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Gastrointestinal (GI) System ORGAN SYSTEMS

Colorectal Cancer

Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine).

Introduction

Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine).

  • #2 M/C cancer
  • M/C GI cancer

Etiology

  • DIET
    • ↑ Risk: Red meat, saturated fat
      • ↑ Cholesterol → ↑ Bile acid (cocarcinogen)
    • ↓ Risk: High fibre diet, calcium, Vitamin A, C, E & Zn
  • GENETIC
    • Family history
    • Common in people with,
      • Adenoma colon
      • Familial adenomatous polyposis (FAP)
      • Gardner’s syndrome
      • Turcot’s syndrome
  • IBD (Ulcerative colitis/Crohn’s disease)
  • Alcohol & cigarette smoking
  • HNCC (Hereditary nonpolyposis colonic cancer)
  • Radiation
  • OTHER TREATMENTS:
    • After cholecystectomy & ileal resection
    • Ureterosigmoidostomy
    • Acromegaly

Pathophysiology

Connection between emerging hallmarks of each acquired capabilities necessary for tumor growth and progression and, Vogelstein’s model of CRC pathogenesis. MicroRNAs’ involved in each way and emerging linc-HOTAIR implication in metastasis features. | Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell 2011, 144, 646–674. | Fearon, E.R.; Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 1990, 61, 759–767.
Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors. | By Bernstein0275 – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=25453056

Spread:

  • LOCAL SPREAD
    • Circumferential spread
    • Surrounding viscera:
      • Liver, stomach, kidney, spleen, diaphragm, mesentery, stomach, pancreas
      • Bladder
        • Obstruct ureter → Hydronephrosis
      • Peritoneum
        • Peritonitis/pericolic abscess/faecal fistula
      • Psoas muscle
      • Ureter, ovary, uterus
        • Colovesical/colovaginal fistula
  • LYMPHATIC SPREAD
    • Upward spread
    • Pericolic, epicolic, intermediate & principal group of lymph nodes
  • HEMATOGENOUS SPREAD
    • Liver (34%)
    • Lungs (22%)
    • Adrenals (11%)
    • Rarely: Other sites of secondary metastasis including brain
  • PERITONEAL DISSEMINATION

Classification

Aetiological classification:

  • NON HEREDITARY COLON CANCER
    • Sporadic colon cancer (60%)
    • Familial colon cancer (30%)
  • HEREDITARY COLON CANCER
    • FAP
    • HNCC
    • Peutz Jeghers syndrome
    • Cronkite-Canada syndrome
    • Juvenile polyposis syndrome

Anatomical classification:

  • Synchronous
    • de novo multiple primary carcinomas in different parts at the same time
  • Metachronous
    • growth in different parts in different periods
  1. Annular (stenosing) type
  2. Ulcerative type
  3. Cauliflower (proliferative) type

Presentation

  • Pericolic abscess/obstruction/perforation/peritonitis
  • Secondaries:
    • Multiple umbilicated liver secondaries. rectovesical secondaries, palpable left supraclavicular lymph nodes

Right-sided (Ascending colon) location

  • Loss of weight & appetite
  • Anaemia
  • Abdominal discomfort
  • Mass per abdomen
  • Other presentations:
    • Acute intestinal obstruction
    • Acute appendicitis
    • Intussusception with intestinal obstruction

Left-sided (Descending colon-sigmoid) location

  • Dark-red mixed stools ± clots
  • Bloating & flatulence
  • ↑ Bowel frequency

Rectal region

  • Bleeding (Earliest & M/C symptom)
  • Tenesmus
    • Distressing straining to empty bowels without resultant evacuation
  • Spurious diarrhoea
    • Often with bloody slime (flatus + blood-stained mucus)
  • Altered bowel habits (alternating constipation & diarrhoea)
    • Early-morning bloody diarrhoea
    • Use of aperient
  • Colicky pain (Late symptom)
    • Severe (if erodes prostate/bladder)
    • When cancer invades sacral plexus,
      • Radiation to back or sciatica
  • Subacute/chronic intestinal obstruction
  • Other presentations:
    • Bladder symptoms

