Download isorders of Gastrointestinal Tract for Dental Students

Disorders of the
Gastrointestinal Tract
For Dental Students
Dr. Rana Bokhary, MD, FRCPC
Disorders of Gastrointestinal Tract for Dental Students 2009
Oral Cavity
Oral Pseudomembranous Candidiasis (Thrush, Moniliasis):
 Candida Albicans is a normal inhabitant of oral cavity in 30-40%
of population.
 Is the most common fungal infection of oral cavity.
 Grossly: Adherent white, curdlike, circumscribed plaque anywhere
within oral cavity.
 Can be scraped off to reveal an underlying granular erythematous
inflammatory base.
 Microscopically: The pseudomembrane is composed of matted
fungal organisms superficially attached to the underlying mucosa.
 The fungi can be identified as boxcar-like chains of tubular cells
producing pseudohyphae from which bud yeast forms.
 Results from impairment of the usual protective mechanisms:
1. Immunodeficiency states, particularly AIDS
2. DM
3. Debilitating diseases as disseminated cancer
4. Aneamia
5. Glucocorticoid therapy or broad spectrum antibiotics
 If gains entry to bloodstream  disseminated candidiasis which is
a life-threatening condition that needs aggressive Rx.
Esophagus
Hematemesis:
Definition: Vomiting of blood.
Causes:
1) Diseases of the esophagus:
o Esophageal varices
o Esophagitis
o Peptic ulcer
o Carcinoma
o Mediastinal tumors infiltrating the esophagus
o Aortic aneurysm rupturing into the esophagus
2) Diseases of the stomach:
o Peptic ulcer (65%)
o Gastritis
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Disorders of Gastrointestinal Tract for Dental Students 2009
o Multiple erosions
o Acute ulcer
o Gastric tumors (carcinoma)
3) Diseases of the duodenum:
o Acute ulcer
o Peptic ulcer
o Tumors (carcinoma)
4) Blood disorders:
o Haemophilia
o Leukemias
5) Vitamin deficiency:
o Vitamin C
o Vitamin K
Esophagitis:
Definition: Is an inflammation of the esophageal mucosa 2ry to injury.
Incidence:
 Is a common disorder worldwide.
 In Northern Iran, the prevalence of esophagitis is > 80%.
 It is also extremely high in regions of China .
 This has unknown basis.
 In USA & other western countries it is 10 - 20% “mainly reflux
esophagitis”.
Causes:
 Reflux esophagitis, due to reflux of gastric contents.
 Prolonged gastric intubation.
 Ingestion of irritants “e.g. alcohol, corrosive acids”.
 Cytotoxic anticancer therapy = chemotherapy.
 Infection 2ry to bacteremia, vireamia or fungal infection “e.g.
HSV, CMV, Candida”.
 Uremia.
 Radiotherapy directed to thorax.
 Graft-versus-host disease.
 Systemic conditions such as hypothyroidism “↓LES tone”.
 Is an inflammation of the esophageal mucosa 2ry to injury
Reflux Esophagitis:
Definition: Inflammation of the esophagus 2ry to reflux of gastric
contents into esophagus.
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Disorders of Gastrointestinal Tract for Dental Students 2009
 It is the most common cause of esophagitis in western countries
“affects ~ 0.5% of US adults”.
Clinical features:
 Largely limited to adults > 40 years of age.
 Occasionally seen in infants and children.
 Manifestations:
o Mainly heartburn & sometimes regurgitation of a sour brash.
o Rarely results in severe chest pain mimicking a heart attack.
Complications:
 Bleeding.
 Development of stricture.
 Barrett’s esophagus.
Gross Morphology:
 Depends on causative agent & on duration & severity of the
exposure.
 Mild esophagitis: Simple hyperemia.
 Severe esophagitis: Confluent erosions to total mucosal ulceration.
Microscopic Morphology:
 In uncomplicated reflux esophagitis, three microscopic features are
present:
1. Eosinophils, with or without neutrophils within the surface
epithelial layer.
2. Basal zone hyperplasia.
 Elongation of lamina propria papillae.
Barrett’s Esophagus:
Definition: Is the replacement of normal distal stratified squamous
mucosa by metaplastic columnar epithelium containing goblet cells.
