Ulcerative Colitis

Background

UC is a chronic, relapsing-remitting, non-infectious inflammatory disease of the GI tract, involving the rectum and variable lengths of colon.

• Unlike Crohn’s disease, inflammation is usually only superficial, affecting the mucosal layer.
• UC can be broadly classified by the extent of disease
  • Ulcerative proctitis
    • Inflammation of the rectum only
  • Left sided colitis
    • inflammation extends to the sigmoid colon but not beyond the splenic flexure
  • Extensive colitis (pancolitis)
    • inflammation extends beyond the splenic flexure

Aetiology/Risk factors

• The exact cause of UC is unknown
• Genetic
  • Genetically susceptible individuals- abnormally reactive humoral and cell mediated immunity against intestinal bacteria
  • Family history is a strong risk factor
  • HLA-B27 allele is associated with UC, Ankylosing spondylitis, psoriatic arthritis, uveitis and other spondyloarthropathies
• Autoantibodies e.g. perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) may play a role
• Smoking, in contrast to Crohn’s, is protective against UC
• NSAID use may increase the risk of UC and Crohn’s

Presentation

Onset of symptoms is usually (but not always) insidious/slow.

• Bloody diarrhoea for more than 6 weeks is a cardinal feature
  • Urgency and nocturnal diarrhoea also common
  • Tenesmus (persistent painful urge to pass stool even when rectum is empty)
• Abdominal pain
  • Colicky
  • Lower left quadrant
  • May be relieved by bowel movements
• Weight loss, anorexia
• Extraintestinal manifestations (see Crohn’s disease)
  • Psoriasis/psoriatic arthritis and ankylosing spondylitis are more common in patients with UC (HLA B27 allele association)

Investigations

• Initial Blood investigations
  • FBC- anaemia (chronic disease, blood loss); thrombocytopenia
  • U&Es- Hypokalaemia, hyponatraemia, hypomagnesemia
  • LFTs- Hypoalbuminaemia
    • Also check for extraintestinal manifestations e.g. raised Alk Phos/bilirubin (may suggest hepatobiliary disease)
  • Raised CRP (correlates with disease activity)
  • Serology
    • p-ANCA is positive in 60-80% of patients with UC (50% sensitive and 94% specific)
    • ASCA less common in UC (moreso in Crohn’s)
• The gold standard for the diagnosis of UC is colonoscopy with biopsy
  • abnormal erythematous mucosa (superficial ulceration may be present; deep ulceration rare cf Crohns) extending from the rectum to part or all of the colon
    • the inflammation is uniform, without normal mucosa in between (skip lesions are not a feature of UC but of Crohns)
    • histologically, inflammation is limited to the mucosa/submucosa (cf Crohns).  Crypt abscesses/atrophy is classical but not specific.  Infiltration with inflammatory cells (mainly neutrophils (acute activity)/lymphocytes (chronic), plasma cells, mast cells and eosinophils)
• Imaging may be useful in evaluating the extent of disease
  • Contrast enema studies traditionally most useful but CT colonography becoming increasingly popular

Assessing Severity

• Truelove and Witts’ severity index
• 

NB Subacute UC refers to moderate-severely active UC that would be managed in an outpatient setting

Management

• Inducing remission
  • Mild – moderate (/ first presentation)- 1st line
    • Proctitis/proctosigmoiditis
      • offer topical aminosalicylate alone or combined oral and topical aminosalicylate
      • Oral aminosalicylate may be used alone but is not as effective
        • if this is not suitable a topical / oral corticosteroid may be offered
      • Subacute disease may be offered oral prednisolone
    • Left-sided and extensive disease
      • high induction dose of oral aminosalicylate
      • consider a topical aminosalicylate or oral beclometasone diproprionate
        • if these aren’t appropriate, consider oral prednisolone
    • 2nd/3rd line – any extent
      • add oral prednisolone (stop beclometasone treatment prior to this)
      • consider adding oral tacrolimus to prednisolone if this is inadequate
      • NB Infliximab is NOT recommended for mild-moderate disease)
  • Acute Severe disease; all extents
    • Offer IV corticosteroids
      • Where this is not tolerable or contrainidicated- consider IV ciclosporin (or surgery)
    • Assess need for surgery
      • more likely if >8 stools/day; pyrexic; tachycardic; colonic dilation on AXR
• Maintaining remission
  • For 1st time, or after mild-moderate disease
    • Proctitis/proctosigmoiditis
      • Topical +/- oral aminosalicylate (daily or intermittent)
    • Left sided/extensive disease
  • For 2+ flare-ups in 12 months, if remission is not maintained with oral aminosalicylates, or after a severe flare up:
    • consider oral azathioprine/mercaptopurine (see Crohn’s for monitoring)
• Other management issues
  • Screen and monitor for osteopenia/osteoporosis
  • Regular colonoscopy for colorectal cancer screening (as well as disease activity)

Crohn’s disease

Background

Chronic relapsing-remitting, non-infectious inflammatory disease of the GI tract

• Can affect any part of the GI tract from mouth to anus, and usually presents as ‘skip’ lesions i.e. abnormal lesions with normal mucosa between (this is in contrast to UC)
  • Around 30% involve small bowel (terminal ileum most common); 20% only the colon; 45% involve both
• It has an incidence of around 10 per 100,000 per year and a prevalence of around 115000 in the UK
  • It usually presents around either 15-30 or 60-80.  More common in adult females (1.8:1)

