According to molecular biology, cancer is a genetic disease that starts
when a vital gene of a normal cell is changed, transforming it into a neoplasm
that ultimately destroys the organism (1). While in all other ailments, the
organism actively resists disease, in cancer it appears to be helpless. Even
the immune system does not protect the host against its tumor, and attempts
to develop an anti-cancer vaccine failed. On the other hand, immunity is not
the only protective mechanism in our body, other processes might be more adequate.
A myocardial infarct heals without immunological assistance. Dead heart cells
trigger a (sterile) inflammation that clears necrosis and replaces it with a
scar. Could this mechanism be harnessed for cancer treatment? Imagine the same
inflammation replacing a breast tumor with a scar. . . Such ideas are not even
considered by the prevailing dogma since they do not fit into its genetic framework.
This example illustrates how an overpowering simplistic dogma bars medicine
for creative ideas. Particularly since inflammation accompanies many cancers
(2).
Hodgkin Disease
This enigmatic disease is still regarded as "The Hodgkin's maze" (3), since
it is a combination of lymphoma and inflammation. It is manifested by a bimodal
age specific mortality distribution. Its first peak occurs between ages 15 and
35 years, and the second, around the age of 50 years (3). Apparently Hodgkin's
disease starts as a chronic inflammation that turns into a lymphoma. Granulomatous
manifestation are observed mainly in young adults, while patients over 50 years,
suffer from a lymphoma (4). In 284 patients with Hodgkin's disease, Reed-Sternberg
cells, eosinophils and the extent of fibrosis were more pronounced in young
adults, while atypical mitoses and other features of malignancy were more common
in older persons (5). The authors were struck also by the epidemiological similarity
between Hodgkin's disease and multiple sclerosis, suggesting that both could
result from a very prevalent infection of low pathogenicity which is characteristic
also of poliomyelitis (6). Hodgkin's disease belongs to a distinct group of
cancers called here inflammatory. It is manifested epidemiologically by a bimodal
age specific mortality distribution, and histopathologically, by a mixture of
inflammation and lymphoma.
Inflammatory cancers
Seminoma also exhibits both markers. A bimodal age specific distribution,
on one hand, and a mixture of inflammation and neoplasia, on the other (7).
Colon cancer following ulcerative colitis should also be placed in this group.
It exhibits both markers. Other examples include, hepatoma following chronic
hepatitis, cervix carcinoma following chronic papilloma virus infection (8),
and nasopharyngeal carcinoma. Even childhood leukemia seems to be of infective
origin (9). In some cancers, e.g., osteosarcomas, and connective tissue tumors,
the first peak is less pronounced but well defined. The nosology of inflammatory
cancers differs from the current nosology of cancer. Traditionally, cancers
are classified either by the organ of their appearance e.g., breast, colon and
prostate, or histopathologically, e.g., carcinoma, lymphoma, and sarcoma. The
present classification highlights the association between inflammation and neoplasia,
and opens new vistas of research in cancer.
When inflammation accompanies neoplasia it is generally regarded as a carcinogen
causing cancer by chronic irritation (2), which may not be so. Inflammation
and cancer may both be caused by an independent agent. It is assumed here that
inflammatory cancers start as inflammations. Suppose that Hodgkin's disease
and seminoma evolve in the same way as hepatoma and cervix cancer. Both should
start as "pure" and smoldering inflammations, that are clinically asymptomatic,
and therefore undiagnosed. They proceed through an asymptomatic pre clinical
phase, and surface clinically as inflammatory neoplasms. Prevention of seminoma
should be directed to its pre clinical phase. In the same way as done in chronic
hepatitis and its subsequent hepatoma. By treating hepatitis, or a cervical
infection, the incidence of their respective cancers may be reduced. In some
cases infection may be treated with antibiotics.
Helicobacter pylori induced cancers
Apparently, two histomorphologically distinct cancers, carcinoma and lymphoma,
are triggered by Helicobacter pylori. "Past infection with Helicobacter pylori
significantly increases the risk of developing gastric carcinoma." "Moreover,
mucosal lesions that are clearly associated with gastric carcinoma, namely,
chronic multifocal atrophic gastritis and intestinal metaplasia, are known to
be caused by H. pylori infection" and the author asks "Is gastric lymphoma an
infectious disease? "(10). Why not then "treat the infection and cure cancer?"
(11), by antibiotics for instance. If the authors are correct, gastric carcinoma
and lymphoma are inflammatory cancers.
Inflammatory cancers respond to chemotherapy
Cancer treatment is generally hampered by a mounting resistance to chemotherapy
and radiotherapy. When applied for the first time both measures are effective,
yet with time, cancers cease responding to treatment. Mounting resistance to
chemotherapy is pathognomonic of cancer. This attribute may serve for distinguishing
cancerous from non cancerous processes. In other words, "genuine" cancers become
resistant, while non-cancerous ailments, do not become resistant to chemotherapy.
This may seem odd since chemo- and radiotherapy are extremely effective in Hodgkin's
disease and seminoma. But closer analysis of the response suggests that chemotherapy
may be effective mainly against the inflammatory component and fails when the
disease becomes a neoplastic. The same may be true also in childhood leukemia.
The notion of inflammatory cancers rescues medicine from the deadlock of
the molecular biology dogma that regards cancer as a genetic and hopeless disease.
Inflammatory cancers are treatable!
G. Zajicek
References
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2 Gordon LI and Weitzman SA. Inflammation an Cancer. The Cancer Journal
6:257-261,1993.
3 Wright DH. Out of the Hodgkin's maze? J. Pathology 177:331-333, 1995
4 MacMahon B. Epidemiology of Hodgkin's Disease. Cancer Res. 26:1189-1195,1966
5 Newell GR, Mills PK,Johnson DE. Age differences in the histology of Hodgkin's
disease. Natl Canc. Inst. J. 45:311-316,1970
6 Newell GR. Etiology of multiple sclerosis and Hodgkin's disease.
Am. J. Epidemiol. 91:119-124,1970
7 Mostofi PK, Price Jr EB. Tumors of the male genital system.
Armed Forces Inst. Pathol. 8:28-100,1970
8 Schiffman MH Recent progress in defining epidemiology of human papillomavirus
infection and cervical neoplasia. JNCI 84: 394-398, 1992.
9 Kinlen LJ. Epidemiological evidence for an infective basis in childhood
leukemia. Br. J. Cancer. 71:1-5,1995.
10 Isaacson PG. Is gastric lymphoma an infectious disease? Human Pathol.
24:569-570,1993.
11 Eidt S., Bayerdorffer E, Stolle M. Treat infection and cure cancer. The
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