Incidence:
 It is a complication of long-standing GE reflux, occurring in 5-15%
of patients with persistent reflux disease.
 M:F = 4:1 & occurs mainly in white individuals.
Complications:
 Bleeding.
 Ulceration  stricture.
 Esophageal adenocarcinoma: Patients have ~ 30 to 100-fold greater
risk compared to normal population. The greatest risk is associated
with high-grade dysplasia.
 Therefore, periodic endoscopy & screening biopsies is recommended.
 High-grade dysplasia requires intervention by surgery, photodynamic
ablation or very careful surveillance.
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Disorders of Gastrointestinal Tract for Dental Students 2009
Esophageal Carcinoma:
 Two major types: squamous cell carcinoma (SCC) & adenocarcinoma.
Epidemiology:
 In USA there is continuous increase in incidence of
adenocarcinoma 2ry to Barrett esophagus (> SCC).
 But Worldwide, SCC constitute 90% of esophageal cancers.
 Striking geographic differences.
 Areas of high incidence include China & Iran (20% of all cancer
deaths, affect ~ 100 / 100,000 yearly) – mainly SCC.
 In USA, it affects ~ 6 / 100,000 yearly. Blacks> whites (1-2% of
all cancer deaths).
 Adenocarcinoma is more common in whites while SCC is more
common in blacks.
I) Esophageal Squamous cell Carcinoma:
Risk Factors:
 Esophageal disorders:
o Long standing eosophagitis
o Achalasia
o Plummer-Vinson syndrome “esophageal web, microcytic
hypochromic anemia & atrophic glossitis”
 Dietary factors:
o Fungal contamination of foodstuffs
o High content of nitrosamine/nitrites “China”
o Vitamin deficiencies “A & C, pyridoxine, riboflavin”
o Deficiency of trace metals “Zinc”
 Life-style:
o Smoking “tobacco”
o Alcohol consumption
 Genetic predisposition:
o Tylosis “hyperkearatosis of palms & soles”
Gross Morphology:
 Like squamous cell carcinomas arising in other locations, those of
the esophagus begin as epithelial dysplasia  carcinoma in-situ 
invasive cancer
 Site:
 20% of these tumors are located in the upper third
 50% in the middle third
 30% in the lower third of the esophagus
 Early lesions appear as small, thickening or elevation of mucosa.
 Advanced lesion may take one of three forms:
1. Polypoid exophytic mass protruding into the lumen (60%).
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Disorders of Gastrointestinal Tract for Dental Students 2009
2. Diffuse, infiltrative form  thickening & rigidity of the wall with
narrowing of the lumen (15%).
3. Necrotizing cancerous ulceration (25%) that may erode into:
A. Respiratory tree (causing pneumonia)
B. Aorta (with catastrophic exsanguination)
C. May permeate the mediastinum & pericardium
 Local extension into adjacent mediastinal structures occurs early
and limits the chance of curative resection.
 Prognosis is generally poor.
 Remain asymptomatic, often discovered too late to permit cure.
 Gradual dysphagia & obstruction appear late.
Microscopic Morphology:
 Most squamous cell carcinomas are moderately to well
differentiated malignant tumors.
II) Esophageal Adenocarcinoma:
Epidemiology & Risk Factors:
 They represent > half of cancers in the distal third of the
esophagus.
 More common in whites.
 Occur in individuals >40 years of age.
 Males > females.
 Barrett esophagus is the only recognized precursor lesion.
 May be discovered early during course of endoscopic screening.
 Poor prognosis, <15% 5-year survival.
Gross Morphology:
 Usually located in the distal esophagus & may invade the adjacent
gastric cardia.
 Initially they look like flat or raised patches.
 Later they look as large nodular masses,
 Diffusely infiltrative or
 Ulcerative lesion.
 At the time of diagnosis, most tumors have invaded through the
wall of the esophagus into serosa.
Microscopic Morphology:
 Most are mucin-producing glandular tumors.
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Disorders of Gastrointestinal Tract for Dental Students 2009
Stomach
Gastritis:
Definition: It is inflammation of the gastric mucosa.
Types:
o Acute gastritis
o Chronic gastritis “most common”
Acute Gastritis:
Definition: It is an acute gastric mucosal inflammation, usually of a
transient nature.