Aetiology

• The exact cause(s) is unknown but there are several risk factors
  • Genetics- 15-20% will have an affected family member; siblings of an affected individual are 17-35 times more likely to develop crohn’s
    • At least 200 genes have been identified- complex polygenic factors
  • Smoking
    • In contrast to UC, smoking increases the risk of CD (OR 1.76 compared to general population)
  • Appendectomy
    • Relative risk after 1 year was 6.7 and after 5 years was 1.1

Pathophysiology

• Chronic inflammation from inappropriate T cell activation
• Initially, focal inflammatory lesions form around the crypt cells of the GI mucosa, followed by ulceration of the superficial mucosa.
  • Invasion of inflammatory cells into the deep mucosa allows the formation of noncaseating granulomas.
  • Crypt and villous atrophy is a consequence of neutrophillic infiltration into the crypts

Presentation

• Crohn’s is a relapsing/remitting disease- as such symptoms/signs will often be episodic in nature
• Symptoms
  • Change in bowel habit- most commonly diarrhoea
    • May be bloody (not frequently); more often with mucus
    • May be chronic
    • Bowel movements may partially relieve abdominal pain
  • Abdominal pain- most commonly in the right lower quadrant
  • Weight loss
• On examination,
  • the abdomen may be tender or distended
  • there may be mouth ulcers or perianal lesions (e.g. fistulae, skin tags etc)
• Extraintestinal features
  • More common in crohn’s than in UC, particularly with related colitis
  • Can be split into
    • Related to disease activity
      • Pauci-articular arthritis
        • <5 large joints e.g. ankles, knees, hips, wrists, elbows, shoulders
        • usually asymmetric, acute and self-limiting (~few weeks rather than months)
        • although the joints aren’t usually permanently damaged, there is often associated enthesitis (tendon attachment); tenosynovitis (tendon + sheath) or dactylitis.
      • Erythema nodosum
      • Aphthous ulcers (painful, clearly defined, shallow ulcers of the mouth and underside of the tongue)
      • Episcleritis
      • Osteoporosis (both a manifestation and a complication of treatment)
    • Not related to disease activity
      • Axial arthritis (e.g. ankylosing spondylitis); polyarticular arthritis (small joints; >5 joints; symmetrical; persistent; damaging)
      • Pyoderma gangrenosum (erythematous papules/pustules that can ulcerate; most commonly on the shins/previous trauma sites)
      • Uveitis (bilateral)
      • Hepatobiliary conditions
        • e.g. primary sclerosing cholangitis (mainly in UC- serious, cholangitis, steatosis, chronic hepatitis, cirrhosis, gallstones
        • May be a complication or secondary to treatment; most commonly detected with deranged LFTs
    • Rarer manifestations include bronchial disease; pancreatitis; renal stones; VTE

Investigations

• Blood tests
  • FBC
    • Anaemia- chronic disease; iron deficient; chronic blood loss; malabsorption of B12/folate
    • Leucocytosis- inflammation, abscess or steroid treatment
  • U&Es
    • Hydration status- hyponatraemia
    • Kidney function
    • Micronutrient/electrolyte deficiencies e.g. hypocalcaemia/hypomagnesaemia
  • LFTs
    • Check liver/biliary status for extraintestinal manifestations
    • Hypoalbuminaemia
  • Inflammatory markers
    • Raised CRP
  • Serology
    • Anti-S cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (p-ANCA)
      • Crohn’s more likely to be ASCA positive
      • UC more likely to be p-ANCA positive (can be positive in CD too)
• Imaging
  • First line used to be contrast studies (barium or otherwise; swallow + follow through and enema studies)
    • ‘Cobblestone appearance’- patches of normal and ulcerated mucosa
    • fistulae
  • CT is being used more often
• Endoscopy
  • Ileocolonoscopy with biopsy is the gold-standard investigation for Crohn’s disease

Assessment of Severity

• Crohn’s disease activity index
  • Complex method of assessment that takes into account bowel habit and abdominal pain (amongst other factors) over a 1 week period
    • For calculator- see http://www.ibdsupport.org.au/cdai-calculator
• Harvey-Bradshaw Index
  • Simple index of CD activity, taking into account general well-being, abdo pain, no of stools, abdo masses and complications
    • see http://www.janssenmedicalinformation.ca/assets/pdf/HarveyBradshaw_English.pdf

