Table of Contents
1
UI - 11332082
AU - Pomjanski N; Motherby H; Buckstegge B; Knops K; Rohn BL; Bocking A
TI -
Early diagnosis of mesothelioma in serous effusions using AgNOR
analysis.
SO - Anal Quant Cytol Histol 2001 Apr;23(2):151-60
AD - Institute of Cytopathology, Heinrich Heine University, Moorenstrasse 5,
D-40225 Dusseldorf, Germany.
OBJECTIVE: To compare the results of conventional cytology, DNA image
cytometry, immunocytochemistry and argyrophilic nucleolar organizer
region (AgNOR) analysis for the diagnosis of malignant cells in serous
effusions. STUDY DESIGN: One hundred twenty effusions, 40 with
carcinoses, 40 with malignant mesotheliomas and 40 without tumor cells
on follow-up were studied by conventional cytology and three adjunctive
methods. RESULTS: Unequivocal tumor cells were detected in 92.5% of
effusions due to carcinoses and in 45% due to mesotheliomas. Applying
immunocytochemistry with BerEP-4 positivity and DNA image cytometry with
aneuploidy as a marker revealed 100% of carcinoses and 71.7% of
mesotheliomas. Applying the experimentally found thresholds of 2.5
AgNORs as "satellites" and 4.5 AgNORs as "satellites and clusters"
together as mean values per nucleus resulted in a 95% correct rate of
mesothelioma and 100% rate of carcinoma cell identification without
false positive diagnoses. CONCLUSION: AgNOR analysis may be a useful
adjunct to other methods in the routine diagnosis of malignant serous
effusions. It seems to be the most sensitive method in early cytologic
diagnosis of mesotheliomas in effusions. Seventy-three percent of
malignant mesotheliomas were diagnosed cytologically at first on
effusions. Forty-seven percent of patients with malignant mesotheliomas
were identified at the early tumor stage T1 N0 M0.
2
UI - 11417405
AU - Montanaro F; Vitto V; Lagattolla N; Lazzarotto A; Bianchelli M; Puntoni
TI -
R; Gennaro V
[Occupational exposure to asbestos and recognition of pleural
mesothelioma as occupational disease in the province of Genoa]
SO - Epidemiol Prev 2001 Mar-Apr;25(2):71-6
AD - Registro Mesoteliomi della Liguria (REM), c/o Servizio di epidemiologia
ambientale, Istituto nazionale per la ricerca sul cancro (IST), Genova.
The present study compares the data of pleural mesothelioma (PM)
patients resident in the province of Genoa (Italy) who, in the period
1994-1996, applied to the Italian National Insurance Institute for Work
Accident (INAIL), for workers' compensation for asbestos-related
diseases due to occupational exposure, with the dataset of PM patients
collected by the Mesothelioma Registry of Liguria (REM) in the same
period and in the same area. As PM is a malignant tumor of a prevalently
occupational origin, it is recognized and acknowledged as such by INAIL
when clinical and etiological characteristics are matched. Objectives of
this study were to describe observed PM cases, to evaluate completeness
of collected data and differences between those who requested
compensation and those who did not. The REM describes the incidence of
PM among Ligurian residents, proposing patients with a specific
questionnaire to assess occupational, environmental and indoor asbestos
exposures. The REM collected 199 new cases of PM among the residents of
both the city of Genoa (1994-96) and the province of Genoa (1995-96). In
the same period, INAIL received 48 (24%) applications for compensation.
Among these, 43 subjects were included in a subgroup of 98 patients
registered in the REM as cases with definite diagnosis and ascertained
asbestos exposure; 32 were awarded compensation, while 11 are under
evaluation. The data collected by REM do not show proven asbestos
exposure and/or PM diagnosis for five other subjects (two compensated
and three under judgment). This study reveals that: a) only a 24% of the
patients with a diagnosis of PM and asbestos exposure apply for
compensation; b) an exchange of information among institutions involved
in primary prevention, in the evaluation of occupational exposures to
carcinogens and in insurance compensation is useful.
3
UI - 11571532
AU - Mohiuddin I; Cao X; Fang B; Nishizaki M; Smythe WR
TI -
Significant augmentation of pro-apoptotic gene therapy by pharmacologic
bcl-xl down-regulation in mesothelioma.
SO - Cancer Gene Ther 2001 Aug;8(8):547-54
AD - Section of Thoracic Molecular Oncology, Department of Thoracic and
Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer
Center, Houston, Texas 77030, USA.
The ratio of pro-apoptotic (PAP) and anti-apoptotic (AAP) bcl-2 proteins
is important in apoptosis regulation. We sought to determine if
inhibition of the AAP bcl-xl by sodium butyrate (SB) would augment
apoptotic cellular death in mesothelioma when combined with adenoviral
pro-apoptotic gene therapy (PAGT) by simultaneously increasing PAP and
decreasing AAP in these cells. Human mesothelioma cell lines were
exposed to AdBax, AdBak, Adp53, and SB alone as well as all vectors
combined with SB at varying doses and time points. Cell death was
assessed, and apoptosis evaluated by morphology and FACS. Isobologram
analysis evaluated additive or synergistic effect. Cellular death and
apoptosis were augmented by PAGT/SB combinations compared to
monotherapy. Following AdBax/SB and AdBak/SB, a decrease of the AAP
bcl-xl was noted in combination with increases in PAP bax and bak. By
isobologram analysis, additive or synergistic cell killing was noted
with both combinations. SB treatment did not significantly augment cell
killing or apoptosis in combination with Adp53. PAGT/SB was more
effective than monotherapy in induction of apoptotic cell death. Synergy
may be due to the ability of SB to decrease bcl-xl with marked increases
in PAP engendered by PAGT. Combination therapy with agents that
down-regulate AAP in addition to PAGT may prove useful clinically.
