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Biomedical subjects

W Yeo

Publications and source records attributed to W Yeo.

At least 55 records · Page 3Linked to original sources

Lamivudine in the treatment of hepatitis B virus reactivation during cytotoxic chemotherapy.

Hepatitis B virus (HBV) reactivation has been described in cancer patients who received cytotoxic/immunosuppressive therapy and may result in liver damage of varying degrees of severity. There is no known effective treatment. Lamivudine, a nucleoside analogue, has been found to suppress HBV replication and to improve histology in chronic carriers of hepatitis B virus. The outcome of lamivudine therapy (at doses of 100 or 150 mg/day) in eight patients who developed HBV reactivation while receiving cytotoxic chemotherapy is described. Each of the eight patients had >98% suppression of the pretreatment HBV DNA levels. Three of the five patients who were initially HBeAg positive underwent seroconversion. Five patients had normalization of liver function tests and improvement in clinical condition. However, one patient died of hepatic failure due to HBV-related submassive liver necrosis, and two died of widespread metastases (including liver) from the primary malignancies. It is concluded that early commencement, i.e., at the onset of HBV reactivation before severe hepatic decompensation, of lamivudine may be effective in the control of HBV reactivation during chemotherapy. In Hong Kong, where hepatitis B infection is endemic, we propose to screen all cancer patients for hepatitis B surface antigen before immunosuppressive/cytotoxic therapy, and to closely monitor liver function of those who are found to be HBsAg seropositive.

Adult↗

Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes.

A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.

Adult↗

A multi-centre randomized phase II study of nolatrexed versus doxorubicin in treatment of Chinese patients with advanced hepatocellular carcinoma.

PURPOSE: A multi-centre randomized phase II study of single agent nolatrexed dihydrochloride versus doxorubicin was undertaken in Chinese patients with advanced hepatocellular carcinoma (HCC) to study and compare the clinical efficacy of the two drugs. METHODS: Fifty-four patients with clinical or histological diagnosis of HCC were randomized in a 2:1 ratio to receive nolatrexed or doxorubicin. Nolatrexed 725 mg/m(2)/day was given by continuous infusion via a central venous device for 5 days and doxorubicin 60 mg/m(2) was given as a rapid intravenous infusion every 3 weeks. RESULTS: No objective responses were observed in either treatment arm. Two patients in the nolatrexed arm and none in the doxorubicin arm had >50% decline in serum alpha-fetoprotein. The median survival for the patients in the nolatrexed and doxorubicin arms was 139 days and 104 days, respectively. Moderate toxicities including leukopenia, thrombocytopenia, mucositis and skin rash were observed in both treatment arms. CONCLUSION: Nolatrexed and doxorubicin are minimally active in the treatment of advanced HCC. Given the small sample size, no difference is observed between the two drugs.

Adult↗

Imaging of iliopsoas metastasis.

The imaging features of four patients with metastasis to the iliopsoas are presented with emphasis on the ultrasound, CT and MRI appearances. In patients with a known primary tumour, the possibility of iliopsoas metastasis, although uncommon should be considered.

Adult↗

Hepatitis B envelope protein mutants in human hepatocellular carcinoma tissues.

Hepatitis B virus (HBV) envelope mutants in the region encoding the highly immunogenic major hydrophilic region (MHR) of surface antigen (HBsAg) have been associated with vaccine failure and chronic infection. To determine if these mutants are associated with the development of human hepatocellular carcinoma (HCC), we measured the frequency and nature of such mutants in 23 HBV-associated HCC and various control tissues by performing Southern blot analysis, the polymerase chain reaction (PCR) and direct sequencing. The HBV genome was present mainly in an integrated form and, in most of the samples, the envelope gene was intact. Amino acid substitutions, involving the MHR region in the HCC tissues, were analysed in 11 (61. 1%) of 18 patients with HCC. The mutation Gly145Arg, which has been reported to be associated with immunoevasion, was found in seven of the 18 HCC tissues. A significantly higher frequency of mutations was found in HCC tissues (11 of 18) than in the corresponding non-tumorous tissue of the same patients (one of eight), and in samples from patients with acute (one of 19) or chronic (three of 31) HBV infection (P < 0.001, Fisher's exact test). The accumulation of these envelope mutants in the HCC tissue suggests that such envelope protein mutations may play a role in the process of oncogenesis and that specific vaccines may need to be developed to prevent the occurrence of mutant HBV-associated HCC. Alternatively, the progressive accumulation of mutants in patients with acute hepatitis, chronic hepatitis and HCC may reflect the increased length of duration of HBV infection in these groups of liver lesions.

Adult↗

Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma.