Management

• Patient support and information
  • Smoking cessation
• Inducing remission
  • Glucocorticosteroid treatment (prednisolone; methylprednisolone or IV hydrocortisone)
  • NB In children where growth is a concern, enteral nutrition (nutrition shakes) may be an alternative
    • Budesonide (a steroid with low bioavailability) is preferred in mild-moderate crohn’s)
  • Consider adding azathioprine or mercaptopurine in patients who do not respond adequately to glucocorticoids or who have had a previous episode within the last 12 months
    • NB Do NOT use as monotherapy.  If glucocorticoids are not suitable, try 5-aminosalicylate (5-ASA) for first/mild presentations
    • IMPORTANT: Before starting either- assess thiopurine methyltransferase (TPMT) activity.
      • Do NOT offer if activity is very low/absent
    • ALSO MONITOR WCC, and drug levels
    • Major side-effects of azathioprine include myelosuppression, hepatitis and pancreatitis; minor, often transient effects, include nausea, vomiting and flu-like symptoms.
    • If these are not suitable, consider methotrexate
• Cytokine modulators (Infliximab/adalimumab- block TNF-alpha activity)
  • Infliximab can be considered for severe Crohn’s disease, where conventional treatment has failed or is contraindicated
    • Severe disease is defined as very poor general health and one or more symptoms of weight loss, fever, severe abdominal pain, and diarrhoea (CDAI >300; HBI >=8)
      • Active fistulating Crohn’s disease is also a relative indication
    • Treat until treatment failure (e.g. need for surgery) or for 12 months
    • Treat only if active disease i.e. not in remission
• Total parenteral nutrition may be suitable in severe disease too
• Surgery
  • Only offer surgery as an alternative to medical therapy in early Crohn’s disease limited to the distal ileum/proximal  caecum
  • Surgery may be offered for the management of secondary strictures (balloon dilation)
  • Surgery is not routinely offered in Crohn’s as disease is systemic and recurrence is almost certain (only really used for complications)
• Maintenance of remission
  • Smoking cessation
  • Azathioprine/mercaptopurine may be used as monotherapy (particularly in those who have required their use in inducing remission)
    • Where these are not suitable, consider methotrexate
    • Do NOT offer glucocorticosteroids unless this is required for the management of extraintestinal manifestations e.g. erythema nodosum/uveitis
  • Offer colonoscopic surveillance for colorectal cancer; monitor for osteopenia/osteoporosis

Pancreatic Cancer

Background

• Pancreatic cancer is the second most common tumour of the digestive tract
  • Most occur in 70-90 year old patients
  • It has a very poor prognosis
    • overall 5-year survival remains <5%
    • It is the 5th most common cause of cancer death (6% of cancer deaths) despite being the 11th most common cancer
    • 98% of pancreatic cancer is metastatic and over half present with metastatic disease at diagnosis
• More common in males (2:1)
• Most are adenocarcinomas (90%) and most pancreatic cancers arise from the pancreas itself and 10% arise from the distal common bile duct
  • 75% in the head/neck; 15-20% in the body and 5-10% in the tail

Aetiology

• NB 40% are sporadic
• Smoking
• Alcohol is not necessarily a risk factor unless it is associated with chronic pancreatitis
• Chronic pancreatitis
• Diabetes mellitus in patients over 50
• Obesity
• Genetic factors
  • KRAS2 gene; p53
  • Familial cancer syndromes e.g. BRCA; MEN

Presentation

• Early symptoms are often vague and non-specific
  • Epigastric pain and/or back pain (often dull and achey)
  • Often worse lying down- can be nocturnal and awakening
• Anorexia and weight loss
• Nausea
• Obstructive jaundice may present early if the tumour arises in the common bile duct/head of the pancreas but may be a late sign or a sign of metastatic disease if the tumour is from the body/tail
  • Painless
  • NB Ascites is a late sign
• Acute/subacute pancreatitis
  • Steatorrhea
• Features of metastases e.g. SOB, jaundice, bone pain etc
• Abdominal masses are uncommon and are often a late sign

Investigations

• Blood tests
  • FBC- normochromic anaemia, thrombocytosis
  • LFTs- deranged either due to obstruction (bilirubin and ALP) but also raised AST/gGT (particularly in metastatic disease)
  • Hyperglycaemia
  • CA19-9
    • 80% sensitivity and 73% specificity
    • most useful in assessing response to treatment
• Imaging
  • USS is usually first line
  • CT is preferred and is most useful in staging (see below)
    • MRI and PET may add to staging process
  • Endoscopic USS

Staging

1.  
   • A- T1 (<2cm; restricted to the pancreas); N0; M0.
   • B- T2 (>2cm; restricted to the pancreas); N0; M0
2. • A- T3 (extending into adjacent structures); N0; M0
   • B- T1-3; N1 (nearby lymph node involvement); M0
3. T4 (grown into nearby blood vessels); N1-2; M0
4. T1-4; N1-2; M1 (distant disease)

• Most (47.5%) patients present at stage 4
• Resectable disease is rare- stages 1-2- and account for only 15% of cases at presentation

Management

• All management should be decided in a MDT meeting with oncology, surgery, and palliative care.
• Surgery
  • Only chance of cure (but only suitable in 15% of patients)
  • Different kinds of surgery depending on the location/extent of the tumour
    • Whipple’s procedure (for pancreatic head/neck cancers)
      • Proximal pancreaticoduodenectomy with antrectomy
        • Involves resecting the proximal pancreas, duodenum and antrum of the stomach and joining the hepatobiliary duct, pancreatic duct and stomach to the jejunum
      • Ocreotide must be given one week after to reduce pancreatic secretions
    • Modified Whipple’s procedure (preserves the gastric antrum and pyloric sphincter to maintain gastric emptying)
      • No increase in 5-year mortality compared to Whipple’s, less morbidity
    • Distal pancreatectomy (for body/tail tumours)
    • NB Total pancreatectomy is rarely done
  • Even successful resections have only a 15-20% 5 year survival (mean 12-19 months)
• Chemotherapy
  • Usually resistant but may be used adjuvantly/palliatively for increased chance of survival or improvement of symptoms (respectively)

