Colorectal cancer

Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the third most common form of cancer and the second leading cause of cancer-related death in the Western world.[1] Many colorectal cancers are thought to arise from adenomatous polyps in the colon. These mushroom-like growths are usually benign, but some may develop into cancer over time. The majority of the time, the diagnosis of localized colon cancer is through colonoscopy. Therapy is usually through surgery, which in many cases is followed by chemotherapy.
Symptoms
The first symptoms of colon cancer are usually vague, like bleeding, weight loss, and fatigue (tiredness). Local (bowel) symptoms are rare until the tumor has grown to a large size. Generally, the nearer the tumor is to the anus, the more bowel symptoms there will be.
Symptoms and signs are divided into local, constitutional and metastatic.
Local symptoms
* Change in bowel habits
o Change in frequency (constipation and/or diarrhea),
o Feeling of incomplete defecation (tenesmus) and reduction in diameter of stool, both characteristic of rectal cancer,
o Change in the appearance of stools:
+ Bloody stools or rectal bleeding
+ Stools with mucus
+ Black, tar-like stool (melena), more likely related to upper gastrointestinal e।g। stomach or duodenal disease
* Bowel obstruction causing bowel pain, bloating and vomiting of stool-like material।
* A tumor in the abdomen, felt by patients or their doctors.
* Symptoms related to invasion by the cancer of the bladder causing hematuria (blood in the urine) or pneumaturia (air in the urine), or invasion of the vagina causing maloderous vaginal discharge. These are late events, indicative of a large tumor.

Constitutional (systemic) symptoms
* Unexplained weight loss is a worrying symptom caused by lack of appetite and systemic effects of a malignant growth. However, weight loss is not as much a feature of colorectal cancer as it is of other cancers (e.g. oesophageal carcinoma). * Anemia, causing dizziness, fatigue and palpitations. Clinically, there will be pallor and blood tests will confirm the low hemoglobin level.
Metastatic symptoms
* Liver metastases, causing:
o Jaundice
o Pain in the abdomen, more often the upper part of epigastrium or right side of the abdomen
o liver enlargement, usually felt by a doctor
* Blood clots in the veins and arteries, a paraneoplastic syndrome related to hypercoagulability of the blood (the blood is "thickened")
Risk factors
The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person's risk of developing the disease.[2] These include:
* Age. The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present.
* Polyps of the colon, particularly adenomatous polyps, are a risk factor for colon cancer. The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer.
* History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer.
* Heredity:
o Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives
o Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated
o Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome
* Smoking. Smokers are more likely to die of colorectal cancer than non-smokers. An American Cancer Society study found that "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked."[3]
* Diet. Studies show that a diet high in red meat[4] and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the European Prospective Investigation into Cancer and Nutrition suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently eat fish showed a decreased risk.[1] However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding.[5] The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial.
* Physical inactivity. People who are physically active are at lower risk of developing colorectal cancer.
* Virus. Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer.
* Primary sclerosing cholangitis offers a risk independent to ulcerative colitis * Low levels of selenium.
* Inflammatory Bowel Disease. [6] [7] About one percent of colorectal cancer patients have a history of chronic ulcerative colitis. The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Patients with colorectal Crohn's disease have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis. [8]
* Environmental Factors. [6] Industrialized countries are at a relatively increased risk compared to less developed countries or countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers.
* Exogenous Hormones. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some sex-specific risk factor; one possibility that has been suggested is exposure to estrogens [9]. There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast,there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors. [10]
* Alcohol. Drinking, especially heavily, may be a risk factor.

