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Biomedical subjects

P-H Lee

Publications and source records attributed to P-H Lee.

At least 19 recordsLinked to original sources

Clinicopathological differences between hepatitis B viral genotype B- and C-related resectable hepatocellular carcinoma.

Clinical and pathogenic differences exist between hepatitis B viral (HBV) genotypes B and C, and genotype C has a higher risk of hepatocellular carcinoma (HCC) development than genotype B. The aim of this study was to investigate whether HBV genotypes B and C influence the clinicopathological features of patients with resectable HCC. Stored serum samples from 193 patients with resectable HBV-related HCC were tested for HBV genotypes by a molecular method. Of 193 patients undergoing resection of HCC, 107 (55%) and 86 (45%) were infected with genotypes B and C, respectively. Compared with genotype C patients, genotype B patients were less likely to be associated with liver cirrhosis (33%vs 51%, P = 0.01). Pathologically, genotype B patients had a higher rate of solitary tumour (94%vs 86%, P = 0.048) and more satellite nodules (22%vs 12%, P = 0.05) than genotype C patients. Our results indicate that genotype B-related HCC is less associated with liver cirrhosis and has a higher frequency of solitary tumour as well as more satellite nodules than genotype C-related HCC. These characteristics may contribute to the recurrence patterns and prognosis of HBV-related HCC in patients with genotype B or C infection.

Alanine Transaminase↗

Multimedia article. Laparoscopic abdominoperineal resection for lower rectal cancers: how do we do it?

BACKGROUND: The appropriateness of the laparoscopic approach for the resection of rectal cancer has been controversial, although it is well established in colon cancer. This is a phase II study of laparoscopic abdominoperineal resection (APR) in the treatment of lower rectal cancers. METHODS: Patients with lower rectal adenocarcinoma located within 6 cm above the anal verge were recruited and subjected to laparoscopic APR. The surgical principle included en bloc resection with high ligation of inferior mesenteric vessels by no-touch isolation and total mesorectal excision. Details of the surgical procedures are presented in the video. The technical efficiency and outcome of this surgical approach were evaluated prospectively. This study was approved by the institutional review board of National Taiwan University Hospital (NTUH). RESULTS: A total of 22 patients were enrolled in the study from January 2003 to December 2004 under the ethical guidelines of clinical trials in NTUH. There were 12 females and 10 males, with an age distribution of 62.5 +/- 10.4 years. The body mass index was 24.8 +/- 4.0 kg/m2. Physical status (American Society of Anesthesiology classification) was class I in 12, class II in eight, and class III in two patients. Tumor size was 44.0 +/- 12.0 mm in diameter. Two patients were in pathologic TNM stage I, 14 in stage II, and six in stage III. The operation time was 214.0 +/- 28.4 min. Blood loss was 54.0 +/- 14.0 ml. Because the tumor specimen was retrieved from a perineal wound, the five 5 to 12 mm working ports constituted the abdominal wound. There were no major complications. However, wound infection of port sites was detected in one patient. The patients had a quick convalescence, as evaluated by the length of postoperative ileus (48.0 +/- 12.0 h), length of hospitalization (8.0 +/- 2.0 days), and degree of postoperative pain (3.5 +/- 0.5 visual analogue scale). Return to partial activity, full activity, and work was 2.0 +/- 0.5, 4.0 +/- 0.8, and 6.0 +/- 0.5 weeks, respectively. The number of cleared lymph nodes was 14.0 +/- 2.0. During follow-up (median, 18 months; range, 6-30), lung metastasis and local pelvic recurrence developed in one and two patients, respectively. Besides the expenses covered by the National Bureau of Health Insurance of Taiwan, the additional payment by patients undergoing laparoscopic procedures was NTD 24,000 +/- 3000 (1 U.S. dollar = 32 NTD). CONCLUSIONS: In our clinical setting, laparoscopic APR can be performed with good technical efficiency, quick functional recovery, and mild disability. The short-term oncologic results of laparoscopic APR seem to be acceptable, but further long-term follow-up for these patients is mandatory to define the oncologic outcomes of this approach.

Abdomen↗

Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma.