Chronic Pancreatitis

Background/Pathophysiology

• Chronic pancreatitis is a chronic, irreversible, inflammation and/or fibrosis of the pancreas, often characterised by disabling pain and progressive endocrin and exocrine insufficiency.
• It was initially thought that chronic pancreatitis involved a distinct process from acute pancreatitis.
  • Acute pancreatitis involves a neutrophilia, oedema and raised serum pancreatic enzymes
  • Chronic pancreatitis involves a lymphocytic inflammation, fibrosis and calcification, often without raised serum pancreatic enzymes
    • It is thought that chronic pancreatitis occurs in people who have an altered immune response to the inflammation of acute pancreatitis
      • Obstruction or Reduction in bicarbonate excretion
      • Alcoholic damage can cause protein deposition in the ductular structures of the pancreas (not seen in acute episodes)
• It is most common in men 40-50 years old
• There are thought to be 2 different pathological subtypes of chronic pancreatitis: small duct and large duct pancreatitis.
  • NB Either can be associated with all aetiologies, and they may actually represent part of a spectrum of disease (i.e. same process)
  • 

Aetiology

• Alcohol
  • 70-90% of cases
  • Exact mechanism uncertain
    • ?Increased protease secretion from acinar cells and decreased secretion of bicarbonate/fluid by ductal cells.
      • Resulting mixture obstructs the ductal lumen and causes upstream acinar atrophy and fibrosis.
    • ?Increased oxidative stress
  • NB Liver cirrhosis and chronic pancreatitis rarely occur together
• Autoimmune
  • 5-6% of cases
  • 2 types (type 1 & 2)
    • Type 1 is more common in East cf 2 in the Western world
  • Presentation similar to alcoholic pancreatitis but can be asymptomatic
  • NB IMPORTANTLY, autoimmune chronic pancreatitis is steroid-responsive and may be reversible if caught early
  • Increased gGT/IgG4 and autoantibodies a.g. antinuclear antibody and rheumatoid factor
  • Associated with other autoimmune conditions e.g. rheumatoid arthritis, Sjogrens syndrome, primary biliary cirrhosis, primary sclerosing cholangitis and IBD
• Hereditary
  • Rare, autosomal dominant condition mostly due to a mutation in the cationic trypsinogen gene (PRSS1)
    • Interferes with inactivation of trypsin, allowing active trypsin to autodigest the pancreas
  • Tend to present in young adults/adolescents (i.e. <20 years)
  • Associated with pancreatic cancer also
• Idiopathic
  • Diagnosis by exclusion but accounts for up to 15% of cases
  • Thought to be due to a number of factors
    • ?Hypersensitivity to alcohol
    • Genetic factors
    • ?Trauma
• Drugs
  • NB Usually cause more of a recurrent acute pancreatitis scenario which can develop into a chronic pancreatitis
  • 

• Smoking is an independent risk factor
• Other rare causes include metabolic disorders (hypertriglyceridaemia, hypercalcaemia); trauma; cystic fibrosis; iatrogenic (ERCP); radiotherapy

Presentation

• Typical presentation is of recurrent/chronic epigastric pain that radiates to the back
  • Often very severe and dull (may require opiate analgesia); commonly precipitated by eating
  • Lasts several hours at a time
  • Associated with nausea and vomiting
• Other symptoms include:
  • Reduced appetite; weight loss
  • Steatorrhea
    • Loose, greasy, fatty, foul-smelling stool that are difficult to flush
    • May present as incontinence
• On examination,
  • Epigastric tenderness
  • May be signs of chronic alcohol excess e.g. liver stomata
    • Jaundice may be present either as a result of concomitant liver disease or stone disease
    • Finger clubbing (more likely to be secondary to steatorrhea)
• Patients may also present with hyperglycaemia (due to endocrine dysfunction)

Investigation

• Blood tests
  • FBC- WBC count is often normal
  • LFTs may be abnormal if there is coexistant liver disease or obstruction of the intra-pancreatic bile duct
  • U&E
  • NB serum amylase is usually normal in chronic pancreatitis and does not warrant investigation unless investigating a differential diagnosis
• Secretin stimulation test
  • Secretin is usually released by the small intestine in the intestinal phase (III) in response to a decrease in intestinal pH as food enters the duodenum
    • It acts on the pancreas to release bicarbonate-rich digestive juices
    • Tests involves administering secretin and measuring (endoscopically or in conjunction with ERCP) the release of pancreatic juices
  • A test will be positive if 60% of the exocrine pancreas is damaged
• Serum trypsinogen and urinary D-xylose or faecal elastase if malabsorption (diarrhoea, steatorrhoea, weight loss) is present
• Imaging
  • CT may show calcification of the pancreas
  • Endoscopic USS is becoming increasingly used
• Pancreatic biopsy is the gold standard
  • Lymphocytosis, fibrosis and focal necrosis with plugs of precipitated proteins

Management

• Pain management
  • paracetamol + NSAID +/- opiates (depending on severity)
• Malabsorption
  • Creon and lipase
  • May also require PPI or H2 antagonist to increase their absorption
• Ocreotide (somatostatin analogue)
  • Decreases pancreatic activity and CCK levels
  • Useful in patients with persisting pain due to pancreatitis
• ERCP may be used to decompress blocked pancreatic ducts
• Surgery (Rarely done in cases with intractable pain or severe malabsorption problems)
  • Decompression/drainage (e.g. removal of pseudocysts)
  • Local resection
  • Pancreatodueodenectomy

Dyspepsia & Gastroduodenal Ulcer

Gastroduodenal ulceration is a breach of the epithelium that penetrates the muscularis mucosa (of the gastric or duodenal lining).  It must be confirmed endoscopically for the diagnosis to be made.