4
UI - 11570906
AU - Foster MR; Johnson JE; Olson SJ; Allred DC
TI -
Immunohistochemical analysis of nuclear versus cytoplasmic staining of
WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas.
SO - Arch Pathol Lab Med 2001 Oct;125(10):1316-20
AD - Department of Pathology, Vanderbilt University Medical Center,
Nashville, TN 37232, USA.
CONTEXT: Previous studies have indicated certain immunohistochemical
markers, including WT1, may be helpful in distinguishing adenocarcinomas
from mesotheliomas, but to date there are no reliable, widely accepted,
commercially available antibodies positive in mesotheliomas and negative
in adenocarcinomas. We compared the nuclear and cytoplasmic staining
patterns of WT1 in these 2 malignancies using a commercially available
antibody and examined the expression of 2 other previously reported
positive markers, calretinin and thrombomodulin. METHODS: Sixty-seven
mesotheliomas and 51 adenocarcinomas, all paraffin embedded, were
retrieved from recent case files. The diagnosis of mesothelioma was
based on typical clinical and morphologic features, as well as
immunohistochemistry; electron microscopy had been performed on 16
cases. The diagnosis of adenocarcinoma was based on typical light
microscopic findings and a positive stain for mucin. Commercially
available antibodies to WT1, thrombomodulin, and calretinin were
applied. Because of the conflict surrounding calretinin, 2
anticalretinin antibodies (from Chemicon Inc and Zymed Laboratories)
were utilized. RESULTS: Fifty of 67 mesotheliomas showed strong nuclear
staining with WT1. No adenocarcinomas (0/51) showed nuclear staining.
Twenty-three of 67 mesotheliomas were positive for thrombomodulin, and
35 of 67 mesotheliomas were positive for calretinin with the Chemicon
antibody. Nine of 15 mesotheliomas were positive for calretinin with the
Zymed antibody. CONCLUSIONS: Thrombomodulin and calretinin did not prove
useful in discriminating between mesotheliomas and adenocarcinomas. The
degree of positivity with calretinin may be dependent on the specific
antibody utilized. Nuclear staining for WT1 is highly specific for
mesothelioma and, in the appropriate clinical setting, can be a helpful
adjunct in the distinction between adenocarcinomas and mesotheliomas.
5
UI - 11577123
AU - Roberts F; McCall AE; Burnett RA
TI -
Malignant mesothelioma: a comparison of biopsy and postmortem material
by light microscopy and immunohistochemistry.
SO - J Clin Pathol 2001 Oct;54(10):766-70
AD - Department of Pathology, Victoria Infirmary, Langside Road, Glasgow G42
9TY, UK. f.roberts@spr.co.uk
AIMS: The diagnosis of malignant mesothelioma in pleural biopsies can be
difficult. Survival is short and consequently many of these cases are
submitted to necropsy to assist with medicolegal claims. This study
compares the histological appearances and immunohistochemical profile of
nine biopsy specimens with corresponding postmortem specimens. METHODS:
Archival, formalin fixed, paraffin wax embedded material was obtained
from nine biopsy and corresponding postmortem cases of malignant
mesothelioma. The specimens were examined by light microscopy and
stained with an immunohistochemical panel of 12 commercially available
antibodies including CAM5.2, HBME-1, and Ber-EP4, and antibodies to
thrombomodulin, calretinin, CD44H, WT-1, carcinoembryonic antigen,
Leu-M1, epithelial membrane antigen and p53. RESULTS: There was greater
variation in the range of histological appearances of mesotheliomas in
postmortem specimens compared with biopsy specimens. There was also
variability in the immunohistochemical staining pattern for certain
antibodies including HBME-1, and Ber-EP4 and antibodies to calretinin,
CD44H, WT-1, and p53. CONCLUSIONS: All available information should be
taken into account in the histological diagnosis of malignant
mesothelioma. Interpretation of the immunohistochemical profile should
be regarded with some caution when only postmortem material is
available. When reporting a postmortem case of suspected mesothelioma,
the pathologist should seek to review all available biopsy material in
conjunction with the necropsy.
6
UI - 11581615
AU - Rusch VW; Rosenzweig K; Venkatraman E; Leon L; Raben A; Harrison L;
TI -
Bains MS; Downey RJ; Ginsberg RJ
A phase II trial of surgical resection and adjuvant high-dose
hemithoracic radiation for malignant pleural mesothelioma.
SO - J Thorac Cardiovasc Surg 2001 Oct;122(4):788-95
AD - Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer
Center, New York, NY 10021, USA. ruschv@mskcc.org
BACKGROUND: Surgical resection of malignant pleural mesothelioma is
reported to have up to an 80% rate of local recurrence. We performed a
phase II trial of high-dose hemithoracic radiation after complete
resection to determine feasibility and to estimate rates of local
recurrence and survival. METHODS: Patients were eligible if they had a
resectable tumor, as determined by computed tomographic scanning, and
adequate cardiopulmonary function for extrapleural pneumonectomy or
pleurectomy/decortication. After complete resection, patients received
hemithoracic radiation (54 Gy) and then were followed up with serial
computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients
(73 men and 15 women; median age, 62.5 years) were entered into the
study. The operations performed included 62 extrapleural pneumonectomies
(70%) and 5 pleurectomies/decortications; procedures for exploration
only were performed in 21 patients. Seven (7.9%) patients died
postoperatively. Adjuvant radiation administered to 57 patients (54
undergoing extrapleural pneumonectomy and 3 undergoing
pleurectomy/decortication) at a median dose of 54 Gy was well tolerated
(grade 0-2 fatigue, esophagitis), except for one late esophageal
fistula. The median survival was 33.8 months for stage I and II tumors
but only 10 months for stage III and IV tumors (P =.04). For the
patients undergoing extrapleural pneumonectomy, the sites of recurrence
were locoregional in 2, locoregional and distant in 5, and distant only
in 30. CONCLUSION: Hemithoracic radiation after complete surgical
resection at a dose not previously reported is feasible. This approach
dramatically reduces local recurrence and is associated with prolonged
survival for early-stage tumors. Stage III disease has a high risk of
early distant relapse and should be considered for trials of systemic
therapy added to this regimen of resection and radiation.
