Colorectal cancer

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 third 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-shaped 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 symptoms of colorectal cancer depend on the location of tumor in bowel and whether it has spread to elsewhere in the body (metastasis). Most of the symptoms may occur in other diseases as well, and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. Symptoms and signs are divided into local, constitutional (affecting the whole body) and metastatic (caused by spread to other organs).

Local symptoms: Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (new-onset constipation or diarrhea in the absence of another cause), and a feeling of incomplete defecation (tenesmus) and reduction in diameter of stool; tenesmus and change in stool shape are both characteristic of rectal cancer. Lower gastrointestinal bleeding, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus. Melena, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer) but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel.

A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. This situation is characterized by constipation, abdominal pain, abdominal distension and vomiting. This occasionally leads to the obstructed and distended bowel perforating and causing peritonitis.

Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination. The disease may invade other organs, and may cause blood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract).

Constitutional symptoms: If a tumor has caused chronic occult bleeding, iron deficiency anemia may occur; this may be experienced as fatigue, palpitations and noticed as pallor (pale appearance of the skin). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite.

More unusual constitutational symptoms are an unexplained fever and one of several paraneoplastic syndrome. The most common paraneoplastic syndrome is thrombosis, usually deep vein thrombosis.

Metastatic symptoms: Colorectal cancer most commonly spreads to the liver. This may go unnoticed, but large deposits in the liver may cause jaundice and abdominal pain (due to stretching of the capsule). If the tumor deposit obstructs the bile duct, the jaundice may be accompanied by other features of biliary obstruction, such as pale stools.

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.[3]
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:

Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated
Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives.[4]
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."[5][6]
Diet. Studies show that a diet high in red meat[7] 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.[8] 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.[9] 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.[10][11]
Inflammatory bowel disease.[12][13] 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.[14]
Environmental factors.[12] Industrialized countries are at a relatively increased risk compared to less developed 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.[15] 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.[16]
Alcohol. Drinking, especially heavily, may be a risk factor.[17]

Colorectal cancer Diagnosis, screening and monitoring:
Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. The National Cancer Policy Board of the Institute of Medicine estimated in 2003 that even modest efforts to implement colorectal cancer screening methods would result in a 29 percent drop in cancer deaths in 20 years. Despite this, colorectal cancer screening rates remain low.[32] Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose.

Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test.
Fecal occult blood test (FOBT): a test for blood in the stool. Two types of tests can be used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specifity.[33]
Endoscopy:
Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities.
Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be immediately removed. Tissue can also be taken for biopsy.

In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options.

Other screening methods

Double contrast barium enema (DCBE): First, an overnight preparation is taken to cleanse the colon. An enema containing barium sulfate is administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp.
Virtual colonoscopy replaces X-ray films in the double contrast barium enema (above) with a special computed tomography scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy.
Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons.
Blood tests: Measurement of the patient's blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. These tests are frequently false positive or false negative, and are not recommended for screening, it can be useful to assess disease recurrence.
Genetic counseling and genetic testing for families who may have a hereditary form of colon cancer, such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP).
Positron emission tomography (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rate, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases.
Whole-Body PET imaging is the most accurate diagnostic test for detection of recurrent colorectal cancer, and is a cost-effective way to differentiate resectable from non-resectable disease. A PET scan is indicated whenever a major management decision depends upon accurate evaluation of tumour presence and extent.
Stool DNA testing is an emerging technology in screening for colorectal cancer. Pre-malignant adenomas and cancers shed DNA markers from their cells which are not degraded during the digestive process and remain stable in the stool. Capture, followed by PCR amplifies the DNA to detectable levels for assay. Clinical studies have shown a cancer detection sensitivity of 71%-91%.[34]

Colorectal cancer Treatment:
The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However, when it is detected at later stages (when distant metastases are present) it is less likely to be curable.

Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.

Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest that "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management.[40]

All treatments have complications, which may sometimes result in death.
Surgery

Surgeries can be categorised into curative, palliative, or open-and-close.

Curative:
Curative surgical treatment can be offered if the tumor is localized.

Very early cancer that develops within a polyp can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy.
When a colon tumor is larger than a polyp, it typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce the probability of local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created.
Curative surgery for rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision.
Surgical removal of a single isolated metastasis to the liver may be curative in a few patients; improved chemotherapy has increased the number of patients who are candidates for this treatment.

Laparoscopic-assisted colectomy is a minimally invasive procedure that can reduce the size of the incision and post-operative pain.

Palliative:
In case of multiple metastases, curative surgery is not possible. However, palliative (non curative) resection of the primary tumor may reduce morbidity caused by tumor bleeding, invasion, obstruction, and its catabolic effect. If an obstructing tumor invades into adjacent vital structures which makes excision impossible, the surgeons may prefer to perform an intestinal bypass (e.g., ileotransverse bypass) or to do a proximal fecal diversion through a stoma.

Open-and-close:
The worst case would be an open-and-close surgery, when surgeons cut open the abdomen and then find the tumor unresectable (for example, because the the small bowel is involved); any more procedures would do more harm than good. Therefore they close the abdomen. This is uncommon with the advent of CT scans and MRI. Most cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided.

