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The Cancer Journal - Volume 9, Number 3 (May-June 1996)


Inflammatory cancers

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 have 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 from 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 manifestations are observed mainly in young adults, while patients over 50 years suffer from lymphomas (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 also struck 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 also characteristic of poliomyelitis (6). Hodgkin's disease belongs to a distinct group of cancers, here called 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 preclinical phase, and surface clinically as inflammatory neoplasms. Prevention of seminoma should be directed at its preclinical phase in the same way as is 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 to respond 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. However, closer analysis of the response suggests that chemotherapy may be effective mainly against the inflammatory component and fails when the disease becomes neoplastic. The same may also be true 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!

Gershom Zajicek

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