7
UI - 11591556
AU - Schouwink H; Rutgers ET; van der Sijp J; Oppelaar H; van Zandwijk N; van
TI -
Veen R; Burgers S; Stewart FA; Zoetmulder F; Baas P
Intraoperative photodynamic therapy after pleuropneumonectomy in
patients with malignant pleural mesothelioma: dose finding and toxicity
results.
SO - Chest 2001 Oct;120(4):1167-74
AD - Department of Thoracic Oncology, The Netherlands Cancer Institute,
Amsterdam, the Netherlands.
OBJECTIVE: To determine the optimal administered dose of
meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic
therapy (IPDT) in resected malignant pleural mesothelioma (MPM). The
primary objective of this combination treatment was to improve local
tumor control. DESIGN: Phase I/II dose escalation study. SETTING: Two
Dutch cancer centers. PATIENTS: The study included 28 patients (2 women,
26 men), with pathologically confirmed MPM. The mean age was 57 years
(age range, 37 to 68 years), and the World Health Organization
performance score was 0 to 1. Epithelial mesotheliomas were found in 17
patients, a sarcomatous mesothelioma was found in 1 patient, and mixed
epithelial sarcomatous mesotheliomas were found in 10 patients. METHODS:
Patients were injected with 0.075 mg/kg (4 patients), 0.10 mg/kg (19
patients), or 0.15 mg/kg (5 patients) mTHPC 4 or 6 days before
undergoing surgery and IPDT. Complete surgical resection (i.e.,
pleuropneumonectomy) was followed by integral illumination with
monochromatic light of 652 nm (10 J/cm(2)). The real-time fluence rate
measurements were performed using four isotropic detectors in the chest
cavity to calculate the total light dose. RESULTS: Dose-limiting
toxicity was reached at the level of 0.15 mg/kg mTHPC. Three patients
died in the perioperative period, and one death was directly related to
photodynamic therapy. Real-time dosimetry identified 12 patients in whom
additional illumination had to be given to the diaphragmatic sinuses,
which were unavoidably shielded during integral illumination. In two
patients, illumination was cancelled due to the insufficient
resectability of the tumor. The median survival time for all 28 patients
was 10 months. Local tumor control, 9 months after treatment, was
achieved in 13 of the 26 patients treated with IPDT. CONCLUSION: IPDT
using mTHPC, combined with a pleuropneumonectomy, resulted in local
control of disease in 50% of the treated cases. The considerable
toxicity associated with the procedure, however, precludes its
recommendation for widespread use. Stricter patient selection and
improvements of the IPDT technique may reduce the toxicity.
8
UI - 11599101
AU - Simsir A; Fetsch P; Bedrossian CW; Ioffe OB; Abati A
TI -
Absence of SV-40 large T antigen (Tag) in malignant mesothelioma
effusions: an immunocytochemical study.
SO - Diagn Cytopathol 2001 Oct;25(4):203-7
AD - Department of Pathology, New York University Medical Center, New York,
New York 10016, USA. simsia01@med.nyu.edu
Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of
malignant mesothelioma. The oncogenic capacity of SV-40 is a function of
a nuclear protein, the large T antigen (Tag). SV-40 Tag DNA sequences
are detected by the polymerase chain reaction in 40-80% of malignant
mesothelial proliferations. However, the role of immunohistochemistry
(IHC) in demonstrating the nuclear localization of Tag is controversial.
We sought to determine the clinical utility of SV-40 Tag IHC in pleural
effusion cytology as an ancillary tool in the cytologic diagnosis of
malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell
block sections from 100 pleural effusions (32 MMs, 25 benign reactive,
43 metastatic adenocarcinomas) were immunostained for the SV-40
anti-Tag, using two primary monoclonal SV-40 Tag antibodies: clone Pab
416 and clone Pab 101. Despite strong and consistent immunoreactivity in
positive controls, no nuclear immunostaining was observed in any case.
We believe the small sample size in cytology cell block sections, the
low viral copy number in infected cells, and the effect of formalin
fixation may have resulted in absence of immunoreactivity. The role of
SV-40 Tag IHC in diagnostic cytopathology remains unclear unless further
studies reliably show its detection. Copyright 2001 Wiley-Liss, Inc.
9
UI - 11673120
AU - Magnani C; Dalmasso P; Biggeri A; Ivaldi C; Mirabelli D; Terracini B
TI -
Increased risk of malignant mesothelioma of the pleura after residential
or domestic exposure to asbestos: a case-control study in Casale
Monferrato, Italy.
