Metastatic Cancer Symptoms

Metastatic Disease Without Obstruction

• Patients with isolated liver/lung secondaries should also undergo treatment with a radical approach as even in these cases with resection of the primary and adequate liver/lung resection, good disease control can be achieved.
• A typical course of neoadjuvant therapy comprises concurrent 5-FU/Capecitabine and radiation in cases of large lesions abutting the abdominal wall or down into the pelvis.
• A dose of 45–50 Gy is used to treat the pelvis including the growth and the draining lymphatic regions followed by a 5 Gy boost to the tumour itself.
• Following neoadjuvant therapy, the patient should be reevaluated using CT/MRI for the possibility of resection.
• Surgery is usually considered after 6–8 weeks following neoadjuvant therapy as the maximal response to the treatment may take up to 2 months.
• Further adjuvant treatment is to be given following surgery depending upon the histopathological report.

Management Of Liver Secondary

• CT scan and PET scan are done to evaluate local/ systemic disease. Provided there is no systemic spread, liver secondaries have to be treated aggressively.
• The pattern of recurrence in colonic carcinomas is more commonly distant, i.e. they tend to recur more commonly at distant sites such as the liver, and lungs. As a result, systemic treatment is essential.
• Liver-directed therapies such as hepatic arterial chemotherapy infusion/embolisation, radiofrequency ablation, and radiotherapy should be used in the treatment of isolated liver metastasis.
• Isolated liver metastasis is not a contraindication for definitive resection of the primary.
• Indications for liver resection

Novel Agents in Colorectal Cancers:

• Bevacizumab—anti-VEGF (vascular endothelial growth factor) monoclonal antibody. It has anti-angiogenesis properties, thereby controlling tumour growth.
• Cetuximab and panitumumab—anti-EGFR (epidermal growth factor) monoclonal antibody is given, only if K-RAS is negative.

Follow-up:

• Most of the colonic cases are curable if diagnosed and treated early. Also metachronous lesions can occur in the rest of the colon.
• Hence, certain tests are necessary during follow-up.

Treatment Of Recurrent Or Metastatic Cancer

• Recurrence or metastasis is suspected during follow-up by abnormal values of investigation.
• The recurrent tumour should be resected en bloc—it may amount to a more radical procedure including resection of the duodenum, liver, and kidney.
• Metastasis in the liver.

Indication for Resection of Liver Metastasis:

• Solitary metastasis or metastasis confined to one lobe
• <3 metastasis in both lobes
• Absence of extrahepatic disease

Follow-up of Colorectal Cancer:

 

Chemoprevention Of Colonic Cancer

1. Folic acid:
   • It is an important vitamin with many functions. In the absence of folic acid, hypomethylation can occur. As a result of this overexpression of protooncogenes such as K-RAS and c-Myc can occur.
   • Deficiency of folic acid causes imbalances in the nucleotide pool leading to DNA break and mutation. Thus folic acid supplementation should be given in adenoma specially when baseline levels of folic acid is low.
2. Dietary fibres:
   • Fibres decrease the transit time, dilute the carcinogens and are used to prevent development of cancer.
   • Cellulose, hemicelluloses and pectin are a few examples. Fibres also produce short chain in fatty acids causing fermentation by faecal flora.
   • Thus colonic pH becomes more acidic which in turn inhibits carcinogenesis.
3. Aspirin, calcium, and sulindac also have been used to prevent cancer developing in an adenoma.

Colon Screening

• The large bowel is the 4th most common site for cancer after lung, stomach and breast.
• More common in North America, North Europe and Australia. Lowest rates in Africa, India.
• 75% of CRC develops in people with no known risk factors apart from older age.

Screening Options:

1. Faecal occult blood test (FOBT):

• It is a guaiac test which will detect elevated level of blood in stool. It requires two samples from each of three consecutive stools which are smeared onto cards.
• False positive: Vegetables, fruits, red meat, aspirin or any other bleeding lesion proximal to colon screening, FOBT has shown to decrease mortality by 20 to 30%.

2. Flexible sigmoidoscopy (FS):

• Reduces incidence and mortality of distal CRC by around 60%.
• Single FS at the age of 60 is recommended in UK.
• In US, 5-yearly screening is being done.