Clinical Features:
 May be asymptomatic.
 May cause epigastric pain, nausea, vomiting, hematemesis, melena
“black stool” & potentially fatal blood loss.
Causes:
 Heavy use of NSAIDs, especially aspirin.
 Excessive alcohol consumption.
 Heavy smoking.
 Treatment with cancer chemotherapeutic drugs.
 Uremia.
 Systemic infections (e.g., salmonellosis).
 Severe stress (e.g., trauma, burns, surgery).
 Ischemia & shock.
 Suicidal attempts with acids and alkali.
 Mechanical trauma (e.g., nasogastric intubation).
 Following distal gastrectomy  reflux of bile.
Gross Morphology:
 Diffuse hyperemia & edema of gastric mucosa. These changes can
be localized.
 Ingestion of acids and alkalis produces severe mucosal damage.
May  charred the gastric mucosa.
 Superficial focal erosions & hemorrhages can be seen in some
cases.
Microscopic Morphology:
 Gastric mucosa demonstrates edema & infiltration by neutrophils.
Gastric Ulceration:
Definition: Is a breach in the mucosa of the alimentary tract that
penetrates through the muscularis mucosa into the submucosa or deeper
 heals within weeks to months.
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Disorders of Gastrointestinal Tract for Dental Students 2009
Types:
 There are 2 types of ulcers:
1) Chronic peptic ulcers
2) Acute gastric ulceration
Peptic Ulcers (PUs):
Definition: They are chronic, remitting & relapsing, most often solitary,
lesions that occur in any portion of the GIT exposed to the aggressive
action of acid-peptic juices
 98% of PUs occur either in 1st part of duodenum or in stomach
(4:1).
 Other locations for PUs:
o GEJ: in reflux esophagitis
o Margins of gastrojejunostomy
o Meckel diverticulum
Epidemiology:
 Most often diagnosed in middle-aged to older adults, but they may
first become evident in young adult life.
 Prevalence in USA is: 6-14% for men & 2-6% for women.
 Male : female duodenal ulcers is about 3:1.

gastric ulcers about 2:1.
 In US, the life time risk of developing PU is ~ 10%.
 No significant racial or genetic role.
 DUs are more frequent with alcoholic cirrhosis, chronic obstructive
pulmonary disease, chronic renal failure & hyperparathyroidism.
Pathogenesis:
 PUs are produced by an imbalance between mucosal defense
mechanisms & damaging forces
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Disorders of Gastrointestinal Tract for Dental Students 2009
 Mucosal defense mechanisms:
o Mucous secreted by surface epithelial cells
o Bicarbonate secretion to buffer acidity
o Epithelial regenerative capacity
o Effective mucosal blood flow
o Production of prostaglandins which maintain blood
circulation
 Mucosal damaging forces:
o Mucosal exposure to gastric acid & pepsin
o There is a strong association with H. pylori infection
o NSAIDs are the major cause in persons who don’t have H.
pylori “higher dose, prolonged use & advanced age”
 H. pylori are present in 70 – 90% of patients with DUs & in ~70%
of those with GUs.
 Antibiotic treatment of H. pylori promotes healing of ulcers &
prevents their recurrence.
 Only 10 – 20% of infected individuals will actually develop PUs.
 Zollinger-Ellison syndrome caused by gastrinoma (tumor of
neuroendocrine gastrin producing cells) excess gastrin secretion
and acid production  multiple peptic ulcerations in stomach,
duodenum & even jejunum.
 Other promoting factors:
o Cigarette smoking
o Alcohol especially with alcoholic cirrhosis
o Corticosteroids
o Personality & psychological stress
Morphology:
 DUs:
o Occur in the first portion of the duodenum
o Anterior wall or posterior wall “A>P”
 GUs:
o More along the lesser curvature
o Occasionally occur in the anterior or posterior walls or
along the greater curvature
 Free perforation into the peritoneal cavity may occur  localized
or generalized peritonitis.
 A thrombosed or an eroded artery may be seen at the base 
significant bleeding.
 Size does not differentiate a benign from a malignant ulcer.
Microscopic Morphology:
 In chronic ulcers four zones are seen:
1) Superficial thin layer of necrotic fibrinoid debris.
