Download - Colorectal carcinoma ( crc)
Colorectal Cancer (CRC)Colorectal Cancer (CRC)
One of the most common cancers in the worldOne of the most common cancers in the world
US:US: 4th most common cancer (after lung, 4th most common cancer (after lung, prostate, and breast prostate, and breast
cancers)cancers) 2nd most common cause of cancer 2nd most common cause of cancer deathdeath (after lung cancer)(after lung cancer)
2001:2001: 130,000 new cases of CRC130,000 new cases of CRC 56,500 deaths 56,500 deaths
caused by CRCcaused by CRC
Anatomic Location of CRCAnatomic Location of CRC
CecumCecum 14 %14 %
Ascending colonAscending colon 10 %10 %
Transverse colonTransverse colon12 %12 %
Descending colonDescending colon7 %7 %
Sigmoid colonSigmoid colon 25 %25 %
Rectosigmoid junct.9 Rectosigmoid junct.9 %%
RectumRectum 23 %23 %
Symptoms associated with CRCSymptoms associated with CRC
Colon cancers result from a series of pathologic changes that Colon cancers result from a series of pathologic changes that transform normal epithelium into invasive carcinoma. Specific transform normal epithelium into invasive carcinoma. Specific genetic events, shown by vertical arrows, accompany this genetic events, shown by vertical arrows, accompany this multistep process. multistep process.
WHO Classification of CRCWHO Classification of CRC
Adenocarcinoma in situ / severe dysplasiaAdenocarcinoma in situ / severe dysplasiaAdenocarcinomaAdenocarcinomaMucinous (colloid) adenocarcinoma (>50% Mucinous (colloid) adenocarcinoma (>50% mucinous)mucinous)Signet ring cell carcinoma (>50% signet ring Signet ring cell carcinoma (>50% signet ring cells)cells)Squamous cell (epidermoid) carcinomaSquamous cell (epidermoid) carcinomaAdenosquamous carcinomaAdenosquamous carcinomaSmall-cell (oat cell) carcinomaSmall-cell (oat cell) carcinomaMedullary carcinomaMedullary carcinomaUndifferentiated CarcinomaUndifferentiated Carcinoma
Risk factors for CRCRisk factors for CRC
AgeAge
Adenomas, PolypsAdenomas, Polyps
Sedentary lifestyle, Diet, ObesitySedentary lifestyle, Diet, Obesity
Family History of CRCFamily History of CRC
Inflammatory Bowel Disease (IBD)Inflammatory Bowel Disease (IBD)
Hereditary Syndromes (familial Hereditary Syndromes (familial adenomatous polyposis (FAP))adenomatous polyposis (FAP))
Development of CRCDevelopment of CRC
Result of interplay between environmental and Result of interplay between environmental and genetic factorsgenetic factors
Central environmental factors: Central environmental factors:
Diet and lifestyleDiet and lifestyle
35% of all cancers are attributable to diet 35% of all cancers are attributable to diet
50%-75% of CRC in the US may be preventable 50%-75% of CRC in the US may be preventable through dietary modificationsthrough dietary modifications
Dietary factors implicated in Dietary factors implicated in colorectal carcinogenesiscolorectal carcinogenesis
Increased riskIncreased risk
consumption of red consumption of red meatmeat
animal and saturated animal and saturated fatfat
refined carbohydratesrefined carbohydrates
alcoholalcohol
Dietary factors implicated in Dietary factors implicated in colorectal carcinogenesiscolorectal carcinogenesis
Decreased riskDecreased risk
dietary fiberdietary fiber
vegetablesvegetables
fruitsfruits
antioxidant vitaminsantioxidant vitamins
calciumcalcium
folate (B Vitamin)folate (B Vitamin)
Specimen containing an invasive colorectal carcinoma and Specimen containing an invasive colorectal carcinoma and two adenomatous polyps.two adenomatous polyps.
Multiple adenomatous polyps of the cecum are seen here in a Multiple adenomatous polyps of the cecum are seen here in a case of familial polyposiscase of familial polyposis..
Familial polyposis in which mucosal surface of the colon is a carpet Familial polyposis in which mucosal surface of the colon is a carpet of small adenomatous polyps. Even though they are small , there is of small adenomatous polyps. Even though they are small , there is a 100% risk over time for development of adenocarcinoma, for a 100% risk over time for development of adenocarcinoma, for which total colectomy is recommendedwhich total colectomy is recommended
Adenocarcinoma of the rectosigmoid region . Heaped up margin of Adenocarcinoma of the rectosigmoid region . Heaped up margin of tumor at each side with a central area of ulceration. Normal mucosa at tumor at each side with a central area of ulceration. Normal mucosa at the right. The tumor encircles the colon and infiltrates into the wall. the right. The tumor encircles the colon and infiltrates into the wall. Staging is based upon the degree of invasion into and through the wall.Staging is based upon the degree of invasion into and through the wall.
Adenocarcinoma of the cecum demonstrates an exophytic growth Adenocarcinoma of the cecum demonstrates an exophytic growth pattern.pattern.
