Updated: 03/13/08 12:38 PM
HOME HEAL EDUCATE RESEARCH DIRECTORY OUTREACH

Authors: S. Shimoda, F. Silverstein, and D.R. Saunders
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I. Some Colonic Diseases

1. Polyps

Polyps are a heaping up of the lining of the gut. Most polyps are of epithelial origin. There are two types of polyps: neoplastic and non-neoplastic (see following table). Only neoplastic polyps have a tendency to become malignant.
  1. Neoplastic:
    1. tubular adenoma
    2. villous adenoma
    3. tubulo-villous adenoma
  2. Non-Neoplastic:
    1. hyperplastic (commonest, usually <0.5 cm diameter)
    2. inflammatory
    3. hamartomatous
Polyps at higher risk for cancer are > 1 cm All segments of the gut may host polyps, but the highest frequency is in the colon. At least one adult in three will eventually develop a polyp. Polyp histology is a spectrum from pedunculated, tubular adenoma to a sessile, villous adenoma. The presenting symptom is usually painless rectal bleeding. There is a small chance (3-5%) that the polyp contains a cancer; the chance increases with larger polyps. Most of these adenomatous polyps have a pedicle or stalk covered by normal mucosa and can be safely excised with an electrocautery snare. Villous lesions are usually broad based or sessile and may present with bleeding; but if they are large (>2-3 cm), they may secrete a potassium-rich fluid and cause diarrhea and hypokalemia. The chance of malignancy is much higher in these lesions, up to 15% in the larger polyps. These lesions are usually biopsied endoscopically and removed surgically. Many polyps are mixed (i.e., part villous and part tubular in structure).



Figure 9

In the hereditary disease of familial polyposis the colon is studded with polyps; adenocarcinoma invariably develops in such colons. The only therapy is to remove the colon. Other family members should also be examined to detect polyps.

Synchronous vs. metachronous lesions Patients with a polyp or a cancer have a 20% chance of having a second (synchronous) neoplasm at the time of presentation and a 7% chance of developing a later (metachronous) lesion in the subsequent year. Two to three percent (2 - 3%) of colon cancers are multifocal at the time of diagnosis. For these reasons, a colonoscopic evaluation is needed on initial presentation and long-term follow-up is essential at intervals determined by the type of initial lesion and the clinical situation.

2. Cancer

















Genetics of colon cancer 		Cancer of the colon and rectum represent 15% of all malignant neoplasms in the United States and is increasing in frequency with over 100,000 new cases detected annually. Cancer of the colon is second only to cancer of the lung as the most common cause of death from malignant disease in the U.S.A. Unlike lung or stomach cancer, colonic cancer has a good chance of being curable, especially if diagnosed early. Colonic cancer is rare in patients under 45 years of age; about 80% of newly discovered cases are in patients older than 55 years. There is a great deal of controversy over the possible connection with carcinogens, colonic stasis and prolonged transit times caused by low residue diets, high fat and high beef diets, bacterial toxins, and carcinogens either ingested or resulting from metabolic breakdown of substances such as bile acids. The genetics of some colon cancers is becoming understood. There are several well-described hereditary colon cancer family syndromes in which affected individuals have a very high likelihood of developing colon cancer. These syndromes include the “polyposis” and “nonpolyposis” colon cancer family syndromes (about 10% of all colonic cancers). The polyposis syndromes can be divided into adenomatous polyposis syndromes, which include Familial Adenomatous Polyposis (FAP) and attenuated FAP, and hamartomatous polyposis syndromes, which include Peutz-Jeghers syndrome (PJS), Juvenile Polyposis syndrome (JPS), and Cowden’s syndrome. FAP and attenuated FAP are caused by germline mutations in the APC gene, which encodes for a scaffold protein that regulates the Wnt signaling pathway, or by the MYH gene, which is a base excision repair gene. When APC gene mutations are the cause of FAP, the syndrome is inherited in an autosomal dominant fashion. When MYH mutations are the cause of FAP, the syndrome is inherited in an autosomal recessive fashion.