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Disorders of Gastrointestinal Tract for Dental Students 2009
2) Zone of active nonspecific inflammatory infiltrate, with
predominating neutrophils.
3) Granulation tissue.
4) Fibrous, collagenous scar.
 Vessels entrapped within the scarred area are typically thickened &
occasionally thrombosed
 Chronic gastritis & H. pylori infection in adjacent mucosa are
extremely common findings & they help to distinguish PUs from
acute gastric erosions
Clinical Features:
 Epigastric gnawing, burning, or boring pain, that is worse at night
and occurs usually 1 - 3 hours after meals during the day.
 Classically the pain is relieved by alkalis or food.
 Nausea, vomiting, bloating, belching, & significant weight loss are
additional manifestations.
 Minority may present with complications:
o Bleeding in 1/3 of patients & can be life-threatening or if
chronic  anemia
o Perforation (5%)
o Pyloric obstruction “rare”
o Malignant transformation “rare in GU (2%) & none in DU”
Gastric Carcinoma:
 Carcinoma is overwhelmingly the most common (90 to 95%)
malignant tumor of the stomach.
 Other malignant gastric tumors are:
o Lymphomas (4%)
o Carcinoids (3%)
o Stromal spindle cell tumors (2%)
Epidemiology:
 It is a worldwide disease which is the 2nd leading cause of cancer
related deaths in the world.
 Its incidence varies widely, being highest in Japan & South Korea,
high in China, Chile & Costa Rica & considerably low in the USA,
UK & Western Europe.
 There is a steady decline in its incidence & mortality in most
countries.
 Yet it remains among the leading killer cancers, representing ~2%
of all cancer deaths in US (5-year survival rate is <20%).
Classification:
 It exhibits two morphologic types:
1) Intestinal Variant
 Occurs in the setting of chronic gastritis.
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Disorders of Gastrointestinal Tract for Dental Students 2009
 Arises from gastric mucous cells that have undergone
intestinal metaplasia.
 Is better differentiated.
 Is the more common type in high-risk populations.
 Is progressively diminishing in incidence in the US.
 Occurs primarily after age 50.
 2:1 male predominance
2) Diffuse Variant
 Arises de novo from native gastric mucous cells.
 No association with chronic gastritis.
 Is poorly differentiated.
 Constitutes ~ half of gastric carcinomas in US.
 The incidence has not significantly changed in the last 60
years.
 Occurs at an earlier age than intestinal variant.
 Female predominance.
Risk Factors For Intestinal Type:
 Diet:
o Lack of refrigeration  food preservation by: nitrites 
carcinogenic nitrosamines & niterosamides “found in food,
drinking water & used as preservatives in prepared meats”.
o Smoked foods & pickled vegetables.
o Excessive salt intake.
o Decreased intake of fresh fruit and vegetables
“antioxidants”.
 Chronic gastritis with intestinal metaplasia:
o Infection with H. pylori.
o Pernicious anemia.
 Altered Anatomy:
o After partial gastrectomy.
Risk Factors For Diffuse Type:
 Risk factors remain undefined.
 Not related to H. pylori or chronic gastritis.
 No identified precursor lesions.
 Rare autosomal dominant inherited germ-line mutation of Ecadherin.
Morphology:
 The location of gastric carcinomas within the stomach is as
follows:
o Pylorus & antrum, 50 to 60%
o Cardia, 25%
o Remainder in the body & fundus
o Lesser curvature is involved in ~ 40%
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Disorders of Gastrointestinal Tract for Dental Students 2009
o Greater curvature is involved in 12%
 Thus, the favored location is the lesser curvature of the
antropyloric region.
 Although less frequent, an ulcerative lesion on the greater
curvature is more likely to be malignant.
Macroscopic Growth Patterns:
(1) Exophytic: Protrusion of the tumor mass into the lumen.
(2) Flat or depressed: in which no tumor mass is visibly obvious whithin
mucosa.
(3) Excavated “Ulcerated”:
o Shallow or deep.
o May closely mimic in size & appearance chronic PUs.
o In advanced cases, cancerous ulcers can be identified by
their heaped-up, irregular margins & shaggy, necrotic bases
as well as the overt neoplastic tissue extending into the
surrounding mucosa and wall.
