Keith B. Shilkin

Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation.

Objective: To determine trends in incidence of malignant mesothelioma (MM) caused by exposure to asbestos during home maintenance and renovation.

A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit

Aims: Cytological diagnosis of malignant pleural mesothelioma (MPM) is controversial, but has been used in our institution for over 30 years. To assess the role of effusion cytology in mesothelioma diagnosis we conducted an audit of pleural fluid cytology results over a 20 year period (1988–2007). Methods: Pleural samples were received from 6285 patients; data linkage with Western Australian Cancer and Mesothelioma Registries demonstrated that 815 of these patients had a diagnosis of MPM. Cytological examination of a pleural effusion specimen had been performed in 517 (63%) of these 815 patients. Results: Definitive cytological diagnosis of MPM was made in 377/517 cases, resulting in an ‘absolute’ sensitivity of 73%. An additional 66 patients were diagnosed as atypical/suspicious, resulting in a ‘complete’ sensitivity of 86%. If only biopsy/necropsy proven cases are considered, the absolute sensitivity is 68% and the complete sensitivity is 82%. There were no false positive diagnoses of malignancy; two patients with metastatic adenocarcinoma were initially diagnosed as MPM, prior to the availability of specific mesothelial markers, resulting in a positive predictive value of 99%. Conclusions: Effusion cytology is an inexpensive, minimally invasive procedure which should be included in the diagnostic work-up of cases of suspected MPM.

Predicting survival in malignant mesothelioma

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2–1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1–1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0–198), 177 (48–350), 221 (97–504), 238 (108–502) and 301 (134–611) days; ∼4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

Comparison of measures of exposure to asbestos in former crocidolite workers from Wittenoom Gorge, W. Australia

Determinations of exposure-response relationships between crocidolite and the major asbestos-related diseases in the Wittenoom cohort have previously depended on the validity of estimates of airborne exposure to asbestos. This work aims to validate the airborne exposure measurements by obtaining measurements of the concentrations of uncoated crocidolite fibers and asbestos bodies retained in the lungs of individual workers, and to estimate the half-life of crocidolite fibers in the lungs. Samples of lung tissue, excluding tumor, of all former Wittenoom workers known to have died in Western Australia (WA) were sought from teaching hospitals, pathology departments, and the Coroners pathologist. The lung specimens were processed using Pooleys method with TEM for counts of fibers of all types and using Smith and Naylors method with conventional light microscopy for asbestos bodies (AB). Multiple linear regression was utilized to examine the associations between crocidolite concentrations in the lung and duration of employment at Wittenoom, time since last employed at Wittenoom, nature of job, estimated average fiber concentration at the worksite, and estimated cumulative crocidolite exposure (CCE) in fiber-years/ml for each subject. Lung tissue from 90 cases was processed and there was good agreement between counts of crocidolite fibers, asbestos bodies, and CCE. Correlations were 0.77 for AB and fibers, 0.54 for AB and CCE, and 0.58 for CCE and fibers, after log transformation. The half-life of crocidolite fibers in the lung was estimated at 92 months (95% CI 55-277 months). Previous estimates of airborne exposure to Wittenoom crocidolite have been reasonably reliable. The relatively simple technique of light microscopy for counting ABs in lung tissue also provides a useful and reliable indication of the level of past occupational exposure to crocidolite in subjects whose exposure has been only to crocidolite. The half-life of crocidolite fibers in the lungs of former Wittenoom workers is about 7-8 years.

The fine needle aspiration cytology of mediastinal lesions

Fine needle aspiration cytology was performed in 19 mediastinal lesions. Of seven malignant neoplasms six were correctly diagnosed as malignant and in five of these accurate tumor classification was possible. Of the 12 benign lesions only four cases, all thymomas, could be diagnosed cytologically. No falsepositive diagnoses of malignancy were made. The only complication of the procedure was minor pneumothorax in two patients. In five cases the use of the technique spared the patient from more invasive diagnostic procedures; in several others, valuable information was obtained prior to surgery.

Carbamazepine Hepatotoxicity: Another Cause of the Vanishing Bile Duct Syndrome

Serious carbamazepine hepatotoxicity is being recognized more frequently and is usually manifest as an acute granulomatous hepatitis that is self-limiting if the drug is withdrawn. The case of a 59-year-old man who developed the vanishing bile duct syndrome after 2 months of treatment with carbamazepine for glossopharyngeal neuralgia is reported. The characteristic histological features of this syndrome may also be seen in primary biliary cirrhosis, primary sclerosing cholangitis, graft-vs.-host disease after allogeneic bone marrow transplantation, chronic liver allograft rejection, and other drug reactions. The progress of this patient to date suggests that irreversible liver injury resulting in chronic liver disease is likely, in keeping with the clinical course of the vanishing bile duct syndrome in most cases.

Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with benefit from one course of perioperative chemotherapy in patients with negative lymph node status: results from International Breast Cancer Study Group Trial V.

The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin‐dependent kinase inhibitor p27(Kip1) in patients with early‐stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers.

Detection of tissue CEA-like substance as an aid in the differential diagnosis of malignant mesothelioma

Summary Sections of various adenocarcinomas and malignant mesotheliomas were tested for carcinoembryonic antigen (CEA) localized in tissues by the immunoperoxidase technique; epithelial mucin was demonstrated with the PAS technique. While CEA and mucin were found in many adenocarcinomas, both were absent in the 43 cases of malignant mesothelioma we investigated. In the problem of distinguishing between adenocarcinoma and mesothelioma, the CEA‐test in combination with conventional stains for mucin is a useful technique and clearly identifies most adenocarcinomas. A dual negative result for CEA and mucin, although not proving that a given lesion is a mesothelioma, adds considerable support to this histological diagnosis.

Premalignant epithelial lesions of the gall bladder: A prospective study of 120 cholecystectomy specimens

&NA; One hundred and twenty gall‐bladders obtained at cholecystectomy for gall bladder diseases formed the basis of a prospective study of premalignant epithelial lesions. Six cases displayed abnormal mucosa (5%); 4 had atypical hyperplasia (dysplasia) and 2 gall‐bladders had carcinoma‐in‐situ; all were associated with chronic cholecystitis and lithiasis. These changes are considered premalignant and are probably precursors of gallbladder carcinoma. It is impossible to predict which patient with chronic gall‐bladder disease is likely to harbour premalignant epithelial changes. In any event, thorough histological examination of all gall bladders removed surgically is more than justified.

Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumour

Abstract :A 44‐year‐old man with past minor exposure to blue asbestos presented with supraclavicular lymphadenopathy and miliary shadowing on his chest radiograph. Cytology and electronmicroscopy on material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. Malignant mesothelioma cells were also present in bronchoalveolar lavage fluid and on transbronchial lung biopsy. At autopsy the right pleural cavity was studded with small tumour nodules. This case demonstrates that malignant mesothelioma may present as metastatic disease and without evidence on conventional investigations of a primary pleural tumour. (Aust NZ J Med 1991; 21: 460–462)