Liver transplantation for hepatocellular carcinoma: how far can we push the envelope?
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Biomedical subjects
Publications and source records attributed to K C Tan.
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METHODS: Twenty orbital defects (2 x 2 cm) were created in ten adult Yorkshire pigs. Two software products (Velocity and Mimix) were evaluated with regard to image processing, three-dimensional reconstruction, and fabrication of individually shaped polycaprolactone (PCL) scaffolds to reconstruct these defects. Four different techniques were tested for the reconstruction: group 1 = no reconstruction, group 2 = polylactide sheet, group 3 = PCL scaffold, group 4 = bone marrow-coated PCL scaffold. The pigs were sacrificed at 3 months. RESULTS: In group 1 soft tissue scar formation could be found, but without any new bone. Group 2 showed a thick fibrous capsule around the PLLA sheet, whereas at the border zone of the defect signs of new bone formation could be detected. In group 3 the PCL scaffolds were filled with fibrous tissue and some areas that showed new bone formation (6.4% of the area of the defect). In group 4 the new bone formation (17.8% of the area of the defect) was significantly higher in quantity than in group 3. CONCLUSION: The PCL scaffold coated with bone marrow seems to be a material that effectively provides osteoinduction with formation of new bone. Long-term results at 12 months are still pending.
This paper presents the optimal control of drug scheduling in cancer chemotherapy using a distributed evolutionary computing software. Unlike conventional methods that often require gradient information or hybridization of different approaches in drug scheduling, the proposed evolutionary optimization methodology is simple and capable of automatically finding the near-optimal solutions for complex cancer chemotherapy problems. It is shown that different number of variable pairs in evolutionary representation for drug scheduling can be easily implemented via the software, since the computational workload is shared and distributed among multiple computers over the Internet. Simulation results show that the proposed evolutionary approach produces excellent control of drug scheduling in cancer chemotherapy, which are competitive or equivalent to the best solutions published in literature.
Today there is an array of therapeutic modalities available for the patients with hepatocellular carcinoma (HCC). However, surgery, be it resection or transplantation, offers the only hope of long-term disease-free survival. Unfortunately, because the majority of HCC in Asia is associated with cirrhosis, surgical resection is restricted to only a small proportion of these patients. However, in selected candidates resection may offer a 5-year survival of up to 70%. With the clinical application of adult-to-adult living donor liver transplantation, an increasing number of patients with small HCC and decompensating cirrhosis are undergoing transplantation.
This study provides estimates for the cost of smoking in Singapore in 1997.A first attempt for Singapore, the paper reports on two different methods used, namely, the human capital approach and the demographic approach. These two measures are similar in that they compare the economic cost of smoking in the actual situation with the hypothetical alternative where there had been no smoking. The direct cost of smoking includes the amount spent on hospital care for five main diseases related to smoking whilst the indirect cost includes the value of lost income. The mortality cost of smoking is derived from the aetiological fractions of these diseases. The results from the human capital approach show that the social cost of smoking in 1997 ranged from S$673 million to S$839 million. Assuming there has been no smoking since 1990, calculations from the demographic approach indicate that national output would have increased by S$614 million in 1998. Nonetheless, the results from both approaches show that most of the cost of smoking is incurred by males.
A number of different processing techniques have been developed to design and fabricate three-dimensional (3D) scaffolds for tissue-engineering applications. The imperfection of the current techniques has encouraged the use of a rapid prototyping technology known as fused deposition modeling (FDM). Our results show that FDM allows the design and fabrication of highly reproducible bioresorbable 3D scaffolds with a fully interconnected pore network. The mechanical properties and in vitro biocompatibility of polycaprolactone scaffolds with a porosity of 61 +/- 1% and two matrix architectures were studied. The honeycomb-like pores had a size falling within the range of 360 x 430 x 620 microm. The scaffolds with a 0/60/120 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 41.9 +/- 3.5 and 3.1 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 29.4 +/- 4.0 and 2.3 +/- 0.2 MPa, respectively. In comparison, the scaffolds with a 0/72/144/36/108 degrees lay-down pattern had a compressive stiffness and a 1% offset yield strength in air of 20.2 +/- 1.7 and 2.4 +/- 0.1 MPa, respectively, and a compressive stiffness and a 1% offset yield strength in simulated physiological conditions (a saline solution at 37 degrees C) of 21.5 +/- 2.9 and 2.0 +/- 0.2 MPa, respectively. Statistical analysis confirmed that the five-angle scaffolds had significantly lower stiffness and 1% offset yield strengths under compression loading than those with a three-angle pattern under both testing conditions (p < or = 0.05). The obtained stress-strain curves for both scaffold architectures demonstrate the typical behavior of a honeycomb structure undergoing deformation. In vitro studies were conducted with primary human fibroblasts and periosteal cells. Light, environmental scanning electron, and confocal laser microscopy as well as immunohistochemistry showed cell proliferation and extracellular matrix production on the polycaprolactone surface in the 1st culturing week. Over a period of 3-4 weeks in a culture, the fully interconnected scaffold architecture was completely 3D-filled by cellular tissue. Our cell culture study shows that fibroblasts and osteoblast-like cells can proliferate, differentiate, and produce a cellular tissue in an entirely interconnected 3D polycaprolactone matrix.