SO - Environ Health Perspect 2001 Sep;109(9):915-9
AD - Cancer Epidemiology Unit, Centre for Cancer Epidemiology and Prevention,
CPO Piemonte, S. Giovanni Hospital and University of Torino, Italy.
corrado.magnani@cpo.it
The association of malignant mesothelioma (MM) and nonoccupational
asbestos exposure is currently debated. Our study investigates
environmental and domestic asbestos exposure in the city where the
largest Italian asbestos cement (AC) factory was located. This
population-based case-control study included pleural MM (histologically
diagnosed) incidents in the area in 1987-1993, matched by age and sex to
two controls (four if younger than 60). Diagnoses were confirmed by a
panel of five pathologists. We interviewed 102 cases and 273 controls in
1993-1995, out of 116 and 330 eligible subjects. Information was checked
and completed on the basis of factory and Town Office files. We adjusted
analyses for occupational exposure in the AC industry. In the town there
were no other relevant industrial sources of asbestos exposure.
Twenty-three cases and 20 controls lived with an AC worker [odds ratio
(OR) = 4.5; 95% confidence interval (CI), 1.8-11.1)]. The risk was
higher for the offspring of AC workers (OR = 7.4; 95% CI, 1.9-28.1).
Subjects attending grammar school in Casale also showed an increased
risk (OR = 3.3; 95% CI, 1.4-7.7). Living in Casale was associated with a
very high risk (after selecting out AC workers: OR = 20.6; 95% CI,
6.2-68.6), with spatial trend with increasing distance from the AC
factory. The present work confirms the association of environmental
asbestos exposure and pleural MM, controlling for other sources of
asbestos exposure, and suggests that environmental exposure caused a
greater risk than domestic exposure.
10
UI - 11603562
AU - Loggie BW; Fleming RA; McQuellon RP; Russell GB; Geisinger KR; Levine EA
TI -
Prospective trial for the treatment of malignant peritoneal
mesothelioma.
SO - Am Surg 2001 Oct;67(10):999-1003
AD - Wake Forest University Baptist Medical Center, Winston-Salem, North
Carolina, USA.
Malignant peritoneal mesothelioma (MPM) is a rare and often rapidly
fatal disease with median survival of 5 to 12 months for untreated cases
and 16 months reported after multimodality treatment. We report a
prospective clinical treatment study using cytoreductive surgery
combined with intraoperative intraperitoneal heated chemotherapy (IPHC)
perfusion using mitomycin C for MPM. Twelve patients (11 male with a
mean age 51 years) were treated. Seven patients presented with bulky
disease and seven with ascites. All underwent exploratory laparotomy
with histologically confirmed diagnosis of MPM. Surgical debulking as
feasible was performed. Complete gross tumor removal was possible in
only one patient. Cytoreduction was followed by a 2-hour closed
low-volume IPHC using mitomycin C. One patient died 50 days
postoperatively from complications relating to small bowel perforation.
Hematologic toxicity of the procedure was minimal. Ascites was
controlled in all patients and permanently in 86 per cent of patients
presenting with ascites. To date median survival is 34.2 months with
median follow-up of 45.2 months. One patient was re-explored for ventral
hernia 2 years post-IPHC, had negative peritoneal biopsies, and remains
disease-free at 5 years. Given the dismal prognosis associated with MPM
the results of treatment with cytoreductive surgery combined with IPHC
perfusion are encouraging. The rarity of MPM makes appropriately powered
prospective randomized trials unlikely. Therefore, we now offer this
approach off protocol; however, further study of this combined modality
therapy is warranted.
11
UI - 11605063
AU - Zimmerman RL; Fogt F
TI -
Evaluation of the c-Met immunostain to detect malignant cells in body
cavity effusions.
SO - Oncol Rep 2001 Nov-Dec;8(6):1347-50
AD - Presbyterian Medical Center, University of Pennsylvania Health System,
Philadelphia, PA 19104, USA. robertz@mail.med.upenn.edu
The cytologic diagnosis of malignant cells in serous effusions can be
difficult. A wide variety of immunostains and other diagnostic
techniques have been studied but without widespread acceptance of one
staining panel or technique. Expression of the tyrosine kinase c-Met has
been associated with several malignancies but not with benign
mesothelium. We investigated the diagnostic value of the c-Met
immunostain in serous effusions. Cell block material from 76 cases of
unequivocally benign or malignant effusions were studied. Cases were
stained with c-Met using the avidin-biotin complex method following
antigen retrieval. The presence of strong granular cytoplasmic staining
that was distinct from background staining was considered positive.
Positive cells were identified in 38 of 42 (90%) malignant cases and in
18 of 34 (53%) benign cases. Typically, benign cases contained only
individual positive cells, but positive cell clusters were also
identified. The c-Met immunostain lacks sufficient specificity to be
clinically useful in this cytologic setting. The expression of c-Met in
benign mesothelium may reflect mesothelial proliferation.
12
UI - 11605070
AU - Papp T; Schipper H; Pemsel H; Unverricht M; Muller KM; Wiethege T;
TI -
Schiffmann D; Rahman Q
Mutational analysis of the PTEN/MMAC1 tumour suppressor gene in primary
human malignant mesotheliomas.
SO - Oncol Rep 2001 Nov-Dec;8(6):1375-9
AD - Department of Biological Sciences, Institute for Cell Biology and
Biosystems Technology, University of Rostock, D-18051 Rostock, Germany.
thilo.papp@biologie.uni-rostock.de
Eighteen primary human malignant mesotheliomas obtained from 18 patients
were screened for point mutations and microdeletions/insertions in all
exons of the tumour suppressor gene PTEN/MMAC1 by SSCP analysis. No
mutation could be found. Our preliminary data indicate that
disarrangements of PTEN/MMAC1 are at least not frequently involved in
mesothelioma formation.
