Peritoneal Mesothelioma
By: R. John Clement, MRCS., LRCP., Medical
Director Lawrence Burton, BSC, MSC, PhD., Experimental Zoologist
Gerald N. Lampe, P.T., Research Associate
Mesotheliomas arise from the surfaces of any mesothelial lined
body cavity. Mesotheliomas most frequently occur in the pleural
cavity; less in the peritoneal; and, least in the pericardial cavity.
The tumors are most often malignant and usually are detected late
in the course when they begin to interfere with organ function.
The onset of symptoms is insidious, but once the diagnosis is made,
death commonly ensues within one year. Initially, peritoneal mesotheliomas
are white nodules widely dispersed over the visceral and parietal
peritoneum, but the nodules later coalesce and form plaques and
masses. Even with massive tumor growth in later states, rarely does
the tumor invade the adjacent viscera of the bowel. Instead, the
tumor encases the intraperitoneal contents and produces mechanical
obstruction.
Epidemiologic studies indicate an increasing trend of incidence
of malignant mesothelioma, present and future, largely due to wide
utilization of asbestos. Because of the long latency from asbestos
exposure to onset of mesotheliomas, neoplasms associated with environmental
exposure to asbestos may continue to be evidenced well into the
1990's.
In view of the findings of epidemiologic studies, it is prudent
to survey the results of therapeutic modalities presently available.
Most notably there is no reported evidence of one cure of a malignant
mesothelioma patient. The paucity of cases and clinical experiences
have produced few controlled clinical studies which allow adequate
evaluation of the effect of various single or combined therapeutic
modalities.
Recent analysis of eleven persons with peritoneal mesothelioma has
promoted this review of direct clinical experiences at the Immunology
Researching Center (IRC), Freeport, Grand Bahama and of the literature.
MATERIALS AND METHODS
Each case reviewed and analyzed had previous histological confirmation
of diagnosis at laparotomy or autopsy and a pattern of clinical
responses compatible with malignant peritoneal mesothelioma. All
patients (cases) reported a history of non-specific abdominal pain
and related diffuse symptoms for a minimum of one year prior to
diagnosis. Characteristically subacute intestinal obstruction preceded
diagnosis. Ascites were present in six of eleven of the cases.
Eleven of eleven cases demonstrated a characteristic immune profile
upon assessment of immuno-competence. Elevated titers of a pre-albumin
blocking protein factor and suppressed levels of an alpha 2 macroglobulin
de-blocking protein factor were assayed in all eleven cases. Immunoglobulin
IgA, IgG and IgM were variously suppressed in this population and
tumor complement factor was universally suppressed. Immuno-augmentation
was attempted by subcutaneous and intramuscular injections of human
serum protein components (immuno-globulin serum antibodies and alpha
2 macro-globulin deblocking factor) derived from volunteer donors
without neoplastic disease, and of tumor complement factor derived
from human serum of the persons with malignant mesothelioma.1
The subject population consisted of four females and seven males,
which reflects the reported trend that the incidence is higher in
males.
Four males and one female are alive with survival among the five
ranging from 22 months to 80 months. The mean survival for those
living is 43 months and the median is 52 months. Of
the other six cases, mean survival was 23 months and the median
was 16 months, with a range of
seven months to 50 months.
The total subject population represents mean survival of 35 months
and a median survival
of 30 months; with a range for all cases from seven months to 80
months.
There was no common response to differentiate survival experiences
in patients who had surgery and adjuvant chemotherapy prior to the
therapeutic modality of immuno-augmentation from those that did
not have prior adjuvant therapy. All eleven subjects demonstrated
a common biological response to immuno-augmentation in a universal
pattern of weight gain and an increase of endurance for physical
activity as indicated by improved tolerance for walking distance;
for upper extremity exercise; and self-care capabilities.
DISCUSSION
The subject population of this analysis was consistent with the
pattern of clinical presentation anticipated of malignant peritoneal
mesothelioma. Common physical finding of abdominal distension from
tumor, obstruction, or from ascites were presented, but only after
a prolonged period of prior nonspecific abdominal pain. Laboratory
tests employed were not helpful to primary physicians not affiliated
with IRC in the diagnostic processes* but cytology studies of aspirated
fluids and ultrasound scans were somewhat more helpful. All eleven
patients received exploratory laporotomies, and the five patients
with subtotal resections appeared to have a more favorable response
to therapy than did those with open biopsy alone.
*Histological confirmation of the diagnosis is
uniformly required to have occurred prior to admission to the Immunology
Researching Center, and it must be confirmed by physicians or institutions
not in the Bahamas.
In 1979, Jones and Silver2 reported on the experiences
of the University of Missouri and peritoneal mesotheliomas. Six
of the reported subjects died within one year after diagnosis. One
subject living at the time the report occurred was alive but symptomatic
three months after diagnosis, and the second was alive with a benign
tumor and free of symptoms 10 months after diagnosis. Survival ranged
from 9 days (less than 1 month) to 180 days (6 months).
