Cancer

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Cancer refers to a wide variety of diseases that have in common uncontrolled cell proliferation. Malignant growth entails uncontrolled cell division, lack of normal cell death (apoptosis), and failure of the cells' environment to help control its growth. At a certain point, a cancer can also gain the ability to escape from its point of origin and "metastisize", or spread. As clumps of cancer cells grow, then can form "tumors". Not all cancers form tumors. For instance, in most leukemias, the cancer cells are circulating through the blood, rather than forming discrete masses. Cancers, especially rapidly growing ones, can consume a great deal of energy, and can secrete various substances that cause a general decline in health.

Cancer can cause symptoms in a number of ways: by direct effect on the organ involved (i.e. a cough with lung cancer), by growing into a vital structure (i.e. prostate cancer obstructing the urethra), or by causing generalized malaise and anorexia. This last topic is less well understood.

Since cancers arise from so many different cell types, treatments are often very specific. There is no one treatment for "cancer".

Classification

Cancers are generally classified by the cell and/or tissue type of origin (i.e., histological classification), and by location, and Latin or Greek prefixes are often used to name the tissue involved. English names are used frequently for common cancers. For example, an epithelial-derived cancer in the bowel is a "colon carcinoma". Other terms that refer to cancer are "malignancy" and "malignant neoplasm" (or simply neoplasm, although neoplasm can also refer to benign growths.

Histological classification

The following general categories are usually accepted:

This introductory article will give a brief description of what a malignancy is, and how cells are thought to become malignant. That understanding is important as a basis to comprehend the medical and surgical treatment of cancers, and effective approaches to their prevention. After a general introduction to malignancies, major types of carcinomas (epithelial malignancies) are surveyed, with links provided for further information. The clinical emphasis is on human cancers, but references to cancers in other species of animals is also made. Although the frequencies and the aggressiveness of the various types of cancers vary according to species, generally, the basic biology of cancers is true for all species of vertebrate animals, including humans and domestic animals.

Location

Tumors are named using -oma as a suffix with the organ name as the root. For instance, a benign tumor of the smooth muscle of the uterus is called "leiomyoma" (the common name of this frequent tumor is fibroid). If the tumor is malignant, the appropriate suffix is added, for example, "leiomyosarcoma" is the cancerous version of a fibroid tumor.

Cancer vs. other tumors

Many types of growths can be found on and in the human body. The term neoplasm is generally used for any abnormal growth. Not all growths, however, are cancerous, or malignant. Historically, illnesses of human and animals that were progressive and fatal, and that involved tumors that destroyed flesh, were well known. Although the word "cancer" has been used to describe such conditions, today the term cancer is only used when malignant cells are present in the body. Many processes can cause the body to form masses (lumps), including infections, and scarring from trauma and burns. Since malignant cells can almost always be recognized under the microscope, if the tissue is properly prepared, a biopsy is virtually always required to make a firm diagnosis of cancer.

Initial evaluation

Even before biopsy, physical examination and imaging can provide the first information used in staging: the size of the mass and the level to which it penetrates nearby tissue.

Types of Biopsies

There are several general types of biopsies, which include, in order of invasiveness, aspirational, incisional and excisional. An inspirational biopsy involves inserting a hypodermic needle, often guided by imaging techniques such as ultrasonography or X-ray computerized tomography, into the mass and withdrawing cells for pathological examination.

Incisional biopsy involves cutting into the mass and removing part of it. For skin or other surfaces, a punch biopsy is intermediate between aspirational and incisional: it removes a piece of tissue rather than free cells, but uses what is effectively a large-diameter hollow needle without the flexibility of an incision. Incisional biopsies must take precautions not to spread malignant cells.

If an area is suspicious for a possible malignancy, and it is both small and accessible, the entire lesion is usually removed in the biopsy. So, for example, a small freckle of the skin that shows signs of possible melanoma would be removed completely, rather than simply sampled. On the other hand, if excision would entail extra risk to the patient or is better done in continuity with other structures of the body, such as lymph nodes or bone, then an incisional biopsy, in which only a relatively small portion of the lesion is removed, is a better choice.