Epidemiology

• It has a reported incidence of 1-4/1000, and is much more common in men (particularly duodenal ulcers- 5:1)
• Incidence has reduced in recent years due to widespread prescription of PPIs, awareness of NSAID use and risk, and eradication of the causal organism, H Pylori, with antibiotic treatment

Aetiology

• Helicobacter pylori
  • In the western world, the most common site of H pylori infection is the antrum of the stomach
    • In patients from the developing world (particularly Asia) and those with a family history of gastric cancer- a chronic atrophic pangastritis may be caused by H pylori infection affecting the entire stomach
      • This is thought to be due, at least in part, to a difference in H pylori strains
        • The VacA and CagA genes in H pylori are thought to play an important role in carcinogenesis and ulceration (respectively, although CagA may be important in both)
        • Human genetics, e.g. IL1B gene cluster, may also play a role
  • Causes local inflammation resulting in dysfunction of D cells located there.  This causes a reduction in somatostatin production
    • Somatostatin is important in acting on parietal cells in the fundus of the stomach to reduce secretion of gastric acid
    • It also acts to reduce the release of pro-secretory hormones such as gastrin, secretin and histamine (therefore, in an infected state, the levels of these hormones increase)
  • This increases acid causes increased cell turnover in the duodenum, metaplasia and eventually ulceration, particularly in those with other risk factors (it is not certain whether gastric ulcers follow the same pathophysiology)
• NSAIDs
  • COX-1 inhibition prevent the production of protective prostaglandins, which are important in maintaining the integrity of the gastric wall
  • If there is an underlying H pylori infection, this could precipitate ulceration
• Smoking
• Alcohol (alcohol induced gastritis precipitating a peptic ulcer)

Presentation

• Symptoms may be vague and non-specific
  • Epigastric pain
    • Classically post-prandial with gastric ulcer and 2-3 hours after a meal with duodenal ulcer (hunger-pangs)
    • Epigastric pain may be relieved by food in a duodenal ulcer (often not so with gastric)
    • Often wakens sleep (more common in duodenal)
    • Pain radiating to the back may indicate a complicating pancreatitis (posterior gastric ulcer)
    • May be worsened by fatty foods
  • Nausea
  • Oral flatulence, bloating/distention (may be associated with chronic duodenal ulcer causing stricture/obstruction)
• There might not be many signs (maybe epigastric tenderness)

What is important is to be able to assess patients for dyspepsia with alarm features e.g.

• Chronic GI bleeding
• Unintentional weight loss
• Progressive dysphagia
• Persistant vomiting
• Iron deficiency anaemia
• Epigastric mass
• If patients are >55 years with persistent or unexplained recent-onset dyspepsia

Investigation/Management of Dyspepsia

• For patients with dyspepsia and acute GI bleeding- admit to hospital
• For patients with dyspepsia and alarm features
  • Arrange urgent endoscopy
  • Stop any NSAIDs and modify any other drugs which may be contributing
  • Advise on lifestyle
    • Lose weight
    • Stop smoking
    • Stop alcohol consumption
    • Stop food that worsens symptoms
  • Prescribe either an alginate e.g. sodium bicarbonate, or an antacid.  DO NOT PRESCRIBE H2 antagonists OR PPIs for at least 2 weeks prior to endoscopy
• For patients without alarm features
  • FBC- check anaemia
  • Review drugs
  • Prescribe an antacid or an alginate
  • If it is possible to stop any NSAIDs
    • If not possible, consider switching NSAID from aspirin to another NSAID e.g. clopidogrel, plus a PPI
  • For persistent symptoms, either prescribe a PPI (full dose for 1 month) or test and treat for H pylori (NB if the former doesn’t work, test for H pylori anyway)
    • Tests for H pylori
      • Urea breath test or stool antigen test (contraindicated if taken antibiotics in the past four weeks or a PPI in the past 2)
        • The latter is best for re-testing should this be required (e.g. in poor compliance, FHx of gastric cancer, those requiring NSAIDs, severe symptoms etc)
      • Serology may be used if the other tests have failed
    • Treatments for H pylori infection
      • Amoxixillin 1g + Clarithromycin 500mg + either lansoprazole 30mg or omeprazole 20mg for 7 days
      • Clarithromycin 250mg + metronidazole 400mg + either lansoprazole or omeprazole for 7 days
  • If neither treatment for H pylori nor PPI treatment for 1 month works, consider referral or a month trial of either a prokinetic (e.g. domperidone) or an H2-receptor antagonist
• NB PPI prescriptions for peptic ulcer disease should not be indefinite.  Patients should stop taking the PPI once symptoms have resolved.  If symptoms return, the PPI can be restarted or alternative drugs considered.  In any case, a regular review of patient drugs should be arranged, particularly in patients with polypharmacy.