Colorectal cancer
Campylobacter Infections Pneumonia Carcinoid Tumors Spleen Diseases Bacterial vaginosis Toxoplasmosis Meningococcal Disease Vaginal Diseases Stomach cancer Ingrown Nail Giardiasis Cardiogenic shock Scoliosis Chronic Diarrhea Urinary Tract And Bladder Infections Aortic Stenosis Mitral Valve Prolapse Colorectal cancer Liver cancer Yersinia Enterocolitica Kaposi's Sarcoma Leukemia, Adult Acute Shigellosis Sickle-cell disease Adenoviridae Coming Soon	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 third 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-shaped 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 symptoms of colorectal cancer depend on the location of tumor in bowel and whether it has spread to elsewhere in the body (metastasis). Most of the symptoms may occur in other diseases as well, and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. Symptoms and signs are divided into local, constitutional (affecting the whole body) and metastatic (caused by spread to other organs). Local symptoms: Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (new-onset constipation or diarrhea in the absence of another cause), and a feeling of incomplete defecation (tenesmus) and reduction in diameter of stool; tenesmus and change in stool shape are both characteristic of rectal cancer. Lower gastrointestinal bleeding, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus. Melena, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer) but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel. A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. This situation is characterized by constipation, abdominal pain, abdominal distension and vomiting. This occasionally leads to the obstructed and distended bowel perforating and causing peritonitis. Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination. The disease may invade other organs, and may cause blood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract). Constitutional symptoms: If a tumor has caused chronic occult bleeding, iron deficiency anemia may occur; this may be experienced as fatigue, palpitations and noticed as pallor (pale appearance of the skin). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite. More unusual constitutational symptoms are an unexplained fever and one of several paraneoplastic syndrome. The most common paraneoplastic syndrome is thrombosis, usually deep vein thrombosis. Metastatic symptoms: Colorectal cancer most commonly spreads to the liver. This may go unnoticed, but large deposits in the liver may cause jaundice and abdominal pain (due to stretching of the capsule). If the tumor deposit obstructs the bile duct, the jaundice may be accompanied by other features of biliary obstruction, such as pale stools. 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.[3] 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: Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives.[4] 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."[5][6] Diet. Studies show that a diet high in red meat[7] 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.[8] 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.[9] 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.[10][11] Inflammatory bowel disease.[12][13] 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.[14] Environmental factors.[12] Industrialized countries are at a relatively increased risk compared to less developed 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.[15] 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.[16] Alcohol. Drinking, especially heavily, may be a risk factor.[17] Colorectal cancer Diagnosis, screening and monitoring: Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. The National Cancer Policy Board of the Institute of Medicine estimated in 2003 that even modest efforts to implement colorectal cancer screening methods would result in a 29 percent drop in cancer deaths in 20 years. Despite this, colorectal cancer screening rates remain low.[32] Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose. Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test. Fecal occult blood test (FOBT): a test for blood in the stool. Two types of tests can be used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specifity.[33] Endoscopy: Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities. Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be immediately removed. Tissue can also be taken for biopsy. In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options. Other screening methods Double contrast barium enema (DCBE): First, an overnight preparation is taken to cleanse the colon. An enema containing barium sulfate is administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp. Virtual colonoscopy replaces X-ray films in the double contrast barium enema (above) with a special computed tomography scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy. Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons. Blood tests: Measurement of the patient's blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. These tests are frequently false positive or false negative, and are not recommended for screening, it can be useful to assess disease recurrence. Genetic counseling and genetic testing for families who may have a hereditary form of colon cancer, such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP). Positron emission tomography (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rate, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases. Whole-Body PET imaging is the most accurate diagnostic test for detection of recurrent colorectal cancer, and is a cost-effective way to differentiate resectable from non-resectable disease. A PET scan is indicated whenever a major management decision depends upon accurate evaluation of tumour presence and extent. Stool DNA testing is an emerging technology in screening for colorectal cancer. Pre-malignant adenomas and cancers shed DNA markers from their cells which are not degraded during the digestive process and remain stable in the stool. Capture, followed by PCR amplifies the DNA to detectable levels for assay. Clinical studies have shown a cancer detection sensitivity of 71%-91%.[34] Colorectal cancer Treatment: The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However, when it is detected at later stages (when distant metastases are present) it is less likely to be curable. Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors. Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest that "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management.[40] All treatments have complications, which may sometimes result in death. Surgery Surgeries can be categorised into curative, palliative, or open-and-close. Curative: Curative surgical treatment can be offered if the tumor is localized. Very early cancer that develops within a polyp can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy. When a colon tumor is larger than a polyp, it typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce the probability of local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created. Curative surgery for rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision. Surgical removal of a single isolated metastasis to the liver may be curative in a few patients; improved chemotherapy has increased the number of patients who are candidates for this treatment. Laparoscopic-assisted colectomy is a minimally invasive procedure that can reduce the size of the incision and post-operative pain. Palliative: In case of multiple metastases, curative surgery is not possible. However, palliative (non curative) resection of the primary tumor may reduce morbidity caused by tumor bleeding, invasion, obstruction, and its catabolic effect. If an obstructing tumor invades into adjacent vital structures which makes excision impossible, the surgeons may prefer to perform an intestinal bypass (e.g., ileotransverse bypass) or to do a proximal fecal diversion through a stoma. Open-and-close: The worst case would be an open-and-close surgery, when surgeons cut open the abdomen and then find the tumor unresectable (for example, because the the small bowel is involved); any more procedures would do more harm than good. Therefore they close the abdomen. This is uncommon with the advent of CT scans and MRI. Most cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided.
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