Colon cancer: highest and lowest rates worldwide (Men)

Colon & Rectal Cancer

GEORGE G. LIM, MD, FPSCRS, FPSGS, FPCS

Associate Professor 3
Department of Surgery
Faculty of Medicine & Surgery
University of Santo Tomas

Colon cancer: highest and lowest rates worldwide (Women) Colorectal cancer incidence by age in the US

Colorectal cancer death rates in men in US, by age Concepts of environmental cause of colon cancer

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Abnormal proliferation is a hallmark of neoplasia Genetic alterations in progression to colorectal cancer

Gene mutations that cause colon cancer Hereditary nonpolyposis colorectal cancer

Mutation Type Genes Involved Type of Disease Caused

Germline APC Familial adenomatous polyposis Amsterdam Criteria

MMR HNPCC (Lynch syndrome)
At least three relatives with colon cancer and all of the following:
Somatic Oncogenes: Sporadic disease One affected person is a first-degree relative of the other two
myc, ras, src, erbB2 affected persons
Tumor suppressor
Two successive generations affected
genes: At least one case of colon cancer diagnosed before age 50 years
Familial adenomatous polyposis excluded
TP53, DCC, APC

MMR genes:
Modified Amsterdam Criteria
hMSH2, hMLH1,
hPMS1, hPMS2,
hMSH6, hMSH3 Same as the Amsterdam criteria, except that cancer must be
associated with HNPCC (colon, endometrium, small bowel,
Genetic
APC
Familial colon cancer in Ashkenazi ureter, renal pelvis) instead of specifically colon cancer
polymorphism Jewish persons

Hereditary nonpolyposis colorectal cancer Inheritance in family with cancer family syndrome

Bethesda Criteria

The Amsterdam criteria or one of the following:

Two cases of HNPCC-associated cancer in one patient, including
synchronous or metachronous cancer
Colon cancer and a first-degree relative with HNPCC-associated
cancer and/or colonic adenoma (one case of cancer
diagnosed before age 45 years and adenoma diagnosed
before age 40 years)
Colon or endometrial cancer diagnosed before age 45 years
Right-sided colon cancer that has an undifferentiated pattern
(solid-cribriform) or signet-cell histopathologic
characteristics diagnosed before age 45 years
Adenomas diagnosed before age 40 years

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HNPCC clinical characteristics Multiple pedunculated polyps

TABLE 3 - 13. HNPCC CLINICAL CHARACTERISTICS

Characteristics HNPCC Sporadic

Mean age at diagnosis, y 44.6 67

Multiple colon cancers, % 34.5 4 - 11

Synchronous 18.1 3-6

Metachronous 24.3 1-5

Proximal location, % 72.3 35

Excess malignancies at other

Yes No
sites

Mucinous and poorly

Common Infrequent
differentiated cancers

RER + % 79 17

Large pedunculated polyp Large sessile polyp

Tubular adenoma of the colon cut in cross section Tubulovillous and villous adenomas (A)

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Tubulovillous and villous adenomas (B) Model of Colorectal Carcinogenesis

Percent of adenomas containing invasive cancer Carcinoma within a polyp

Pedunculated adenoma containing focus of adenocarcinoma Colectomy specimen

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Radiograph of a barium enema Mucocutaneous pigmentation in Peutz-Jeghers syndrome (A)

Mucocutaneous pigmentation in Peutz-Jeghers syndrome (B) Photomicrographs of Peutz-Jeghers polyp (A)

Juvenile polyp Probability of developing colorectal carcinoma in Ulcerative Colitis

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Distribution of colorectal cancer in colon Adenocarcinomas and carcinomas affecting colon (A)

Annular constricting or napkin-ring carcinoma of colon (B) Annular constricting or napkin-ring carcinoma of colon (B)

Small polypoid carcinoma of colon Annular constricting or napkin-ring carcinoma of colon (A)

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Adenocarcinomas and carcinomas affecting colon (B) Adenocarcinomas and carcinomas affecting colon (C)

Adenocarcinomas and carcinomas affecting colon (D) Adenocarcinomas and carcinomas affecting colon (E)

Adenocarcinomas and carcinomas affecting colon (F)