The nonpolyposis colon cancer family syndrome is called Lynch syndrome or Hereditary Nonpolyposis Colon Cancer (HNPCC). It is caused by germline mutations in genes that encode for members of the mutation mismatch repair proteins, which include MLH1, MSH2, PMS1, PMS2, and MSH6. This syndrome is inherited in an autosomal dominant fashion and is also associated with an increased risk for endometrial cancer, stomach cancer, and cancers of the genitourinary tract.

About 30% of colonic cancers seem to be associated with an inherited tendency to form colonic adenomas (fewer than in FAP); the family genes has not yet been discovered.
Death from colon cancer is preventable; treatment at stage of Duke A can be curative Digital rectal examination and flexible sigmoidoscopy will diagnose about 50% of these cancers. If the tumor is diagnosed before it has spread to lymphatic and blood vessels, there is an excellent chance of cure. This is really a diagnosis well worth making early and possibly the present mortality could be considerably lowered if existing diagnostic methods were used more effectively by physicians. In fact, there has been very little variation for many years in the stage of the disease at the time of surgery; about 40% are localized to the bowel wall and do not extend beyond the serosa and are therefore of the highest potential for cure. There has been little improvement in postoperative prognosis for many years. Adenocarcinoma spreads by invasion of the bowel wall and contiguous structures. It then enters lymphatics, regional nodes and veins which carry tumor cells to distant sites (metastases). Pathologists have developed a staging system for colorectal carcinomas. Stage A tumors are confined to the mucosa. Stage B1 tumors extend into but not beyond the muscularis propria while Stage B2 tumors have penetrated through the bowel wall. Stage C tumors have metastasized to regional lymph nodes. The 5-year survival rate, following surgical treatment alone, is about 80% for stage A, 65% for stage B1 and 30% for stage C. Hopefully screening for occult rectal bleeding followed by colonoscopy of heme-positive subjects will increase the number of cancers being diagnosed at the localized stage.

Carcinomas of the left and right hemicolon have distinctly different life histories. (Figure 10).



Figure 10

The capacious right colon is not easily obstructed because of its size and the liquid nature of its fecal content, therefore tumors in this area can grow to a large size without causing symptoms of obstruction such as cramping and distention. They rather present as anemia of obscure cause. The stools are found to be guaiac positive and the reason for this symptom is the oozing of blood from the ulcerated surface of the tumor. Patients with guaiac positive stools must be completely worked up with sigmoidoscopy and barium enema, or colonoscopy if we are to detect early colonic cancer. The left colon syndrome, on the other hand, is more typically one of obstruction because of the smaller diameter and the usual napkin ring obstructing nature of lesions on the left side. Furthermore, the stool is solid in this area of the colon. At least 50% of these patients have constipation, and it is especially significant if it is recent and progressive. Usually the pain from right colonic carcinoma is referred to the epigastrium or periumbilical area and that from the left colon syndrome goes to both lower quadrants.

Rectal carcinoma expresses itself mostly through interference with defecation. Bloody stools are frequent and changes in subjective sensations during defecation are not unusual.

The only curative treatment for colonic carcinoma is excision. If the tumor is well above the peritoneal reflection covering the rectum and if there is no extracolonic involvement, it can be excised with reestablishment of continuity of the bowel. If the tumor is near or below the peritoneal reflection, it is sometimes necessary to remove the whole rectum and anus and to establish a new opening of the remaining colon on the abdominal wall (colostomy).

3. Appendicitis

Appendicitis results from a closed-loop obstruction Appendicitis is the most common cause of acute abdominal pain requiring surgery in our country. It affects approximately one in every 600 people. In two-thirds of patients the acute attack is explained by obstruction of the appendix and in the others the cause is unknown. The obstruction may be caused by a fecalith, a foreign body, a fibrous stricture or hyperplastic lymph nodes. When the appendix is obstructed, the luminal contents cannot back up as they do in a bowel obstruction because both ends of the appendix are closed (closed-loop obstruction). This type of obstruction rapidly leads to distention, strangulation of the blood supply and subsequent infarction with perforation of a portion of the wall that has been destroyed. Adherent omentum or adjacent loops of bowel can prevent free perforation and in this situation a local abscess forms. Free perforation is more likely in children because the omentum is short and fragile and in the old because pre-existent arteriosclerosis of the appendiceal artery causes early appendiceal infarction before an abscess can form.

