Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma.

PURPOSE: Recent studies have shown that tissue factor (TF) may be involved in tumor angiogenesis and metastasis. The role of TF in hepatocellular carcinoma (HCC) was unknown. This study evaluated whether TF expression correlates with microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, tumor invasiveness, and prognosis in human HCC. EXPERIMENTAL DESIGN: Tissue samples were obtained from 58 specimens of resected HCC. Immunohistochemical expression of TF was examined, and tumor MVD was evaluated using CD34 as the endothelial marker. TF and VEGF protein levels in the tumor cytosol were quantified by ELISA. Clinicopathologic and follow-up data of patients were prospectively collected. RESULTS: The immunohistochemical expression of TF in the tumors correlated significantly with tumor MVD (P = 0.002). The median cytosolic TF protein level in the tumors was 720 pg/mg total protein (range, 67-2406 pg/mg total protein). A significant positive correlation was found between TF and VEGF levels in the tumor cytosol (r = 0.475, P < 0.001). High tumor cytosolic TF level was associated with venous invasion (P = 0.004), microsatellite nodules (P = 0.024), unencapsulated tumor (P = 0.007), and advanced tumor stage (P = 0.010). A higher than median tumor cytosolic TF level was an independent predictor of poor survival (risk ratio, 1.836; 95% confidence interval 1.130-5.312, P = 0.023). CONCLUSIONS: This study shows that TF is related to tumor angiogenesis and invasiveness in HCC. Evaluation of tumor TF expression may be useful as a prognostic indicator in patients with HCC.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Coexistent gallbladder carcinoma in Mirizzi syndrome

A 52‐year‐old woman presented with right upper quadrant pain and obstructive jaundice. Computed tomographic scan showed Mirizzi syndrome type 1 and a thickened and calcified gallbladder wall, raising the possibility of coexistent gallbladder carcinoma that was later confirmed on histology post‐cholecystectomy.     

Comparing sulindac with indomethacin for closure of ductus arteriosus in preterm infants

Objectives: A prospective study comparing the efficiacy and side-effects of oral sulindac with intravenous indomethacin in clinically stable preterm infants (<1750 g) requiring non-invasive closure of haemodynamically significant patent ductus arteriosus.
Methodology: As maturity and birthweight are the two major determinants of ductal closure, infants were matched as closely as possible for these parameters. An eligible patient was first assigned to the sulindac group and a subsequent patient with similar gestational age (± 1 week) and birthweight (±100 g) to the previously recruited infant would automatically receive indomethacin. A total of eight infants were enrolled in each group.
Results: The ductus arteriosus was successfully closed in all eight infants receiving indomethacin, and in seven of eight infants receiving sulindac. No significant differences were found with regards to the ductal size between the two groups at diagnosis or on each of the consecutive days of treatment ( P >0.25). More renal adverse effects were encountered in the indomethacin group. Significant differences in changes from baseline value for urine output, plasma sodium, urea and creatinine concentrations were noted at 24, 48 and 72 h after commencement of treatment between the two groups ( P <0.05). All the parameters returned to normal or pre-treatment levels 48 h after stopping therapy. Unexpectedly, severe gastrointestinal complications were encountered in the sulindac group.
Conclusions: Sulindac is capable of promoting ductal constriction in clinically stable preterm infants without compromising the renal function. The spectrum of gastrointestinal complications observed in sulindac treated infants were similar to those described for indomethacin. The use of sulindac for ductal closure in the preterm infant should remain experimental.     

A follow-up study of infants ≤ 2000 g birthweight treated in central Queensland

This follow-up study was undertaken in an effort to ascertain the morbidity in the survivors of infants ≤2000 g birthweight cared for in the two Rockhampton intensive care nurseries.

Methodology:

The records of all infants ≤2000 g delivered in or transferred to Rockhampton during the 11 year period 1979 through 1989 inclusive were extracted. Efforts were made to contact and examine all of these children. Those found to be disabled were assessed as being mildly, moderately or severely affected.

Results:

Of the 482 infants of birthweight ≤2000 g treated in the period under review, 393 survived to be discharged from hospital. Eight were known to have died subsequently. Of the remaining 385 children, 288 (74.8%) were able to be contacted and their health status determined. A total of 36 infants were found to have significant disabilities. Twenty-four were mildly affected, five moderately and seven severely affected. Severe disability in infants of ≤1000 g was 16% (3/19).

Conclusions:

The incidence of disability was established in 74.8% of the surviving population, It was not dissimilar to the incidence of disability in similar birthweight groups in some Australian tertiary centres for the years under study. It is emphasized that the follow-up was incomplete and recognized that the survival rates and incidence of disability in survivors has improved in tertiary centres since the time frame of this study.     

Factors associated with osteoarthritis of the hip and knee in Hong Kong Chinese: obesity, joint injury, and occupational activities

In 1998, a case-control study was conducted in Hong Kong on hospital patients with osteoarthritis of the hip (n = 138) and osteoarthritis of the knee (n = 658). Age- and sex-matched controls were recruited consecutively from general practice clinics in the same region. The following three risk factors were found to be associated with osteoarthritis of both the hip and the knee: first, a history of joint injury: for osteoarthritis of the hip, the odds ratio = 25.1 (95% confidence interval (CI): 3.5, 181) in men and 43.3 (95% CI: 11.7, 161) in women; for osteoarthritis of the knee, the odds ratio = 12.1 (95% CI: 3.4, 42.5) in men and 7.6 (95% CI: 3.8, 15.2) in women; second, climbing stairs frequently: for osteoarthritis of the hip, the odds ratio = 12.5 (95% CI: 1.5, 104.3) in men and 2.3 (95% CI: 0.6, 8.1) in women; for osteoarthritis of the knee, the odds ratio = 2.5 (95% CI: 1.0, 6.4) in men and 5.1 (95% CI: 2.5, 10.2) in women; third, lifting heavy weight frequently: for osteoarthritis of the hip, the odds ratio = 3.1 (95% CI: 0.7, 14.3) in men and 2.4 (95% CI: 1.1, 5.3) in women; for osteoarthritis of the knee, the odds ratio = 5.4 (95% CI: 2.4, 12.4) in men and 2.0 (95% CI: 1.2, 3.1) in women. In addition, subjects whose height and weight were in the highest quartile were at increased risk of osteoarthritis of the hip and knee, respectively (p < 0.05).     