13
UI - 11688466
AU - Butnor KJ; Sporn TA; Hammar SP; Roggli VL
TI -
Well-differentiated papillary mesothelioma.
SO - Am J Surg Pathol 2001 Oct;25(10):1304-9
AD - Department of Pathology, Duke University Medical Center, Durham, North
Carolina 27710, USA. butno001@mc.duke.edu
Well-differentiated papillary mesothelioma is an unusual variant of
epithelial mesothelioma considered to be of low malignant potential. The
majority of previously reported cases developed in the peritoneum of
young women without a history of asbestos exposure. The authors report
14 cases of well-differentiated papillary mesothelioma, seven of which
originated in the pleura, six in the peritoneum, and one in the tunica
vaginalis. Eleven of the patients were male and three were female, with
an average age at presentation of 58 years (range 32-82 years). Six of
the patients had a quantifiable history of asbestos exposure. Of the
nine cases with complete follow-up, six had clinically indolent disease,
one showed resolution after adjuvant chemotherapy, one pursued an
aggressive course, and one died of other causes. These findings indicate
that well-differentiated papillary mesothelioma is a rare variant of
mesothelioma with a variable clinical prognosis that is etiologically
related to asbestos exposure in some cases.
14
UI - 11679187
AU - Ceresoli GL; Locati LD; Ferreri AJ; Cozzarini C; Passoni P; Melloni G;
TI -
Zannini P; Bolognesi A; Villa E
Therapeutic outcome according to histologic subtype in 121 patients with
malignant pleural mesothelioma.
SO - Lung Cancer 2001 Nov;34(2):279-87
AD - Department of Radiochemotherapy, San Raffaele H Scientific Institute,
Via Olgettina 60, 20132 Milan, Italy. ceresoli.giovanni@hsr.it
One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM)
seen between 1986 and 1999 at the authors' Institution were reviewed.
Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%)
and mixed in 12 (10%). Ninety-one patients received a treatment (38
palliative pleurectomy and no further therapy, 16 palliative pleurectomy
followed by chemotherapy, 37 chemotherapy alone), while 30 were referred
to supportive care only. Median survival of the whole population was
10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%,
respectively. Univariate analysis of subgroups showed that poor
performance status (PS), non-epithelial histotype, Butchart stage>I and
International Mesothelioma Interest Group (IMIG) stage>I were
individually associated with lower survival. Patients receiving any
therapy survived longer than patients treated with supportive care only
(P=0.0004). Treatment modality had an independent prognostic value
(P=0.00005), with a survival advantage for patients receiving surgery
and adjuvant chemotherapy. Multivariate analysis confirmed the
independent prognostic value of PS (P=0.001; HR=2.48) and treatment
modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and
treatment modality (P=0.01) was confirmed in the subset of patients with
epithelial histology. On the contrary, therapy had no impact on survival
in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of
a retrospective non-randomized evaluation of treatment-related factors,
patients with good PS and epithelial histology seemed to have a survival
benefit from surgery or multimodality therapy, as opposite to patients
with poor PS or non-epithelial histotype. However, these results must be
confirmed in a larger prospective trial with uniform treatment.
15
UI - 11679188
AU - Kosty MP; Herndon JE 2nd; Vogelzang NJ; Kindler HL; Green MR
TI -
High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant
mesothelioma: a phase II study-Cancer and Leukemia Group B 9631.
SO - Lung Cancer 2001 Nov;34(2):289-95
AD - Division of Hematology/Medical Oncology, MS217, Scripps Clinic, 10666
North Torrey Pines Road, La Jolla, CA 92037, USA. mkosty@scripps.edu
Doxorubicin is the most widely studied agent for the treatment of
malignant mesothelioma. In conventional doses, the response rate is
approximately 17%. Higher dose doxorubicin has been successfully
employed in other tumor types. Dexrazoxane has been demonstrated to
reduce the cardiac toxicity associated with long term, chronic use of
doxorubicin. Based upon phase I data generated by the Cancer and
Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120
mg/m(2) when combined with dexrazoxane and GM-CSF could be safely
administered, the CALGB undertook a phase II study of high-dose
doxorubicin in patients with malignant mesothelioma. Toxicity was
excessive, necessitating protocol modification and ultimately protocol
termination. There were no objective responses observed. We conclude
that high-dose doxorubicin administered with dexrazoxane is unacceptably
toxic in this patient population.
16
UI - 11689458
AU - Romano M; Catalano A; Nutini M; D'Urbano E; Crescenzi C; Claria J;
TI -
Libner R; Davi G; Procopio A
5-lipoxygenase regulates malignant mesothelial cell survival:
involvement of vascular endothelial growth factor.
SO - FASEB J 2001 Nov;15(13):2326-36
AD - Department of Human Pathology, University of Messina, Messina, Italy.
mromano@unich.it
Evidence indicates that lipoxygenases (LO) may play a role in cancer
cell survival. We show that human malignant pleural mesothelial (MM)
cells, but not normal mesothelial (NM) cells, express a catalytically
active 5-LO. Pharmacological or genetic inhibition of MM cell 5-LO
determined nucleosome formation and induced a DNA fragmentation pattern
typical of apoptosis. This was completely reversed by exogenously added
5(S)-HETE but not by 12(S)-, 15(S)-HETE, or leukotriene (LT)B4. A 5-LO
antisense oligonucleotide potently and time-dependently reduced vascular
endothelial growth factor (VEGF) mRNA and constitutive VEGF accumulation
in the conditioned media of MM cells. When NM cells were transfected
with a 5-LO cDNA, basal and arachidonic acid-induced VEGF formation
increased consistently by 6- and 12-fold, respectively. This was
associated with a significant increase in DNA synthesis that was
counteracted by a specific anti-VEGF antibody. Arachidonic acid and
5(S)-HETE also potently stimulated the activity of a VEGF promoter
construct. Thus, 5-LO is a key regulator of MM cell proliferation and
survival via a VEGF-related circuit.