Bladder cancer

Bladder cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder.[1] The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called urothelial cell or transitional cell carcinoma (UCC or TCC).
Signs and symptoms
Bladder cancer characteristically causes blood in the urine; this may be visible to the naked eye (frank hematuria) or detectable only by microscope (microscopic hematuria). Other possible symptoms include pain during urination, frequent urination (Polyuria) or feeling the need to urinate without results. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate infections and cystitis.
Causes
Risk factors
Tobacco smoking is the main known cause of urinary bladder cancer: in most populations, smoking causes over half of bladder cancer cases in men and a sizeable proportion in women. There is a linear relationship between smoking and risk, and quitting smoking reduces the risk.[2] In a 10-year study involving almost 48,000 men, researchers found that men who drank 1.5L of water a day had a significantly reduced incidence of bladder cancer when compared with men who drank less than 240mL (around 1 cup) per day. The authors proposed that bladder cancer might partly be caused by the bladder directly contacting carcinogens that are excreted in urine. It is postulated, therefore, that by drinking higher quantities of water, urine is more dilute, thereby reducing the chance of disease.[citation needed] Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. 2-Naphthylamine which is found is cigarette smoke has also been shown to increase bladder cancer risk. Occupations at risk are metal industry workers, rubber industry workers, workers in the textile industry and people who work in printing. Some studies also suggest that auto mechanics have an elevated risk of bladder cancer due to their frequent exposure to hydrocarbons and petroleum-based chemicals.[3] Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes. It has been proposed that hair dyes are a risk factor, and some have shown an odds ratio of 2.1 to 3.3 for risk of developing bladder cancer among women who use permanent hair dyes, while others have shown no correlation between the use of hair dyes and bladder cancer.[citation needed] Certain drugs such as cyclophosphamide and phenacetin are known to predispose to bladder TCC.[citation needed] Chronic bladder irritation (infection, bladder stones, catheters, bilharzia) predisposes to squamous cell carcinoma of the bladder.[citation needed] Approximately 20% of bladder cancers occur in patients without predisposing risk factors.[citation needed]
Genetics
Like virtually all cancers, bladder cancer development involves the acquisition of mutations in various oncogenes and tumor supressor genes. Genes which may be altered in bladder cancer include H19, FGFR3, HRAS, RB1 and TP53. Several genes have been identified which play a role in regulating the cycle of cell division, preventing cells from dividing too rapidly or in an uncontrolled way. Alterations in these genes may help explain why some bladder cancers grow and spread more rapidly than others.[citation needed]
A family history of bladder cancer is also a risk factor for the disease. Many cancer experts assert that some people appear to inherit reduced ability to break down certain chemicals, which makes them more sensitive to the cancer-causing effects of tobacco smoke and certain industrial chemicals.[citation needed]
Diagnosis
The gold standard of diagnosing bladder cancer is urine cytology and transurethral (through the urethra) cystoscopy. Urine cytology can be obtained in voided urine or at the time of the cystoscopy ("bladder washing"). Cytology is very specific (a positive result is highly indicative of bladder cancer) but suffers from low sensitivity (a negative result does not exclude the diagnosis of cancer). There are newer urine bound markers for the diagnosis of bladder cancer. These markers are more sensitive but not as specific as urine cytology. They are much more expensive as well. Many patients with a history, signs, and symptoms suspicious for bladder cancer are referred to a urologist or other physician trained in cystoscopy, a procedure in which a flexible tube bearing a camera and various instruments is introduced into the bladder through the urethra. Suspicious lesions may be biopsied and sent for pathologic analysis.
Pathological Classification
90% of bladder cancer are Transitional cell carcinomas (TCC) that arise from the inner lining of the bladder called the urothelium. The other 10% of tumours are squamous cell carcinoma, adenocarcinoma, sarcoma, small cell carcinoma and secondary deposits from cancers elsewhere in the body.
TCCs are often multifocal, with 30-40% of patients having more than one tumour at diagnosis. The pattern of growth of TCCs can be papillary, sessile (flat) or carcinoma-in-situ (CIS).
The 1973 WHO grading system for TCCs (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO [4] grading (papillary neoplasm of low malignant potential (PNLMP), low grade and high grade papillary carcinoma.
CIS invariably consists of cytologically high grade tumour cells.
Bladder TCC is staged according to the 1997 TNM system:
* Ta Non-invasive papillary tumour

* T1 Invasive but not as far as the muscular bladder layer

* T2 Invasive into the muscular layer

* T3 Invasive beyond the muscle into the fat outside the bladder

* T4 Invasive into surrounding structures like the prostate, uterus or pelvic wall
Staging
The following stages are used to classify the location, size, and spread of the cancer, according to the TNM (tumor, lymph node, and metastasis) staging system:
* Stage 0: Cancer cells are found only on the inner lining of the bladder.
* Stage I: Cancer cells have proliferated to the layer beyond the inner lining of the urinary bladder but not to the muscles of the urinary bladder.
* Stage II: Cancer cells have proliferated to the muscles in the bladder wall but not to the fatty tissue that surrounds the urinary bladder.
* Stage III: Cancer cells have proliferated to the fatty tissue surrounding the urinary bladder and to the prostate gland, vagina, or uterus, but not to the lymph nodes or other organs.
* Stage IV: Cancer cells have proliferated to the lymph nodes, pelvic or abdominal wall, and/or other organs.
* Recurrent: Cancer has recurred in the urinary bladder or in another nearby organ after having been treated.[5]
Treatment
The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope. Immunotherapy in the form of BCG instillation is also used to treat and prevent the recurrence of superficial tumors.[6] BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy, such as valrubicin (Valstar) into the bladder can also be used to treat BCG-refractory CIS disease when cystectomy is not an option[7].
Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.
A combination of radiation and chemotherapy can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.
There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statins is associated with failure of BCG immunotherapy.[8]
The hemocyanin found in Concholepas concholepas blood has immunotherapeutic effects against bladder and prostate cancer. In a research made in 2006 mice were primed with C. concholepas before implantation of bladder tumor (MBT-2) cells. Mice treated with C. concholepas showed a significant antitumor effect as well. The effects included prolonged survival, decreased tumor growth and incidence and lack of toxic effects.[9]
Epidemiology
In the United States, bladder cancer is the fourth most common type of cancer in men and the ninth most common cancer in women. More than 47,000 men and 16,000 women are diagnosed with bladder cancer each year. One reason for its higher incidence in men is that the androgen receptor, which is much more active in men than in women, plays a major part in the development of the cancer.[10]

Anal cancer

Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a squamous cell carcinoma that arises near the squamocolumnar junction.

