Study on the interzonal migration of airborne infectious particles in an isolation ward using benign bacteria.

UNLABELLED: Negative pressure isolation wards are essential infection control facilities against airborne transmissible diseases. Airborne infectious particles are supposed to be contained in the isolation room. However, negative pressure may break down by door-opening action or by human movement. Understanding the interzonal transport of airborne infectious particles in the isolation wards can aid the design and operation strategy of isolation facilities. In this work, the interzonal migration of airborne infectious particles by human movement was studied experimentally in an isolation ward. Artificial saliva solution with benign E. coli bacteria was aerosolized to simulate bacterium-laden infectious particles. The interzonal migration of aerosolized bacteria was characterized by biological air sampling. Less than 1% of airborne infectious particles were transported to the higher pressure zone when door was closed. With human movement, 2.7% of the particles were transported from the anteroom to the corridor. From high-to-low pressure zones, as much as 20.7% of airborne infectious particles were migrated. Only a minimal amount of particles was transported from the corridor to the positive pressure nurses' station. Infection risk of tuberculosis of the healthcare workers and other occupants in the isolation wards were also assessed based on the measured migration ratios. PRACTICAL IMPLICATIONS: Human movement is an important factor governing interzonal migration. It is the main cause of migration of airborne infectious particles to a relatively negative pressure zone. This study provides a set of experimentally obtained particle migration ratios by human movement. Other than serving as empirical data for further studies on the mechanics, these migration ratios can also be used to assess the infection risk for occupants in the isolation ward.

What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres?

BACKGROUND/AIMS: The survival duration of patients with nonresectable hepatocellular carcinoma confined to the liver and treated with intraarterial yttrium-90 microspheres was highly variable. METHODOLOGY: Eighty-two patients treated by this method were analyzed. Thirty-one patients who lived for one year or longer from the date of first treatment were classified as 'long survivors' and 51 patients who died within 1 year were classified as 'short survivors'. RESULTS: Comparison between the 2 categories suggested that lower pretreatment level of alpha-fetoprotein and higher tumor-to-normal uptake ratio of yttrium-90 microspheres favored longer survival. Results also indicated that the treatment was effective even for large tumors and for postoperative recurrence. Repeated treatment of viable residual or recurrent tumors offered further palliation and prolongation of survival. CONCLUSIONS: Pretreatment alpha-fetoprotein level, tumor-to-normal uptake ratio of yttrium-90 microspheres and the number of treatments determine survival duration.

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.

High frequency of p16INK4A gene alterations in hepatocellular carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR-SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

Combating hepatocellular carcinoma with an integrated approach.

This short review summarizes an integrated approach to new methods of managing hepatocellular carcinoma (HCC) developed at our centre. HCC-specific isoforms of alpha-fetoprotein were detected by isoelectric focusing and their value in the differential diagnosis of early HCC on a background of chronic liver disease has been shown. Selective internal radiation therapy using yttrium-90 (90 Y) microspheres has been shown to be an effective treatment for inoperable HCC in a phase I and II study. A partition model for estimating the radiation doses from the 90 Y microspheres to the tumour and the non-tumorous liver during the therapy was then formulated, verified by correlating with intraoperative dosimetry, and evaluated in clinical settings. This permits 90 Y microspheres to be administered safely without the need of an open surgery and a randomized therapeutic controlled trial is in progress. Another randomized controlled trial using iodine-131 Lipiodol as a post-operative adjuvant therapy, aiming at reducing the recurrence rate is also on-going. HCC may be more effectively combated with a better understanding of its pathogenesis from chronic liver disease.

Percutaneous biopsy of small hepatic lesions using an 18 gauge automated needle.

This study evaluates the efficacy of ultrasound guided percutaneous biopsy using an 18 gauge automated side-cutting needle in the diagnosis of small (< or = 3 cm) focal hepatic lesions. 137 consecutive percutaneous biopsies of 131 different small (< or = 3 cm) focal hepatic lesions were included. 11 biopsies were performed on lesions of < or = 1 cm in diameter, 56 were on lesions 1.1-2 cm in size and 70 on lesions 2.1-3 cm in size (average 2.3 +/- 0.7 cm; median 2.3 cm; range 0.7-3 cm). The biopsy specimen was sufficient for diagnosis in 135 cases (98.5%). The sensitivity for diagnosing malignancy was 96.4%; specificity was 100%, positive and negative predictive values were 100% and 94.6%, respectively; accuracy was 97.8%. There was no statistically significant difference in the diagnostic efficacy for lesions of different pathology and size. No significant post-biopsy complication occurred. It is concluded that the 18 gauge Temno needle is safe and effective in diagnosing small hepatic lesions.