Stathmin, a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. This study aimed to elucidate its role in the progression, early tumour recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Stathmin mRNA was overexpressed in 88/156 (56%) resected, unifocal, primary HCCs, while p53 mutation was present in 72 (46%) and osteopontin mRNA overexpression in 79 (51%). Stathmin mRNA expression exhibited high concordance (93%) with protein expression in 107 cases examined by immunohistochemistry. Stathmin overexpression correlated with high alpha-fetoprotein (>200 ng/ml, p = 0.02), larger tumour size (>5 cm, p = 0.012), high tumour grade (p < 0.0002), high tumour stage (stage IIIA-IV) with vascular invasion and various degrees of intrahepatic metastasis (p < 1 x 10(-8)), ETR (p = 0.003), and lower 5-year survival (p = 0.0007). Stathmin protein expression was often more intense in the peripheral regions of tumour trabeculae, tumour borders, and portal vein tumour thrombi. Stathmin overexpression correlated with p53 mutation (p = 0.017) and osteopontin overexpression (p = 1 x 10(-8)), both of which were associated with vascular invasion (both p < 0.0001) and poorer prognosis (p < 0.0004 and p = 0.0004, respectively). Regardless of the status of p53 mutation or osteopontin expression, stathmin overexpression was associated with higher vascular invasion (all p < 0.0001). Approximately 90% of HCCs harbouring stathmin overexpression with concomitant p53 mutation or osteopontin overexpression exhibited vascular invasion, and hence the lowest 5-year survival, p = 0.00018 and p = 0.0009, respectively. However, we did not find that stathmin overexpression exerted prognostic impact independent of tumour stage. In conclusion, stathmin expression correlates with metastatic potential, is an important prognostic factor for HCC, and may serve as a useful marker to predict ETR.

Biomarkers, Tumor↗

Elective laparoscopically assisted sigmoidectomy for the sigmoid volvulus.

BACKGROUND: The laparoscopic approach for the treatment of sigmoid volvulus has been a rare surgical indication. This phase 2 study investigated the feasibility and surgical outcomes of elective laparoscopic surgery for sigmoid volvulus. METHODS: Patients with sigmoid volvulus were first offered colonoscopic decompression for their acute colonic obstruction. If the colonic decompression was successful, complete bowel preparation was performed, followed by elective laparoscopically assisted sigmoidectomy. The details of the laparoscopic procedures are shown in the video. Briefly, the redundant sigmoid colon is totally mobilized by a laparoscopic medial-to-lateral dissection sequence, after which it is exteriorized, transected, and reconstructed by end-to-end anastomosis. In the authors' experience, the medial-to-lateral approach is highly efficient for the laparoscopic mobilization of the redundant sigmoid colon. We believe that the longer the lateral abdominal wall attachment of the sigmoid colon is preserved, the better the exposure and the easier the dissection. If the risk of anastomotic leakage is considered high in a specific case, protective ileostomy is selectively preformed. Before entering the current study, the patients were well informed about the advantages and disadvantages of laparoscopic surgery. The enrollment of patients was selective according to the appropriate eligibility criteria. This study was approved by the Institutional Review Board of the National Taiwan University Hospital. The patients' clinicopathologic data and surgical outcomes were prospectively evaluated. RESULTS: Between August 2001 and April, 2005, a total of 14 patients (10 men and 4 women) with sigmoid volvulus were treated with the described procedure. The age distribution of the patients was 68.4 +/- 12.2 years. The attack of sigmoid volvulus was the first episode for eight patients, the second episode for 4 patients, and the third episode (or more) for two patients. The body mass index (BMI) of the patients was 26.8 +/- 4.4 kg/m(2). The physical status (classification of American Society of Anesthesiology [ASA]) was 1 for five patients, 2 for eight patients, and 3 for 1 patient. During the laparoscopy, all the patients presented with the pathognomonic findings of sigmoid volvulus including redundant sigmoid colon, narrow sigmoid mesenteric pedicle, and mesosigmoiditis with mesenteric fibrosis and scarring, as shown in the video. The length of the resected colon was 32 +/- 6 cm. The operation time was 194.6 +/- 32.4 min, and the blood loss was 44.0 +/- 12.4 ml. The abdominal wound consisted of four 5 to 12 mm working ports and a 5 cm major wound for exteriorization of the sigmoid colon. Some surgeons have shown that a sigmoid volvulus can be resected through a 5-cm left lower quadrant incision with very little mobilization of the colon because of its redundancy. In this context, the laparoscopic approach competed with the minilaparotomy method in terms of adequate sigmoid resection, lysis of mesosigmoid adhesion, and tension-free colorectal anastomosis. Protective ileostomy was performed for the only patient with a physical status of ASA 3. There was no mortality in this case series. However, pneumonia developed postoperatively in one patient, acute myocardial infarction in one patient, and wound infection in two patients. Excluding the two patients who experienced postoperative pneumonia and acute myocardial infarction, the duration of the postoperative ileus was 48 +/- 12 h, the postoperative hospitalization was 7 +/- 1 days, and the degree of postoperative pain was 3.5 +/- 0.5 according to the visual analog scale. The return to partial activity required 18 +/- 2.5 days, and the return to full activity required 28.4 +/- 5.6 days. As compared with the overall costs for a conventional sigmoid colectomy, which are completely covered by the National Bureau of Health Insurance of Taiwan, the expenses for the patients undergoing laparoscopic procedures were significantly higher by approximately 24,000.0 NT dollars +/- 2,635.0 (1 U.S. dollar = 32 NT dollars). These higher expenses must be borne by the patients themselves. CONCLUSION: Considering that patients with sigmoid volvulus often are elderly and chronically ill, laparoscopic elective surgery after a successful colonoscopic decompression may be a good choice for a selected group of patients in terms of minimized surgical complications and quick convalescence.