Symptoms and signs depend on the position of the appendix The major initial symptom of acute appendicitis is (intermittent) epigastric or periumbilical pain. The initial location of the pain in the epigastrium and at times in the periumbilical area reflects the derivation of the appendix from the midgut. Once the inflammation involves the serosa, the pain changes so that localized pain that is continuous now occurs wherever the inflamed serosa touches the parietal peritoneum. If the appendix is retrocecal, it may involve the ureter, kidney or posterior abdominal muscles and mimic renal disease by being felt in the flank or loin. If the appendix is buried deep in the pelvis, the pain may be mild and located in the hypogastrium (lower abdomen). If the appendix touches the peritoneum over the bladder, rectum or other pelvic organs, then any movement on rectal or vaginal examination will make the pain worse. A high retrocecal appendix may even mimic gallbladder disease where the pain is felt in the right upper quadrant. The usual site of pain is the right lower quadrant with localized tenderness to palpation in the same area.

When the appendix perforates, the pain of intestinal colic caused by increased pressure disappears abruptly, soon to be replaced by the severe steady pain of generalized peritonitis.

4. Ulcerative Colitis

Present evidence suggests that idiopathic inflammatory bowel diseases are a heterogenous family in which susceptibility to disease, phenotype, and response to therapy depend on a complex interplay of genetic and environmental factors.

Mucosa is involved predominantly














Disease is most severe distally 		Idiopathic ulcerative colitis is the most common chronic inflammatory disease of the colon in North America. Its cause is unknown (idiopathic). Ulcerative colitis primarily affects the mucosa, enabling it to be distinguished from Crohn's disease of the colon which involves the full thickness of the bowel wall and the mesentery (transmural colitis). Ulcerative colitis does not involve the small bowel. The main cause of symptoms is the widespread inflammation and ulceration of the colonic mucosa. One of its most characteristic early findings is a small abscess within the lamina propria which breaks into a crypt of Lieberkuhn - a crypt abscess. The abscesses and ulcers explain the blood, pus, fibrin, mucus in the stool and the anemia. There may be sufficient protein loss to cause hypoproteinemia. If the whole colon is involved, water resorptive function is lost and the stools become liquid and frequent, i.e. diarrhea. In general, the disease is most severe within the rectum and less severe or absent more proximally, thus sigmoidoscopy is the prime method of diagnosis. Usually, the more severe and diffuse the involvement the more ill the patient is. The majority of patients with the illness have a chronic intermittent problem although others have chronic continuous difficulty. More rarely the disease can be acute and fulminant with rapid loss of fluid, electrolytes and protein in the stools, requiring IV replacement or early colectomy to save the patient's life. Can you see why such patients develop malnutrition, electrolyte deficiencies, hypoproteinemia, and iron deficiency anemia?

A premalignant condition Patients with chronic ulcerative colitis have an increased risk of colonic adenocarcinoma, especially after ten years of disease. Colonoscopy has a role in evaluating patients with chronic ulcerative colitis, to search for cancer and to determine the extent of disease.







Colectomy is curative 		The majority of patients with idiopathic ulcerative colitis can be managed during acute attacks with parenteral replacement of fluid and electrolyte losses and corticosteroid therapy. The recurrence rate can be decreased by 5-amino salicylates if taken chronically. If the patient doesn't get well, there fortunately is a cure, i.e., removal of the entire colon (total colectomy). Intestinal continuity can be restored by using a loop of ileum as a neo-rectum which is sewn to the anal mucosa, or by bringing the terminal ileum out through an opening in the abdominal wall. These are far more acceptable solutions than one would suppose. Such patients can be completely rehabilitated and lead a normal life.