3. Colonoscope screening:

• This should be done if there is distal adenoma (chances of proximal adenoma are high).
• 70% of all advanced colorectal neoplasia will be detected with this strategy.
• Procedure is painful, and requires sedation and analgesics.
• The chances of perforation are 1 in 500 to 2000 cases.
• It requires skills of an experienced endoscopist.

4. Virtual colonoscopy:

• It is an alternative but not yet become popular because of time, cost and preparation.
• It is done with the help of CT scan.
• Biopsy cannot be taken.

Diverticular Disease Of Colon

It is an acquired condition, in which colonic mucosa herniates through the circular muscle fibres at weak points, where blood vessels penetrate the colonic wall. Since it is acquired, it lacks the muscle coat. They are thin, and more prone to infections and perforation. Hence, they are termed pseudodiverticuli.

Aetiopathogenesis

• The disease is common in western population wherein the diet is very poor in fibres because of the refining of sugar and flour.
• Nonstarch polysaccharides (NSP) or low dietary fibres are the chief factors for diverticulosis of the colon.
• It requires very high pressure for propulsion of faecal matter and this is believed to cause characteristic thickening of muscles and herniation of mucosa.
• Hence, it is called pulsion diverticulum.

NSP and Diseases:

• Diverticular disease
• Obesity and diabetes mellitus
• Constipation, and piles
• Breast cancer and colonic cancer

• In Africans and Indians, the disease is rare because of the high fibre content of the diet.
• The disease starts after the age of 40. Any stress or emotional disorders may add to the constipation already caused by dietary factors and result in diverticular formation.
• 90% of them affect sigmoid colon. Rectum is spared in the majority. Rarely, it affects right colon.
• Diverticulae project between antimesenteric and mesenteric borders with taenia but they never penetrate taenia.
• There is muscle hypertrophy, which projects into the lumen as obstructive folds. The mucosa is essentially normal. Slowly, the luminal diameter is narrowed.
• Inflammation occurs in the pericolic tissue with or without abscess formation

Structural Changes in the Colonic wall of Patients with Diverticulosis

• Mycosis
• Thickening (neither hypertrophy nor hyperplasia) of
• the circular muscle layer.
• Shortening of the Taenia coli
• Luminal narrowing
• ↑ elastin deposition in Taenia coli
• ↑ Type 3collagen synthesis
• ↑ collagen cross-linking

Segmentation

• Law of Laplace: Pressure = K × Tension/Radius
• The sigmoid colon has a small diameter resulting in highest pressure zone.
• Segmentation = motility process in which the segmental muscular contractions separate the lumen into chambers.
• Segmentation → increased intraluminal pressure → mucosal herniation → diverticulosis.
• May explain why high fibre prevents diverticula by creating a larger diameter colon and less vigorous segmentation.

Collagen connective tissue diseases such as Ehlers-Danlos syndrome, Marfan’s syndrome, and autosomal-dominant polycystic kidney disease result in structural changes in the bowel wall, leading to decreased resistance of the wall to intraluminal pressures and thus allowing protrusion of diverticula.

Colonic Clinical Features:

• Diverticulosis: It refers to the presence of diverticulosis without many symptoms. However on careful questioning, patients do have lower abdominal distention, heaviness, flatulence, etc. Vague abdominal pain is also felt in the left iliac fossa.
• Diverticulitis: Left-sided lower abdominal pain, moderate to severe, is associated with the passage of loose stools. The pain is partially relieved on passing flatus.
  • Bleeding per rectum can be the presenting feature, sometimes it can be massive.
  • Low-grade fever, tenderness, rigidity and even mass may be present in the left iliac fossa (like left-sided appendicitis). The mass is thickened, inflamed, tender and sigmoid. Such attacks result in abscess which rupture into hollow organs and give rise to fistulae.
• Internal fistulae: Colovesical fistulae (commonest) give rise to pneumaturia (flatus in the urine) and rarely faeces in the urine. Other fistulae are colovaginal, coloenteric, and colocutaneous.

Causes of Internal Fistulae:

• Diverticular disease of the colon (commonest)
• Carcinoma of colon
• Crohn’s disease
• Radiation
• Tuberculosis

Classification/Staging System

Hinchey Classification:

• Pericolic abscess
• Walled off pelvic abscess
• Generalised purulent peritonitis
• Generalised faecal peritonitis

Hinchey stages 1 and 2 may be treated by sigmoid colectomy and primary anastomosis (a one-stage operation). Hinchey stages 3 and 4 are treated by sigmoid colectomy followed by end-colostomy and Hartmann pouch.