The barium enema instills the radiopaque barium sulfate into the colon, The barium enema instills the radiopaque barium sulfate into the colon, producing a contrast with the wall of the colon that highlights any masses producing a contrast with the wall of the colon that highlights any masses present. In this case, the classic "apple core” lesion is present, representing an present. In this case, the classic "apple core” lesion is present, representing an encircling adenocarcinoma that constricts the lumen.encircling adenocarcinoma that constricts the lumen.
Staging of CRCStaging of CRCTNM systemTNM system
Primary tumor (T) Primary tumor (T)
Regional lymph nodes (N)Regional lymph nodes (N)
Distant metastasis (M)Distant metastasis (M)
*Note: Tis includes cancer cells confined within the glandular basement membrane *Note: Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through the (intraepithelial) or lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa. muscularis mucosae into the submucosa.
**Note: Direct invasion in T4 includes invasion of other segments of the colorectum **Note: Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa; for example, invasion of the sigmoid colon by a carcinoma by way of the serosa; for example, invasion of the sigmoid colon by a carcinoma of the cecum. of the cecum.
Dukes staging systemDukes staging system
AA MucosaMucosa 80%80%
BB Into or through M. propriaInto or through M. propria50%50%
C1C1 Into M. propria, + LN !Into M. propria, + LN !40%40%
C2C2 Through M. propria, + LN!Through M. propria, + LN!12%12%
DD distant metastatic spread <5%distant metastatic spread <5%
Sites of metastasisSites of metastasis
Liver
Lung
Brain
Bone
Via blood
Lymph nodes
Abdominal wall
Nerves
Vessels
Via lymphatics Per continuitatem
TherapyTherapy
Surgical resection the only curative Surgical resection the only curative treatmenttreatment
Likelihood of cure is greater when disease Likelihood of cure is greater when disease is detected at an early stageis detected at an early stage
Early detection and screening is of pivotalEarly detection and screening is of pivotal
importanceimportance
Surgery is the mainstay of treatment of RCSurgery is the mainstay of treatment of RC
After surgical resection, local failure is commonAfter surgical resection, local failure is common
Local recurrence after conventional surgery:Local recurrence after conventional surgery:
15%-45% (average of 28%)15%-45% (average of 28%)
Radiotherapy significantly reduces the number Radiotherapy significantly reduces the number of local recurrences in rectal cancers, its use in of local recurrences in rectal cancers, its use in colon cancer is not routine due to the sensitivity colon cancer is not routine due to the sensitivity of the bowels to radiation. of the bowels to radiation.
Radiotherapy in the management Radiotherapy in the management of Rectal Cancerof Rectal Cancer
In at least 28 randomised trials the value of In at least 28 randomised trials the value of either preoperative or postoperative RT has either preoperative or postoperative RT has been testedbeen tested
Preoperative RT (30+Gy): 57% relative Preoperative RT (30+Gy): 57% relative reduction of local failurereduction of local failurePostoperative RT (35+Gy): 33% relative Postoperative RT (35+Gy): 33% relative reductionreduction
Colorectal Cancer Collaborative Group. Lancet Colorectal Cancer Collaborative Group. Lancet 2001;358:12912001;358:1291
Gamma C. JAMA 2000;284:1008Gamma C. JAMA 2000;284:1008
Adjuvant Therapy of Rectal Adjuvant Therapy of Rectal CancerCancer
1990 US NIH Consensus Conference1990 US NIH Consensus Conference
Postoperative chemoradiotherapy = Postoperative chemoradiotherapy = standard of care for RC Stage II,IIIstandard of care for RC Stage II,III
The consensus statement was based The consensus statement was based upon the results of three randomised trialsupon the results of three randomised trials
ESMO RecommendationsESMO Recommendations
Resectable casesResectable cases
Surgical procedure: TMESurgical procedure: TME
Preoperative RT: recommendedPreoperative RT: recommended
Postoperative chemoradiotherapy: T3,4 or Postoperative chemoradiotherapy: T3,4 or N+N+
Non-resectable cases: local recurrencesNon-resectable cases: local recurrences
Preoperative RT with or without CT Preoperative RT with or without CT
Predicting risk of recurrence in Predicting risk of recurrence in Rectal CarcinomaRectal Carcinoma
Surgery-relatedSurgery-related-Low anterior resection-Low anterior resection-Excision of the -Excision of the mesorectummesorectum-Extend of -Extend of lymphadenectomylymphadenectomy-postoperative -postoperative anastomoticanastomotic
leakageleakage-Tumor perforation-Tumor perforation
Tumor-relatedTumor-related-Anatomic location-Anatomic location-Histologic type-Histologic type-Tumor grade-Tumor grade-Pathologic stage-Pathologic stage-radial resection -radial resection
marginmargin-neural, venous, -neural, venous,
lymphatic invasionlymphatic invasion
Incidence of local failure in RCIncidence of local failure in RC
T1-2,No,MoT1-2,No,Mo <10% <10%
T3,No,MoT3,No,Mo 15-35%15-35%
T1,N1,MoT1,N1,Mo 15-35%15-35%
T3-4,N1-2,MoT3-4,N1-2,Mo 45-65%45-65%
Total Mesorectal Excision Total Mesorectal Excision (TME)(TME)
Local recurrence rates after surgical Local recurrence rates after surgical resection of RC have decreased from resection of RC have decreased from about 30% to < 10%about 30% to < 10%
1. Radio(chemo)therapy1. Radio(chemo)therapy
2. Importance of circumferential margin 2. Importance of circumferential margin (TME)(TME)
ScreeningScreening
What is screening?What is screening?
