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Biomedical subjects

S T Fan

Publications and source records attributed to S T Fan.

At least 127 records · Page 7Linked to original sources
PubMed1999

Ultrasound contrast agent Levovist in colour Doppler sonography of hepatocellular carcinoma in Chinese patients.

In a phase IIIb clinical trial of the ultrasound contrast agent Levovist (Schering AG, Berlin, Germany), the role of Levovist in the management of patients with clinically suspected hepatocellular carcinoma (HCC) was evaluated and its efficacy was assessed. The assessment included the duration of diagnostically usable Doppler signal enhancement, and safety and tolerance of intravenous administration. All patients with clinically suspected hepatocellular carcinoma were referred for Doppler sonographic examination over a 5-month period and lesions with absent or suboptimal Doppler signals were included in the trial. A total of 300 mg/mL in concentration (8.5 mL) of Levovist was administered through a peripheral vein while Doppler signal intensity in the lesion, based on a visual score, was recorded. Blood pressure and pulse were recorded before and after injection. Thirty-eight patients were examined, of which 29 were included in the trial. The lesions were subsequently proven histologically to be 19 HCC, one cholangiocarcinoma, two regeneration nodules and one colonic metastasis. For six patients in whom histological proof was not available, the diagnosis of HCC was suggested based on markedly elevated serum alpha-fetoprotein levels. All but one (96%) of the 25 HCC demonstrated increased Doppler signal after Levovist. There were no Doppler signals before and after Levovist injection in three non-HCC lesions (two regeneration nodules and one colonic metastasis). Two patients (6.9%) suffered minor adverse reactions of nausea and vomiting. The results show that Levovist is safe and is able to improve lesion characterization and increase diagnostic confidence of hepatocellular carcinoma by enhancing tumour vascularization Doppler signal intensity.

Adult↗
PubMed1999

Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.

OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment.

Adult↗
PubMed1999

Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.

OBJECTIVE: The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate. SUMMARY BACKGROUND DATA: In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997. METHODS: Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome. RESULTS: Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate. CONCLUSION: With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated.

Adolescent↗
PubMed1999

Hepatocellular carcinoma in the elderly: results of surgical and nonsurgical management.

OBJECTIVE: This study evaluated the results of surgical and nonsurgical treatments of hepatocellular carcinoma (HCC) in the elderly to determine the optimal management strategy. METHODS: Clinicopathological data and treatment results of 222 elderly (> or = 70 yr) and 1116 younger patients with HCC managed between 1989 and 1997 were prospectively collected and compared between the two groups. RESULTS: The resection rate in the elderly (14%) was lower than in younger patients (27%) (p < 0.001). Among patients who underwent resection, there were no significant differences in morbidity rate (48% vs 40%, p = 0.354), hospital mortality rate (10% vs 6%, p = 0.431), or long-term survival (median, 38 vs 42 months, p = 0.940). Comparing the periods 1989-1992 and 1993-1997, hospital mortality rate in the elderly was reduced from 25% to 4% (p = 0.079). Sixty-seven elderly and 317 younger patients underwent transarterial oily chemoembolization (TOCE), with similar morbidity rate (24% vs 26%, p = 0.775), mortality rate (7% vs 5%, p = 0.365), and long-term survival (median, 12 vs 9 months, p = 0.277). The results of other nonsurgical treatments were also similar between the two groups. CONCLUSIONS: Hepatic resection for HCC is safe in selected elderly patients, and the improved results in recent years indicate that more elderly patients could benefit from surgical management. TOCE is well tolerated in elderly patients and is the treatment of choice for unresectable HCC. The overall management strategy of HCC in the elderly should not be different from that in younger patients.

Age Factors↗
PubMed1998

Long term prognosis after hepatectomy for hepatocellular carcinoma: a survival analysis of 204 consecutive patients.

BACKGROUND: Intrahepatic recurrence continues to be the main cause of late death among hepatocellular carcinoma patients after hepatic resection. The aims of the current study were to identify the prognostic factors affecting long term survival and to evaluate the clinical value of pTNM classification as a prognostic factor for these patients. The identification of significant prognostic factors plays an important role in the selection of patients for postoperative adjuvant therapy and counseling. METHODS: From January 1989 to August 1995, 204 consecutive patients underwent hepatectomy for hepatocellular carcinoma. The overall cumulative and disease free survival rates for these patients were analyzed. Univariate and multivariate analyses of 16 clinicopathologic factors, including factors associated with pTNM classification, were performed to determine the significant prognostic factors. RESULTS: The median periods of overall cumulative survival and disease free survival were 35 months and 12.4 months, respectively. By univariate analysis, all factors associated with tumor (T) classification, namely, tumor size, vascular invasion, the number of tumor nodules, and tumor localization, were correlated with survival. By Cox regression analysis, preoperative indocyanine green retention value at 15 minutes, tumor size, and number of tumor nodules were independent prognostic factors of long term survival, whereas the number of tumor nodules, tumor size, and venous permeation were the most powerful predictors of tumor recurrence. The cumulative 5-year survival rates for patients with Stages I, II, III, and IVA tumors were 72%, 55%, 34%, and 8%, respectively. Significant differences in cumulative survival curves were observed among the categories of pTNM classification. CONCLUSIONS: The results of this study showed that pTNM classification correlated well with postoperative survival. Preoperative evaluation of hepatic functional reserve with an indocyanine green clearance test plays an important role in determining the long term prognoses of patients with hepatocellular carcinoma.