Aged↗

The hDAF exogene protects swine endothelial and peripheral blood mononuclear cells from xenoreactive antibody mediated cytotoxicity in hDAF transgenic pigs.

Xenoreactive antibody-induced complement activation and cytotoxicity poses a major obstracle to xenograft survival in humans. Previously, we have generated transgenic pigs carrying the hDAF exogene to help overcome this problem. In this study, we examined whether the hDAF exogene in various swine cells shows an equally protective effect for the complement-mediated cytotoxicity induced by human xenoreactive antibodies. Pig peripheral blood mononuclear cells (PBMCs) and aortic endothelial cells (PAECs) were used as targets. Fresh human serum was harvested from a single healthy human donor as the source of human xenoreactive antibodies and complement. The target cells cocultured with medium containing various concentrations of human serum for 24 hours were evaluated using the 3-[4,5-dimethylthiaolyl]-2,5-diphenyl-tetrazolium bromide assay for cellular viability. We observed that xenoreactive antibody plus human complement-mediated cellular cytoxicity dose-dependently correlated with the concentration of human serum in the culture medium. As compared with the PBMCs from the normal pigs, PBMCs from hDAF transgenic pigs showed significantly better survival after treatment with human serum (P < .05). Similarly, the survival of PAECs from the hDAF transgenic pig were also significantly higher than that from normal pigs (P < .05). Our data demonstrated a protective effect from human xenoreactive antibodies and complement-mediated cytoxicity of hDAF exogenes in pig PBMCs and PAECs. These observations support the clinical value of the hDAF transgenic pig as an organ donor in xenotransplantation.

Animals↗

Impact of liver donation on quality of life and physical and psychological distress.

UNLABELLED: Our objectives were to assess the characteristics of donors for living-donor liver transplantation (LDLT) and to examine the impact of donation on LDLT donor quality of life (QOL) regarding physical and psychological distress. METHODS: Data were collected from a mailed survey or an interview using a cross-sectional prospective study design. We used the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF), Physical Symptom Disturbance Scale, and Psychological Distress Scale. LDLT donors were recruited from a teaching hospital located in a metropolitan area of northern Taiwan. RESULTS: The 35 LDLT donors have a mean age 34.0 +/- 8.6 years and were recruited at a median of 25.9 months after donation (range, 0.6-92 months). The average scores in the four domains of the WHOQOL-BREF scale ranged from 13.5 to 14.9. LDLT Donors reported higher QOL scores in social and environment domains but lower scores in physical and psychological domains than healthy adults. Numbers of physical symptoms experienced by each donor ranged from one (n = 4) to 27 (n = 2). Feeling throbbing, itching or numbness around the wound was the most common physical symptom disturbance reported by donors (n = 26, 74%). Approximately 40% of the donors reported having one to three metrics of psychological distresses. "Easily feel distress and angry" was the most common psychological distress reported by 57% (n = 20) of donors. CONCLUSIONS: This study indicated that liver donation had a mild negative impact on donors physical and psychological facets of QOL. These results may assist professionals to provide appropriate clinical management.

Adult↗

Microvessel density, cyclo-oxygenase 2 expression, K-ras mutation and p53 overexpression in colonic cancer.

