Michael Huncharek

Chemoembolization of hepatocellular carcinoma: Results of a metaanalysis

Transcatheter arterial chemoembolization is considered the mainstay of therapy for unresectable hepatocellular carcinoma. The purpose of this study was to assess the impact of such treatment on survival by performing a metaanalysis of all available randomized clinical trials comparing this form of therapy to supportive care. A MEDLARS search was conducted covering the years 1970 to 2002. Data analysis was performed according to methods described by Peto. The primary outcome of interest was the proportion of patients surviving 3 and 6 months after treatment. All analyses were performed on an intent-to-treat basis. A literature search yielded 1,100 citations, from which four met protocol-specified inclusion criteria. All studies contained an experimental and control arm totalling 268 patients. The odds ratio for 3- and 6-month survival were 1.31 (95% CI: 0.66—2.58) and 0.91 (95% CI: 0.49—1.68), which was not statistically significant. These data fail to show a survival advantage associated with therapeutic embolization versus supportive care alone in patients with unresectable hepatocellular carcinoma. Existing survival data from randomized controlled trials are of poor quality, and the paucity of patients in these trials eliminates the possibility of drawing meaningful conclusions regarding the effect of chemoembolization on patient survival from these studies.

Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies.

AbstractObjective: Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors. A meta-analysis was performed statistically pooling all available observational studies on this topic in order to evaluate this suspected association. Methods: Using previously described methods, a protocol was developed for a meta-analysis examining the association between maternal smoking during pregnancy and subsequent development of primary brain tumors in their offspring. Literature search techniques, study inclusion criteria and statistical procedures were prospectively defined. Data from epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of childhood brain tumor development associated with mothers smoking during the index pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity and/or to evaluate the impact of demographic or study characteristics on the summary estimate of effect. Results: Twelve observational studies meeting protocol specified inclusion criteria were obtained via a comprehensive literature search. These studies enrolled a total of 6566 patients. Analysis for homogeneity demonstrated that the data were homogeneous (P>0.50) and could be statistically combined. Pooling all twelve reports yielded an RRs of 1.05 (0.90–1.21), a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development. Numerous sensitivity analyses examining the possible effect of study design and various patient characteristics failed to show any influence on the RRs further supporting the observed lack of association. Conclusion: The available epidemiological data do not support a clear association between maternal smoking during pregnancy and pediatric brain tumor development. Although it appears likely that no association exists, limitations in study designs limit definitive conclusions based on available data.

Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis.

Objective. This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. Methods. Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analyses were performed to explain any observed statistical heterogeneity and to explore the influence of specific study characteristics of the summary estimate of effect. Results. Initially combining homogenous data from six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92, 1.11), suggesting no association between hair dye use and bladder cancer development. Sensitivity analyses examining the influence of hair dye type, color, and study design on this suspected association showed that uncontrolled confounding and design limitations contributed to a spurious non-significant summary RR. The sensitivity analyses yielded statistically significant RRs ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use. Conclusion. The available epidemiological data suggest an association between personal use of hair dye products and increased risk of bladder cancer.

A Meta-Analysis of Maternal Cured Meat Consumption during Pregnancy and the Risk of Childhood Brain Tumors

Objective: N-Nitroso compounds (NOCs) are recognized neural carcinogens in animal models and are suspected human carcinogens. A meta-analysis was performed examining the possible association of maternal intake of cured meat (an important source of dietary NOCs) during pregnancy and the risk of pediatric brain tumors. Methods: Data from epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals described by Greenland in 1986. The outcome of interest was a summary relative risk (RR) reflecting the risk of childhood brain tumor (CBT) development associated with maternal intake of cured meats during pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity. Results: Seven observational studies were found that met the protocol-specified inclusion criteria. Analysis for heterogeneity demonstrated a lack of statistical heterogeneity (p = 0.59), indicating that the data could be statistically combined. Pooling data from the 6 reports containing data on maternal cured meat intake of all types yielded an RR of 1.68 (1.30– 2.17), being a statistically significant result. Analyzing CBT risk by type of cured meat ingested showed that hot dog consumption increased CBT risk by 33% (1.08–1.66), with a similar increase shown by frequent ingestion of sausage, i.e. 44%. Conclusion: The data provide support for the suspected causal association between ingestion of NOCs from cured meats during pregnancy and subsequent CBT in offspring. Limitations in study design preclude definitive conclusions, but the relationship warrants exploration via additional observational and laboratory-based studies.

Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA): Design of a Prospective, Multicenter Trial of Diagnostic Tests

Background and Relevance: Intracranial atherosclerosis is responsible for 70,000 ischemic strokes each year in the USA. Noninvasive testingsuch as transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) to identify intracranial atherosclerosis is in widespread use, but has not been rigorously validated against the gold standard, catheter angiography. The recently NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial will compare warfarin with aspirin for stroke prevention in patients with intracranial atherosclerosis. WASID requires performance of angiography along with TCD and MRA, providing an opportunity to critically evaluate these noninvasive tests. Main Objective: The purpose of the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study is to develop the noninvasive diagnosis of intracranial atherosclerosis. The primary aim of SONIA is to define velocity values on TCD and anatomic abnormalities on MRA that identify severe (50–99%) intracranial stenosis of large, proximal arteries seen on catheter angiography. SONIA will define the criteria, or ‘cutpoints’, for an abnormal TCD or MRA and show that they perform with a reliable positive predictive value (PPV). Study Design: SONIA will be conducted in collaboration with WASID. Study-wide cutpoints defining positive TCD and MRA have been developed and reviewed by the site investigators of WASID. Hard copy angiography, TCD and MRA generated in WASID will be centrally read in SONIA. TCD and MRA cutpoints seek to achieve a target PPV of 80% for the identification of severe intracranial stenosis on angiography. Conclusions: Central readings will be used to validate the cutpoints and to develop measures of negative predictive value, and inter- and intra-observer variability. Sensitivity and specificity will be determined after adjustment for verification bias and employed in receiver-operator characteristic analyses. SONIA will use these techniques to develop TCD and MRA cutpoints that minimize the clinical consequences of test errors occurring in the noninvasive evaluation of patients with suspected intracranial atherosclerosis.

Metastatic breast carcinoma presenting as a large pulmonary embolus: case report and review of the literature.

Involvement of the pulmonary vasculature by carcinoma of the breast typically occurs in the form of microscopic tumor emboli involving the small arteries, arterioles, or capillaries. Obstruction of a large pulmonary artery by a tumor embolus has not been reported. We describe a patient with a history of breast carcinoma diagnosed 5 years previously who sought treatment for dyspnea and a large mass in the right pulmonary artery suggestive of a pulmonary embolus. After failure of both systemic and intraarterial thrombolytic therapy, a biopsy of the mass was obtained, which revealed adenocarcinoma of the breast. Systemic chemotherapy with doxorubicin and cyclophosphamide was initiated and resulted in the complete resolution of her symptoms.

Presentation of malignant pleural mesothelioma with symptomatic brain metastasis: report of a case.

Central nervous system metastases from diffuse malignant pleural mesothelioma are rare. Here we describe a patient without known asbestos exposure who presented with chest pain, increasing shortness of breath and persistent headache. Evaluation found biphasic malignant mesothelioma of the right hemithorax and a single brain metastasis confirmed by computed tomography. This represents only the second case of a patient with pleural mesothelioma presenting with symptomatic central nervous system metastases.