Prevalence

The ACS estimates that in 2008 about 5,070 new cases of anal cancer will be diagnosed in the United States (about 3,000 in women and 2,000 in men).[1] It is typically found in adults, average age early 60s.[1]In the US, an estimated 680 people will die of anal cancer in 2008.[1]

Risk factors

* Human papillomavirus (HPV) infection: An examination of squamous cell carcinoma tumor tissues from patients in Denmark and Sweden showed a high proportion of anal cancers to be positive for the types of HPV that are also associated with high risk of cervical cancer (90% of the tumors from women, 100% of the tumors from homosexual men, and 58% of tumors from heterosexual men).[2] In another study done, high-risk types of HPV, notably HPV-16, were detected in 84 percent of anal cancer specimens examined.[3]

* Sexual activity: Having multiple sex partners or having anal sex, due to the increased risk of exposure to the HPV virus.[4]

* Smoking: Current smokers are several times more likely to develop anal cancer compared with nonsmokers.[4]

* Immunosuppression, which is often associated with HIV infection.[4]

* Benign anal lesions. (inflammatory bowel disease (IBD)[5], hemorrhoids, fistulae or cicatrices) Inflammation resulting from benign anal lesions, such as hemorrhoids and anal fistulas, has been considered to cause a predisposition to anal cancer [6] [7]

* Men who have sex with men are 17 times more likely to develop anal cancer than men who do not have sex with men.[8]

Prevention

Since many, if not most, anal cancers derive from Human papillomavirus infections, and since the HPV vaccine prevents infection by some strains of the virus and has been shown to reduce some potentirally precancerous lesions[9], scientists surmise that HPV vaccination may prevent anal cancer.[10]

Screening

Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals.[11][12] There is concern among researchers that the CDC is exhibiting prejudice and homophobia toward their stance on anal papsmear and cancer prevention. According to the CDC’s fact sheet, "there is no clear benefit to knowing you have this virus – since HPV in unlikely to affect your health and cannot be treated." But some researchers believes that HPV can and does affect the health of thousands of men, especially those living with HIV. In a 1987 report, it was estimated that incidence of anal cancer among HIV-negative men who engage in receptive anal intercourse with other men was up to 35/100,000 – a rate on a par with the incidence of cervical cancer before routine Pap smears were initiated in the 1940s. The incidence of anal cancer among gay men with AIDS was suggested in one report to be twice that of men of the same age, race, and sexual orientation in the years before AIDS (1975 to 1979). In other words, the incidence of anal cancer may be more than 70 of every 100,000 HIV-infected men who have a history of receptive anal intercourse with other men. In one San Francisco cohort consisting of more than 600 MSM, anal dysplasia was found in 36% of the HIV-positive men and 7% of the HIV-negative men. According to Dr. Joel Palefsky of the University of California, San Francisco, these and other observations "would suggest that we should be mounting all-out campaigns to educate people around these issues and immediately implement screening and treatment programs to prevent anal cancer, modeled after the highly successful programs to prevent cervical cancer."[13]

Treatment

Localized disease

Anal cancer is most effectively treated with surgery, and in early stage disease (i.e., localized cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies.

In more recent years, physicians have employed a combination strategy including chemotherapy and radiation treatments to reduce the necessity of debilitating surgery. This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy active in anal cancer includes cisplatin and 5-FU; mitomycin has also been used, but is associated with increased toxicity.

Metastatic or recurrent disease

Up to 10% of patients treated for anal cancer will develop distant metastatic disease. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. J.D. Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU.

Prognosis

Based on series of 270 patients, the five year survival by stage was[citation needed]:

T1 — 86 percent
T2 — 86 percent
T3 — 60 percent
T4 — 45 percent
N0 — 76 percent
Node-positive — 54 percent

Signs and symptoms

Roughly, cancer symptoms can be divided into three groups:

* Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice (yellowing the eyes and skin)

* Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom

* Systemic symptoms: weight loss, poor appetite, fatigue and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Classification

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. These are the histology and the location, respectively. Examples of general categories include:

* Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer

* Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells

* Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cell

* Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull)

* Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.

Malignant tumors (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumors (which are not cancers) 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). Unfortunately, some cancers also use the -oma suffix, examples being melanoma and seminoma.

Cancer

Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age.[1] Cancer causes about 13% of all deaths.[2] According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007.[3] Cancers can affect all animals.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells[citation needed]. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers are usually affected by complex interactions between carcinogens and the host's genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.