Figure 11



Figure 12

5. Aganglionic Megacolon (Hirschsprung's Disease)




The narrowest bowel is the aganglionic segment 		This is a congenital disorder which occurs more often in males and in familial clusters. Almost always constipation begins at birth and, if the patient survives beyond early infancy without surgical decompression, the more classical signs of the disease appear. There is abdominal enlargement from progressive dilatation of the large bowel and colonic peristalsis is often visible. On rectal examination the ampulla is empty and the anal sphincter tone is normal. Barium enema examination shows a narrowed area in the upper rectum or lower sigmoid with distended bowel proximal to this constricted segment. Pathologically it has been found that there is complete absence or a severe paucity of ganglia in Auerbach's and Meissner's plexuses. Although the aganglionosis is usually limited to the rectum and rectosigmoid, it may involve longer segments and occasionally includes the entire colon. At the present time there is controversy as to whether there is actual spasm of the narrowed segment or not. The other view is that this area simply cannot participate in coordinated propulsion. At any rate, either condition would lead to functional obstruction.

Treatment of Hirschsprung's Disease is mainly surgical. However, there is a spectrum of severity and the borderline cases can sometimes be managed by measures designed to empty the colon. Operations have been devised where the segment with defective innervation is removed while preserving proper anal sphincter control. The prognosis following adequate surgical treatment is usually good.

6. Diverticular Disease of the Colon

Is it a disease of the muscularis propria? Experts in the field now prefer to speak of a "diverticular disease of the colon" to include both "diverticulosis" and "diverticulitis." The reason for this is to shift attention from the diverticula to the colon itself. It used to be thought that the diverticula were the primary abnormality, but recent evidence indicates that an abnormality in behavior of colonic musculature precedes the diverticula and that this is responsible for the symptoms except when frank infection (i.e., diverticulitis) occurs.

A diverticulum is an acquired condition where there is herniation of the mucosa through the colonic muscle wall at the points of entry of the blood vessels. Any part of the colon may be affected but the sigmoid is involved most commonly.

In the presence of sigmoid diverticulosis the most striking associated finding is the marked thickening of the muscular coat. The taenia appear thick and the circular muscle is greatly thickened, giving the barium enema a "saw-toothed" appearance. It is not yet known if this represents muscular hypertrophy or hyperplasia. This muscle thickening suggests that the diverticula form because of increased intraluminal pressure. It has been shown that there is an increase in basal activity and pressures in these patients who, in addition, develop higher pressures than normal with food intake or injections of morphine or parasympathomimetics. Because of these above findings, it is presently believed that this is primarily a muscular disorder and that the diverticulosis is a late manifestation of it.

Is it a dietary disease? Diverticulosis is a common finding in Western countries and a recent English study found that one-third of persons over the age of 60 had them. On the other hand, diverticulosis appears to be far less common in areas such as Japan, China, West Africa and Russia. It is presently postulated that diverticulosis is seen in people who eat a low-residue diet. There is experimental evidence that rats fed a low-residue diet develop colons of narrow diameter and diverticula and that the addition of dietary fiber prevent this from happening.

Diverticulosis is usually symptomless although it is now believed by some that vague symptoms such as flatulence, belching and sensations of abdominal distention may be attributed to the underlying muscle abnormalities if other causes are excluded. The diagnosis of diverticulosis is made by barium enema, and sigmoidoscopy. If one is concerned that the patient's symptoms may be due to diverticulosis (once other diseases such as carcinoma have been excluded), one may prescribe a high-residue diet to increase stool size and thereby increase colonic luminal diameter, thus reducing intraluminal pressure.

May present as "left-sided appendicitis" Localized sigmoid diverticulitis with pericolic inflammation is the most common complication of diverticulosis. These episodes are thought to be caused by perforation of the diverticulum into its surrounding tissue. The symptoms and signs of the resulting peridiverticulitis can be identical with those of appendicitis except that the pain is usually felt in the left iliac fossa. In fact, diverticulitis is often referred to as left-sided appendicitis. There is usually an elevated temperature and white blood cell count and tenderness in the left lower quadrant. In contradistinction to appendicitis, diverticulitis often responds to conservative therapy consisting of intravenous feeding and the administration of broad-spectrum antibiotics. Surgery is usually reserved for complications of diverticulitis since it appears that the incidence of recurrent diverticulitis (about one-third over 5 - 15 years) is not appreciably lessened by local resection.