 Uncommonly; a broad region of the gastric wall or the entire
stomach is extensively infiltrated by malignancy  rigid &
thickened stomach “leather bottle stomach or linitis plastica”.
 Metastatic carcinoma, from the breast and lung, may generate a
similar picture.
Histologic Appearances:
 Intestinal variant:
o Composed of neoplastic intestinal glands resembling those
of colonic adenocarcinoma.
 Diffuse variant:
o Composed of gastric-type mucous cells that do not form
glands but rather preset as scattered individual “signet-ring”
cells or small clusters in an “infiltrative” growth pattern.
o Strong stromal desmoplastic reaction (fibrosis) creates local
rigidity of the wall.
Small & Large Intestine
Bleeding Per Rectum:
Causes:
1) Intestinal Lesions:
o Tumors
o Piles “hemorrhoids”
o Infection
 Bilharziasis
 Tuberculosis
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Disorders of Gastrointestinal Tract for Dental Students 2009
 Bacillary dysentery
 Amoebic dysentery
 Typhoid ulcer
o Anal fissure
o Anal fistula
o Colitis “e.g. IBD”
2) Bleeding Disorders:
o Haemophilia
o Purpura
o Leukemias
3) Vitamin Deficiency:
o Vitamin C
o Vitamin K
Idiopathic Inflammatory Bowel Disease (IBD):
Two types: Crohn disease (CD) & ulcerative colitis (UC).
 They share many common features.
 They are chronic, relapsing inflammatory disorders of unknown
origin.
 CD: is a noncaseating granulomatous disease “in ½ cases” that
may affect any portion of GIT from mouth to anus but most often
involves the ileum.
 UC: is a nongranulomatous disease limited to colon.
Feature
CD (SI)
CD (colon)
UC
Clinical
Fat/vitamin malabsorption
Malignant potential
Response to surgery
Yes
Yes
Poor
Yes, if ileum
Yes
Fair
No
Yes
Good
Ileum +/- colon
Skip lesions
Early
Thickened
No
Colon +/- ileum
Skip lesions
Variable
Variable
Yes
Colon only
Diffuse
Late/rare
Thin
Yes
None to slight
Deep, linear
Marked
Marked
Marked
Yes “40-60%”
Yes
Marked
Deep, linear
Marked
Moderate
Variable
Yes “40-60%”
Yes
Marked
Superficial
Mild
Mild
Mild to none
No
No
Macroscopic
Bowel region
Distribution
Stricture
Wall appearance
Dilation
Microscopic
Psudopolyps
Ulcers
Lymphoid reaction
Fibrosis
Serositis
Granulomas
Fistulas/sinuses
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Disorders of Gastrointestinal Tract for Dental Students 2009
Tumors:
Terminology:
 Polyp: is a mass that protrudes into the lumen of the gut:
o Stalked or pedunculated polyp.
o Sessile polyp “no stalk”.
Classification:
 Polyp can be:
o Non-neoplastic: These are the result of inflammation,
abnormal mucosal maturation or abnormal architecture.
o Neoplastic: These result from epithelial proliferation &
dysplasia = adenomas or adenomatous polyps. These are
precursors for malignancy.
o Hyperplastic: Most common polyps in rectum & colon.
Single  have no malignant potential. Sessile serrated
adenoma  have malignant potential.
o Can be caused by submucosal or mural tumors.
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Disorders of Gastrointestinal Tract for Dental Students 2009
Gastrointestinal Polyps
Non-neoplastic polyps
Hyperplastic polyps
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Inflammatory polyps
Lymphoid polyps
Neoplastic epithelial lesions
Benign polyps
Adenomas
Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus
Other tumors
Gastrointestinal stromal tumors
Carcinoid tumor
Lymphoma
Neoplastic Polyps – Adenomas:
 Arise as the result of epithelial proliferation & dysplasia, which
may range from mild to severe as to represent transformation to
carcinoma .
 There is strong evidence that most sporadic invasive colorectal
adenocarcinomas arise in a pre-existing adenomatous lesion.
 Range from small, often pedunculated, lesions to large neoplasms
that are usually sessile.
 Incidence in SI is very low.
 Prevalence of colonic adenomas:
o 20 to 30% < age 40
o 40 to 50% > age 60
 M=F
 Familial predisposition to sporadic adenomas among 1st degree
relatives.