Examining the biopsy sample

The next general step is microscopic examination of the sample, and looking for differences from normal tissue or distinct signs of cancer. Pre-cancerous lesions may simply show more irregularity, in shape or nuclei, to the trained eye. They may be dividing at a faster rate than other cells.

Grading is relevant within tissue types. The more "high-grade" a lesion, the more disorganized the tissue.

Malignancy: How do malignant cells develop?

carcinogens are mutagens

"Cancer can be defined as a genetic disease at the cellular level" [1] That's because the rate of cell division and the amount of differentiation of a cell are controlled by genes. When mature cells become more like embryonic cells, they are said to de-differentiate. Although this process is not thought to be the exact opposite of differentiation of cells, it does describe the loss of characteristics of mature cells that cancer cells undergo.

DNA repair

When DNA is damaged in normal cells, by such environmental processes as exposure to sunlight or by errors that occur in cell division, then, ideally, repairs are made and normal DNA is restored. If there are defects in the ability of a cell to repair DNA, this can lead to the daughters of that cell eventually becoming malignant. Since a small number of defects are expected to occur with each cell division, an inability to repair them can lead to more and more abnormalities in successive generations of cells.

Oncogenes

Common malignancies that are not epithelial cancers

Cancer by location

Skin Cancer

Basal cell carcinoma

Squamous cell carcinoma

Head & neck cancer

Mouth, throat and larynx

Esophagus

Thyroid gland

Lung Cancer

Breast Cancer

Colon Cancer

other gastrointestinal cancers

Prostate cancer

Brain tumors (cancers)

Oncology, Hematology and specialties that treat cancer

The two medical specialties that focus on malignancies are oncology and hematology. Oncologists are physicians who are fully trained in Internal Medicine and have further training in the treatment of malignant tumors, primarily solid tumors. Hematologists are also physicians who are fully trained in Internal Medicine, in their case further training is in disorders of the blood, including the bone marrow, which produces blood cells. Both hematologists and oncologists have advanced training in giving the drugs that inhibit cancer growth, called chemotherapy.

Some types of cancers and other malignancies are at least equally the province of other specialists, because of the part of the body they affect, or because the treatments they require, are the focus of those particular specialties. So, for example, radiation oncologists, who are trained in the use of external beam radiation and other kinds of radiation treatments, and surgeons who are specialists in the areas of the body that the cancer affects, like the breast or larynx, are important in cancer care, and depending on the type and extent of the cancer, may be the main physician directing the cancer patient's care. For several decades, the notion of a "team approach" has been embraced in the treatment of cancer. A team approach offers the support of an entire group of professionals, including the physicians of the specialties mentioned, nurses, social workers and others. The team also includes diagnostic physicians, like surgical pathologists and diagnostic radiologists who have special expertise in evaluation of the studies important for confirming and staging cancer.

Screening

Harms

About half of patients will have a false positive result when undergoing serial screening for multiple cancers.[2]

Overdiagnosis

Not all cancers lead to death or even to symptoms. Overdiagnosis occurs for cancer of the breasts[3], lungs[4], and prostate[5]. Regarding breast cancer, about 50% of cancers represent overdiagnosis; this fraction is reduced to 35% if carinoma in situ is removed and only invasive cancer is considered.[3]

Common complications and their treatments

Deep venous thrombosis

Deep venous thrombosis (DVT) may occur in patients with cancer. In patients with cancer who have a DVT, lifelong anticoagualation with low molecular weight heparin may help. Patients with cancer are more likely to have bleeding complications with warfarin.

Cachexia and anorexia

Megestrol acetate may help with appetite and weight gain.[6][6]

Fatigue

Fatigue may improve with psychostimulants such as methylphenidate.[7]

Fatigue may be secondary to a hypercatabolic state associated with cachexia, paraneoplastic syndrome.

Prevention

Aspirin may prevent death from cancer.[8] No dietary supplements - except possibly vitamin D and calcium - are proven to reduce the risk of cancer.

