Special Surgery 18. Malignant Diseases of the Large Intestine: Symptoms, Diagnosis, Treatment

I. Definition, Etiology and Spread

Definition and Epidemiology

Colorectal cancer = malignant tumor arising from epithelial lining of colon or rectum
Most common histology: adenocarcinoma
One of the most common cancers worldwide and a major cause of cancer-related death
Peak age: 50-70 years
Incidence is increasing in younger adults
Most cases are sporadic; minority are hereditary

Etiology and Risk Factors

Adenoma-carcinoma sequence:

Normal mucosa → adenoma → dysplasia → invasive adenocarcinoma
APC, KRAS, p53 pathway in classical model

Serrated pathway: sessile serrated lesions can progress through MSI/CIMP-type biology
Diet:

Low fiber
High red/processed/fatty meat intake
Low fruit/vegetable intake

Alcohol
Smoking
Obesity and physical inactivity
Type 2 diabetes mellitus
Inflammatory bowel disease:

Ulcerative colitis
Crohn colitis
Risk increases with duration, extent and inflammation severity

Hereditary syndromes:

FAP: APC tumor suppressor gene mutation
Lynch syndrome / HNPCC: mismatch repair defect → microsatellite instability
MUTYH-associated polyposis and other rarer syndromes

Localization and Clinical Logic

Right-sided colon: cecum, ascending colon, hepatic flexure
Left-sided colon: descending colon, sigmoid colon
Rectal cancer has separate local staging and neoadjuvant treatment logic because of the pelvis and mesorectum

Routes of Spread

Local invasion through bowel wall into adjacent organs
Lymphatic spread to regional mesocolic/mesorectal lymph nodes
Hematogenous spread:

Liver: most common via portal venous drainage
Lung, especially rectal cancer through systemic venous drainage

Peritoneal seeding / carcinomatosis
Bone and brain metastases: late-stage disease

II. Symptoms, Complications and Diagnosis

Right-Sided / Proximal Colon Cancer

Occult bleeding → iron-deficiency anemia
Fatigue, pallor, weakness
Vague abdominal pain or discomfort
Weight loss, anorexia
Melena or dark stool can occur
Palpable mass may occur in advanced cecal/ascending cancer
Obstruction is less common early because stool is liquid and lumen is wide
Often presents later and can have worse prognosis if diagnosed after anemia/weight loss

Left-Sided / Distal Colon Cancer

Change in bowel habits:

Constipation
Diarrhea
Alternating pattern
Narrow stools

Hematochezia / visible rectal bleeding
Mucus in stool
Colicky abdominal pain from partial obstruction
Mechanical bowel obstruction more common than in right-sided cancer
Tenesmus if rectal involvement

Complications

Bowel obstruction
Perforation:

At tumor site
Cecal blowout proximal to obstructing left-sided tumor

Bleeding and anemia
Abscess or fistula formation
Peritoneal carcinomatosis
Liver metastases

Diagnosis

History and Physical Examination

Bleeding, anemia symptoms, bowel habit change, pain, obstruction symptoms
Family history and hereditary syndrome clues
Abdominal examination: distension, mass, hepatomegaly, ascites
DRE:

Mandatory in suspected colorectal cancer
Can detect rectal mass
Assesses bleeding and sphincter tone

Laboratory Tests

CBC: anemia, decreased Hb/Hct
Iron studies: iron-deficiency pattern
Liver enzymes: metastatic liver disease or obstruction
Renal function before contrast CT and chemotherapy
CEA:

Baseline before treatment
Used for follow-up/recurrence monitoring
Not diagnostic and not useful as screening test alone

Screening Tests

Fecal occult blood test / FIT:

Screening tool
Positive result requires colonoscopy

Screening colonoscopy detects and removes premalignant polyps
Higher-risk patients need earlier/more frequent surveillance

Colonoscopy and Biopsy

Gold standard diagnostic test
Direct visualization + biopsy for histology
Examines whole colon for synchronous cancers/polyps
Can tattoo lesion for surgery
Allows polypectomy if malignant polyp/early lesion is removable
CT colonography can be used if colonoscopy is incomplete, but cannot biopsy

Staging Imaging

CT chest/abdomen/pelvis:

Standard staging for colon cancer
Liver, lung, peritoneal metastases
Local complications and obstruction

MRI pelvis:

Required for rectal cancer local staging
Assesses mesorectal fascia/circumferential margin, T stage, nodes, sphincters

Liver MRI: if liver lesions are indeterminate or liver metastasis surgery is planned
PET-CT: selected cases, e.g. potentially resectable metastases with unclear extrahepatic disease

III. Staging and Curative Treatment

TNM Staging

T Stage

Tis: carcinoma in situ / lamina propria
T1: submucosa
T2: muscularis propria
T3: through muscularis propria into pericolorectal tissue
T4a: penetrates visceral peritoneum/serosa
T4b: invades adjacent organs/structures

N and M Stage

N0: no regional lymph node metastasis
N1: 1-3 regional lymph nodes
N2: 4 or more regional lymph nodes
M0: no distant metastasis
M1: distant metastasis