Abscess The complications of diverticulitis include pericolic abscess, peritonitis, fistula formation and obstruction.

Rectal bleeding The site of hemorrhage in a patient with multiple diverticula can be sought by selective angiography of the superior and inferior mesenteric arteries if bleeding is severe. Why would such information be important to the surgeon? Could this diagnostic technique also be used for therapy in certain cases?

Elective surgical treatment of diverticular disease is needed for patients with severe persistent disease, irreversible complications, and when malignancy cannot be excluded. Emergency surgery is reserved for patients with life-threatening complications. The essential of surgical treatment is resection of the affected segment with construction of an anastomosis to restore intestinal continuity. Such a procedure may be carried out in one operation if there are no complications present. In the presence of infection, a two-stage procedure consists of resection of the diseased colon, closure of the distal segment and establishment of a proximal colostomy as the first stage. The second stage is closure of the colostomy and reanastomosis of the colon in continuity.

7. Oxalate Renal Stones

Patients with steatorrhea may absorb oxalate excessively Patients who have had an ileal resection have an increased risk of developing calcium oxalate renal stones. The two conditions necessary for enhanced oxalate absorption are steatorrhea and the presence of some of the colon. Ordinarily, unabsorbed calcium precipitates with unabsorbed oxalate to form unabsorbable Ca oxalate. If there is steatorrhea, excess unabsorbed fatty acids precipitate with the calcium, so that more oxalate is able to be absorbed in The Colon. There is also some evidence that excess fatty acids and bile salts increase the permeability of the colonic mucosa to oxalate.

8. Antibiotic-Associated Colitis

Any antibiotic may be culpable Clindamycin, cephalosporins and ampicillin are the most common culprits, but any antibiotic may be associated with diarrhea and inflammation of colonic mucosa. The disorder is often recognized by finding an exudate (pseudomembrane) adhering to rectal or colonic mucosa. Biopsy reveals necrosis of superficial epithelium with a polymorphonuclear infiltrate, and an exudate of fibrin, white blood cells, and debris. The spectrum is from an appearance which resembles mild ulcerative colitis (reddened, friable rectal mucosa) to a picture which resembles toxic colitis (dilated colon with deep mucosal ulcerations).

Often it is acquired in hospitals The pathogenesis is an alteration of colonic bacteria so that there is an overgrowth of Clostridium difficile which produces cytopathic toxins. Clostridium difficile colitis may account for 20% of cases of antibiotic-associated diarrhea. C. difficile forms spores so the organism is disseminated in institutions.

The treatment of antibiotic-associated colitis consists of stopping the offending antibiotic, and, if necessary, using an antibiotic to quell the Cl. difficile.

9. Infectious Colitis

Infectious colitis is the most common cause of acute bloody diarrhea. This illness is self-limited, and lasts less than two weeks. The most common bacteria which cause colitis are Salmonella, Shigella, Campylobacter, and enterohemorrhagic E. coli. Yersinia can cause colitis but more commonly presents as acute ileitis, thus mimicking acute appendicitis.

Receptive anal sexual intercourse may lead to rectal inflammation; several different organisms have been implicated, including Chlamydia trachomatis, N. gonococcus, syphilis, and Herpes virus type II.

The proctoscopic findings of diffusely friable mucosa are very nonspecific and do not differentiate between infectious colitis and idiopathic ulcerative colitis.

Amebiasis may also present as acute diarrhea - discrete ulcers in the rectal mucosa are seen at sigmoidoscopy.

Stool culture and exam for ova and parasites is probably the easiest and cheapest method of discovering infectious colitis. Rectal biopsy can usually distinguish between acute self-limited colitis and inflammatory bowel disease.

Specific antibiotic therapy depends on the organism involved. Often no specific pathogen will be cultured. The illness is usually self-limited and may resolve without therapy.

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