy. Such an approach in our program is analyzed and reported. At our institution, 42 LTs were performed between October 1999 and April 2003. Of these, 18 recipients (15 men, 3 women) had 27 HCC. The average number and size of HCC was 1.59 (1 to 4) and 2.31 (0.2 to 6.5) cm, respectively. Thirteen (72%) patients were transplanted primarily for the HCC, whereas five (28%) others were incidental HCC cases. Seven patients (5 LRLT, 2 cadaveric LT) were transplanted soon after listing, and thus did not require tumor control therapy. Six patients waited for 11 (6 to 19) months before LT. Three patients underwent microwave coagulation therapy, and one had additional alcohol injections. One patient received the novel PIAF (cisplatin, interferon, adriamycin, and 5-FU) chemotherapy regimen followed by selective internal irradiation (SIR) treatment. One patient received conformal radiation therapy and another received SIR treatment before LT. Besides 2 postoperative deaths, the remaining 16 patients have been well, with a mean follow-up of 20.4 (3.6 to 41.2) months. In conclusion, for patients with unresectable HCC, in areas with poor cadaveric donor rate, living donation should be the first option. If a suitable live donor is not available, aggressive multimodality therapy is recommended while waiting for cadaveric LT.

Impact of severe acute respiratory syndrome on liver transplantation service.

Severe acute respiratory syndrome (SARS) struck 1755 patients in Hong Kong and developed into a global health crisis. Although the World Health Organization and national health authorities are sparing no effort to contain the disease and to find a cure for the potentially deadly infection, SARS has an impact on our liver transplantation (LTx) program. Before the SARS outbreak, an average of 1 LTx was performed per month in our center. For 6 months since the outbreak, there had been no LTx performed. The intensive care unit had to be dedicated to patients with SARS. Two of the LTx team members were struck by SARS. A survey conducted among LTx recipients and their family members (n = 45) demonstrated symptoms of anxiety and stress in all. Some LTx recipients were treated at the Emergency Department for suspected SARS, which were later confirmed to be false alarms. Many LTx patients were too frightened to come back for follow-up. A new strain of coronavirus was identified as the causative agent. The origin of this virus is uncertain but the probability of zoonoses is being seriously discussed. Not only are immunosuppressed patients exposed to higher risk of infection, but also the waiting list mortality is also expected to increase. The SARS outbreak has demonstrated the vulnerability of an organ transplantation service and reminds us of the fearful possibility of zoonoses in future xeno-transplantation.

Absence of impact of donor hepatic steatosis and posttransplantation lamivudine resistance in a patient with chronic hepatitis B.

A patient with chronic hepatitis B underwent liver transplantation for end-stage cirrhosis. The donor liver graft had moderate steatosis and fibrosis. He was placed on lamivudine for hepatitis B prophylaxis but developed viral relapse due to emergence of a lamivudine-resistant mutant at week 72 posttransplantation. Results of liver biochemistry were normal liver histology revealed minimal steatosis and inflammation at weeks 151 and 128, respectively. This report illustrates that the use of a steatotic donor liver and the emergence of lamivudine resistance posttransplantation are not necessarily associated with significant graft damage. A marginal donor graft can be considered due to the donor shortage. Lamivudine monoprophylaxis for hepatitis B virus-related liver diseases post liver transplantation can be used in areas where hepatitis B immunoglobulin is not affordable.

The longest survivor and first potential cure of an advanced cholangiocarcinoma by ex vivo resection and autotransplantation: a case report and review of the literature.

Bismuth type IV hilar cholangiocarcinoma (CC) carries a poor prognosis; however, ex vivo liver resection and autotransplantation (Atx) is theoretically a treatment option. There are only five previously reported cases of this procedure for hilar CC in the English literature, and most of them died early in the postoperative period. The only reported survivor died of tumor recurrence at 13 months. We are reporting a patient who has survived for 17 months without any sign of tumor recurrence. This probably represents the world's first cure for CC using this technique. This patient is a 26-year-old woman with a Bismuth Type IV CC. Portal vein involvement at the confluence was shown on angiogram, and in situ resection was deemed impossible. Ex vivo resection of segments five, six, seven, eight, and part of segment four was performed followed by a partial liver Atx. The pathology specimen demonstrated CC with clear margins. MRI and CT examinations done over the subsequent 17 months showed no evidence of recurrence. In conclusion ex vivo liver resection and Atx can be a viable option for cure among highly selected patients with CC.

Induction of Fas and Fas ligand expression on malignant glioma cells by Kupffer cells, a potential pathway of antiliver metastases.

Kupffer cells play an important role in controlling the growth and development of liver metastases. However, the pathway of Kupffer cells against tumor metastases is not clear. In the present study, we set up an experimental model to investigate the mechanisms on how Kupffer cells kill tumor cells which metastasize to the liver. Malignant glioma cells were cocultured with Kupffer cells or treated with culture medium collected from lipopolysaccharide (LPS)-activated Kupffer cells. The results showed that the interaction between Kupffer cells and malignant glioma cells significantly stimulated the generation of tumor necrosis factoralpha (TNFalpha). TNFalpha was mainly produced by Kupffer cells, as its level in culture medium obtained from LPS-treated Kupffer cells was not significantly different from that of malignant glioma cells treated with the same medium. Both Kupffer cells and LPS/Kupffer cell-conditioned supernatants induced expression of Fas and Fas ligand on malignant glioma cells. Subsequently a significant proportion of malignant glioma cells became apoptotic, as evidenced by positive staining of annexin V and propidium iodine and an increase in cellular DNA fragmentation. Therefore, this study supports a novel pathway of Kupffer cells against liver metastases, in which tumor cells were apoptotic via the Fas-Fas ligand system induced by TNFalpha released from Kupffer cells.