Cosmetic outcome of breast-conserving therapy in Chinese patients with early breast cancer.

BACKGROUND: Breast-conserving surgery combined with radiotherapy has emerged as an alternative to mastectomy for women with early breast cancer, and cosmetic outcome has correlated closely with the psychosocial and physical well-being of the patient. Cosmetic outcome assessment after breast-conserving therapy in Chinese patients has so far not been conducted among the clinicians, the patients or their spouses. METHODS: The cosmetic results from breast-conserving therapy were evaluated in a group of 33 patients who had been selected as suitable for undergoing local excision, axillary dissection and postoperative radiation therapy for early stage breast cancer. The success of the procedures was assessed by the patients, the clinicians and the patient's spouse, and their ratings were compared with each other. RESULTS: Eighty per cent of the patients and their spouse were satisfied with the cosmetic outcome. Using McNemar's test, when the groups were evaluated on a case-by-case basis, there was a good level of concordance between the patients and their spouses, and that of the patients and the clinicians. CONCLUSIONS: Evaluation of the cosmetic and psychosocial sequelae of breast cancer patients is essential when new approaches to treatment are introduced; our data suggest that cosmetically successful breast conservation is feasible in a selected group of Chinese women with early breast cancer.

Safety of percutaneous biopsy of hepatocellular carcinoma with an 18 gauge automated needle.

OBJECTIVE: Accurate histological diagnosis and subtyping of hepatocellular carcinoma (hepatoma) is likely to be enhanced if a large biopsy tissue specimen is made available to the pathologist. However biopsy of this tumour can be dangerous, especially if the liver is cirrhotic and the lesion is superficial. This study evaluates the safety of an 18 gauge spring loaded side-cutting needle in the percutaneous biopsy of hepatoma in cirrhotic patients under ultrasonographic (US) guidance. Particular attention was paid to establishing the necessary length of needle track through interposing liver parenchyma to be certain of maximum safety. MATERIALS AND METHODS: One hundred and thirty-nine consecutive biopsy procedures were performed on 129 hepatomas which belonged to 113 men and 12 women of average age 57 +/- 15 years old (median 60, range 8 months-88 years). Ninety-six (69.1%) of these biopsies were performed in cirrhotic livers. The length of biopsy needle track traversing interposing liver parenchyma was less than 1 cm in two cases, 1 cm in 41 cases, between 1 and 2 cm in 46 cases and > 2 cm in 50 cases. The mean tumour size was 7.2 +/- 4.5 cm (median 6.8 cm, range 0.7-25 cm). The average number of needle pass in each biopsy was 2.1 +/- 0.8 times (median 2, range 1-5). RESULTS: One hundred and twenty-six (90.6%) of the biopsy procedures were diagnostic of hepatoma. There were two cases of post-biopsy bleeding, both occurred in procedures with an interposing liver parenchymal track less than 1 cm in length. CONCLUSION: The biopsy technique described was found to be safe for diagnosing hepatoma in patients with or without liver cirrhosis provided that the length of interposing liver parenchymal track is not < 1 cm.

Arteriovenous shunts in patients with hepatic tumors.