A public health service in which members of a A public health service in which members of a defined population are examined to identify those defined population are examined to identify those individuals who would benefit from treatmentindividuals who would benefit from treatment
To benefit: To benefit: to reduce the risk of a disease or its to reduce the risk of a disease or its complications complications
Types of ScreeningTypes of Screening
Fecal occult blood test (FOBT)Fecal occult blood test (FOBT)Chemical test for blood in a stool sample. Chemical test for blood in a stool sample. Annual screening by FOBT reduces Annual screening by FOBT reduces colorectal cancer deaths by 33%colorectal cancer deaths by 33%
Flexible sigmoidoscopy can detect about Flexible sigmoidoscopy can detect about 65%–75% of polyps and 40%–65% of 65%–75% of polyps and 40%–65% of colorectal cancers. colorectal cancers. Rectum and sigmoid colon are visually Rectum and sigmoid colon are visually inspectedinspected
Current Screening GuidelinesCurrent Screening Guidelines
Regular screening for all adults aged 50 years Regular screening for all adults aged 50 years or older is recommended or older is recommended
FOBT every yearFOBT every year
Flexible sigmoidoscopy every 5 yearsFlexible sigmoidoscopy every 5 years
Total colon examination by colonoscopy every Total colon examination by colonoscopy every 10 years or by barium enema every 5–10 10 years or by barium enema every 5–10 yearsyears
NORMAL COLONIC MUCOSANORMAL COLONIC MUCOSA
Concept of differentiation is demonstrated by this small Concept of differentiation is demonstrated by this small adenomatous polyp of the colon. Note the difference in staining adenomatous polyp of the colon. Note the difference in staining quality between the epithelial cells of the adenoma at the top and quality between the epithelial cells of the adenoma at the top and the normal glandular epithelium of the colonic mucosa below.the normal glandular epithelium of the colonic mucosa below.
At high magnification,normalal epithelium at the left contrasts with the At high magnification,normalal epithelium at the left contrasts with the atypical epithelium of the adenomatous polyp at the right. Nuclei are atypical epithelium of the adenomatous polyp at the right. Nuclei are darker and more irregularly sized and closer together in the darker and more irregularly sized and closer together in the adenomatous polyp than in the normal mucosa.adenomatous polyp than in the normal mucosa.
Poorly differentiated neoplasm, it is difficult to tell the cell of origin. Poorly differentiated neoplasm, it is difficult to tell the cell of origin. It is probably a carcinoma because of the polygonal nature of the It is probably a carcinoma because of the polygonal nature of the cells. Note that nucleoli are numerous and large in this neoplasm.cells. Note that nucleoli are numerous and large in this neoplasm.
CK staining reaction for carcinomas helps to distinguish carcinoma from CK staining reaction for carcinomas helps to distinguish carcinoma from sarcomas and lymphomas. Immunoperoxidase staining is helpful to determine sarcomas and lymphomas. Immunoperoxidase staining is helpful to determine the cell type of a neoplasm when the degree of differentiation, or morphology the cell type of a neoplasm when the degree of differentiation, or morphology alone, does not allow an exact classification.alone, does not allow an exact classification.
Changes resulting in colon cancerChanges resulting in colon cancer
Molecular Biology & PathologyMolecular Biology & Pathology
CRCs arise from a series of histopathological and molecular CRCs arise from a series of histopathological and molecular changes that transform normal epithelial cellschanges that transform normal epithelial cells
Intermediate step is the adenomatous polypIntermediate step is the adenomatous polyp
Adenoma-Carcinoma-Sequence (Vogelstein & Kinzler)Adenoma-Carcinoma-Sequence (Vogelstein & Kinzler)
Polyps occur universally in FAP, but FAP accounts for only Polyps occur universally in FAP, but FAP accounts for only 1% of CRCs1% of CRCs
Adenomatous Polyps in general population:Adenomatous Polyps in general population:33% at age 5033% at age 5070% at age 7070% at age 70
SummarySummary
CRC is a leading cause of deathCRC is a leading cause of death
Early stages are detectableEarly stages are detectable
Screening can prevent CRC Screening can prevent CRC
REFERENCESREFERENCES
Katie Couric: Katie Couric: http://http://www.nccra.com/about/videos.htmwww.nccra.com/about/videos.htm
http://http://en.wikipedia.org/wiki/File:Colon_cancer.jpen.wikipedia.org/wiki/File:Colon_cancer.jpgg
http://http://ehumanbiofield.wikispaces.com/colon+canehumanbiofield.wikispaces.com/colon+cancer+class+work+EATcer+class+work+EAT