17
UI - 11745800
AU - Merritt N; Blewett CJ; Miller JD; Bennett WF; Young JE; Urschel JD
TI -
Survival after conservative (palliative) management of pleural malignant
mesothelioma.
SO - J Surg Oncol 2001 Nov;78(3):171-4
AD - Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
BACKGROUND AND OBJECTIVES: Malignant mesothelioma is a lethal disease.
Aggressive multimodality treatment protocols are reportedly associated
with improved survival, but the apparent survival benefits may simply
reflect patient selection and the variable natural history of this
malignancy. Before embarking on our own protocol of experimental
treatment for mesothelioma, we sought to identify important prognostic
factors and document the survival of patients treated conservatively
(with palliative intent only) in our region. METHODS: We performed a
retrospective review of all patients with a diagnosis of malignant
mesothelioma seen at our center between 1987 and 1999. Since curative
intent treatment had not been given, we assumed that measured survival
would largely reflect the natural history of the malignancy. RESULTS:
There were 101 patients (80 males and 21 females). Mean age was 65 +/-
9.2 years. Symptoms of disease were present for a median time of 5
months before the diagnosis was established. The most common presenting
symptoms were dyspnea (46 patients), chest pain (30 patients), and
weight loss (22 patients). Sixty-eight patients (68%) had a history of
asbestos exposure. Mesothelioma subtypes included epithelial (43
patients), sarcomatous (26 patients), mixed (19 patients), desmoplastic
(4 patients), and unspecified (9 patients). All 101 patients were
treated with palliative intent. Talc pleurodesis was performed in 70
patients. At the time of analysis, 90 patients had died and 11 remained
alive. Median survival was 213 (95% CI 137-289) days. Survival for the
three major histological subtypes was significantly different (log rank,
P = 0.0016). Histological subtype (epithelial favorable) was the only
significant independent prognostic factor (Cox proportional hazard
regression, P = 0.0009). CONCLUSIONS: Patients with epithelial
mesothelioma survive longer than those with other histological subtypes.
Conservatively managed patients with pleural malignant mesothelioma have
a median survival of approximately 7 months. These data from
conservatively treated patients can serve as baseline information for
future studies of experimental treatments. Copyright 2001 Wiley-Liss,
Inc.
18
UI - 11707487
AU - Bridgman S
TI -
Community health risk assessment after a fire with asbestos containing
fallout.
SO - J Epidemiol Community Health 2001 Dec;55(12):921-7
AD - Industrial and Community Health Research Centre, Department of
Postgraduate Medicine, University of Keele, UK.
Stephen.Bridgman@lnsha.wmids.nhs.uk
BACKGROUND: A factory fire in Tranmere, Merseyside, England, deposited
asbestos containing fallout in an urban area. There was considerable
community anxiety for months after the incident. Therefore an assessment
of the long term health risks of this acute environmental incident were
requested by the local health authority. METHODS: The facts of the
incident were gathered and appraised from unpublished and press reports,
involved personnel, and further analysis of material collected at the
time of the incident. The literature on the long term health risks of
asbestos was reviewed, and combined with evidence on asbestos exposure
to estimate community health risk. RESULTS: Risk was almost entirely
from exposure to fire fallout of chrysotile in asbestos bitumen paper
covering the factory roof. Amosite was only detected in a few samples
and in trace amounts. The number of people who lived in the area of
fallout was 16 000 to 48 000. From a non-threshold model with
assumptions likely to overestimate risk, the lung cancer risk is
estimated to be undetectably small. Risk of mesothelioma from chrysotile
exposure, and risks of lung cancer and mesothelioma from amosite
exposure were based on observational studies and were estimated to be
even lower than that of lung cancer risk from chrysotile exposure.
Academically, there are assumptions that while reasonable cannot be
proven, for example, the validity of extrapolating observed risk from
much higher exposures to lower exposures, estimates of individual
exposure, and that there is no threshold for asbestos to cause cancer.
CONCLUSIONS: The author is unaware of a similar study on long term
health risks in a community exposed to asbestos in a fire. It is
concluded that, using methods that do not underestimate risk, risk is
undetectably small. Practical lessons from this methodology and approach
to health risk assessment are discussed.
19
UI - 11523570
AU - Pujolar AE; Gonzalez C; Agudo A; Calleja A; Beltran M; Gonzalez-Moya J;
TI -
Hernandez S; Panades R; Ramirez J; Turuguet D
Information about occupational exposure to asbestos given to cases in an
etiological study: ethical aspects.
SO - Eur J Epidemiol 2001;17(1):1-6
AD - Servicio de Medicina Preventiva y Salud Publica, Hospital Universitario
Puerta del Mar, Cadiz, Spain. antonio.escolar@uca.es
The aim of the study is to consider some ethical aspects of the
provision of information, to the cases or their families, about the
assessment of occupational asbestos exposure obtained in a case-control
study of malignant mesothelioma of the pleura. An informative letter
with the result of the evaluation of their occupational exposure to
asbestos was sent to the participating cases (and/or their family).