Colorectal Cancer

Background/Epidemiology

• Most common cancer in the UK after breast and lung.  Second most common cause of cancer death.
• More common in older (>65) men

Risk factors/Aetiology

Colorectal cancer is multifactorial.

• Three types
  • Sporadic (95%); HNPCC (5%); FAP (<1%)
• Genetic predisposition is a strong risk factor.  Those with a family history are at much higher risk.
  • Hereditary adenomatous diseases of the colon e.g. FAP and HNCCS, increase the risk to up to 100% and 50%, respectively
• Environmental factors- namely diet rich in red meat and saturated fat, poor in fibre, folate and calcium
• Obesity, smoking, alcohol excess
• Inflammation of the bowel (e.g. IBD); diabetes; other cancer

Screening

• In Scotland, all patients between the ages of 50 and 74 years are invited for screening for bowel cancer
• A Cochrane review showed that bowel screening programmes decrease the risk of dying from colon cancer by 16%
• The screening programme is distributed by sending patients a Faecal Occult Blood (FOB) kit.
  • Collect samples of stool to check for microscopic and biochemical blood products in the stool
  • NB FOB does not diagnose colon cancer
    • 10 in 500 patients will have abnormal result.  Out of these patients, one will have cancer, others will have polyps or another benign source of bleeding, and one will be a false positive.
    • An abnormal result should be investigated further, ideally with colonoscopy

Presentation

• Presentation can depend on the site of the cancer
  • Right sided/Caecal cancers
    • Often picked up by screening early.
    • If not, they may present late with vaguer signs/symptoms e.g.
      • weight loss, anaemia, mild diarrhoea, mass in the RIF
  • Left sided/Sigmoid cancers
    • Often more apparent and usually presents earlier (if not detected early by screening)
      • Colicky pain, rectal bleeding, large bowel obstruction, change in bowel habit, tenesmus, mass in LIF
  • Rectal cancer
    • Often rectal bleeding and mucus discharge
• Symptoms of anaemia, change in bowel habit, and rectal bleeding
  • Any of these symptoms (particularly in people >60 years old) warrants further investigation
    • together, suspicion is high, and patients >40 should be referred immediately
  • more rarely jaundice, ascites and hepatomegaly may also be present (liver/peritoneal mets are common)
  • Any abdominal mass requires further investigation

Recommendations for referral

• Urgent referral (within 2 weeks)
  • patients > 40 years old, reporting rectal bleeding with a change of bowel habit towards looser stools and/or increased stool frequency persisting for 6 weeks or more
  • patients > 60 years old, with rectal bleeding persisting for 6 weeks or more without a change in bowel habit and without anal symptoms
  • patients > 60 years old, with a change in bowel habit to looser stools and/or more frequent stools persisting for 6 weeks or more without rectal bleeding
  • any patient presenting with a right lower abdominal mass consistent with involvement of the large bowel
  • any patient with a palpable rectal mass
  • unexplained iron deficiency anaemia in men or non-menstruating women (Hb < 11 g/dl in men, < 10 g/dl in women)

Investigations

• Colonoscopy should be offered to confirm the diagnosis
  • Flexible sigmoidoscopy can be used as an alternative in patients with comorbidity
    • NB Considering the similarities between the procedures and the difference in scope (sigmoidoscopy can detect around 60% of tumours), a colonoscopy should always be the preferred choice
    • CT colonography may also be used if scoping is not possible, however a biopsy is not possible with this investigation, limiting its helpfulness compared to colonoscopy
• FBC, U&Es, LFTs
  • Unexplained iron-deficient anaemia is a cause for referral in men of any age and in non-menstruating women
  • Liver USS should be done should there be any liver signs, symptoms or deranged LFTs
• Abdominal CT and MRI are crucial to do prior to surgery and will aid diagnosis in the absence of colonoscopy too

Staging

• Duke’s staging- NB TNM staging has largely superseded Duke’s staging

1.  Invasion into but not through the bowel wall (90% 5-year survival)
2. Invasion through the bowel wall but not involving lymph nodes (70% 5-year survival)
3. Involvement of lymph nodes (30% 5-year survival)
   1. local lymph nodes
   2. distal lymph nodes
4. Widespread metastases (<10% 5-year survival)

Management

• Surgery
  • Right hemicolectomy/left hemicolectomy/ sigmoid colectomy/ anterior resection/ AP resection
    • Laparoscopic or open
  • A note about which surgery
    • With most bowel operations, there is the option to resect and rejoin (anastomosis) or to ‘defunction’ to protect the distal section by joining the proximal section to the skin.  These can be temporary (usually loop stomas
      • Right hemicolectomy for caecal tumours (even obstructing- but not if septic)
      • Left hemicolectomy for left-sided colon tumours (distal transverse and descending colon)
      • Anterior resection (essentially the same portion removed as left hemicolectomy) for sigmoid tumours (high) and high rectal tumours (with total mesorectal excision)
        • For low rectal tumours (<5cm from the dentate line) it may be more appropriate to perform abdominoperoneal resection (although generally a level of <2cm is the cut off) or anterior resection + defunctioning stoma (loop colostomy)
        • For anal tumours, an abdominoperineal excision of the rectum is preferred with end colostomy
      • A Hartmann’s procedure is often used in the emergency situation for rectosigmoid tumours where the surgeon will not want to anastomose the two ends of bowel/rectum.  Therefore, there is an end colostomy and a rectal stump
• Radiotherapy and Chemotherapy
  • FOLFOX (Folinic acid/Fluorouracil/Oxaliplatin) then Irinotecan +/- further fluorouracil and folinic acid (FOLFIRI)