Investigations: 

1. Sigmoidoscopy: Mucosa may be normal or may show erythematous and oedematous changes. Ulcers are absent. Opening of diverticulae can be seen.
2. Barium enema: Contraindicated in acute cases.
   • It may show a saw-tooth appearance due to muscle hypertrophy.
   • It may show a long stricture.
   • Champagne glass sign: Partial filling of diverticula by barium with stercolith inside the diverticula.
3. Colonoscopy: Colonoscopy to to confirm the findings and to rule out carcinoma colon.
4. Ultrasound and CT scan: Are the investigations of choice in acute diverticulitis.

Diverticular Disease Of Colon Complications:

1. Massive haemorrhage per rectum: Haemorrhage is due to vessels in the base of diverticula, more so in atherosclerotic or hypertensive patients.

2. Stricture: Stricture of sigmoid colon can develop due to recurrent attacks resulting in intestinal obstruction.

CT Scan Acute Diverticulitis:

• Can detect thick muscular folds—confirms the diagnosis.
• Detects an abscess and can confirm complications.
• Detects extraluminal air or contrast—confirms perforation.
• Can rule out other causes—acute pancreatitis with pericolic collection, etc.
• It is the investigation of choice in acute diverticulitis.
• Thickened colonic wall >4 mm.
• Pelvic abscess can be diagnosed

3. Perforation: Perforation may result in peritonitis, pericolic abscess or pelvic abscess.

4. Fistula formation:  Internal fistulae occur due to inflammatory adhesions and abscess formation which ruptures resulting in fistulae. Thus, colovesical, colovaginal, and colointestinal fistulae can occur.

Differential Diagnosis: 

• Carcinoma of the colon
• Inflammatory bowel disease
  Ischaemic colitis
• Irritable bowel syndrome
• Pelvic inflammatory disease

Indications for Surgery:

• Failure to respond to conservative/dietary advice
• Two attacks of diverticulitis
• Complications

Diverticular Disease Of Colon Treatment:

1. Stage of diverticulosis: Stage of diverticulosis or in those patients who have recovered from one attack of diverticulitis.

• High residue diet
• Fruits and vegetables
• Whole meal bread and flour
• Bulk purgative
• To avoid constipation
• Diet:
• High fibre diet, the optimal amount of daily fibre is unknown.
• 20 to 30 g per day is widely recommended.
• Recommendation to avoid seeds, nuts and popcorn.

Pericolic Abscess:

• Abscess depends on the ability of the pericolic tissues to localise the spread of the inflammatory process.
• Intra-abdominal abscesses are formed by—anastomotic leakage: 35%—diverticular disease: 23%.
• Limited spread of the perforation forms an inflammatory phlegm, while further (but still localised) progression creates an abscess.
• Signs and symptoms: High-grade fever with or without leukocytosis despite adequate antibiotics, tender mass.

Pericolic Abscess Treatment:

1. Small pericolic abscess: 90% will respond to antibiotics and conservative management alone. Often it is retrocolic. May present as swelling in the loin.
2. Percutaneous abscess drainage (PAD): PAD is the treatment of choice for small, simple (>4 cm), well-defined collections. 100% success in simple unilocular abscesses.
3. Open drainage: In cases of multilocular collection, abscesses associated with enteric fistulas, and b abscesses containing solid material, drainage of pus, resection and Hartmann’s operation is the ideal choice. Closure of colostomy is done after 6–8 weeks.

2. Acute diverticulitis with pericolic abscess:

1. Rest, hospitalisation, correct hydration
2. IV antibiotics: Bactericidal against gram –ve and
3. anaerobes.
4. Abscess is aspirated under ultrasound guidance.
5. After 4–6 weeks, elective sigmoid colectomy and anastomosis is done.

3. Diverticulitis with peritonitis:

• Hartmann’s procedure is the choice: Sigmoid colon is resected, and end-colostomy is done by using descending colon followed by closure of the rectal stump.
• After 4–6 weeks, colorectal anastomosis is done.
• However, if a perforation is small and the general condition is good after the resection, the colon is irrigated with 8–10 litres of saline till the contents are clear. This is followed by colorectal anastomosis in the same sitting.

4. Treatment of fistulae: As an elective procedure, with good preparation, after confirming the site of the fistula, resection of the sigmoid colon with the closure of the fistula can be done.