BACKGROUND: Tumour angiogenesis, cyclo-oxygenase (COX) 2 expression, K-ras mutation and p53 overexpression are commonly involved in colorectal tumorigenesis, but their interrelationship and clinicopathological effects remain inconclusive. METHODS: Clinicopathological data from 114 consecutive patients with primary stage III colorectal cancer were evaluated prospectively. Microvessel density (MVD) of the tumour was defined by counting the number of microvessels in hotspots, visualized by immunocytochemical staining of endothelial CD34. K-ras mutation was analysed by the restriction enzyme cleavage method. COX-2 expression and p53 overexpression were determined by immunocytochemistry. RESULTS: Increased MVD in hotspots was significantly associated with COX-2 expression (P < 0.001), K-ras mutation (P = 0.007) and p53 overexpression (P = 0.006). COX-2 expression was not associated with either K-ras mutation or p53 overexpression. Clinicopathologically, greater MVD and COX-2 expression were significantly associated with vascular invasion of cancer cells (MVD, P = 0.027 and COX-2 expression, P = 0.006), but p53 overexpression and K-ras mutation were not. Multivariate analysis indicated that greater MVD (P = 0.002) and p53 overexpression (P = 0.016) were significant independent predictors of tumour recurrence, whereas COX-2 expression (P = 0.634) and K-ras mutation (P = 0.356) were not. CONCLUSION: Tumour angiogenesis may be associated with tumour metastasis and is significantly influenced by K-ras mutation, p53 overexpression and COX-2 expression in patients with colonic cancer.

Adult↗

Effects of and predictors for tacrolimus rescue therapy among renal transplant patients under cyclosporine-based immunosuppression.

BACKGROUND: Though cyclosporine has dramatically decreased rejection rates and improved graft survival rates of renal allografts, there is still a remarkable rate of acute rejection and progressive deterioration of renal function after transplantation. Rescue therapy with tacrolimus has been used for allografts failing under cyclosporine-based treatment in order to get some renal functional recovery or stabilization. The aim was to evaluate tacrolimus rescue therapy for failing allografts under cyclosporine-based immunosuppression for possible prediction factors for success. PATIENTS AND METHODS: Thirty-five renal allograft recipients with failing transplants under cyclosporine-based immunosuppression were enrolled into this study. Renal function was evaluated by reciprocal serum creatinine level (1/Cr) and calculated CCr. The slope of changes in 1/Cr and CCr were calculated before and after tacrolimus therapy. The possible risk factors that affect the outcome of tacrolimus rescue therapy were analyzed. RESULTS: Nineteen patients showed improved renal function (group 1) and 16 patients, persistent deterioration (group 2) after rescue therapy. Group 1 showed positive slopes of changes of 1/Cr and CCr after rescue therapy. Group 2 patients showed persistent negative slopes although less negative than before rescue therapy. Only the posttransplant time was the significant predictive factor for successful tacrolimus therapy (P = .018). CONCLUSION: Tacrolimus rescue therapy improved or stabilized renal function in some patients with failing grafts under cyclosporine-based immunosuppression. To assure a successful rescue effect, it should be given early after transplantation, if there is a tendency toward deterioration of renal function.

Creatinine↗

Evaluation of cyclosporine C2 levels in long-term stable renal allograft recipients.

BACKGROUND: The use of cyclosporine was traditionally monitored by the trough level (C(0)). However, the immunosuppressive effects of cyclosporine correlate with its drug exposure, represented by the area under curve (AUC). It was also noted that cyclosporine C(0) level correlated with AUC poorly, while C(2) level (concentration at 2 hours after drug administration) satisfactorily correlated with AUC. Most recent studies concern the use of C(2) levels in de novo renal transplant patients; target levels of C(2) have been suggested. There is rare discussion about the C(2) target level for long-term cyclosporine-maintenance patients. Our objectives were to analyze the cyclosporine C(2) levels of patients more than 12 months after transplantation as well as changes in C(2) with time and the correlation between C(2) level and renal function. METHODS AND PATIENTS: This was a cross-sectional case-controlled study of 101 kidney recipients immunosuppressed with a cyclosporine-based regimen for at least 12 months. Both C(0) and C(2) levels were examined at various time points during outpatient clinic follow-up. The patients were stratified according to the time after transplant surgery, or to their renal function. RESULTS: The 101 patients were divided into three groups based on the time after renal transplant surgery. Groups 1, 2, and 3 represented patients transplanted for 1 to 3 years (n = 16), 4 to 6 years (n = 35), and more than 6 years (n = 50), respectively. The C(2) levels for each group were 657 +/- 232, 561 +/- 186, and 580 +/- 243 ng/mL, respectively, (P = NS). When stratified into low versus high C(2) groups, there were no significant differences in renal function both at the beginning and at the end of 1 year follow-up. Seven of 67 patients shifted to stronger immunosuppression in the low C(2) group, but only 2/34 in the high C(2) group, a difference that was not significant (P = .234 by Fisher Exact Test). Patients with creatinine levels greater than 1.5 mg/dL or lower than 1.5 mg/dL showed no difference in C(2) on C(0) levels. Patients with deterioration of renal function during this period had no different C(2) levels as those with no deterioration of renal function. CONCLUSION: The average C(2) levels among long-term cyclosporine-maintained patients were significantly lower than those previously suggested. C(2) levels did not correlate with the long-term outcome of renal function in patients at least 1 year after renal transplantation.