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Genetic variation in the hepatic lipase (HL) gene (LIPC) promoter is an important determinant of HL activity in Caucasians. As HL activity is increased in patients with type 2 diabetes mellitus, we have investigated whether the -514 C-to-T polymorphism acted independently of type 2 diabetes to regulate HL activity. The frequency of this polymorphism and its effect on plasma HL activity and lipids were examined in 203 Chinese patients with type 2 diabetes and 205 controls. The frequency of the T allele was 0.343 and 0.376 in male and female diabetic patients, respectively, compared with 0.371 and 0.372 in male and female controls. The effect of LIPC genotype on HL activity was similar between men and women, and between diabetic patients and non-diabetic controls, with the lowest HL activity being found in those subjects with the TT genotype. On multivariate analysis, gender, LIPC genotype, the presence of type 2 diabetes and body mass index were independent predictors of HL activity, accounting for 22, 9, 5 and 3%, respectively, of the variance in HL activity (whole model adjusted R(2)=0.39, P<0.0001). The T allele was associated with higher high-density lipoprotein in the controls but not in the diabetic patients, and no associations were found between LIPC genotype and low-density lipoprotein subfractions in either groups. In conclusion, despite the higher frequency of the T allele in Chinese than in Caucasians, gender was the best predictor for HL activity, with LIPC gene polymorphism and type 2 diabetes making relatively smaller contributions to the variation in HL activity.
Gastrointestinal haemorrhage is a rare but well-recognised complication of extensive burns, the site of haemorrhage usually being in the upper gastrointestinal tract. The case of an 18-year old female patient who developed sudden massive rectal bleeding 1 month after suffering 45% body surface area burns is presented. The source of the haemorrhage was a Dieulafoy-type lesion at the anorectal junction associated with mucosal ulceration, a cause of bleeding not previously described in a patient with major burns. Angiographic embolisation failed to control the haemorrhage and surgical arrest was required, following which the patient made a complete recovery with no recurrence of bleeding. Haemorrhage from the lower gastrointestinal tract is rarely associated with major burns but may be significant when it occurs. The aetiology is unclear but sepsis, mucosal ischaemia and ulceration may be implicated.
Human cadaveric allograft is the most commonly used alternative wound closure material for excised burn wounds when limited donor sites or the overall patient condition does not permit immediate grafting with autologous skin.The Skin Bank in Singapore has supplied a total of 33,000 cm(2) of cryopreserved cadaveric allograft to the Burns Centre in Singapore for the early post-burn treatment of 17 severely burned patients with body surface area (BSA) burn wounds averaging 58% (range 33-90). An average of 13% (range 3-30%) cadaveric allograft was transplanted on 17 patients. Seven patients had recovered from their burn injuries and ten patients died of multiple complications related to their burn injuries. Our clinical observation has shown good adherence of cadaveric allograft when applied on clean and debrided wound bed after 4-7 days of post-operation.The availability of cadaveric allograft permits early excision and wound coverage before the patients' condition is further compromised. Our clinical experience using cryopreserved cadaveric allograft is proving to be indispensable in the management of patients with severe burns.
OBJECTIVE: To determine the relationship between percent body fat and body mass index (BMI) in the Chinese population of Hong Kong and to investigate whether the newly proposed lower BMI cut-offs for obesity in the Asia-Pacific Region recommended jointly by the International Association for the Study of Obesity, the International Obesity Task Force and the WHO are appropriate for Hong Kong Chinese. METHODS: A total of 190 female and 140 male healthy subjects were recruited from the community. BMI was calculated as weight/height(2). Body fat content (%BF) was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Comparing %BF measured by DEXA with predicted %BF derived from BMI using a prediction formula developed in Caucasian population showed that the formula significantly under-predicted %BF by 1.1% in males and 3.4% in females. A predicted BMI of 25 and 30 kg/m(2) using a Caucasian-based formula corresponds to an actual BMI of 23 and 25 kg/m(2), respectively. On linear regression analysis, 25% BF corresponds to a BMI of 24.6 kg/m(2) in males and a waist circumference of 86 cm; 35% BF corresponds to a BMI of 22.6 kg/m(2) and a waist circumference of 73.5 cm in females. CONCLUSION: Hong Kong Chinese population have a higher %BF for a given BMI which would partly explain why the health risks associated with obesity occur at a lower BMI. Our results would support the recommendations of using lower BMI cut-offs to define obesity in the Asia Region.
Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.
OBJECTIVES: Sleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin LAR, a long-acting somatostatin analogue, on these parameters. PATIENTS: Fourteen subjects with acromegaly were recruited. MEASUREMENTS: Subjects were assessed at baseline and those with apnoea-hypopnoea index (AHI) > or = 5 were reassessed after 6 months of treatment with Sandostatin LAR 20-30 mg IMI 4-weekly. Biochemical activity was assessed with levels of GH and IGF-1. Sleep disordered breathing was assessed with overnight polysomnography. Upper airway anatomic profile was defined with computerized tomographic cephalometry. RESULTS: Of 14 subjects (age 42.0 +/- 8.1 years, mean +/- SD; 11 men) at baseline, there was a positive correlation between GH and tongue length (VT; P = 0.004), and between AHI and cephalometric indices: length of soft palate (PMU; P = 0.002); mandibular plane-hyoid bone distance (MPH; P = 0.017), maximum thickness of soft palate (Max-SP; P = 0.018) and VT (P = 0.027). Eight patients had sleep disordered breathing (AHI > or = 5) which was predominantly obstructive in nature (AHI = 29.4 +/- 22.6). After treatment, there were significant improvements in hormonal profile: GH, mU/l (before, 51.5 +/- 27.8; after, 8.0 +/- 7.4; P = 0.017) and IGF-1, nmol/l (before, 95.5 +/- 23.4; after, 35.0 +/- 12.4; P = 0.012); sleep-disordered breathing: AHI (before, 29.4 +/- 22.6; after, 13.4 +/- 11.12; P = 0.025), snoring episodes (before, 486 +/- 240; after, 165 +/- 170; P = 0.05); cephalometric indices, mm: MPH (before, 18.8 +/- 12.1; after, 14.8 +/- 8.4; P = 0.018), VT (before, 72.3 +/- 4.4; after, 69.7 +/- 4.3; P = 0.05). There was a positive correlation between the reduction in GH and AHI (r = 0.738, P = 0.037). CONCLUSIONS: The findings demonstrated that there was correlation between sleep apnoea severity and soft tissue overgrowth at the upper airway region in acromegaly. They also suggest that Sandostatin LAR improved obstructive sleep apnoea in acromegaly, and the effect might be partly mediated via a reduction in upper airway soft tissue, in particular that of the tongue, concomitant with a reduction in GH levels.
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Standard microvascular anastomosis using only sutures is a well-established and successful technique; however, it is time-consuming and may cause vessel narrowing, needle trauma, and tissue reaction. The authors' hypothesis was that 2-octylcyanoacrylate could simplify microvascular anastomosis and reduce wall trauma and reaction. End-to-end anastomoses of the femoral arteries were performed in 20 adult rats. Each animal served as its own control. The time taken for each anastomosis (from first stitch to release of clamps) was noted, and the patency assessed. At day 7, the anastomoses were reassessed for patency, and the vessels evaluated histologically. 2-octylcyanoacrylate reduced the need to insert more sutures. Anastomotic time in the study group was statistically significantly shorter (p < 0.001), and the patency rate was 90 percent, compared to 85 percent with the standard suture technique. There was also less intense inflammatory reaction, with fewer foreign-body granulomata. This is the first report on the use of 2-octylcyanocrylate, currently approved for cutaneous use, for vessel anastomosis. Further work on the biomechanics and long-term histologic effects will be carried out. 2-octylcyanoacrylate has the potential for simplifying and improving the patency rates of arterial microanastomosis.
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INTRODUCTION: Liver transplantation is a curative treatment modality in children with end stage liver disease in Alagille syndrome. CLINICAL PICTURE: We report a 3-year-old child with this condition who had severe hypercholesterolaemia, pruritus and extensive xanthomatosis. TREATMENT: Liver transplantation was performed in this patient. OUTCOME: He recovered well with normalisation of his lipid profile. This procedure also resulted in resolution of the disfiguring xanthomatosis.