The purpose of this Phase II study was to determine the response rate, the toxicity, and the effect on survival of the combination of cisplatin, doxorubicin, 5-fluorouracil, and alpha-IFN (PIAF) in advanced unresectable hepatocellular carcinoma. Fifty patients with either unresectable or metastatic disease were treated with PIAF: cisplatin (20 mg/m2 i.v., days 1-4), doxorubicin (40 mg/m2 i.v., day 1), 5-fluorouracil (400 mg/m2 i.v., days 1-4), and alpha-IFN (5 MU/m2 s.c., days 1-4). Treatment was repeated every 3 weeks to a maximum of six cycles. All patients were evaluable for response, toxicity, and survival. As assessed by conventional imaging criteria, there were no complete responses, but 13 patients (26%) had a partial response. Among the 36 patients who had an initially high alpha-fetoprotein level (>500 ng/ml), 15 (42%) had a >50% fall after therapy. Nine patients underwent surgical resection after achieving partial response and, in 4 of these patients, histological examination of the resected specimens revealed no viable tumor cells. All these nine patients are alive, and eight patients remain in complete remission at between 7.6 and 25.8 months at the time of analysis. The overall median survival was 8.9 months. Toxicity was mainly myelosuppression and mucositis. There were two treatment-related deaths due to neutropenic sepsis. PIAF is active in hepatocellular carcinoma despite considerable hematological toxicity. Complete pathological remission is possible with this systemic combination. Apparently, persistent radiological lesions may still represent complete pathological resolution of active disease.

Adolescent↗

Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma: a quantitative analysis.

The only hope of long-term survival for patients with hepatocellular carcinoma (HCC) is surgical resection or liver transplantation. However, recurrence or metastasis formation is common after surgery. We aim to assess whether surgical resection leads to hematogenous dissemination of malignant and nontumor hepatocytes and determine the quantity and timing of hepatocyte shedding into the circulation. Using semiquantitative reverse transcription-PCR for alpha-fetoprotein (afp) and albumin (alb) mRNAs, we measured the mass of malignant and nontumor hepatocytes in 53 peripheral blood samples collected preoperatively, intraoperatively, and postoperatively from 13 HCC patients. We compared these data with those in 54 control samples collected from 24 healthy subjects and patients with chronic hepatitis/cirrhosis and 10 hepatocellular adenoma patients who underwent resection. Clinicopathological information of HCC patients was obtained during 3-year follow-up. In 100% (23 of 23) of HCC and adenoma patients, alb mRNA levels increased 10-10(6)-fold intraoperatively and then markedly declined within 8 weeks after operation. Levels of afp mRNA increased 5-7600-fold preoperatively in 8% (1 of 13) and postoperatively in 70% (9 of 13) of HCC patients. All five HCC patients with persistently elevated afp mRNA levels died from intrahepatic/extrahepatic metastasis, liver recurrence, or persistent HCC within 1 year after surgery. The absence/clearance of afp mRNA in 75 % (six of eight) of survivors was strongly associated with the absence of metastasis/recurrence (P = 0.02). We present evidence that alb-expressing hepatocytes are released intraoperatively into the circulation, and afp-expressing tumor cells are disseminated mostly postoperatively that may potentially be the source of recurrence or metastasis. Sequential quantification of both alb and afp mRNAs may provide insights for risk assessment and prognostic indication.

Adenoma↗

Phase II study of Temodal in the treatment of patients with advanced nasopharyngeal carcinoma.

PURPOSE: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal carcinoma was undertaken to determine the efficacy and safety of the drug in this population. METHODS: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study. One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m2 daily on days 1-5 every 28 days. RESULTS: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease after 2 (84.6%) or 4 (15.4%) courses. CONCLUSION: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma.

Adult↗

Injection sclerotherapy for variceal bleeding in patients with hepatocellular carcinoma: cyanoacrylate versus sodium tetradecyl sulphate.

BACKGROUND: Patients with hepatocellular carcinoma complicated by variceal bleeding have a very limited life span. Recurrent bleeding after endoscopic injection sclerotherapy is common. Our aim was to compare the efficacy of endoscopic injection of cyanoacrylate versus sodium tetradecyl sulphate in the control of variceal bleeding in patients with hepatocellular carcinoma. METHODS: Patients known to be suffering from inoperable hepatocellular carcinoma who presented with upper gastrointestinal bleeding underwent endoscopy within 24 hours of admission. After bleeding from esophageal varices was confirmed, they were randomized to receive endoscopic injections of either cyanoacrylate (1:1 mixture with Lipoidol) or sodium tetradecyl sulphate (1.5%). Injection were given intravariceally into each visible column for up to four injections for cyanoacrylate and up to 30 mL for sodium tetradecyl sulphate. RESULTS: A total of 50 patients were recruited for this study with 25 cases randomized to each endoscopic treatment group. Control of acute bleeding failed in four patients (16%) in both treatment groups, and two patients in each group died during the index episode of bleeding. Six patients (24%) in the cyanoacrylate group and four patients (16%) in the sodium tetradecyl sulphate group developed recurrent bleeding during their hospital stay (p = 0.48). Recurrent bleeding within 30 days after the index episode of bleeding was documented in seven patients (28%) who received cyanoacrylate injection and five patients (20%) who received sodium tetradecyl sulphate injection (p = 0.51). Median survival in the cyanoacrylate group was 16 days (range 1 to 485 days) and that of the sodium tetradecyl sulphate group was 13 days (range 1 to 407 days). There was no difference in cumulative survival between the two groups as analyzed by the Kaplan-Meier method. Patients with portal vein thrombosis had a higher risk of recurrent hemorrhage. Patients with Child's C liver disease had a significantly higher mortality. CONCLUSIONS: Cyanoacrylate did not improve the outcome of hepatocellular carcinoma patients with variceal hemorrhage.