The mean survival of those who died was 91 days (3 months) and the
median was 82 days (less than 3 months). The mean survival for the
subjects alive was 7 months.
Chahinian and Holland3 surveyed treatment of diffuse malignant mesothelioma
and reported in 1978 the following literature summary:
Table 2 overall Survival of Patients with Diffuse Malignant Mesothelioma
of the Peritoneum.
(Including Treated Cases)
|
| Authors/Year |
# of Cases |
|
Survival in months
after onset Of Symptoms |
|
% pts dead at 1 Year |
|
|
Mean |
Median |
Range |
|
| Goodwin 1957 |
4 |
12 |
11 |
1-26 |
86 |
| Newhouse & Thompson 1960 |
12* |
18 |
11 |
1-60 |
58 |
| 1965 |
21 |
14.8 |
12 |
3-54 |
50 |
| Elmes 1972 |
45* |
6 |
- |
- |
- |
| Lilis & Selikoff 1974 |
68 |
9.5 |
- |
2-29 |
- |
*cumulative literature series
They reported that there is no general evidence that RT (radiotherapy)
is effective in peritoneal malignant mesothelioma.@ They did report
that better results are reported for combined therapy including
intra-peritoneal installation of 10mc of p32 followed by abdominal
radiotherapy4 and combined radiotherapy and chemotherapy with procarbazine5.
Chan, Balfour, Bouke and Smith6 reported two cases of peritoneal
malignant mesothelioma. One subject survived 12 months, the second
survived 14 months. Surgery was performed with no adjuvant therapy
modalities administered.
The March 1980 American Journal of Medicine7 reported on patients
with a histologic diagnosis of malignant mesothelioma treated at
the Sidney Laber Cancer Institute and the Peter Bent Brigham Hospital
between 1965 and 1978. Six subjects of analysis had primary peritoneal
mesothelioma. Their analysis revealed a median survival of 15.0
months from diagnosis to death.
CONCLUSIONS
There are no published series in which matched groups of patients
have been subjected to a variety of treatments in a prospective
study.
Standard treatment of malignant peritoneal mesothelioma has not
been established.
Analysis of the literature indicates that when possible, these patients
should benefit from maximal resection of tumor. Retrospective analysis
of the subject population receiving immuno-augmentation indicates
responses which are consistent with this recommendation.
Radiotherapy does not appear to be effective for mesotheliomas3,
but combination therapy does appear to be active and does appear
to affect favorably these patients= survival.
Recent analysis of Immuno-Augmentative Therapy reveals that it is
active and does not affect survival favorably. The effectiveness
of this modality does not conclusively indicate a difference of
responses in patients who did or did not receive prior chemotherapy.
Review of subjects in this analysis finds the survival range from
7 - 80 months with mean and median survivals of 35 months and 30
months respectively. Clearly, Immuno-Augmentative Therapy for malignant
peritoneal mesothelioma can be justified, and this modality should
be included in the continued efforts to establish effective therapy
for this disease. Prospective epidemiologic studies anticipate escalation
of new cases into the 1990's and retrospective analyses show that
for malignant peritoneal mesotheliomas, survival is measured in
months. The gloomy outlook may be modified by immune system augmentation.
Prospective, multi-centered controlled studies are needed to determine
the most efficacious treatment and the most effective integration
of immuno-augmentation with several different treatment modalities.
If longer term experiences uphold the trend indicated by this present
analysis, Immuno-Augmentative Therapy, which has not before been
reported in single or multimodality studies, will provide a significant
modality in the treatment of malignant peritoneal mesotheliomas.
1 Immuno-Augmentative Therapy: Cancer Research and Treatment; IAT
Communications, Olathe, KS, @ (1984) IAT Communications, Inc.
2 D. E. Casey Jones, M.D., Donald Silver, M.D.: Peritoneal Mesotheliomas;
Surgery,
p. 556-560 0039-6060/79/100556 & 00.50/0 @ 1979 The C. V. Mosby
Co.
3 A. Philippe Chahinian, M.D. and James F. Holland, M.D.; The Sinai
Journal of Medicine, Vol. 45, No. 1, January-February, 1978 Printed
in USA, p. 57-67.
4 Rogoff, Huvas cancer 32;656-665, 1973.
5 G. Falkson personal communication with Chahinian/Holland.
6 Br. J. Surg., Vol 62 (1975) 576-550.
7 Multimodality Therapy for Malignant Mesothelioma Based on A Study
of Natural History (Antman, Blum, Greenberger, Flaverden, Skarin,
Canellos); American Journal of Medicine, March 1980, Vol. 68.
This report covers the period May 1980 to February 1987
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