A new recommendation for maternal weight gain in Chinese women

OBJECTIVE: To characterize the distribution of maternal weight gain in Chinese women living in a well-nourished community, to recommend target weight gains from quartile values derived from women with good pregnancy outcomes, and to quantify the risk for adverse pregnancy outcomes encountered among subjects with weight gain outside these recommendations. DESIGN: A retrospective study on maternal anthropometry and pregnancy outcomes was conducted among Chinese women who delivered a singleton pregnancy in a university hospital in Hong Kong. SUBJECTS: Nine hundred eight women who delivered during the study period were identified. Among them, 754 (83%) had complete anthropometry data. The normative distribution of maternal weight gain was derived from 504 women who had a good pregnancy outcome. STATISTICS: Analysis of variance was used to compare total weight gain among women of different prepregnancy weight. Fisher exact test was used in the univariate analysis of the association between risk factors and corresponding adverse pregnancy outcomes. Adjusted odds ratios for adverse outcomes were determined by multiple logistic regression models controlling for the following factors: maternal age, duration of gestation, prepregnancy body mass index (BMI), height, parity, and smoking. RESULTS: A maternal weight-gain chart and recommendations for total weight gains in Chinese women were derived from the distribution of weight gain in subjects with good pregnancy outcomes. The recommended total weight gain was 13 to 16.7 kg, 11 to 16.4 kg, and 7.1 to 14.4 kg respectively for women of low (BMI < 19), moderate (BMI: 19 to 23.5), and high (BMI > 23.5) prepregnancy BMI. Women who did not achieve the lower quartile value had more than twice the risk of having low-birth-weight infants. Those with excessive weight gain were at risk for needing assisted delivery. APPLICATIONS: As maternal anthropometry differs across ethnic groups, different recommendations should be made for specific populations.     

Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study

Background: Edatrexate and carboplatin are each active single agents in the treatment of non-small-cell lung cancer (NSCLC). Preclinical studies in NSCLC lines have demonstrated schedule-dependent synergy of edatrexate followed by carboplatin. In a phase I trial, we demonstrated the tolerability of this combination, the ability of ice-chip cryotherapy to ameliorate dose-limiting mucositis, and promising activity in NSCLC. This phase II trial (SWOG 9207) was undertaken to investigate the efficacy of this regimen in stage IV NSCLC. Methods: A total of 24 patients with stage IV disease were accrued to this Southwest Oncology Group (SWOG) multicenter study. Treatment consisted of edatrexate 80 mg/m² (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m² every 28 days. Results: Of the 24 patients, 23 were assessable for toxicity and response; one was ineligible for study entry. Myelosuppression was the most significant toxicity; grade 3–4 neutropenia was seen in 8/23 patients. Two patients died of neutropenic sepsis during the first cycle of therapy, in both instances associated with the presence of pleural effusions. Although mild mucositis was common, it was dose-limiting (grade 3) in only three patients. Objective response was observed in 3/23 patients (13%). The median survival time was 7 months, and 30% of patients remained alive at one year. Conclusions: This study suggests that ice-chip cryotherapy is effective in reducing the severity of mucositis typically associated with this edatrexate schedule of administration. However, unexpectedly severe myelosuppression resulted in death from neutropenic sepsis in two patients with third space fluid collections, leading to a protocol amendment to exclude such patients from study entry. Furthermore, response and median survival with this dose schedule of edatrexate and carboplatin do not appear to be improved compared to other chemotherapeutic regimens tested by SWOG in this patient population. Received: 12 August 1996 / Accepted: 8 May 1997     

Imaging of non-small-cell lung cancer with indium-111 pentetreotide

PURPOSE: Lung cancer is the leading cause of cancer deaths in the United States. Non-small-cell lung cancer (NSCLC) accounts for 75% to 85% of lung cancers. CT has been the standard anatomic study for localizing and staging NSCLC, although it is associated only with moderate accuracy. In-111 pentetreotide, a radiolabeled somatostatin analog largely used in the scintigraphic localization of neuroendocrine tumors, has been shown incidentally to identify NSCLC lesions. This observation is important in the workup for metastatic disease for neuroendocrine tumors, because presumed metastatic lesions may actually be second primary tumors of NSCLC. In-111 may also serve as a potentially useful adjunct to CT in the anatomic evaluation of NSCLC. The purpose of this study was to determine the likelihood of detecting and localizing NSCLC using In-111 pentetreotide scintigraphy. MATERIALS AND METHODS: Ten patients with known or possible NSCLC were examined using In-111 pentetreotide. Scans were compared with the patients' previously performed chest radiographs and CT scans. RESULTS: In-111 pentetreotide imaging correctly identified sites of tumor involvement as detected by chest CT and surgery in all 10 patients with NSCLC. CONCLUSION: This study demonstrates the uptake of In-111 pentetreotide by NSCLC. This important observation should be considered in the workup for metastatic disease of neuroendocrine tumors with In-111 pentetreotide, because NSCLC can be a source of false-positive findings. In-111 pentetreotide imaging may also serve as a potentially useful adjunct to CT for identifying obscured or equivocal lesions and as an aid in localizing tissue for biopsy.