Carcinoma, Hepatocellular↗

A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma.

The aim of this study was to determine the efficacy and toxicity of combination paclitaxel and carboplatin chemotherapy in patients with metastatic and/or locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with metastatic and/or locoregionally advanced NPC were treated with carboplatin calculated according to an AUC of 6 mg ml/min (based on Calvert formula) given as an intravenous (i.v.) bolus, followed by paclitaxel 135 mg/ml2 given as an i.v. infusion over 3 h with standard premedication. Cycles were given 3 weekly to a maximum of six. From January 1996 to November 1997, 27 patients were entered and assessable for response and toxicity. A total of 122 cycles were given and the median number of cycles given was five. The overall response rate was 59% (16/27). There were 3 (11%) complete responses, 13 (48%) partial responses, 5 (19%) static disease and 6 (22%) progressive disease. Toxicity was mainly haematological including: grade 3/4 neutropenia (39 cycles, 32%), grade 3/4 anaemia (nine cycles, 7%), grade 3/4 thrombocytopenia (eight cycles, 7%). There were three episodes of neutropenic fever (3%). Non-haematological toxicities were mild and infrequent. Paclitaxel and carboplatin combination chemotherapy is active in NPC and has tolerable toxicity. Further study with dose escalation is required to assess its optimal efficacy.

Adult↗

Nasal lymphoma: results of local radiotherapy with or without chemotherapy.

BACKGROUND: Primary nasal lymphoma is a rare disease. Although most patients are initially seen in early Ann Arbor stages, their prognosis is poor. The prognostic significance of local tumor bulk has not been well studied. METHODS: Twenty-one patients with nasal lymphoma treated between 1985 and 1992 were retrospectively studied. Sixteen patients (76%) below the age of 75 years received combined radiotherapy and chemotherapy. One young patient with early disease and 4 elderly patients had radiotherapy alone. Twelve cases (57%) were diagnosed as pleomorphic T-cell lymphoma based on typical histologic features alone. Immunophenotyping was performed in 10 cases; 8 were T cell and 2 were B cell. Seventeen patients (81%) had Ann Arbor clinical stage IE disease, and 4 had stage IIE disease. The local tumor extent was assessed by endoscopy in all patients and by computerized tomography (CT) in 14 patients. Eleven local tumors (52%) extended to the posterior ethmoids, sphenoid sinus, orbit, or beyond. Using a T-stage system, the prognostic significance of local tumor bulk was evaluated for stage IE patients. RESULTS: At a median follow-up time of 16.8 months, the lymphoma recurred in 13 patients; 10 patients had systemic relapse and 10 patients, local relapse. The 5-year actuarial overall survival rate was 24%. Complete response to chemotherapy was achieved in 5 of 16 patients (31%). Four of the 6 patients who remained alive and disease-free were chemotherapy complete responders. Among stage IE patients, those with early and those with advanced local disease did not have significantly different survival. CONCLUSIONS: In view of the high systemic and local relapse rates, more-effective chemotherapy is needed to improve the survival rates, and the role of combined chemotherapy and radiotherapy should be evaluated. Further studies are required to identify patients at high risk of relapse for clinical trials with investigational treatment.

Adult↗

MRI and CT of metastatic hepatocellular carcinoma causing spinal cord compression.

We report the imaging features in five patients with metastatic hepatocellular carcinoma causing spinal cord compression, three of which were biopsy proven and two were in patients with known diagnosis of hepatocellular carcinoma. The radiographic, magnetic resonance imaging (MRI) and computed tomography (CT) features are highlighted. Although the occurrence of metastatic disease in hepatocellular carcinoma is exceedingly rare, it may be increasingly encountered as survival of patients is improved with advancing methods of therapy, both surgical and palliative. It often accompanies local recurrence, and invariably signals a grave prognosis with extremely short life expectancy. Unusually, two of the five patients in this series presented initially with skeletal metastases which led to the diagnosis of hepatocellular carcinoma.

Adult↗