UNLABELLED: The study aimed to investigate the influence of tumor type, tumor size, tumor vascularity and treatment on arteriovenous shunts between the liver and lungs in patients with hepatic cancer. METHODS: Our previous assessment of the degrees of lung shunting using intra-arterial 99mTc-macroaggregated albumin in 125 patients with hepatocellular carcinoma (HCC) was extended to include 377 patients with HCC and 25 patients with colorectal liver metastases. Patients were given 111 MBq (3 mCi) of 99mTc-macroaggregated albumin during hepatic angiography. The lungs and the liver were localized as regions of interest on the digitized gamma scintigraphic image. The total counts taken over the lungs divided by the total counts taken over both the lungs and the liver gave the percentage of lung shunting. Tumor size was measured by computerized tomography or ultrasound scan. Tumor vascularity was assessed based on the degree of neovascularization. Linear regression and Wilcoxon rank test were used for statistical analysis. RESULTS: Patients with HCC had a higher median (7.6%) and a wider range (< 1-75.4%) of percentages of lung shunting when compared with those with colorectal liver metastases (median, 4.7%; range, < 1-23.9%). The lung shunting correlated with the tumor size in the 377 patients with HCC (r = 0.359; p < 0.0001). Excluding one outlier, we found a similar correlation in 24 patients with colorectal metastases (r = 0.686; p < 0.0001). In HCC, the mean lung shunting increased with increasing tumor size, up to 15 cm, and then remained almost unchanged, up to a size of > 20 cm. The mean lung shunting also increased with increasing vascularity grades, as assessed by hepatic angiography. The difference between any two vascularity grades was statistically significant (p = 0.0001-0.0148). Similar analysis by subgroups in colorectal liver metastases was impossible because of the small number of patients. Lung shunting decreased in HCC patients after the tumors were treated, but it might increase or decrease when the disease recurs. CONCLUSION: The lung shunting was influenced by the type, size and vascularity of the hepatic tumor. The change in lung shunting with the status of the tumor after treatment further suggests a neoplastic nature of the blood vessels involved in the arteriovenous shunt.

Assessment of proliferating cell nuclear antigen in nasopharyngeal carcinoma tissue and its relation to clinical findings.

47 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were studied using the proliferating cell nuclear antigen (PCNA) immunostaining technique. The results were reproducible as shown by assessment of three separate sections performed for each patient. No statistical correlation was found between PCNA labelling index (LI) and Ho's clinical staging or time required to achieve complete remission of the local disease. A higher PCNA LI was associated with a poorer disease-free survival. The literature on the use of PCNA in human tumours is reviewed.

'Hepatoma-specific' alphafetoprotein may permit preclinical diagnosis of malignant change in patients with chronic liver disease.

The only hope for effective treatment of hepatocellular carcinoma (HCC or 'hepatoma') lies in early diagnosis. Measurement of the serum alphafetoprotein (AFP) level is potentially a useful screening test. When grossly raised, it is almost diagnostic of HCC. However, modestly elevated levels may also arise in patients with benign chronic liver disease, and this markedly decreases the test's specificity and hence its clinical value. In 582 consecutive attendees at an outpatient clinic for people with chronic liver disease, a single blood sample was taken for analysis of 'total' AFP and the 'hepatoma-specific' AFP isoform. Using ultrasonography as the primary screening method, patients with AFP levels > or = 50 ng ml-1 were followed up throughout the study or until HCC was diagnosed on the basis of conventionally defined criteria. On entry into the study, 53 patients had an AFP concentration > = or 50 ng ml-1 and the 'hepatoma-specific' AFP isoform was detected in 26 of these. During an 18-month follow-up period, a diagnosis of HCC was established by conventional methods in 19 (17 'definite' and two 'probable') of these 26 patients. In only two cases was there ultrasound evidence of tumour development at the time AFP was first found to be elevated; in the remainder a diagnosis of HCC, based on ultrasound screening, was established at a median time of 3.6 months (range 1-18 months) after entry into the study. Among those 27 without the 'hepatoma-specific' isoform, one developed a 'definite' HCC and two developed 'probable' tumours. With the application of 'hepatoma-specific' AFP, the positive predictive value of the test was 73.1%, compared with only 41.5% using the conventional 'total' AFP test. Application of this test for the 'hepatoma-specific' AFP markedly increases the positive predictive value of AFP and, in some cases, permits the presence of tumour to be inferred before it could be detected by routine ultrasound examination.

Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in monitoring of therapy.

CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of nasopharyngeal carcinoma and 19 patients who developed distant metastases. A reference range of < 2 U/ml for our local Chinese population was established in 55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients had significantly higher marker levels than the healthy controls and the mean level increased with advancing stage. However, the low percentage of elevation in early stages means that the marker is not useful for screening. The overall percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of the nasopharynx is comparable to that of squamous cell carcinoma of the lungs, suggesting that the expression of CYFRA 21-1 is related to the cell type rather than the tissue type of the carcinoma, 46 (95.8%) of 48 patients with metastatic nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely high percentage implies that it is very unlikely for a patient with a normal value to have distant metastasis. This may permit major economies in radiological screening for distant metastasis. Preliminary results from serial measurement of the marker indicated its potential for monitoring response to treatment and for early detection of distant metastasis.