Adolescent↗
PubMed1998

p21/WAF1, p53 and PCNA expression and p53 mutation status in hepatocellular carcinoma.

The cyclin-dependent kinase inhibitor p21/WAF1 is regulated by p5S3-dependent and p53-independent pathways. In addition, p21/WAF1 binds with proliferating cell nuclear antigen (PCNA) and inhibits the action of PCNA. To investigate the possible role of p21/WAF1 in human hepatocellular carcinomas (HCCs), we examined the expression of p21/WAF1 and its relation with PCNA and p53 expression in 97 surgically resected HCCs by immunohistochemistry and with the mutation status of p53 in 26 HCCs. p53 mutation status was examined by direct DNA sequencing using 3 sets of primers covering exons 5-9. Six of the 26 tumors showed p53 point mutations and only 33% of these HCCs demonstrated p21/WAF1 expression. In contrast, 75% of HCCs without p53 mutations showed p21/WAF1 expression. Of all 97 HCCs, p21/WAF1 expression was significantly higher in the tumors than in corresponding non-tumorous liver. When the tumors were stratified into 2 groups by the median tumor p21/WAF1 score, those with higher expression were found to have a lower incidence of multiple tumor nodules (p = 0.008) and tumor microsatellite formation (p = 0.050). The tumor p21/WAF1 score was positively associated with tumor PCNA expression (p = 0.036) but not with tumor p53 expression. Thus, in HCC, expression of p21/WAF1 is in part dependent on p53 status, but a p53-independent pathway also plays a significant role in the regulation of p21/WAF1 expression. High p21/WAF1 expression is significantly associated with solitary tumor nodules and, to a lesser extent, tumor microsatellites but may not be enough to suppress tumor progression.

Adult↗
PubMed1998

Identification and characterization of a novel human aldose reductase-like gene.

We have identified a novel human protein that is highly homologous to aldose reductase (AR). This protein, which we called ARL-1, consists of 316 amino acids, the same size as AR, and its amino acid sequence is 71% identical to that of AR. It is more closely related to the AR-like proteins such as mouse vas deferens protein, fibroblast growth factor-regulated protein, and Chinese hamster ovary reductase, with 81, 82, and 83%, respectively, of its amino acid sequence identical to the amino acid sequence of these proteins. The cDNA of ARL-1 was expressed in Escherichia coli to obtain recombinant protein for characterization of its enzymatic activities. For comparison, the cDNA of human AR was also expressed in E. coli and analyzed in parallel. These two enzymes differ in their pH optima and salt requirement, but they act on a similar spectrum of substrates. Similar to AR, ARL-1 can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. While AR mRNA is found in most tissues studied, ARL-1 is primarily expressed in the small intestines and in the colon, with a low level of its mRNA in the liver. The ability of ARL-1 to reduce various aldehydes and the locations of expression of this gene suggest that it may be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs. Interestingly, ARL-1 and AR are overexpressed in some liver cancers, but it is not clear if they contribute to the pathogenesis of this disease.

Adult↗
PubMed1998

Retinoic acid selectively inhibits lipopolysaccharide induction of tissue factor gene expression in human monocytes.

Expression of tissue factor (TF) by activated monocytes in several diseases leads to disseminated intravascular coagulation. Lipopolysaccharide (LPS)-induced monocyte TF expression is downregulated by the nuclear hormone all-trans retinoic acid (ATRA). In this study, we examined the mechanism by which ATRA inhibits monocyte TF expression. We show that ATRA selectively inhibited LPS induction of TF expression in human monocytes and monocytic THP-1 cells without affecting LPS induction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). Inhibition of TF expression occurred at the level of transcription as determined by nuclear run-on. ATRA did not significantly alter the binding or functional activity of the transcription factors c-Fos/c-Jun and c-Rel/p65, which are required for LPS induction of the TF promoter in monocytic cells. In contrast to the ATRA inhibition of the endogenous TF gene, LPS induction of the cloned TF promoter was not inhibited by ATRA in transiently transfected THP-1 cells. Our results demonstrate that ATRA selectively inhibited LPS-induced TF gene transcription in human monocytic cells by a mechanism that does not involve repression of AP-1- or NF-kappaB-mediated transcription.