Usual Presentation of Colorectal CA

Obstruction
Change in bowel habits
Blood streaked stools
Palpable abdominal mass

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 Other Information Management

Weight loss Diagnosis

Family history of colorectal cancer Staging
Other GI symptoms Operability
Rectal examination Optimum treatment strategy

Ancillary Tests Staging

Double contrast Barium Enema Tumor characteristics

Colonoscopy ► Histology
► Grading
CT scan
MRI Local conditions
► Local extent of tumor
Virtual colonoscopy
► Invasion to other organs
Metastatic workup
► Other organ involvement
Prognosis

Modifications of Dukes' staging system Staging of colorectal cancer

TABLE 3 - 43. STAGING OF COLORECTAL CANCER–AMERICAN JOINT COMMITTEE ON CANCER USING THE TNM
CLASSIFICATION
Stage 0
Carcinoma in situ Tis N0 M0

Stage I
Tumor invades submucosa T1 N0 M0
Tumor invades muscularis propria T2 N0 M0

Stage II
Tumor invades through muscularis propria into subserosa or into nonperitonealized pericolic or perirectal tissues T3 N0 M0
Tumor perforates the visceral peritoneum or directly invades other organs or structures T4 N0 M0

Stage III
Any degree of bowel wall perforation with regional lymph node metastasis
N1 1 to 3 pericolic or perirectal lymph nodes involved
N2 4 or more pericolic or perirectal lymph nodes involved
N3 Metastasis in any lymph node along a named vascular trunk
Any T N1, M0
Any T N2, N3 M0

Stage IV
Any invasion of bowel wall with or without lymph node metastasis but with evidence of distant metastasis
Any T Any N M1

Dukes' B (corresponds to Stage II) is a composite of better (T3, N0, M0) and worse (T4, N0, M0) prognostic groups as is Dukes' C (corresponds to Stage
III) (any T, N1, M0) and (any T, N2, N3, M0)

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Survival probabilities according to stage of disease (A) Survival probabilities according to stage of disease (B)

Staging: Tumor Characteristics Staging: Local Conditions

Histology Colon cancer

► Signet ring adenocarcinoma ► PE findings especially if mass is palpable
► Mucinous adenocarcinoma ► ? CT scan
Grading ► ? MRI

► Poorly differentiated adenocarcinoma Rectal cancer

Others ► Rectal examination findings

► Age at diagnosis ◘ Gynecologic examination

◘ Worse for younger patients ► Endorectal ultrasound
► ? CT scan
► ? MRI

EUS of a rectal colonic leiomyoma (A)

Staging: Metastatic Workup

Lungs
► Chest x-ray
Liver
► CT scan of the Liver
► Ultrasound of the Liver
CEA determination
► For follow-up after treatment

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Metastasis cascade Pathologic features affecting prognosis

CLINICAL FEATURES THAT MAY AFFECT PROGNOSIS IN PATIENTS WITH

COLORECTAL CANCER
Clinical features Effect on prognosis
Diagnosis in asymptomatic patients ?Improved prognosis
Duration of symptoms No demonstrated effect
Rectal bleeding as presenting symptom Improved prognosis
Bowel obstruction Diminished prognosis
Bowel perforation Diminished prognosis
Tumor location ?Colon better than rectum
?Left colon better than right colon
Age < 30 Diminished prognosis
Diminished prognosis with high CEA
Preoperative serum CEA
level
Deletions in chromosome 18 (DCC
Diminished prognosis
gene)
Distant metastases Markedly diminished prognosis

Perivenous and perineural invasion

Operability

Cardiopulmonary status
► Anemia
Co-morbid conditions
► Nutritional status
► Renal function
► Liver function

Extent of surgical resection for cancer of colon

Right hemicolectomy
Optimum Treatment Strategy

Surgery is the only hope for CURE

Adjuvant chemotherapy for Colon CA
► Stage 111 disease
► High risk Stage 11 disease
◘ Obstruction / Perforation
◘ High grade histology
Adjuvant chemo-radiotherapy for Rectal CA
► ≥ Stage 11 disease
► Pre-operative chemoradiation or radiation alone,
both followed by postoperative chemotherapy