 Patients have 4-fold greater risk of colorectal carcinoma.
 4 subtypes based on the epithelial architecture:
1) Tubular Adenomas (TA):
 Mostly tubular glands, resembling normal mucosa.
 Most common adenoma.
 Most are small & pedunculated.
2) Villous Adenomas (VA):
 Villous projections.
 1% of adenomas.
 Mainly large & sessile.
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Disorders of Gastrointestinal Tract for Dental Students 2009
3) Tubulovillous Adenoma (TVA):
 A mixture of the above two.
 5-10% of adenomas.
4) Sessile Serrated Adenoma (SSA):
 Serrated dysplastic epithelium lining the crypts.
 Malignant risk is correlated with:
o Polyp size:
 Maximum diameter is the chief determinant of the risk
of an adenoma harboring carcinomas.
o Histologic architecture:
 Cancer is rare in TA < 1 cm in diameter.
 Cancer likelihood is high in sessile VA > 4 cm in
diameter.
 Severe dysplasia is often found in villous areas.
o Severity of epithelial dysplasia
Tubular Adenomas:
 May occur anywhere in colon, but ~ 50% are found in the
rectosigmoid, but they can occur in the stomach and small
intestine.
 ½ are single & ½ are multiple.
 Smallest TAs are sessile.
 Larger ones pedunculated & have slender stalks 1-2 cm long with
raspberry-like heads.
 Uncommonly exceed 2.5 cm in diameter.
 Most pedunculated polyps are TAs.
Histological Features:
 The stalk is covered by normal colonic mucosa.
 The head is composed of neoplastic epithelium, forming branching
glands lined by tall, hyperchromatic, somewhat disorderly cells
which may be mucin secreting.
 The glands are separated by lamina propria.
 Mild dysplasia & epithelial atypia .
 However, all degrees of dysplasia up to intramucosal carcinoma or
invasive carcinoma into the submucosa of the stalk may be seen.
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Disorders of Gastrointestinal Tract for Dental Students 2009
Villous Adenomas:
 May occur anywhere in colon, but mainly in the rectum and
rectosigmoid.
 Occur in older individuals.
 Generally are sessile, up to 10 cm in diameter.
 Are velvety or cauliflower-like masses projecting 1-3 cm above the
surrounding normal mucosa.
Histological Features:
 Frondlike villiform extensions of mucosa covered by dysplastic,
sometimes very disorderly, sometimes piled-up, columnar
epithelium.
 All degrees of dysplasia may be encountered.
 Invasive carcinoma is found in up to 40% of cases, the frequency
correlates with the size of the polyp.
Tubulovillous Adenomas:
 Are composed of a broad mix of tubular and villous areas.
 They are intermediate between TAs & VAs in their frequency of
having a stalk or being sessile, their size, the degree of dysplasia &
the risk of harboring intramucosal or invasive carcinoma.
Clinical Features of Adenomas:
 Smaller ones are usually asymptomatic.
 May cause anemia with time due to occult bleeding.
 VA, more frequently symptomatic than others & may cause:
 Rectal bleeding; overt or occult.
 The most distal ones may secrete copious amounts of
mucoid material rich in protein and potassium 
hypoproteinemia or hypokalemia.
 Adenomas of the small intestine may be present with anemia and
rarely with obstruction or intussusceptions.
 All adenomas must be considered potentially malignant  requires
adequate excision.
Familial Adenomatous Polyposis Syndrome (FAP):
 Uncommon autosomal dominant disorder.
 Affected persons develop 500 to 2500 colonic adenomas that
carpet the mucosal surface.
 A minimum of 100 polyps is required for diagnosis.
 Multiple adenomas may also be present elsewhere in GIT,
including 100% lifetime incidence of duodenal adenomas.
 Most are tubular adenomas; they are occasionally villous.
 Polyps may become evident in adolescence or early adulthood.
 Have 100% frequency of progression to colon cancer by midlife.
 Some patients already have colorectal cancer at the time of
diagnosis.
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Disorders of Gastrointestinal Tract for Dental Students 2009
 Prophylactic colectomy is required as soon as possible.
 The genetic defect: APC gene on chromosome 5q21.