Cells, Cultured↗
PubMed1998

Biliary complications after hepatic resection: risk factors, management, and outcome.

OBJECTIVE: To identify the risk factors for the development of biliary complications after hepatic resection and to evaluate management in relation to the outcomes of these patients. DESIGN: Biliary complications are a common cause of major morbidity after hepatic resection. A survey was made of all patients undergoing hepatic resection at 1 institution. Perioperative risk factors related to the development of biliary complications were identified using multivariate analysis. Management and outcome were analyzed also. SETTING: A tertiary referral center. PATIENTS: From January 1, 1989, to October 31, 1995, 347 consecutive patients underwent 229 major and 118 minor hepatic resections. MAIN OUTCOME MEASURE: Development of postoperative biliary complications. RESULTS: Biliary complications developed in 28 (8.1%) of 347 patients; these complications carried high risks for liver failure (35.7%) and operative mortality (39.3%). Stepwise logistic regression analysis identified increasing age, higher preoperative white blood cell count, left-sided hepatectomy, and prolonged operation time as the independent predictors of development of biliary complications. Conservative treatment or nonoperative measures alone, such as percutaneous drainage or endoscopic therapy, were effective in treating the complication in 13 of 19 patients, but those who required reoperation had a high mortality rate (7 [77.8%] of 9 patients). Patients with demonstrable leakage from the common bile duct or its bifurcation tended to have poor outcomes. CONCLUSIONS: Biliary complications are a common and serious cause of morbidity after hepatic resection. Preresection cholangiography for finding biliary tract anomaly is recommended before left-sided hepatectomy. Although nonoperative measures are the preferred approach for selected patients with biliary complications, those with demonstrable leakage from the common bile duct or its bifurcation have a grave prognosis and may benefit from early surgical intervention.

Adult↗
PubMed1998

Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial.

OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.

Antineoplastic Agents↗
PubMed1998

Endoscopic retrograde cholangiopancreatography and endoscopic endoprosthesis insertion in patients with Klatskin tumors.

OBJECTIVE: To assess the value and the associated morbidity of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic endoprosthesis insertion in the treatment of patients with Klatskin tumors. DESIGN: Retrospective study. SETTING: A tertiary referral center. PATIENTS: Fifty-five consecutive patients with Klatskin tumors diagnosed through typical cholangiographic and computed tomographic findings. INTERVENTION: Standard ERCP with endoscopic stenting technique was employed. Once the diagnosis of Klatskin tumor was confirmed on cholangiogram, endoscopic stenting was performed to bypass the stricture. Multiple stents were inserted if necessary to ensure adequate biliary drainage. MAIN OUTCOME MEASURES: The success rate of ERCP and endoscopic endoprosthesis insertion, successful drainage rate, early complications of endoscopic procedure, procedure-related mortality, and long-term outcome of endoprosthesis. RESULTS: Of the 55 patients, cholangiography was performed in 53 (96%). In the 49 patients in whom endoscopic stenting was attempted, the procedure was successful in 28 patients (57%) at the first attempt and 8 patients (16%) at the second attempt, resulting in a cumulative success rate of 73%. Only 20 of these patients had satisfactory biliary drainage, resulting in an overall successful drainage rate of 41%. Early complications, including acute cholangitis, acute pancreatitis, and postpapillotomy bleeding occurred in 14 patients (25%). Three patients (5%) died of procedure-related complications. The median patency of the first endoprosthesis inserted was 1 week (range, 0-8 wk). The 30-day mortality rate was 18%. CONCLUSIONS: In patients with Klatskin tumors, ERCP and endoscopic endoprosthesis insertion have a low successful drainage rate, are associated with high morbidity and procedure-related mortality, and have a limited effect on long-term palliation. Endoscopic retrograde cholangiopancreatography and endoscopic endoprosthesis insertion have a limited value in the management of patients with Klatskin tumors.

Adult↗
PubMed1998

Hepatic cryosurgery for recurrent hepatocellular carcinoma after hepatectomy: a preliminary report.

BACKGROUND AND OBJECTIVES: The treatment of choice for recurrent hepatocellular carcinoma (HCC) is repeated resection. However, only a small percentage of patients are suitable for further hepatic resection. The aim of this study was to evaluate the surgical risk and operative outcome of hepatic cryosurgery in patients with recurrent HCC. METHODS: A retrospective analysis of patients with recurrent HCC after previous curative hepatectomy treated with cryosurgery. Four patients with recurrent HCC not suitable for further resection were enrolled for cryosurgery, their clinical parameters, the operative details and outcome were studied. RESULTS: No intraoperative or postoperative complications were noted. The duration of operation ranged from 3-5.2 hr and the operative blood loss from 173-1,300 ml. All patients are still alive with survival after cryosurgery ranging from 12-23 mo (25-63 mo after the hepatic resection). Three patients showed evidence of recurrent disease and one patient was disease free. CONCLUSIONS: Hepatic cryosurgery is a safe therapy for patients with unresectable recurrent HCC.