Case-Control Studies↗

Use of simulect can reduce the incidence of acute rejection and demonstrates with superior 3-year patient and graft survival rates in renal transplantation.

BACKGROUND: Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation. OBJECTIVES: We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated. METHOD: Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid. RESULTS: There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%. CONCLUSIONS: Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.

Adolescent↗

Liver transplantation for acute hepatic failure.

INTRODUCTION: The mortality rate of acute hepatic failure (AHF) with conservative treatment is 40% to 90%, depending on the etiology. Hepatitis B infection is the major cause of AHF in Asia. In this study, we examined the role of liver transplantation for adult patients with AHF. METHODS: Sixteen patients with AHF received liver transplants in the past 6 years. Eight patients received cadaveric donor and another 8 living-related donor grafts. Fifteen patients suffered from hepatitis B-related disease and 1 had drug-induced AHF. Extracorporeal charcoal hemoperfusion was used as a bridge to liver transplantation in the first 2 patients and plasma exchange was used in the following patients. RESULTS: One patient died 1 month after the operation due to primary nonfunction. The other 15 patients are alive with good graft function at 2 months to 6 years follow-up. The success rate is 94%. Postoperative complications included infection in 10 patients (62.5%), acute rejection in 4 patients (25%), and biliary complication in 2 patients (12.5%). No neurological complications were noted. CONCLUSION: Liver transplantation is the most effective treatment for patients with AHF. Living donors may be considered due to the organ shortage and the critical patient disease.

Cadaver↗

Liver transplantation for patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the clinical findings and outcome of cirrhotic patients with HCC undergoing liver transplantation. METHODS: Our study consisted of 13 HCC patients who underwent liver transplantation during October 1996 to March 2003. The medical records and pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in three patients, one of whom is still alive with HCC recurrence 2 years after LT. The other two patients died of HCC recurrence 1 and 2 years after LT, respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were noted in all three patients with HCC recurrence. In contrast, only one of the ten patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four patients did not meet Milan criteria, two of whom had HCC recurrence. However, the other two patients with microscopic vascular invasion survived and were free of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence, although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor for HCC recurrence after LT. In addition to Milan criteria, histologic tumor grading should be considered in patient selection. Microscopic vascular invasion may not affect the outcome of the patients with early HCC.

Carcinoma, Hepatocellular↗

Surgical complications and outcome of living related liver transplantation.

INTRODUCTION: Living donor liver transplantation (LDLT) is now widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation and expansion of the procedure, both outcome and complication analyses of LDLT are still incomplete. OBJECTIVES: To analyze the outcome of LDLT, with particular reference to complications of those in need of surgical or radiological intervention. METHODS: Forty-eight LDLTs performed at National Taiwan University Hospital between December 1997 and April 2003 were reviewed retrospectively. RESULTS: Forty-two (87.5%) patients survived the operation. The 1-year graft and patient survival rate was 81.5%. Seventeen of the 48 LDLT patients had at least one postoperative complication, which needed surgical or radiological intervention. The complications included bile leakage (n = 3), biliary stricture (n = 4), internal bleeding (n = 7), intra-abdominal abscess (n = 2), liver abscess (n = 1), hepatic artery thrombosis (n = 2), duodenal ulcer bleeding (n = 1), jejunal perforation (n = 1), adhesion ileus (n = 1), and intracranial hemorrhage (n = 1). Nine of the 17 patients with complications died. In contrast, only 2 of the other 31 patients died. Seven of the mortalities were related to the complications. All survivors received only one definite intervention early after the complications were diagnosed. However, the others received an average of 1.71 +/- 0.95 (0 to 3) interventions. CONCLUSIONS: Complications requiring surgical or radiological treatment caused major mortality of LDLT. Early and definite treatment of these complications is important to improve the patient's outcome.

Follow-Up Studies↗