Appendicitis

Anatomy

• Hollow, blind-ended, narrow tube arising from the posteromedial wall of the caecum, at the point of convergence of the taeniae coli.  ~2cm below the ileocaecal valve
  • Length varies (between 2-25cm; average 6-9cm)
  • Externally, located one third of the way between the right ASIS and the umbilicus (McBurney’s point)
  • It’s position also varies (depends on length and mobility)
    • Pelvic position commonly seen during laparoscopy but most appendices will be retrocaecal on post-mortem
      • Retrocaecal 70%; Pelvic 21%; Post-ileal (behind ileus) 4%; Paracaecal 2%; Subcaecal 2% and Pre-ileal 1%
• Blood supply
  • Appendicular artery (branch of ileocolic artery) via mesentery (mesoappendix)

Epidemiology

• Most common cause of acute abdomen in the UK requiring surgery
  • ~15% of the population will undergo appendicectomy for presumed appendicitis
    • Appendix is normal in 10-20% of procedures
  • Most common in children aged 8-14

• Inflammation of the vermiform appendix that can spread
  • Risk of tissue ischaemia, necrosis and ultimately perforation
    • communication between the peritoneum and colonic lumen -> peritonitis

Aetiology/Pathophysiology

• It is thought that appendicitis is caused by obstruction of the appendix
  • most commonly due to lymphoid hyperplasia seen in inflammatory bowel disease or childhood infections
  • may also be faecoliths, faecal stasis, parasites, foreign bodies, tumours…
• Causes a rise in intraluminal pressure as the mucosa continues to secrete fluids (and even increases secretions in response to inflammation)
• Bacteria are able to overgrow and cause further infective inflammation and swelling
• Blood flow to the appendix is eventually impaired and ischaemia ensues, leading to breakdown of tissues and bacterial invasion into deep structures
• Ultimately, the combination of increasing pressure, lack of blood supply and bacterial infection can lead to perforation.

Presentation

• Classic presentation (NB only seen in around 50% of patients)
  • Pain & tenderness
    • Early non-specific peri-umbilical pain which localises with time (around 24 hours) to the right iliac fossa (McBurney’s point) as the surrounding peritoneum becomes involved.  This may be worsened with movement/coughing.  Guarding and rebound tenderness are often seen.
    • Rovsing’s sign (deep palpation of the LIF causes tenderness in the RIF) may be seen in late appendicitis
  • Nausea, anorexia and constipation are common (vomiting/diarrhoea may also be present)
  • Pyrexia
  • Other examination tests include DRE (rectal tenderness may be a sign of retrocaecal appendicitis); psoas test (extend and abduct the hip- will be painful- another sign of retrocaecal appendix)
• In children, a significant pyrexia is uncommon, but they may have a low-grade fever and facial flushing.  Vomiting may also be more common.  They may also not present with the initial non-specific, central discomfort but rather just the localised RIF pain.
• In the elderly, patients tend to present much later and with less specific signs/symptoms: a pyrexia is not common, generalised pain is more common and vomiting may be the presenting complaint rather than pain.

Investigations

• FBC: WCC is commonly raised but a normal value doesn’t exclude the diagnosis (similarly with CRP)
• CT abdo is the gold-standard
  • Often, where the diagnosis is uncertain, and USS will be performed first
• Urinalysis and pregnancy test are important to exclude alternative diagnoses of UTI or ectopic pregnancy (respectively)
  • NB Urinalysis may be false positive in up to half because of adjacent inflammation
• Laparoscopic diagnosis may be required- particularly in young girls in whom peritonitis may cause subsequent infertility

Management

• Appendicectomy

3rd degree heart block

Background/Pathophysiology

• Complete AV block i.e. no transmission through the AV node.
  • Separate activity of the atria and ventricles (not synchronised)
• Ventricular contraction is instead mediated by junctional (AV node) or ventricular escape activity
  • This ‘ventricular dissociation’ is a feature of 3rd degree heart block
    • NB Ventricular dissociation is not restricted to complete heart block e.g. it also occurs in ventricular tachycardias, where the ventricular rate exceeds the sinus rate.
  • In most cases, the rhythm is derived from below the His bundle (around 2/3rds)
    • Heart rate tends to be <45bpm and patients tend to be less haemodynamically stable and rate is unresponsive to stress/exercise.  The QRS is usually broad (asynchrony of ventricular spread/contraction)
  • The remainder either come from the AV node itself or the His bundles
    • These tend to fire at around 45-60bpm and are more responsive to exercise/stress.  Therefore patients are generally more stable and less symptomatic.  The QRS is narrow.