Carcinoma, Hepatocellular↗
PubMed1998

Primary biliary stones: diagnosis and management.

To review the results of treatment of primary biliary stones, 96 consecutive patients managed from 1991 to 1996 were studied retrospectively. Acute cholangitis and abdominal pain were the presenting symptoms in 57 patients (59%) and 29 patients (30%), respectively. Fifty-four patients (56%) had a history of biliary surgery. Endoscopic retrograde cholangiopancreatography, ultrasonography, and computed tomography were frequently employed for diagnosis of primary biliary stones and were performed on 84 patients (88%), 90 patients (94%), and 89 patients (93%), respectively. Intrahepatic stones were identified in 91 patients (95%) and biliary strictures in 34 patients (35%). Concomitant cholangiocarcinoma occurred in 15 patients (16%). Hepatic resection was required in 55 patients (57%) for removal of an atrophic liver lobe or a segment related to repeated infection, biliary strictures, liver abscesses, or cholangiocarcinoma. Intraoperative choledochoscopy was routinely performed in all patients to detect, remove, or confirm clearance of biliary stones. A hepaticocutaneous jejunostomy (HCJ) was constructed in 70 patients (73%) to facilitate postoperative choledochoscopic examination or biliary stone extraction. Twenty-two patients (23%) had residual stones and required postoperative choledochoscopic extraction. Complete eradication of residual stones was achieved in all patients. Postoperative morbidity occurred in 28 patients (29%), and there was one hospital death (a patient with cholangiocarcinoma). With a median follow-up of 26 months (range 2-62 months), stones recurred in three patients. In conclusion, the early results of treatment of primary biliary stones were satisfactory owing to a systematic, aggressive approach that consisted of hepatic resection, frequent construction of an HCJ, and postoperative choledochoscopy.

Adult↗
PubMed1998

Surgical strategy for insulinomas in multiple endocrine neoplasia type I.

BACKGROUND: Hyperinsulinemia in multiple endocrine neoplasia type I (MEN-I) is a rare but potentially curable condition that presents difficulties not encountered in sporadic cases. METHODS: The present report documents our surgical approach to 3 MEN-I patients with hyperinsulinemia. RESULTS: Primary hyperparathyroidism was manifested in all 3 patients at the time of presentation. Distal subtotal pancreatectomy with enucleation of tumor at the head of pancreas detected intraoperatively resulted in immediate cure of 2 patients. Persistent disease occurred in 1 patient after enucleation of tumor at the head of the pancreas guided by preoperative imaging elsewhere. The patient was subsequently cured by distal subtotal pancreatectomy. Pathology revealed multiple tumors (4 to 14) in all patients. CONCLUSIONS: A different surgical strategy with an aim of distal subtotal pancreatectomy and enucleation of any tumor identified in the head of pancreas is the treatment of choice for hyperinsulinemia in MEN-I patients.

Adult↗
PubMed1998

The role of hepatic arterial embolization in the treatment of spontaneous rupture of hepatocellular carcinoma.

Thirty-three patients presenting with spontaneous rupture of hepatocellular carcinomas (HCCs) were referred for emergency transcatheter arterial embolization. Blood was present in the ascitic fluid on abdominal paracentesis in all 33 patients. Seventeen patients underwent emergency computed tomography (CT). HCCs were demonstrated on CT in all 17 patients. Blood was detected in the peritoneal cavity or around the liver surface on CT in 15 patients (88.2%), one of whom also had active extravasation of the contrast medium into the peritoneal cavity. Vascular tumours were present in the hepatic angiograms prior to embolization in all 33 patients but extravasation of the contrast medium from the HCC was seen on angiography in only six patients (18.2%). Bleeding from the ruptured HCC was stopped at the end of the procedure in 32 patients who had undergone successful embolization. The overall median survival time was 9 weeks. The median survival time of patients with a serum total bilirubin level of 50 micromol/l or below was 15 weeks, while that of patients with a serum total bilirubin level above 50 micromol/l was only 1 week, the difference being statistically significant. Embolization is therefore the treatment of choice in arresting life-threatening bleeding in ruptured HCC in patients with a serum total bilirubin level of 50 micromol/l or below, but the procedure is rarely effective in prolonging survival in patients with a serum total bilirubin above this critical level.

Adult↗