Closed-loop obstruction (Transverse Colon)

  • Enormously dilated right colon:
    • Stercoral ulcer
    • Perforation
    • Faecal peritonitis

Complications

  • LOCAL COMPLICATIONS:
    • Intestinal obstruction
    • Closed loop obstruction
    • Perforation & peritonitis
    • Vesicocolic Fistula
    • Invasion of ureter
    • Perocolic abscess

Diagnosis

  • Digital rectal examination
  • Flexible sigmoidoscopy
    • Identify adenoma
  • Colonoscopy (M/accurate & complete investigation)
    • Biopsy, polypectomy, control of bleeding, stricture dilation

Lab studies:

  • Faecal occult blood test (FOBT)
    • Nonspecific test for peroxidase in Hb
  • ↑ CEA (Chorioembryonic antigen)
    • Nonspecific test for cell-surface glycoprotein for cell-adhesion
    • > 5 ng/ml (SIGNIFICANT)
      • Normal: < 2.5 ng/ml
    • Also found in:
      • Pancreatic, gastric, lung, breast carcinomas
  • Routine blood test
    • Hb%, PCV, hematocrit, ESR
  • Stool examination
    • Occult blood
  • LFT
    • Alkaline phosphatase, SGPT

Histopathology (Biopsy):

Imaging:

  • CT Colonography (Virtual Colonoscopy)
  • Barium enema
    • Irregular filling defect
    • Apple core lesion (left-sided)
      • Constriction of lumen (like an apple core after being eaten)
  • USG
    • Secondaries in liver, peritoneum, lymph node status, retrovesical secondaries

Modified Duke’s Classification

  1. Growth up to submucosa (rectal wall)
  2. Growth up to submucosa + extra rectal tissue
    • B1: Invading muscularis mucosa
    • B2: Invading into/through serosa
  3. Lymph node secondaries
  4. Distant metastasis (liver, lungs, bone, brain)

TNM staging

Histological classification

  • Low-grade
  • Average-grade
  • High-grade

Differential diagnosis:

  • Ileocaecal TB
  • Appendicular mass
  • Actinomycosis
  • Ectopic kidney
  • Mesenteric lymph nodes
  • Ovarian tumour (Females)
  • Retroperitoneal tumour
  • Amoeoboma

Management

Right-sided CRC:

  • Early growth:
    • Right radical hemicolectomy + ileo-transverse anastomosis
  • Inoperable growth:
    • (Bypass surgery) ileo-transverse anastomosis

Transverse colon growth:

  • Extended right hemicolectomy

Left-sided CRC:

  • Early growth:
    • Left radical hemicolectomy
  • Stenosing type of growth
    • 3 stage operation:
      1. Colostomy
      2. Proper procedure
      3. Colostomy closure 
  • With obstruction:
    1. Resection of tumour
    2. Saline lavage
    3. Catheterization
    4. Primary anastomosis
  • Multiple synchronous primaries:
    • Total abdominal colectomy + ileorectal anastomosis
  • Liver secondaries:
    • Segmental hepatic resection
    • Hhemihepatectomy
    • Metastasectomy
  • Owen Wangensteen’s Second-look Surgery

Adjuvant therapy:

  • CHEMOTHERAPY
    • Indications:
      • Positive Nodes
      • T4-lesions
      • Hematogenous spread
      • Signet type cell
      • Poorly differentiated tumour/aneuploidy
      • CEA level changes
    • Regimes:
      • FOLFOX regimen (Treatment of choice)
        • Folinic acid (LV)/5FU/Oxaliplatin
      • 5FU (fluorouracil) + folinic acid (leucovorin/LV)
      • Levamisole + 5FU
  • EGFR & VEGF blockers
    • In combination with chemotherapy
    • Cetuximab (EGFR blocker) & bevacizumab (VEGF blocker)
  • RADIOTHERAPY
    • Colorectal cancer is radioresistant
    • Indications:
      • Locally advanced tumour
      • Inoperable recurrent tumour

Follow-up:

  • Once 3-6 months for 3 years

Summary

Final words

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