Colorectal Carcinoma:
Epidemiology:
 98% of all cancers in large intestine are adenocarcinomas.
 Peak incidence is age 60 – 70 years of age.
 < 20% of cases occur under 50 years of age.
 M > F by 20%.
 Almost always arises from adenomatous polyps.
 When found in a young person, pre-existing UC or one of the
polyposis syndromes must be suspected.
 Individuals with hereditary nonpolyposis colorectal cancer
syndrome “HNPCC or Lynch syndrome” are at high risk for
developing colorectal cancer.
 Above syndrome is caused by germ-line mutation of DNA
mismatch repair gene.
 These patients are also at increased risk of developing other
tumors, such as cholangiocarcinomas.
 Both genetic & environmental influences contribute to its
development
 Worldwide but highest incidence rates are in the US & other
developed countries
 Incidence is 30-fold lower India, South America, and Africa
 Intermediate incidence level in Japan & UK
Dietary Factors:
1. Low content of unabsorbable vegetable fibers.
2. High content of refined carbohydrates.
3. High fat content (as from meat).
4. Decreased intake of protective micronutrients, such as vitamin A,
C & E.
Colorectal Carcinogenesis:
 There are 2 pathogenetically distinct pathways for development of
colorectal cancer:
1) Adenoma – carcinoma sequence or APC/ß-catenin pathway
2) Mismatch repair or micostaellite instability pathway
 Both involve stepwise accumulation of multiple genetic mutations
but the genes in both are different.
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Disorders of Gastrointestinal Tract for Dental Students 2009
 Adenoma – Carcinoma Sequence or APC/ß-Catenin Pathway:
 Account for 80% of sporadic colon cancers.
 Genetic abnormalities are:
a. Loss of APC tumor suppressor gene
b. Mutation of K-RAS
c. 18q21 deletion
d. Loss of p53
 Mismatch Repair or Microsatellite Instability Pathway:
 Is involved in 10-15% of sporadic colon cancers.
 There is no detectable antecedent lesions or they may develop from
SSAs
 Main genetic abnormality is:
a. Inactivation of DNA mismatch repair genes
Gross Morphology:
 Distribution:
• 25% in the cecum or ascending colon
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Disorders of Gastrointestinal Tract for Dental Students 2009
• 25% in rectum & distal sigmoid
• 25% in the descending colon & proximal sigmoid
• 25% scattered elsewhere
 Mostly single & outgrew their adenomatous origin.
 Tumors in proximal colon tend to grow as polypoid, exophytic
masses. Obstruction is uncommon.
 Tumors in distal colon tend to be annular, encircling lesions 
“napkin-ring” constrictions of the bowel & narrowing of lumen.
The margins of the napkin ring are classically heaped up.
 Both penetrate bowel wall over time  firm masses on serosal
surface.
Microscopic Morphology:
 Both right-sided & left-sided colonic cancers are adenocarcinomas.
 Their differentiation range from well-differentiated to
undifferentiated, frankly anaplastic masses.
 Many tumors produce mucin, which is secreted into the gland
lumina or into the interstitium of the gut wall. These mucinous
cancers have poorer prognosis.
 80 % of anal canal cancers are squamous cell carcinomas.
 Desmoplastic stromal response  firm to hard consistency.
Clinical Features:
 Remain asymptomatic for years.
 Symptoms develop insidiously.
 Cecal and right colonic cancers: Fatigue, weakness, weight loss &
iron-deficiency anemia.
 Left-sided lesions:
o Occult bleeding “melena”.
o Changes in bowel habit.
o Crampy left lower quadrant discomfort.
 Iron deficiency anemia in an old man means GIT cancer until
proven otherwise.
Spread:
 All colorectal tumors spread by direct extension into adjacent
structures & by metastasis through lymphatics & blood vessels.
 The favored sites of metastatic spread are the regional lymph
nodes, liver, lungs, and bones, followed by many other sites,
including the serosal membranes of the peritoneal cavity.
 Metastasis is present in 25 - 30% of patients at time of diagnosis.
 Anal region carcinomas are locally invasive & metastasize to
regional lymph nodes and distant sites.
 Stage “extent” at time of diagnosis is the single most important
prognostic indicator of colorectal carcinoma.
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