Aetiology

• Drugs
  • Anti-arrhythmic drugs: particularly Beta blockers, calcium channel blockers and digoxin
• Infections
  • myocarditis, endocarditis, rheumatic fever
• Rheumatic/connective tissue disease
  • Scleroderma, ank spon, rheumatoid arthritis
• Infiltrative disease
  • Amyloidosis, sarcoidosis, tumours, multiple myeloma, Hodgkin’s lymphoma
• Ischaemic disease
  • Inferior wall MI, more seriously in an anterior MI
  • Blockage of the RCA (supplies the AV node)
    • Usually resolves after revascularisation
• Metabolic
  • Hypoxia, hyperkalaemia, hypothyroidism
• Iatrogenic
  • Cardiac surgery

Commonly, 3rd degree heart block has developed from a 2nd degree heart block.

Presentation

• Fatigue
• Light headed/dizzy
  • Pre-syncope +/- syncope (occasionally without warning – morgagni-adams-stokes attacks) 
  • confusion
• Symptoms worse during exercise/activity (reduced exercise tolerance)
• Dyspnoea may be present
• Chest pain is uncommon

Investigations

• FBC (anaemia, infection), U&Es (metabolic disturbance- including magnesium), clotting
•  

12-lead ECG shows complete dissociation between P waves and QRS complexes (signs of MI may also be present e.g. in example below).  There may also be right axis deviation

3rd degree heart block in a patient with inferior myocardial infarction: complete dissociation of p waves (red) and QRS complexes (blue) (Photo credit: Wikipedia)

Management

• Adjust medications (reduce beta blocker dose, adjust digoxin etc) and heart block may resolve
• If the heart block is permanent, then a pacemaker is needed

2nd degree heart block

Background

• Second degree heart block is characterised by a disturbance, delay or interruption of atrial impulses through the AV node resulting in only partial conduction of signals to the ventricles (i.e. in contrast to 1st degree where every P wave has a QRS, this is not the case with 2nd degree heart block)
• 2nd degree heart block can be classified as either
  • Mobitz Type 1 (Wenckebach)- this is where there is progressive lengthening of the PR-interval until the atrial impulse cannot be conducted and a QRS (and ventricular contraction) does not occur.  The main site of dysfunction is usually the AV node itself and can be vagally mediated.
  • Mobitz Type 2- this is where the PR interval is constant (may be prolonged or not) but there is a ‘dropped beat’.  This may occur in a pattern e.g. 2:1 (can’t actually be differentiated from type 1), or 3:1.  The main site of dysfunction is usually in the bundle of His.
    • Can cause QRS widening and more likely to progress to 3rd degree heart block

Aetiology

• Although some could be classed as idiopathic, it is important to identify an underlying cause/risks
  • Any cardiac disease (MI, CHD, IHD, heart failure, cardiomyopathy, rheumatic heart disease, infection, tumours etc) can potentially cause heart block
  • Drugs can also cause heart block (local anaesthetics, beta blockers, benzylpenicillin, lithium)
  • other conditions e.g. sarcoidosis, amyloidosis, ank spond, dermatomyositis (and other connective tissue disorders)
  • alcohol may also precipitate/exacerbate heart block

Presentation

• Type 1- usually asymptomatic; occasionally presyncopal episodes or syncope, dizziness etc
• Type 2- more likely to be symptomatic (light-headed, dizzy, presyncope/syncope, palpitations etc)

Investigations

• ECG will show features described above.
• Lying/standing blood pressure
• Blood count, U&Es

Management

• Mobitz Type 1 can generally be managed without any active treatment
• Type 2 (because of risk of development into 3rd degree block) should be given a pacemaker (particularly if symptomatic)

1st-degree AV Heart block

First degree heart block is defined as the prolongation of the PR interval (on the ECG) to >200ms (normally 120-200ms; marked 1st-degree block >300ms).  In contrast to other heart blocks, every P wave is transmitted to a QRS complex (and ventricular contraction i.e. no ‘missed’ beats, just slowing).

Pathophysiology

1st degree heart block rarely shows any abnormalities of the ECG other than prolonged PR interval (i.e. no QRS widening, no absent QRS etc).  This is a result of dysfunction, almost always, at the level of the AV-node.  Rarely, 1st degree heart block is accompanied by widening of the QRS complex, signifying block at the level of the His-purkinje complex.

Aetiology/Risk Factors

• Ischaemic heart disease (inc coronary heart disease)
  • AV block is common post MI (in particular inferior MI)
• Other heart disease e.g. infection (endocarditis, rheumatic fever, diphtheria, TB) may also be a cause of AV block
• Several drugs (particularly antiarrhythmics e.g beta blockers, calcium channel blockers etc)
• Electrolyte disturbances
  • hypokalaemia, hypomagnesemia
• More rarely, intrinsic AVN disease may be the cause

Presentation

• Most patients are asymptomatic
  • May have reduced exercise tolerance
  • May also present with pre-syncope/syncope (particularly on exertion)

Investigations

• ECG
  • PR interval exceeds 200msec (1 big square)

Management

The risk is that these patients will develop 2nd degree heart block.  However, this risk is pretty small and, unless they are symptomatic, pharmacological treatment is not usually necessary (aside treatment of an underlying cause)