10.6 Lower Gastrointestinal Disorders & Colonic Neoplasia

4. Lower GI Disorders & Colonic Neoplasia

Diverticular Disease

Colonic diverticula are acquired pseudodiverticula (mucosa and submucosa herniating through defects in the circular muscular layer where the nutrient vasa recta penetrate). Most prevalent in the sigmoid colon (~95%) in Western societies.

• Diverticular Bleeding: Caused by eccentric arterial intimal thinning and rupture of the stretched vasa recta over the diverticular dome. Represents the single most common cause of acute, massive, painless lower GI haemorrhage in older adults. Resolves spontaneously in ~80% of cases.
• Acute Diverticulitis: Micro- or macroscopic perforation of a diverticulum initiated by inspissated faecaliths. Manifests with left iliac fossa pain, pyrexia, altered bowel habit, and elevated CRP/WCC. Contrast-enhanced CT of the abdomen and pelvis is the diagnostic gold standard. Colonoscopy is strictly contraindicated in the acute phase due to high perforation risk.
• Hinchey Classification of Acute Diverticulitis:
  • Stage I: Pericolic or mesenteric abscess / phlegmon.
  • Stage II: Pelvic, retroperitoneal, or distant intra-abdominal abscess.
  • Stage III: Generalized purulent peritonitis (ruptured abscess).
  • Stage IV: Generalized feculent peritonitis (free perforation with faecal contamination).
• Management: Stages I–II with small abscesses (<3–4 cm) respond to intravenous antibiotics; larger abscesses require CT-guided percutaneous drainage. Stages III–IV mandate emergency resuscitation and surgical intervention, classically via a Hartmann's procedure (sigmoid colectomy, end colostomy in the left iliac fossa, and closure of the distal rectal stump) or primary resection with anastomosis and diverting loop ileostomy.

Colorectal Cancer Screening & Hereditary Syndromes

Colorectal cancer (CRC) is the fourth most common cancer in the UK. Population screening relies on the Faecal Immunochemical Test (FIT), which uses specific antibodies against human globin to detect occult faecal bleeding at low concentrations without dietary restrictions. Approximately 5% of colorectal cancers are driven by well-characterized monogenic germline mutations:

Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer - HNPCC)

• Genetic Architecture: Autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes: MLH1 (~40%), MSH2 (~35%), MSH6 (~15%), and PMS2 (~5%), or epigenetic hypermethylation of the MLH1 promoter. Defective MMR machinery leads to replication slippage and the accumulation of mutations in repetitive nucleotide sequences, termed microsatellite instability (MSI-H).
• Clinical Characteristics: Accounts for ~3% of all CRCs. Tumours develop at a young age (mean age ~45 years), exhibit a marked predilection for the proximal / right colon (caecum and ascending colon in ~70%), and display distinct histological features: poorly differentiated, mucinous, signet-ring morphology, with dense lymphocytic infiltration (tumour-infiltrating lymphocytes).
• Amsterdam II Criteria (The 3-2-1 Rule):
  • At least 3 relatives with a Lynch-associated cancer (one of whom is a first-degree relative of the other two);
  • At least 2 successive generations affected;
  • At least 1 cancer diagnosed before age 50;
  • Familial adenomatous polyposis (FAP) excluded; tumours verified by pathology.
• Extracolonic Malignancies:
  • Endometrial Adenocarcinoma: The most prevalent extracolonic cancer in women with Lynch syndrome (lifetime risk 40–60%, frequently presenting before the colorectal cancer).
  • Ovarian, gastric, small bowel (duodenum/jejunum), transitional cell carcinoma of the renal pelvis and ureter, hepatobiliary, and cutaneous sebaceous adenomas / keratoacanthomas (Muir-Torre variant); glioblastoma multiforme (Turcot syndrome type 1).
• Surveillance & Prevention: Total colonoscopy every 2 years starting at age 20–25 (or 5 years earlier than the youngest affected family member). Prophylactic daily aspirin reduces long-term colorectal cancer incidence by ~50% (CAPP2 trial). Prophylactic total hysterectomy and bilateral salpingo-oophorectomy should be considered once childbearing is complete.

Familial Adenomatous Polyposis (FAP)

• Genetic Architecture: Autosomal dominant disorder caused by germline inactivating mutations in the APC (Adenomatous Polyposis Coli) tumour suppressor gene on chromosome 5q21. The APC protein forms a destruction complex that degrades cytosolic beta-catenin; loss of APC causes constitutive activation of the Wnt/beta-catenin signalling pathway, driving cellular hyperproliferation.
• Clinical Characteristics: Characterized by the development of hundreds to thousands of colorectal adenomatous polyps carpeting the entire colon and rectum, typically emerging in puberty (second decade). If left untreated, progression to colorectal adenocarcinoma occurs in 100% of patients by age 40–50.
• Extracolonic Features:
  • Duodenal and Ampullary Adenomas: Occur in >90% of FAP patients; the second leading cause of cancer death in FAP. Requires lifelong surveillance using forward- and side-viewing duodenoscopy graded via Spigelman staging.
  • Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE): Present at birth in >80% of patients. Asymptomatic, pigmented, bilateral oval fundoscopic lesions that serve as an invaluable clinical phenotypic marker in at-risk children.
  • Gardner Syndrome Phenotype: FAP plus prominent extra-abdominal manifestations: desmoid tumours (locally invasive, non-metastasizing fibroblastic mesenteric tumours; high surgical morbidity), osteomas (particularly of the mandible and skull), epidermoid cysts, and dental abnormalities (impacted or supernumerary teeth).
  • Turcot Syndrome Type 2: FAP associated with central nervous system medulloblastoma.
• Management: Annual flexible sigmoidoscopy/colonoscopy starting at age 12–14. Definitive management mandates prophylactic restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) or total colectomy with ileorectal anastomosis (IRA), typically performed in late adolescence before malignant transformation ensues.

Diverticular Disease, Ischaemic Colitis and Angiodysplasia

Three non-neoplastic colonic conditions account for most lower gastrointestinal bleeding in older UK patients, and they are separated by pain, pattern of bleeding and vascular risk.

Heyde syndrome links calcific aortic stenosis to angiodysplastic bleeding through acquired type 2A von Willebrand factor deficiency, caused by shear-induced cleavage of high-molecular-weight multimers across the stenotic valve; valve replacement corrects the coagulopathy.

Colorectal Cancer: Presentation and UK Screening

Right-sided tumours present late with iron deficiency anaemia and weight loss because the caecal lumen is wide and the stool liquid; left-sided tumours present earlier with change in bowel habit and obstruction. Unexplained iron deficiency anaemia in any man, or in any woman after the menopause, requires investigation of both upper and lower gastrointestinal tracts.

The NHS bowel cancer screening programme uses the faecal immunochemical test (FIT), which detects human globin and therefore does not require dietary restriction, offered to eligible adults every two years, with colonoscopy for those above the threshold. FIT is also used in symptomatic primary care patients to prioritise referral.

Hereditary Syndromes Beyond Lynch and FAP

• Peutz-Jeghers syndrome: autosomal dominant STK11 mutation, mucocutaneous pigmentation of lips and buccal mucosa, hamartomatous polyps causing intussusception, raised risk of gastrointestinal, breast and pancreatic cancer.
• MUTYH-associated polyposis: autosomal recessive, phenotypically similar to attenuated FAP — the pedigree without vertical transmission is the clue.
• Juvenile polyposis syndrome: SMAD4 or BMPR1A, with SMAD4 cases overlapping hereditary haemorrhagic telangiectasia.