Those whose exposure was classified as certain/probable were also
informed of the legislation regarding occupational diseases. Of the 132
cases, 32.6% of subjects and/or their families made telephone calls
expressing interest in the content of the informative letter. Among the
63 cases classified as certain/probable exposure, this proportion was
47.6%. Out of 43 cases in which the age at diagnosis was < or = 65 years
and the exposure to asbestos was certain/probable, only two (4.6%) were
signed off work owing to occupational disease. Only one of the
mesothelioma cases was recognized by the Spanish National Institute for
Social Security (INSS) as having an occupational disease. The process of
communication of the results of an epidemiological research should
include the provision of information on the exposure data to each one of
the subjects, and/or their families. There is a great disparity between
the number of cases of certain/probable exposure to asbestos identified
in our study, and the number registered as an occupational disease by
the INSS.
20
UI - 11713768
AU - Banerjee D
TI -
Technology evaluation: gene therapy (mesothelioma), NCI.
SO - Curr Opin Mol Ther 1999 Aug;1(4):517-20
AD - Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
banerjed@mskcc.org
The National Cancer Institute is sponsoring a phase I clinical trial by
the University of Pennsylvania involving administration of recombinant
adenovirus containing the HSV-tk gene and subsequent tumor kill by
ganciclovir, for the gene therapy of malignant mesothelioma. Twenty one
patients have been enrolled into the trial.
21
UI - 11603959
AU - Wong O
TI -
Malignant mesothelioma and asbestos exposure among auto mechanics:
appraisal of scientific evidence.
SO - Regul Toxicol Pharmacol 2001 Oct;34(2):170-7
AD - Applied Health Sciences, Inc., P.O. Box 2078, San Mateo, CA 94401, USA.
In 1986 the U.S. Environmental Protection Agency (EPA) issued an
official guideline on the prevention of asbestos disease among auto
mechanics. In the EPA guideline, malignant mesothelioma was listed as a
consequence of exposure to asbestos fibers from brake linings and clutch
facings among auto mechanics. EPA formulated its 1986 opinion by relying
solely on a few outdated case reports and not on epidemiologic studies.
A review of the literature indicates that there are six epidemiologic
studies providing relevant information on malignant mesothelioma among
auto mechanics. Three of the six studies had already been published by
1986, the year in which EPA issued its guideline. The results of the six
studies were remarkably consistent in that all six studies reported no
increased risk of malignant mesothelioma among auto mechanics. The
relative risks reported in the six studies ranged from 0.62 to 1.00.
Based on a meta-analysis of the combined data of all six studies
consisting of approximately 1500 malignant mesothelioma cases, the
mesothelioma relative risk for auto mechanics is 0.90 (95% confidence
interval 0.66-1.23). An application of Hill's causation criteria to
epidemiologic data of malignant mesothelioma among auto mechanics
clearly demonstrates that auto mechanics do not have an increased risk
of malignant mesothelioma as a result of exposure to asbestos fibers
from brake linings and clutch facings. However, in spite of the
scientific evidence, EPA has not modified or revised its 1986 guideline.
Occupational regulatory policies and guidelines, when based on proper
scientific evidence, are invaluable and can prevent avoidable diseases
in workers or other exposed individuals in the general public. On the
other hand, it is the regulators' responsibility to develop, modify, and
revise policies and guidelines in accordance with the most relevant and
the latest scientific data. In this instance EPA as a regulator has not
fulfilled its responsibility of providing the most accurate and
up-to-date information to the workers or the general public. Copyright
2001 Academic Press.
22
UI - 11745209
AU - Tot T
TI -
The value of cytokeratins 20 and 7 in discriminating metastatic
adenocarcinomas from pleural mesotheliomas.
SO - Cancer 2001 Nov 15;92(10):2727-32
AD - Department of Pathology and Clinical Cytology, Central Hospital, Falun,
Sweden. tibor.tot@ltdalarna.se
BACKGROUND: Immunohistochemistry is a useful method in the differential
diagnosis between pleural mesotheliomas and metastatic adenocarcinomas
to the pleura. Cytokeratin (CK) 5-6 is one of the most specific
mesothelioma-associated antibodies. Cytokeratin 20 and CK7 have been
used successfully in studies determining primary location of
adenocarcinomas from metastases. In the current study, the value of
these CKs in differential diagnosis of malignant pleural lesions was
examined. METHODS: Ninety-three autopsy-verified cases (14 mesotheliomas
and 79 adenocarcinomas including 42 primary lung tumors and 37
adenocarcinomas metastatic to the pleura) were stained on CK20, CK7, and
CK5-6 with commercially available primary antibodies. The staining was
conducted in an automated immunohistochemical system. The results were
analyzed statistically at different positivity thresholds: 10% and 0%.
RESULTS: None of the mesotheliomas stained positively for CK20 at the
10% positivity level, but 3 cases showed focal positivity in < 10% of
the tumor cells. Eighty-six percent (12 of 14) of these tumors were CK7+
and 64% (9 of 14) were CK5-6+. None of the mesotheliomas expressed the
CK20+/7- pattern. Lung adenocarcinomas, both primary and metastatic, and
breast carcinomas were very similar to mesotheliomas with regard to
expression of CK20 and CK7 but differed significantly with regard to
expression of CK5-6. Conversely, gastrointestinal adenocarcinomas and
pancreaticobiliary tumors expressed CK20 positivity in a high
proportion, 86% (13 of 15) and 77% (7 of 9), respectively. The
gastrointestinal tumors stained positively for CK7 in only 20% (3 of 15)
of cases and differed significantly from the other adenocarcinomas in
this aspect. The CK20+/7- pattern was typical for gastrointestinal
tumors. CONCLUSIONS: Adding CK20 and CK7 to the panel of antibodies in
the differential diagnosis of pleural mesothelioma versus metastatic
adenocarcinomas is useful because diffuse CK20 positivity seems to be an
indicator of metastasis. Furthermore, CK7 negativity most often is
associated with metastases, and the CK20+/7- pattern, typical of
colorectal adenocarcinomas, is absent in pleural mesotheliomas.