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Extent of surgical resection for cancer of colon Extent of surgical resection for cancer of colon
Transverse colectomy Left hemicolectomy
Sigmoid colectomy

Extent of surgical resection for cancer of rectum Sphincter-saving procedure

Abdominoperineal resection (APR)
Low anterior resection

Chemotherapy of colon cancer in Dukes' C disease Combined therapy for stages II and III rectal cancer

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Arteries of the colon and rectum Venous drainage of the colon

Slide tests for fecal occult blood

Screening

Fecal Occult Blood Test

Digital rectal examination
Colonoscopy

Algorithm for colon cancer surveillance

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 Diverticular disease of the colon

Diverticular Disease of the Colon

GEORGE G LIM, MD, FPSCRS, FPSGS, FPCS

Associate Professor 3
Department of Surgery
Faculty of Medicine & Surgery
University of Santo Tomas

Circular and longitudinal muscle layers in colon Pathogenesis of diverticular disease of the colon

Colonoscopic finding of diverticular disease of the colon Uncomplicated acute diverticulitis of the colon

Manifestations
• “Left sided appendicitis”

Treatment of Acute diverticulitis

• NPO
• IVF
• Antibiotics

Risk of second episode: 20-30%

Risk of third episode: > 50%

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Complicated diverticular disease of the colon Hinchey Classification of perforated diverticular disease

Stage I: Pericolic or mesenteric abscess

Stage II: Walled-off pelvic abscess

Stage III: Generalized purulent peritonitis

Stage IV: Generalized fecal peritonitis

Diverticular disease of the colon. (C) Diverticular disease of the colon. (D)

Diverticular disease of the colon. (E) Diverticular disease of the colon with bleeding. (F)

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An air-contrast barium enema demonstrates scattered Pancolonic diverticulosis is demonstrated in this barium enema
diverticulosis of the left colon. and may occur in up to 10% of patients.

This operative specimen demonstrates numerous diverticula. This operative specimen demonstrates the serosal surface of a
perforated colonic diverticulum.

This barium enema demonstrates a classic case of acute Sigmoid diverticulitis can mimick a carcinoma.
sigmoid diverticulitis.

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This case of sigmoid diverticulitis has produced a stricture that Peridiverticulitis
causes obstructive symptoms and dilation of the proximal colon.

Diverticular abscess

Colonic Volvulus

GEORGE G LIM, MD, FPSCRS, FPSGS, FPCS

Associate Professor 3
Department of Surgery
Faculty of Medicine & Surgery
University of Santo Tomas

Colonic volvulus Sigmoid volvulus

Volvulus Elongated segment of bowel accompanied by

►Bowel becomes twisted on its mesenteric
axis
►Results in partial or complete obstruction
of the bowel lumen
►Variable degree of impairment of its blood
supply
►Involves the sigmoid or the cecum
a lengthy mesentery with a very narrow
parietal attachment
Chronic constipation and aging, with the
average age at presentation being in the
seventh to eighth decade of life

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Sigmoid volvulus Sigmoid volvulus

Manifestations
►Usually a sudden onset of severe
abdominal pain, vomiting, and obstipation
►The abdomen is usually markedly
distended and tympanitic
►Ominous signs: severe abdominal pain,
rebound tenderness, and tachycardia

Sigmoid volvulus Sigmoid volvulus

Treatment
►Appropriate resuscitation
►Attempt non-operative decompression
◘ Rectal intubation or colonoscopy
►Elective surgical resection
◘ Recurrence of 20-50%

►Emergency surgical decompression

◘ Resection with or without anastomosis
◘ Detorsion with delayed elective resection

Sigmoid volvulus Sigmoid volvulus

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Cecal volvulus Cecal volvulus

Axial rotation of the terminal ileum, cecum,

and ascending colon with concomitant
twisting of the associated mesentery
Lack of fixation of the cecum to the
retroperitoneum
Risk factors: previous surgery, pregnancy,
malrotation, and obstructing lesions of the left
colon

Cecal volvulus

Treatment
►Most cases will require operation to correct
the volvulus and prevent ischemia
►Right colectomy with primary anastomosis
is the procedure of choice
◘ Cecopexy is an alternative