Selected systematic reviews and subsequent randomized controlled trials of
supplements for the prevention of cancer
Intervention Type of cancer Study type / year Conclusion
Antioxidants Gastrointestinal cancer Systematic review[9] of twenty randomized controlled trials
2008 (search date 10-2007)
• "We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers"
• "Antioxidant supplements seem to increase overall mortality"
• "The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials."
• Total cancer
• Prostate cancer
Randomized controlled trial[10]
2009
"Neither vitamin E nor C supplementation reduced the risk of prostate or total cancer"
• Total cancer
• Prostate cancer
Randomized controlled trial[11]
2009
"Selenium or vitamin E...did not prevent prostate cancer"
B Vitamins All cancer Randomized controlled trial[12]
2008
"No significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era"
Calcium + Vitamin D Colorectal cancer Systematic review[13] of two randomized controlled trials
2008 (search date 7-2007)
• "Calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps"
• "This does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer"
Total cancer Randomized controlled trial[14]
2007
"Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women"

The final randomized controlled trial in the table was not addressed in the systematic review by the Cochrane Collaboration. This trial was a secondary analysis and used 1000 IU Vitamin D per day to reduce cancer.[14]

References

  1. J. Larry Jameson, Peter Kopp:Chapter 56. Principles of Human Genetics. Harrison's Online Featuring the complete contents of Harrison's Principles of Internal Medicine, 16th Edition (Dennis L. Kasper, Eugene Braunwald, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Kurt J. Isselbacher, Eds.)Copyright © 2005. Mcgraw-Hill's Access Medicine)
  2. Croswell JM et al. (2009). "Cumulative incidence of false-positive results in repeated, multimodal cancer screening". Ann Fam Med 7: 212–22. DOI:10.1370/afm.942. PMID 19433838. Research Blogging.
  3. 3.0 3.1 Jorgensen, KJ; PC Gotzsche (2009-07-09). "Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends". BMJ 339 pages = b2587. DOI:10.1136/bmj.b2587. Retrieved on 2009-07-10. Research Blogging.
  4. Marcus PM et al. (June 2006). "Extended lung cancer incidence follow-up in the Mayo Lung Project and overdiagnosis". J Natl Cancer Inst. 98 (11): 748–56. DOI:10.1093/jnci/djj207. PMID 16757699. Research Blogging.
  5. Schröder FH et al. (March 2009). "Screening and prostate-cancer mortality in a randomized European study". N Engl J Med 360: 1320–8. DOI:10.1056/NEJMoa0810084. PMID 19297566. Research Blogging.
  6. 6.0 6.1 Berenstein EG, Ortiz Z (2005). "Megestrol acetate for the treatment of anorexia-cachexia syndrome.". Cochrane Database Syst Rev (2): CD004310. DOI:10.1002/14651858.CD004310.pub2. PMID 15846706. Research Blogging.
  7. Minton O, Richardson A, Sharpe M, Hotopf M, Stone P (2010). "Drug therapy for the management of cancer-related fatigue.". Cochrane Database Syst Rev 7: CD006704. DOI:10.1002/14651858.CD006704.pub3. PMID 20614448. Research Blogging.
  8. Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW (2010). "Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.". Lancet. DOI:10.1016/S0140-6736(10)62110-1. PMID 21144578. Research Blogging.
  9. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2008). "Antioxidant supplements for preventing gastrointestinal cancers". Cochrane Database Syst Rev (3): CD004183. DOI:10.1002/14651858.CD004183.pub3. PMID 18677777. Research Blogging.
  10. Gaziano JM, Glynn RJ, Christen WG, et al (January 2009). "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial". JAMA 301 (1): 52–62. DOI:10.1001/jama.2008.862. PMID 19066368. Research Blogging.
  11. Lippman SM, Klein EA, Goodman PJ, et al (January 2009). "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)". JAMA 301 (1): 39–51. DOI:10.1001/jama.2008.864. PMID 19066370. Research Blogging.
  12. Zhang SM, Cook NR, Albert CM, Gaziano JM, Buring JE, Manson JE (November 2008). "Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial". JAMA 300 (17): 2012–21. DOI:10.1001/jama.2008.555. PMID 18984888. Research Blogging.
  13. Weingarten MA, Zalmanovici A, Yaphe J (2008). "Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps". Cochrane Database Syst Rev (1): CD003548. DOI:10.1002/14651858.CD003548.pub4. PMID 18254022. Research Blogging.
  14. 14.0 14.1 Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP (June 2007). "Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial". Am. J. Clin. Nutr. 85 (6): 1586–91. PMID 17556697[e]