Stage Groups

Stage 0: Tis
Stage I: T1-2 N0
Stage II: T3-4 N0
Stage III: N+
Stage IV: M1

Treatment by Stage: Colon Cancer

Stage 0:

Endoscopic polypectomy/local excision if complete and no invasion beyond mucosa
Segmental resection if not endoscopically removable

Stage I:

Oncologic surgical resection with lymphadenectomy
Endoscopic resection can be enough for selected malignant polyps with favorable features and clear margins

Stage II:

Surgical resection
Adjuvant chemotherapy only for selected high-risk cases

High-risk stage II features:

T4 tumor
Perforation or obstruction
Poor differentiation, except MSI-high context
Lymphovascular/perineural invasion
Positive/close margin
Too few lymph nodes examined

Stage III:

Surgical resection + adjuvant chemotherapy
Common regimens: FOLFOX or CAPOX depending on risk/tolerance

Rectal cancer stage II-III differs:

Neoadjuvant chemoradiotherapy or total neoadjuvant therapy often used before TME surgery

Oncologic Surgical Principles

En bloc segmental colectomy with lymphovascular pedicle ligation and regional lymphadenectomy
Remove tumor-bearing bowel segment with adequate proximal/distal margins
Do not cut through tumor
Assess entire abdomen for metastases
Laparoscopic or robotic surgery acceptable when oncologic principles are maintained and patient/tumor suitable

Surgical Procedures by Location

Tumor Location	Operation	Main Vascular / Nodal Logic
Cecum / ascending colon / hepatic flexure	Right hemicolectomy	Ileocolic, right colic if present, right branch of middle colic; not ligation of whole SMA
Proximal / mid transverse colon	Extended right hemicolectomy or transverse colectomy selected	Middle colic drainage; operation depends on exact site
Splenic flexure / descending colon	Left hemicolectomy	Left colic / IMA branch drainage; not right hemicolectomy
Sigmoid colon	Sigmoid colectomy / anterior resection depending on rectosigmoid involvement	Sigmoid arteries and superior rectal/IMA pathway depending on level
Upper/mid rectum	Low anterior resection with TME or tumor-specific mesorectal excision	Mesorectal lymphadenectomy, sphincter preservation if safe
Very low rectum with sphincter/levator involvement	Abdominoperineal resection	Permanent colostomy

Emergency Surgery

Indications:

Mechanical bowel obstruction
Perforation
Uncontrolled bleeding
Sepsis/abscess not controlled otherwise

Options depend on site and patient stability:

Resection with primary anastomosis if safe
Hartmann procedure for left-sided obstruction/perforation in high-risk setting
Diverting stoma as bridge/palliation
Self-expanding metal stent as bridge to surgery or palliation in selected left-sided obstruction

IV. Stage IV, Palliative Treatment and Follow-Up

Stage IV / Metastatic Disease

Treatment depends on:

Metastasis site and resectability
Symptoms from primary tumor
Performance status
Molecular profile

Potentially curative metastatic setting:

Resectable liver metastases
Resectable lung metastases
Selected limited peritoneal disease in specialized centers
Surgery/ablation + systemic therapy can produce long survival in selected patients

Unresectable metastatic disease:

Systemic therapy
Conversion therapy if metastases might become resectable
Palliative symptom control

Systemic and Targeted Therapy

Cytotoxic backbones:

FOLFOX
CAPOX
FOLFIRI
FOLFOXIRI in selected fit patients

Targeted therapy depends on molecular testing:

RAS wild-type left-sided tumors: anti-EGFR therapy such as cetuximab/panitumumab can be used with chemotherapy
VEGF inhibition: bevacizumab with chemotherapy in many settings
BRAF V600E mutation: BRAF-targeted combination strategies in advanced disease
MSI-high/dMMR metastatic cancer: immunotherapy is important and can be first-line
HER2 amplification, NTRK fusion and other rare targets if present

Palliative Local Treatment

Obstruction:

Endoscopic stent in selected left-sided/rectosigmoid tumors
Diverting colostomy/ileostomy
Palliative resection or bypass in selected patients

Bleeding:

Endoscopic hemostasis if feasible
Radiotherapy especially for rectal bleeding/pain
Palliative resection only if necessary

Perforation/sepsis:

Emergency source control, resection/stoma/drainage depending on condition

Follow-Up After Curative Treatment

CEA monitoring
Colonoscopy:

Clear colon preoperatively or soon after if obstructing tumor prevented full exam
Surveillance colonoscopy to detect metachronous cancer/polyps

CT chest/abdomen/pelvis according to stage and recurrence risk
Clinical review: symptoms, bowel function, stoma/anastomosis issues, neuropathy after oxaliplatin
Rectal cancer follow-up also includes local pelvic surveillance when indicated

Prognosis

Depends mainly on stage, nodal status, margin status, tumor biology and treatment response
Stage I has excellent prognosis
Stage III prognosis improves with adjuvant chemotherapy
Stage IV prognosis is poor overall but can be substantially better in selected patients with resectable liver/lung metastases
Poor prognostic factors:

Advanced T stage
Multiple positive lymph nodes
Perforation/obstruction
Positive margin
Lymphovascular/perineural invasion
BRAF mutation and aggressive molecular biology