Strong association between hyperferritinaemia and metastatic disease in nasopharyngeal carcinoma.

We have investigated the role of serum ferritin, in relation to disease stages, in patients with nasopharyngeal carcinoma. Patients with localised disease (Ho's stage I-IV) had levels which were not significantly different from age, sex matched normal subjects and there was no relationship between mean serum ferritin levels and stage. However, in patients with metastatic disease levels were grossly elevated with mean levels increased more than 6-fold compared to normal subjects and patients with localised disease. Furthermore, among the small group of patients with localised disease but hyperferritinaemia, the subsequent development of metastatic disease within 1 year was significantly much higher (32.4%) than in those with levels falling within the reference range (10.3%). Hyperferritinaemia is strongly associated with, and may predict, metastatic disease in patients with nasopharyngeal carcinoma.

Early tumour response and treatment toxicity after hyperfractionated radiotherapy in nasopharyngeal carcinoma.

The aim of the present study was to undertake a planned interim analysis of a prospective randomized trial comparing the tumour response and the acute and subacute complications of hyperfractionated radiotherapy and conventional radiotherapy in non-metastatic nasopharyngeal carcinoma (NPC). 100 patients with newly diagnosed non-metastatic NPC were randomized to receive either conventional radiotherapy (Arm I) or hyperfractionated radiotherapy (Arm II). Stratification was done according to the T-Stage (modified Ho's T-Stage classification). The biological effective dose (10 Gy) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Hyperfractionated radiotherapy was associated with significant mucositis which is of higher grade than conventional radiotherapy (p = 0.0001), but the duration of mucositis was similar between the two Arms and all study patients completed radiotherapy on schedule without interruption of radiotherapy. Early survival and tumour recurrence rates were comparable between the Arms. The preliminary results indicate that the hyperfractionated radiotherapy has excellent patient compliance in Chinese patients, with acceptable acute and subacute toxicities and the local and regional complete tumour response rates being comparable with conventional radiotherapy. The significance of the time required after start of radiotherapy to achieve a complete tumour response is discussed.

In vitro uptake of bromodeoxyuridine by human nasopharyngeal carcinoma (NPC) and its relation to clinical findings.

A cell kinetic study of 27 newly diagnosed patients with nasopharyngeal carcinoma (NPC) using the in vitro bromodeoxyuridine (BrdU) technique was performed. The results were reproducible as demonstrated by three independent sections performed on each patient. No correlation between BrdU labelling index (LI) and Ho's clinical staging was found. A higher LI was associated with the development of distant metastases (P = 0.057). Statistically significant correlation was found between low LI and longer duration required to achieve complete remission in the primary site of disease (P = 0.026). This study suggests a potential role for in vitro BrdU labelling index as a prognosticator for NPC prior to treatment.

Quantitative evaluation of thallium-201 uptake in predicting chemotherapeutic response of osteosarcoma.

Thallium-201 has been shown to be useful in predicting tumour viability in patients undergoing neoadjuvant chemotherapy for osteogenic sarcoma. Early studies relied upon qualitative assessment of analog images to obtain predictive results. Recently, the lesion to normal tissue uptake ratio of 201Tl has been used in evaluating bone and soft tissue sarcomas. This study attempts to quantitate changes in tumour to normal tissue ratio following chemotherapy. Eight consecutive patients with classical osteosarcoma received standard preoperative chemotherapy with a combination of cisplatin, adriamycin and high-dose methotrexate. 201Tl gamma scintigraphic images were obtained both before and after chemotherapy. The average counts taken over the tumour divided by that from the contralateral normal tissue area yielded a tumour-to-normal tissue (T/N) ratio. The percentage change in the T/N ratio before and after preoperative chemotherapy was correlated with the percentage of tumour necrosis from pathological section. The median post-chemotherapy T/N ratio was 1.85 (range 0.5-7.7). The median percentage change in T/N ratio after chemotherapy was -58% (range +26% to -83%). The median percentage of necrosis from pathological section was 80% (range 0%-95%). There was a good correlation between the percentage of tumour necrosis and the percentage change in T/N ratio (rank correlation coefficient r = 0.84, P = 0.0085). Quantitative assessment of changes in 201Tl uptake by osteosarcoma correlates well with tumour necrosis after preoperative chemotherapy. This method may be used to predict response to chemotherapy at an earlier stage, enabling the clinician to consider alternative chemotherapeutic regimens or salvage surgery.