Copyright 2001 American Cancer Society.
23
UI - 11717937
AU - Xu G; Jiang Y; Dai Q; Li J; Fu X
TI -
[Ultrasonographic diagnosis of peritoneal mesothelioma]
SO - Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1998 Dec;20(6):445-8
AD - Beijing Hospital, Beijing 100730.
OBJECTIVE: To investigate the sonographic features of peritoneal
mesothelioma and its relationship with the gross pathology. METHODS: The
ultrasonographic results of 14 cases with peritoneal mesothelioma were
summarized, the sonographic features were compared with the gross
pathology. RESULTS: With ultrasound examination a sheetlike mass was
seen in two patients and a localized irregular mass was seen in one.
Involvement of "cakelike omentum" was present in five. Pelvic mass was
seen in eight and two were also with abdominal mass; one presented
abdominal mass only. Bowel adhesion was found in one. Ascites was
presented in all patients except one. CONCLUSIONS: It is possible for
ultrasonography to suggest the diagnosis of peritoneal mesothelioma,
when the sheetlike or irregular mass of peritoneum was founded.
Ultrasound guided biopsy was helpful in diagnosis of peritoneal
mesothelioma before operation.
24
UI - 11563601
AU - Neumann V; Gunthe S; Mulle KM; Fischer M
TI -
Malignant mesothelioma--German mesothelioma register 1987-1999.
SO - Int Arch Occup Environ Health 2001 Aug;74(6):383-95
AD - German Mesothelioma Register, Institution of the Central Federation of
Industrial Berufsgenossenschaften, Bergmannsheil Bochum, University
Hospital.
OBJECTIVES: The study group comprised a collective of 1,605 patients
with malignant mesotheliomas and with lung tissue available for lung
dust analyses. METHOD: Clinical features, occupational histories,
expositions and individual data were evaluated, and the asbestos bodies
concentrations (asbestos bodies/cm3 lung tissue or g wet tissue) were
determined. RESULTS: Mesotheliomas developed mainly in men (94.5%). Of
the cases, 96.4% were of pleural origin and only 3.3% were peritoneal
mesotheliomas. The biphasic subtype predominated (61.3%), followed by
the epithelioid type (29.3%). The sarcomatoid subtype was rarely
developed (9.4%). Mean age at first diagnosis was 60.4 years. The mean
survival time from time of symptom onset was 13.5 months. Patients with
epithelioid subtypes had a longer survival time (16.9 months) than those
with biphasic (13.1 months) and sarcomatoid subtypes (5.5 months). Of
the patients, 73% presented pleural effusions as initial symptoms of the
disease. An increased asbestos burden was identified by light microscopy
in 84.8% of the patients. There was no association between histological
subtypes and the asbestos burden of the lungs. Patients with peritoneal
mesotheliomas had distinctly higher asbestos burdens in the lungs than
patients with pleural mesotheliomas. There exists no association between
lung asbestos burdens and survival times. The mean latency period was
37.8 years. A trend: higher asbestos burden of the lung/shorter latency
periods was suggested. About 70% of the patients had a history of
occupational exposure to asbestos dust. Most patients worked in the
building trade, the locksmith and machine building industries and in the
steel and blast-furnace industries. Of the patients, 25.6% had
asbestos-associated lung fibroses, in 40.7% of the cases pleural plaques
were identified. CONCLUSIONS: The most important causal factor for
development of mesotheliomas is still asbestos, primarily amphibole
asbestos. The recurring occurrence of mesotheliomas in younger people
without known asbestos exposure needs the urgent investigation of other
inducing factors for mesotheliomas.
25
UI - 11713097
AU - Cao XX; Mohuiddin I; Ece F; McConkey DJ; Smythe WR
TI -
Histone deacetylase inhibitor downregulation of bcl-xl gene expression
leads to apoptotic cell death in mesothelioma.
SO - Am J Respir Cell Mol Biol 2001 Nov;25(5):562-8
AD - Department of Thoracic and Cardiovascular Surgery, Section of Thoracic
Molecular Oncology, the University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030, USA.
It has been shown that mesothelioma expresses the antiapoptotic protein
BCL-XL, but not BCL-2, rendering bcl-xl gene expression a potential
therapeutic target. Sodium butyrate (NaB) is a histone deacetylase
inhibitor capable of alteration of bcl-2 family protein expression in
other tumor types. Mesothelioma cell lines (REN, I-45) were exposed to
NaB, and viability (colorimetric assay) and apoptosis (TUNEL, Hoescht
staining, flow cytometry) were evaluated. Effects on bcl-2 family
protein, fas-fas ligand, and caspases were examined by Western blot
analysis and functional assay. An RNase assay evaluated bcl-2 family
messenger RNA (mRNA) expression. Overexpressing BCL-XL mesothelioma
clones were created by plasmid transfer. Cells were sensitive to NaB at
low IC(50) (REN, 0.3 mM; I-45, 1 mM) and demonstrated apoptosis
(percentage of cells below G1 phase by flow cytometry [sub-G1]: REN,
38.5%; I-45, 30.9%). A significant decrease in BCL-XL protein expression
was noted with BAK, BAX, and BCL-2 unchanged, and this was corroborated
at the transcriptional level with selectively decreased bcl-xl mRNA
production after sodium butyrate exposure. Fas expression and fas-fas
ligand s
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