Minimal hepatic toxicity of Onyx-015: spatial restriction of coxsackie-adenoviral receptor in normal liver.

We administered an adenoviral vector, Onyx-015, into the hepatic artery of patients with metastatic colorectal cancer involving the liver. Thirty-five patients enrolled in this multi-institutional phase I/II trial received up to eight arterial infusions of up to 2 x 10(12) viral particles. Hepatic toxicity was the primary dose-limiting toxicity observed in preclinical models. However, nearly 200 infusions of this adenoviral vector were administered directly into the hepatic artery without significant toxicity. Therefore, we undertook this analysis to determine the impact of repeated adenoviral exposure on hepatic function. Seventeen patients were treated at our institution, providing a detailed data set on the changes in hepatic function following repeated exposure to adenovirus. No changes in hepatic function occurred with the first treatment of Onyx-015 among these patients. Transient increases in transaminase levels occurred in one patient starting with the second infusion and transient increases in bilirubin was observed in two patients starting with the fifth treatment. These changes occurred too early to be explained by viral-mediated lysis of hepatocytes. In addition, viremia was observed starting 3-5 days after the viral infusion in half of the patient, but was not associated with hepatic toxicity. To further understand the basis for the minimal hepatic toxicity of adenoviral vectors, we evaluated the replication of adenovirus in primary hepatocytes and tumor cells in culture and the expression of the coxsackie-adenoviral receptor (CAR) in normal liver and colon cancer metastatic to the liver. We found that adenovirus replicates poorly in primary hepatocytes but replicates efficiently in tumors including tumors derived from hepatocytes. In addition, we found that CAR is localized at junctions between hepatocytes and is inaccessible to hepatic blood flow. CAR is not expressed on tumor vasculature but is expressed on tumor cells. Spatial restriction of CAR to the intercellular space in normal liver and diminished replication of adenovirus in hepatocytes may explain the minimal toxicity observed following repeated hepatic artery infusions with Onyx-015

A Review of Superior Vena Cava Obstruction in Hong Kong Chinese Patients

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Nasopharyngeal carcinoma: presenting symptoms and duration before diagnosis

This is a retrospective analysis of 4768 patients with undifferentiated or non-keratinising carcinoma of the nasopharynx who were treated during 1 January 1976 to 31 December 1985. The mean duration of symptoms before diagnosis was 8 months (range, 1-36 months for 95% of patients). A significant association between the duration of symptoms and the presenting stage was observed (P<0.001); 58% and 39% of stage I and stage V patients, respectively, reported as having had symptoms for less than 6 months. Of the later presenters (those having had symptoms for 6 months or longer), 89% were given a full course of radical megavoltage radiotherapy, but 6% were too advanced for any irradiation attempt. Consequently, the 10-year actuarial disease-specific survival was significantly higher among the early presenters: 48% versus 42% (P<0.001). The importance of early detection is emphasised.published_or_final_versio

Breast Conservation Treatment in Hong Kong – Early Results of 203 Patients: Retrospective Study

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Nasopharyngeal carcinoma: time lapse before diagnosis and treatment

This is a descriptive study of 168 patients with nasopharyngeal carcinoma who were referred to public oncology departments for primary treatment between July and September 1996. The mean duration from the onset of the symptoms to histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for patients presenting with nasal symptoms) to 1.8 months (for those with cranial nerve dysfunction). The mean period between the onset of symptoms and the seeking of medical advice was 2.9months. For 54% of the patients, there was a further delay of up to 2.4 months between the initial medical consultation and referral to the appropriate specialist. The majority (84%) of patients attended public institutions for histological confirmation. The mean total time taken from the onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3-74.0 months)---45% of the delay was attributed to the patient, 20% to initial consultations, 14% to diagnostic arrangement, and 21% to preparation for radiotherapy. Concerted efforts are needed to minimise further the time between the onset of symptoms and treatment. A substantial reduction in this delay can be achieved if both public and primary care doctors were made more aware of the significance of relevant symptoms.published_or_final_versio

Factors predicting patient satisfaction in women with advanced breast cancer: a prospective study

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Adolescents' experience of comments about their weight – prevalence, accuracy and effects on weight misperception

<p>Abstract</p> <p>Background</p> <p>Weight comments are commonly received by adolescents, but the accuracy of the comments and their effects on weight misperception are unclear. We assessed the prevalence and accuracy of weight comments received by Chinese adolescents from different sources and their relation to weight misperception.</p> <p>Methods</p> <p>In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006–07, 22612 students aged 11–18 (41.5% boys) completed a questionnaire on obesity. Students responded if family members, peers and professionals had seriously commented over the past 30 days that they were "too fat" or "too thin" in two separate questions. The accuracy of the comments was judged against the actual weight status derived from self-reported height and weight. Self-perceived weight status was also reported and any discordance with the actual weight status denoted weight misperception. Logistic regression yielded adjusted odd ratios for weight misperception by the type of weight comments received.</p> <p>Results</p> <p>One in three students received weight comments, and the mother was the most common source of weight comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Adolescents receiving incorrect comments had increased risk of having weight misperception in all weight status groups. Receiving conflicting comments was positively associated with weight misperception among normal weight adolescents. In contrast, underweight and overweight/obese adolescents receiving correct weight comments were less likely to have weight misperception.</p> <p>Conclusion</p> <p>Weight comments, mostly incorrect, were commonly received by Chinese adolescents in Hong Kong, and such incorrect comments were associated with weight misperception.</p

Organic pollutants in sea-surface microlayer and aerosol in thecoastal environment of Leghorn—(Tyrrhenian Sea)

The levels of dissolved and particle-associated n-alkanes, alkylbenzenes, phthalates, PAHs, anionic surfactants and surfactant fluorescent organic matter ŽSFOM. were measured in sea-surface microlayer ŽSML. and sub-surface water ŽSSL. samples collected in the Leghorn marine environment in September and October 1999. Nine stations, located in the Leghorn harbour and at increasing distances from the Port, were sampled three times on the same day. At all the stations, SML concentrations of the selected organic compounds were significantly higher than SSL values and the enrichment factors ŽEFsSML concentrationrSSL concentration. were greater in the particulate phase than in the dissolved phase. SML concentrations varied greatly among the sampling sites, the highest levels Žn-alkanes 3674 mgrl, phthalates 177 mgrl, total PAHs 226 mgrl. being found in the particulate phase in the Leghorn harbour. To improve the knowledge on pollutant exchanges between sea-surface waters and atmosphere, the validity of spray drop adsorption model ŽSDAM. was verified for SFOM, surface-active agents, such as phthalates, and compounds which can interact with SFOM, such as n-alkanes and PAHs. q2001 Elsevier Science B.V. All rights reserved